Corporate manipulation of research: strategies are similar across five industries.
The release of over forty-three million pages of internal industry documents as part of a number of legal settlements in the 1990s, most notably the Master Settlement Agreement with forty-six state attorneys general in 1998, (1) has revealed the inner workings of the tobacco industry. Recently several other industries have been required to release to the public many of their internal documents as a result of litigation, and in some cases congressional inquiry. In an era when thousands of newly engineered products are being developed and marketed and novel production processes implemented with insufficient regulatory oversight and little understanding of the long-term risks, industries worldwide are greatly expanding their sponsorship of risk research. The release of these documents provides an opportunity to systematically examine the strategies each industry used to manipulate research in ways that would promote their products, or create doubt about the deleterious health effects of their products and manufacturing processes--thereby enhancing their credibility and profits, and shielding them against unwanted regulation or legal liability. Corporate manipulation of research has been described through case studies of individual industries or products. (2) The objective of this study is to systematically categorize these practices across a specific set of industries, using a consistent data source of internal corporate documents.
Using a previously developed framework, (3) we compare the strategies used by the tobacco, pharmaceutical, lead, vinyl chloride, and silicosis-generating industries (mining, foundries, sandblasting, and others) to manipulate research. Strategies included manipulation of the research question to obtain predetermined results; funding and publishing research that supports industry interests; suppressing unfavorable research; distorting the public discourse about research; changing or setting scientific standards to serve corporate interests; and disseminating favorable research directly to decision makers and the public, bypassing the normal channels of scientific discourse. We hypothesize that the five industries used similar strategies to manipulate research.
The tobacco documents were made available through settlement of major lawsuits against the industry in the 1990s, culminating in the Master Settlement Agreement. The Legacy Tobacco Documents Library at the University of California, San Francisco (UCSF) has over eleven million of these documents on its website. (4) The pharmaceutical industry documents were also obtained through litigation and drawn from UCSF's Drug Industry Document Archive (DIDA). (5) Hard copies of the lead, vinyl chloride, and silica industry documents were provided by Dr. David Rosner, author of Deadly Dust, on the silicosis crisis, and Deceit and Denial, on the lead and vinyl chloride industries. The lead and vinyl chloride documents were originally obtained through discovery proceedings in lawsuits against these industries.
The first author undertook the initial review of the document archives. She reviewed over a thousand documents in the DIDA, searching on "research" and terms such as "product defense" and "publication strategy," then extending the search using document numbers, individual names, and other terms found in the documents. She reviewed all 103 documents provided by Rosner for the lead and silicosis-related industries. For vinyl chloride, the second author reviewed extensive notes prepared by Rosner and Markowitz for their book Deceit and Denial on a thousand available documents, and selected thirty-nine of these that were relevant to research practices. The original documents were then obtained at the Chemical Industry Archives website. (6) These examples were supplemented with additional searching on keywords ("publish," "OSHA," names of researchers, etc.) in the archives. As numerous articles have already been published on tobacco industry manipulation of science, the authors relied on documents that have been cited in previous peer-reviewed publications. (7) After review and discussion by the two authors, each document was coded using previously developed categories of research manipulation,8 as follows: (1) fund research that supports the industry's interests, (2) publish in scientific literature research that supports the industry's interests, (3) suppress industry-sponsored research in cases where the results do not support the industry's interests, (4)distort public discourse on research that does not support the industry's interests, (5) set scientific standards that favor the industry's interests, and (6) disseminate favorable research directly to decisionmakers and the public.
We identified 241 episodes of research manipulation in the approximately 2250 documents reviewed and entered them into a database. We then selected exemplars from each industry for each category based on the following: 1) the example is unambiguous as an indicator of research manipulation; 2) it is representative of a number of statements in our dataset; 3) it concerns projects that were implemented, rather than just discussed in the planning stage and then dropped; and 4) it reflects an important development in the history of the industry's promotion or defense of its activities.
We present exemplars of the six manipulative techniques that reflect common practices and perspectives of the time for each industry. We include historical, political, or scientific contexts for examples as needed. We calculated the total number of incidences we found in the databases for each type of strategy and each industry. We then tested for independence of distribution of strategy between the tobacco industry, which had the highest frequency of incidences, and the other industries. (We were not able to compare all industries simultaneously because the expected frequencies were too small in some cells.) We used exact two-sided tests of independence of contingency table frequencies. The overall significance level for all four tests was 5%, so we used a significance level of 0.05/4 = 0.0125 for each of the four tests.
Table 1 shows the numerical occurrences of each strategy by industry. The distribution of strategies used by tobacco was different from each of the other industries. The null hypothesis of independence was rejected for all four tests with an overall significance level of 5%. An exploratory analysis of the source of this lack of independence looked at the largest differences between frequencies expected (assuming independence) and the observed frequencies for each strategy, using the chi-square contribution. The largest differences in strategy frequency between the five industries are explained at the bottom of Table 1. (The P-VALUE for each test is very small for each comparison, far less than the significance level of 0.0125 for each test.)
I. MANIPULATION STRATEGIES
A. Fund Research that Supports the Industry's Interests
Each of the five industries sponsored research (both internal and external) intended to produce findings that would support their commercial interests. Internal documents indicate that much of this research was designed specifically to refute independent research. A lack of disclosure, or even deliberate secrecy, about research funding from industry is also a characteristic of these funding arrangements. The federal government has promulgated numerous policies and standards regarding conflicts of interest, to which private entities in contract with the government must adhere. (9) The nongovernmental American Academy for the Advancement of Science (AAAS) has also published guidelines on conflict of interest. (10) These various standards can serve as guides for research practices in the private sector, but this is not always the case.
In 1976, Brown & Williamson's General Counsel stated explicitly to company executives that the purpose of the tobacco industry's investment in tobacco and health research was to raise doubts about tobacco's harmfulness:
During the past 20 years the industry has committed more than $50 million to scientific research related to tobacco and health. The significant expenditures on the question of smoking and health have allowed the industry to take a respectable stand along the following lines--"After millions of dollars and over twenty years of research, the question about smoking and health is still open." (11)
STEPS (Study of Neurontin: Titration to Effectiveness and Profile of Safety) was an uncontrolled, open-label dosing study in which physicians were recruited to prescribe Neurontin to epilepsy patients. (12) While the purpose stated in the published article was to examine the effectiveness of Neurontin, internal documents state the purposes as to "communicate with ... patients ... the benefits of adding Neurontin" and "teach physicians to titrate Neurontin to clinical effect." (13) The ultimate goal was to increase market share and per patient dosage of Neurontin, and to preempt launch of competitor drugs. (14)
In 1935 the head of the Lead Industry Association (LIA) complained to members that:
We are constantly investigating alleged cases of lead poisoning and endeavoring to correct misstatements about lead poisoning, to calm misapprehension about the toxic properties of the metal.... [In this regard,] [a]t the request of Dr. Aub of the Harvard Medical School ... we are contributing $10,000 to Harvard College to continue the lead investigations.... (15)
Aub's research generally minimized the harm of lead. (16)
4. Vinyl Chloride
In 1967 the Manufacturing Chemists' Association (MCA) agreed to fund a study "hopefully expected to ... confirm that the condition [a degenerative bone disease called acroosteolysis] is purely an occupational disease and in no way affects the general public using polyvinyl chloride products." (17) In fact, vinyl chloride was used in aerosol propellants such as hair sprays, shower curtains, car upholstery, and a host of other consumer products. When the results of the study included some that were unfavorable to the industry, they were deleted from the final report. (18)
In the 1930s, publicity around the epidemic of silicosis, union activism, and insurance liability put mining, foundry, and other "dusty trades" on the defensive. They sought to defuse the crisis by reasserting the predominance of professional experts employed by or allied to these industries. In 1935, companies set up the Air Hygiene Foundation to conduct research on silicosis and to influence government policy and public perceptions. The Foundation was organized so that:
[T]he work could be carried out in a most confidential manner as to who was supporting the research and no one would know what industries or individuals were contributing to the fund. This would enable the organization to get soundly established, so that if later on it was desired to come out in the open this could be arranged. (19)
B. Publish Research in the Scientific Literature that Supports the Industry's Interests
Publishing research in the scientific literature enhances a corporation's credibility and can be a valuable marketing strategy. These publications may or may not be the results of an actual research study. In addition to publishing in scholarly journals and books, corporations can also fund publication of symposia proceedings and industry-supported journals. (20) Industry spokespersons can then cite these as if they are peer reviewed articles, and often with no funding disclosure. Generally, industries have been careful to control all aspects of publication, including careful review of the drafts, selective publishing of results, and precise wording of any disclosures. The International Committee of Medical Journal Editors has promulgated standards regarding disclosure of authorship and conflicts of interest for scientific articles to be published in medical journals. (21) In addition, the Council of Science Editors (22) and the British-based Committee on Publication Ethics (13) have produced white papers or issued standards for non-medical as well as medical journals. However, none of these standards are universally adhered to by all of the thousands of journals being produced worldwide. In general, nonbiomedical journals have not adopted broad statements regarding conflicts of interest.
