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.

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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.

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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.

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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.

 

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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.

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Are Michigan Courts Shifting the Burden of Proof to Defendants?

One explanation for Genna v. Jackson (a new opinion out of the Michigan Court of Appeals) and Gass v. Marriott Hotel Services, Inc is that the courts thought about it and decided to shift the burden of proof regarding causation to the defendant any time a plaintiff suffers an injury that is consistent with the possible harm, as set out on a warning label or MSDS, associated with a potentially toxic material. In Genna the court reversed summary judgment in favor of the defendant in part because "[h]ere, like in Gass, defendant has not submitted any scientific evidence that the mold in her condominium could not have cause [sic] plaintiffs' injuries." In Gass the 6th Circuit noted "Defendants have offered no evidence to refute the MSDS's representation of Demand CS as a chemical which could have caused Plaintiffs' symptoms". The court later continued saying "[p]laintiffs are not required to produce expert testimony on causation where Defendants have failed to offer scientific evidence regarding the effects of Demand CS or Suspend SC."

The Genna court concluded, on the issue of causation, "[t]his is not a complicated case: the children were sick, the children were removed from the home, the mold was discovered, and the children recovered." Noting evidence that there was lots of mold and that mold in general had been reported to cause some of "the types of symptoms suffered by the children" the court concluded [i]t does not take an expert to conclude that, under these circumstances, defendant more likely than not is responsible for plaintiffs' injuries." (citing Gass). "Here, there was ample circumstantial evidence that would "facilitate reasonable inferences of causation, not mere speculation."

Under this view of an unannounced burden-shifting approach taken by these two courts it appears that in Michigan if a plaintiff develops ailments consistent with a those listed on a product's label or MSDS the jury is free to infer causation even in the absence of evidence of what dose produces those ailments and what dose plaintiff suffered and even in the absence of an expert to opine that the product in question caused the harm at issue.

Another explanation for these cases is that Michigan does not require toxic tort plaintiffs to show what some call specific causation - a concept common in cases in which causal inferences are derived from epidemiological evidence. The idea is that when dealing with an illness that has been associated with multiple causes, among which is the chemical at issue, the plaintiff must show that the putative cause was more likely than not the cause in fact of his illness.  Evidence for this view can be found in the following passage from Genna: "Defendant urges this Court to adopt the requirement that, in order to prove causation in a toxic tort case, a plaintiff must show both that the alleged toxin is capable of causing injuries like those suffered by the plaintiff in human beings subjected to the same exposure as the plaintiff, and that the toxin was the cause of the plaintiff's injury. They urge this Court to find that direct expert testimony be required to establish the causal link, not inferences. We decline to adopt this requirement. There is no published Michigan case law on the subject."

A final explanation is that more attention to Aristotle's Rhetoric is needed. As Chief Judge Boggs, dissenting in Gass wrote the problem here is the logical fallacy behind post hoc, ergo propter hoc causal inferences such as those suggested by the plaintiffs in Genna and Gass. "It is the fallacy of saying that because effect A happened at some point after alleged cause B, the alleged cause was the actual cause. Such logic has never been enough to survive summary judgment. See, e.g., Abbott v. Federal Forge, ("[P]ost hoc, ergo propter hoc is not a rule of legal causation.") 912 F.2d 867, 875 (6th Cir.1990).

Equally importantly Chief Judge Boggs understands that lay juries are in no position to judge whether there has been a breach of the duty of care without evidence of what levels are harmful and the levels to which plaintiffs were actually exposed. If you don't know the dose you can't know what risk, if any, the defendant imposed on the plaintiff. He wrote: "Thus presented, the question is whether the plaintiffs needed expert testimony in this case to prove how much chemical exposure is too much chemical exposure or to prove whether the amount of exposure actually caused the alleged harmful consequence. In my view, the majority pays too little attention to this issue, rushing from the fact of exposure and odd symptoms to the legal conclusion of fault." He continued: "As I understand it, these cases require expert testimony in complex, professional, or scientific-based negligence cases in order to limit the dangers associated with indulging the post hoc impulse: it is too easy to charge an uncommon harm to the presence of a mysterious substance. Properly credentialed expert testimony operates as a bulwark against such fallacious attribution of guilt. As in the Daubert context, our concern in applying these cases should be to "assure that the powerful engine of tort liability ... points towards the right substances and does not destroy the wrong ones." General Electric v. Joiner, 522 U.S. 136, 148-49, 118 S.Ct. 512, 139 L.Ed.2d 508 (1997) (Breyer, J. concurring).

Whatever the explanation these cases will be a boon for Michigan toxic tort plaintiffs.

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

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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.
 

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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.

 

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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.

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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.

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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.

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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. 

 

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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.

Risks and Values

Yesterday we posted a link to a story in The New York Times covering the American Cancer Society’s decision to update its guidance on screening. The ACS is acting on years of research indicating that for breast and prostate cancers, at least in certain age groups, the benefits of mass screening are probably significantly outweighed by the harm inflicted due to unnecessary treatments among those with false positives and those whose cancers would never have produced any symptoms. Many readers who commented on the story were outraged.

Numerous people expressing anti-insurance/pharma/business/capitalism/doctors/etc views denounced the ACS’ decision as a shameless attempt to put insurance companies, pharmaceutical companies, etc. ahead of people. On the other end of the political spectrum Rush Limbaugh saw it as part of a conspiracy to reduce government expenditures on health care by consciously refusing to detect disease in the first place. In the blogosphere one headline proclaimed “ACS Throws Women Under The Bus”.

What’s going on here? At least one aspect of the problem pertinent to rhetoric has to do with the fact that facts are never just facts. Facts come laden with values, or their impact upon belief in already held values is readily apparent, or both. Facts that confirm our beliefs are warmly received; those that threaten to upend our beliefs get colder reception and the messenger who brought them fares especially poorly.

Widespread regular screenings have come to be seen as a duty, an obligation and a right. Early detection is seen as an unalloyed good. Those in whom a cancer is detected and successfully treated become “survivors” and their voices, on these matters at least, are often privileged. Mass cancer screening, like Mom and apple pie, has then a value independent of the data it generates. And changing values is notoriously difficult and takes far longer than even a lengthy jury trial.

Another pertinent aspect has to do with risk. Most people aren’t very good at estimating it, tend to worry about small but salient risks, ignore big but common risks and tend to go completely off the rails when it comes to cancer. If you argue the numbers some will reply, as did several commenters, that people aren’t statistics and “how would you like to be the one whose cancer could have been cured but wasn’t detected in time because you thought you’d wait until you were 50 to have a mammogram?” Thus, for a significant portion of the population, and many of your jurors, you’ll have a hard time trying to argue around their loss aversion. One way to counter the “what if you’re the one” argument is to respond by pointing out that screening for prostate cancer takes your risk of death from 3% down to 2.4% while vastly increasing your risk of incontinence and other morbidities. That’s just what the Times did in today’s follow on to yesterday’s story.

So again, remember that facts aren’t just facts. Facts impact values and are perceived accordingly. Contextualize the facts in harmony with your audience’s values and they’ll look more kindly on you and your case.

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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.

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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.

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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.

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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 Healh 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.

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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.

 

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