Kara D. Lewis, Amy M. Brownawell, Michael C. Falk, Keith Lenghaus, Paula M. Nixon, Catherine St. HilaireThe Life Sciences Research Office, 9650 Rockville Pike, Bethesda, Maryland 20814.

ABSTRACT

EVALUATING THE SCIENCE BASE FOR ASSESSING CLAIMS OF REDUCED RISK FOR TOBACCO BASED POTENTIAL REDUCED EXPOSURE PRODUCTS

About LSRO: History and MissionAbout LSRO: History and Mission

Since 1962, the Life Sciences Research Office (LSRO) in Bethesda, MD has provided clients with expert evaluation of issues, opportunities, data, programs, and proposals in basic and clinical research. LSRO has carefully built an international reputation for objectivity and is regarded as a widely accepted authoritative source, independent from special interest groups and politics. LSRO reports are timely, comprehensive, state-of-the-science reviews. Moreover, LSRO’s experience with regulatory and governmental processes has proven useful to clients from the public and private sector alike. For more information, please refer to www.LSRO.org. Funding for this project was provided by Philip Morris USA.

BACKGROUND

PROCESS

The Life Sciences Research Office, Inc. (LSRO), a Bethesda, Maryland-based non-profit organization that provides scientific evaluation, analysis and advice of biomedical research scientists, is evaluating the science base necessary to support claims of reduced risk for tobacco-based “potential reduced exposure products” (PREPs) and identifying areas of research where additional information could contribute to an assessment of reduced risk. If the current state of the science is adequate, LSRO will develop a scientific framework for assessing whether tobacco PREP products are likely to decrease the risk of cancer, cardiovascular disease and chronic obstructive pulmonary disease for tobacco product users. The aim of the project is to extend the work described in the Institute of Medicine (IOM) report Clearing the Smoke: Assessing the Science Base for Tobacco Harm Reduction (CTS) by providing further detail on approaches reviewed in CTS and evaluating scientific approaches developed since the IOM report was published in 2001. LSRO has assembled four committees of experts with diverse, relevant backgrounds to advise the project. The Core Committee will evaluate the state of the science within a risk assessment framework for potential reduced risk tobacco products and provide overall guidance for the project. Three satellite committees will review the current state of the science for tobacco product related Hazard Identification and Dose Response Assessment, Individual Exposure Assessment, and Population Exposure and Behavior Assessment. The reports produced by the state-of-the-science review committees will provide the basis for the Core Committee’s risk assessment framework. LSRO held an Open Meeting in April, 2005 to solicit public comment on the project and the Core Committee has met five times to date. The state of the science review committees have been meeting over the last several months and summaries of their findings will be forwarded to the Core Committee in early 2006. The project is sponsored by Philip Morris USA.

Expert CommitteesA Core Committee of experts from diverse relevant disciplines is providing oversight of the project, and is responsible for the assessment of potential reduced-risk tobacco products. Three state-of-the-science review committees, Hazard Identification and Dose-Response Assessment (HIDRA), Individual Exposure Assessment (IEA), and Population Exposure and Behavior Assessment (PEBA), will address scientific questions relevant to the project (Figure 1).

The HIDRA Committee is identifying and reviewing currently available in vitro assays, animal models, and clinical studies that can be used to arrive at scientific conclusions regarding reduced-risk for tobacco products. The primary focus will be on the identification of human studies that are able to provide information on the risk of lung cancer, cardiovascular disease, and chronic obstructive pulmonary disease.

The IEA Committee is evaluating current methods for determining external and internal exposure to constituents of smokeless tobacco products and tobacco smoke (both for users of tobacco products and individuals passively exposed to environmental tobacco smoke) that can be applied to draw scientific conclusions as to whether tobacco products are likely to reduce exposure associated with cigarette smoking.

The PEBA Committee is assessing the potential consequences on the population of the availability of potential reduced-risk tobacco products both the potential consequences on the population of the availability of potential reduced-risk tobacco products and surveillance methods of population level use patterns. Some specific issues being addressed include altered initiation/recruitment of non-smokers (especially adolescents) and changes in patterns of cessation and relapse.

