The State of Scientific Review at the FDA

Commissioner addresses CSSP meeting

By George B. Corcoran, Past President, Society of Toxicology

hamburgpic.jpgOne highlight of the CSSP winter meeting was an address given by Dr. Margaret Hamburg, commissioner of the Food and Drug Administration. Hamburg was confirmed in May 2009 by unanimous vote of the U.S. Senate as FDA Commissioner, the second woman to serve in this capacity. She is a graduate of Radcliffe College and Harvard Medical School who completed her residency in internal medicine, pursued neurosciences and neuropharmacology research at Rockefeller University and NIMH, and AIDS research as Assistant Director of the NIAID. She served as Commissioner of Health for New York City where she emerged as a leading public health innovator and advocate. She served as Assistant Secretary of Planning and Evaluation at DHHS and is one of the youngest scientists to be elected to the Institute of Medicine. 

Hamburg's remarks to the Council addressed two important challenges facing the agency and the citizens of our nation. The first was the state of science at the agency and regulatory sciences overall, and the second was the more recent concern over conflict of interest of members of FDA committees advising on regulatory decisions. The FDA is a crucial and unique science-based regulatory agency with the mission of protecting public health, ranging to assuring safety of drugs, vaccines, food and food additives, medical and radiation-emmiting products, veterinary products, cosmetics, and the foods people eat every day. More than 25% of all consumer spending in the US is on products regulated by the FDA.  For these great and important historic responsibilities, the agency has under-appreciated and seriously underfunded. Despite attention that is turning now to new challenges like the regulation of tobacco, the approval of novel products from emerging areas of science, and expanded expectations brought on by globalization, there is a growing sense at the agency that it is now beginning to turn a major corner.

Medical review by FDA includes product safety and efficacy as well as considerable post-marketing monitoring. The science capability of the agency must be equal to this task. Currently, the nation is not investing to keep pace in science, particularly in the regulatory sciences. China plans to invest over $10B and the EU of over $5B, dwarfing those of the US which is in the low $Ms.  FDA scientists need the knowledge, tools and professional stakeholder interactions to support the agency in achieving its mission.  Dr. Hamburg reiterated that the US must increase its recognition of and support for the regulatory sciences involving basic and applied research, training, and cross-cutting multidisciplinary approaches.  A successful agency is an important driver of the US health, its economy, and its global competitiveness. FDA Chief Scientist, Dr. Jesse Goodman, has been charged to increase scientific collaboration with academia, industry, and agencies like NIH and CDC, to increase scientific development of agency scientists, and encourage the creation of centers for food regulatory sciences.

Hamburg directed her remaining comments to FDA scientific advisory boards and committees, and specifically addressed the issue of conflict of interest (COI). The agency has 49 committees with over 600 members across a large number of sub-specialty areas.  Some committees provide guidance and others the basis for agency regulations. FDA needs the best experts to serve on these committees, but this is not always easy to achieve because of extensive and time paperwork needed to satisfy appointment requirement and the demanding workload on committees once appointed. The issue of COI can be a challenge where the committee requires expertise in highly technical areas where the number of true experts is small. The agency has authority to grant COI waivers, but they can not exceed 13% of committee membership. COI waivers are currently 5%. Hamburg acknowledged that use of necessary COI waivers is controversial and can undermine confidence in the agency. FDA has recently held many "listening" sessions with stakeholders including patient and consumer groups, trade organizations, and others. When asked for top issues with the agency, it was not avoiding COI but that it was important to have the expertise at the table and to manage conflict appropriately.  

Appointing a committee member with a COI is a difficult judgment that is made by senior agency officials who themselves are free of COI.  While there are no absolute answers to the issues of COI at this point, the agency welcomes feedback on how to move forward. Two principles are driving current thinking: 1. Not all COI is equal [example - an organization receives funding from a conflicted source but the individual researcher on the committee should not be classified with a COI], and 2. Not all committees and meetings are equally sensitive to COI (example - general advice versus regulatory approval committees). Disclosure is a crucial part of managing COI, including why a committee member with a COI waiver is essential for the capabilities of a committee and what avenues were exhausted resulting in use of the member with the COI. The waiver process must be fully transparent.  Approaches discussed during question and answer included non-voting status for COI members, and public release of information on all committee members under the uniform disclosure policy of the International Committee of Medical Journal Editors. Hamburg closed her remarks noting the positive change in administration support of the importance of science in advancing the FDA responsibility of ensuring the safety and high quality of more than a trillion dollars worth of products that are critical for the survival and well-being of all Americans.