Avandia's Posthumous Pardon

We've been covering the Avandia witch hunt story for more than three years now (see e.g. Avandia: Burn Her Anyway? and Avandia: A Fair Cop? )  and would like to take this opportunity to say "We told you so" and point you to this month's New England Journal of Medicine where you can read her posthumous pardon (such as it is) in The Cardiovascular Safety of Diabetes Drugs — Insights from the Rosiglitazone [Avandia] Experience. The story will be a familiar one made all the more appalling by the fact that the FDA again played the role of the fool who was tricked into thinking he was a superhero - just as it had been in the breast implant affair. 

In Act I, a meta-analysis of prior epi studies showed an increase in risk of cardiovascular events among those taking Avandia (rosiglitazone). Yet those first epidemiological studies hinting at a problem post-marketing "had substantial methodologic shortcomings, including multiplicity, which meant that a statistically positive finding might be a false positive result". Meanwhile, analyses of pre-marketing data was "relatively insensitive in assessing cardiovascular risk" in large part because nobody suspected that improving glycemic control (an approach taken by a whole class of diabetes drugs) would increase the risk of cardiovascular events. Nevertheless, Avandia was suddenly deemed to be dangerous.

In Act II the RECORD study, one that could actually uncover any increased risk and which in fact had demonstrated none, was denounced as hopelessly flawed "corporate science" based largely (or at least most stridently) on a claim of conflict of interest given that it was done at the behest of the manufacturer.

In Act III The New York Times and other news outlets decided Avandia was a perfect example of a narrative they were advancing; specifically that new drugs were no better than older generic versions, were only designed and marketed in order to gouge health care consumers and were more dangerous too. For months they hyped the story often claiming that tens of thousands of Avandia users had already suffered serious cardiovascular events and often death due to the drug. Eventually The NYTimes would quote the author of the meta-analysis that started it all as as calling the licensing of Avandia "one of the worst drug safety tragedies in our lifetime."

Act IV, meant to be the last, began with an emboldened FDA severely restricting the use of Avandia despite the growing need for effective type 2 diabetes treatments. Then the FDA killed  the TIDE trial - "a large cardiovascular-outcome trial designed to evaluate the benefit of rosiglitazone and pioglitazone (a/k/a Actos - Avandia's cheaper rival) as compared with placebo ... and the safety of rosiglitazone as compared with pioglitazone". It was the one study that could have answered the question of whether or not Avandia was better and safer than its generic rival (which btw itself is now the subject of considerable litigation ). So, Avandia having been hauled off to the stake and the evidence that might have acquitted her having been forbidden from being gathered it looked like the story would have a heroic and happy ending. A suddenly cocksure and vastly more powerful FDA, heedless of uncertainty, rushes in and rescues the helpless consumer from the clutches of Big Pharma.

But like all true stories this one didn't end so cleanly. Over the usual objection that anything, including data, ever touched by a corporation is forever corrupted the FDA did what it's actually supposed to do. It was curious and it asked a question. What, it asked, would the RECORD trial data reveal if it was handed off to and reanalyzed by a wholly independent group researchers with impeccable credentials and reputations. The answer came earlier this year and it "provided reassurance that rosiglitazone (Avandia) was not associated with excess cardiovascular risk."

So what had the FDA really done? Because almost nothing was known about the cardiovascular risk posed by other diabetes drugs " the FDA decision may have had unintended consequences. The intense publicity about the ischemic cardiac risk of rosiglitazone may have diverted attention from the better-established risk of heart failure that is common to the drug class. Restricted access led patients to switch from rosiglitazone to other diabetes drugs of unproven cardiovascular safety." In short the FDA had snatched consumers from uncertainty and delivered them into greater uncertainty.

The authors of the perspective conclude their piece hopefully and delicately. "Perhaps the recent experience with rosiglitazone will allow the FDA to become more targeted in its adjudication of the cardiovascular safety of new diabetes drugs, focusing the considerable resources needed to rule out a cardiovascular concern only on drugs with clinical or preclinical justification for that expenditure." We can only hope.

Tags:

"The sophisticated user doctrine is thus not an exception to the duty to warn, but an application of it."

That quote is from an opinion issued at the end of July that we wanted to bring to your attention. Dehring v. Keystone Shipping Co. involved an able-bodied seaman who lost his thumbs to a winch. He brought negligence and unseaworthiness claims against the ship owners and product liability claims against the company that designed and manufactured the winch. The manufacturer moved for summary judgment on the product claims and plaintiff sought a partial summary judgment on the ship owners' contributory negligence defense. The motions were referred to the magistrate who recommended that the defendant's be granted and the plaintiff's denied. Rather than some dull, perfunctory order adopting those recommendations Judge Ludington authored a gem of an opinion. Concise and insightful it contains an excellent account of the evolution of thinking about product design defect claims as well as a useful reminder about the nature of, and purpose behind, the duty to warn.

Why for example do courts often resort to negligence-like language even when addressing a design defect claim within a strict liability framework? Because design defect was never supposed to be rolled into strict liability. Design defect claims inevitably involve questions of was there a risk, was it a risk worth taking, was it foreseeable (ie an appreciable risk), and was there some feasible, risk-reducing alternative. Those after all are also the questions at the heart of the negligence inquiry.

And what must plaintiff show in a design defect to carry his burden of proving that the risk posed by the product outweighed its usefulness? Is it enough to show that what happened was foreseeable and that the resulting harm outweighed the cost to make the product safer? No. Doing so skips the vital question of what was the probability of the harm occurring in the first place. The foreseeability inquiry comes after the "how likely was it" question, not before.

Finally, are sophisticated user cases premised on the "no duty" argument that so many courts reject out of hand? No. There is a duty but [t]he purpose of the duty to warn is to inform the audience of a product's non-obvious risks. What risks are non-obvious depends on the audience - risks that may not be obvious to a layman may be obvious to the skilled professional. The sophisticated user doctrince is thus not an exception to the duty to warn, but an application of it."

The winch in question had been in use on the ship for 55 years and plaintiff had been working aboard her for several years when the accident occurred. Nevertheless he could point to no other accidents in which it, or even one of similar make on some other ship, had ever caused an injury. His only possible evidence of risk (with himself as the sole data point) was that it extremely small. And by testifying that he knew (from prior experience and training) that moving the switch on the winch control panel would cause it to begin the operation of a device used to moor with 7/8 inch steel cables a 767 foot freighter the plaintiff put himself in the category of persons for whom what followed was the opposite of "non-obvious". The winch-maker accordingly prevailed.

 

Tags:

Very Little Authority For Now, But Maybe Not For Long

Two yellow pads are full of notes, diagrams, thoughts and arguments and still the answer eludes me. So, rather than continue not to post anything about all the interesting stuff going on in mass torts while I try to figure it out I'll just throw out what I've got so far over a series of posts and move on to something less difficult (and likely more interesting). On then to the question that's been bugging me for a month.

Should alternative liability, in the form of burden of proof shifting, apply in the following case: (1) a neonate contracted a Cronobacter sakazakii infection and was seriously injured; (2)  C. sakazakii is a ubiquitous pathogen and readily forms biofilms on stainless steel, inside household water pipes and upon other surfaces (3) C. sakazakii infections in neonates have also been repeatedly traced to PIFs; (4) plaintiff's experts opined that it's more likely than not that the source of C. sakazakii was the powdered infant formula (PIF) fed to the neonate; (5) PIFs are not sterile since the process of sterilization would destroy the nutritional value of the PIF; (6)  there were two or more suppliers of PIF whose product was prepared for the neonate; (7) none of the remaining PIF fed to the newborn, nor any of the lots from which they were drawn, were found to contain C. sakazakii; and, (7) the wrong complained of was a failure to warn that full term neonates, like the plaintiff, were at risk of C. sakazakii infections.

Alternate liability analysis often begins with Summers v. TiceIn that case both hunters who had fired their weapons in plaintiff's direction had been sued and both could be shown to have breached their duty to safely handle those weapons. Because it was impossible for the plaintiff to show whose buckshot was responsible for his injury, and because it was deemed just that the consequence of that impossibility fall on the culpable defendants rather than the innocent and injured plaintiff, the court held that the defendants, rather than the plaintiff, should bear the burden of proving from which shotgun the pellets had originated. Fair enough.

Here, in Burks v. Abbott Laboratories, both of the manufacturers of PIF consumed by the plaintiff had also been sued. Furthermore, neither's product bore a warning about the hazard which plaintiff claimed they had a duty to disclose. However, not all the possible sources of C. sakazakii (Mother Nature being judgment-proof) were before the court. Nevertheless, the court held, though it "located very little authority on this specific question" that  the determination of whether it was more likely than not  that the source of plaintiff's C. sakazakii infection was the defendants' PIF should be applied to the defendants collectively.

Ponder the consequences. Let's say that 51% of all C. sakazakii infections in neonates are due to PIFs even when C. sakazakii can't be isolated from the product or the lot from which it was drawn, and that 49% of all C. sakazakii infections in neonates are due to C. sakazakii found in the household water used to reconstitute the PIF or on kitchen surfaces. Also, assume the warning could fairly be said to be lacking (which in this case is not at all a given and in fact raises as many questions as stacking defendants to get to the 51% threshold - but that'll be addressed in subsequent posts).

If there's only one supplier of PIF there's no need for alternative liability so assume there are at least two. But what happens when you start dividing up the 51% among the defendants? Unless one of them was responsible for ~99% of the product the result is that you've stacked two defendants who might, but probably didn't, have something to do with plaintiff's infection and handed them all of the liability for it. Is that fair? What if there were 100 suppliers? And what's the justification for stacking defendants? Is it because they're in the same business? If so, how similar must their businesses be to permit such stacking? If in order to get to a 51% likelihood as to the source of the infection you had to stack PIF manufacturers with stainless steel kitchen appliance manufacturers (because C. sakazakii happily lives on stainless steel and creates biofilms that makes it nearly impossible to remove with household cleaning products) could you justify handing them the burden of proof by saying they were all in the food business? 

Or what about reducing defendants' liability by Mother Nature's share? Would that solve the "overdeterrence" problem? What follows from the fact that the potential for these sorts of infections, due to the nature of pathogens, is essentially binary (you get it or you don't) and not of the dose-response variety seen in typical mass tort cases?  These are the sorts of questions that have led to a lot of head scratching but so far few answers.Over the next couple of days I'll type up more of these questions and the paths down which they lead (at least the ones I've thought of and followed).

How a fact pattern like the one in Burks gets resolved is I think a very big deal. That's because an awful lot of diseases laid over the last forty years at the feet of man-made substances and bad habits turn out to have been due to pathogens all along. It also appears we're entering an era in which old scourges reemerge thanks to having evolved antibiotic resistance and new ones arise thanks to globalization.  The resulting morbidity and mortality will makesevery other mass tort pale in comparison and so far juries aren't having much trouble blaming defendants for the depredations of Mother Nature's tiniest critters. We think there's a wave of litigation coming in which plaintiffs will assert liability for facilitating the transmission of pathogenic agents. The answers to questions like those posed by Burks will be critical in determining how it all plays out. 

Discretizations

The Annual Report to the Nation on the Status of Cancer (covering 1979 - 2009) is out. The good news is that overall death rates for some of the biggest killers continues to decline. The bad news is that deaths from cancers caused by infectious agents like HPV and hepatitis-C are up; doubling in some cases. Get your daughters, and sons, vaccinated.

It took several decades but the egg has now been cleared on the charges of murder by heart attack and stroke.

It also took decades to clear caffeinated coffee on all charges of murder by cancer. Now drinking 4+ cups per day has been shown to cut your risk of some cancers by half.

Many common food ingredients have been scientifically demonstrated to double or halve, and often double and halve, your risk of cancer. Click here to find out why.

The human breast milk microbiome is far more diverse than previously imagined and it's composition is impacted by factors such as obesity and Cesarean delivery. Could it be that her microbes, rather than a mother's genes, are to blame for her obese children? Could it be that it's the absence of certain breast microbes in mothers who underwent Cesarean delivery that's responsible for the increased risk of asthma in their children?

In the past, proponents of the Precautionary Principle have tended to deny that hormesis exists. As the evidence in favor of hormesis has gotten harder to ignore their narrative has changed to (1) it hasn't been shown to be the sort of general phenomenon that would permit an inference of hormesis for all toxins and (2) too little is known about the mechanism to permit its incorporation in to risk models.

Causation is Hard: Multiverse Edition

While we wait to critique Steve Gold's upcoming defense of Milward v. Acuity (the paper is available at SSRN but, alas, it's flagged as a work in progress, neither to be quoted nor cited) we'll have a go at his new paper on causation titled "When Certainty Dissolves Into Probability: A Legal Vision of Toxic Tort Causation for the Post-Genomic Era".

It takes twenty eight pages to get to the meat of the paper and upon arrival, despite some serious disputes with his take on causality, we were pleased when we finally made it (for awhile at least).  That's because it read as though Gold seemingly endorsed the same sort of approach to causal apportionment that we've been advocating here (and elsewhere) for years. Consider his suggestion:

I propose that courts should adopt an expressly probabilistic view of causation when the dominating evidence comprises population-based data of toxic effect. To frame the standard, an exposure should be considered a cause of disease if it was a contributing factor to the disease's occurrence. To be a contributing factor, an exposure would be shown by a preponderance of the evidence - not limited to any single favored type of evidence - to have added incremental risk that the plaintiff would develop a disease that the plaintiff has, in fact, developed. Damages should be apportioned to that contributing factor in proportion to its contribution to the plaintiff's risk.

Thereafter he even goes on to state that de minimis contributions to risk ought not be actionable. So what's not to like? Well, lots, actually. And it begins with a fundamental misunderstanding about "but for" causation.

Gold begins with the claim that "but for" (i.e. counterfactual) causal reasoning somehow doesn't work in toxic tort cases. He writes, "[p]roof of toxic tort claims conform poorly to the traditional deterministic legal model of but-for causation, because toxic injuries almost never involve an easily observed chain of physical events connecting a particular defendant's conduct with a particular plaintiff's harm." Gold's worry is that biomarkers, sequenced genes and the data from molecular epidemiology have delivered only more causal complexity rather than the allegedly promised "deterministic" certainty necessary for old-fashioned legal reasoning. So if "but for" causal thinking doesn't lead to the right legal solution, what does?

After pondering the conclusion that necessarily follows from the realization that e.g. cancer is the consequence of genes + epigenetic regulation + socioeconomic status + gender + microbiota + environmental exposures + unknown unknowns + bad luck (i.e. stochastic processes) Gold thinks he's fallen down the rabbit hole and met Schrodinger's cat and it's both alive and dead all at once. Confusing the uncertainty (which is to say ignorance) described by the statistics used in population studies with quantum indeterminancy, Gold declares that the real problem is one of "scientific indeterminacy". By this he seems to think that because the precise chain of events leading to disease is not only unknown but ultimately unknowable, and because randomness may lie literally at the root of the universe, it is therefore impossible to say that "but for" a particular exposure plaintiff would not have developed her illness.

That's bad enough because we know it's not the wave function that killed Schrodinger's cat . It was the decaying atom; and every time the atom decays the cat must surely die. But it gets worse.

Gold then suggests that the answer is not to live with the uncertainty - i.e. to make our best judgment about whether a gene or exposure or whatever was more likely than not a cause such that the disease would otherwise not have arisen, determine the risk it posed ex ante, and then apportion liability among those non-de minimis tortious risks ex post. Instead he suggests we throw every black box risk factor that passes his lowered Milward v. Acuity test of so-called general causation out for the jury's consideration, bad genes included and then let the them apportion liability among all risk factors, tortious and otherwise. He's thus changed the formula from Liability = Duty + Breach + Causation + Harm, to Liability = Duty + Breach + Risk + Any-disease-that-has-ever-been-associated-with-that-risk-even-if-it-probably-wasn't-causative-in-this-case.

In part II tomorrow we'll explain why such a formulation would vastly expand the number of defendants swept up into toxic tort litigation and why his belief that even with a tiny risk "someone somewhere" is ultimately harmed is true only if A) risk factors mean something beyond how likely it is we're wrong about our causal inferences; and, B)  there's a whole lot more universes out there besides our own.

How A Charity Exploits Innumeracy

Before I get to the substance of the post I want to apologize for the dearth of postings of late. I was in Corpus Christi trying a bank case (go figure). I lost. It's been awhile since a jury branded me with the scarlet "L"; and it still feels like a punch in the gut. Anyway ...

For years we've been harping on risk, Bayes' Rule, our collective blind spot for base rates and mass confusion about the proper use, interpretation and limits, of percentages. So when we saw "How A Charity Oversells Mammography" in British Medical Journal taking on Susan G. Komen for the Cure for exploiting our cognitive weaknesses we knew instantly that it was blogworthy.

We've previously addressed the issue of why mammography leads to so many false positives but what's really interesting about the BMJ article is its take down of the following fallacy: early detection leads to a much greater chance of winning the "five year survival rate" award - the most common metric for assessing outcomes in cancer cases.

The problem is that mammography often doesn't make a difference even when it does accurately detect breast cancer. First, we all come with an expiration date. For some people the cause of expiration will be cancer because sadly for many cancers, including some breast cancers, there is no cure. Now let's say that in 2011 someone was diagnosed with a form of breast cancer that was refractory to treatment and that person died in 2012. She clearly didn't make it 5 years. But what if, thanks to mammography, she'd been diagnosed with the breast cancer in 2006 and then had succumbed to it in 2012? She'd be just as dead but would get counted as a success story.

Second, some cancers grow very slowly, some never grow at all and some even go away on their own. Thus, when mammography detects a breast cancer that was never going to be the cause of the patient's death anyway that patient gets counted as a mammography success even though her cancer had no effect on her expiration date.

Saying that mammography screening saves lives is true only because the way we count lives saved is so deeply flawed.

 

Tags:

Discretizations

The Best Causation Opinion of 2012

In fact, it may well be the best causation opinion of the last half century; and we're willing to bet it will be one of the most important causation opinions going forward. Dixon v. Ford Motor Company nails substantial factor causation and in the process proves that there are still plenty of judges willing to think deeply about causal inference, about uncertainty and about the limits of liability in a world of inevitable risk. Ultimately, the court held that risk is the measure of legal causation in those cases where causal inferences are made probabilistically, and therefore when a causation expert opines that a putative cause was a "substantial factor" without saying how much risk it imparted she fails to answer the question she was called to give; and so has nothing helpful to say about the matter.

Dixon is another tragic mesothelioma case in which a defendant, having contributed to the victim's cumulative asbestos exposure something between nothing and next to nothing, was hammered by the jury. It then appealed, after taking a few judicial deductions, a $3+ million judgment. As usual the defendant complained that plaintiff's causation expert (this time an epidemiologist) ought not to have been allowed to testify because she had "extrapolated downward" from the known segment of the asbestos/mesothelioma dose/response curve to an area in which hard data was lacking and thus could not reliably say that the defendant's small contribution to the victim's dose was a substantial causative factor. 1) That's not plaintiffs' game these days, as we said in Small Glasses; but more importantly, 2) as the court made plain in Dixon, "substantial factor" in such cases isn't about causation, it's about risk.

"'Substantiality' is a legal concept and not an objective property testable by the scientific method", wrote the Dixon court. The question thus required to get at the essence of substantial factor causation in a dose/response disease case is not "was it a big cause or a little cause?" It's not even "was it really and truly a cause?" The first question is nonsensical and the second is unanswerable. Instead, the question is: "assuming it was a cause, was the risk it imparted prospectively of such a degree as to justly warrant the imposition of liability?" Risk, said the court, is thereby the measure of (legal) causation and proving that the risk imparted was substantial is plaintiff's burden. Showing that defendant imparted a substantial degree of risk, according to the Dixon court, is thereby what is required to bridge the "analytical gap" between "asbestos causes mesothelioma" and "plaintiff's exposure to defendant's asbestos caused her mesothelioma".

Accordingly, the court held that when all plaintiff's causation expert could say about causation was that "every exposure to asbestos is a substantial contributing cause" the only thing she wound up saying about the risk given plaintiff by Ford was that it was "more than nothing." "For obvious reasons an infinitesimal change in risk cannot suffice to maintain a cause of action in tort". Thus, the opinion of plaintiff's expert "merely implied that there was some non-zero probability that [plaintiff] was exposed to asbestos from Ford's product, and that this resulted in some non-zero increase in her risk of contracting mesothelioma. As such, [the conclusion of plaintiff's expert] that the risk and probability of causation was 'substantial' provided the jury with nothing more than her subjective opinion of 'responsibility,' not scientific evidence of causation."

So how does a plaintiff establish a substantial risk? Not by proving the exact dose and thus exact risk incurred.The Dixon court disposed of the straw man argument that requiring plaintiff to show risk (and thereby dose) quantitatively demands an impossible degree of certainty and precision. Such a rule, wrote the court, would obviously be "folly". Rather, all plaintiff is being asked to do is to "estimate exposure and risk with reasonable scientific or medical certainty." Once such an estimate is made the jury can decide whether it is sound and if so whether the risk imparted was substantial - subject to the law's requirement that it be more than de minimis.