In 1991, Philip Morris and other tobacco companies recruited two independent Japanese scientists to refute Hirayama's influential paper demonstrating that secondhand smoke was associated with lung cancer. (24) The project was managed by an industry law firm, Covington & Burling. While the Japanese scientists were initially named as the Principal Investigators, in 1993 Covington & Burling's "Senior Scientific Advisor" wrote tobacco industry executives: "After considerable effort working with Dr. Yano at Teikyo University, we feel it is time to recommend that Mr. Peter Lee [a PM consultant] be asked to submit the Japanese spousal study research for publication in the British Medical Journal." (25) By the time the manuscript was published in 1995 in the International Archives of Occupational and Environmental Health, the sole author was listed as Peter Lee, with just a brief mention of one of the Japanese researchers in the Acknowledgements. The study concluded that Hirayama's research was flawed by misclassification bias, and that "[t]here is no direct evidence that workplace environmental tobacco smoke (ETS) increases lung cancer risk." (26) In 2005, Dr. Yano published a renunciation of the findings of the Lee study in Tobacco Control, pointing out that "[i]n addition to the misrepresentation of the facts demonstrated in his own paper, Lee did not report some of the important findings obtained in the project." (27) "Using all the data from this project changes the conclusion of the [Lee] report," (28) and even "strengthens Hirayama's findings." (29)
Industry involvement in publication of research in scholarly journals has taken two forms: ghostwriting of articles signed by prestigious "guest authors," and pre-publication review of original research articles. In 1997, medical communications company Medical Education Systems (MES) submitted a proposal to Parke-Davis "requesting an educational grant to publish a series of scientific articles in peer reviewed journals surrounding antiepileptic drug use." (30) The grant totaled $160,500, for "editorial development, honoraria, and miscellaneous fees." (31) Of the twelve proposed articles, nine were eventually published using the suggested guest authors. (32) Among the articles was one by Michael Merren titled Gabapentin for Treatment of Pain and Tremor, to be published in the Journal of Southern Medicine. The favorable results of his study were published in this journal in August 1998 with no disclosure of the funding source, Parke-Davis, or the participation of MES. (33)
Another researcher, Gary Mellick, received twenty-nine payments totaling over $21,000 between September 1994 and September 1996 for various promotional activities. (34) His favorable case report on pain relief for six patients, published in 1997, served a promotional purpose for the drug while disclaiming any financial benefit from the drug's manufacturers: "No commercial party having a direct or indirect interest in the subject matter of this article has or will confer a benefit upon the authors or upon any organization with which the authors are associated." (35)
Figure 1 shows a 1997 Parke-Davis status report on the commissioned articles. Comments from the recipient written in the right column are revelatory: the Parke-Davis executive writes "[r]ewrite" next to Merren's article. In the third row down, the memo reads, "[a]uthor ready to submit." The executive responds, "[n]o." In the seventh row, Parke-Davis announces that the second draft has been provided to the author (rather than the reverse). (36)
[FIGURE 1 OMITTED]
The first report from the United States Bureau of Mines on the study of Exhaust Gases from Engines Using Ethyl Gasoline concluded that leaded "ethyl gasoline" exhaust fumes were not harmful. (38) The Bureau of Mines itself, under President Calvin Coolidge, deferred to the lead industry's concerns in preparing the report. In fact the Ethyl Corporation, which partially funded the study, specified in its contract with the Bureau of Mines that "before publication of any papers or articles by your Bureau, they should be submitted to [Ethyl] for comment, criticism, and approval." (39)
4. Vinyl Chloride
In 1980, the Manufacturing Chemists' Association (now renamed the Chemical Manufacturers' Association (CMA)) hired Environmental Health Associates of Berkeley to conduct an epidemiological study "to gain information to help in future lawsuits." (40) The chief researcher on the project published the results in the American Journal of Industrial Medicine without first consulting with his funders. (41) The results were alarming for the industry, showing "significant mortality excesses" for various cancers. A plant manager complained that "the authors prematurely published the study without submitting it to the CMA for review before publication." (42) After teleconferencing with the CMA's Vinyl Chloride Monomer Panel, the authors wrote a letter to the journal retracting some of their most damaging findings, for example concluding that "our finding of an excess of brain cancer among U.S. vinyl chloride workers reported earlier was not likely related to the chemical." (43)
At a 1939 meeting of the Air Hygiene Foundation, engineer Philip Drinker reported to members that:
For the past three years, the Foundation has rendered generous help to the Journal of Industrial Hygiene & Toxicology in the form of an annual gift which has helped defray the cost of publishing the Journal's abstracts of the world's literature on industrial hygiene. In return, the Journal has assisted the Managing Director of the Foundation in the publication of his own abstracts. It is the hope of both parties that this arrangement will continue in the future. (44)
No concern was expressed over the conflict of interest this arrangement entailed.
C. Suppress Research that Does Not Support the Industry's Interests
Our category of suppression involves withholding or strategically delaying dissemination of research. Data have been withheld or deleted from articles submitted to scholarly journals, presentations before legislative hearings and regulatory agencies, reports to independent corporate boards, and the media. Both the tobacco industry (45) and the pharmaceutical industry (46) have used lawyers as intermediaries in order to assert attorney-client privilege and work product privilege to prevent their research from being disseminated. Forms of suppression include excluding some cases, reducing or eliminating some exposure data, partial deletion of results, and suppressing entire articles or project results. (47)
As the groundbreaking 1964 Surgeon General's Report was being prepared, Brown & Williamson's general counsel advised withholding research commissioned by, but possibly problematic for, Brown & Williamson from the Tobacco Industry Research Council's (TIRC) Scientific Advisory Board (SAB) or the Surgeon General. Battelle was a research institute whose closely guarded research compared the sedative and addictive effects of nicotine with pharmaceutical tranquilizing agents.
Hoyt [Executive Director of TIRC/Council for Tobacco Research] ... agreed to withhold disclosure [of the] Battelle Report to TIRC members or SAB until further notice from me. Finch [Brown & Williamson executive] agrees submission Battelle or Griffith developments to Surgeon General undesirable and we agree continuance of Battelle work useful but disturbed at its implications re cardiovascular disorders. (48)
In 1994 and 1995, Parke-Davis internal researchers undertook two clinical studies, numbered 945-77 (western Europe) and 945-177 (an identical extension in eastern Europe), both evaluating Neurontin in differing doses and in comparison with another drug. When the results of the 945-177 study "failed to establish dose differentiation and statistically significant efficacy," (49) the research team recommended that Parke-Davis "evaluate the feasibility of not filing 945-177" with its FDA New Drug Application "especially since the study may adversely impact promotion." (50) One month later, the "Neurontin Core Marketing Team" met and concluded that while the results of 945-177 "must be included in the U.S. FDA [application]," (51) the results "will not be published [in the scientific literature], nor will the combined results of 945-77 plus 945-177 be published." (52) However, "945-77 [a favorable study] will result in two publications: A short communication in the Lancet, and [a] full manuscript in Epilepsia later." (53) These were published. (54)
The Lead Industry Association's 1956 Annual Report recounted an incident where adverse research was suppressed at a very late stage of publication:
Getting wind of a forthcoming report on the suitability of plastic pipe for potable water supplies in preparation at the University of Michigan, we [the LIA] arranged to see the galley proof of the report and, through contacts with members of the advisory committee on the report, were able to secure elimination of a number of statements adverse to the use of lead stabilizers. (55)
4. Vinyl Chloride
In 1973, following FDA confirmation that vinyl chloride could migrate from plastic bottles to the liquids contained in them, the National Institute of Occupational Safety and Health (NIOSH) published a request for information from scientists, corporations, and public health officials. This posed a dilemma for the industry. (56) MCA's Vinyl Chloride Research Coordinators decided that "possible consumer safety and related potential hazards would not be pertinent to a presentation to NIOSH which is concerned with employee health matters." (57) Thus "all references to use of vinyl chloride in aerosol propellants were removed, since it is a minor part of the industry and is not a worker-exposure problem except for beauticians and can-fillers." (58) The industry was alarmed that information about vinyl chloride in consumer products such as hair sprays and air fresheners might be revealed to a public agency.
