Modified-Risk Research Update

Institute of Medicine issues report on scientific standards for studies

WASHINGTON -- The Institute of Medicine (IOM) released a report yesterday on the types of research that the U.S. Food & Drug Administration (FDA) will take into consideration in the assessment and ongoing review of modified-risk tobacco products and should require before allowing tobacco companies to sell or advertise modified-risk tobacco products as being capable of reducing the health risks of tobacco use.

A modified-risk tobacco product is any tobacco product sold or distributed for use to lower the harm or risk of tobacco-related disease associated with other tobacco products. Examples of modified-risk tobacco products may include e-cigarettes and tobacco lozenges.

This report adds to comments and recommendations submitted to the FDA on this topic, including information obtained from a public workshop held in August 2011 and an associated open public docket. Experts within the FDA's Center for Tobacco Products will take these recommendations into consideration in developing its guidance and/or regulation on the scientific evidence required for the assessment and ongoing review of modified risk tobacco products.

While modified risk tobacco products could be one part of a comprehensive strategy to lower tobacco-related death and disease in the United States, especially among tobacco users who are unable or unwilling to quit entirely, little is currently known about the products' health effects and whether they pose less risk than traditional tobacco products, the IOM said.

It said that companies and other sponsors developing modified-risk tobacco products should consider using FDA-approved independent third parties to oversee health and safety research on their products, added the report, which was completed to fulfill a congressional mandate. Independent oversight would ensure that the data submitted to FDA are reliable and credible, and it could help re-engage the mainstream scientific community in research.

"Right now there's a shortage of scientific evidence on the health effects of modified-risk tobacco products, and the tobacco industry currently lacks the trustworthiness, expertise and infrastructure to produce it," said Jane Henney, chair of the committee that wrote the report, and professor of medicine and public health sciences at the University of Cincinnati.

The Family Smoking Prevention & Tobacco Control Act of 2009 requires that modified-risk tobacco products undergo a pre-market approval process similar to drugs and devices. According to the act, a company that wants to market a lower-risk tobacco product in the United States must offer scientific proof to FDA that the marketing of the product will not only reduce harm to individual users, but also benefit the health of the population as a whole. The act also directed FDA to consult with IOM on how scientific studies of modified risk tobacco products should be designed and conducted.

The FDA must publish regulations or guidance on the scientific evidence required for assessment and ongoing review of modified risk tobacco products by April 2012.

The IOM's report said that the studies should examine all of the areas needed to forecast and monitor a proposed product's impact on public health, including its composition and addiction potential; the amount of human exposure to harmful components; perceptions about the product's effects and likelihood of addiction; and effects on human health. Studies should be generalizable to the whole population and should also include populations of special relevance, including current and former smokers, beginning smokers, adolescents and populations at high risk for tobacco use.

While studies submitted to FDA to demonstrate products' safety are usually conducted or sponsored by the companies themselves, the tobacco industry at present lacks the capacity and expertise to conduct such research, the report said.

"The industry's history of improper manipulation of data undermined the credibility of its research and left it isolated from the mainstream scientific community," said the IOM. "Many major universities have policies against acceptance of tobacco funding, for example, and many high-impact scientific and medical journals will not accept manuscripts supported by the tobacco industry."

Using independent, FDA-approved third parties to conduct, provide oversight of, and distribute funding for research could distance the influence and reputation of the tobacco industry from the scientists who are researching their products, it added.

Making data publicly available will also build public trust and will allow for independent analysis of data and methods, the report said. FDA should require sponsors of modified-risk tobacco products to place all data generated during a product's development and marketing in a public repository selected by the agency.

FDA should also require that studies offered in support of an application to market modified-risk tobacco products conform to established standards of good research governance, including appropriately qualified investigators, transparency, independent institutional review board or ethical review and adherence to federal regulations that ensure the protection of human participants in biomedical research.

Click here to download a free PDF of the uncorrected version of the IOM report.