We analyzed previously secret tobacco industry documents in the University of California, San Francisco Legacy Tobacco Documents Library, and IOM public access files. (A limitation of this method includes the fact that the tobacco companies have withheld some possibly relevant documents.) Tobacco companies considered the IOM report to have high-stakes regulatory implications. They developed and implemented strategies with consulting and legal firms to access the IOM proceedings. When the IOM study staff invited the companies to provide information on exposure and disease markers, clinical trial design for safety and efficacy, and implications for initiation and cessation, tobacco company lawyers, consultants, and in-house regulatory staff shaped presentations from company scientists. Although the available evidence does not permit drawing cause-and-effect conclusions, and the IOM may have come to the same conclusions without the influence of the tobacco industry, the companies were pleased with the final report, particularly the recommendations for a tiered claims system (with separate tiers for exposure and risk, which they believed would ease the process of qualifying for a claim) and license to sell products comparable to existing conventional cigarettes (“substantial equivalence”) without prior regulatory approval. Some principles from the IOM report, including elements of the substantial equivalence recommendation, appear in the 2009 Family Smoking Prevention and Tobacco Control Act.

Spurred by the creation of potential modified risk tobacco products, the US Food and Drug Administration (FDA) commissioned the Institute of Medicine (IOM) to assess the science base for tobacco “harm reduction,” leading to the 2001 IOM report Clearing the Smoke. The objective of this study was to determine how the tobacco industry organized to try to influence the IOM committee that prepared the report.

These findings suggest that tobacco companies used their legal and regulatory staff to access the IOM committee that advised the FDA on modified risk tobacco products and that they used this access to deliver specific, carefully formulated messages designed to serve their business interests. Although these findings provide no evidence that the efforts of tobacco companies influenced the IOM committee in any way, they show that the companies were satisfied with the final IOM report and its recommendations, some of which have policy implications that continue to reverberate today. The researchers therefore call for the FDA and other regulatory bodies to remember that they are dealing with companies with a long history of intentionally misleading the public when assessing the information presented by tobacco companies as part of the regulatory process and to actively protect their public-health policies from the commercial interests of the tobacco industry.

The researchers searched the Legacy Tobacco Documents Library (a collection of internal tobacco industry documents released as a result of US litigation cases) for documents outlining how tobacco companies tried to influence the IOM Committee to Assess the Science Base for Tobacco Harm Reduction and created a timeline of events from the 1,000 or so documents they retrieved. They confirmed and supplemented this timeline using information in 80 files that detailed written interactions between the tobacco companies and the IOM committee, which they obtained through a public records access request. Analysis of these documents indicates that the tobacco companies considered the IOM report to have important regulatory implications, that they developed and implemented strategies with consulting and legal firms to access the IOM proceedings, and that tobacco company lawyers, consultants, and regulatory staff shaped presentations to the IOM committee by company scientists on various aspects of tobacco harm reduction products. The analysis also shows that tobacco companies were pleased with the final report, particularly its recommendation that tobacco products can be marketed with exposure or risk reduction claims provided the products substantially reduce exposure and provided the behavioral and health consequences of these products are determined in post-marketing surveillance and epidemiological studies (“tiered testing”) and its recommendation that, provided no claim of reduced exposure or risk is made, new products comparable to existing conventional cigarettes (“substantial equivalence”) can be marketed without prior regulatory approval.

Tobacco companies have a long history of working to shape scientific discussions and agendas. For example, they have produced research results designed to “create controversy” about the dangers of smoking and secondhand smoke. In this study, the researchers investigate how tobacco companies organized to try to influence the IOM committee that prepared the Clearing the Smoke report on modified risk tobacco products by analyzing tobacco industry and IOM documents.