In 1936, Roosevelt's Secretary of Labor Frances Perkins called for a national conference on silicosis, to include labor unions and workers as well as scientists and industry representatives. An editorial in the Engineering News-Record asserted that such a broad-based meeting would "accomplish nothing. The conference would be a modern Tower of Babel, for the several groups do not speak the same language or understand each other's viewpoints." (59) Attempting to return the discussion to the arcane and closed world of industry-affiliated scientists, he wrote that silicosis is "far too complex, too involved and too little understood to be suited to mass-meeting methods." (60)
D. Distort Public Discourse About Research that Does Not Support the Industry's Interests
Each of the five industries has engaged in criticism of independent research that does not support its interests. This can take the form of attacking the methodology of opponents, obtaining and then reanalyzing existing data, (61) or insisting that more research is needed. Corporate interests have been shown to use misleading epidemiological arguments to criticize legitimate independent research. (62) Corporate-sponsored critics also tend to focus on specific studies or even single aspects of a study rather than the body of evidence as a whole in regulatory proceedings, in order to cast doubt on well-established science. (63) As Michaels points out, for many industries "debating the science is much easier and more effective than debating the policy." (64) Policy and profit concerns are in fact disguised as scientific questions. (65)
The Environmental Protection Agency's (EPA's) 1993 report classifying environmental tobacco smoke as a Group A carcinogen was a major setback for the industry. The report created a flurry of counterattack plans, such as that shown in Figure 2, in which Philip Morris planned to "create a sense of doubt about [the] EPA report" and attack it as "flawed science." (66)
[FIGURE 2 OMITTED] (67)
When an observational analysis raising questions about the safety of Vioxx was presented at a major international conference in 2004, Merck sent out a template "issue response letter" to its marketing representatives to answer physicians' questions about the drug's safety:
Merck believes that conclusions from retrospective, observational analyses should be interpreted with caution. Observational studies, even those conducted in as rigorous a manner as possible, are often unable to completely control for differences between groups, which may produce confounded results. These types of analyses must always be considered in light of their limitations and within the context of randomized, controlled clinical trials. (68) Observational studies are usually used to detect harm. Because adverse events are rare, randomized clinical trials are not as useful in this area. Merck was attempting to minimize the impact of numerous published observational studies which were undermining its arguments that Vioxx was safe. (69)
The American Council on Science and Health (ASCH) describes itself as a consumer education consortium. Its funders have included the Ethyl Corporation, Exxon, Ford, Shell, Union Carbide, Dow, and Monsanto. A 2000 posting on its website raised doubts by stating that "[c]laims of subtle neurobehavioral effects in children due to elevated BLL [blood lead levels] are not based on firm evidence." (70) ASCH then sought to weaken the evidence of independent research that implicated lead by emphasizing the role of potential confounders: "[M]any studies that attempt to link low-level lead exposure with learning disabilities, behavioral problems, attention deficit disorders, and lowered IQ are complicated by multiple confounding socioeconomic and familial factors." (71)
4. Vinyl chloride
In April 1976, The Lancet published an article by Infante et al. reporting a significantly increased fetal death rate among wives whose husbands had been exposed to vinyl chloride monomer. (72) The Society of the Plastics Industry reported in a November 1978 press release that it:
[E]ngaged eminent scientists--Dr. Brian MacMahon ... of the ... Harvard University Graduate School of Public Health, and Dr. Thomas Downs, ... University of Texas ... to undertake independent reviews of this study. Both Dr. MacMahon and Dr. Downs were highly critical of the analytical methods used. Dr. Downs said that the "misleading conclusions" drawn by the authors were brought about through the "selection and use of their control group." Dr. MacMahon called the data "worthless," the analysis "naive" and the test "inadequate and misleading." (73)
Despite the intense criticism of the two hired doctors, Infante's study was corroborated by numerous subsequent studies. (74)
The silica industries present a somewhat different case from the other industries in that they focused their criticism on non-scientists, who were urgently calling attention to the silicosis epidemic in the 1930s. These included affected workers and their unions, individual physicians caring for them, and progressive leaders including Secretary Perkins. As Rosner and Markowitz point out, "[i]ndustry ... wanted to return the discussion of silicosis to the realm of science and medicine, where experts from the Public Health Service, industry, and other academic and research entities could reassert the dominance of industry-sponsored professionals over politicians and labor unions." (75) Thus, the summary report from the industry-organized National Silicosis Conference in 1937 declared:
During the past few years so many conflicting statements have been made about ... silicosis that many persons have become confused.... Alarmed workers have filed claims against their employers, sometimes unjustly.... A few incompetent attorneys and physicians, particularly in court cases, have further complicated the situation, so that today a condition exists that fully deserves ... some definite declarations by those that are competent to speak. (76)
E. Set Scientific Standards That Favor the Industry's Interests
Setting of scientific standards takes two forms: determining the methodological criteria for scientific proof, and establishing exposure thresholds above which a product or process is deemed unsafe. Standards set by governmental agencies or professional societies can have major impacts on worker and consumer safety, and yet the role standards play is often ignored by health advocates, policy analysts, and the public. Industry strategists, however, understand their importance and work to play a major role in the setting of both national and international standards to ensure that they benefit corporate interests. Ong and Glantz have described how the tobacco industry used the concept of "good epidemiological practices" (GEP) to raise the standards of scientific proof for the harms of their products to an unattainable and self-serving level. (77) Michaels and Egilman (78) have discussed how these demands for absolute proof were appropriated by other industries to undermine efforts to move proactively to reduce exposure to harmful products.
As mentioned above, the tobacco industry was threatened by the EPA's 1993 report classifying secondhand smoke as a Group A carcinogen. One way of attacking the report was to criticize methodology standards. A consultant lawyer to Philip Morris wrote Tom Borelli, Philip Morris's Director of Science and Environmental Policy, recommending that Philip Morris's focus on criticizing meta-analysis as a methodology:
Meta-analysis is a new technique, used only a few times ... by EPA or the courts. My understanding is that there are few, if any, guidelines for the proper use of meta-analysis and possibly even some question about whether it is a scientifically valid method of analysis. ... [Y]ou might wish to encourage an evaluation of meta-analysis--without direct reference to the ETS risk assessment. ... [E]xpanding this effort to an academic forum, an industry forum (drinking water, power utilities, etc.), and perhaps the EPA Risk Assessment Commission.... Even though this effort might not focus on ETS ..., it could be of great use in the future.... ... in a regulatory proceeding. (79)
The tobacco industry also has been heavily involved in setting standards for tobacco products. The ISO (International Organization for Standardization), a network of national standards institutes of 157 countries, is the world's largest developer and publisher of international standards for products and services* It is a non-governmental organization whose member institutes are from both the public and private sector. Standards for tobacco products are developed for the ISO by the Cooperation Centre for Scientific Research Relative to Tobacco, or CORESTA. (80) In 1993, a Philip Morris executive described the tobacco industry's relationship to these two entities: "There are two international organizations which are controlled by the Industry: CORESTA and ISO.... CORESTA ... is 100% controlled by the Industry.... Representation within the ISO technical committee 126 [concerning tobacco/tobacco products] is made up of approximately 80% Industry...." (81)
Among standards promulgated by ISO/CORESTA are methods for measuring tar and nicotine deliveries and determining pesticide residues in cigarettes. (82)
We did not identify any examples of attempting to change scientific standards for the pharmaceutical industry. In order to gain approval for new drugs (or new uses for existing drugs), the industry must conduct its research according to FDA standards of practice ("Good Laboratory Practices"). While the pharmaceutical industry has lobbied and presented at hearings before Congress and state legislatures regarding regulatory standards, we were limited by the documents in DIDA, which are primarily related to marketing.
The American National Standards Institute--previously called the American Standards Association--is a private, non-profit organization that oversees the development of voluntary consensus standards for U.S. products and services. Two members of the Lead Industry Association served as Chair and Member of the ASA's Committee on Toxic Dusts and Gases in 1955. In these positions they pressed for "raising the long-accepted standard" for maximum acceptable concentration of lead and its compounds in the atmosphere of work places, "from 1.5 mg. per 10 cubic meters to 5.0 mg. for lead sulfide and 2.0 mg. for metallic lead and other compounds, substantial increases which should be of material engineering aid to our industries." (83) This standard was later promulgated. (Recent research, in fact, "suggest[s] that there is no safe threshold for the toxicity of lead in the central nervous system." (84))
4. Vinyl Chloride
The chemical industry is subject to standards set by the Environmental Protection Agency and participates in ANSI standard-setting as well. These standards and practices were not as fully in place in May 1974, when OSHA proposed a threshold limit value (TLV) of one part per million (ppm)--a "no detectable level" of exposure to VC among workers--and called for comment and criticism. (85) Shortly after, Senator Tunney's Commerce Subcommittee on the Environment held a hearing on the subject. While an industry-commissioned study at the University of Michigan in 1969 found that a safe threshold for vinyl chloride should be below fifty ppm, (86) industry representatives did not reveal these findings to the Committee. Instead, the President of the Society of the Plastics Industry cited another study, from Dow Chemical, in his testimony:
The only study to date ... show[s] a general cancer increase among heavily exposed workers--above 200 parts per million ... --but none among workers below that level. No angiosarcomas were found. In general, the Dow study tends to show that low levels of VCM exposure do not result in an excess of disease." (87)
As of the 1930s, neither the U.S. government nor any other entity had set a standard for maximum levels of silica dust in a workplace. The silicosis epidemic of that time forced a discussion of the issue. While industry consultant Philip Drinker admitted at the 1937 silicosis conference that "[t]here is no accurate scientific justification for ... [a] suggested standard of 5 million [ppm]," (88) the conference final report concluded, "[g]ood practice requires that concentrations of high siliceous dust be kept at five million particles per cubic foot or less." (89) Seven years earlier, an American Public Health Association committee had found that five ppm "only protected workers ... from contracting tuberculosis as well as silicosis." (90) Nonetheless, eleven years after the 1937 conference, the Industrial Hygiene Foundation was still arguing that five ppm was an adequate standard: "if the product is below five million particles per cubic foot, then a silicosis hazard is presumed not to exist." (91)
F. Disseminate Favorable Research Directly to Decision-Makers and the
"Decision-makers" include policymakers--legislators and regulatory agencies--and, in the case of pharmaceuticals, individual physicians. Dissemination to the public includes public testimony, press releases, sponsored articles written for the lay press, and media advertising. Direct dissemination of scientific findings in these ways can sidestep the normal scientific process of peer review and publication in scholarly journals. In addition, industries can boost the impact of peer-reviewed articles if they disseminate them directly to the decision-makers.