That's exactly what we've been arguing since a client was kind enough to let us write an amicus in Borg-Warner v. Flores. Make the plaintiff say what dose, and thereby what risk, was given. Why? The effect of plaintiff's estimate of dose in one of the first post-Borg-Warner cases should suffice for an answer. Using their expert's dose estimate the calculated risk of death posed by our client's product was demonstrated to have been less than 1 in six billion; that's equivalent to the risk of death (from cancer caused by radon) imparted by spending just fifteen minutes in a building constructed of brick or stone. Such calculations and comparative risk exercises serve to vividly demonstrate both the de minimis nature of the risks imparted and the absurdity of imposing liability for them.

The Burden of Occupational Cancer in Britain

Would you like to read a great summary of all the newest and best data on occupational cancer risks? Would you like to know what percentage of cancer deaths would not have occurred but for occupational exposures? Would you like to see which risks cause the most deaths? If so, read this month's British Journal of Cancer and its special supplement "Occupational Cancer in Britain" (100% open access).

Here are some highlights:

Occupational cancers are responsible for far more deaths than workplace accidents. Overall about 5.3% of all cancer deaths nationwide can be attributed to work.

Exposures are down but lots of people are still exposed to levels of carcinogens estimated to increase risk. For some forms of cancer, e.g. lung, the web of workplace risk is extraordinarily complex.

Among women a surprising number of cancer deaths are attributable to things you might not think of as occupational exposures (e.g. breast cancer due to night shift work).

The GI cancer burden is low (especially for vinyl chloride and TCE); painters seem to be most at risk.

Blood cancer deaths due to occupational exposures to benzene, butadiene, etc. are very low (note the latency period JKH).

Blame wood dust before formaldehyde when considering nasopharyngeal cancers.

Asbestos, silica, diesel engine exhaust and mineral oils (untreated/mildly treated) rank 1, 2, 3 and 4 respectively for occupational respiratory cancers.

Skin cancer deaths due to occupation are rare and sunlight causes more of them than mineral oils and PAHs combined.

For urinary tract cancers mineral oils and diesel engine exhaust top the list.

Dioxin and non-arsenical insecticides combined are estimated to have caused fewer than two dozen deaths from brain, bone, soft tissue and thyroid cancers.

As you might suspect, construction, mining and manufacturing is estimated to produce the vast majority of occupational cancer deaths.

Bottom line: excess cancer deaths divided by exposure (risk) times estimated exposure =  occupational cancer deaths. Nothing earthshaking. Just a sort of accounting. Nevertheless, the estimated attributable fraction of deaths due to occupational exposures drawn from the calculation is certainly sobering. If the risks in the U.S. are similar to those in Britain our deaths from occupational cancers approach 40,000 annually.

h/t LKD

 

Tags:

Joe Schreiber Has An Article In The Oil & Gas Journal About What We've Learned In Our Benzene Frac-Fluid Litigation

See: Frac-Fluid Recipes Threaten To Become Pressure Points In Benzene Litigation

Tags:

Discretizations

Small Glasses

The Betz v. Pneumo Abex commentary has generally sounded the following themes:

(a) The "novelty" threshold requirement for a Frye hearing has a broader meaning than previously thought. Henceforth, "a Frye hearing is warranted when a trial judge has articulable grounds to believe that an expert witness has not applied accepted scientific methodology in a conventional fashion in reaching his or her conclusion."

(b) The trial judge, who "was unable to discern a coherent methodology supporting the notion that every single fiber from among, potentially, millions is substantially causative of disease", did not abuse his discretion by excluding the "every fiber" causal theory of Dr. Maddox.

(c) Maddox' opinion that "every fiber was a substantial factor in causing plaintiff's mesothelioma" is riven by an "irreconcilable conflict with itself" because "one cannot simultaneously maintain that a single fiber among millions is substantially causative, while also conceding that a disease is dose responsive."

(d) Maddox reached his conclusion about causation not by his claimed "series of 'small bridges'" but rather by improperly extrapolating from known portions of the asbestos/mesothelioma dose-response curve to find causation at much lower levels - levels never demonstrated by epidemiological studies to be associated with the disease.

We're glad, of course, that the court found that novelty doesn't wear off expert opinions (i.e. they don't become immune to scrutiny under Frye) just because they've been peddled to many juries for many years. And we're similarly pleased so see shot down the untestable/unverifiable/unfalsifiable claim that a single fiber not only might have caused, but was in fact a substantial cause, of a given case of mesothelioma. But we're afraid the court missed the subtle game Maddox was really playing.

He wasn't extrapolating down. He wasn't playing the one-hit, linear no-threshold, conflate causation with risk game (though he does in other jurisdictions). And his causal model can account for both a single fiber being a necessary cause of a given plaintiff's mesothelioma and a correlation between dose and disease without any tension. Best of all, it's perfect for exploiting jurisdictions with naive liability attribution schemes such as Pennsylvania's at the time Maddox's opinion was rendered (Pennsylvania finally overhauled its joint and several liability scheme in 2011).

To understand what's up think about the following opinions of Maddox:

1) "it is the total and cumulative exposure that should be considered for causation purposes."

2) "Cumulative exposure, on a probability basis, should thus be considered the main criterion for the attribution of a substantial contribution by asbestos to lung cancer risk."

and,

3) "[T]he more common analogy that has been used is the example of a glass of water. One drops marbles into the glass of water until the water finally overflows from the glass. Is it the first marble or the last marble that causes the glass to overflow? Well, both, all of them. The marbles cause the glass to overflow. That's a cumulative effect."

So it's clearly not a one-hit model that he's proposing; and for good reason. As more and more courts have become savvy about risk it's been harder and harder for plaintiffs to survive the objection that a de minimis exposure presents a de minimis risk and thus cannot by necessity be a "substantial factor". That's what the Pennsylvania Supreme Court was getting at in Betz when it wondered how "if all Dr. Maddox could say is that a risk attaches to a single asbestos fiber - that he could also say that such risk is substantial when the test plaintiffs may have been (and likely were) exposed to millions of other fibers from other sources including background exposure."

The point is made explicitly a few pages later when the court refers back to its discussion in Gregg about the plaintiff's proof problem in such cases:

"... we do not believe that it is a viable solution to indulge in a fiction that each and every exposure to asbestos, no matter how minimal in relation to other exposures, implicates a fact issue concerning substantial-factor causation in every "direct-evidence" case. The result, in our view, is to subject defendants to full joint-and-several liability for injuries and fatalities in the absence of any reasonably developed scientific reasoning that would support the conclusion that the product sold by the defendant was a substantial factor in causing the harm."

So what sort of model makes each asbestos fiber a substantial factor in causing mesothelioma and yet is consistent with a dose-response relationship between asbestos and mesothelioma? It's something we're seeing more and more often. It's the idea that each person has, to apply Maddox' metaphor from above, her or his own unique water glass of a defense mechanism. Some people's defense capacities are bigger and some are smaller and some are microscopic. But whatever the size, once they're overwhelmed mesothelioma or leukemia or whatever ensue. Thus, when Maddox says that every fiber to which plaintiff was exposed contributed to his risk and "once an individual develops a mesothelioma, the risk becomes the cause" what he's really saying is that though some marbles dropped in the glass might be bigger than others (e.g. crocidolite > amosite > chrysotile) and some might have been added with thimbles while others with coal shovels the only thing that really matters is whether or not the body's defenses were breached. Once they are the glass overflows, the mesothelioma develops and every last fiber was literally a necessary "but for" cause of the disease.

So what does the dose-response curve for asbestos and mesothelioma actually represent in such a model? It describes the outcomes of varying abilities to withstand asbestos across varying levels of exposure to asbestos. A lower defense capacity (small glass) requires less asbestos to trigger mesothelioma; higher defenses require more, etc. Think of the data points on the curve then as small glasses that have overflowed. What such a model suggests is a human population that mostly has large glasses {which fits the observation that even the most heavily exposed workers have less than a 1 in 10 chance of developing mesothelioma); a small portion has small glasses; and a tiny portion have smaller glasses still - all the way down until you get to those rare but unlucky souls who have no defense whatsoever. For them the background exposure dose doesn't increase their risk since it's already 1.

It's an especially clever model for for litigation because:

a) every fiber is a necessary element of a sufficient causal set (NESS) so causation is a snap;

b) it escapes the no duty problem posed by de minimis exposures in states that view substantial factor causation from a risk/foreseeability perspective;

c) it turns modern victims into eggshell plaintiffs and so makes every case that much more foreseeable; and,

d) because it's a Landers v. East Texas Salt Water Disposal Co sort of cumulative causal claim it's especially dangerous in states with joint and several liability schemes.

The problem is that there's no evidence for the model. It rests solely on the following two generalizations (that do little more than highlight our ignorance of the mechanisms whereby asbestos causes mesothelioma) and the conclusion drawn from them:

Mesothelioma is caused by exposure to asbestos fibers

A victim's asbestos exposure consists of every fiber inhaled

Therefore, a victim's mesothelioma was caused by every asbestos fiber inhaled

As for the equally evidence-free small glasses theory it goes like this:

Not everyone exposed to asbestos develops mesothelioma

But every victim's mesothelioma was caused by her or his asbestos exposure

And every victim has had a different asbestos exposure

Therefore something about the victim (small glasses) determines the outcome of exposure

If you haven't seen it yet it's surely on its way to a courtroom near you. Our advice? Attack the premises - they're made of clouds.

 

 

 

 

Discretizations

5-Methylene-1,3-Cyclopentadiene

I thought of fulvene, also known as 5-methylene-1,3-cyclopentadiene, when I read the following in a new law review article (funded, strangely enough, by a National Science Foundation grant):

Tort actions may impel industry to take voluntary steps to redesign chemical molecules ... to be less toxic.

Fulvene you see is made up of six carbon and six hydrogen atoms. So is benzene and so are a few other molecules. The point of course is that while you might be able to rearrange a car's component parts to make it somehow safer while leaving it a car you can't rearrange benzene's atoms (or those of any other complex molecule for that matter) without turning benzene into something else. Something with a different boiling point, solubility, reactivity and the like. Something that cannot, as benzene can, be used to make the breast cancer drug tamoxifen.

The law review article is "Litigating Toxic Risks Ahead of Regulation: Biomonitoring Science in the Courtroom" and it dovetails with "How Chemicals Affect Us" which you've likely seen in the NYTimes. Each claims that very low levels of exposure to substances previously thought safe may be causing subtle changes and each ends with a call for regulation; the former by way of lowering evidentiary standards in tort proceedings so as to bring about more claims and bigger awards and the latter by way of the regulatory state. Irrespective of wielder the same tool is urged: one that resolves all uncertainties in favor of stasis, of inaction, i.e. the Precautionary Principle.

"Litigating Toxic Risks", funded under a $366,785 research grant for "Toxic Ignorance and the New Right-to-Know: The Implications of Biomonitoring for Regulatory Science", proceeds from the hypothesis that "toxic tort litigation has emerged as a means of controlling risks." It recounts 1) the number of chemicals that have never been tested for toxicity (tens of thousands); 2) the non-stop synthesis of new ones; 3) the purported shortcomings of TSCA; 4) the fact that asbestos and lead paint are made of chemicals and turned out to adversely affect some of those exposed; 5) the apparently obvious conclusion "it follows that many of today's routine chemical exposures are cause for great health concern"; and, finally, 6) the ability of biomonitoring to demonstrate those chemicals to which we've been exposed. The authors then deduce that the effort to regulate chemicals via toxic tort litigation "depends greatly on whether courts are able to apply tort theories to the scientific data used in appraising the health risks of chemicals".

They lament, however, that there's no cause of action for simply being exposed to the activities of other people; that plaintiffs must show harm - an adverse health effect - before they can prevail. Regarding those chemicals to which everyone is exposed in low doses they complain that it's not practical for plaintiffs to do epidemiological studies since there is (unsurprisingly) no unexposed reference population. Furthermore, the cost and time involved in doing epi and tox studies are significant. So, if standards of proof could just be lowered the class action mechanism would expose potential defendants to existential liability risks for harms they probably didn't cause (see pg. 6) so that vast sums could be extracted from them and the production of synthetic chemicals would be thereby curtailed or eliminated.

Additional helpful measures would include dropping the requirement that class members demonstrate that they have actually been exposed to the substance in question. As support for this assertion the authors write "[t]he courts' current stance contradicts standard scientific procedure, where it is well recognized that sampling can lead to reliable assumptions about population characteristics". (Really? A calculated sample mean is superior to knowledge of the actual population mean for making conclusions about the population? And superior to even knowing the actual exposure of each member of the population?)

To make sure that as many people as possible can assert medical monitoring claims the article's authors urge "implementation of the precautionary principle in the legal standards required to show significant exposure and increased risk of disease". The precautionary principle apparently will turn every "is it likely" hurdle to plaintiffs' recovery into an "is it possible" speed bump.

As for damages "courts can accept, as legally actionable injuries, subtle health and developmental impacts as well as emotional concern and stress related to chemical exposure."

So far some 50 million different chemical substances have been cataloged and 12,000 new ones are added every day. Most were synthesized by nature rather than by man. Over the eons our ancestors managed to survive in this sea of chemicals, surrounded and inhabited by countless biochemical factories constantly synthesizing new molecules in order to survive in and/or exploit their ever-changing environment - and our ancestors largely did it by synthesizing their own new molecules. We've only had trouble when we've been out-engineered by our biochemical competitors or when we've violated the rule: "all things in moderation". So what's with the chemohysteria over trace exposures and the discovery that our bodies notice and adapt to them on the fly?

I think a large part of it stems from the fact that we've come to realize our genetic code is more toolbox than blueprint; that we're far more impermanent than we ever imagined; and, that so much of what we believed about how it all works, especially decades old myths about the principal causes of human diseases, is being swept away by remorseless empiricism. The attempt to incorporate the Precautionary Principle into the law can thus be seen as part of a deeply conservative movement, standing athwart science, yelling Stop!

 

 

 

Discretizations

Bending the Dose Response Curve

The linear no-threshold model of dose-response meant that plaintiffs could continue to prevail on toxic tort claims even though their exposures had occurred in the modern era and thus were tiny fractions of those that led to epidemics in years past. Either courts permitted plaintiffs to rely on a one molecule / one particle theory of causation (consistent with the view that some risk is associated with a single molecule or particle) or they allowed plaintiffs to conflate causation with risk.

Eventually some courts began to grasp the absurdity that follows from basing proximate cause on a "one-hit" model in a world of trillions of hits while others began to take notice of the fact that despite probing larger and larger populations with low exposures epidemiology was unable to verify the linear no-threshold model for numerous diseases; thereby suggesting that there is indeed a threshold for diseases including leukemia (a new case making the latter point is Schultz v. Glidden Company.) Meanwhile we have argued that the old cases got it right - that causation in an individual toxic tort case is unfathomable and that the most sensible approach is to estimate the risk imparted (e.g. by a single molecule); to ask why it makes sense to impose liability for creating a 1:1,000,000,000,000,000,000 chance of harm; and, further asking why it wouldn't make sense to impose liability for a 1:100,000 or greater risk.

But all of that assumes risk goes to zero or at least continues to decrease as exposure is reduced below previously measured levels. If that assumption is false, if risk starts heading back up as exposure goes down, especially if unpredictably so, then all bets are off. We will have entered another period of great uncertainty, And it's in such times that toxic tort claims flourish. The horsemen of this new age of uncertainty have published a review paper on the topic and if you want to understand what's coming, why it's pitch perfect for the health and wellness movement and why what happened to BPA will be repeated again and again for other chemicals until some new way is established to either verify or refute their claim that dose doesn't make the poison you need to read it:  "Hormones and Endocrine-Disrupting Chemicals: Low-Dose Effects and Nonmonotonic Dose Responses"

Discretizations

When it comes to lung cancer, keep your chickens close but keep your flock closer.

"They've internalized their own confusion": watch this video if you want to understand the difference between humble falsificationist evidence-based science and the authoritarian "because I say so" approach adopted by the 1st Circuit in Milward.

Antibiotic use in children less than six months old is strongly associated with the subsequent development of asthma, especially in those without a family history of asthma, and the greater the intake of antibiotics the greater the odds of developing asthma.

Attacks on randomized controlled trials (RCTs) miss the point.

A new paradigm for cancer prevention, indeed.

 

Duty, Palsgraf, The Hand Rule and Public Interest: This Take Home Case Has It All

 

IN RE ASBESTOS LITIGATION, JANINE McCOY and MARVIN McCOY Limited to: PolyVision Corp., Superior Court of Delaware, New Castle County

Turning, ultimately, on the peril of limitless liability the Delaware court in McCoy reasoned that Pennsylvania, which has yet to weigh in on the issue, would not find a duty to the spouse of an employee allegedly grievously injured as a result of being exposed to asbestos dust carried home on her husband's work clothes.

First, on the issue of foreseeability, Palsgraf made an appearance (just long enough to introduce the relationship test of the limits of duty) but it merely cancelled out other opinions taking a limitless view of foreseeability. Next up was the Hand Rule comparing the expected value (loss) of an injury to the cost of prevention. Noting that extending duty to a spouse would necessarily imply extending a duty to everyone her husband might foreseeably have come in contact with the court found the burden of prevention sought to be imposed too high. Finally canvassing the states neighboring Pennsylvania, those likely to follow similar precedents and reasoning, the court found that 4 out of 5 refused to extend duty from employee to spouse.

And so the court came to the right answer though, as we keep saying, quantitative risk assessment as a proxy for substantial factor analysis reaches the same conclusion but in, we think, a cleaner and more predictable fashion.

 

 

Tags: ,

Discretizations

Plaintiffs' Experts Call for Research on the Health Effects of Fracing; looking for a link to disease

There is a hearing today in front of the House Energy and Environment Subcommittee, of the Committee on Science, Space and Technology. The subcommittee is studying the draft report by the EPA on the effects of unconventional natural gas drilling in and around Pavilion, Wyoming which found some groundwater contamination, particularly from gas drilling wells which were not cased to a depth below the bottom of nearby water wells.

Bernie Goldstein, MD, a frequent paid expert on behalf of plaintiffs in benzene litigation has released the outline of his testimony. He calls repeatedly for money from congress to prospectively study the health impacts of unconventional shale gas drilling, commonly known as hydraulic fracturing or fracing.

While no health effects have currently been found to result from fracing, Dr. Goldstein implores Congress to study not just whether fracing fluids are somehow getting in the water or air (which is currently being studied) and is a necessary precursor to eventual disease caused by fracing. Instead, Dr. Goldstein seems to want to study all of the chemicals used in fracing fluids (as well as noise, truck exhaust, and anything else that goes on at a well site) and see if any can cause disease, if they are released in the water, air, or some other way. He cites community groups who are worried about the potential harm as evidence that there is a potential harm. His stated major concern is that “It is possible that unconventional gas drilling will cause index cases of unusual diseases over time given how little we know about the health implications of the fracking mixtures.” It is possible, but not shown because as of now, there is neither a signature disease of fracing fluids or an established mode of exposure.

Dr. Goldstein’s real conclusion is that it is a virtual certainty that adverse health effects will be statistically associated with unconventional gas development activities. This may be because statistics can be found to support almost any association if the data are parsed to fit the conclusion sought.

The plaintiffs’ attorneys are clearly gunning to make fracing the next toxic tort.

Tags:

"Does It Matter Whether One Risk Is Of A Minor Adversity To Many People While Another Is A Major Impact On A Few?"

Let's face it, the linear no-threshold argument has nothing to do with logic, nor even public health (though everything to do with redistributionist politics). For the politics-free argument that it carries the seeds of its own demise see:

"By looking only at one dimension at a time – one agent to which more or less exposure can occur and one endpoint affected by it – it is possible to think that one is being protective by assuming a linear/no-threshold dose-response. But if this idea is widely applied, then the world is cast as sitting on a multidimensional knife’s edge in which any change in one dimension affects everything else with no level of tolerance."

That's a profoundly good sentence.

Tags:

Hydraulic Fracturing (a/k/a fracing a/k/a fracking) Roundup

Yesterday our energy partners reported on the EPA's claim of water contamination in Wyoming due to hydraulic fracturing fluids used in natural gas production. Today The New York Times is wondering whether earthquakes can be blamed on fracing. Thus it sounds like a good time to provide you some links to recent studies of the process that you may find of interest. Here goes:

Scientific American has the truth about "fracking" and thinks that engineering science has gotten ahead of safety

The comment period for New York's Supplemental Generic Environmental Impact Statement just ended and some public health advocates don't like it

Two miles underground amidst the shale and gas, where the pressures and temperatures are extreme lives a fascinating community

And some of its members traveled there via drilling muds

Finally, some public health advocates and journals tend to overlook one important aspect of the energy business - that it provides lots of high paying jobs and benefits from free laundry service to transportation to health care and often excellent pension benefits; not to mention an interesting and disciplined work environment - a big boost to socioeconomic status which bestows dramatic economic, physical and even mental health benefits that echo through succeeding generations. So let's not forget when balancing risks and benefits of fracing to add the profound public health benefits that flow from good jobs to the benefit side of the ledger.