Up to half of tobacco users will die of cancer, lung disease, heart disease, stroke, or another tobacco-related disease. Cigarettes and other tobacco products cause disease because they expose their users to nicotine and numerous other toxic chemicals. Tobacco companies have been working to develop a “safe” cigarette for more than half a century. Initially, their attention focused on cigarettes that produced lower tar and nicotine yields in machine-smoking tests. These products were perceived as “safer” products by the public and scientists for many years, but it is now known that the use of low-yield cigarettes can actually expose smokers to higher levels of toxins than standard cigarettes. More recently, the tobacco companies have developed other products (for example, products that heat aerosols of nicotine, rather than burning the tobacco) that claim to reduce harm and the risk of tobacco-related disease, but they can only market these modified risk tobacco products in the US after obtaining Food and Drug Administration (FDA) approval. In 1999, the FDA commissioned the US Institute of Medicine (IOM, an influential source of independent expert advice on medical issues) to assess the science base for tobacco “harm reduction.” In 2001, the IOM published its report Clearing the Smoke: Assessing the Science Base for Tobacco Harm and Reduction, which, although controversial, set the tone for the development and regulation of tobacco products in the US, particularly those claiming to be less dangerous, in subsequent years.

Funding: This work was supported by National Cancer Institute grant CA-087472. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Copyright: © 2013 Tan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

The tobacco companies have a long history of working to shape scientific discussions and agendas [1] , [4] , [5] , including producing research results designed to “create controversy” about the dangers of smoking and secondhand smoke [1] , [10] , [11] , [12] and influencing scientific standards of how research is conducted or interpreted [13] , [14] , [15] . The cigarette companies used this experience as the basis for their efforts to influence the IOM. They worked with consultants and lawyers to gain access and involvement with the IOM process and to contribute scientific information to the IOM committee that was largely produced by industry insiders and consultants and carefully vetted by lawyers. While available evidence does not permit cause-and-effect conclusions, and the IOM may have come to the same conclusions without the influence of the tobacco industry, in the end, the companies were pleased with the report and sought ways to use it to advance their business and regulatory agendas.

The final report, Clearing the Smoke: Assessing the Science Base for Tobacco Harm Reduction [3] was issued in 2001 and set the tone for future development and regulation of tobacco products, particularly products claiming to be less dangerous than conventional cigarettes. The report, which included a set of Regulatory Principles ( Box 1 ) in addition to a review of the science base, generated controversy within the tobacco control community because some believed the recommendations did not adequately protect public health [9] .

In response, the IOM formed its Committee to Assess the Science Base for Tobacco Harm Reduction, composed of 12 experts in fields ranging from toxicology to epidemiology from inside and outside tobacco control [3] , supported by IOM staff, nonvoting liaisons from other IOM boards, and nonvoting consultants. The committee gathered information from scientists and advocates representing public health and academia and compiled a draft report, which was submitted to peer reviewers selected by the study staff before being released to the public.

The question of how to assess the relative harm of different tobacco products gained further currency in 1996, when the US Food and Drug Administration (FDA) asserted jurisdiction over tobacco products. To inform its regulatory efforts in 1999 the FDA commissioned the Institute of Medicine (IOM) to formulate scientific methods and standards to assess tobacco products that could potentially reduce exposure to toxicants. The IOM is part of the National Academies (which consists of the National Academy of Sciences, The National Academy of Engineering, the Institute of Medicine, and the National Research Council), elite self-selected professional organizations whose purpose is to provide scholarly advice to policy makers. Originally chartered by Congress in 1863 as the National Academy of Science, the National Academies describe their role as “produc[ing] groundbreaking reports that have helped shape sound policies, inform public opinion, and advance the pursuit of science, engineering, and medicine” [7] . The National Academies describe their reports as influential because, “Over many decades, the National Academy of Sciences (NAS), National Academy of Engineering (NAE), Institute of Medicine (IOM), and National Research Council have earned a solid reputation as the nation's premier source of independent, expert advice on scientific, engineering, and medical issues” [8] . Thus, while not a regulatory body per se, the IOM's advice carries much weight with policy makers and regulatory bodies, including the FDA.

The issue of new tobacco products that were designed to deliver nicotine accompanied with lower levels of other toxins reemerged as a public health issue in 1988 when R.J. Reynolds Tobacco (RJR) introduced its new “Premier” product, which worked by delivering a heated aerosol of nicotine rather than by burning tobacco [6] .

