A moment of truth for JAMA.
January 4, 2017
Dr. Howard Bauchner
Editor-in-Chief
Journal of the American Medical Association
American Medical Association
330 N. Wabash Ave, Suite 39300
Chicago, IL 60611-5885
Re: Request for retraction/amendment recent article and editorial
Dear Dr. Bauchner,
I am writing to request that the Journal of the American Medical Association either amend or retract the study, “Association of Short-term Exposure to Air Pollution With Mortality in Older Adults” (JAMA study), and the accompanying editorial, “Low-Level Air Pollution Associated With Death: Policy and Clinical Implications” (JAMA editorial), both of which appear in the December 26, 2017 issue of JAMA. The basis for this request is scientific misconduct on the part of the JAMA study authors.
In summary of the study, the JAMA study reports that any non-zero inhalation of airborne fine particulate matter (ambient microscopic soot and dust referred to as “PM2.5”) can cause death on the same day. Although the study result is based on 22+ million deaths occurring among the U.S. Medicare population between 2000-2012:
- Study subject exposures to PM2.5 from outdoor air are mere guesstimates that do NOT include exposures to other major PM2.5 sources like smoking, secondhand-smoking, dust, pet dander and occupational exposures ⎯ some of which easily dwarf outdoor air exposures to PM2.5 by orders of magnitude.
- Although the study purports to link inhalation of PM2.5 to same-day death, the actual causes of death for 22+ million study subjects are not known. Study subject deaths actually include deaths from accidents, violence, cancer, disease and other causes that have absolutely nothing to do with inhalation of outdoor PM2.5.
Despite having no information on actual inhalation of PM2.5 by any study subject or cause of death of any study subject, the JAMA study authors purport to report a hazard ratio of 1.05 between PM2.5 inhalation and same-day death. Although their data is obviously extremely imprecise, the JAMA study authors nevertheless claim to report ⎯ and have been touting in the media ⎯ very precise results. Keep in mind these basic methodological flaws as you read through the misconduct allegations.
I. The JAMA study authors intentionally omitted material contradictory information, thereby rendering the study false and misleading.
The JAMA study intentionally omits material information and data that contradict its conclusions.
First, there is not even an allusion to the existence of the contradictory findings of other recent and large studies despite the study authors’ direct knowledge of their existence. Just some examples of recent significant contradictory findings include the following (Citation/Excerpt from Abstract/Comment):
- Young S et al. Air Quality and Acute Deaths in California. Regul Toxicol Pharmacol. https://doi.org/10.1016/j.yrtph.2017.06.003. (In press, online June 13, 2017). “Neither PM2.5 nor ozone added appreciably to the prediction of daily deaths. These results call into question the widespread belief that association between air quality and acute deaths is causal/near-universal.” Although this study became available at Regulatory Toxicology and Pharmacology in June 2017, it was first made available on Cornell University’s arXiv.org web site on February 10, 2015 (https://arxiv.org/abs/1502.03062) and was presented at a poster session at the 2016 annual meeting of the Health Effects Institute (HEI). Please note that HEI is one of the funders of the JAMA study. This study is particularly relevant in that it, like the JAMA study, also examined the purported association between PM2.5 and short-term mortality.
- Enstrom J. Fine Particulate Matter and Total Mortality in Cancer Prevention Study Cohort Reanalysis. Dose-Response. (Published March 28, 2017). “No significant relationship between PM2.5 and total mortality in the CPS II cohort was found when the best available PM2.5 data were used.”
- Greven S et al. An Approach to the Estimation of Chronic Air Pollution Effects Using Spatio-Temporal Information. Journal of the American Statistical Association. (Published January 12, 2012). “[W]e are not able to demonstrate any change in life expectancy for a reduction in PM2.5.” One of the co-authors of this study, Francesca Dominici, is also a co-author on the JAMA study.
The JAMA study authors are aware of these contrary findings yet opted to disregard them so as not to distract from their apparently pre-determined conclusions.
II. Omission of material information is scientific misconduct.
According to the standards for scientific misconduct applicable to studies funded by the Department of Health and Human Services established in 42 CFR Part 93 ⎯ Public Health Service Policies On Research Misconduct:
“Research misconduct” means:
… fabrication, falsification, or plagiarism in proposing, performing or reviewing research or in reporting research results.
(a) Fabrication is making up data or results and recording or reporting them.
(b) Falsification is manipulation research materials, equipment or processes or changing or omitting data or results such that the research is not accurately represented in the research record. [Emphasis added]
(c) Plagiarism is the appropriation of another person’s ideas, processes, results or words without giving appropriate credit.
III. The JAMA study omitted key information in violation of federal rules.
Albert Einstein is credited with the observation that:
No amount of experimentation can ever prove me right; a single experiment can prove me wrong.