From 1958 to 1969, the Tobacco Institute disseminated a quarterly publication entitled Tobacco and Health Research (THR), mailing it free of charge to 340,000 U.S. doctors, scientists, dentists, and medical schools. THR provided summaries of research published in scientific and medical journals, and sometimes unpublished papers delivered at scientific meetings. Table 2 shows public relations firm Hill & Knowlton's suggested criteria for selection of reports to be published in THR:
DrugDex is an authoritative system providing comprehensive information on all FDA-approved and investigational drugs and is used by clinicians, pharmacists, researchers, and governments worldwide. Parke-Davis altered the conclusions of a study submitted to DrugDex to present Neurontin as more efficacious, especially in higher dosages. In 1996, the company funded a clinical trial by Gorson et al. on the efficacy of Neurontin in treatment of painful diabetic neuropathy. Gorson's 1997 draft abstract submitted to his funders concluded that "Gabapentin, at a dose of 900 mg/day, is probably no more effective than placebo in the treatment of painful diabetic neuropathy." (93) By January 1998, Parke-Davis's internally circulated version of the Gorson paper concluded, "[g]abapentin may be effective in the treatment of painful diabetic neuropathy. Our results suggest that further studies evaluating higher dosages of gabapentin are warranted." (94) The final version of the Gorson study, published in 1999, concludes simply, "[t]he results of this study suggest that gabapentin is probably ineffective or only minimally effective for the treatment of painful diabetic neuropathy at a dosage of 900 mg/day." (95) During this time Parke-Davis' Lesley Fierro served on the Pharmaceutical Advisory Panel of DrugDex. In this capacity Fierro reviewed and participated in editing the DrugDex monograph on Neurontin, (96) which cited the 1999 published Gorson study and added the following altered conclusion: "The authors suggest that higher doses of gabapentin are needed." (97) This assertion is nowhere to be found in the published Gorson study.
The Lead Industry Association put its research directly in front of government policymakers, as in the appearance by LIA head Felix Wormser, who in 1966 responded to growing public concern about lead poisoning by appearing before Senator Muskie's Subcommittee on Pollution and declaring: "From results of extensive scientific investigations, 'I can positively assert that lead constitutes no public health hazard in America today.' ... [O]n the basis of 'vast clinical evidence' ... 'the general public is not now, nor in the immediate future, facing a lead hazard.'" (98)
4. Vinyl Chloride
In 1977, a draft epidemiological study of vinyl chloride workers by consulting firm Equitable Environmental Health was presented to the Manufacturing Chemists' Association Review Committee for comments. Union Carbide's Robert Wheeler objected to the report's characterization of problems as an epidemic, writing that "the summary and conclusions should accentuate the positive, discuss the in-between and not try so hard to accentuate the negative." (99) A Uniroyal toxicologist agreed, pointing out the strategic political uses of the study if appropriately edited: "It is up to industry to cite this report to show that VC has turned out to be much less of a problem than first feared and to put the whole carcinogen problem in better perspective." (100) After extensive revision, MCA distributed the final version of the study to sponsoring companies (with instructions that all previous drafts should be destroyed), (101) and to "all pertinent government agencies." (102)
The Science News Letter was a prominent news service that played a major role in disseminating science information to the public and the media in the twentieth century. In 1946, scientists from the Industrial Hygiene Foundation announced in the newsletter that "silicosis, once a great hazard to the health of industrial workers, is no longer a threat." (103) It was a "triumph of scientific research.... Potentially poisonous dusts, fumes and gases can and are being used every day in modern industry without danger. Not infrequently we find nuisance dust exposures to be more injurious to the mechanical equipment than to workmen." (104) In fact, government reports indicated that the same number of workers were at risk of silicosis in the 1950s as in the 1930s. (105)
The five industries examined used similar strategies to manipulate research on risk: funding and publishing research that supports their interests, suppressing unfavorable research, distorting public discourse about unfavorable research, setting scientific standards that favor industry interests, and disseminating favorable research directly to decision-makers, thereby bypassing usual methods of scientific discourse. These strategies have been increasingly used to challenge the science underlying government regulations and legislation, while protecting industries from litigation. In all five industries, lawyers and industry executives were involved in the science, making decisions not only about funding but also about the design, conduct, and dissemination of research, and basing their decisions on strategic corporate interests rather than the weight of the evidence. The difficulties in detecting these strategies were compounded by the industries' failure to disclose their involvement, thereby sabotaging mechanisms of open scientific inquiry. It took litigation and public disclosure of court documents to finally bring these data to light.
The specifics of these strategies varied among industries. While pharmaceutical companies used peer-reviewed publication as a marketing tool, the other industries were more concerned to control publication in order to minimize any negative publicity about the health effects of their products. Their goal was to promote controversy in order to create doubt about the health risks of their products or manufacturing processes. Pharmaceutical companies are unique in this group in that their products are expressly intended to benefit human health. The strategic focus of the silica-ridden dusty trades was to hold the line against attempts to lower the atmospheric dust threshold for workplaces, setting standards industry managers could live with.
Michaels and Bero have documented the close association between reported results of a study and desired results of the study's corporate funder. (106) Gennaro and Tomatis have described how industries have manipulated study design characteristics of research they fund to underestimate risk. The authors describe fifteen different ways, including classifying exposed subjects as unexposed; comparing exposed workers with the generally less healthy general population (the "healthy worker effect"); and disaggregating homogeneous pathologies (e.g. through dividing a multi-factory cohort), thus making statistical significance harder to obtain. (107) Bero and Rennie have described how pharmaceutical industry funding has affected the content and quality of drug studies by, for example, a research question that is too narrow, a non-representative study population, nonrandom allocation of treatment, choice of comparison groups that favor a new drug, inappropriate choice of outcome measures, and misleading data presentation and analysis. (108)
Producing and disseminating favorable research has become a business in itself; numerous consulting firms advertise "product defense" or "litigation support." (109) The firms, and the scientists who own and operate them, sell not just their scientific expertise, but their knowledge of and access to regulatory agencies. The financial success of these firms depends on their ability to help their clients avoid or delay increased regulation, and achieve protection from litigation. Many industries used common resources for product defense as well as dissemination of research, and also met together to forge common strategies. (110)
Our study has several limitations. Most of the documents were obtained through litigation and may not represent a complete picture of the research activities of the five industries. Pharmaceutical industry documents were limited to activities surrounding just two drugs, gabapentin and rofecoxib. Quantitative analysis was limited as we could not examine all existing documents. The number of documents available for each industry varies widely, from seven million tobacco industry documents to the twenty-two for the silicosis industries (although the latter included conference proceedings over 100 pages long). The documents cover very different time periods, ranging from lead and silicosis documentation primarily from the 1920s to the 1960s, to the much more recent pharmaceutical documents. The complexities of the development of each of these industries within different historical periods made it beyond the scope of this paper to conduct a historical analysis of the forms of research manipulation. However, the consistencies in strategies used over such a long period of time suggest that manipulating research has been a vital tool throughout for all these industries.
While there is some variation in type of harm, purpose of product, source data, and specifics of industry strategies, the five industries do not differ in the overall strategies they use to manipulate research. Thus, potential solutions for safeguarding the integrity of corporate research apply to all of these industries, as well as others. First and foremost, there should be complete transparency, including disclosure not only of funding sources, but also the roles of the sponsor in designing or modifying the research, and also the corporate financial ties of investigators--and critics as well. As industry cannot be relied on to make its data public, there must be other ways of obtaining it. As has been suggested for pharmaceuticals, all clinical trials should be registered prospectively with an independent agency such as the National Institutes of Health or World Health Organization. To encourage full publication of any results that are relevant to public health, trial registration should be extended to observational studies, including studies of compounds and substances other than drugs. In addition, independent scholars and regulatory agencies should have access to raw data from corporate-funded studies for reanalysis, just as government-funded investigators currently are required to release their data through the provisions of the Data Access Act. (111) Sponsored investigators should retain control over the publication of their research regardless of the results. (112) Corporate whistleblowers should have protection through legislation or regulation.