One idea that attracted wide public and scientific acceptance beginning in the 1960s was the idea that cigarettes that produced lower tar and nicotine yields (based on machine-smoking tests) would be less toxic. This assumption led to their widespread use but ultimately provided no benefit to the public health [2] , [3] , [4] , [5] . Health authorities later learned that machine smoking tests translate poorly to how smokers actually smoke and the dose of toxins they receive. Low-yield cigarettes performed better in machine tests because cigarette companies modified the filters with ventilation holes to dilute the smoke with air, lowering the machine-measured yields. In contrast, smokers covered these holes with their fingers or lips and inhaled the unvented smoke or smoked more intensively, a process that the industry called “smoker compensation,” to maintain or even increase nicotine delivery and exposure to smoke toxins. For many years, low-yield cigarettes were perceived as “safer” products, and the tobacco industry used direct marketing claims and later, implied claims, to encourage people to initiate smoking or delay quitting [1] , [2] , [4] .

Because cigarettes and other tobacco products deliver a wide range of toxic chemicals along with nicotine, the addictive drug in tobacco, the cigarette companies mounted efforts dating back to at least the 1950s [1] to develop a “safe” cigarette. These efforts waned in the 1980s as a result of technical failures combined with industry lawyers' concerns that success in creating a “safer” cigarette would create liabilities for other “less safe” brands.

In addition, documents were obtained via a public records access request to the NAS for documents associated with the IOM Committee to Assess the Science Base for Tobacco Harm Reduction. The Public Access Records Office (PARO) provided a master list of 268 documents meeting these criteria. We requested all 268 files; PARO provided 16 hard-copy documents and 64 digital files. The remaining items were papers, books, government documents, and media reports that were publicly available and not explicitly generated for or by the IOM committee. The 80 files we obtained contained all known written interactions between the tobacco companies and IOM. The timeline of events developed from the tobacco industry documents and supplemented and confirmed by the IOM documents naturally coalesced into thematically united sections; that is, documents from a particular period tended to address the same topic. Examples include: information gathering about IOM, lawyers editing presentations of industry scientists, and executives discussing the report after release. The final paper was written based on these thematically united segments.

The remaining tobacco industry documents (about 1,000 documents) were analyzed for internal consistency. This was conducted by placing the documents in chronological order and quoting or summarizing each document to create an extensive timeline of events. The timeline was verified for content and internal consistency by authors CET and SAG. In cases where content of documents was ambiguous, additional searches for related documents were run to provide context and clarify meaning; if no supporting documents could be identified, the document was excluded from the analysis. No major conflicts arose within the documents or between the documents and known events.

The tobacco industry documents were analyzed for relevance, novel information, and internal consistency. Documents that were irrelevant (i.e., misclassified with metadata attributed to the wrong year, author, or topic) were excluded from the analysis. Documents that did not provide novel information (i.e., providing information that was already corroborated by other documents) were considered in the analysis for internal consistency (see below) but may not have been quoted in the final paper and do not appear in the reference list.

Initial keyword and snowball searches yielded several thousand documents pertaining to the IOM project. Searches were narrowed to documents from specific years, namely 1999 and beyond. For documents that were exact duplicates, only one copy was included in the analysis. If the same document appeared with minor changes (i.e., handwritten notes or tracked changes in a word editing program), both versions were included.

Between May 2011 and February 2012, we searched the UCSF Legacy Tobacco Documents Library (LTDL, http://legacy.library.ucsf.edu ) for documents outlining how the tobacco companies tried to influence the IOM committee. We used standard snowball techniques [16] , starting with terms including “Institute of Medicine,” “IOM committee,” “Clearing the Smoke,” and “Assessing the Science Base for Tobacco Harm Reduction.” We identified key persons, concepts, and events and viewed documents with adjacent Bates numbers.

