FDA Advisory Committees: Independent, Informed, Essential, and Evolving

By: Robert M. Califf, M.D.

One of the most common concerns raised when I meet with medical leaders is the need to improve the function of FDA’s Advisory Committees (ACs). ACs play a key role in FDA’s decision-making process by providing independent expert advice on extraordinarily complex issues. Just as importantly, they offer a forum for open and transparent discussion about these processes. As their name suggests, ACs are only advisory, but they can yield unique insights into understanding the balance of benefits and risks of products.

Not every product is brought to an advisory committee — when the answers are clear, the FDA makes decisions without consulting an AC. But when products present challenging issues or involve developing areas of science, the views of experts in relevant fields can provide essential perspective needed to make good decisions.

They also provide a barometer for the public on Agency thinking in a given field and offer insight into Agency decision-making and requirements for successful product development in a particular setting. The views expressed and votes taken can have financial impacts on companies and can lead to changes in how investments are made in therapeutic areas. So it is not surprising that the deliberations and views of ACs often receive significant media attention.

ACs have been the subject of ongoing discussions concerning their impartiality, their transparency, and how they affect decisions made about FDA-regulated products. In response to these concerns, the FDA is taking a closer look at the AC meeting process to determine what changes may be needed to ensure that ACs remain able to provide crucial expert advice relevant to the uncertainties that prompt such meetings.

Robert Califf

The process of engaging the expertise needed for ACs requires careful consideration, and the goal of ensuring that such a critical function leads to the best advice with optimal public trust by eliminating or managing conflicts is embedded in both law and culture at FDA. Experts who comprise ACs generally are classified as “special government employees” (SGEs) of the FDA. As such, they must declare any potential conflicts of interest and undergo a rigorous financial screening to ensure that they do not have a conflict or apparent conflict that could preclude their participation. SGEs are also expected to be free of intellectual bias that may foreclose their ability to consider the data and questions with an open mind.

Sometimes, a compelling interest can justify allowing a SGE with a potential conflict to participate. In such a case, the prospective AC member must be granted a waiver or appearance authorization, which provide a mechanism for clearly delineating the reasons for allowing that person to participate and requires disclosing the conflict. This aspect of the AC process has evolved over time, becoming increasingly complex and burdensome.

In 2007, the Food and Drug Administration Amendments Act (FDAAA) restricted the FDA’s ability to use waivers for SGEs as part of an effort to reduce bias among AC members by allowing minimal or no financial conflicts. This led to concerns from multiple stakeholders about whether the FDAAA provision was in fact discouraging the most qualified experts from serving on ACs and thus depriving FDA of the best possible guidance on important scientific issues.

In response to these concerns, Congress included a provision in the 2012 Food and Drug Administration Safety and Innovation Act (FDASIA) that encouraged FDA to weigh an AC member’s conflicts against the need for that participant’s scientific expertise. However, despite this added flexibility, there are many who believe FDA has not been aggressive enough in advocating for waivers — a circumstance that they believe has sometimes resulted in difficulty obtaining the optimal expertise needed to address the complex problems typically brought to ACs. And some outside the Agency have wondered whether this means FDA is moving to reduce use of ACs.

The process for AC participation itself has led to other criticisms. Across academia, the AC system is seen as overburdened with unnecessary paperwork. Additionally, FDA has faced criticism that the concept of an “imputed interest” is interpreted so that academic leaders with significant experience and insight are considered to have conflicts relating to grants and contracts held by faculty members at the same institution — even if they themselves have no involvement with the project. The proliferation of roadblocks to serving as an SGE has led some within FDA and key leaders in various scientific fields to question the value of ACs in their current form.

After indepth discussion with the medical product and tobacco Centers, OMPT initiated a process improvement evaluation using Lean concepts, which comprise an industrial engineering toolset used for process improvement. These tools were applied to the AC process to fully understand the administrative requirements for planning meetings and screening potential SGEs. We are confident that administrative processes, both inside FDA and for SGEs, will be streamlined as a result.

The next step will be to evaluate current policies and identify areas where the evaluation of conflicts of interest for SGEs can be modernized. We must consider questions such as the criteria for disqualifying AC members from specific activities, the appropriate scope of “imputed interests,” and the interrelationship between the advisory role of AC members and the decisional role of Agency employees.

Even more importantly, we must engage in wide-ranging discussions inside and outside FDA about the best ways for the Agency to get the advice it needs to make critical decisions that protect and promote the health and safety of all Americans. To obtain the best expertise possible, we must optimally configure and administer our ACs.

There is no question that we must appropriately address potential conflicts for our SGEs.  However, we must also ensure that experts working in their fields are not unnecessarily foreclosed from participation in the AC process. As we continue to improve the mechanics of ACs and to reduce unnecessary administrative burdens, we must also address the appropriate mix of expertise on committees, so that FDA scientists and staff get the advice they need to make the best decisions on behalf of the American public.

