Strengthening a Workforce for Innovative Regulatory Science in Therapeutics Development

The development and application of regulatory science – which FDA has defined as the science of developing new tools, standards, and approaches to assess the safety, efficacy, quality, and performance of FDA-regulated products – calls for a well-trained, scientifically engaged, and motivated workforce. FDA faces challenges in retaining these regulatory scientists and providing them with opportunities for professional development. In the private sector, advancement of innovative regulatory science in drug development has not always been clearly defined, well coordinated, or connected to the needs of the agency. Moreover, resource constraints and an increasingly complex workload make it difficult for FDA scientists to interact with other scientists and enhance their scientific knowledge base. Several barriers to the advancement of regulatory science have been identified – including workforce and resource constraints in all sectors, systemic barriers to collaboration and scientific exchange, and deficiencies in the regulatory science infrastructure.

In 2010, the IOM’s Forum on Drug Discovery, Development, and Translation held a workshop that examined the state of regulatory science and considered approaches to enhance it. As a follow-up to that workshop, the Forum held a workshop on September 20-21, 2011, to provide a format for establishing a specific agenda to implement the vision and principles relating to a regulatory science workforce and infrastructure as discussed in the 2010 workshop. At the workshop, speakers considered opportunities and needs for advancing innovation in the discipline of regulatory science for therapeutics development through an interdisciplinary regulatory science workforce and examined specific strategies for developing a discipline of innovative regulatory science through the development of a robust workforce within academia and industry and at FDA. This document summarizes the workshop. 

Institute of Medicine of The National Academies. December 21, 2011

Strengthening a Workforce for Innovative Regulatory Science in Therapeutics Development

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Scientific Standards for Studies on Modified Risk Tobacco Products

Dec. 14, 2011.WASHINGTON. A new Institute of Medicine report specifies the types of research that the Food and Drug Administration 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.  While modified risk tobacco products could be one part of a comprehensive strategy to lower tobacco-related death and disease in the U.S., 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. Examples of modified risk tobacco products may include e-cigarettes and tobacco lozenges.

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, adds 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.  Because of the tobacco industry’s well-documented history of improper conduct, many institutions and scientists currently refuse to conduct or publish research supported by the tobacco industry.

“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.  “Having trusted third parties oversee the conduct of research could help re-engage scientists and enable generation of credible research data on the health effects of these products.”

The Family Smoking Prevention and 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 U.S. 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 IOM’s report says 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 says.  The industry’s history of improper manipulation of data undermined the credibility of its research and left it isolated from the mainstream scientific community.  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.  Examples of third-party partnerships between industry and government include the Health Effects Institute and the Reagan-Udall Foundation. No similar organization currently exists for the tobacco industry.

Making data publicly available will also build public trust and will allow for independent analysis of data and methods, the report says.  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.

The study was sponsored by the Food and Drug Administration.  Established in 1970 under the charter of the National Academy of Sciences, the Institute of Medicine provides independent, objective, evidence-based advice to policymakers, health professionals, the private sector, and the public.  The National Academy of Sciences, National Academy of Engineering, Institute of Medicine, and National Research Council make up the National Academies. 

Scientific Standards for Studies on Modified Risk Tobacco Products

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Breast Cancer and the Environment:A Life Course Approach

WASHINGTON — Women may be able to reduce their risk for breast cancer by avoiding unnecessary medical radiation, forgoing use of combination estrogen-progestin menopausal hormone therapy if possible, limiting alcohol consumption, maintaining a healthy weight, exercising regularly, and avoiding tobacco use, says a new report from the Institute of Medicine. These preventive steps focus on the environmental risk factors for which there is consistent scientific evidence of an association with breast cancer. 

The evidence also indicates a possible, though currently less clear, link to increased risk for breast cancer from exposure to benzene, 1,3-butadiene, and ethylene oxide, which are chemicals found in some workplace settings and in gasoline fumes, vehicle exhaust, and tobacco smoke.  Avoiding personal use of hair dyes and non-ionizing radiation emitted by mobile devices and other technologies likely will not impact a woman's risk for breast cancer, as multiple studies have found no connection to the disease.