What To Do When a Miracle Drug Is Found to be The Cause of a Host of Unexpected Maladies?

There's an epidemic of immune disorders in America.  Allergies (especially food allergies), asthma, atopy, hypersensitivity disorders including Stevens Johnson Syndrome, Crohn's disease, type1 diabetes, obesity and more are being laid at the feet of perinatal use of antibiotics.  Evidence is mounting rapidly that the use of antibiotics in newborns or their mothers disrupts the intestinal microbiota essential to a well-functioning immune system. The consequences are seen in the host of immune-related disorders which have become perhaps the most significant cause of morbidity and mortality in the United States today.  For a new primer try: Perinatal Programming of Asthma: The Role of Gut Microbiota.

So what should we make of a drug that when first administered saved a young woman, allowing her to have a family and to live to 90* and yet which (because the role that gut bacteria play in generating a healthy immune system was decades away from being known) would eventually precipitate a wave of autoimmune disease in the United States?  If antibiotics are indeed responsible for as many cases of debilitating illness as is now widely suspected, should we ban them and vilify their makers?  Should their makers be driven to ruin by our tort system to ensure that nothing like penicillin is ever unleashed on the public again?  Or should we instead finally recognize that we must take the good with the bad;  that with every advance comes risk; and, that unintended consequences, the nature and extent of which may not be known for years to come, is the price of progress?

* The First American Civilian Saved by Penicillin

The first U.S. civilian whose life was saved by penicillin died in June 1999 at the age of 90 years. In March 1942, a 33-year-old woman was hospitalized for a month with a life-threatening streptococcal infection at a New Haven, Connecticut, hospital. She was delirious, and her temperature reached almost 107 F (41.6 C). Treatments with sulfa drugs, blood transfusions, and surgery had no effect.

As a last resort, her doctors injected her with a tiny amount of an obscure experimental drug called penicillin. Her hospital chart, now at the Smithsonian Institution, indicates a sharp overnight drop in temperature; by the next day she was no longer delirious. She survived to marry, raise a family, and meet Sir Alexander Fleming, the scientist who discovered penicillin. In 1945, Fleming was awarded the Nobel Prize in Physiology and Medicine, along with Ernst Chain and Howard Florey, who helped develop penicillin into a widely available medical product.
 

Discretizations

The Sixth Circuit (almost) Gets Substantial Factor Causation

In Moeller v. Garlock Sealing Technologies, LLC the 6th Circuit held that while the decedent's exposure to the defendant's gaskets "may have contributed to his mesothelioma, the record simply does not support an inference that it was a substantial cause of his mesothelioma. Given that the Plaintiff failed to quantify [decedent's] exposure to asbestos from [Defendant's gaskets] and that the Plaintiff concedes that [decedent] sustained massive exposure to asbestos from [other] sources, there is simply insufficient evidence to infer that [Defendant's] gaskets probably, as opposed to possibly, were a substantial cause of [decedent's] mesothelioma... On the basis of this record, saying that exposure to [Defendant's] gaskets was a substantial cause of [decedent's] mesothelioma would be akin to saying that one who pours a bucket of water into the ocean has substantially contributed to the ocean's volume. Cf. Gregg. v V-J Auto Parts, Col, 943 A.2d 216, 223 (Pa. 2007)."

So what's the problem? The problem is that the court is not asking whether the exposure in question created a substantial risk - one that may have been (though we'll never know because there were other possible sufficient causes) the cause of plaintiff's injury. No, the court is asking whether the exposure was likely to have been the "actual cause" of plaintiff's injury. That's made clear when the court writes: "Substantial causation refers to the probable cause, as opposed to a possible cause". Thus, it's not an inquiry as to the conduct (i.e. did Defendant produce more than a de minimis risk) but rather an inquiry as to the amount of the exposure to Defendant's product relative to other exposures.

For defendants then, who increasingly face a litigation environment in which their product contributed a bucket of water into an ocean the size of a bathtub, a few more victories like Moeller v. Garlock threaten to utterly undo them.

Hat tip Nina Webb-Lawton

Bostic: Baron & Budd Swings For The Fences

As we've discussed previously, the Dallas Court of Appeals in Bostic made it logically impossible for a plaintiff injured as the result of multiple potentially causative exposures to recover from any of those responsible for the exposures. They did so by holding that a plaintiff must not only show that the aggregate dose was the "but for" cause of his injury, but also that each defendant's component dose was the "but for" cause of his injury. Thus, if plaintiff were exposed to two doses, each sufficient to have caused his injury, both defendants could argue with equal force under a "but for" standard "had my product never existed plaintiff would still have been injured because of the other guy's product and so my product cannot possibly have been the 'but for' cause of plaintiff's injury".

The source of the problem seems to originate in confusion over what the Texas Supreme Court means by "substantial factor", We've been arguing since our amicus in Borg-Warner that the essence of every court's discussion of foreseeability or proximate cause is risk. Since, as the National Academies put it in Science and Decisions, "[v]irtually every aspect of life involves risk", what courts have been doing is drawing boundaries between those risks for which the imposition of liability would be just and those for which the imposition of liability would be unjust. Substantial factor then means substantial risk and in toxic tort cases risk is measured by exposure, or dose. A plaintiff need only show that "but for" his exposure to asbestos (in the aggregate) he would not have developed mesothelioma but if he's to carry his burden of showing substantial factor causation he must estimate dose for each defendant's contribution to the overall dose. And that's what we thought Borg-Warner said.

Bostic argues in her brief however that any requirement that a plaintiff show what the dose received from an individual defendants product or premises was likely to have been would make it "scientifically impossible" for any plaintiff to prevail. She says that her expert Dr. Longo testified "that it would be scientifically impossible for him to calculate the precise dose of asbestos" that Bostic experienced as a result of his use of Georgia-Pacific's products. Of course Borg-Warner specifically says that a plaintiff is not required to state with mathematical precision the dose-contribution of each defendant. A supportable approximation is good enough. Bostic further implies that coming up with even an approximation of dose is impossible. Is it?

In 1995 Harvey Checkoway wrote: "Quantitative estimation of exposure has become a central focus in occupational epidemiology over the past decade as a result of the increasing emphasis put on exposure-response characterisation for occupational hazards." He concluded by writing: "Methods of assessment of exposure have been given much more attention in recent years. As a result, increasingly sophisticated approaches to retrospective assessment have been developed ... Nevertheless, no amount of foresight and prospective monitoring will replace the need for sound approaches to retrospective estimation of exposure, and the variety of methods now available provide a basis for that work." Not only have such methods been available to expert witnesses for years their use in benzene and other toxic tort litigation is nowadays utterly unexceptional.  

Of course a supportable retrospective dose estimation is possible and it's done all the time. The attempt to substitute Dr. Longo's estimation of the highest dose from a one time use of Georgia-Pacific's product for Bostic's estimated total dose from its product is akin to substituting the amount of tar and other particulate generated by one cigarette for a plaintiff's pack-years of smoking - it evades the real question of "what was the risk?" and answers instead another question "was there any risk?" It's an effort to conflate risk and causation and so, without saying so, to get the Texas Supreme Court to adopt the Restatement (Third) of Torts and its attempt to substitute any risk for a substantial risk as the outer boundary of liability. Should they prevail they'll have knocked the cover off the ball.

 

Discretizations

A risk-based tax on rubber duckies?

Tumors are superorganisms.

Kentucky adopts the economic loss rule. (An especially well written opinion btw).

To be injured, you have to be injured. (Wis Ct of Appeals: another well-reasoned opinion worth reading)

Roggli shows that brake repair workers got their meso from commercial amphiboles.

The Attempted "Reshapement" of Toxic Torts

Building up to the publication of the Restatement (Third) of Torts and now reaching what must surely be a crescendo has come one law review article after another assailing various courts' (re)adoption of the Enlightenment's view of causation and their (re)embrace of empiricism. Last Friday for example we posted a link to a recent paper making the case that loose causation standards (as opposed to those of "classical liberalism") in toxic tort cases are vital to the consolidation and empowerment of "the administrative state". And a couple of days before that we wrote about another new article that attempts to provide intellectual support for the proposition that the consequence of courts' application of strict causation standards has been to tip the scales in favor of defendants. Today we'll address an assertion from the second article.

On page 107 author Gold makes the following claim: "To the extent courts treat general and specific causation as separate elements requiring distinct proof, plaintiffs who already confront scientific uncertainty may be required to jump two hurdles instead of one - increasing the likelihood of false negative adjudications on causation." What he's done is to confuse what happens when we estimate the probability of the conjunction of two events (here: e.g. the likelihood that tetra-methyl death (TMD) can cause prostate cancer and the likelihood that plaintiff's prostate cancer was actually caused by TMD) with the manner in which false positives and negatives are identified and the manner in which the odds of being false negative or false positive are estimated. A simple illustration will hopefully suffice.

On chromosome 19, carried by both men and women, is a gene, KLK3, a variant of which is highly correlated with prostate cancer. There's a test for prostate cancer that looks for the KLK3 variant. Since both men and women carry the gene what happens to the number of false negatives (the KLK3 test shows they don't have the variant but later they're found to have prostate cancer after all) and false positives (the test says they have it but they really don't) if a general causation "hurdle" like "can women even get prostate cancer?" is placed before the KLK3 test? The number of false negatives is unchanged (good) and the number of false positives is cut in half (great).

What we suspect Gold is trying to complain about is the following: If we're 51% sure that TMD is a cause of toe cancer and 51% sure that of the possible causes of plaintiff's toe cancer TMD was actually the cause of it then across the set of toe cancer plaintiffs there will be some who recover nothing because of the extreme uncertainty in the science. But that's really just proof that the law is far too lenient towards plaintiffs in toxic tort cases.

What are the odds that our hypothetical toe cancer plaintiff actually got his toe cancer from TMD? Only 26.01% (51% x 51%) - hardly "more likely than not". Yet every court in the country will let a toxic tort plaintiff stack uncertainty upon uncertainty, "more likely than not" upon "more likely than not" to get to a cumulative "more likely than not" in spite of the fact that mathematically that ain't how it works. Furthermore, given the fact that courts will allow plaintiffs to establish both general and specific causation with a single study demonstrating a relative risk (RR) of 2.0 and given the fact that most published research findings with low (less than 4-ish) RRs are false anyway the odds that our toe cancer plaintiff waving his toe cancer - TMD peer reviewed paper actually got his cancer from TMD is no more than 13% (51% x 51% x 51%) and likely much lower - yet he'll get to a jury, meaning he'll be offered a settlement, in every courthouse in the land.

At the end of the day the "Reshapement" of toxic torts won't increase the odds of truly wronged plaintiffs being compensated but it will, where adopted, swamp unfavored companies with meritless claims - perhaps that's the whole point of it.

 

 

Risk, Duty and Foreseeability

The Restatement (Third) of Torts shrivels duty into an if-then statement executable by even obsolete jurists: if an actor's conduct creates a risk of physical harm then he owes a duty to exercise reasonable care.

Duty supposedly needed a new and simple algorithm because opinions turning on the question of duty were seen as incoherent and generally the result of a court having invaded the province of the fact finder (jury, hereafter). Foreseeability, the reporters decided, isn't the sort of legal or policy question judges decide - it's fact and case specific and thus something lay people relying upon common sense and communal norms of behavior ought to decide.

So that judges need not be completely replaced by computers the Restatement's reporters added that in exceptional cases a court may find that due to some other explicitly stated policy a defendant may not owe a duty. Furthermore, a court may on rare occasions properly find that reasonable people could not conclude that an outcome was foreseeable and so hold that the duty auto-generated by the new formulation had not been breached. Very simple indeed. But how's it working out?

If Nebraska (an early adopter of the Restatement's new duty formulation) is any indication the answer is "same results; different justification". Does a landlord who allows a renter to keep a pit bull owe a duty to a third party bitten by the dog? Sure; but it wasn't foreseeable so defendant wins. See Monica S. v. Nguyen. Does the owner of a road grader that can only be turned off while it's still in gear owe a duty to a mechanic called to fix it who twice accidentally bumps the ignition button causing it to start up and run over him? Sure; but it wasn't foreseeable so defendant wins. See Riggs v. Nickel.

What's going on? Look at the gold disk in my graphic. It contains all the acts, however remote, that created the risk of an injury that came to pass (e.g. the risk the road grader owner's great grandmother created by having his grandfather). American courts have pretty much uniformly taken the position that whatever risk the jury is to focus on should not be too remote. Whether because they recognized that "security is mostly a superstition" or that "a man sits as many risks as he runs" courts have in the past made essentially policy decisions to the effect that only a subset of all risks, those that aren't insubstantial, may be subjected to a foreseeability analysis. It's only for that subset of substantial risks that an actor assumes a duty and only for those risks that a jury may find to have been foreseeable that he can be made liable. Now in Nebraska (and Iowa) courts are finding a duty for every risk but then holding that whatever risks they would have formerly found to have been insubstantial are instead simply unforeseeable.

Rather than deciding the limits of tort liability those courts that have adopted the Third Restatement's concept of duty are instead engaged in the business of deciding the limits of human foresight. Hardly sensible and no improvement over the old rule: "you're under no duty to do the impossible i.e. guard against every 1-in-a-million risk you create". Oh well, at least it's frustrating what I suspect was the real purpose of the new duty formulation - to backdoor the Precautionary Principle into the law of torts.

Prevnar and ActHIB: Here We Go, Again

Post hoc, ergo propter hoc. There'd be far fewer toxic tort claims if it weren't for that little logical fallacy which informs so many opinions.

Today there's word from Japan that the use of Prevnar and ActHIB has been suspended following the deaths of four children who died after immunization against bacterial meningitis and pneumonia. Though the vaccines came from separate lots indicating that contamination was not an issue and despite the fact that pneumonia and bacterial meningitis are dreadful diseases the news prompted the usual outpouring of vaccine denunciations.

Here in Houston the news produced claims that (a) the autism-derived and fact-free belief that children get too many shots or that they're given "too close together" means lazy doctors are to blame; (b) vaccines lower I.Q. and cause a 700% increase in cancer; (c) the U.S. Supreme Court has put us at the mercy of drug companies so that "you give those vaccines to your children at their peril"; and, (d) there's a dark conspiracy, in which the media is complicit, to bury stories about the harmful effects of vaccinations. See them all at "The MomHouston Blog".

You may not know people like these but they show up on your juries. Ignore them at your peril.

What is Cancer?

In toxic tort cases plaintiffs' attorneys and their experts tend to rely on one of two theories about the cause of cancer. The first is the "one-hit" model in which a single mutagenic molecule, particle or fiber causes DNA damage leading to a malignant cell that self-replicates uncontrollably. The second theory imagines that the damage leading to the malignancy is the result, somehow (the hypothesis is never set out in any great detail) of the cumulative effect of exposure to many molecules, particles or fibers. They say "it's like a glass of water that finally overflows when one last drop is added, each drop in the glass was a necessary cause of the overflow."

The one-hit theory is rolled out in low dose cases involving from one to a handful of exposure sources. Here the idea is that carcinogenesis is like playing the skull and crossbones lottery. The more tickets you buy (i.e. exposures you encounter) the more likely you are to wind up with the losing ticket. "All it takes is one bullet and they shot trillions of bullets at my client".

The cumulative dose theory is deployed when there are many sources of exposure and where those responsible for the biggest portion of the exposures are bankrupt or have already settled.  Here the idea is that once the individual's defenses are overtopped a malignant clone is born (initiation) or conditions for propelling the spread of an existing malignant clone are created (promotion). The most odious example of this argument was directed, despite my objection, against a client in an asbestos trial in state court in Galveston  - "It takes several men to have a lynching. One to hold the man, one to get the horse; one to get the rope, etc. They (meaning my client) want you to believe that each and every man in the lynch mob must go free just because the act of each man alone would not have resulted in my client's death. I know that's wrong and you know that's wrong!"

Either way, whether it's a matter of each cell playing the cancer lottery one molecule at a time or of  each cell slowly filling over the years it's carcinogenic reservoir you'd think that the more cells you have in your body the more likely you'd be to hit the losing ticket or see a chemoprotective dam collapse. Even for cancers thought to be caused by mishaps during normal cell division you'd think that if you had a lot more cells you'd have a lot more opportunity for mishaps.

But you'd think wrong. People don't get cancer more often than mice and neither do whales - even though they (obviously) have a lot more cells and also live long enough to have them and their progeny divide many many more times. See  "The Mere Existence of Whales" and "Why Don't All Whales Have Cancer? A Novel Hypothesis Resolving Peto's Paradox". Hat tip Marginal Revolution.

So what's going on? Do bigger organisms have better cancer defenses? Does size confer some advantage as suggested by the hypertumor hypothesis? 

Maybe it's the underlying deterministic model that needs tweaking. Maybe cancer rates scale up with physical size because cancer is a system, or a subystem, rather than a simple switch, Indeed there's a growing body of literature showing a tight association between reproductive optimization, energy availability, aging and cancer. Maybe the 30% cancer rate seen across mammalian species represents an evolutionarily determined risk-of-cancer/benefit-of-plasticity ratio that holds true from mice to whales.

If so, that would mean that we're programmed to run a high risk of cancer.  Not exactly the "cancer is a man-made problem" meme in which labor, environmentalists and their lawyers found a common purpose and a common tool.

Reruns of The NORM Show

Yesterday the NYTimes published "Regulation Is Lax for Water From Gas Wells". It's the result of nine months of work and the review of 30,000 pages of documents, some of which were "leaked" by government insiders. The reporters' conclusion is that the gas exploration industry is inadequately regulated and that as a result people are at risk thanks mainly to radium (the biggest concern due to NORM, naturally occurring radioactive material) and to a lesser extent benzene from recovered drilling fluids being run through local waste treatment facilities.

The benzene levels were absurdly low (yes, it's a carcinogen and so is the sun but we're not vampires who burst into flames when exposed to the sun nor are we life forms that can do without the benzene ring). Meanwhile, the radon levels downstream of the waste plants were, well, undocumented. But that doesn't matter apparently because there were some data on the amount of NORM, recovered in fluids returned to the surface from gas wells, and some of the readings were up to 1,500 times higher than the permissible levels for drinking water. Thus, be afraid. Be very afraid because the waste is run through water treatment plants and so contaminates the water of those downriver who drink it.

But that's where the irony comes in. What's already one of the biggest sources of NORM (or TENORM, technologically enhanced radioactive material - i.e. concentrated NORM)? Drinking water treatment plants. According to EPA, thanks to regular old water wells 700 hundred treatment facilities produce lots of NORM already. Undoubtedly people on private well water, one flush at a time, have been producing NORM all by themselves and have been doing so since long before horizontal drilling and hydraulic fracking were invented (we're all frackers, actually).

According to the EPA's site on NORM from well water (Drinking Water Treatment Wastes) the amount of radionuclides in water treatment residue can vary by an order of six magnitudes. In all some 260,000 metric tons of TENORM are generated every year by U.S. water treatment plants. For a detailed overview of the issue see "A Regulators' Guide to the Management of Radioactive Residuals from Drinking Water Treatment Technologies".

So you see uranium has been decomposing into radon and dissolving into well water quite naturally and without causing alarm for as long as there have been wells producing water for humans.

Some other day I'll post funnies from the West Texas yellow cake litigation (teaser: "you mean there's uranium in the ground, around here?!" but for now I suggest you have a look at the Natural Gas Drilling Tip Line documents in the NYTimes article. There are lots of scared, lonely, confused and paranoid people out there (e.g. "Caller is the Wife of Jesus Christ and Billy Idol (the rock singer) is in fact Jesus Christ. Caller is thus co-owner of the earth and she is upset over the Marcellus Shale drilling..." What's more interesting are all the tips/calls from the media; several of which the NYTimes redacted extensively. It's obvious that the media is trying to fan the flames by provoking the sorts of people prone to be provoked. The question is, why?

Tags:

Cherry Picking on My Cherry Coke

Today's scare du jour was just launched by the Center for Science in the Public Interest. They claim that the caramel coloring in Coke (and in dark beer and lots of other good stuff) is carcinogenic and ought to be banned. See "FDA Urged to Prohibit Carcinogenic 'Caramel Coloring'".

The claim can be summed up as follows: industrial caramel is unnatural and the product of scary-sounding processes involving scary-sounding chemicals; one of the resulting constitutive chemicals, 4-methylimidazole, has been found "in significant levels" of five brands of cola; 4-methylimidazole causes cancer in lab rodents; therefore, my Cherry Coke is a cancer hazard. Is there anything to it?

Well, sure enough there's a study of lab rats and mice that found small increases in the risk of lung cancer and leukemia that increased as doses (the rodents got the equivalent of thousands of cans of cola per day worth of 4-methylimidazole) increased. See "Toxicity and Carcinogenicity Studies of 4-Methylimidazole in F344/N Rats and B6C3F1 Mice". But something else very interesting happened along the way to a good health scare - something not mentioned by the CSPI.