The thrust of the comment is axiomatic to science. It applies to the JAMA study as follows: If PM2.5 kills, then it kills everywhere, all the time, and every study result should either be consistent with that hypothesis or be explained away as flawed or faulty.
There are many studies that fail to associate PM2.5 with death ⎯ e.g., the three studies cited above. But the JAMA study fails to mention or even allude to the existence of this contradictory evidence, let alone explain it away.
Omitting to even mention the existence of contradictory results is a clear misrepresentation of the research record. Worse, this misrepresentation can only be viewed as intentional as the existence of contradictory results are provably known to the JAMA study authors and at least one of its funders. There is no reasonable excuse for the omissions.
Although omission of the aforementioned significant contradictory evidence constitutes scientific misconduct on its own, there were other key omissions as well.
As every epidemiologist knows, epidemiology is merely statistical in nature and statistics cannot establish causation by themselves. As the U.S. Environmental Protection Agency, which is responsible for regulating PM2.5 in outdoor air, acknowledged to a federal court in litigation involving PM2.5:
[E]pidemiological studies do not generally provide direct evidence of causation; instead they indicate the existence or absence of a statistical relationship. Large population studies cannot assess the biological mechanisms that could explain how inhaling [PM2.5] can cause illness or death in susceptible individuals.
To assess the “biological mechanisms” that could explain how inhaling PM2.5 could cause death or illness, animal toxicology or human clinical research is necessary. But none of the extant PM2.5 animal toxicology, human medical research or human clinical research studies supports the hypothesis that PM2.5 kills. In short, there is absolutely no medical or physical evidence that supports the notion that PM2.5 kills.
In addition to the absence of biological, medical or other physical evidence supporting the notion that PM2.5 in outdoor air kills, there is a host of real-world evidence ranging from the smoking epidemiology to the epidemiology workers with high exposure to PM2.5 (e.g., coal miners) to other high, real-world PM2.5 exposures that plainly contradict the PM2.5-kills hypothesis. In short, if PM2.5 kills hundreds of thousands of Americans per year and millions around the world, as regulatory agencies claim, no physical evidence of this phenomenon has ever been produced.
The JAMA study also relies on a statistical precision that simply doesn’t exist in epidemiology because of unavoidable uncertainty surrounding the data. This is the “garbage-in, garbage-out” phenomenon. While the JAMA study pretends to condemn PM2.5 based on a hazard ratio on the order of 1.05, every professional epidemiologist knows that hazard ratios below the level of 2.0 are unreliable. This is has been a long-held view maintained by the National Academy of Sciences, National Cancer Institute, World Health Organization, Food and Drug Administration and as well as the original Bradford Hill guidelines for interpreting epidemiologic results.
The unreliable data problem is writ large in the JAMA study as it lacks, for example, information on cause of death for any individual in the Medicare population, relies on entirely guesstimated exposure data, and fails to consider confounding factors such as smoking, socioeconomic status and any of the other myriad potential competing risk factors for death.
All this key information is omitted from the JAMA study discussion section.
IV. The JAMA study fails to adjust its results with the results of an earlier, similar study by the same authors using the same data.
Earlier this year, the JAMA study authors published a similar study using the same data in the New England Journal of Medicine (NEJM study). In the NEJM study, the study authors reported that long-term (years) exposure to ambient levels PM2.5 was associated with mortality. The JAMA study, in contrast, claims that any exposure (even one molecule) to ambient PM2.5 is associated with short-term (same-day) mortality.
So between the NEJM study and the JAMA study, the study authors have now claimed that PM2.5 can cause death within 24-hours of inhaling any amount of PM2.5 and/or after more than a decade of inhaling relatively vast amounts of PM2.5. Moving past the toxicological absurdity (there is no toxin or agent known to science that works this way), if the JAMA study result (same-day mortality from inhaling PM2.5) were correct, how could the study authors have any confidence that the NEJM study (mortality after long-term exposure to PM2.5) result is valid? That is, how would one have any confidence that reported long-term mortality wasn’t actually caused by same-day inhalation of PM2.5, or vice-versa?
Moreover, in the JAMA study, the study authors admitted that the study doesn’t consider or adjust for the results of the NEJM study (See p. 2454, “the case-crossover design does not allow estimation of mortality rate increase associated with long-term exposure to air pollution. Long term risks in the same study population have been estimated elsewhere [footnote to the NEJM study].”)
The study authors’ “design” change claim is an obvious canard of an excuse. The NEJM and JAMA study claims are mutually exclusive and cannot both be true. The study authors know this but have intentionally deceived the public as to the inherent contradiction of their claimed results.