Results

Phillip Morris Engages the IOM Committee In 1999, when the FDA commissioned the IOM to prepare the report, the tobacco industry and FDA were engaged in a protracted legal contest over authority to regulate tobacco products ([3], p. 127–128; [17]). Despite their outward resistance, tobacco companies were internally acknowledging and preparing for regulation [17],[18]. A 1999 internal presentation at Philip Morris (PM) titled “Potential for Worldwide Product Regulation” described not only the IOM committee but also tracked the progress of several other tobacco regulatory efforts in Canada, the European Union, and the World Health Organization (WHO). This presentation identified harm reduction as a “critical regulatory issue” and suggested an approach by which, “in situations where significant questions remain, such as identifying important smoke components, obtaining meaningful exposure information and developing measures of harm reduction, it would be desirable to work with regulators to jointly address and answer these questions [emphasis added]” [18]. In October 1999, the IOM announced the creation and goals of the committee [19]. PM recognized an opportunity to influence the scientific evaluation and regulation of reduced-harm products. Through its Worldwide Regulatory Affairs (WRA) and Worldwide Scientific Affairs (WSA) divisions, PM began working with lawyers and consultants to collect information and plan ways to become involved. Established in 1993, WRA was a central resource to develop strategies and provide resources for PM Corporate Affairs staff to address smoking restrictions globally. WRA guided WSA to “develop scientific resources and contributions to the scientific debate” [20], initially on secondhand smoke and later on a wider range of scientific domains, including reduced-harm products. In mid-November 1999 Arnold & Porter (A&P), a law firm representing PM, wrote Mark Berlind, Senior Assistant General Counsel of WRA, and Rick Solana and Bruce Davies, respectively Vice President and Manager of WSA, describing a telephone conversation A&P had had with Dr. Kathleen Stratton, the IOM study director. A&P reported that Stratton explained the committee structure, funding source (the FDA), staff, membership, and schedule [21]. A&P also gathered information about the degree to which industry representatives could be involved at every stage; A&P's memo to PM indicated that although IOM committees typically did not permit industry participation given potential conflict of interest situations, Stratton had anticipated that industry (both pharmaceutical and tobacco companies) would be encouraged to present information to the committee, either through testimony or submissions (including reference to relevant documents). A&P also indicated that, because peer reviewers on the draft committee are not subject to conflict of interest rules, it would be possible for members of industry to serve as peer reviewers. (The IOM used a lawyer from the Covington & Burling law firm, which represents the tobacco industry, as a peer reviewer.) PM hired Multinational Business Services, Inc. (MBS), a lobbying and consulting firm founded by former Reagan White House Office of Management and Budget deputy administrator Jim Tozzi that specializes in regulatory issues and has a long history of working for the tobacco industry [13],[14] to provide options for PM to “enter the IOM process” [22]. To overcome the IOM's closely guarded decision-making process, MBS suggested two ways PM could approach the IOM: Option 1: Efforts could be made to work with a nationally renown [sic] scientific organization to establish a panel which could undertake a course of inquiry parallel to that of the IOM committee. This new panel would work in concert with Philip Morris scientists in conducting its research. At a suitable time, the panel, in the course of its interactions with the IOM committee, could bring Philip Morris officials into the dialogue. Option 2: Philip Morris and MBS could jointly approach the IOM Committee through our established contacts. [22] PM's Solana began coordinating efforts to contact the IOM committee along with other members of WSA who would become key players: Richard Carchman, vice president of WSA; Wolf Reininghaus, head of Institut für Biologische Forschung (INBIFO, PM's biological research lab in Germany [23], renamed Philip Morris Research Laboratories GmbH in 2002 [24]); PM principal scientist George Patskan; PM scientific