Scientific Standards
FOR STUDIES ON
Modified Risk Tobacco Products

Committee on Scientific Standards for Studies on
Modified Risk Tobacco Products

Board on Population Health and Public Health Practice

INSTITUTE OF MEDICINE
OF THE NATIONAL ACADEMIES

THE NATIONAL ACADEMIES PRESS

Washington, D.C.

THE NATIONAL ACADEMIES PRESS 500 Fifth Street, NW Washington, DC 20001

NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of the committee responsible for the report were chosen for their special competences and with regard for appropriate balance.

This study was supported by Contract No. HHSF22301011T, Task Order #17 between the National Academy of Sciences and the Food and Drug Administration of the U.S. Department of Health and Human Services. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the view of the organizations or agencies that provided support for this project.

International Standard Book Number-13: 978-0-309-22398-0
International Standard Book Number-10: 0-309-22398-9

“Knowing is not enough; we must apply.
Willing is not enough; we must do.”

—Goethe

INSTITITE OF MEDICINE
OF THE NATIONAL ACADEMIES

Advising the Nation. Improving Health.

THE NATIONAL ACADEMIES

Advisers to the Nation on Science, Engineering, and Medicine

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COMMITTEE ON SCIENTIFIC STANDARDS FOR STUDIES ON MODIFIED RISK TOBACCO PRODUCTS

Jane E. Henney (Chair), Professor of Medicine and Public Health Sciences, University of Cincinnati, Ohio

Timothy B. Baker, Professor of Medicine and Associate Director, Center for Tobacco Research and Intervention, University of Wisconsin, Madison

Rebecca Bascom, Professor of Medicine, Milton S. Hershey Medical Center, The Pennsylvania State University, Hershey

Shyam Biswal, Professor, Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland

Daniel Carpenter, Professor of Government, Center for Government and International Studies, Harvard University, Boston, Massachusetts

Constantine Gatsonis, Henry Ledyard Goddard University Professor and Chair, Department of Biostatistics, Brown University, Providence, Rhode Island

Study Staff

Kathleen Stratton, Study Director (through September 2011)

Joel Wu, Study Director (from September 2011)

Michelle C. Catlin, Senior Program Officer (from September 2011)

Erin Rusch, Research Associate (from September 2011)

Hannan Braun, Research Assistant

Malcolm Biles, Senior Program Assistant

Rose Marie Martinez, Director, Board on Population Health and Public Health Practice

Consultants

Suchitra Krishnan-Sarin, Associate Professor of Psychiatry and Vice Chair, Human Investigations Committee, Yale University School of Medicine

Holly E. R. Morrell, Assistant Professor, Department of Psychology, Loma Linda University

Gary Stoner, Professor of Medicine, Department of Medicine, Medical College of Wisconsin

Wendy Theobald, Researcher, Center for Tobacco Research and Intervention, University of Wisconsin Medical School

Robert B. Wallace, Irene Ensminger Stecher Professor of Epidemiology and Internal Medicine, Department of Epidemiology, College of Public Health, The University of Iowa

Reviewers

This report has been reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise, in accordance with procedures approved by the National Research Council’s Report Review Committee. The purpose of this independent review is to provide candid and critical comments that will assist the institution in making its published report as sound as possible and to ensure that the report meets institutional standards for objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the deliberative process. We wish to thank the following individuals for their review of this report:

Linda S. Birnbaum, National Institute of Environmental Health Sciences

Richard J. Bonnie, University of Virginia

David B. Coultas, The University of Texas Health Science Center at Tyler

Louis Anthony Cox, Jr., Cox Associates

Sean P. David, Stanford University School of Medicine

Jonathan Foulds, Penn State College of Medicine

Mitchell H. Gail, National Cancer Institute

John R. Hughes, University of Vermont College of Medicine

Donald S. Kenkel, Cornell University

Caryn Lerman, University of Pennsylvania

Dean Lillard, Cornell University

Ana Navas-Acien, Johns Hopkins Bloomberg School of Public Health

Dan Romer, The Annenberg Public Policy Center of the University of Pennsylvania

Barry Sickels, AstraZeneca

Brian L. Strom, Perelman School of Medicine at the University of Pennsylvania

Clifford H. Watson, Centers for Disease Control and Prevention

Although the reviewers listed above have provided many constructive comments and suggestions, they were not asked to endorse the conclusions or recommendations, nor did they see the final draft of the report before its release. The review of this report was overseen by May R. Berenbaum, University of Illinois, and Robert S. Lawrence, Johns Hopkins Bloomberg School of Public Health. Appointed by the National Research Council and Institute of Medicine, they were responsible for making certain that an independent examination of this report was carried out in accordance with institutional procedures and that all review comments were carefully considered. Responsibility for the final content of this report rests entirely with the authoring committee and the institution.