MeetingsLSRO held an Open Meeting in April 2005 to encourage input from scientific and other interested parties. Approximately 75 people attended the all-day meeting to listen to presentations from academic and industry speakers. Written comments submitted to LSRO prior to and following the Open Meeting have been forwarded to the Core Committee members for their consideration. Comments on the project are welcome throughout the course of the project.

The Core Committee has convened five times to discuss the structure and content of the report and has additional meetings planned for the first half of 2006. State-of-the-science review committee meetings are planned through late 2005. Committee meetings of the Reduced Risk Review Project usually include an information-gathering session at the beginning of each meeting that is open to the public. Individuals interested in attending should register via the LSRO website (www.LSRO.org).

Figure 1. . Committee Structure of the Reduced Risk Review Project.

LSRO STUDY OBJECTIVES:

CORE COMMITTEE

APPROACH

REFERENCESInstitute of Medicine (2001) Clearing the Smoke. Assessing the Science Base for Tobacco Harm Reduction. (Stratton, K., Shetty, P., Wallace, R. & Bondurant, S., eds. ). Washington, DC: National Academy Press.

Alwynelle Ahl, Ph.D., D.V.M.Highland Rim Consulting, Inc.Lyles, TN

Elizabeth Anderson, Ph.D.Sciences International, Inc.Alexandria, VA

Nancy L. Buc, Esq.Buc & BeardsleyWashington, D.C.

Carroll Cross, M.D.School of MedicineUniversity of California, Davis Davis, CA

Louis D. Homer, M.D., Ph.D.Legacy ResearchPortland, OR

Joseph V. Rodricks, Ph.D.ENVIRON InternationalArlington, VA

Emanuel Rubin, M.D.Jefferson Medical CollegeThomas Jefferson University Philadelphia, PA

Richard C. Schwing, Ph.D.Sustainable Visions, Inc.West Bloomfield, MI

Richard Windsor, M.S., Ph.D., M.P.H.School of Public Health and Health ServicesGeorge Washington UniversityWashington, D.C.

• To provide an independent, comprehensive evaluation of the science base necessary to determine whether potential reduced-risk tobacco products are likely to reduce risk,• To develop a detailed research agenda to address gaps in the science base and, if feasible, • To develop an evaluative process for the scientific assessment of potential reduced- risk tobacco products.

CORE COMMITTEE

HIDRA

ASSESS ADVERSEHEALTH EFFECTS

REDUCTION

PEBA

ASSESS POPULATION EFFECTS

IEA

ASSESS EXPOSURE REDUCTION

Medical, scientific, and public health organizations have concluded that the best way to protect individual and public health from tobacco harms are to achieve abstinence, prevent initiation and relapse, and eliminate environmental tobacco smoke exposure. However, consideration is also being given to the concept that reducing adverse effects on the health of tobacco-users who will not or can not abstain from the use of tobacco products (i.e., risk-reduction) may also be a valuable component of a comprehensive tobacco control program (Institute of Medicine, 2001).

LSRO’s Reduced Risk Review builds on the work of a committee of the Institute of Medicine (IOM) to formulate scientific methods and standards for assessing ‘potential reduced-exposure products’ (PREPs) detailed in the report, Clearing the Smoke: Assessing the Science Base for Tobacco Harm Reduction (Institute of Medicine, 2001). In contrast to the IOM report, the Reduced Risk Review addresses only tobacco based products and refers to them as ‘potential reduced risk tobacco products’. The specific findings and recommendations of the IOM report serve as the departure points for the LSRO study.

Work ProductThe results of these investigations and deliberations will be presented as a Reduced Risk Core Committee report with an expected completion date of July 2006. State-of-the-science reports from the HIDRA, IEA, and PEBA Committees are expected in late 2006.

The Reduced Risk Review will evaluate the science base necessary to assess whether potential reduced-risk tobacco products are likely to reduce the risks of cigarette smoking by identifying and evaluating:•Exposure characteristics of potential reduced-risk products under conditions of actual use,•Surrogate biological markers of lung cancer, cardiovascular disease, and chronic obstructive pulmonary disease,•Potential population risks and groups at greatest risk associated with potential reduced risk tobacco products, and •Methods to predict or estimate population risk prior to marketing and to monitor population risk after a potential reduced risk tobacco product is marketed.