Because of insufficient or contradictory evidence, the scientific jury is still out on whether many chemicals of concern, including bisphenol A (BPA), pesticides, ingredients in cosmetics and dietary supplements, and other substances alter the risk for breast cancer, the report says.  Women may choose to minimize their exposure to some chemicals, but the committee found the research inadequate to draw conclusions about the potential benefit of such actions.  Chemical ingredients in cosmetics, dietary supplements, and other products undergo only very limited testing before they are put on the market, and the committee noted the value of efforts to help consumers become more aware of this issue.

The steps identified in the report have the potential to reduce risk for breast cancer among women in general, but the committee cautioned that the evidence on how much risk reduction any of these steps offers is inconclusive.  Whether it is small or significant, the impact on individuals will vary considerably because women are exposed to a range of substances throughout their lives; in addition, biological, physical, and genetic factors influence their individual chances for developing the disease. 

The report's conclusions are the result of a detailed review of scientific research on environmental factors that may affect breast cancer risk.  The committee also explored challenges to studying possible links between environmental exposures and breast cancer and recommends future research directions.  Areas where there is provocative but as yet inconclusive evidence and that warrant priority attention include overnight shift work and accompanying disruptions of the sleep cycle; chemicals that mutate genes, alter gene expression, or affect hormones such as estrogen; and gene-environment interactions.  More research needs to be conducted on the effects of exposures throughout the entire life span, including at specific stages of breast development, and on the cumulative effects of exposures at different life stages or multiple exposures that occur together, the report emphasizes.  Most research has focused on adults and on exposures occurring within a few years prior to a diagnosis, but recent studies have shown the importance of exposures at various life stages, such as childhood, adolescence, pregnancy, and menopause.

In many cases, more information also needs to be gathered to determine whether preventive steps can be taken and how they can be most effective.  For example, we do not yet know when weight loss is most likely to be beneficial in reducing postmenopausal cancer risk.   

"Breast cancer develops over many years, so we need better ways to study exposures throughout women's lives, including when they are very young," said committee chair Irva Hertz-Picciotto, professor, department of public health sciences, and chief, division of environmental and occupational health, School of Medicine, University of California, Davis.  "We also need improved methods to test for agents that may be contributing to breast cancer risk and to explore the effects of combined exposures."

The study was sponsored by Susan G. Komen for the Cure.  Established in 1970 under the charter of the National Academy of Sciences, the Institute of Medicine provides independent, objective, evidence-based advice to policymakers, health professionals, the private sector, and the public.  The National Academy of Sciences, National Academy of Engineering, Institute of Medicine, and National Research Council make up the National Academies. 

Breast Cancer and the Environment: A Life Course Approach

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Applications to Integrated Biosurveillance

After the September 11, 2001, terrorist attacks and subsequent anthrax mailings, the U.S. government prioritized a biosurveillance strategy aimed at detecting, monitoring, and characterizing national security health threats in human and animal populations, food, water, agriculture, and the environment.

A variety of agencies share biosurveillance responsibilities, and efforts have been made to improve national biosurveillance through data exchanges and collaboration. However, gaps and challenges in biosurveillance efforts and integration of biosurveillance activities remain.

September 8-9, 2011, the IOM held a workshop to explore the information-sharing and collaboration processes needed for the nation’s integrated biosurveillance strategy. Presenters at the workshop

examined the strengths and limitations of different models of information analysis, control, and distribution;

considered examples and lessons learned from other similar information sharing collaborations;

explored approaches to developing an effective and sustainable concept of operations that includes join rules, procedures, and performance measures; and
illustrated the value added in collaboration through scenarios and real-life examples.

This document summarizes the workshop.

