Alex Philippidis Senior News Editor Genetic Engineering & Biotechnology News
Agency is still reviewing draft guidance for clinical investigators.
FDA has retreated from earlier plans to relax its conflict rules governing experts who serve on its advisory panels. Commissioner Margaret A. Hamburg, M.D., on February 1 told a House subcommittee, “We don’t, at the moment, see major areas where a legislative fix is required.” The agency faces pressure from industry to relax rules that it says have slowed down the regulatory process but also from citizen groups that want to ensure tight limits.
At issue are 1988 rules barring individuals from participating in FDA advisory committees if they, their spouse, or minor children have more than $50,000 in potentially conflicting financial interests. Those who vouch for loosening the rules say the instituted limits have resulted in too many empty spots on advisory panels and members not always having the necessary expertise.
The other conflict-of-interest issue currently under discussion relates to rules for principal investigators in drug and device studies who have financial interests that could be impacted by the results of the study. Last May FDA drafted guidelines on this issue to update FDA regulations issued in 2001. The agency is still reviewing comments received on the draft, FDA spokesman Morgan Liscinsky pointed out to GEN.
Comments received thus far fall along similar lines as comments made for advisory panel rules; i.e., those who want the rules loosened profess negative impact on the drug development process and industry and those who want tighter guidelines point to safety concerns and say that financial conflicts are bound to bias investigators.
FDA aims to have no more than 10% of its advisory seats vacant in 2012 but is not yet achieving that, though some may say it is getting better. As of October 2011, vacancies were at 19%, down from 23% in July 2011 and 25% in January 2011.
The agency is allowed to grant waivers to panelists if it deems that the panelists’ afford a certain expertise to the advisory committee. Waivers, however, cannot be issued if an advisor is the principal investigator on a clinical trial of a product about which the committee will provide advice.
FDA’s goal for 2012 is to issue 12.78% or fewer waivers. This percentage has fluctuated between October 2010 and October 2011 from a high of 4% right down to zero. “In recent years, waivers for FDA advisory committees have not exceeded five percent annually,” Liscinsky pointed out. Dr. Hamburg also cited this fact saying that FDA is no longer “bumping up against our cap in terms of waivers.”
Dr. Hamburg’s comments are a change from a July 2011 address before the public health watchdog group Public Citizen, when she cited vacancies on advisory committees in contending: “We have to be sure that FDA has subject-matter experts that we need for our important decision making,” according to a quote published by Bloomberg. Dr. Hamburg and FDA have been squeezed by two sides of the political spectrum: Republicans want more help and less red tape for industry, while progressives like Public Citizen say that the current rules work and no change is needed at all.
“Although I don’t think that reason is always the number one feature of the way our Congress acts, there isn’t going to be any reason to say we need to relax the financial conflict of interest rules for FDA advisory committee members,” Sidney M. Wolfe, M.D., Director of Public Citizen’s Health Research Group, told GEN. Dr. Wolfe, a member of FDA’s Drug Safety and Risk Management Advisory Committee whose term ends May 31, pointed to the decrease in vacancies over the past year as evidence of improvement. He said that the agency is slowly but surely filling its advisory panel positions, which is also how the FDA now feels.
The views of FDA and Dr. Wolfe contrast with those of some industry speakers at the recent PDUFA hearing. For example, David E. Wheadon, svp, scientific and regulatory affairs at Pharmaceutical Researchers and Manufacturers of America (PhRMA), and Richard F. Pops, chairman and CEO of Alkermes, said the quality of scientific discourse on FDA advisory panels had suffered.
He said that since conflict rules for experts were tightened, the agency sometimes relied on panel members lacking relevant expertise, particularly in rare diseases. “In recent years, arbitrary limits and unnecessarily restrictive interpretations of conflict of interest rules have created barriers that have prevented FDA from consistently recruiting highly qualified scientific advisors,” said Pops, who spoke for BIO; he serves on BIO’s Health Section Governing Board.
Last October two bills surfaced in Congress that aimed to ease how conflicts were defined, but neither bill has been heard yet. Rep. Michael Burgess (R-TX) introduced the Cultivating Scientific Expertise to Foster Innovation Act (HR 3206) to eliminate limits on the number of conflict of interest waivers FDA can issue. Also, Sens. Amy Klobuchar (D-MN), Richard Burr (R-NC), and Michael Bennet (D-CO) introduced the Medical Device Regulatory Improvement Act (S.1700) to subject FDA to the same conflict policy as the rest of the federal government.
The other side of the conflict-of-interest story relates to principal investigators. No surprise that comments have followed the same division of opinion as with rules governing advisory panels. One respondent said FDA’s draft guidance didn’t go far enough: “Make it more restrictive. Your first priority is to protect the public from crap, corruption, and bribery,” according to ‘anonymous.’ “The revolving door at the FDA is beyond belief: You do in the public for money, and when you leave FDA, you get big money in big pharma. We need to stop that revolving door.”
Representing the other side of the coin, David Verbraska, Pfizer’s vp, regulatory policy, said, “Should FDA choose to mandate public disclosure of investigator financial information, Pfizer recommends that the agency not require listing of specific payments or dollar amounts. The implication of such disclosures is that the payments do or have the potential to introduce bias or influence, which is highly unlikely to be the case.”
HHS issued new conflict-of-interest rules in August 2011 for researchers receiving funding from the US Public Health Service. It lowered the minimum threshold for disclosure from $10,000 to $5,000. Unlike HHS’ prior 1995 rules, any equity interest in privately held entities must be disclosed.
HHS’ final regulations exceed FDA’s current draft guidance, which requires disclosure of:
- any equity interest in any sponsor of the study if the sponsor is a public company and the interest exceeds $50,000 in value;
- SPOOS totaling $25,000 or more made by any sponsor to the investigator or the investigator’s institution outside the cost of conducting the study (including ongoing consultation or honoraria);
- compensation made to the investigator by any study sponsor in which the value of compensation could be affected by the outcome;
- a proprietary interest in the tested product including patents and copyrights; and
- any ownership or financial interest in any sponsor of a covered clinical study, whose value cannot be readily determined from public prices.
FDA and HHS will have to reach a decision about rules surrounding principal investigators. The two agencies should consider combining their regulations into a single biomedical conflict-of-interest standard that offers researchers more clarity about what information they have to disclose to regulators.
FDA and HHS seem to be more on the same page regarding conflict of interest rules for advisory panels. These rules will no doubt get challenged by industry groups looking to ease guidelines and will be an ongoing tussle. To address their concerns, FDA and Congress should agree on a percentage of vacancies that might trigger FDA action such as easing up on conflict rules. That would stave off problems related to too many vacancies should that occur while also heading off any changes during times when the system seems to be working.
Alex Philippidis is senior news editor at Genetic Engineering & Biotechnology News.