It turns out that while there were small and at best equivocal indications that 4-methylimidazole might be associated with one or two rodent cancers there were big, statistically significant and dose-dependent associations between cancer prevention and 4-methylimidazole consumption. For example, compared to the rodents not given 4-methylimidazole the female rodents drinking cola by the barrel were essentially completely protected from mammary tumors as well as a host of other cancers. Overall, rodents on a cola binge experienced a greatly reduced risk of many cancers and saw some tumor rates reduced by orders of magnitudes compared to their cousin rats and mice not given 4-methylimidazole.

There was no call for research into the protective effects of caramel coloring. The great big silver lining wasn't even disclosed. Instead, the two insignificant bits of data showing a small risk of tumors in rodents were cherry picked from the forest of data and the big effect, a cancer-protective effect, was completely ignored.

I'll go out on a limb and predict that this scare, like the CSPI acrylamide in bread, chips and roasted coffee is going to give everybody cancer scare, is also headed for the dustbin of history.

 

The Man Who Didn't Fall

On the matter of negligence in personal injury cases the first draft of the Restatement (Third) of Torts eliminated the element of duty altogether. After an uproar the authors eviscerated duty and stuck back in what was left. Ultimately, while they failed to restate the law as it pertains to duty they did manage to restate the era of unjustified fears and risk aversion that has persisted since about the time the Restatement (Second) was published.

The Restatement (Third) takes the position that case law as well as scholarship pertaining to duty is largely incoherent. The essence of the claim is that limits to liability couched in terms of relationships or foreseeability are nothing but ad hoc justifications for taking the real question, whether defendant breached a duty of reasonable care owed to society, out of the hands of the jury where it belongs. Thus, dismissing as insupportable judicial inquiries about the connectedness of plaintiff and defendant (the relational approach) as well as those as to the proximity of cause and effect (proximate cause), the Restatement (Third) of Torts, Liability for Physical and Emotional Harm Section 7(a) reads "[a]n actor ordinarily has a duty to exercise reasonable care when the actor's conduct creates a risk of physical harm." It goes on to add that save in "exceptional cases" judges "need not concern themselves with the existence or content of this ordinary duty." In other words, once it has been established that a defendant created a risk the court's work regarding duty is finished and the question of whether defendant's conduct was reasonable is exclusively for the jury to decide.

That's a very long way from either position taken in  Palsgraf v. The Long Island Railroad Company . On one side Chief Justice Cardozo for the majority wrote "[t]he risk reasonably to be perceived defines the duty to be obeyed, and risk imparts relation; it is risk to another or to others within the range of apprehension". On the other Justice Andrews dissented writing both that "[e]very one owes to the world at large the duty of refraining from those acts that may unreasonably threaten the safety of others" and yet that "there is one limitation (on liability). The damages must be so connected with the negligence that the latter may be said to be the proximate cause of the former." He continues "[w]hat we do mean by the word "proximate" is, that because of convenience, of public policy, of a rough sense of justice, the law arbitrarily declines to trace a series of events beyond a certain point."

Cardozo marks the boundary of liability by a circle of close if fleeting relationships while Andrews bounds it within a circle of causes that are close to the injury producing event. Whether measured by the remoteness of the relationship or of the cause from effect both sides agreed that there was a limit to the duty of reasonableness even when a risk has been created. It's that idea of a limit on the duty of reasonableness that was cut out of duty in the Restatement (Third). Consequently foreseeability, the catchall for the various efforts to limit the scope of the duty of reasonable care, is said to have been purged from duty.

The objection that the collection of limitations on the duty of reasonable care (whether Cardozo's or Andrews' or the many iterations based on foreseeability) is incoherent is based, I suspect, on an understandable misunderstanding of what these jurists are trying to say. What I think they've been trying to say is that risk is an inevitable part of life and that some risks are so small that liability isn't warranted even if an injury should follow their creation.

But foreseeability doesn't sound much like risk. Isn't it about predicting the future; about foretelling future events based on what's already known? Yes, but that ex ante calculation of the effects that likely follow causes is what risk is all about.

But why limit liability by the degree of risk? And if a boundary is drawn how can it be done other than arbitrarily? Isn't it better that we follow the Precautionary Principle? Aren't we Addicted to Risk? Wouldn't the world be a better place if we quit taking risks?

To answer those questions let's go back to the railroad guards who created the risk that caused Ms Palsgraf's injury. As a train began to leave the station two men ran to catch it. One safely boarded but the other, "carrying a package, jumped aboard the car, but seemed unsteady as if about to fall. A guard on the car, who had held the door open, reached forward to help him in, and another guard on the platform pushed him from behind. In this act, the package was dislodged, and fell upon the rails." What might the future have looked like had the guards taken the time to consider all of the possibilities that might follow from their effort to keep the man from falling? What might the future have held for him assuming gravity acted upon him as it did upon his package? And what about the rest of us, if inaction were the only way for our fellow citizens to avoid being hauled into court?

For several decades now the merchants of fear have been telling us that everything we thought was progress is instead the cause of human suffering. Vaccines? Autism or worse. Electricity?  Electromagnetic fields, migraines, MS, cancer. Internal combustion engines? Global warming, pm2.5, etc. Plastics? Endocrine disruption, heart attacks, cancer. Pesticides (e.g. DDT) and herbicides? Sterility, cognitive deficits, cancer, overpopulation. Cars? Runaway acceleration, rollovers, fireballs. Computers? ADHD, too many choices, too little control. Shouldn't we have waited until all the kinks were worked out before acting? Click on the vaccines link in this paragraph and also consider the price of fear of regret as expressed by Benjamin Franklin.

It is, I'm afraid, a duty to stop and not act until you've considered all the possible consequences of every action, however improbable, that the Restatement (Third) ultimately embraces. It is an embrace of the Precautionary Principle - an embrace therefore of a political viewpoint; not a restatement of the law regarding duty.

When you think of foreseeability as risk you see what the law really has to say about the duty of reasonable care and the analysis of any claim that it was breached. What it truly says is that the court, taking an ex ante perspective, is to decide whether the risk created was one for which, if found unreasonable and causative by a jury, liability may fairly be imposed. Thereafter, for any act amenable to liability, it's for the jury to express their community's tolerance for risk. Risk, or foreseeability, is thus sensibly in two places. First in the law where the limits of liability are drawn and thereafter with the fact finder who considers the reasonableness of the conduct given the context in which the various factors played out. 

Is there some bright line that can be drawn? Not always though we're certainly arguing down here that in cases where good quantitative risk assessment is available it can be. For example, in one case involving a minute exposure to a carcinogen we can take the plaintiff expert's epidemiology studies and show that the exposure his industrial hygienist calculated produced, at most, a 1 in 13 million risk of death. Compared to other known risks you're much more likely to slip and fatally hit your head on the toilet than to die from the exposure of which plaintiff complains. Our argument is that it make sense then to have the law, i.e. the court, set some reasonable outer limit on liability - perhaps at the 1 in 1 million level. Otherwise we either open up toilet makers and everyone else to ruinous liability for creating risks running towards the impossible end of the spectrum or we without any sound reason decide that some one in a million risks of death are fine while others aren't.

Unsurprisingly it didn't take long for the simplicity and predictability arguments advanced in support of the new and hollow version of risk to run off the rails. Consider Feld v. Borkowski. Iowa's supreme court eagerly adopted the new conception of duty in 2009  (see Thompson v. Kaczinski) only to start tortuously creating exceptions to it less than a year later. (Slow pitch softball is a contact sport? Who knew? By the way, with all due deference to the Creighton coach I suspect angular momentum and early application of torque rather than recklessness answers the question). Rather than clarifying duty I'm afraid the Restatement (Third) has only created a risk of even more obscure and incoherent formulations of exceptions so as to avoid the consequences of duty without limit.

Anyway, whatever the facts and whatever the content of duty courts will in the end have to recognize the wisdom of another famous American, Henry David Thoreau, who wrote "A man sits as many risks as he runs." And that "if a man is alive, there is always a danger that he may die ..." It's exactly that essence of the inevitability of risk that the courts, if not the Restatement (Third), have been trying to express when they talk about duty.

 

 

 

Population Mixing, Childhood Leukemia, Viruses and Vaccines

There's good epidemiological evidence that population mixing is responsible for several clusters of childhood leukemia (acute lymphocytic leukemia, or ALL). Some have hypothesized that viruses are to blame but there hasn't been much evidence to support that hypothesis; at least not until now.

In the current Journal of Pediatrics you'll find "Associations Between Vaccination and Childhood Cancers in Texas Regions" which compares the risk of ALL to vaccination rates in different public health regions. With all the caveats that must go along with hypotheses generated by statistical analysis it is nevertheless quite intriguing to see that children vaccinated against a wide range of viruses had a large and consistent reduction in their risk of ALL; so much so that it leading the researchers to conclude that "[s]ome common childhood vaccines appear to be protective against ALL at the population level."

Be sure to also note that 4 doses of diptheria-tetanus-pertussis, 3 doses of polio, 1 dose of measles-mumps-rubella, 3 doses of H. influenza, type B, 3 doses of hepatitis B and one dose of Varicella, the 4-3-1-3-3 vaccine regimen claimed by some anti-vaccine activists to be capable of "overloading young immune systems" and thereby (some-unstated-how) causing autism, produced a 38% decrease in the risk of a child developing leukemia.

Hopefully the anti-vaccine crowd is paying attention. The list of harms to children for which they may be made to answer is apparently growing.

El Dorado's Lost City of Uranium and Good Health?

In epidemiology, whenever lower incidence and lower rates of mortality from cancer occurs in a population commonly assumed to be at risk cognitive dissonance is always lurking. What generally happens is that the good news is shrugged off as "the healthy worker effect" and epidemiologists resolve to re-sift the data in order "to get the right answers". The "right answers" of course are often only those that support our preconceptions.

That means there aren't many people willing to even consider the possibility that working in a chemical plant or going off to war or spending a career mining / processing uranium while being exposed to low levels of gamma radiation might actually confer a health benefit. Nevertheless, the so-called healthy worker effect (which is called the healthy warrior effect for those who served in the armed forces) appears so commonly and across so many trades that you have to wonder if something besides simply screening employees for good health is at work. If you're interested here are three studies worth pondering.

In this month's journal of Occupational Medicine you'll find an excellent discussion in "The Healthy Worker Effect in US Chemical Industry Workers". The study was of thousands of Dow Chemical employees - three million years worth of employment combined. The overall risk of death from any cause was lower than expected as was the risk of dying from nine types of cancer thought to be related to smoking. Nevertheless the authors, an epidemiological team working for the Dow Chemical Company, concluded that the findings were likely due to the healthy worker effect though with a caveat. Some have suggested that the healthy worker effect arises because employers dismiss employees with health problems. However, in this study the health outcomes of those employed for a decade or more were the same as those who didn't last very long with the company. The finding thus suggests that the presumed healthy worker effect was generated as each employee was considered for employment such that workers destined to get cancer decades later somehow were never hired in the first place making it in fact a "healthy hire effect".

For another example see "Psychiatric Diagnoses in Historic and Contemporary Military Cohorts: Combat Deployment and the Healthy Warrior Effect". Despite some claims in the media that might make one assume otherwise those who serve in the military see lower than expected numbers of ailments including psychological ones. Here the suggestion is that those prone to psychological illness  are screened out as what risk there was of developing psychological issues after combat was concentrated in those with preexisting mental health issues.

Finally, published last month in the journal Radiation Research, there's "Mortality (1950 - 1999) and Cancer Incidence (1969 - 1999) in the Cohort of Eldorado Uranium Workers". With the exception of lung cancer incidence and mortality which demonstrated a small increase in risk, the Eldorado uranium miners managed to have significantly lower risks of dying from any cause, lower risks of dying from all cancers combined (lung cancer included) and a lower risk of developing any type of cancer cumulatively (lung cancer again included).

Now be honest. If someone had asked you yesterday whether you'd pick (A) uranium workers, or (B) the average Canadian male, as the group likely to have a much larger risk of getting cancer and of dying of cancer which would you have chosen?

So what's at work here? Is it simply that those prone to developing cancer in the distant future are somehow weeded out and never hired in the first place? Or does it perhaps have something to do with the nature of blue collar employment over the last 50 years? To me it all looks a lot like the compliance effect - the phenomenon whereby e.g. those who lead very ordered and structured lives and who thus always take their placebo at the appointed time manage not only to do better than those less disciplined and also on a placebo but oftentimes better even than those less disciplined but at least irregularly taking real medication. So I'll go out on a limb and guess that the claims of toxic tort plaintiffs notwithstanding, large employers engaged in manufacturing not only didn't shorten the lives of their workers they lengthened them by imposing the very order and rigidity about which so many bitterly complain in their depositions.

Nulliparous Plaintiffs, Fault and Causation

It has been known for a couple of decades now that women who never have children (i.e. women who are nulliparous) and women who do have children but not until they are 30 or older suffer a striking increase in their risk of developing breast cancer. The evidence for the association between never giving birth or delaying having a child continues to accumulate and now it appears that the increased risk is focused on hornmone receptor-positive breast cancers. See "Associations of Breast Cancer Risk Factors With Tumor Subtypes: A Pooled Analysis From the Breast Cancer Association Consortium Studies" in the current issue of the Journal of the National Cancer Institute. So let's say you've got a nulliparous plaintiff alleging that your drug or device or chemical caused or accelerated her hormone receptor-positive breast cancer; how do you handle her status?

The first problem a defendant faces in such a case is the risk of inadvertently wandering into the minefield called "blaming the victim". The plaintiff has either freely made a choice or has tragically been unable to have a child. Either way the jury will react strongly and negatively to any discussion about parity status and causation that makes even the slightest trespass into the issue of fault. Keep the discussion limited to risk factors and their relative potency. But that leads to another problem.

In some of the jurisdictions in which I practice plaintiff's counsel will successfully argue to the trial court that only evidence about about the actual cause of plaintiff's injury is admissible. In other words, unless my expert is prepared to say e.g. that "to a reasonable degree of medical probability plaintiff's breast cancer was caused by her not having children when she was young" testimony about "mere risks" is irrelevant and so inadmissible. The practical effect of such a ruling is that only junk science is admissible on the issue of the actual cause of plaintiff's cancer since my experts tend to be modest about the claims science can make regarding the cause of any individual's cancer. We're stuck then trying to prove a negative, showing we acted reasonably and preserving error.

In this age in which much that was certain (e.g. that we've conquered infectious diseases) is proving not to be so it's time I think for courts to recognize not only that the reasonableness of actions can fairly and effectively be judged according to the risks they conferred but also that causation is in many cases most precisely weighed when competing risks are allowed to be compared against one another.

Finally, and hopefully still on topic, for more evidence of the complexity of causation see "Does Pregnancy Provide Vaccine-Like Protection Against Rheumatoid Arthritis?" Why would pregnancy protect against auto-immune disorders and what's the connection with breast cancer? There are a variety of hypotheses offered but so far no one knows.

 

Wealthy and Healthy

Wealth strongly and consistently correlates with good health and an overall reduced mortality risk. A new paper summarizing past research and presenting new data which confirms the link has just been published in the American Journal of Epidemiology. It's titled "Long-Term Effects of Wealth on Mortality and Self-rated Health Status". The study focused on self-reported perceptions of health status and the results mirrored those of the objective measure for mortality: socioeconomic status is a good predictor of health status.

Why do the least wealthy (aka the poor) tend to be the least healthy? Those pushing the cause of so-called environmental justice claim that the poor, who unsurprisingly live in the cheapest and thus least pristine areas, are exposed to toxic chemicals, electro-magnetic fields and ionizing radiation at levels far higher than the rich (who tend not to build their mansions next to refineries) and that such exposures are to blame. Others, the "real food" activists, claim that the poor live in a junk food environment and, the W.I.C. program notwithstanding, have not the means to come by nutritious food. Still others claim that the poor suffer from inadequate health care. There is though another reason the poor might be so afflicted. It was best stated by a now deceased safety man who spent his career with one of the oil companies in Port Arthur, TX as follows: "Poor folks got poor ways."

We were at the deposition of a retired refinery worker who was suffering from leukemia and who was giving a deposition before he passed away to be used by his wife in a subsequent gross negligence case against his and the safety man's employer. The deponent was asked by plaintiff's counsel, "If you'd have known about the dangers these chemicals like benzene posed would you have come to work for xxxx Oil Company?" The man, obviously prep'd for the question answered "No way. I'd 'a stayed in the piney woods loggin' like my daddy done. It might not 'a paid as much but I wouldn't 'a got this cancer". The safety man leaned over and said "Yeah, and he'd have died of cirrhosis at 48 just like his daddy done."

That old safety man went on to explain that the men who came out of the woods, and the cane fields and off the pogy boats to work hourly at those refineries often signed their job applications with an "X" but they wound up solidly in the middle class and their children or grandchildren made it to college and beyond. "Some couldn't even write their name when they got here and nobody ever went back to bein' a gawddamned logger from the xxxx Oil Company."

The epidemiological studies of those refinery work forces have repeatedly found that overall the men lived significantly longer, were significantly healthier and had a lower risk of all cancers combined than similar men in the general U.S. population - despite exposures to asbestos, benzene, butadiene and the like. Compared to loggers, and boat crews and farm laborers the average refinery worker bought himself six more years of healthy life just by going to work for better pay in an environment where middle class values were the norm.   

More Evidence That Exposure to Poultry Viruses and Bacteria Causes Cancer in Humans

Significant increases in mortality risk for some forms of leukemia has again been identified in a cohort of poultry workers. See "Update of Cancer and Non-Cancer Mortality in the Missouri Poultry Cohort". Given the profound changes in the demographics of the poultry industry in recent years it would be interesting to see if population mixing might have been responsible for some or all of the increased risk.

What To Do About Too Many Calories for "Sedentary Young Children"?

The Center for Science in the Public Interest (CPSI) has sued McDonald's over their Happy Meals. The complaint argues that Happy Meals are "unhealthy" and cause obesity, that its marketing is "unfair" because it makes six year old lead plaintiff Maya pester her mother with her "clamor for Happy Meals" and that McDonald's seeks by way of its Happy Meals, like James Dean before it, "to subvert parental authority".

There is much in the complaint to blog about. Far too much actually given that I've got a brief due in the Texas Supreme Court by Friday. For now though consider the claim that Happy Meals provide too many calories for the typical, which is to say sedentary, child. When and how did the typical child get to be sedentary and so at risk of obesity? I'd argue that it has everything to do with turning schools into warehouses for children.

Want some evidence that even moderate exercise protects children from overeating or too much TV/video-gaming? See "Health Status and Behavior Among Middle-School Children in a Midwest Community: What are the Underpinnings of Childhood Obesity?" See also "The Fat-Mass and Obesity-Associated (FTO) Gene, Physical Activity, and Risk of Incident Cardiovascular Events in White Women". Apparently the "fat gene" only causes problems when combined with inactivity.

All in all it looks like the solution to childhood obesity is more about revving up the body's engine than starving it of fuel.

The Linear No-Threshold Theory: A Crumbling Foundation

The idea that a known cause of cancer, e.g. ionizing radiation, poses a risk of cancer at any dose, no matter how small, is a central thesis informing modern environmental and occupational regulations and modern, which is to say low dose, toxic tort cancer litigation. In the toxic tort context plaintiffs regularly employ the logical fallacy of the appeal to ignorance (argumentum ad ignorantiam) to prove that even the slightest exposure was risky. They say that because defendants cannot establish a safe level of exposure it follows that every exposure is necessarily unsafe. The formal name for the idea that risk doesn't drop to zero until exposure drops to zero is the linear no-threshold dose theory or LNT. The LNT theory, always longer on theory and politics than evidence is increasingly under attack. Now even NIOSH has had to concede that at least in some circumstances there is indeed a safe dose for a carcinogen.

In "Checking the Foundation: Recent Radiobiology and the Linear No-Threshold Theory" the author states "a large and rapidly growing body of radiobiological evidence indicates that cell and tissue level responses to [radiation damage], particularly at low doses and/or dose-rates, are nonlinear and may exhibit thresholds ... this evidence directly contradicts the assumptions upon which the microdosimetric [LNT] argument is based". The idea that a substance that is harmful at high levels can be harmless or better yet beneficial or protective (the idea of hormesis) at low levels is discussed at length in this month's issue of Human & Experimental Toxicology.

The claim that "if it takes an ounce to kill ten men then a drop will thousands" was itself just a theory based on the idea that carcinogenesis was a stochastic process. Getting cancer was sort of like hitting the anti-lottery and the more tickets you bought (exposures you sustained) the more likely you were to lose yet if you were unlucky enough just one ticket could do it. Like black box epidemiology LNT was simply a way to ignore the formerly incomprehensible molecular biological mechanisms responsible for cancer. Now that those mechanisms are being uncovered and understood they can no longer be ignored as they shatter one paradigm after another.