affairs manager Bruce Davies; and WSA group director Edward Sanders. Their initial plan was to critique the committee's “limited” range of expertise [25],[26],[27],[28],[29]. Davies recommended additional or alternate committee members, all of whom were affiliated with the tobacco industry: Bill (William) Rickert, who had been chair and editor of the 1996 and 1998 reports of Canada's Expert Committees on Cigarette Modifications and Cigarette Toxicity Reduction [30],[31] and owner of Labstat Corporation, which within the next year would sign a two-year US$950,000 contract with PM “to provide services relating to the testing and chemical analysis of tobacco, cigarettes, and cigarette smoke for constituents of interest” [32]; PM's Richard Carchman; and Oak Ridge National Laboratory's Roger Jenkins, a scientist who had a history of producing research that supported the industry's positions, particularly on secondhand smoke [33],[34]. Shortly after WSA's discussion of the IOM committee, MBS's Tozzi wrote PM that “the next step would be to raise the possibility of … data sharing with the IOM Committee” [35]. Using the information and recommendations from A&P and MBS, Solana and his WSA colleagues addressed a letter to the IOM committee on behalf of PM: You have posted invitation for public comment on the committee for “Assessing the Science Base for Tobacco Harm Reduction” … …[I]t is not clear that you have scientists with an in depth knowledge of cigarettes and cigarette smoke. I understand that industry scientists are not allowed to be on the committee. We are, therefore, available to you to share our knowledge, experience and expertise in product design and product performance, biological and chemical evaluation of cigarettes, and capability of different tests for use in toxicological evaluation. Attached is a reference list of some of our applicable publications and presentations. [36] Solana's letter also followed MBS's advice [22] to cite the example of Canada's Expert Committees on Cigarette Modifications (1996) and Cigarette Toxicity Reduction (1998), which were Canada's attempts to establish priorities in tobacco harm reduction [36]. The Canadian committees had a strong tobacco industry presence; they included industry scientists J. Donald Bethizy (RJR), Patrick Dunn (Imperial Tobacco), and David Townsend (RJR) on the 1996 10-member committee; Bethizy and Hoffman again as well as Richard Carchman (PM) and Stewart Massey (British American Tobacco, Imperial Tobacco) on the 1998 11-member committee; non-disclosed industry consultant Roger Jenkins; and chair Bill Rickert. The Canadian reports included pro-industry minority opinions in the main report, immediately underneath the majority conclusions [30],[31]. These minority opinions from the industry representatives challenged widely accepted facts, including what Rickert described in his preface as committee chair as “major disagreement” about whether nicotine was addictive [30]. MBS and A&P attended the first IOM committee meeting (open to the public) in December 1999 and provided PM with detailed reports on the charge to the committee, the questions asked by the committee members, and their reactions to the answers. A&P also prepared detailed personal reports on all the committee members that included publications and sponsors [37],[38], which PM supplemented with resumes [39],[40],[41],[42],[43],[44],[45],[46],[47],[48],[49],[50],[51],[52],[53],[54],[55],[56],[57],[58],[59]. Shortly after the first committee meeting, IOM study director Stratton responded to Solana's request stating: I am currently working with some of the committee members to develop a strategy for engaging the pharmaceutical and tobacco industries in order to broaden the input to and the scientific base of our committee's deliberations. I am happy to know of your personal interest in our work and will take the liberty of contacting you directly once this working group plans its next steps. [emphasis added by PM] [60]. Solana forwarded the email to several PM scientists who would play key roles in the company's upcoming interactions with the IOM: Bruce Davies, Hans-Juergen Haussman, George Patskan, Wolf Reininghaus, Edward Sanders, and Roger Walk, as well as Jack Nelson, PM senior VP of Operations [61]. Though only Solana communicated directly with Stratton, he shared their communications with many PM scientists, executives, and lawyers who worked together to collectively formulate his responses.