Biomedical journals can take the lead in ensuring transparency in all published research, letters to the editor, and editorials. International Committee of Medical Journal Editors (ICMJE) policy requires that any published author retain and declare full responsibility for findings, including complete control over publishing decisions. (113) However, these requirements are not adhered to by all journals. A 2002 national survey by Schulman et al. showed that "academic institutions routinely engage in industry-sponsored research that fails to adhere to ICMJE guidelines regarding trial design, access to data, and publication rights." (114) Other journals--and federal and state regulatory agencies as well--should also not accept corporate-sponsored research and reanalyses of research conducted under contracts in which clinical trial investigators do not have complete control of and responsibility for the data and findings. (115)
Ultimately, conflicts of interest need to be eliminated, not just managed. Shafer and Doucet and Sismondo propose a complete separation of funding decisions and sponsors (sequestration), using independent scientific panels to make funding decisions. (116) In Italy, pharmaceutical companies are required to contribute to a fund to support orphan drug trials, head to head comparisons of drugs, and pharmacoepidemiology studies. These pooled funds are administered by the Italian Drug Regulatory Authority. Funds are granted to independent investigators based on scientific review by an independent panel. (117) Some academic institutions, particularly schools of medicine and public health, have already instituted bans on tobacco industry funding. This list includes Harvard University and Johns Hopkins Medical Schools and Schools of Public Health, the London School of Hygiene and Tropical Health, and M.D. Anderson Cancer Center.
In the short term, these suggestions have prompted concerns that such bans and regulations will inhibit much-needed funding of academic research by industry, given the paucity of government funding currently available. However, regulatory and administrative reforms can be implemented that in the long term will allow industry funding of research to continue at current and even increased levels. This can be done by using mechanisms, such as the ones proposed above, that ensure transparency and sequestration of industry funds.
(1.) TOBACCO CONTROL RES. CTR., THE MULTISTATE MASTER SETTLEMENT AGREEMENT AND THE FUTURE OF STATE AND LOCAL TOBACCO CONTROL (Graham Kelder & Patricia Davidson eds., 1999), available at http://www.tobacco.neu.edu/tobacco_control/resources/msa/msa_analysis.pdf.
(2.) See GERALD MARKOWITZ & DAVID ROSNER, DECEIT AND DENIAL: THE DEADLY POLITICS OF INDUSTRIAL POLLUTION (2002); DAVID ROSNER & GERALD MARKOWITZ, DEADLY DUST: SILICOSIS AND THE POLITICS OF OCCUPATIONAL DISEASE IN TWENTIETH-CENTURY AMERICA (1991); Deborah E. Barnes & Lisa A. Bern, Industry-Funded Research and Conflict of Interest: An Analysis of Research Sponsored by the Tobacco Industry Through the Center for Indoor Air Research, 21 J. HEALTH POL. POL'Y & L. 515 (1996); Lisa A. Bero & Drummond Rennie, Influences on the Quality of Published Drug Studies, 12 INT'L. J. TECH. ASSESSMENT HEALTH CARE 209 (1996); Lisa Bero et al., Lawyer Control of the Tobacco Industry's External Research Program: The Brown and Williamson Documents, 274 JAMA 241 (1995); Lisa A. Bero, Tobacco Industry Manipulation of Research, 120 PUB. HEALTH REP. 200 (2005) [hereinafter Bero, Tobacco Manipulation]; David Egilman & Samantha Howe, Against Anti-Health Epidemiology: Corporate Obstruction of Public Health via Manipulation of Epidemiology, 13 INT'L J. OCCUPATIONAL & ENVTL. HEALTH 118 (2007); David Egilman et al., Manipulated Data in Shell's Benzene Historical Exposure Study, 13 INT'L J. OCCUPATIONAL & ENVTL. HEALTH 222 (2007); David S. Egilman & Susanna Rankin Bohme, Over a Barrel: Corporate Corruption of Science and its Effects on Workers and the Environment, 11 INT'L J. OCCUPATIONAL & ENVTL. HEALTH 331 (2005); Mi-Kyung Hong & Lisa A. Bero, How the Tobacco Industry Responded to an Influential Study of the Health Effects of Secondhand Smoke, 325 BMJ 1413 (2002); David Michaels, Manufactured Uncertainty: Protecting Public Health in the Age of Contested Science and Product Defense, 1076 ANNALS N.Y. ACAD. SCI. 149 (2006) [hereinafter Michaels, Manufactured Uncertainty]; David Michaels & Celeste Monforton, Manufacturing Uncertainty: Contested Science and the Protection of the Public's Health and Environment, 95 AM. J. PUB. HEALTH S39 (Supp. 1 2005); Michael A. Steinman et al., Narrative Review: The Promotion of Gabapentin: An Analysis of Internal Industry Documents, 145 ANNALS INTERNAL MED. 284 (2006).
(3.) Bero, Tobacco Manipulation, supra note 2.
(4.) University of California, San Francisco, Legacy Tobacco Documents Library, http://legacy.library.ucsf.edu (last visited Jan. 10, 2010).
(5.) University of California, San Francisco, Drug Industry Documents Archive, http://dida.library.ucsf.edu (last visited Jan. 10, 2010).
(6.) Chemical Industry Archives, http://www.chemicalindustryarchives.org (last visited Jan. 10, 2010).
(7.) See STANTON A. GLANTZ ET AL., THE CIGARETTE PAPERS (1996); Annamaria Baba et al., Legislating "Sound Science": The Role of the Tobacco Industry, 95 AM. J. PUB. HEALTH S20 (Supp. 1 2005); Deborah E. Barnes et al., Environmental Tobacco Smoke: The Brown and Williamson Documents, 274 JAMA 248 (1995); Barnes & Bero, supra note 2; Deborah E. Barnes & Lisa A. Bero, Scientific Quality of Original Research Articles on Environmental Tobacco Smoke, 6 TOBACCO CONTROL 19 (1997); Deborah E. Barnes & Lisa A. Bern, Why Review Articles on the Health Effects of Passive Smoking Reach Different Conclusions, 279 JAMA 1566 (1998) [hereinafter Barnes & Bero, Different Conclusions]; Lisa A. Bero, Accepting Commercial Sponsorship: Disclosure Helps--But Is not a Panacea, 319 BMJ 653 (1999) [hereinafter Bero, Commercial Sponsorship]; Lisa Bero, Implications of the Tobacco Industry Documents for Public Health and Policy, 24 ANN. REV. PUB. HEALTH 267 (2003); Bero et al., supra note 2; Lisa A. Bern et al., Publication Bias and Public Health Policy on Environmental Tobacco Smoke, 272 JAMA 133 (1994) [hereinafter Bero et al., Publication Bias]; Lisa A. Bero et al., Science in Regulatory Policy Malting: Case Studies in the Development of Workplace Smoking Restrictions, 10 Tobacco Control 329 (2001) [hereinafter Bero et al., Regulatory Policy Making]; Lisa A. Bero et al., Sponsored Symposia on Environmental Tobacco Smoke, 271 JAMA 612 (1994) [hereinafter Bero et al., Sponsored Symposia]; L.A. Bero et al., The Limits of Competing Interest Disclosures, 14 TOBACCO CONTROL 118 (2005); Bero, Tobacco Manipulation, supra note 2; Lisa A. Bero, Tobacco Industry Manipulation of Research on Environmental Tobacco Smoke, in POUL HARREMOES ET AL., LATE SCIENTIFIC LESSONS FROM EARLY WARNINGS (Poul Harremoes et al. eds., [date]) [hereinafter Bero, Environmental Tobacco Smoke]; Lisa A. Bero & Stanton A. Glantz, Tobacco Industry Response to a Risk Assessment of Environmental Tobacco Smoke, 2 TOBACCO CONTROL 103 (1993); Stella A. Bialous & Derek Yach, Whose Standard Is It, Anyway? How the Tobacco Industry Determines the International Organization for Standardization (1SO) Standards for Tobacco and Tobacco Products, 10 TOBACCO CONTROL 96 (2001); Katherine Bryan-Jones & Lisa A. Bero, Tobacco Industry Efforts to Defeat the Occupational Safety and Health Administration Indoor Air Quality Rule, 93 AM. J. PUB. HEALTH 585 (2003); Pascal A. Diethelm et al., The Whole Truth and Nothing But the Truth? The Research that Philip Morris Did Not Want You to See, 366 LANCET 86 (2005); Stanton A. Glantz et al., Looking Through a Keyhole at the Tobacco Industry: The Brown and Williamson Documents, 274 JAMA 219 (1995); Peter Hanauer et al., Lawyer Control of Internal Scientific Research to Protect Against Products Liability Lawsuits: The Brown and Williamson Documents, 274 JAMA 234 (1995); Hong & Bero, supra note 2; Mi-Kyung Hong & Lisa A. Bero, Tobacco Industry Sponsorship of a Book and Conflict of Interest, 101 ADDICTION 1202 (2006); Peggy Lopipero & Lisa A. Bero, Tobacco Interests or the Public Interest: 20 Years of Industry Strategies to Undermine Airline Smoking Restrictions, 15 TOBACCO CONTROL 323 (2006); R.E Malone & L.A. Bero, Chasing the Dollar: Why Scientists Should Decline Tobacco Industry Funding, 57 J. EPIDEMIOLOGY & COMMUNITY HEALTH 546 (2003); Theresa Montini et al., Assessing the Evidence Submitted in the Development of a Workplace Smoking Regulation: The Case of Maryland, 117 PUB. HEALTH REP. 291 (2002); Monique E. Muggli et al., Science for Hire: A Tobacco Industry Strategy to Influence Public Opinion on Secondhand Smoke, 5 NICOTINE & TOBACCO RES. 303 (2003); Monique E. Muggli et al., The Smoke You Don't See: Uncovering Tobacco Industry Scientific Strategies Aimed Against Environmental Tobacco Smoke Policies, 91 AM. J. PUB. HEALTH 1419 (2001); Elisa K. Ong & Stanton A. Glantz, Constructing "Sound Science" and "Good Epidemiology": Tobacco, Lawyers, and Public Relations Firms, 91 AM. J. PUB. HEALTH 1749 (2001); Marieka S. Schotland & Lisa A. Bero, Evaluating Public Commentary and Scientific Evidence Submitted in the Development of a Risk Assessment, 22 RISK ANALYSIS 131 (2002); John Slade et al., Nicotine and Addiction. The Brown and Williamson Documents, 274 JAMA 225 (1995).