Robert M. Califf, M.D., is Commissioner of the U.S. Food and Drug Administration

Committees, Conflicts and Everything in Between

 By Jill Hartzler Warner, J.D.

One of the strengths of this agency is the breadth of experience and diversity of opinion that exists among the more than 11,000 employees who work on FDA’s behalf around the world.

As with any organization that relies on science to guide its decision-making, robust scientific debate is expected and encouraged. In circumstances where agency staff seeks additional input because of such things as emerging research, the complexity of a new technology, or conflicting scientific data, FDA may turn to outside experts to provide important insights that would help inform our decision-making.

We often ask these experts to advise us on a range of scientific questions – including whether the safety of a drug is properly characterized for patients or if a new device would provide meaningful benefit for patients.

Health care professionals and patients should know that FDA ultimately makes the final decision on all regulatory activities. However, our advisory committee experts, which include patients, provide invaluable insights to the agency on how the broader public will approach a particular product or issue.

There has been a lot of public discussion in recent years about how we engage these outside experts through our advisory committee process. Typically, that discussion centers on how we evaluate committee members’ financial interests and prior involvement with regulated industry.

A lack of understanding about our selection and evaluation process, as well as federally mandated limitations on the type of information we can share publicly, have sometimes resulted in confusion and misunderstanding among the public.

Advisory committees play an important role in FDA’s mandate to promote and protect the public health by allowing the agency to engage independent, technical experts from a variety of disciplines. Our committees are often comprised primarily of individuals working in academia; but also may have representation from private practices, professional and patient groups, regulated industry, and other government agencies.

Before each meeting, FDA screens all advisory committee members who are special government employees or regular government employees for financial conflicts of interest. We ask the members to report to FDA any past and all current involvement or relationships with the products, companies, and issues related to the meeting. Members are required to report all current financial interests that could be affected by the outcome of the advisory committee proceedings and any FDA decision based on the committee’s recommendations.  For example, this might include stocks and investments and consulting arrangements.  In addition, they report involvements that might present an appearance of a conflict, to the best of their knowledge.

FDA carefully reviews each financial interest reported by each potential committee member and determines whether any would disqualify them from participating. If a member has a financial conflict of interest, they may not participate unless a waiver is granted, allowing them to participate. The agency also reviews other interests that may raise an “appearance” of a conflict and has the discretion to have the member not participate if the circumstances would cause a reasonable person with knowledge of the relevant facts to question his or her impartiality in the matter.

When the FDA decides to grant a waiver to a committee member, we post it to FDA’s website before the meeting, along with the type, nature and magnitude of the waived financial interest. If no financial conflict was determined by the agency, the information submitted by the committee members is considered confidential and by law we do not release that information to the public.

We make clear to our committee members that failure to report relevant known financial interests to FDA prior to participation in an FDA advisory committee meeting is illegal and subject to possible criminal penalties.  

I want to specifically address recent reports related to the December 8, 2011 advisory committee meeting that discussed drospirenone-containing oral contraceptives. Based on our review of the members’ reported financial interests, we did not identify any financial interests that would have precluded their participation.

In April 2010, Commissioner Hamburg highlighted a draft guidance for FDA staff and advisory committee members that outlined her desire to create a more consistent and transparent process for disclosing conflict of interest waivers granted by the agency. This is a vision I share.

It is worth noting that since FY2007, the rate of conflict of interest waivers granted by the FDA has been declining sharply. In FY2007, the agency granted waivers for 15 percent of meeting participants; in FY2011, we granted only one percent. How to handle conflicts, while obtaining the best expertise available, is not a challenge unique to FDA. In fact, other government organizations, academic institutions, and peer-reviewed journals are frequently confronted with how to obtain this information from prospective staff and authors as well. Given our interest in this area, we have been working closely with outside stakeholders and theInstituteofMedicineto explore whether a common financial disclosure form or website could be created making it easier for individuals to report their financial interests.

I’m personally excited about what an approach like this could mean for the agency. In its design, this approach could allow individuals to report information in a standard and consistent way, serving as a resource for agencies like FDA looking to receive reliable information while at the same time reducing burden on our experts. We are also exploring the administrative steps in review of conflict of interest screening and evaluating whether the process can be streamlined.   

I want to personally thank each and every one of the past and current members of FDA’s 50 advisory committees and panels. They have been generous with their time and expertise and have played an instrumental role in allowing the agency to fulfill its commitment to protecting the public health.

Jill Hartzler Warner, J.D., is FDA’s Acting Associate Commissioner for Special Medical Programs