Baron & Budd Takes Georgia-Pacific v. Bostic to the Supreme Court of Texas

Georgia-Pacific v. Bostic, which prompted us to write The End of Toxic Tort Litigation in Texas? may be on its way to the Texas Supreme Court. Here's Baron & Budd's Petition For Review. Bostic is a mesothelioma case in which plaintiff prevailed at trial against a peripheral defendant but lost the claim on appeal when the Fifth Court of Appeals held that she had failed to prove that her decedent's exposure to that peripheral defendant's product was a "but for" cause of his fatal cancer.

Bostic's best argument is that the application of a "but for" standard of causation to a particular exposure by the appellate court makes it impossible for any toxic tort plaintiff whose illness was allegedly caused by one or more of several exposures to prevail. Here, plaintiffs get it exactly right. Whenever plaintiff's injury has been proved to have been caused "but for" a bullet (as in the "one hit" case of Summers v. Tice) or "but for" a sufficiently high concentration of salt (as in a cumulative injury as in Landers v. Texas Salt Water Disposal Co.), and where each actor's conduct was tortious, plaintiff is relieved of the logically impossible task of proving that each tortfeasor's conduct was a "but for" cause. The Texas Supreme Court has already made this point in in the asbestos context in  Borg-Warner v. Flores.

Baron & Budd gets it wrong however when they argue that (1) Borg-Warner only demands a Lohrmann-esque frequency, regularity and proximity exposure qualification in malignancy cases in general and in mesothelioma cases in particular; (2) that dose, and therefore risk, quantification is only required when the parties dispute what, in general, caused plaintiff's injury (e.g. it ought not be required when the parties agree that asbestos exposure was responsible for a plaintiff's mesothelioma); and, (3) that the standard for substantial factor causation somehow changes according to the facts of the case.

The whole point of Borg-Warner and the almost two decades of Texas Supreme Court cases that preceded it is to put the requirement for demonstrating wrongful, unreasonable conduct back into the state's law of torts. For Georgia-Pacific to have prevailed on appeal it should have been because its product posed at most a de minimis risk of mesothelioma,.not because plaintiff couldn't prove that its asbestos contributed to Bostic's cancer.  

If all your product poses is a vanishingly small risk of harm, in this a world of inevitable and uncountable risks, then you've acted neither unreasonably nor wrongfully and the substantial factor test, which is a combined query about causation and legal responsibility, will decide the matter and you'll not be deprived of your property. It's precisely because calculations of risk (the measure of the reasonable man and which are derived from estimates of dose) often show peripheral defendants to have acted neither wrongfully nor unreasonably that plaintiffs' counsel hate dose estimation.

Cell Phones and Brain Cancer: What Was The New York Times Thinking?

Recently the NYTimes published "Should You Be Snuggling With Your Cellphone?" in which it reported that the question of whether cell phones pose a risk of brain cancer is far from settled. Indeed, largely ignoring the overwhelming evidence that electromagnetic radiation does not increase the risk of brain cancer the article references an unidentified study showing an increased rate of brain cancer in the presumably cellphonophilic 20-29 year old age group, "400 scientific papers" that support the theory that radio waves cause "damaged brain DNA", and concludes with this quote by epidemiologist and author of the newly published "Disconnect" Devra Davis: "I do think I'm looking at an epidemic in slow motion". 

Google serves up a link to Environmental Health Trust which has front and center handy links to a "press kit", and variety of write-ups including (1) that the best evidence does support a causal link; (2) a warning to women to keep cell phones away from their chests as the radio waves "seep directly into soft fatty tissue" and may cause breast cancer; (3) heavy cell phone use decreases sperm count by 50%; (4) that we should be horrified by the sight of young children using iPhones as they are frying their young brains; (5) a conspiracy by industry and lobbyists to obfuscate the facts and prevent urgently needed anti-cell phone legislation; and, (6) the inevitable lawsuit by someone with an unidentified form of brain cancer who claims cell phones are as addictive as cigarettes and just as deadly - the evidence that cell phones caused his cancer seems to be limited to the fact that he was athletic, a non-drinker / non-smoker who led "an over-the-top healthy lifestyle".

Well, increasing risk of brain cancer in young adults, "damaged brain DNA", a corporate conspiracy and a plaintiff who talked on his phone four hours per day 365 days per year, how is this NOT the start of a massive mass tort? Here's how.

Let's take that troubling trend of increasing brain cancer in 20 - 29 year olds. Open up this month's journal of Neuro-Oncology and you'll find "Brain Cancer Incidence Trends in Relation to Cellular Telephone Use in the United States". Yes, there's small increase in incidence for males but the increase began "before cell phone use was highly prevalent". Yes there was an increase for women in that age group too but it was limited to frontal lobe cancers and since I've never seen a woman use her cell phone by holding it to her forehead I have to wonder if the absence of any increased risk in brain cancers near the ears isn't the most important finding of this huge study. And in fact its authors conclude "these incidence data do not provide support to the view that cellular phone use causes brain cancer". See also: "Mobil Phone Base Stations and Early Childhood Cancers: Case-Control Study" which found "no association between risk of early childhood cancers and estimates of the mother's exposure to mobile phone base stations during pregnancy" and, of course, "Brain Tumour Risk in Relation to Mobile Telephone Use: Results of the INTERPHONE International Case-Control Study" which showed that most cell phone users were if anything at a decreased risk of cancer.

Damaged brain DNA (whatever that is)? "Analysis of Proteome Response to the Mobile Phone Radiation in Two Types of Human Primary Endothelial Cells".

And the claim of industry bias or outright conspiracy to silence the truth or co-opt scientists? Try "Studies of Mobile Phone Use and Brain Tumor Risk Are Independent of Industry Influence".

Finally, brain cancer is always tragic, whether it strikes down a U.S. Senator or my next door neighbor at age 48; and their drinking, smoking and exercising status makes no difference as none are risk factors, positive or negative.

To this day the cause or causes of brain cancer remain unknown. All you can do is drink your coffee or tea and hope that one of life's deadly bolts out of the blue doesn't strike you.

New Voir Dire Question: Do You Own Shares in Any Lawsuit?

Mass tort litigation is big business. In the past, thanks to rules prohibiting fee sharing with non-lawyers, it was a big business in which only lawyers could participate. Not anymore; at least not if you're in private equity, a hedge fund or are a bank. All it takes is cash, high tolerance for risk and an appetite for big returns.

Today the NYTimes has an excellent (save for one common misperception) article on the subject: "Putting Money on Lawsuits, Investors Share in the Payouts".  My quibble is with the claim that the money pouring into investments in contingent fee recoveries "... is helping to ensure that cases are decided by merit rather than resources ". It's not true and hasn't been for decades; at least not for the big dogs and not for mass tort cases. They already (a) have bigger and faster jets than the companies they're suing; (b) own or control their own banks; (c) only have to focus their efforts in one jurisdiction; and, (d) can readily syndicate really big cases within a network of very business savvy lawyers. Those entrepreneurial lawyers who started all this vowed long ago never to be outspent and I've yet to see it happen.

Tags: ,

Risk Assessment From In Vitro Testing: Staggeringly Complex or Just Impossible?

In vitro testing has been proposed as a way to clear out the backlog of toxicity testing on thousands of chemicals currently in use. It's quicker and cheaper and lab animals needn't be "sacrificed". The plan is to use the results to estimate the dose response curve in humans so that regulatory agencies can regulate accordingly. Too bad it won't be that easy.

In this month's Environmental Health Perspectives, Kenny Crump et al discuss the daunting task of using data from in vitro testing to set reasonably safe exposure limits. See (free): "The Future Use of In Vitro Data in Risk Assessment to Set Human Exposure Standards".

The problem of course is that it's not a matter of exposing some cells in a petri dish to the chemical of interesting and watching what happens. There are multiple pathways and multiple feedback mechanisms involving multiple types of cells that define the pathways to toxicity, not to mention any that work to offset and fix the ill effects. How many might there be and in how many ways might they interact? A model of how E. coli protects against heat shock "consists of a set of 31 differential-algebraic equations with 27 kinetic parameters, data for many of which are not yet available." Just finding these pathways will be a huge undertaking and billions of dollars in funding are being sought over the next decade to find and elucidate them.

Nevertheless, the authors conclude: "Use of in vitro data in risk assessment has great promise toward allowing chemicals to be tested more quickly and cheaply and for reducing or eliminating the need for subjecting animals to toxic insults. It is our hope that the bar for accepting approaches based on in vitro data will not be set too high. In view of the numerous serious limitations of current approaches, results from these methods based on whole-animal data should not be held up as gold standards. This point is particularly important considering that almost all whole-animal data are obtained from high doses that may operate through different sets of [toxicity pathways] than do low doses."

That last sentence is the key. We're entering a whole new world of toxic torts. One in which many heretofore innocuous chemicals will be claimed to be toxic at very low doses.

Toxoplasma gondii: Sheep and Goats Have a Vaccine Against It. Why Don't We?

It''s becoming apparent that Toxoplasma gondii is responsible for an awful lot of human suffering around the world. The parasitic organism causes birth defects and spontaneous abortions, neurolgical impairment, eye damage and is increasingly suspected in Alzheimer's, schizophrenia and Parkinson's.

T. gondii infects human cells and reproduces within them eventually setting up shop in cysts throughout the central nervous system, heart, muscle, bone marrow and other organs. Persons infected are infected for life. Human infection is most commonly the result of consuming un-/under-cooked cyst-bearing meat though contact with the feces of animals, especially cats, T. gondii's ultimate host, are another avenue of exposure.

While 11% of Americans are infected with the parasite, that figure rises to as high as 70% in some South American countries. The European Food Safety Authority, worried that foodborne infection by T. gondii is on the rise and is responsible for significant yet underreported and undetected diseases within the EU, has recommended Toxoplasma monitoring of lifestock. Recent estimates of the impact of T. gondii-induced disease reveal it to be "one of the most significant causes of foodborne disease worldwide."

The good news is that thanks to demand from sheep and goat producers there's a vaccine that works well in sheep and goats. The problem is that it's a live cell preparation like the Sabin vaccine discussed during oral argument in Bruesewitz, et al v. Wyeth, Inc.,So what's the problem? The problem is that while it works really well, much better than bits of a dead organism, it's more likely to cause adverse effects. Meanwhile, finding all the bits of a dead organism that prime the immune system while weeding out those that might produce harm is a terribly complicated and expensive process. Add to that the threat posed by litigation over the inevitable errors in science's slow but steady progress through trial and error and it ought not be surprising that sheep and goats get protected while human suffering due to T. gondii spreads.

For a new, free and enlightening paper on the topic see "Vaccination Against Toxoplasma gondii: An Increasing Priority for Collaborative Research?"

Citing a 16% Increase in Risk of Major Adverse Cardiovascular Events FDA Recommends Meridia Use be Discontinued

New data from the Sibutramine (Meridia) Cardiovascular Outcomes (SCOUT) trial showed little weight loss but significant increased risk of non-fatal heart attack, stroke, a cardiovascular event requiring resuscitation and cardiovascular death. The FDA suggests that those taking Meridia for weight loss stop taking it, speak to their physician about alternate treatments and contact a physician "right away" should they experience chest pain, palpitations, etc. The FDA recommends physicians stop prescribing Meridia, contact patients currently on Meridia and ask that they stop taking it, inform patients of these risks, assess patients for evidence of outcomes associated with Meridia use and to report any side effects to the FDA's MedWatch program.

Abbott Laboratories has agreed to withdraw Meridia and advises patients to discontinue the use of sibutramine and to consult their physician for alternatives. Abbott's press release contains an extensive discussion of the risks, what patients need to do and the potential side effects of which they ought to be aware. For additional information see www.sibutramine.com .

Given what's happened of late with any drug remotely associated with the treatment of Type II diabetes I'll go out on a limb and predict that companies will in the future be very wary of developing treatments for this malady or any underlying factor such as obesity.

All Things in Moderation: Drinking While Pregnant Edition

Does the dose make the poison? In toxic tort litigation plaintiffs have long argued that at the unmeasured and unobserved low dose end of the dose-response curve risk doesn't reach zero until the dose reaches zero. To support their claim they point to regulators' linear no-threshold risk models, they try to throw the burden of proof on defendants and they conclude by saying that since defendants can't prove there's an absolutely safe level for exposure, all levels must therefore be unsafe.

This "no safe level" argument isn't confined to cancer cases and plaintiff lawyers aren't the only ones who make it. Advocacy groups for a variety of human ailments stake out similarly extreme positions. For example, March of Dimes claims that some 40,000 American children are born annually with fetal alcohol syndrome disorders (FASDs). In addition to claiming "no level of alcohol use during pregnancy has been proven safe" they cherry pick data from weak studies to assert that mothers who consume as little as one alcoholic drink per week have children with (a) small heads ("a possible indicator of brain size"); (b) a 300% increase in risk of growing up to be delinquents; (c) a variety of emotional and learning disorders; and, (d) an increased risk of becoming alcoholics and drug addicts. Finally, March of Dimes flatly states "[t]here is no cure for FASDs."

The good news is that there never has been much evidence to support these horror stories and the better news is that there's a brand new study showing that not only are the children of light drinkers at no increased risk of cognitive defects (at least through age 5), they're likely to have fewer problems, be less prone to hyperactivity disorders and have higher cognitive test scores. See "Light Drinking During Pregnancy: Still No Increased Risk for Socioemotional Difficulties or Cognitive Deficits at 5 Years of Age?"

There's no doubt that chronic binge drinking during pregnancy can do lasting harm to a woman's fetus. Similarly, there's no doubt that roasting yourself in the sun all summer and continuing to irradiate yourself in a tanning bed the rest of the year can lead to malignant melanoma. Yet extrapolating from such findings to declare that there's no safe level of exposure to sun or alcohol or whatever not merely panics parents needlessly; it may well result in the infliction of needless harm on the very people for whose benefit such advocacy is intended.

Trichloroethylene + Gene Variant = Renal Cancer?

Workers exposed to trichloroethylene (TCE) who carry at least one copy of the GSTT1 allele are reported to have an 88% increase in risk of renal cancer in the new paper "Occupational Trichloroethylene Exposure and Renal Carcinoma Risk: Evidence of Genetic Susceptibility by Reductive Metabolism Gene Variants." Those workers without the polymorphism had a slight decrease in risk. Given that the allele occurs on a gene coding for cysteine β-lyase, which plays an important role in the metabolism of TCE among other molecules, the finding demonstrates biologic plausibility as well as increased risk.

So back to yesterday's post about risk : which risk, if any, would be relevant in a TCE toxic tort case? The risk given to all workers collectively; the risk at a particular range of exposure; the risk given to those carrying the polymorphism; or, the risk to those with the polymorphism exposed at high levels? And could it be the case that one risk is relevant to the question of whether a defendant's conduct was reasonable while another was relevant to the question of causation? How would that work?

However it works, as the causes of individual susceptibility are identified expect these sorts of challenges to multiply. 

When You Have to Prove a Doubling of the Risk Ask "For Whom and During What Time Period?"

Despite the fact that the Texas Supreme Court in Merrell Dow Pharmaceuticals, Inc. v. Havner wrote "[w]e do not hold, however, that a relative risk of more than 2.0 is a litmus test..." many lawyers and some courts believe that Havner (and even Daubert) require that plaintiff establish epidemiological evidence of a "doubling of the risk" before she can establish so-called specific causation. In my view all those two courts ever said was that if you wanted to play the game of epidemiological causal inference then you had to play by epidemiology's rules; and, furthermore, that if all you had was probabilistic evidence then that evidence had better show that defendant's product probably did it.

Whatever the interpretation, we mass tort lawyers often wind up fighting over whether there has been a doubling of the risk. One thing we're just beginning to fight over is "when do you measure the risk?" Take for instance the Women's Health Initiative and hormone replacement therapy (HRT).

Depending on when you decide to look HRT either caused an 80% increased risk (after one year of treatment) of coronary disease or a 30% decreased risk (after five years) of coronary disease. So how do you choose which risk is the "real" one?

In what promises to become an epidemiology blog posted for free at Epidemiology is a copy of "The Hazards of Hazard Ratios". In it the author makes the point that hazard ratios, an approximation of risk ratios, often vary over time and may be subject to biases, as when, hypothetically, over time the exquisitely sensitive, by virtue of suffering the malady earlier, manage to be deselected from subsequent years' calculations.

The phenomenon is well known to those doing benzene litigation. Had the study of the Pliofilm workers been done today the very same cohort would demonstrate a relative risk less than 2.0 quickly trending towards 1.0. The obvious retort is that "latency" somehow is responsible but that doesn't explain the fact that no member of the cohort has developed leukemia in decades. The most sensible answer is that those susceptible of getting it get it and those who aren't don't just fail to get it - they can't.

In other words, the distinction in toxic torts between "general causation" and "specific causation" is likely often (if not usually) a false one. Thanks to the laws of physics, bullets can reliably be said to be a general cause of bullet holes in people since all are susceptible to the effect. The same cannot, however, be said of benzene or HRT. Apparently they only increase the risk (perhaps to 1.0) in those people who, due to genetics, epigenetics, microbiota, environment or some other factor(s), are primed to produce the effect while simultaneously imposing an increase of 0.0 on everyone else.

So how, other than flawed post hoc "reasoning", do we determine whose injury was caused but for an exposure? Biomarkers have clearly failed of their promise. Now what? The way things have been going I bet it'll look something like this: "Discovering Graphical Granger Causality Using the Truncating Lasso Penalty" but maybe we'll get lucky and it'll look more like: "Causal Diagrams and Change Variable". In the meantime plaintiffs without biomarkers need to do a better job of demonstrating how they are like those in the time interval with the biggest risk.

Thinking About Risk

What does it mean to say that I've given someone a 1 in 1 million risk of death? Is he now just 99.9999% alive? Is he 0.0001% dead? Is either a "loss"? Must we await the verdict of the Fates to decide the reasonableness of my conduct? If so, why does some other agency decide whether an act in the past was good or bad?

What does it mean to say that I've given one million customers a 1 in 1 million risk of death? Is my conduct judged myopically on the basis of the one who died; or, shall we consider the 999,999 who wound up with a useful product and suffered no harm? And how is my conduct to be judged? Shall we add up all the good, subtract out the bad (consequence's books having been audited by the trial court), and have the jury decide whether my decision-making was, being Monday morning after all, "good" in light of the final tally?

If 1 in 1 million is too risky then so is getting out of bed in the morning. Yet 1 in 1 million is 300 American lives nonetheless. And if 1 in 1 million is a reasonable risk why isn't 1 in 100,000 or 1 in 1,000 or 1 in 10? Where do we draw the line, and why?

Does it, or should it, make any difference whether I actually knew the person on whom I imposed a risk? Does the answer change if the risk materializes? Does it, or should it, make any difference whether I actually estimated the risk before imposing it? Why do jurors punish the diligently knowledgeable while being far less wrathful towards the consciously ignorant? What, if anything, should the law do about it?

Ultimately, how should courts deal with the risks we impose on each other in this world of inevitable risks? A very good discussion can be found in "Statistical Knowledge Deconstructed".

I have one quibble and a few takes. First, the effort seems sometimes to be aimed at reconciling a Bayesian decision-making approach ("degress of belief" tending to sound rather appealingly deontological to me) with a consequentialist ex post assessment of the ultimate utility of an act. Consequentialism isn't generally thought to be informative on the ex ante side of decision-making - thus my objection to "... I mean to endorse an epistemic and (thusly) Bayesian conception of risk, not a frequentist conception". Second, his comments about cost/benefit analyses are dead on. Companies are abandoning the process and adopting "Nobody gets hurt, ever!" policies instead. One has to wonder about a legal system that advantages willful ignorance. Third, his suggestion that we let risk more openly inform determinations about where an act falls along the intentional - reckless - negligent - non-negligent spectrum would be especially helpful in mass tort cases in which risks are widely distributed.

Finally, we are in the midst of a scientific revolution in which the product of biological systems are being discovered to be unpredictable and invariably greater than the sum of their parts. Emergent phenomena arising out of vastly complex systems means that the balance sheets needed to make a consequentialist assessment of an act can never be closed nor the credits and debits ever intelligently summed. Perhaps then, like the earth's most ancient and successful organisms, we ought to have rules, or principles, as our guides rather than approaching every problem ad hoc. In that case, knowingly, or willfully ignorantly, imposing a significant risk on your fellow man that manifests might be such a rule for liability.

10th Circuit Sheds Light on "But For" Causation. Substantial Factor Causation, Not So Much

In Wilcox v. Homestake Mining Company plaintiffs argued that in toxic tort cases involving an injury with multiple potential causes "causation in such cases may be proven through a substantial factor test, without regard to whether the injuries would likely have occurred in the absence of the defendant's actions." Plaintiffs further argued that a "but for" causation requirement would make recovery all but impossible in toxic tort cases. The court rejected those arguments.

All a plaintiff has to do to get to a jury is to develop testimony that that the putative cause (e.g. radiation) was more likely than not a necessary cause of her injury (e.g. bladder cancer) and if there are multiple tortious sources of that cause then she can avail herself of alternate causation approaches (e.g. Summers v. Tice)  to assert liability against a specific defendant. On the other hand, it's not enough merely to show that the defendant brought plaintiff into contact with one of the known causes of her injury and it's not enough to show that the putative cause is one of the more common causes of that such injuries.