IOM Invites Tobacco Companies to Share Information In January 2000, Stratton sent identical letters to the scientific division leaders at PM [62], RJR [63], and Brown & Williamson (B&W) [64] inviting participation in an IOM meeting. The invitation advised that an IOM working group wished to “explore how you can best provide meaningful scientific information for the committee's consideration” and asked the companies for scientific articles and company documents made public under the Master Settlement Agreement or by congressional action. The letter further noted, “…The invitation to meet with the working group and solicitation of input is not an endorsement of the products of your company or positions you might take regarding the health effects of tobacco or nicotine” [62],[63],[64]. Solana responded to Stratton's request for materials and references [65] and sent several copies of Analytical Determination of Nicotine and Related Compounds and Their Metabolites [66], a 772-page monograph on nicotine analysis PM commissioned, sponsored, and primarily written by industry scientists, consultants, and grantees [67]. Though the monograph stated that PM paid some of the cost of the book and that some contributors were employees, affiliates, or consultants of tobacco companies, it did not disclose that PM scientists, lawyers, and management at PM and RJR actively revised chapters or that PM agreed to purchase a minimum of 500 copies to make production of the monograph profitable for the publisher [67]. PM selected six speakers to present to the IOM: Richard A. Carchman (VP of WSA), Hans-Juergen Haussman (Executive Manager, Bioresearch at INBIFO), George Patskan (Director of Product Integrity), Richard Solana, and Principal Scientists from both PM and PM International [68]. Their presentations were carefully vetted by the “Core Team” of WSA and INBIFO research scientists [69] as well as in-house lawyers (Senior Vice President and Associate General Counsel and Vice President of Litigation and Associate General Counsel) [70]. Another PM lawyer, Kevin Osborne, helped edit the presentations [71],[72],[73]. A list of scheduled planning sessions for the presentations also indicated that a 4-hour session would involve a review by PM Vice President of Operations Jack Nelson [69]. Thus, while the primary work was conducted by the science personnel, they operated under the guidance of PM's legal, regulatory, and executive arms. Sanders presented research by British statistician Peter Lee on low tar cigarettes and argued that “direct epidemiological evidence suggest[s] some reduction in risk for lung cancer” while “indirect epidemiological evidence appears to suggest the reverse” and that this “require[s] further research” [74]. Lee, a longtime tobacco industry consultant, had written articles denying or minimizing the health effects of cigarette smoking on behalf of British American Tobacco, PM, the Tobacco Institute, and others ([4], p. 86; [1],[10],[75],[76],[77],[78]), and in this case wrote an article concluding that “the switch to low tar/filter cigarettes has led to a substantial reduction in risk of lung cancer” [79]. This statement directly contradicted the scientific consensus, developed over several decades, that low-yield products failed to reduce population-wide risks of smoking [2]. When the IOM working group asked PM for a copy of Lee's study, which PM stated had been submitted to British Medical Journal [80], PM did not comply. Sanders informed the PM staff member fulfilling the IOM data request that, “The reason for [the refusal] is, of course, that if the article is rejected, it may be changed considerably” [81]. BMJ subsequently rejected the manuscript, and it was eventually published [82],[83] in 2001 in Inhalation Toxicology, a journal whose editor-in-chief [84] was a paid RJR consultant [85],[86],[87],[88],[89],[90], after receiving a positive review by peer reviewer Chris Coggins, Senior VP of Science and Technology at RJR, who declared it a “fine piece of epidemiological research [that] is suitable for publication with very minor changes [emphasis in original]” [91]. Another presentation to the IOM was by PM Principal Scientist Patskan who delivered a presentation about the smoke chemistry and toxicity of electronically heated cigarettes, new devices that claimed to reduce the risk of smoking by heating rather than burning tobacco. Patskan requested that his research colleagues send him results from assays and inhalation studies on a “TPM [total particulate matter] delivery basis” [92]. Previously, in its “Project Mix,” PM used the tactic of normalizing smoke yields by TPM delivery in order to obscure increases in cigarette smoke toxicity that occurred when additives were put in test cigarettes [93]. Like PM, RJR delivered high-priority talking points to the IOM, one of which was that modified products must be as similar to conventional cigarettes as possible, because the “degree of trade-off strongly influences cigarette acceptability” [94]. RJR cited their own data collected from smokers participating in company-run trials of Eclipse, their then-new tobacco-heating “cigarette” that advertised simpler smoke chemistry and reduced biological activity. The data showed that smokers were “unwilling to accept large trade-offs” of the taste, ritual, or performance for a risk reduction, causing RJR to recommend that regulators not require drastic modifications of tobacco products that would make them unattractive to consumers [94]. RJR also presented data showing that Eclipse produced less tar and other target compounds, such as carcinogenic polyaromatic hydrocarbons and tobacco-specific nitrosamines, than conventional low-yield cigarettes according to machine smoking and smoke composition tests [94]. After RJR's presentation to the IOM, the company's public relations department drafted a briefing sheet for media training about Eclipse (also sent to law firm Williams & Connolly to request suggested changes [95]) stating, “We have presented the science behind our claims to … the Institute of Medicine's committee on cigarette risk reduction, and to others in the scientific and public health communities” [96]. PM, RJR, and B&W all recommended similar test batteries for smoke chemistry and toxicology tests (the Ames test, neutral red uptake assay, sister chromatid exchange, chromosome aberration assay, 90-day subchronic inhalation studies in mice, and skin painting tests) as well as similar biomarkers for disease outcomes such as cardiovascular disease, chronic obstructive pulmonary disease, and cancer [94],[97],[98]. Following the presentations to the IOM working group, PM's Solana circulated an email to WSA [99] reporting on the meeting and expressing pleasure that “there was no animosity, and the working group was sincerely interested in our information and thoughts” [100], and that the committee inquired about the company's research collaborations, capabilities, and agenda as well as their opinion on the IOM's work and a regulatory framework for reduced-harm products. He described the “key messages” conveyed by PM, which included “us[ing] a balanced spectrum of assays for pre-market hazard characterization” such as machine smoking, “a useful tool [that] should use a validated, standard method,” and “confirm[ing] harm reduction determination with after-market epidemiology.” Solana reported that he told the working group that “PM will be glad to provide support to, and receive support from, this IOM committee” [101]. Finally, Solana mentioned that the IOM committee would be sending a list of further questions to be answered by the companies.

