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

ABSTRACT

Evaluating the Scientific Evidence for Potential Reduced Risk Tobacco 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

PROCESSThe Life Sciences Research Office (LSRO), a non-profit biomedical research organization, is evaluating the science base necessary to substantiate scientific conclusions for potential reduced-risk tobacco products and is identifying critical research gaps. If feasible, LSRO will also develop an evaluative process for the scientific assessment of potential reduced-risk tobacco products. This review is intended to build on the findings and recommendations of a Committee of the Institute of Medicine, which are detailed in the report, Clearing the Smoke: Assessing the Science Base for Tobacco Harm Reduction. LSRO has convened a multidisciplinary advisory committee to guide the project and provide a risk characterization. Satellite committees will provide independent analyses of the state-of-the-science in three areas: hazard identification and dose-response assessment, individual exposure assessment, and population exposure and behavior assessment. This project is sponsored by Philip Morris USA.

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

The Reduced Risk Review builds on the work done by a Committee of the Institute of Medicine (IOM), which culminated in the report, Clearing the Smoke: Assessing the Science Base for Tobacco Harm Reduction (Institute of Medicine, 2001). The IOM Committee concluded that “…there can be a successful, scientifically-based harm reduction program that is justifiable and feasible − but only if implemented carefully and effectively…” The specific findings and recommendations of the IOM report serve as the departure points for the LSRO study.

Expert Committees

LSRO is conducting the work of the project through two parallel processes. A Core Committee of experts from relevant disciplines is providing oversight of the project and is responsible for the development of a testing and peer-review process to assess 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 critical scientific questions related to the completion of this project (Figure 1).

The HIDRA Committee is identifying and reviewing the current state of the science relating to biological methods employed in the analysis of the effects of tobacco use, highlighting currently available assays, models, and markers that can be used to draw scientific conclusions regarding potential reduced-risk for tobacco products. The primary focus is on the identification of human studies that are able to provide information on the risk of cancer, cardiovascular disease, and chronic obstructive pulmonary disease. In vitro assays and animal models that could support a conclusion of reduced-risk in humans are also being considered.

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 assess potential reduced-risk tobacco products. The IEA Committee is evaluating the validity and utility of various exposure assessment methods as components of a comparative risk assessment. Issues related to the characterization of study populations are also being addressed.

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

Meetings

LSRO hosted an Open Meeting in late April 2005 to encourage input from scientific and other interested parties. Approximately 75 people attended the all-day meeting to listen to presentations from both 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 from interested parties are welcome at any time during the course of the project.

The Core Committee has convened four times to discuss the structure and content of the report and has additional meetings planned for late 2005 and the first half of 2006. The HIDRA, IEA, and PEBA Committees have meetings planned through late 2005. Every committee meeting of the Reduced Risk Review Project includes an information-gathering session, usually at the beginning of each meeting, which is open to the public. Individuals interested in attending should register via the LSRO website (www.LSRO.org).

Work Product

The 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.

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

LSRO STUDY OBJECTIVES:

CORE COMMITTEE

APPROACHThe 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,• Specific diseases/adverse health outcomes associated with significant morbidity and mortality caused by smoking,• Surrogate biological markers associated with lung cancer, chronic obstructive pulmonary disease, and cardiovascular disease,• Changes in smoking behavior and/or alternative tobacco use that could adversely impact the potential for risk reduction,• Behavioral/psychological indicators for increased rates of tobacco usage associated with the introduction of potential reduced-risk products, and• Surveillance approaches for potential reduced-risk products.

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