That's helpful. "But for" goes with the first legal causation question: was it more likely than not that the exposure (e.g. 5 fiber/cc yrs amphibole asbestos) was a necessary cause of plaintiff's cancer (e.g. mesothelioma). So where does "substantial factor" go? The court doesn't say. Like most courts it doesn't even say what it is.

Where should "substantial factor" go? We think it makes sense for it to go with the second legal causation question which is "was the exposure (i.e. the risk imposed) unreasonable?" The ability to estimate the ex ante risk of cancer imposed by exposure to a carcinogen allows both qualitative and quantitative assessments of the reasonableness of the defendant's conduct and informs the question of whether a particular exposure was substantial (and thus a basis for liability) or merely de minimis (and so unable to support a liability claim).

As we argued in Borg-Warner and have argued since, in a toxic tort case the ex ante risk imposed is the best measure of the reasonableness of the man (or woman). And that's what "substantial factor" causation ought to be about - determining whether there's some notion of responsibility associated with the particular risk imparted.

PM2.5: Diabetes, Heart Attack, Lung Cancer, Premature Death, etc

Etc indeed. The list of maladies laid at the feet of inhaled particulate matter smaller than 2.5 micrometers (thus PM2.5) is long and growing. You can add diabetes to the list thanks to "Association Between Fine Particulate Matter and Diabetes Prevalence in the United States" and lung function deficits in early childhood too ("Effect of Prenatal Exposure to Fine Particulate Matter on Ventilatory Lung Function of Preschool Children of Non-Smoking Mothers").

Is it a certain type of ultrafine particle that's responsible? Some studies say yes and others say no. In vitro toxicity testing tends to suggest that altered function is due simply to particle size while epidemiology studies tend to cast blame on one sort of particle rather than another though the findings vary from study to study and often conflict (a common problem when looking for weak effect associations). Do the observed effects meet the so-called specificity criterion for causal inference? At first the reported ill effects of exposure were said to be cardiovascular but now everything's in play especially since several studies have linked PM2.5 and Premature Death - All Causes.

So, is PM2.5 a universal toxicant and among the leading causes of death? Or could it be that people who live in urban areas with higher PM2.5 levels tend to have higher rates of unhealthy living? Is there anything good to be said about PM2.5? For example, why do farmers, who are often exposed to high levels of PM2.5, especially from endotoxins (think bits of bacteria), often have lifelong protection from many allergies that afflict those exposed to lower doses?

There's also the question of what's to be done about PM2.5. Farmers produce lots of it what with their gravel roads, grain bins, diesel tractors and plowed fields. EPA intends to regulate PM2.5 down on the farm and much more strictly than in the past but at what cost? And for those who don't like cost-benefit analyses what if the changes needed to reduce farm PM2.5 simply causes generation of ultrafine dust to be shifted elsewhere; and to increased markedly? See "The Environmental Cost of Reducing Agricultural Fine Particulate Matter Emissions".

Finally, of course, there's the issue of whom shall be sued. The finding that a speck of cotton dust from your shirt is as toxic (or as non-toxic, depending on how things shake out) as soot from combusted diesel fuel is an obvious impediment to to the diesel litigation plus there's a new study of truck drivers demonstrating that their presumed PM2.5 mortality may not be due to their work but rather can be, at least in part, explained by ultrafine dust exposures in and around the home: "Long-Term Ambient Multi-Pollutant Exposures and Mortality". Efforts to target other deep pockets will have to wait until science produces more definitive answers about what's to blame and how it can be determined that the PM2.5 in question was the cause in fact of the plaintiff's demise - likely an impossible task since causation in such circumstances is almost certainly the result of a constellation of factors; a constellation to be explored by something called eco-epidemiology. More on that another day.

Arrogant, Overconfident or Just Like Everybody Else?

Overcoming Bias and Barking Up The Wrong Tree are both commenting about the recent article "Insightful or Wishful: Lawyers' Ability to Predict Case Outcomes". Four hundred eighty one lawyers were queried about their expectations for one of their cases set for trial. After all was said and done the actual outcomes were compared to the trial lawyers' ex ante predictions and they didn't too to well; not even the ones who'd been out for years. So what gives?

Do lawyers overpromise in order to attract business, as Robin Hanson suspects? I'm sure that's sometimes the case. I once had a front row seat, as it were, that afforded me the opportunity to witness (and my client, formerly the target defendant, to benefit from) another firm's Senior Trial Partner's  first jury trial (and believe me his client had to push him to the courthouse kicking and screaming). He was played like a fiddle by the plaintiffs' attorney and by the time he read his closing from across the room he looked like a cornered animal. The verdict was huge.

Yet I don't think overpromising by underperforming trial lawyers accounts for most of the poor predictions. Rather, they likely fell prey to all too common faulty heuristics. They've spent weeks building a narrative that fits the facts and the law and the story ends happily ever after for their clients. And the bad guys' story? They've spent as much time or more poking holes in it so that for every doubt imagined a counterpoint leaps effortlessly from memory. Why isn't this just the usual sort of programmed reasoning exercise that makes most people poor prognosticators?

Finally, how are cases resolved? If settled isn't it usually on terms that nobody's especially thrilled about? And if they're not settled the distribution of outcomes, at least in my experience, tends to be U-shaped with a bunch of $0 verdicts on the left and a bunch of "ring the bell" verdicts on the right and not too many "kiss your sister" verdicts in between. I had a young lawyer recently tell me what he estimated the expected value of his case ought to be. The problem, of course, is that once the bell rings twice (or whatever jurors do in your jurisdiction to signal they've got a verdict) you're about to be, like the owner of Schrodinger's cat, either really really happy or really really sad. When the possible is collapsing into the certain why should it be a surprise that lawyers usually get it wrong when the odds of getting it right are against them?

What's Behind the Rise in Food Allergies?

The incidence of food allergies in children is rising. Wheat, milk, egg, fish, peanut, walnut, shellfish and soy allergies have led to recalls of pork, turkey, cream of wheat mushroom soup, roast beef, ice cream and corn pasta in recent months. What's behind the increase in allergies?

There are at least two good hypotheses for which there's sound evidence. First, despite what our pediatrician told us, it's probably a good idea to introduce babies to e.g. cow milk sooner rather than later (see "Early Exposure to Cow's Milk Protein is Protective Against IgE-Mediated Cow's Milk Protein Allergy") and make sure they get a large enough dose to produce tolerance as it's apparently the low doses of say peanuts that lead to sensitization and allergy (see e.g. "Peanut Sensitization and Allergy: Influence of Early Life Exposure to Peanuts").

The second emerging hypothesis, another of the increasingly common "Grandma was right" sort of ideas, is that lack of sunshine is also responsible for the rise in food allergies in children. It turns out that vitamin D is crucial to a properly functioning immune system and without it you wind up with a gut full of the wrong sorts of bacteria behaving badly. (See "Potential Mechanisms for the Hypothesized Link Between Sunshine, Vitamin D, and Food Allergy in Children" and "The Role of the Gut Mucosal Immunity in the Development of Tolerance Versus Development of Allergy to Food").

And while we're on the topic of the consequences of this needless epidemic of vitamin D deficiency in the U.S. due to four decades of anti-sun/anti-reason activism you should also read: "North-South Differences in U.S. Emergency Department Visits for Acute Allergic Reactions", "Are Active Sun Exposure Habits Related to Lowering Risk of Type 2 Diabetes Mellitus in Women, a Prospective Cohort Study?" and "Vitamin D and Risk of Cognitive Decline in Elderly Persons" along with "Vitamin D: A Place in the Sun?" and "Vitamin D in Asthma: Panacea or True Promise?"

The takeaway here is that by overreacting to rare and likely uncontrollable risks we've been stampeded right into far more common and otherwise avoidable risks. So who should be liable to all of the eggshell plaintiffs manufactured out of junk science? Should it be the companies whose products would not have caused harm but for the activists or should the activists be called to account for what they have done?

Twenty Suspected Carcinogens

The American Cancer Society is calling for new research to settle the issue of whether or not twenty different agents do indeed cause the types of cancer in which they've been implicated. The twenty are:

(1) Lead and lead compounds; (2) indium phosphide (used in many flat screen TVs); (3) cobalt with tungsten carbide; titanium dioxide; (4) welding fumes; (5) refractory ceramic fibers; (6) diesel exhaust; (7) carbon black; (8) styrene oxide and styrene; (9) propylene oxide; (10) formaldehyde (does it cause leukemia?); (11) acetaldehyde; (12) formaldehyde; (13) methylene chloride; (14) trichloroethylene; (15) tetrachloroethylene; (16) chloroform; (17) PCBs; (18) DEHP (a phthalate); (19) atrazine (a herbicide and the subject of a coordinated attack by various activists groups resulting in a new EPA review); and, (20) shift work (the presumed exposure being "light at night" leading to a disruption of circadian rhythms and the most commonly associated malignancy being breast cancer).

You can find the press release here: Report Outlines Knowledge Gaps for 20 Suspected Carcinogens; and you can find the IARC report summarizing past rationale for assigning these suspected carcinogens to groups 2A - 3, the new evidence forming the basis for the recommendation that the status be updated and the sorts of epidemiological and mechanistic studies necessary to answer the question of whether they ought to be added to the list of 107 Group 1 agents known to be carcinogenic to humans, here: Identification of Research Needs to Resolve the Carcinogenicity of High-Priority IARC Carcinogens.

It's Like Deja Vu All Over Again

Well, that didn't take long. A new study published in Lancet Oncology titled "Angiotensis-Receptor Blockade and Risk of Cancer: Meta-Analysis of Randomized Controlled Trials" is the result of yet another ex post assessment of mountains of data from trials of pharmaceuticals. This one found a piddling 1.08 risk ratio based on a 95% CI of 1.01 to 1.15. Run for your lives sort of stuff this ain't.

But of course that didn't stop some from exploiting the study; immediately. In something called "People's Pharmacy" the Houston Chronicle on-line led with the following story on the front page: "Cancer Link Feared With Blood-Pressure Medicine." In response to a letter allegedly from a stressed out reader the People's Pharmacy uncritically notes that the paper found "a modestly increased risk of new cancer" and helpfully suggests 8.5 ounces of beetroot juice as an alternative remedy for high blood pressure.

Presumably they're referring to "Inorganic Nitrate Supplementation Lowers Blood Pressure in Humans. Role for Nitrite-Derived NO". Nowhere in the paper do the authors suggest that patients abandon their blood pressure medications in favor of an unknown number of cans of "beetroot juice". Yet that's almost certainly what many will do.

After decades of effort heart disease, which felled my grandfather at 49, is at last receding as a cause of premature death in Americans. It would be tragic indeed if the product of a data-mining expedition or two reversed the habits of those who have benefited so much from that effort.

Tags:

The Doctor Doth Protest Too Much, Methinks

Today The New York Times, which dutifully fanned the flames of the 2007 "prescription drug crisis" started by those pushing for greater FDA powers and fewer new drugs, published "Caustic Government Report Deals Blow to Diabetes Drug". In essence it reports Dr. Thomas Marciniak's criticism of the RECORD study which in 2007 led the FDA, despite congressional histrionics, to vote 22 - 1 to keep Avandia on the market. What the NYTimes is talking about is this.

What sets off the alarms, to a mass tort lawyer anyway, is slide 22. Why, asks the good doctor, should you believe his numbers? After all he declares that he has "nothing to hide" and that "[n]either my job nor (for me) $100,000,000's are riding on the results." The other slides evidence an effort to dig, but not too much, into the data and upon finding seeming errors to imply, without saying so, that the manufacturer somehow managed to beguile honest researchers from around the world into signing off on bad science. It's the kind of drama you'd expect to see from a certain sort of expert witness testifying at the courthouse in Jefferson County; but hardly the sort of presentation typical of scientific gatherings. Then again the FDA has been hyper-politicized so maybe this is the new normal.

Anyway, the implication that this is the "Government Report" is highly misleading. It is in fact but one of many government reports (if by that we agree to mean presentations generated by government employees/contractors). Indeed, another "Government Report" addresses Dr. Marciniak's claims. You'll find it here.

Dr. Marciniak did the easy thing. Post hoc he rummaged around for evidence of errors that would undermine the RECORD study. When examining the outcomes of thousands of people based on many times that number of documents he found a few seeming inconsistencies. Anyone who does mass tort litigation knows that if a bad data point or two were enough to refute any study then we wouldn't have much to talk about down at the courthouse.

What's also interesting is the fact that throwing in the extra assumed heart attack episodes (even the ones for which there were no biomarkers confirming same) the study still only shows a small increase (1.38) that is statistically significant by the barest margin (C.I. 0.99 - 1.93) (i.e. "not") and still it does not support the Nissen hypothesis (to say nothing of the study of 227,000 Medicare patients that rejects it).

But most interesting of all is the data on the only question we really, ultimately, want answered. Do the people taking the medication live longer, or die sooner, than those who don't? By that measure, the protesting doctor's numbers still show that patients on Avandia were 14% less likely to die than those who weren't. By this most critical measure, even considering the data cherry picking of Dr. Marciniak, the results for Avandia are "reassuring" - according to that other government report.

Data Dredging For The Masses

Part of what Congress passed in response to the perceived prescription drug crisis of 2007, Title IX, Section 921 of the Food and Drug Administration Amendments Act 2007 (FDAAA) (121 Stat. 962), includes a directive that the FDA "conduct regular, bi-weekly screening of the Adverse Event Reporting System [AERS] database and post a quarterly report on the Adverse Event Reporting System Web site of any new safety information or potential signal of a serious risk identified by Adverse Event Reporting System within the last quarter."  A single sufficiently serious adverse event may be enough to constitute a "potential signal".  The number of potential signals being detected are increasing rapidly and on the most recent quarterly Potential Signals report thirteen additional drugs have been listed including such widely prescribed medications as Zithromax (the highly effective Z-pack) and Premarin for producing signals of serious risks of liver failure and angioedema respectively.

What will be the impact of releasing what is essentially raw data divorced from any analysis of its meaning or discussion of the plausibility of what it implies?  In other words, what good will come from this sort of transparency?  Other than tempting the unwary to the wrong conclusion thanks to the post hoc ergo proptor hoc logical fallacy it's hard to see any good coming of this; unless of course you're a personal injury lawyer.  Google "Zithromax lawyer" and you'll find that though the new potential signal report is only a few days old there are already numerous "Zithromax attorneys" anxious to represent you in your claim for liver failure.

At the end of the day it may well be that the so called prescription drug crisis that the Congress was responding to in 2007 was in fact merely a prophecy only now being fulfilled thanks to the AERS Potential Signals reporting system.

Tags: , , ,

Cancer Death Rates Keep Dropping

The American Cancer Society has just published "Cancer Statistics, 2010", its annual estimates of the number of new cancer cases and deaths expected in the United States. Did you know that since 1990 the rate of death from all cancers combined for men of all races combined has fallen 21%? Yet thanks to a longer life expectancy and advances in preventing people from dying from e.g. heart attacks 44 of every 100 men will develop an invasive cancer in their lifetime. Thanks to smoking women are catching up to men on the categories you don't want to be in and falling behind in the ones you do, like decreasing death rates.

After accidents comes cancer on the list of causes of death in children. The good news is that the overall 5-year survival rate is now 81% and the trend is in the right direction. For acute lymphocytic leukemia (ALL) and non-Hodgkin lymphoma (NHL) the 5-year survival rates are now 89% and 95% respectively.

In all, 562,875 Americans died of cancer in the most recent year for which all data has been collected. For men and women aged 40 - 79 cancer is leading cause of death. In fact, it's the leading cause of death among everyone under the age of 85 combined beating out heart disease by a body count of 475,211 to 380,791.

There's lots more in the report and it's free at the link above.

 

Tags:

Avandia: Burn Her Anyway?

Three years ago Dr. Steven Nissen published "Effect of Rosiglitazone on the Risk of Myocardial Infarction and Death from Cardiovascular Causes" in which he reported that those taking Rosiglitazone (Avandia) had about a 40% increased risk of acute myocardial infarction (heart attack). The study was a meta-analysis of published and unpublished data and drew extensively from the manufacturer's unpublished data.

The media simultaneously reported the findings and propagated the following narrative: The pharmaceutical companies collect vast quantities of data; publish only what supports their products; and are at best willfully ignorant of the risks of their products which risks are right before their eyes if only they would look. Dr. Nissen who "has a statistician’s zeal for drilling deep into clinical data, seeking signs that some widely used drugs pose undisclosed risks to patients" was made the hero of the drama. Congress got involved by beating the drums of safety and transparency and demanding that the FDA pay more attention to ensuring that pharmaceuticals are safe.

The FDA reassessed Avandia and panel members voted 21-3 to keep it on the market.

In February of this year, a Congressional investigation conferred near-martyr status on Dr. Nissen after it was revealed that he had secretly tape recorded a meeting with the representatives of the maker of Avandia. The same month, in European Heart Journal, he published the editorial "The Rise and Fall of Rosiglitazone". Meanwhile everyone was waiting for the results of a huge study of Avandia.

Last week that study, "Risk of Acute Myocardial Infarction, Stroke, Heart Failure, and Death in Elderly Medicare Patients Treated with Rosiglitazone or Pioglitazone" (interestingly, for several days JAMA made you click through an ad for a competitor's type 2 diabetes product to get to the article) was published. And what was the risk of heart attack among those elderly patients on Avandia? Essentially no different than those on the older medication - a statistically insignificant 1.06 increase - especially so given the fact that almost three quarters of all type 2 diabetics wind up dying of heart disease in any event. So, was Avandia cleared? Nope. In fact, the calls for removing it from the market have grown even louder.

The new study, while rejecting the original claim that Avandia causes heart attacks, raised the hypotheses that Avandia causes congestive heart failure and stroke and increases the rate of mortality overall. Yet even though the numbers of patients involved in the study (their records were simply culled from Medicare databases) was large (227,000) the increases were relatively small and by the time the increases appeared (after six to fifteen months of medication) only a small and rapidly decreasing fraction of the original cohort were actually still on one of the two medications.

At almost the same time Dr. Nissen published an updated meta-analysis ("Rosiglitazone Revisited: An Updated Meta-Analysis of Risk for Myocardial Infarction and Cardiovascular Mortality"  also free and also, though published in the Archives of Internal Medicine, only after an ad for the same competitor's type 2 diabetes product) that purports to show that Avandia increases the risk of heart attack but doesn't increase the risk of mortality. What? Hey, wait a second! How can ... So, siding with those advocating "safety over certainty" the New York Times quickly editorialized in favor of those demanding Avandia be removed from the market.

The LATimes went so far as to publish a piece calling for "an immediate moratorium on sales as soon as a credible study raises questions about safety." In that same piece the journalist was posed the following question by a researcher being interviewed: "Suppose a drug saves five people and kills one person. Do you keep it on the market?" His answer was "I know this: If that one person killed is my loved one - or yours - the answer is readily apparent."

Yikes. Really? If a data dredge shows any risk of a fatal outcome then the drug should be pulled from the market no matter how many people are killed in the process? We'll save for another day the question of how thinking about risk goes so badly astray. For now though consider how likely it is (yes likely - and in fact, if the number of endpoints examined are sufficiently large, how almost certain it is) that a risk will be found where none exists. Start with "Data Dredging, Bias, or Confounding: They Can All Get You Into the BMJ and the Friday Papers" and then for more on the perils of statistical deep drilling read "Your Intuitions Are Not Magic" and the links therein.

At the end of the day the issue isn't safety versus certainty. Claiming that pharmaceutical manufacturers are insisting upon certainty before warnings are issued or products are pulled is just a straw man argument. The usefulness of statistical analyses of medical outcomes has not been added to "death and taxes".The real question is which course is less uncertain - making vital judgments on the basis of large randomized controlled trials like the one due out on Avandia in 2015 or on the basis of data dredges? The answer ought to be obvious.

Vitamin D Deficiency and Multiple Sclerosis (MS): Who Pays?

In "The Lancet: Neurology" you'll find "Vitamin D and Multiple Sclerosis"  as well as "Vitamin D: Hope on the Horizon for MS Prevention?" Could it be that  the old mocked wisdom of "a healthy dose of sunshine" wasn't so silly after all? Could it be that the health panic precipitated by activists who demanded everyone stay out of the sun actually caused horrific and needless suffering? Could be.

I just got back from a vacation in Destin, Florida. While there I learned that there are people who cover every exposed surface of their kids with zinc oxide before letting them out in the sun. These parents think they're doing the right thing. Their kids seemed about as happy as I'd have been sent out into the world in a powder blue leisure suit. But while powder blue leisure suits don't cause rickets and MS, vitamin D deficiency does. When disease strikes will there be a viable cause of action against the scaremongers who caused it? It's an interesting question.