(8.) Bero, Tobacco Manipulation, supra note 2; Bero, Environmental Tobacco Smoke, supra note 7.
(9.) Improper Business Practices and Personal Conflicts of Interest, 48 C.F.R. pt. 3 (2009); see also U.S. DEP'T OF HEALTH & HUMAN SERVS., NIH GRANTS POLICY STATEMENT (2003), available at http://grants.nih.gov/grants/policy/nihgps_2003/ NIHGPS_Part4.htm; THE NAT'L ACADS., POLICY ON COMMITTEE COMPOSITION AND BALANCE AND CONFLICTS OF INTEREST (2003), available at http://www.nationalacademies.org/coi/ bi-coi_form-0.pdf.
(10.) See AAAS Science & Policy, www.aaas.org/spp/sfrl/projects/research_integrity/scientific_integrity/ policies (last visited Jan. 10, 2010).
(11.) E. PEPPLES, INDUSTRY RESPONSE TO CIGARETTE/HEALTH CONTROVERSY (1976), available at http://legacy.library.ucsf.edu/tid/ntb72d00.
(12.) M.J. Morrell et al., Efficacy of Gabapentin as Adjunctive Therapy in a Large, Multicenter Study, 9 SEIZURE 241, 241-42 (2000).
(13.) Exhibit 69, Parke-Davis, Epilepsy Awareness & Support Exchange, United States ex rel. Franklin v. Parke-Davis, 147 F. Supp. 2d 39 (D. Mass. 2001) (No. 96-CV-11651-pbs), available at http://dida.library.ucsf.edu/tid/nea00a10.
(14.) Exhibit 72, Parke-Davis, Agenda and Related Documents for Meeting in Parke-Davis Executive Conference Room: June 26, 1995, Parke-Davis, 147 F. Supp. 2d 39 (No. 96-CV-11651-pbs), available at http://dida.library.ucsf.edu/pdf/qea00a10.
(15.) FELIX WORMSER, ANNUAL MEETING OF THE MEMBERS OF THE LEAD INDUSTRIES ASSOCIATION 4 (Lead Indus. Ass'n ed., 1935).
(16.) See MARKOWITZ & ROSNER, supra note 2, at 47; see also Joseph C. Aub, The Biochemical Behavior of Lead in the Body, 104 JAMA 87 (1935); Felix Wormser, Preliminary Report of Investigation of 'Time' Article 'Paint Eaters,' in LEAD INDUS. ASS'N, LEAD HYGIENE AND SAFETY BULLETIN 3 (1945).
(17.) Memorandum from W.E. Nessell (Jan. 24, 1967) (documenting MCA Meeting in Ann Arbor, Michigan), cited in MARKOWITZ & ROSNER, supra note 2, at 176.
(18.) MARKOWlTZ & ROSNER, supra note 2, at 177.
(19.) Letter from E. Weidlein, Dir., Mellon Inst. of Indus. Research, Univ. of Pittsburgh, to R. Hitchins, President, Am. Refractories Inst. (Jan. 21, 1935), enclosed in Letter from W.G. Hazard, Owens-Illinois Glass Co., to L.R. Thompson, U.S. Pub. Health Serv. (Mar. 21, 1935) (on file with Mellon Institute National Archives).
(20.) See Bero & Rennie, supra note 2; Bero et al., Publication Bias, supra note 7; Bero et al., Sponsored Symposia, supra note 7; Paula A. Rochon et al., Evaluating the Quality of Articles Published in Journal Supplements Compared with the Quality of Those Published in the Parent Journal, 272 JAMA 106 (1994).
(21.) International Committee of Medical Journal Editors, Uniform Requirements for Manuscripts Submitted to Biomedical Journals, http://www.icmje.org (last visited Jan. 10, 2010).
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(23.) Committee on Publication Ethics, About COPE, http://publicationethics.org/about (last visited Jan. 10, 2010).
(24.) See Takeshi Hirayama, Non-Smoking Wives of Heavy Smokers Have a Higher Risk of Lung Cancer: A Study from Japan, 282 BRIT. MED. J. 183 (1981); Hong & Bero, supra note 2.
(25.) Letter from Christopher J. Proctor, Senior Scientific Advisor, Covington & Burling, to Philip Morris (July 26, 1993), available at http://legacy.library.ucsf.edu/tid/opn34e00.
(26.) Peter N. Lee, "Marriage to a Smoker" May Not Be a Valid Marker of Exposure in Studies Relating Environmental Tobacco Smoke to Risk of Lung Cancer in Japanese Non-Smoking Women, 67 INT'L ARCHWES OCCUPATIONAL & ENVTL. HEALTH 287, 287 (1995).
(27.) E. Yano, Japanese Spousal Smoking Study Revisited: How a Tobacco Industry Funded Paper Reached Erroneous Conclusions, 14 TOBACCO CONTROL 227, 231 (2005).
(28.) Id. at 227 (emphasis added).
(29.) Id. at 231.
(30.) Letter from Leigh A. Beck, Senior Dir., Med. Educ. Sys., Inc., to Nancy Kohler, Parke-Davis (June 18, 1997), available at http://dida.library.ucsf.edu/ tid/xfa00a10.
(32.) Gail D. Anderson, A Mechanistic Approach to Antiepileptic Drug Interactions, 32 ANNALS PHARMACOTHERAPY 554 (1998); Edward P. Armstrong & Catherine Cone, The Cost of Treating Seizure Patients in a Managed Care Organization, 5 J. MANAGED CARE PHARMACY 351 (1999); Ahmad Beydoun, Monotherapy Trials with Gabapentin for Partial Epilepsy, 40 EPILEPSIA S13 (Supp. 6 1999); Barry Gidal & Gail Anderson, Epilepsy in the Elderly: Special Pharmacotherapeutic Considerations, 1 CONSULTANT PHARMACIST 62 (1998); Hans C. Hansen, Treatment of Chronic Pain with Antiepileptic Drugs: A New Era, 92 S. MED. J. 642 (1999); James Knoll et al., Clinical Experience Using Gabapentin Adjunctively in Patients with a History of Mania or Hypomania, 49 J. AFFECTIVE DISORDERS 229 (1998); Michael D. Merren, Gabapentin for Treatment of Pain and Tremor: A Large Case Series, 91 S. MED. J. 739 (1998); Mark H. Pollack & Erin L. Scott, Gabapentin and Lamotrigine: Novel Treatments for Mood and Anxiety Disorders, 2 CNS SPECTRUMS 55 (1997); John M. Pellock, Managing Pediatric Epilepsy Syndromes with New Antiepileptic Drugs, 104 PEDIATRICS 1106 (1999).
(33.) Merren, supra note 32.
(34.) Exhibit 61, Payment Register, United States ex rel. Franklin v. Parke-Davis, 147 F. Supp. 2d 39 (D. Mass. 2001) (No. 96-CV-11651-PBS), available at http://dida.library.ucsf.edu/tid/yda00a10.
(35.) Gary A. Mellick & Larry B. Mellick, Reflex Sympathetic Dystrophy Treated with Gabapentin, 78 ARCHIVES PHYSICAL MED. & REHABILITATION 98, 98 (1997).
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(38.) E. Hayhurst, Editorial, Ethyl Gasoline, 15 AM. J. PUB. HEALTH 239, 239 (1925).
(39.) MARKOWlTZ & ROSNER, supra note 2, at 19 (emphasis added) (quoting Letter from C.A. Straw to R.R. Sayers (Aug. 24, 1924)).
(40.) Letter from Zeb G. Bell, Jr. to F.C. Dehn (Sept. 26, 1980), available at http://www.chemicalindustryarchives.org/search/pdfs/vinyl/ 19800926_001_00003102.PDF.
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(44.) Philip Drinker, Report of the Preventive Engineering Committee, in PROCEEDINGS OF FOURTH FALL MEETING OF AIR HYGIENE FOUNDATION OF AMERICA, INC. 17, 17 (1939) (on file with David Rosner, Columbia University).