IOM Sends Twelve Questions to the Tobacco Companies Six weeks after the company presentations, the IOM sent 12 questions on tobacco products and testing standards to PM, RJR, B&W, and Lorillard (Table 1) [102],[103],[104],[105]. Their responses were collaborative efforts within each company, with input from scientists, lawyers, and regulatory advisors to create carefully crafted responses [106],[107],[108],[109]. PPT PowerPoint slide

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larger image TIFF original image Download: Table 1. IOM's Twelve Questions to the Tobacco Companies, Their Responses, and the Conclusions in Clearing the Smoke. https://doi.org/10.1371/journal.pmed.1001450.t001 The lawyers' influence is evident in PM's answer to a question about collaboration between industry, academia, and government, which was edited by Kevin Osborne, the in-house lawyer who reviewed PM's presentations to the IOM. The lawyers helped distinguish situations in which PM should openly disclose information to boost its credibility from situations in which such disclosure would reveal weaknesses or problems with the company's position. For example, in response to the IOM question about the “best mechanism to foster collaborative studies between tobacco industry, university, and other scientists” [102], PM wrote, “Philip Morris has already set up an ambitious program directed toward the development of harm-reduced products … [that] would involve Philip Morris support of external scientists through an independent funding mechanism” [110]. Osborne commented, “The ‘funding mechanism’ [the PM External Research Program] isn't independent; rather, the contemplated arrangement allows for the funding of independent research” [110]. The final version submitted to the IOM had no mention of PM's then-planned External Research Program. In response to the question about criteria for determining harm, PM recommended a tiered testing system that proposed as many as 20 years of surveillance to either confirm or invalidate a reduced harm claim (Figure 1). PM recommended that the validation process be divided between the premarket phase, with standard toxicology tests “to insure that a new product design change does not increase overall smoke chemistry or measured biological activity” [97] (called “acceptability,” referring to a specific level of acceptable harm and not to be confused with “consumer acceptability,” referring to consumer tastes and preferences), and post-market surveillance. The primary assessment of new products would take place largely in the post-market phase, because “due to the need for large numbers of smokers who currently use a product as their brand, it would be best to conduct the study in an after-market environment” [111]. Adopters of products with potential reduced-harms claims would serve as the test population and tobacco companies would benefit from rapid introduction of their products into the market. PPT PowerPoint slide