USEPA Issues its Draft Toxicological Review of Formaldehyde

On June 2, 2010, USEPA announced a 90-day public comment period for its "Toxicological Review of Formaldehyde Inhalation Assessment: In Support of Summary Information on the Integrated Risk Information System." EPA's Integrated Risk Information System is a human health assessment program that evaluates quantitative and qualitative risk information on effects from chemical exposures. EPA's notice seeks pre-dissemination peer review. A copy of the notice can be seen here.

Clostridium Difficile in the News

Can C. difficile be spread through the air? What does C. difficile have to do with COPD? How should physicians treat the new and especially virulent strain of C. difficile? At what temperature should you cook ground meat to kill C. difficile and its spores? Do alcohol-based gels kill it? Why do antacids administered in hospital increase the risk of infection? Are there new antibiotics that work against C. difficile?

Click on the links for a sense of current thinking on these issues.

Causation is Really, Really, Really Hard

Life would be so much simpler if causation were binary - e.g. stay out of the sun and never get melanoma or worship the sun and die young of skin cancer. That way we'd have real choice, the virtuous would be spared and the heedless would be plagued. It doesn't work that way, of course.

Shockingly (or not) most people who sunbathe, drink or smoke don't die of skin cancer, throat cancer or lung cancer. What gives? Maybe the numbers are wrong or maybe the statistics are just some trick of government / industry / academia / nefarious "other". Those are a few of the explanations offered up by the readers of the San Francisco Chronicle in response to its new article: "Vitamin D Levels Dip" in which the claim that sunbathing might be good for you is explored.

That biological cause and effect, even at the level of a single protein, can't be put into simple one-to-one correspondence doesn't just vex bloggers; it is profoundly troubling to researchers and it's prompting many to reexamine views about causality in biological systems that were being investigated decades ago but which fell out of favor in the modern reductionist era.

In "Order Without Design" Alexei Kurakin nicely sums up the evidence for life, and thus diseases of life, being emergent processes unexplainable by reducing the system to its parts and its inputs. Life (and its afflictions) instead seems to be a dynamic process driven essentially by economic competition for energy and materiel at the molecular level. What is the evidence for this claim? One very big piece of it is found in the amazing plasticity of proteins.

We've all been taught that proteins, especially cytokines, work like locks and keys. It's an easy to grasp metaphor and promised easy-ish cures for what ails us. Disease was the product of missing keys or broken locks. Supply the missing key, or one that worked the broken lock, and the door to good health was open again, right? Too often though it turned out that replacement keys didn't work as expected and that broken locks weren't actually broken - they were just performing other functions.

Closer examination revealed that proteins were often found far from where they were thought to do their work and were twisted and folded into completely unexpected shapes. Further investigations revealed that many if not most proteins exist not in some concrete form with concrete functionality but rather in a "disordered" state waiting to be shaped and directed not by some genetic program or external event but rather by the tides of energy and matter within the cell itself. And it is out of the ebb and flow of those tides that the organized activity of the cell emerges.

There's much more in the paper and those which it cites, of course, but for our purposes suffice it to say that the question of causation in biological systems cannot sensibly be asked, as we do in our courts, "Was chemical "X" a producing cause of Plaintiff's cancer?" Perhaps the question should be something more akin to "Given Plaintiff's condition before exposure to chemical "X"  by how much was her risk of cancer increased by that exposure?" But then that doesn't really get it either. Take mesothelioma and amphibole exposure as an example. 

It's commonly said that amphibole exposure is a risk factor for mesothelioma in humans. But if that's the case why didn't the other 95% of the workforce at say the unibestos plant in Tyler, Texas get mesothelioma? Is it that amphibole-induced mesothelioma is a purely stochastic process such that those who developed the disease were just unlucky? Or rather is it the case that causation, in the case of chronic diseases anyway, isn't generalizable? That's the takeaway - there may not be such a thing as what lawyers call "general causation".

Occupational Exposure to Endotoxins: A Good Thing?

In the newest edition of the journal Cancer Causes and Control you'll find a paper titled "Endotoxin Exposure and Lung Cancer Risk: A Systematic Review and Meta-Analysis of the Published Literature on Agriculture and Cotton Textile Workers". The authors examined 28 studies of workers occupationally exposed to high levels of endotoxins and their risk of developing lung cancer. Previous studies had suggested acute and chronic lung conditions could be caused by endotoxins.

Interestingly, endotoxin exposure was consistently associated with a large and statistically significant decrease in lung cancer. Furthermore, the protective effect was strengthened as dose was increased.

Also this month, in Cancer Epidemiology, Biomarkers & Prevention, you'll find "Lower Risk of Lung Cancer After Multiple Pneumonia Diagnoses". It turns out that getting pneumonia three or more times is even better than high exposure to endotoxins if you want to avoid lung cancer.

What is it about these biological challenges to the lung that leads to significant anti-lung cancer protective effect? It's anyone's guess but perhaps keeping your immune system tuned up is part of the answer.

No Association Between Paint Fumes in the Home and Fetal Growth

See "Non-Occupational Exposure to Paint Fumes During Pregnancy and Fetal Growth in a General Population"

Though about half of the mothers surveyed said they'd been exposed to paint fumes in the home while they were pregnant the data suggested that the more fumes to which they'd remembered being exposed the lower the risk that their baby would be underweight. What? This study probably has more to say about the use of interview data as a proxy for exposure than it does about the relationship being examined.

Long Term Smoking Significantly Reduces the Risk of Parkinson's Disease

A greater than 40% decrease in Parkinson's if you smoke more than 30 years? So it seems from this huge NIEHS study of 305,468 Americans. "Smoking Duration, Intensity, and Risk of Parkinson Disease".

Obviously the risk of getting lung cancer, emphysema, etc from smoking is much higher. Still, if you knew you had the genes that protects you from lung disease (whatever they are) but not the ones that protect you from Parkinson's (whatever they are) would you smoke?

 

You Know Those Mass Screenings for Prostate Cancer? Nevermind.

According to the Houston Chronicle the American Cancer Society has finally come to grips with mounting evidence that indiscriminate screening for prostate cancer causes more harm than good thanks to (a) the inevitable morbidity resulting from needless biopsies and surgeries due to false positive tests; (b) the realization that an awful lot of people who consider themselves "cancer survivors" would never have known they had cancer but for the screening test as their cancers would have gone away on their own or would have grown so slowly that they'd have died of something else before the prostate cancer became threatening; and, (c) the unfortunate fact that early detection, despite what everybody has been led to believe, does not mean that aggressive cancers can be cured - it just means that we get to be treated for them, and worry about them, longer.

Here's a link to the new screening recommendations: "Revised Prostate Cancer Screening Guidelines: What Has -- and Hasn't -- Changed"

Also of interest may be the readers' comments over at the Chronicle and elsewhere. Predictably there are two dominant camps. One sees this change as a nefarious plot by Big Pharma and Big Medicine to prevent early detection so they can make more money by making people wait until they need more expensive medicines and surgeries. The other one sees the new guidelines as a nefarious plot by Big Government to save money by preventing early detection so it can save money on treatment and hasten the deaths of Americans thereby saving money on Social Security payments as the cherry on top. I've run across veniremen able to hold both views simultaneously. But that's a discussion for another day.

Numb(er)struck

Pretend you're not a tort lawyer but instead a criminal lawyer. The judge is going to decide whether your client should be committed or set free. Her decision will turn on the likelihood of your client committing an act of violence in the future. You and the prosecutor reach an agreement on the factors to be weighed and a risk assessment is thereafter produced. It shows that your client has a 26% chance of future violent behavior.

Question: How should you frame your case

(a)   there's only a 26% chance that he'll ever commit an act of violence;

(b)   there's a 74% chance that he'll never commit an act of violence; or

(c)   it doesn't make any difference?

If you answered either (a) or (c) you might want to read "The Effect of Framing Actuarial Risk Probabilities on Involuntary Civil Commitment Decisions" just published in the journal Law and Human Behavior.

Tags: ,

Will Your Jurors Find Your Expert to be Knowledgeable and Trustworthy?

It's likely to depend on whether his or her opinion supports, ultimately, the values of each juror. And if the scientific consensus supports the expert's opinion it's likely to have less persuasive effect than you imagine. It's not a matter of your juror rejecting that consensus. Rather, it's a consequence of your juror assuming, perhaps because instances of agreement come readily to mind, that most experts actually support whatever conclusion about the issue would be deduced from that juror's values. That's my take anyway from the new paper (hat tip: The Situationist) "Cultural Cognition of Scientific Consensus" by Dan M. Kahan, Hank Jenkins-Smith and Donald Braman (part of the Cultural Cognition Project.)

At the conclusion of the paper the authors make a recommendation to those tasked with communicating risk that should be heeded equally by trial lawyers. "It is not enough to assure that scientifically sound information - including evidence of what scientists themselves believe - is widely disseminated: cultural cognition strongly motivates individuals - of all worldviews - to recognize such information as sound in a selective pattern that reinforces their cultural predispositions. To overcome this effect, risk communicators must attend to the cultural meaning as well as the scientific content of information". Swap "trial lawyers" for "risk communicators" and you'll get my point.

One last thing. I wonder what role reputation, and by that I mean the reputation of the subject and not that of the expert, plays in such matters. Here's why I ask. I know people who you'd predict from the authors' "hierarchical individualist" vs "egalitarian communitarian" distinction to fall into the "vaccines don't cause autism" camp instead being fervent anti-vaccination zealots. And I've found the reverse to be true as well. What actually seems most determinative is a like-minded group of friends. From my wholly unscientific observations some views about risk seem to spread among a group of friends or social acquaintances more like a virus. A new concern begins to be discussed, is seen as quirky, slowly spreads, then one day comes a tipping point and almost everyone in that group is announcing they won't be having their kids vaccinated (in the other group calls for the water-boarding of Jenny McCarthy are surprisingly typical) and the rest are feeling like Donald Sutherland in "Invasion of the Body Snatchers" (before the end anyway), and trying to change the subject.

Tags: ,

Indiscriminate Population-Wide Medical Experiments: Part Umpteen

By now you know that the Mayor of New York wants less sodium salt in your diet. You also know that the New England Journal of Medicine published an article in January claiming that if conservative assumptions about the health benefits of reduced salt intake are correct and would be true across the entire population then laws reducing salt intake would save "194,000 to 392,000 quality-adjusted life-years and $10 billion to $24 billion in health costs annually . Sounds like a law we ought to adopt tomorrow, right?

In this month's JAMA Dr. Michael H. Alderman of the Department of Epidemiology and Population Health at Albert Einstein College of Medicine has authored "Reducing Dietary Sodium: the Case for Caution". Alderman does a great job of setting out the positions of both the advocates and the skeptics of mass sodium restriction but then he points out the iron law of unintended consequences. "Multiple randomized clinical trials (RCTs) have established that reduction of sodium intake sufficient to lower blood pressure also increases sympathetic nerve activity, decreases insulin sensitivity, activates the renin angiotensin system, and stimulates aldosterone secretion. The health effects of sodium restriction will be the net of these conflicting effects."

Rather than the "rash route" of "universal sodium reduction" Alderman counsels a more cautious approach involving "rigorous, large-scale, population-based randomized clinical trials". He recognizes that a definitive answer would likely take years but, should it turn out that the supposed benefits don't materialize or the harm done to supposedly few people by universal sodium restriction turn out to be harm done to many many people, a lot of money and maybe lives, will have been saved.

A sensible recommendation given the track record of "consumer advocacy groups" - e.g. switching our diet to a starch pyramid and soon thereafter effecting the substitution of trans fats for traditional saturated fats. Maybe this time we can look before we leap.

Tags:

On to a Fifth Age? How About We Finish the Second?

In a 1971 paper that profoundly influenced how scientists and policy makers approached public health issues Abdel Omran set out his theory of "The Epidemiologic Transition". He hypothesized that societies went through three different ages, or phases, that defined their experience with regard to mortality and life expectancy. In the first, the "age of pestilence and famine", life expectancy is low and episodes of widespread death are common. In the second, the "age of receding pandemics", infectious diseases are overcome and life expectancy increases dramatically. Finally, in the third, the "age of degenerative and man-made diseases", diseases of aging and self-inflicted suffering becomes the predominant determinant of mortality. Eventually others, noting the dramatic increase in life expectancy due to the rapid decline in deaths due to heart attack and stroke, posited a fourth age; essentially the same as the original third age but with cardiovascular disease removed from the "degenerative disease" category.

Now in an editorial in this month's JAMA  Dr. Michael Gaziano asserts that we may be entering a fifth phase, or age, of the epidemiologic transition. We are now, he writes, entering the "age of obesity and inactivity" in which ailments due to gluttony and sloth predominate on death certificates. The editorial references two new articles in the same issue purporting to show Americans are fat and getting fatter; especially the children.

But wait a minute. The age of man-made diseases barely materialized. Certainly there have been many many cases of people suffering terribly as a result of some man-made health hazard. Look no further than the cases of mesothelioma among the men who served aboard amosite laden Navy ships. And smoking continues to exact its terrible toll. Yet if you throw all the deaths due to occupational diseases and every last lung cancer/COPD death into the same category you can't get to 10% using worst case estimates. More sober estimates put the percentage of deaths due to man-made diseases at considerably less than one. Nevertheless, this powerful meme - that most of our woes are self-inflicted and due to some failure to live in a natural way - still propels not only mass tort litigation but also much scientific and political thinking.

However, there's more than just AIDS to demonstrate that we never really saw the "disappearance" of infectious diseases. Go to www.pubmed.gov/ and do some searches on helicobacter pylori and humanpapilloma virus and you'll see just how many cancers are now being attributed to just these two organisms. Investigate mollicutes and you'll find that all sorts of microbes are suddenly being found associated with disease and they're only now being found because the technology to identify them is only now being refined.

Finally, remember to read the fascinating journey of Barry Marshall and Robin Warren from authors of an abstract rejected as one of the year's worst to winners of the Nobel Prize in Medicine for the very same work. In the end, the view, supported by the work of one of the world's preeminent public health researchers, that peptic ulcers were caused by that most modern of man-made insults, stress, only gave way to the understanding that the cause was in fact a bacteria when the evidence was irrefutable.

Facts Don't Have Much Impact on Values

By now you've likely heard that Andrew Wakefield, the British doctor whose 1998 paper published in The Lancet linked autism to the measles, mumps and rubella vaccine, has been found by that country's medical supervisory board to be guilty of "unethical" research, dishonesty, financial impropriety and "serious professional misconduct". And if you've been following the story you know that the paper has been partially retracted by The Lancet, disowned by most of Wakefield's co-authors and its findings have been refuted by subsequent and far more rigorous research. You might even know that the vaccine scare precipitated a sharp drop in vaccinations leading to a 20 fold increase in measles cases and at least 11 unnecessary deaths.

But what you might not know is that for an awful lot of people, none of it matters.

Despite the needless deaths, despite the revelation that Wakefield received $100,000 to conduct his test from lawyers hoping to sue vaccine makers and despite studies of millions of children who received the vaccine (as opposed to the 12 studied by Wakefield) showing no link to autism, as the verdict against Wakefield was read by the board's chairman he was "repeatedly heckled by distraught parents who support Wakefield..." And if you read the comments about the verdict at The Times you'll see that there are an awful lot of people who think that Wakefield is a victim of an elaborate plot to silence him orchestrated by the drug companies (out to make money) and the government (out to save money).

So what gives? One explanation is that our perception of risk is shaped largely our values. In a recent post at The Situationist you'll find a link to a video from the National Science Foundation in which Dan Kahan discusses the "cultural cognition thesis" - the idea that people perceive risk through the lens of their beliefs about what is and isn't good for society. By way of example he discusses the HPV vaccine Gardasil and the aversion to its administration by people who typically support vaccination. Apparently, for some at least, the perceived risk of green lighting sexual activity in young women outweighs the known risk of cervical and head and neck cancers.

What values then compel so many people to cling to the scientifically unsupported belief that  vaccines cause autism? That profiting from preventing disease is morally wrong? That mandating vaccination of children is a violation of rights? Something else? Whatever the answer just remember that you won't ever change a juror's values; not in time for the verdict anyway. Instead, find a way to present the facts so that they fit, or at least do not conflict, with those values and if that's not possible then frame the issue so that some other, shared value decides the question.

 

Tags: ,

A Critique: Recent Epi Studies of Motor Skills and Manganese

In "Risk Assessment of an Essential Element: Manganese" Annette Santamaria and Sandra Sulsky of ENVIRON critically review recent epidemiological literature associating a variety of abnormal psychometrics with relatively low levels of manganese exposure.  

The authors conclude that the available epidemiological data is generally flawed and unreliable at least for the purpose of doing risk assessment. Furthermore, they demonstrate that some exposure levels claimed to pose a risk of neurobehavioral injury produce effective doses well below the amount of manganese recommended in a healthy diet; they also elaborate on the adverse health effects of manganese deficiency. Santamaria and Sulsky conclude by suggesting that more accurate and defensible risk assessments for manganese will have to come from objective data such as the determination of manganese dose via inhalation and the subsequent development of physiologically based pharmacokinetic models to predict the consequences of exposure at various levels and by various routes.

European Commission Seeks Input From Stakeholders on Action Plan for Nanotechnology

Public authorities, citizens and organisations are being asked to weigh in on a new Action Plan for Nanotechnology being considered by the European Commission . Submissions are due by Feb. 19, 2010. There's also an online questionnaire to be filled out that will give you a pretty good idea of the benefits and risks being contemplated for this new technology.

Tags:

Don't Pitch the Water Softener

Have you been worrying that your water softener is significantly increasing your risk of dying from a heart attack? I didn't think so. But just because you haven't been feeling vulnerable around your water softener doesn't mean the WHO hasn't been fretting for you.

Thanks to epidemiological studies going back a decade or more (e.g. "Magnesium and Calcium in Drinking Water and Death from Acute Myocardial Infarction in Women") a worry arose that we were killing ourselves by eliminating the minerals naturally found in most drinking water. Yet subsequent studies have failed to confirm the finding including the just published "Effect of water hardness on cardiovascular mortality: an ecological time series approach". So what gives?

Well, what gives is that most of what gets published in peer reviewed journals is probably false; and when it comes to causal inferences drawn from epidemiological studies "the apparently indiscriminate indentification of particular aspects of daily life as dangerous to health" is, as witty programmers say, a feature, not a bug.

 

A Surprising Number of Americans Fear the Flu Shot is Unsafe

Reuters is reporting on the results of a new poll conducted by the Harvard School of Public Health into the attitudes of Americans towards getting their children vaccinated against swine flu. Slightly more than twenty percent of the parents surveyed had decided not to immunize their children and the main reason disclosed was fear about the safety of the vaccine.

The CDC has been monitoring those who have been vaccinated and has a web page up about the safety of the vaccine, the weekly updated Vaccine Adverse Event Reporting System report and just about anything else you'd want to know about vaccines in general or this one in particular. Nevertheless, and in spite of the fact that by all measurements the vaccine appears to be safe and effective, a sizeable number of Americans fear the vaccine more than they fear a virus that has sickened millions and killed over 10,000. Why?

Part of the answer can be found in a 2002 study in which researchers compared their subjects' reactions to scientific evidence from reliable scientists that debunked a health scare versus inaccurate non-scientific emotional appeals from activists that merely raised the possibility of an adverse health effect. "The surprising result is that when we presented both positive and negative information simultaneously, the negative information clearly dominated. This was true even though the source of the negative information was identified as being a consumer advocacy group and the information itself was written in a manner that was non-scientific." The authors concluded that "even though the scientific evidence is favorable, claims by opponents, even if they are inaccurate and only suggest potential risks, will tend to reduce consumer demand". Hat tip TheGoodTheBadTheSpin

Tags: ,

Some Chemicals Are More Green Than Other Chemicals

California, the state in which a jury recently awarded $16.5 million for a woman’s toxic exposure to H2O (water), plans to force all manufacturers to use only “non-toxic” chemicals in their products. The so-called Green Chemistry program is to be run by the California Department of Toxic Substance Control (DTSC). The department’s director is quoted by ABCNews as saying that the plan will “save the environment and increase our economy”.

As expected, a reading of the actual transcript of the “Green Ribbon Science Panel” proceedings reveals that the benefits of the effort are likely to be neither as overstated (as by the director) nor as absurd (going “chemical free”) as much of the media would have you believe. For example, “Now, I want to be clear about alternatives. You could have no alternatives…You could have an alternative that may not be safer” said DTSC staff member Evelia Rodriguez. There’s also a fair amount of effort to explain the risk/benefit concept; but, that’s about as far as things have really gone. The panel plans on doing something about 10,000 substances in the next two years but appears to be at least partially paralyzed at present as the only sensible approach, starting with the riskiest and working their way down is, not surprisingly, is rejected by those “stakeholders” whose chemical they love to hate would appear distressingly far down on such a list. How the Green Ribbon Science Panel intends to deal with the maxim “the dose makes the poison” also remains to be seen though there is some brief though ultimately fruitless discussion of what’s to be made of “de minimis” exposures.
 

Tags:

Could Mammograms be the Cause of Some Breast Cancers?