(45.) Hanauer et al., supra note 7, at 237.
(46.) David Michaels et al., Selected Science: An Industry Campaign to Undermine an OSHA Hexavalent Chromium Standard, ENVTL. HEALTH, Feb. 23, 2006, at 5, 6 (2006).
(47.) Diethelm et al., supra note 7, at 89-90; Egilman et al., supra note 2, at 228-30.
(48.) Letter from A. Yeaman, Brown & Williamson Tobacco Corp., to M. McDonald (July 3, 1963), available at http://legacy.library.ucsf.edu/ tid/jed72d00.
(49.) Exhibit 120, Neurontin: Core Marketing Team Meeting, United States ex rel. Franklin v. Parke-Davis, 147 F. Supp. 2d 39 (D. Mass. 2001) (No. 96-CV-11651-PBS), available at http://dida.library.ucsf.edu/tid/kcb00a10.
(50.) Minutes, 18th Neurontin Marketing Power Hour (Mar. 6, 1997), available at http://dida.library.ucsf.edu/tid/wcb00a10.
(51.) Exhibit 120, Neurontin: Core Marketing Team Meeting, supra note 49, at 1.
(52.) Id. at 2.
(53.) Id. at 6.
(54.) Ahmad Beydoun, Postherpetic Neuralgia: Role of Gabapentin and Other Treatment Modalities, 40 EPILEPSIA S51 (Supp. 6 1999); Ivan L. Marples & Paul Murray, Neuropathic Pain, 354 LANCET 953 (1999).
(55.) MANFRED BOWDITCH, REPORT OF HEALTH AND SAFETY DIVISION FOR LEAD INDUSTRIES ASSOCIATION 28TH ANNUAL MEETING 2 (Lead Indus. Ass'n ed., 1956).
(56.) MARKOWITZ & ROSNER, supra note 2, at 186-91.
(57.) Minutes, Manufacturing Chemists Association, Vinyl Chloride Research Coordinators (May 21, 1973), available at http://www.chemicalindustryarchives.org/search/pdfs/vinyl/ 19730521_001_00000225.PDF.
(58.) Memorandum from R.N. Wheeler Jr. to J.L. Carvajal et al., Mfg. Chemists Ass'n Vinyl Chloride Research Projects (May 31, 1973), available at http://www.chemicalindustryarchives.org/search/pdfs/vinyl/ 19730531_001_00004243.pdf.
(59.) Editorial, A Tower of Babel, 116 ENGINEERING NEWS-REC. 360, 360 (1936).
(61.) See Baba et al., supra note 7, at 23; David Michaels, Regarding Phenylpropanolamine and Hemorrhagic Stroke in the Hemorrhagic Stroke Project": Mercenary Epidemiology-Data Reanalysis and Reinterpretation for Sponsors with Financial Interest in the Outcome, 16 ANNALS EPIDEMIOLOGY 583, 583 (2006); Michaels et al., supra note 46.
(62.) Neil Pearce, Corporate Influences on Epidemiology, 37 INT'L J. EPIDEMIOLOGY 46, 47, 50 (2008).
(63.) Bero et al., Regulatory Policy Making, supra note 7, at 332-34.
(64.) Michaels, Manufactured Uncertainty, supra note 2, at 151.
(65.) Wendy Wagner, The Perils of Relying on Interested Parties to Evaluate Scientific Quality, 95 AM. J. PUB. HEALTH S99, S103 (Supp. 1 2005).
(66.) Memorandum from the Leo Burnett Agency to Philip Morris, Project Brass: A Plan of Action for the ETS Issue (Mar. 23, 1993), available at http://legacy.library.ucsf.edu/tid/gin58e00.
(68.) Memorandum from William F. Keane, Vice President, U.S. Med. & Sci. Affairs, VIOXX, to Primary Care Representatives with Responsibility for VIOXX et al. (Aug. 26, 2004), available at http://dida.library.ucsf.edu/tid/wib00a10.
(69.) See Peter Juni et al., Risk of Cardiovascular Events and Rofecoxib: Cumulative Meta-Analysis, 364 LANCET 2021, 2024-26 (2004); Godfrey Oakley, Jr., Lessons from the Withdrawal of Rofecoxib: Observational Studies Should Not Be Forgotten, 329 BRIT. MED. J. 1342, 1342 (2004).
(70.) Daland R. Juberg, Lead and Human Health: An Update: Executive Summary, AM. COUNCIL ON SCI. & HEALTH, July 1, 2000, http://www.acsh.org/publications/pubID.384/pub_detail.asp.
(72.) Peter F. Infante et al., Genetic Risks of Vinyl Chloride, 307 LANCET 734, 734-35 (1976).
(73.) Memorandum, Soc'y of the Plastics Indus., Vinyl Chloride and Occupational Health (Nov. 1978), available at http://www.chemicalindustryarchives.org/search/pdfs/vinyl/ 19780301_004_BA000544.pdf.
(74.) See H. Bartsch et al., Mutagenicity and Metabolism of Vinyl Chloride and Related Compounds, 17 ENVTL. HEALTH PERSP. 193, 197 (1976); C. de Meester et al., Vinyl Chloride: Direct or Indirect Mutagen, 87 ARCHIVES INT'L. PHYSIOLOGY & BIOCHEMISTRY 620, 621 (1979); A.J. Garro et al., Vinyl Chloride Dependent Mutagenesis: Effects of Liver Extracts and Free Radicals, 38 MUTATION RES. (1976); B. Singer et al., The Vinyl Chloride-Derived Nucleoside, N2, 3-Ethenoguanosine, Is a Highly Efficient Mutagen in Transcription, 8 CARCINOGENESIS 745, 745-46 (1987); Harri Vainio, Vinyl Chloride and Vinyl Benzene (Styrene)-Metabolism, Mutagenicity and Carcinogenicity, 22 CHEMICO-BIOLOGICAL INTERACTIONS 117, 117 (1978); F. G. Verburgt & E. Vogel, Vinyl Chloride Mutagenesis in Drosophila Melanogaster, 48 MUTATION RES. 327, 330-34 (1977).
(75.) ROSNER & MARKOWITZ, supra note 2, at 107.
(76.) DIV. OF LABOR STANDARDS, U.S. DEP'T OF LABOR, NATIONAL SILICOSIS CONFERENCE SUMMARY OF REPORTS (1937).
(77.) Ong & Glantz, supra note 7.
(78.) Egilman & Howe, supra note 2; Michaels, Manufactured Uncertainty, supra note 2; Michaels & Monforton, supra note 2.
(79.) Letter from Leonard A. Miller, Attorney, Swidler & Berlin, to Thomas Borelli, Dir. of Sci. and Envtl. Policy, Philip Morris Cos. (Feb. 2, 1993), available at http://legacy.library.ucsf.edu/tid/tx112a00.
(80.) Int'l Org. for Standardization, List of ISO Committees in Liaison, http://www.iso.org/iso/about/organizations in liaison/organizations in liaison_details.htm? id=8982&LiaisonList=True (last visited Jan. 10, 2010).
(81.) Memorandum from J.B. Boder to M.C. Bourlas (Mar. 19, 1990), available at http://legacy.library.ucsf.edu/tid/fli98e00.
(82.) Letter from Henri Papenfus, President, Sci. Comm'n, Rothmans of Pall Mall Int'l Ltd., to all members of the Scientific Comm'n and Francois Jacob, Sec'y Gen., CORESTA (July 23, 1997), available at http://legacy.library.ucsf.edu/ tid/dkc 13e00.
(83.) LEAD INDUS. ASS'N, ANNUAL REPORT FOR THE YEAR 1955, at 5-6 (1955).
(84.) Philip J. Landrigan, Pediatric Lead Poisoning: Is There a Threshold?, 115 PUB. HEALTH REP. 530 (2000); see also Bruce P. Lanphear et al., Cognitive Deficits Associated with Blood Lead Concentrations <10 [micro]g/dL in US Children and Adolescents, 115 PUB. HEALTH REP. 521 (2000).
(85.) MARKOWITZ & ROSNER, supra note 2, at 207.
(86.) UNIV. OF MICH. INST. OF INDUS. HEALTH, EPIDEMIOLOGICAL INVESTIGATION OF THE POLYVINYL CHLORIDE INDUSTRY IN REFERENCE TO OCCUPATIONAL ACROOSTEOLYTIS: CONFIDENTIAL REPORT TO THE MEDICAL ADVISORY COMMITTEE (Mfg. Chemists Ass'n ed., 1969), available at http://www.chemicalindustryarchives.org/search/pdfs/vinyl/ 19690201_004_BA000060.PDF.
(87.) Vinyl Chloride: Hearing Before the Subcomm. on Environment of the S. Comm. on Commerce, 93d Cong. 94 (1974) (statement of Ralph L. Harding, President, Society of the Plastics Industries, Inc.).
(88.) DIV. OF LABOR STANDARDS, U.S. DEP'T OF LABOR, NATIONAL SILICOSIS CONFERENCE: REPORT ON MEDICAL CONTROL 23 (1938).