Deepali M.Patel and Steve Olson,Rapporteurs;Planning Committee on Information-Sharing Models and Guidelines for Collaboration: ; Institute of Medicine. Released: November 30, 2011.Type: Workshop Summary.Topic: Public Health. Activity: Information-Sharing Models and Guidelines for Collaboration:Applications to an Integrated One Health Biosurveillance Strategy – A Workshop.Board: Board on Health Sciences Policy

Applications to an Integrated One Health Biosurveillance Strategy A Workshop

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The Science and Applications of Synthetic and Systems Biology

Humans have been modifying the characteristics of plants and animals for thousands of years by breeding species together to promote certain traits and reduce others. The discovery of the DNA structure in 1953, followed by the invention of DNA recombinant technology two decades later, paved the way for the powerful potential to manipulate genes directly – in such a way that the “nature” of an organism can be precisely altered in a single generation.

In the last several decades, researchers have been able to work directly with DNA to genetically engineer changes in cells, leading to advances such as the ability to mass-produce safe and affordable insulin for diabetics. These advances in our understanding of the basic building blocks of life, combined with a concurrent explosion in enabling technologies, have allowed researchers to come tantalizingly close to being able to “design” new organisms and, in effect, create life.

The IOM’s Forum on Microbial Threats hosted a public workshop March 14 and 15, 2011, to explore the scientific and policy dimensions of recent developments in synthetic and systems biology. The workshop explored how these tools and approaches can be applied to new infectious disease diagnostic platforms, new drug discovery, and targeted vaccine therapies.

Participants discussed how these advanced technologies have the potential to improve understanding of infectious microbes and the mechanisms by which they cause disease; the applications of these tools and approaches for disease detection and diagnostic platforms; and the development of new therapeutics, vaccines, and other infectious disease intervention technologies.

Released: November 23, 2011. Authors:Eileen R. Choffnes, David A. Relman, and Leslie Pray, Rapporteurs; Forum on Microbial Threats; Institute of Medicine Type: Workshop Summary.Topics:Diseases, Global Health, Public Health. Activity: Forum on Microbial Threats. Board: Board on Global Health 

The Science and Applications of Synthetic and Systems Biology

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Disposition of the Air Force Health Study

The Institute of Medicine was asked to provide guidance on the future of the Air Force Health Study (AFHS, also known as the Ranch Hand Study), a long-term epidemiologic analysis of Air Force personnel who conducted aerial spraying of herbicides during the Vietnam War.

The committee's final report, Disposition of the Air Force Health Study, concluded that the medical records, data, and biological specimens collected in the study, which closed on September 30, 2006, were a trove of valuable research material.

It recommended that--after the Air Force Health Study's scheduled end--these assets be made available to researchers, through a custodian that takes an active role in fostering their use. Several options for managing the assets were presented. No matter where the AFHS materials go, that custodian would need a secure source of funding. The report also recommended that Congress allocate at least $250,000 annually for three years to promote research using the data and specimens.

Type: Consensus Report.Topic: Veterans Health. Activity: Disposition of the Air Force Health Study. Board: Board on Population Health and Public Health Practice.INSTITUTE OF MEDICINE OF THE NATIONAL ACADEMIES. THE NATIONAL ACADEMIES PRESS. Washington, D.C.

Disposition of the Air Force Health Study

Improving Health Literacy Within a State

Health literacy is the degree to which individuals can obtain, process, and understand the basic health information and services they need to make appropriate health decisions. According to Health Literacy: A Prescription to End Confusion (IOM, 2004), nearly half of all American adults--90 million people--have inadequate health literacy to navigate the healthcare system.

To address issues raised in that report, the Institute of Medicine convened the Roundtable on Health Literacy, which brings together leaders from the federal government, foundations, health plans, associations, and private companies to discuss challenges facing health literacy practice and research and to identify approaches to promote health literacy in both the public and private sectors. On November 30, 2010, the roundtable cosponsored a workshop with the University of California, Los Angeles (UCLA), Anderson School of Management in Los Angeles.

Improving Health Literacy Within a State serves as a summary of what occurred at the workshop. The workshop focused on understanding what works to improve health literacy across a state, including how various stakeholders have a role in improving health literacy. The focus of the workshop was on presentations and discussions that address (1) the clinical impacts of health literacy improvement approaches; (2) economic outcomes of health literacy implementation; and (3) how various stakeholders can affect health literacy.

Authors: Maria Hewitt, Rapporteur; Roundtable on Health Literacy; Institute of Medicine

Improving Health Literacy Within a State