In the on-going debate over when to start getting mammograms and how often to have them the assumption by many of those supporting an "early and often" policy has been that false positives lead to little more than worry and maybe a needle biopsy. Now The New York Times is reporting on a study that appears to demonstrate that young women already at heightened risk of breast cancer double that risk if they start getting mammograms early.

Five prior studies of women carrying a mutation that is thought to put them at increased risk of breast cancer were examined to determine whether low dose radiation exposures from mammograms further increased that risk. The results, which were statistically significant at a 95% confidence interval, showed that women carrying the breast cancer gene who started mammography early in life or who had five or more mammograms were more than twice as likely to develop breast cancer as women with the breast cancer gene who started getting mammogramps later and had fewer of them.

The working hypothesis is that mammography actually causes many cases of breast cancer in susceptible women. An alternate explanation, I suppose, is that about half of all breast cancers detected by mammography either aren't cancerous or were never going to develop into a malignancy.

Hopefully doctors are finally beginning to discuss the large and unsettling uncertainties associated with the diagnosis, treatment and causal attribution of poorly understood diseases like cancer.

Are Big Punitive Awards in HRT Cases Justified?

Law.com is reporting that Philadelphia juries have awarded a total of $103 million in punitive damages alone to two women in separate breast cancer product liability trials. The women claimed that hormone replacement therapy (HRT) was responsible for their subsequent development of breast cancer.

In light of the recent controversy over the use of Bayesian decision-making approaches to mammography and Pap testing in which probabilities of outcomes are estimated and benefits are then weighed against costs (including other bad outcomes) I thought it might be of interest to see if such an approach had been applied to HRT. Sure enough, "Bayesian Meta-analysis of Hormone Therapy and Mortality in Younger Postmenopausal Women" was just published in The American Journal of Medicine.

So what does it show? It shows that across a number of randomized controlled trials of HRT in postmenopausal women under 60 those women had a reduced overall mortality compared to those postmenopausal women under 60 who weren't on HRT.

As is often the case in these modern times science does not yield a cure but does allow one to pick one's poison as it were; not to avoid death but to influence the odds of whether you die of stroke instead of breast cancer.

And Now, New Guidelines for the Pap Test

The New York Times is reporting early this morning that a panel of the American College of Obstetricians and Gynecologists is recommending: a) that women not be tested until 21; b) that beginning at 30, and assuming three consecutive negative test results, screenings be reduced from every year to every third year; and, c) that testing can end altogether after age 65 with three straight tests without an abnormality in the last ten years.

First the PSA test, then mammograms and now Pap tests. An appreciation of the limitations of these tests, combined with the realization that many of the lesions detected by them never posed a risk, is responsible for this seismic-seeming shift. Changing a decades-long culture of screening early and often to catch cancer "when it's treatable" won't be easy and, as is apparent from the mammography fracas, won't happen without a fight.

 

Tags: ,

Figure the Odds

We ended yesterday's post by promising to show you how to more easily understand the debate over breast cancer screening.  Here's a handy way to calculate odds like the ones being discussed in the breast cancer debate. 

First, let's start with another test. Assume the following:

a) The accuracy rate of mammography is 95%

b) The false positive rate for mammography is only 3%

c) Only 1% of women over 50 have breast cancer

d) A woman over 50 has a positive mammogram
 
Question:  What are the odds that she actually has breast cancer?
 
Before we give you the answer let's talk a little bit about percentages.  First most people think they understand them, second they don't, and third even when they do most people tend to have a very difficult time reaching the right answer to a question like the one above.  On the other hand, people tend to do better when dealing with rates or frequencies.  So before we introduce you to Bayes' theorem (not today) let's try solving the question using rates.

If 1% of women over 50 have breast cancer that means that out of 10,000 women 100 of them will have breast cancer.  If all 10,000 women are screened by mammography and the accuracy rate is 95% then the test will detect 95 of the 100 cases.

However, if all 10,000 women are screened and the false positive rate is 3% then, of the 9,900 who don't have breast cancer, 297 (3% x 9,900) of them will have a mammogram indicating that they do have breast cancer.

The total number of positive mammograms thus equals the 95 who actually have breast cancer and whose cancers were detected plus the 297 who don't have breast cancer but who had a positive mammogram for a total of 392 possible cases of breast cancer.  So, if only 95 of the 392 women with positive mammograms actually have breast cancer what are the odds that your hypothetical patient is one of them?

Well, 95 is only 24% of 392 (95 / 392) - slightly less than a one in four chance that she actually has breast cancer.  So how did you do?

Risk is hard because it's counter-intuitive.  Comparing percentages is inevitably an apples to oranges trap.  Instead of thinking that a 95% accuracy rate is really high and 3% false positive rate is really low, maybe try asking yourself whether you'd rather have 95% of $100 or 3% of $10,000.

Tags: ,

Doctors and Screening Tests: Usually Wrong but Rarely in Doubt

The controversy over new breast cancer screening guidelines continues unabated today. There are already more than one thousand comments and letters to the editor addressing the issue at The New York Times alone.

Especially interesting are the statements from some of the physicians in both the articles and the comments. Many express a degree of confidence in the ability of mammograms to detect cancer well beyond what the literature would justify. How typical then is this discrepancy between medical opinion and what the numbers actually reveal? Quite.

Here's a test given to a group of obstetricians from a study published in 2006 :

There's a blood test available that can detect Down's syndrome in the fetuses of pregnant women. If the baby has Down's syndrome there's a 90% chance the test will catch it. The test has a false positive rate of only 1%. Just 1 in 100 fetuses are likely to have Down's syndrome. A pregnant woman walks into your office; she's had the blood test and it's positive for Down's syndrome. What advice do you give her about whether or not her baby actually has Down's syndrome?

Fifty seven percent of obstetricians got it wrong. Of those who got it wrong most got it spectacularly wrong, putting the odds of the baby having Down's syndrome at anywhere from 80% to 100%. And those who were most wrong were the most confident that their diagnosis was correct.

In fact the odds are (52.4%) that the woman's baby DOESN'T have Down's syndrome. Think about what advice that woman would probably get. That's a very real and chilling example of the inadvertent harm inflicted on women by doctors who put too much faith in even the most accurate diagnostic tests.

Want a handy way to figure out the odds in such cases? More on that tomorrow.

Tags: ,

Radiation Therapy for Heart Attack?

Americans are exposed to seven times as much radiation from diagnostic scans as we were in 1980 according to the National Council on Radiation Protection and Measurement. Now Reuters is reporting that a typical heart attack patient receives a radiation dose equivalent to 725 chest X-rays over the course of his or her treatment. That cumulative dose is made of up X-rays, angiograms and CT scans received throughout the patient's care.

While the doses are nonetheless small and the risk therefore de minimis one has to wonder whether or not our fondness for exotic and expensive diagnositic procedures won't ultimately run afoul of the law of unintended consequences.

Tags:

No Mammogram Until 50? Let's Get Ready to Rumble.

Gina Kolata at The New York Times is reporting on new breast cancer screening recommendations by the United States Preventive Services Task Force. They are: a) routine mammograms for most women shouldn't begin until 50; b) even then they should occur only every two years; c) they shouldn't continue past 74; and, d) self examination is of no benefit and should be discontinued. The recommendations are based on analyses of a series of studies showing the cost (including the physical and emotional harm done to women overtreated due to false positives and unalterable cancers) of mass yearly screenings far outweighs the benefits.

That these recommendations will provoke a fight is obvious. But which side will prevail? In one corner: the probabilities and statistics. In the other: our beliefs, hopes, fears and intuitions. If this were Texas Hold 'Em we'd know which side would win. But this is breast cancer and so one side comes with all the psychological, sociological and political weight that tends to make many people poor judges of fights like this.

Expect a litany of logical fallacies, from supporters on both sides, in the comments section - chief among which, sadly, will be of the ad hominem variety. 

 

Tags: ,

Asbestos Fiber Dimensions and Lung Cancer Mortality

A study published last week in Occupational and Environmental Medicine estimated exposures to asbestos fibers of specific sizes of workers exposed to chrysotile using data from transmission electron microscopy (TEM) and investigated the extent to which the risk of lung cancer varies with fiber length and diameter. The study used a cohort of 3803 workers that were employed from January of 1950 and December of 1973 in manufacturing asbestos textile products. Workers’ exposures to asbestos fibers were estimated from work histories and over 3500 industrial hygiene measurements.

Fiber length and diameter were significantly associated with an increasing risk of lung cancer. Exposures to longer and thinner fibers tended to be most strongly associated with lung cancer. The results supported the investigators hypothesis that the risk of lung cancer among workers exposed to chrysotile asbestos increases with exposure to longer fibers.

Coal Ash is Dirty Stuff, But is it Hazardous?

This question has been posed by coal ash’s recent notoriety, and the answer is without consensus. European scientists recently published a paper aimed at determining the levels of mercury in coal ash (one of coal's more dangerous components) and its potential to leach into the surrounding environment. The researchers concluded that concentrations of mercury or leaching values were not so high as to justify considering coal ash a hazardous waste by European standards. (The EPA has made a similar determination but it is being reviewed.)

Such findings, while restricted to mercury, seem to take the fire out of recent lawsuits filed by individuals affected by coal ash spills and/or disposal claiming coal ash mercury and other components are leaching into water sources at dangerous levels. While mercury, arsenic, lead and other compounds are undeniably harmful at certain exposure levels their concentration and propensity to leach are not so clear. Thus, the question of coal ash harmfulness is subject to debate and will be studied in greater detail by courts and administrative agencies grappling with this issue.

Does Smoking Cause Lung Cancer?

Of course it does. But what was the evidence in favor of the hypothesis, what was the evidence against it and how was a judgment about what lawyers call general causation finally reached? Fifty years ago a remarkable paper was published that demonstrates how a causal inference is rationally reached.

The paper itself is important to anyone trying to understand the rise of epidemiology, its methods and the profound respect it earned; and its reasoning is important to anyone who wants see how a causal hypothesis is properly dipped in the acid bath of skepticism; and what it looks like if it survives.

In the case of cigarette smoking the effect, lung cancer, was nine fold higher in smokers than in non-smokers. In retrospect it was an easy case. The question today of course is whether epidemiology can shed any light on subtler risks attributed to suspected carcinogens which are themselves just one part of a staggeringly complex causal web involving genes, epigenes, pathogens and other as-yet undiscovered causes. More about that in a future post.

Tags:

The Linear No Threshold Risk Model: Invalid at Low Doses

In a paper to be published in November’s issue of Health Physics entitled “Does Scientific Evidence Support a Change From the LNT Model for Low-Dose Radiation Risk Extrapolation”, by D Averbeck, the author challenges the conventional thinking about radiation and risk. Citing both molecular biological evidence of efficient repair mechanisms working well at low doses and an absence of animal or human epidemiological data to support the no threshold risk model Averbeck concludes that the linear no threshold assumption “appears to be scientifically invalid in the low-dose range.”

The same linear no threshold assumption is, of course, the basis for claims that each fiber of asbestos or molecule of benzene imposes a significant risk and would, assuming a population large enough to detect it, be causative for mesothelioma or leukemia, respectively. Conflating risk and causation plaintiff lawyers go beyond risk to argue that each fiber or molecule was actually causative in every case of each disease. There was, of course, never any evidence to support such claims; just a conservative regulatory position that is now on increasingly shaky ground.

The November issue of Health Physics contains several articles fleshing out this issue of what risk, if any, is associated with low-level exposure to radiation.

A Stick in Time Saves 69,679

When should Americans get the H1N1 vaccine? How many years of life would be saved if just 40% of the population is vaccinated this month? How many lives would be lost if they wait a month? And if vaccinations are to begin in earnest now rather than one month later would the cost outweigh the benefit? Complete answers to those questions can be found here. For those short on time the short answers are: October; 69,679; 583; and, yes.

COPD is an Independent Risk Factor for Cancer

After adjusting for smoking chronic obstructive pulmonary disease (COPD), chronic bronchitis and emphysema were associated with a doubling of the risk for lung cancer in this just published paper.  It's part of the ongoing Environment and Genetics in Lung Cancer Etiology (EAGLE) study.

Noting that a family history of chronic bronchitis and emphysema alone have been associated with lung cancer, that COPD has been associated with lung cancer in never-smokers and that COPD is thought to be responsible for 10% of all lung cancers, the authors concluded that these findings support the hypothesis that COPD alone causes lung cancer and they further conjectured that chronic inflammation is the essential mechanism in COPD/emphysema-induced lung cancer.

Are Current PELs/TVLs for Manganese Protective?

A risk assessment for impairment measured by five neuropsychological performance parameters showed a statistically significant association with manganese exposures (estimated by air and blood sampling) below permissible levels.  The article is titled "Exposure-Response Relationship and Risk Assessment for Cognitive Deficits in Early Welding-Induced Manganism".  It's published in the Journal of Occupational and Environmental Medicine authored by RM Park, RM Bowler and HA Roels.

Trichloroethylene: A Risk Factor for Cancer?

US EPA has been working on a risk assessment of trichloroethylene (TCE) for some time now. Here’s a link to the EPA Issue Papers through 2005. Now a comprehensive review of the issues has been published in Critical Reviews in Toxicology. The article is entitled “Trichloroethylene risk assessment: A review and commentary” and it provides an excellent overview of the developing molecular biological and molecular epidemiological approach to causal attribution and risk; one we’re sure to see increasingly in asbestos, benzene and other mass tort litigation.

Chemical Management Reform: New EPA Principles

You can read about the Obama Administration's plans for reforming TSCA here.  US EPA Administrator Lisa Jackson is quoted in the press release as saying:

“...as more and more chemicals are found in our bodies and the environment, the public is understandably anxious and confused. Many are turning to government for assurance that chemicals have been assessed using the best available science, and that unacceptable risks haven’t been ignored.

Our oversight of the 21st century chemical industry is based on the 1976 Toxic Substances Control Act....over the years, not only has TSCA fallen behind the industry it’s supposed to regulate - it’s been proven an inadequate tool for providing the protection against chemical risks that the public rightfully expects.

Today I’m announcing clear Administration principles to guide Congress in writing a new chemical risk management law that will fix the weaknesses in TSCA.”

Risk assessment is becoming a hot topic in mass tort litigation and as a result EPA's 2008 efforts regarding a new risk assessment for asbestos were especially contentious. You can read about the Administration's "Essential Principles" for planned reform here.

Tags: , ,

EPA Announces New Nanoparticle Research Effort

The US EPA discusses its upcoming efforts to support research into the uses and potential risks posed by nanoparticles in this press release. You can read more about some of the issues at EPA's Nanotechnology Research: Basic Information webpage.

Does Silica Exposure Cause Lung Cancer?

In a paper titled “Occupational Exposure to Silica and Lung Cancer Risk in the Netherlands” the authors report on the lung cancer experience of men aged 55 – 69 from the Netherlands Cohort Study who recorded workplace exposures to crystalline silica. As duration of exposure to silica increased the risk of lung cancer increased and the finding was statistically significant. Interestingly, the association between amount of exposure and lung cancer was weaker and not significant.

Tags:

Is Soda Raising Blood Pressure in Middle-Aged Men?

Diets high in foods with large amounts of fructose sugar such as sweetened soft drinks increased blood pressure in men, according to a study presented September 23rd that also found that a drug for gout blocked the effect. Most sugar consumption in the U.S. comes from sweetened drinks and foods high in sugar or high fructose corn syrup.  Fructose is the only common sugar known to increase uric acid levels. 

Men in the study who ate a high-fructose diet had their blood pressure rise about 5 percent after two weeks, while those who also were given a gout treatment increased less than 1 percent. Eating great amounts of fructose without the treatment also raised the risk of developing metabolic syndrome, a risk factor associated with the development of heart disease and diabetes.  The gout treatment lowered the body’s uric acid that is linked at elevated levels to high blood pressure, diabetes and heart disease.  So, it’s possible that lowering uric acid levels could become a routine practice in the future, much like lowering cholesterol.

My blood pressure was perfect until middle age when it ticked up a bit and I've not had a sugary soda in many years. The same is true for many men. Thus, I'm betting on correlation rather than causation on this one. Well, correlation and a statin that is ...

The 411 On An Old Health Scare Revived by Congress

Senator Tom Harkin (D-IA), the new head of the Senate Committee on Health, Education, Labor and Pensions promised on Monday to probe deeply into any potential links between cell phone use and cancer. This issue has been extensively studied, particularly in Scandinavian countries where cell phone manufacturers such as Nokia and Ericson are headquartered. Each study to date has found no statistically significant association between cell phone use and cancer, including brain cancer.

However, there are still some who attribute brain cancer to cell phones on the theory that radio waves, a form of radiation, damage brain cells. The debate comes on the heels of the 1980's and 1990's controversy regarding the potential adverse health effects of electromagnetic fields EMFs emanating from power lines. While studies cleared EMFs they implicated population mixing likely via some sub-clinical infection as a cause of cancer in children. More on population mixing to come.

Borg-Warner: Sufficient Cause or Significant Risk?

Williams Kherkher has filed their brief in Bailess v. Kaiser Gysum Company, Inc., et al. on appeal from the MDL court's granting of a summary judgment against their mesothelioma client.  According to the brief at the hearing on the motion for summary judgment the court stated that its ruling would be determined as follows:

This motion is going to be decided straight up on what Borg-Warner says and what Borg-Warner requires... If Borg-Warner requires that the dose from each defendant be enough by itself to be the substantial contributing factor, the motion must be granted.  If Borg-Warner does not require that, then the motion must be denied...

Having granted summary judgment the MDL court apparently settled on the former rather than the latter intrepretation of Borg-Warner.  In my opinion the premise doesn't reflect the true meaning of Borg-Warner.

Texas case law has refined and melded concepts of causality and culpability into a coherent and flexible scheme for determining whether or not liability ought to be imposed for the adverse consequences (negative externalities) of our actions. Essentially, a substantial contributing factor is a "but for" cause resulting from a risk imposed that was more than de minimis. The word "substantial" in "substantial contributing factor" relates, I think, to risk since any candidate cause must we know from Ford v. Ledesma be a "but for" cause and thus no more or less important than any other "but for" cause since without it, or any other such cause, the plaintiff would not have been injured.

The Bailess ruling then appears to impose a requirement that any candidate cause must be shown by plaintiff to be a sufficient cause - in other words, a cause which in and of itself, and without resort to other causes, would have brought about the plaintiff's injury. If so, this change would mark a dramatic shift in our law since in toxic tort cases, as well as in just about any other non-intentional tort case, plaintiff has always been able to recover despite the fact that her injury would not have occurred but for the actions of each of two or more tortfeasors; tortfeasors whose actions were necessary causes but not sufficient causes.  For a good discussion of the difference between sufficient cause and component "but for" causes which collectively produced the injury, see:  www.defendingscience.org/upload/Rothman-Greenland.pdf

I don't think that's where Texas case law is heading.  The question raised by Borg-Warner in a mesothelioma case is not "was defendant's asbestos a cause and if so how big a cause was it" but rather "was the exposure (i.e. the risk) from defendant's product substantial"? In other words, was the risk imposed by defendant's conduct so substantial that it can justly form the basis for liability assuming that it can never be determined which fiber or groups of fibers actually caused the plaintiff's cancer?

Fifteen Substances of Very High Concern

"The European Chemicals Agency (ECHA) has published on its website proposals to identify chemicals as Substances of Very High Concern (SVHC). Interested parties are welcome to comment on these 15 substances within the next 45 days."

The fifteen substances are: Anthracene oil; Anthracene oil, anthracene paste, lght fractions from distillationi; Anthracene oil, anthracene paste, anthracene fraction; Anthracene oil, anthracene-low; Anthracene oil, anthracene paste; Coal tar pitch, high temperature; Acrylamide; Aluminiosilicate, Refractory Ceramic Fibres; Zirconia Aluminosilicate, Refractory Ceramic Fibres; 2,4-Dinitrotoluene; Diisobutyl phthalate; Lead chromate; Lead chromate molybdate sulphate red (C.I. Pigment Red 104); Lead sulfochromate yellow (C.I. Pigment Yellow 34); Tris(2-chloroethyl)phosphate.

Continue Reading...
Tags:

The Dose Doesn't Make the Poison?

From bisphenol-A to benzene some researchers are claiming that some toxic substances not only don't have a no observable effect level (NOEL) but also that the shape of the dose response curve for these substances at low levels is supralinear.  What that all means is that the bane of any toxic tort litigator, the linear dose response assumption implying that even one molecule poses some risk, understates the actual risk associated with very low levels of exposure.

In "Evidence That Humans Metabolize Benzene via Two Pathways" by Rappaport, et al. hypothesize that at low levels of benzene exposure (less than one ppm) humans metabolize  the aromatic molecule much more efficiently than at higher levels due to some as-yet unidentified metabolic pathway.  Consequently "true leukemia risks" from exposure to benzene at what are considered acceptable ambient levels may instead pose significantly greater risks than are currently contemplated by regulators, according to the authors.

More Evidence That Benzene Is Not a Cause of CML

A meta-analysis of six case-control studies of occupationally exposed workers shows that chronic myelogenous leukemia risk is not associated with benzene exposure.

 

Tags: , ,