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larger image TIFF original image Download: Figure 1. PM proposed timeline for assessment of reduced-harm products [219]. https://doi.org/10.1371/journal.pmed.1001450.g001 Although the wording was changed slightly, Regulatory Principle 4 of the IOM report was similar to the tiered testing system PM recommended to the working group. Indeed, an internal draft statement prepared by PM WSA noted that IOM had accepted PM's model in all but name [112]. The WSA scientists proposed this schematic, and after a similar version was published in the IOM report, conducted a post hoc analysis that it would allow PM to make early health claims soon after smoke chemistry, toxicity, and the first round of human biomarker testing, prior to marketing [112],[113], and continue after-market testing among consumers for several years [101]. The IOM took a much firmer stance than the original PM proposal, setting high preliminary testing hurdles. Nevertheless, PM was pleased by the IOM's overall approach and continued to promote this tiered system to other organizations, including the WHO Scientific Advisory Committee on Tobacco Product Regulation later that year [114]. Among members of the academic and public health communities that were invited to present to the committee as independent experts, John Slade, a physician specializing in addiction and tobacco control, specifically tried to counter the influence of the tobacco companies on the IOM. In a presentation about the history of light and filtered cigarettes [115], Slade explained how tobacco companies and PM in particular generated controversy to confuse the public about the dangers of smoking. Since all documents presented to the IOM, including copies of presentations and written submissions, were publicly available, Slade obtained the submissions by the tobacco companies and sent letters to the committee reminding them that tobacco companies had a history of bad behavior and presented a point-by-point rebuttal to the companies' responses to the 12 questions [116],[117],[118]. Slade was also suspicious of RJR's claims for Eclipse and the industry's willing participation in establishing standards for risk reduced products, stating, “All three of the major cigarette manufacturers are eager to have reduced risk products on the market in their own terms, terms which guarantee the continuation of the public health fraud they have perpetuated for decades by promoting poisonous and addictive products to consumers of all ages” [117].

Inviting IOM Committee Members to Apply for Funding from the Philip Morris External Research Program A few months before the release of the IOM report, PM prepared to launch its new PM External Research Program (PMERP), nominally to fund independent research on harm reduction to aid product development [119],[120]. Solana sent identical letters to nine IOM committee members inviting them to apply for funding. Committee member, pathologist Adi Gazdar, planned to submit a research funding application. Prior to serving on the IOM committee, Gazdar had applied for and been refused money from the industry's Council for Tobacco Research [121],[122],[123],[124],[125],[126],[127],[128],[129],[130],[131],[132]. Kern Wildenthal, president of Gazdar's institution, University of Texas Southwestern at Dallas, prevented him from submitting the application. He described his reservations in a letter to Gazdar: [A]lthough Philip Morris intends to make use of peer review and to exert no control over publications after grants are awarded, they make it clear that peer review is only part of the picture and that the grant program is, in fact, for the benefit of the company and under the company's control.

Specifically, they state that “the purpose” of the program is to support “research that… enables Philip Morris to continue its pursuit of product modification(s) or new product design(s) that might reduce the health risk of smoking.” They also state that after peer review, Philip Morris has “final approval,” and that the company must be provided “assurances” that all studies they fund “serve relevant business needs” of the company. [emphasis original] [133] Wildenthal was correct to express reservations about PMERP. An independent retrospective analysis of the first round of funding of PMERP concluded that “the ostensible purpose of the programme is to help develop cigarette designs ‘that might reduce the health risk of smoking.’ Internal company documents also indicate that Philip Morris urgently seeks to restore its scientific ‘credibility,’ as part of a ‘new openness’ in relation to the external community” [120]. Gazdar's interest in PMERP nevertheless persisted. In 2003 he served as a member of PMERP's Scientific Advisory Board [134],[135],[136]. He also gave the keynote speech at the 2007 PMERP symposium, which showcased the work of scientists funded by the program [137]. Consistent with their desire to gain greater credibility in the scientific community, PM scientists shared information with or on behalf of committee members Henderson and Hatsukami at least once more after completion of the IOM report. Henderson invited the industry scientists to speak in a symposium she was organizing at a Society of Toxicology national meeting, on the “scientific basis of reducing harm from cigarette smoking” [138]. Hatsukami communicated with PM's Solana and Walk to obtain an overview of the company's research on biomarkers to assess reduced risk and exposure [139].