Preface

Tobacco use remains the leading cause of preventable morbidity and mortality in the United States. While the adverse health effects of tobacco use are well established in the scientific literature, an understanding of the science is not required to appreciate the human cost; every day, people see close friends and family suffer with the consequences of tobacco use. Every day, cigarette smokers try to quit, and yet, the vast majority of them will fail. An estimated 70 percent of smokers want to quit completely, and while 45 percent attempt to quit each year, only 6 percent of smokers are able to successfully quit.

Instead of quitting, many cigarette smokers have sought a product with less risk, and for decades, the tobacco industry has purposefully misled the public into believing that there have been safer alternatives. The most prominent example is the “light” cigarette—a product implied to be safer, which in fact, when used, was as hazardous as “regular” cigarettes. The prospect of a less hazardous tobacco product is not in and of itself problematic. The fundamental issue is that if a product is going to be marketed as being “safer,” then the claim must be true.

Section 911 of the Family Smoking Prevention and Tobacco Control Act of 2009 directly addresses the problem of false and unfounded claims for modified risk tobacco products (MRTPs). The law remains open to the possibility that less hazardous products that reduce harm to public health may enter the market, but it gives the government the authority and the power to assure that they are actually reducing risk and harm. The law also directed the U.S. Food and Drug Administration (FDA) to develop, in

consultation with the Institute of Medicine (IOM), regulations and guidance on the design and conduct of scientific studies of MRTPs, which was the task of the committee.

Regulating tobacco products creates unique challenges. Unlike most products regulated by the FDA, tobacco is inherently hazardous and offers primarily risks rather than any significant physiological benefit to the user’s health. Recognizing this, the law provides a public health standard and additional requirements of these products that must be considered as the FDA regulates these products. First, the law creates a public health standard that requires the FDA to evaluate the effect of the MRTP on not only users of the product, but also nonusers and the entire population as a whole. Second, the law requires postmarket observational studies of the MRTPs as a condition of approval, and also requires the annual submission of data about the MRTPs to the FDA. Finally, the law sets expiration dates on the orders to market the MRTPs. In addition, the FDA can revoke an order for any failure to comply with regulatory requirements or if there is evidence that the product is in fact harmful to public health.

The evaluation of the effect of MRTPs on public health will require a wide range of evidence and therefore will require many different types of study designs, including studies of the composition of MRTPs and studies of human exposure, human health effects, the likelihood of addiction and abuse, and the perception and understanding of the product by the public. Furthermore, the evidence must be able to reliably support predictions about the effect of marketing the product on public health, and therefore these studies must be properly designed and rigorously conducted. Study designs will need to include all relevant populations including populations at a high risk for tobacco use. Study designs must be able to support not only inferences about the mechanisms of the products effects, but also predictions about the products’ effects in the real world.

Also, relevant to the committee’s deliberations as it considered the conduct of studies is the history of the tobacco industry’s past behavior. The tobacco industry has a long and well-documented history of illegal and improper conduct, and its practices have only recently been regulated. Because of the health impact of its products and the opaque practices that have been engaged by the tobacco industry, many academic institutions and their faculty that would normally be involved in a product’s evaluation have been separated from conducting research related to tobacco products for many years. Thus, the committee concluded that the tobacco industry currently lacks not only the trustworthiness, but also the expertise, infrastructure, and other resources needed to independently produce the scientific evidence necessary to meet the public health standards set by the law. In the report, the committee explores the possibility

of new governance mechanisms to address this problem, including the potential creation of a third-party governance entity. The committee does recognize that there are MRTPs that may not be developed by the tobacco industry and thus believes the need for third-party governance may not be applicable in all cases.

Overall, the committee’s goal was to develop enduring guidelines and considerations for the production of credible and comprehensive evidence of the effects of MRTPs. The committee emphasized that the principle of public disclosure, which adds the sunshine of openness and transparency, must be applied to the entire process of product development. It is hoped that this report will provide guidance not only to the FDA but also to all stakeholders (the tobacco industry, academic researchers, and journal editors, etc.) on how the important work of evaluating these products can move ahead.

This committee has volunteered a great deal of time and energy into completing a remarkably complex task, and for that I am very appreciative. I thank its members for their collective and individual efforts. I would also like to extend my own and the committee’s gratitude to Suchitra Krishnan-Sarin, Holly E. Morrell, Gary Stoner, Wendy Theobald, and Robert B. Wallace for their assistance and expertise as external consultants. On behalf of the committee, appreciation is also extended to each who provided information, data, or even an informed opinion during open sessions or by mail. Finally, the committee and I would like to thank the IOM staff for their hard work and diligence: Kathleen Stratton, Joel Wu, Michelle C. Catlin, Erin Rusch, Hannan Braun, Malcolm Biles, and Rose Marie Martinez.

Jane E. Henney, Chair
Committee on Scientific Standards for
Studies on Modified Risk Tobacco Products

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Contents

BOXES

Acronyms and Abbreviations