V. The study authors provide bogus citations to support their false claim.
The JAMA study authors state:
The association of mortality and PM2.5 exposure is supported by a large number of published experimental studies in animals [footnotes to three studies] and in humans exposed to traffic air pollution, [footnotes to two studies], diesel particles [footnote to one study] and unfiltered urban air [footnote to one study]. [Emphasis added]
The three footnoted experimental animal studies are:
- Tamagawa E et al. Particulate matter exposure induces persistent lung inflammation and endothelial dysfunction. Am J Physiol Lung Cell Mol Physiol. 2008 Jul;295(1):L79-85. doi: 10.1152/ajplung.00048.2007. Epub 2008 May 9.
- Bartoli CR et al. Concentrated ambient particles alter myocardial blood flow during acute ischemia in conscious canines. Environ Health Perspect. 2009 Mar;117(3):333-7. doi: 10.1289/ehp.11380. Epub 2008 Sep 10.
- Nemmar A et al. Pharmacological stabilization of mast cells abrogates late thrombotic events induced by diesel exhaust particles in hamsters. Circulation. 2004 Sep 21;110(12):1670-7. Epub 2004 Sep 13.
But none of these studies report any mortality among animals from their exposures to PM2.5. There are no other studies that do so either.
The four footnoted experimental human studies are:
- Hemmingsen JG et al. Controlled exposure to particulate matter from urban street air is associated with decreased vasodilation and heart rate variability in overweight and older adults. Part Fibre Toxicol. 2015:12:6.
- Langrush JP et al. Beneficial cardiovascular effects of reducing exposure to particulate air pollution with a simple facemask. Part Fibre Toxicol. 2009:6:8.
- Mills NL et al. Ischemic and thrombotic effects of dilute diesel-exhaust inhalation in men with coronary heart disease. N Engl J Med. 2007:357(11);1075-1082.
- Brauner EV et al. Indoor particles affect vascular function in the aged: an air filtration-based intervention study. Am J Respir Crit Care Med. 2008;177(4):419-425.
None of these studies report any clinical health effect, let alone any mortality caused by or associated with PM2.5. Moreover, myriad and all the extant human clinical research studies (inexplicably not cited by the study authors), including many sponsored by the U.S. Environmental Protection Agency and the U.S. Department of Health and Human Services, fail to associate PM2.5 with mortality or even any clinical health effect.
It is worth noting that any human clinical research designed to study whether PM2.5 killed people would violate every law and regulation meant to protect humans participating in scientific research ⎯ from the Nuremberg Code through the federal Common Rule. The fact that humans have often been exposed to exceedingly high levels of PM2.5 in clinical research more reasonably and logically indicates that PM2.5 is NOT associated with mortality. This is particularly relevant to the JAMA study, which purports to associate inhalation of PM2.5 with same-day/short-term death.
So the JAMA study author claims that experimental evidence supports the reported study results are demonstrably and totally false.
VI. The JAMA study authors are irresponsibly exaggerating their results in the media.
Despite the dubious nature of the JAMA study, its authors are in the media irresponsibly touting the product of their misconduct:
- Joel D. Schwartz (New York Times, December 27, 2017):
“This translates to PM2.5 causing an extra 20,000 deaths a year. Separately, a 10 parts per billion decrease in ozone would save 10,000 lives per year.”
This amounts to more deaths per year than caused by AIDS, Dr. Schwartz said. “But unlike AIDS, we know the cure: scrubbers on coal-burning power plants that don’t have them, and reduction in nitrogen oxide emissions because they drive the production of ozone.
- Frederica Dominici (Harvard media release, December 26, 2017):
“This the most comprehensive study of short-term exposure to pollution and mortality to date,” said Francesca Dominici, professor of biostatistics, co-director of the Harvard Data Science Initiative, and senior author of the study. “We found that the mortality rate increases almost linearly as air pollution increases. Any level of air pollution, no matter how low, is harmful to human health.
- Frederica Dominici (XinhuaNet, December 26, 2017):
We found that the mortality rate increases almost linearly as air pollution increases,” Professor Francesca Dominici, co-director of Harvard University Data Science Initiative and senior author of the study, said in a statement. “Any level of air pollution, no matter how low, is harmful to human health.”
- Qian Di (Harvard media release, December 26, 2017):
No matter where you live—in cities, in the suburbs, or in rural areas—as long as you breathe air pollution, you are at risk,” said Qian Di, lead author of the study and a doctoral student in the Department of Environmental Health.
The touted JAMA study results are the product of poor quality data, worse statistical analysis and scientific misconduct.
VII. Conclusion
There can be little doubt that the methodologically flawed JAMA study, as published, intentionally omits key information that would otherwise place the reported results in accurate context. The reasons for this are obvious. I am asking that the JAMA study and JAMA editorial (as fruit of the poisonous tree) be retracted or amended so as not to misrepresent the research record.
In the event that you refuse this request, please provide a detailed explanation of how the aforementioned shortcomings meet the JAMA’s standards of publication.
Please let me know if you require further information.
Sincerely,
/s/
Steven J. Milloy
Publisher
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