(89.) Editorial, Silicosis Conference Files Its Report on Best Ways to Handle Disease, 42 COAL AGE 137 (1937).
(90.) ROSNER & MARKOWITZ, supra note 2, at 117.
(91.) T.F. Hatch, Significance of Occupational History in Diagnosis of Silicosis, 50 RADIOLOGY 746, 747 (1948).
(92.) Memorandum from Carl Thompson, Hill & Knowlton, Inc., to William Kloepfer, The Tobacco Inst., Inc. (Oct. 18, 1968), available at http://legacy.library.ucsf.edu/tid/bgu91f00.
(93.) Exhibit 105, Letter from Kenneth C. Gorson and Attached Draft, United States ex rel. Franklin v. Parke-Davis, 147 F. Supp. 2d 39 (D. Mass. 2001) (No. 96-CV-11651-PBS), available at http://dida.library.ucsf.edu/pdf/sma00a10.
(94.) Exhibit 107, Memorandum from Phil Magistro and Attached Draft, United States ex rel. Franklin v. Parke-Davis, 147 F. Supp. 2d 39 (D. Mass. 2001) (No. 96-CV-11651-PBS), available at http://dida.library.ucsf.edu/pdf/uma00a10.
(95.) Kenneth C. Gorson et al., Gabapentin in the Treatment of Painful Diabetic Neuropathy: A Placebo Controlled, Double Blind, Crossover Trial, 66 J. NEUROLOGY NEUROSURGERY & PSYCHIATRY 252 (1999).
(96.) Transcript of Deposition at 115, United States ex rel. Franklin v. Pfizer Inc., No. Civ.A 96-11651-PBS (D. Mass. Feb. 6, 2002), available at http://dida.library.ucsf.edu/pdf/gca00a10.
(97.) DINA BARTINO ET AL., DRUGDEX DRUG EVALUATIONS: GABAPENTIN 36 (2002), available at http://dida.library.ucsf.edu/pdf/zyc37b10.
(98.) Press Release, Lead Indus. Ass'n, Inc., No Public Hazard from Lead Seen, Muskie Sub-Committee on Pollution Told (June 9, 1966).
(99.) Memorandum from R.N. Wheeler to T.R. Torkelson, Equitable Environmental Health Report on Epidemiology Study of Polyvinyl Chloride Workers (Aug. 24, 1977), available at http://www.chemicalindustryarchives.org/search/pdfs/vinyl/ 19770824_001_00002257.pdf.
(100.) Letter from W.D. Harris to Theodore R. Torkleson (Aug. 31, 1977), available at http://www.chemicalindustryarchives.org/search/pdfs/vinyl/ 19770831_003_00000437.pdf.
(101.) Letter from Theodore R. Torkelson to Joe T. Seawell, Vinyl Chloride Project Manager, Mfg. Chemists Ass'n (Feb. 7, 1978), available at http://www.chemicalindustryarchives.org/search/pdfs/vinyl/ 19780207_003_00000539.pdf.
(102.) Memorandum from Joe T. Seawell, Project Manager, Vinyl Chloride Research to Vinyl Chloride Research Coordinators and Technical Panel (Feb. 14, 1978), available at http://www.chemicalindustryarchives.org/search/pdfs/vinyl/ 19780214_001_00002455.pdf.
(103.) Silicosis Is Not Threat to Workers' Health, 50 SCI. NEWS LETTER 345 (1946).
(105.) ROSNER & MARKOWITZ, supra note 2, at 180.
(106.) Barnes & Bern, Different Conclusions, supra note 7; Joel Lexchin et. al., Pharmaceutical Industry Sponsorship and Research Outcome and Quality: Systematic Review, 326 BMJ 1167 (2003); Michaels, Manufactured Uncertainty, supra note 2.
(107.) Valerio Gennarro & Lorenzo Tomatis, Business Bias: How Epidemiologic Studies May Underestimate or Fail to Detect Increased Risks of Cancer and Other Diseases, 11 INT'L J. OCCUPATIONAL & ENVTL. HEALTH 356 (2005).
(108.) Bero & Rennie, supra note 2.
(109.) Michaels, Manufactured Uncertainty, supra note 2.
(110.) See UNION OF CONCERNED SCIENTISTS, SMOKE, MIRRORS & HOT AIR: HOW EXXONMOBIL USES BIG TOBACCO'S TACTICS TO MANUFACTURE UNCERTAINTY ON CLIMATE SCIENCE (2007), available at http://www.ucsusa.org/assets/documents/global_warming/ exxon_report.pdf; Letter from Robert A. Bussian, Vice President and Gen. Counsel, Aminoil, to H.C. Roemer, R.J. Reynolds, Inc. (Feb. 7, 1983), available at http://legacy.library.ucsf.edu/tid/rm196a00; Memorandum from Max H. Crohn, Jr. to C.A. Tucker, Talk at American Petroleum Institute (Apr. 19, 1982), available at http://legacy.library.ucsf.edu/ tid/alt63a00; Letter from Peter N. Sheridan, Div. Counsel, Plastics & Additives Div., CIBA-GEIGY Corp., to the Asbestos, Chem., Lead, Pharm., Rubber & Tire Indus., A Meeting to Discuss Pooling of Defense Resources in Products Liability Litigation (Jan. 31, 1982), available at http://legacy.library.ucsf.edu/tid/mmv85d00.
(111.) Baba et al., supra note 7; Michaels, Manufactured Uncertainty, supra note 2; Michaels, supra note 61.
(112.) Bero, Commercial Sponsorship, supra note 7.
(113.) Frank Davidoff et al., Sponsorship, Authorship, and Accountability, 345 NEW ENG. J. MED. 825 (2001); Int'l Comm. of Med. J. Editors, Uniform Requirements for Manuscripts Submitted to Biomedical Journals, http://www.icmje.org (last visited Jan. 10, 2010).
(114.) Kevin A. Schulman et al., A National Survey of Provisions in Clinical-Trial Agreements Between Medical Schools and Industry Sponsors, 347 NEW ENG. J. MED. 1335 (2002).
(115.) Michaels, Manufactured Uncertainty, supra note 2.
(116.) M. Doucet & S. Sismondo, Evaluating Solutions to Sponsorship Bias, 34 J. MED. ETHICS 627 (2008); Arthur Schafer, Biomedical Conflicts of Interest: A Defence of the Sequestration Thesis-Learning from the Cases of Nancy Olivieri and David Healy, 30 J. MED. ETHICS 8 (2004).
(117.) See AGENZIA ITALIANA DEL FARMACO, INDEPENDENT RESEARCH ON DRUGS FUNDED BY THE ITALIAN MEDICINES AGENCY (2007), available at http://www.agenziafarmaco.it/wscs_render_attachment_by_id/ tipo_file0109.pdf?id=111.109 018.1188484620191&language=IT&lenient=false.
Jenny White *
Lisa A. Bero **
* Jenny White (presenting author) is a Research Analyst at the University of California, San Francisco's Department of Clinical Pharmacy. This research was funded by the California Tobacco Related Disease Research Program (grant 13RT-0108). We would like to thank David Rosner for providing us with original documents from the lead, vinyl chloride, and silica industries, James Lightwood for statistical analysis of the results, and Elizabeth Boyd for information on federal standard-setting agencies.
** Lisa A. Bero, PhD is Professor, Department of Clinical Pharmacy, School of Pharmacy and Institute for Health Policy Studies, School of Medicine, University of California, San Francisco.
TABLE 1. MANIPULATION OF RESEARCH IN FIVE INDUSTRIES MANIPULATION Tobacco Pharma Lead VC Silica TOTALS CATEGORY Fund 51 7 4 3 1 66 Publish 3 12 4 4 1 24 Suppress 5 11 1 4 1 22 Distort public 56 1 2 3 3 65 discourse Set standards 7 0 2 4 4 17 Disseminate directly 29 7 4 6 1 47 TOTALS 151 38 17 24 11 241 * The pharmaceutical industry publishes more, suppresses research more, and distorts the public discourse less than the tobacco industry (p = 0.000) * The lead industry publishes more than the tobacco (p = 0.0002) * The vinyl chloride industry publishes more than the tobacco (p = 0.000) * The silica industries set standards more than the tobacco (p = 0.003) TABLE 2 EXCERPT OF MEMORANDUM FROM HILL AND KNOWLTON, INC. SUGGESTING TOPICS FOR TOBACCO INSTITUTE PUBLICATION TOBACCO AND HEALTH RESEARCH, OCTOBER 18, 1968 (92) "A report indicating some factor or factors other than smoking may be involved in one of the diseases... * a report in which the statistics of a smoking-associated disease are questioned * one in which death certificates or classifications of such a disease are questioned * One showing that many lung cancers may be metastatic from some other organ * One indicating that a virus may cause human cancer, whether or not that cancer is associated with smoking * One on research with animals, indicating that some other factor may be involved with carcinogenesis or ciliostasis."
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|Author:||White, Jenny; Bero, Lisa A.|
|Publication:||Stanford Law & Policy Review|
|Date:||Jan 1, 2010|
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