FDA Pushes For Scientific Integrity As Staff Criticize Corporate Influence In External Survey

The agency reiterates its commitment to protecting scientific integrity in response to the Union of Concerned Scientists’ survey of FDA scientists; staff cite corporate influence on agency decisions and fear of retaliation for expressing their concerns.

FDA reiterated its commitment to protecting scientific integrity and encouraging staff to express their opinions in response to a survey of FDA scientists that found some internal discord over the agency’s decision-making process.

“I am frequently told that senior management ‘doesn’t want to have to deal with a dispute’ and am therefore subtly pressured to make a favorable decision (to industry),” CDER scientist says.

On March 7, the Union of Concerned Scientists released the results of its 2011 survey, in which 997 FDA scientists (14% of 7,043 scientists queried) answered 33 questions about the state of science at the agency. The nonprofit group noted that FDA has made strides since its 2006 survey of FDA staff, with 652 respondents agreeing that the agency is moving in the right direction and 743 respondents agreeing that the FDA is “acting effectively to protect public health.”

In addition, 582 respondents agreed that their direct supervisor stands behind scientists who put forth positions that may be controversial, a 21% increase from the 2006 survey.

However, the survey found that scientists were concerned about the degree of corporate and political influence on regulatory decisions and the overall transparency and accountability of the agency’s decision-making, and uncertain about their right to publish research and communicate with the public.

Jesse Goodman, FDA chief scientist and deputy commissioner for science and public health, immediately addressed the findings in a March 7 posting on the agency’s FDA Voice blog.

“Even though, as noted, the opinions of those responding to the survey are generally more positive than in 2006, and even though the percent of respondents is low and may not accurately represent all employees’ views, there are some findings that should still concern us,” he stated.

Safety Systems Among Other Concerns

Other survey findings highlight concerns about FDA’s safety functions, with more than one-quarter of surveyed FDAers critical of the agency’s post-market safety systems.

• 37.4% agree or strongly agree that the current level of independence and authority of FDA post-market product safety systems sufficiently serves the public while 27.3% disagree or strongly disagree and 35.4% don’t know.
• Asked what the greatest barriers to timely agency decisions are, 25.7% said uncertainty or disagreement with the science; 19.4% said complexity of the issue; 13.6% said inefficient decision-making process within the agency; and 11.5% said influence of industry stakeholders.
• Asked how often they have experienced public health being harmed by businesses withholding safety information from the agency, 7.6% said frequently, 29.5% said occasionally, 17.5% said seldom, 21.5% said never and 23.9% said the question was not applicable.
• Asked how often corporate interests have forced the withdrawal or significant modification of an FDA policy or action designed to protect consumers or public health, 5.3% said frequently, 23.5% said occasionally, 16.5% said seldom, 28.5% said never, and 26.1% said not applicable.
• As to how often they have experienced members of Congress trying to force the withdrawal or significant modification of an FDA policy or action designed to protect consumers or public health, 7.3% said frequently, 23.4% said occasionally, 17.6% said seldom, 22.9% said never and 28.8% said not applicable.
• Asked how often they have experienced instances in which FDA decision makers made requests to inappropriately exclude or alter technical information or conclusions in an FDA scientific document, 3.1% said frequently, 12.1% said occasionally, 14.4% said seldom, 44.6% said never and 25.8% said not applicable.
• Asked if they have ever been pressured to approve or recommend approval for a new drug application despite reservations about the safety, efficacy, or quality of the drug, 10.1% of 267 CDER scientists said yes, 60.7% said no, and 29.2% said not applicable. Of 80 CBER scientists asked a similar question, 23.8% said yes, 60% said no, and 16.3% said not applicable.

One-Quarter Of Respondents Fear Retaliation For Expressing Concerns

For instance, Goodman said, some scientists still fear retribution for sharing concerns about the FDA and some believe that business interests frequently influence science-based regulatory decisions.

Asked if they “can openly express any concerns about the mission-driven work of [FDA] without fear of retaliation,” 53.7% said they agree or strongly agree while 26.3% said they disagree or strongly disagree and 20% said they don’t know.

As for outside influences on FDA’s decisions, 24.6% said business interests have a lot of weight in final decisions and 37.8% said they have some weight. Similarly, 30.6% said political interests have a lot of weight and 32.8% said they have some weight on FDA’s final decisions.

Goodman emphasized that the agency is continuing to take steps to bolster scientific integrity.

“Preserving and protecting scientific integrity and working to promote an environment where all feel comfortable expressing their opinions and have confidence in the agency’s decision-making must be an ongoing effort and part of our daily life and culture,” he asserted.

To this end, he said, FDA recently put in place a policy that sets forth key principles of scientific integrity and highlights important procedures and policies FDA has instituted to further these principles. The policy is included in a staff manual guide that went into effect on Feb. 3.

The scientific principles include requiring a fair and transparent approach to resolving internal scientific disputes, including hearing and carefully considering differing views; maintaining openness and selecting qualified advisory committee members based on expertise, with transparency about conflicts of interest; and allowing FDA staff to communicate their personal scientific or policy views to the public, even when those views differ from official agency opinions.

Disagreements between FDA staff have surfaced several times over the past two years. For example, cardiology reviewer Thomas Marciniak and Office of Drug Evaluation I Deputy Director Ellis Unger disagreed about the results of a GlaxoSmithKline PLCAvandia (rosiglitazone) cardiovascular safety study at an FDA advisory committee meeting in 2010 (Also see "FDA's Marciniak vs. Unger: Cardio Experts Divided On GSK's RECORD Study" - Pink Sheet, 19 Jul, 2010.).

And earlier this year, Marciniak’s strong criticisms of AstraZeneca PLC’s conduct of a pivotal Brilinta (ticagrelor) trial drew a stinging rebuttal from his boss, Cardio-Renal Division Director Norman Stockbridge (Also see "Brilinta Review Sparks War Of Words Between FDA Cardio-Renal Division’s Marciniak, Stockbridge" - Pink Sheet, 1 Jan, 2012.).

Feedback Shows Anti-PDUFA Sentiment, Concerns About Industry Pressure

The survey also elicited commentary from FDA scientists in response to essay questions that give a sense of their frustrations and the differences of opinion as to how the agency operates.

For example, one scientist from the Center for Drug Evaluation and Research said the agency needed to look at the complexity of science in assessing safety problems.

“There is a serious trend in some disciplines in CDER to overlook the complexity of science as it applies to drug development, to assume that we have complete knowledge of how the human body works and to latch onto simplistic theories and explanations to make safety problems go away” the scientist said.

Another CDER scientist complained of being pressured to approve a drug.

“Subtle pressure from leadership is very difficult to quantify and regulate, but it exists and is a problem,” the scientist stated. “I am frequently told that senior management ‘doesn’t want to have to deal with a dispute’ and am therefore subtly pressured to make a favorable decision (to industry). I have several times been required to provide a special briefing to management if I believe a product should not be approved – this has never been required when I recommend approval.”

However, a scientist from the Center for Biologics Evaluation and Research cited an instance when the agency heeded the review team’s advice against approval.

“In another situation I was aware that there was some public pressure to approve another product (in CBER) but the review team recommended against approval and the product was not initially approved despite a lot of public outcry,” the scientist wrote. “Subsequently additional data was submitted, we recommended approval, and the product is now licensed. Overall I have been impressed with the integrity of FDA management and that is why I continue to work here.”

Another CBER scientist was critical of the Prescription Drug User Fee Act. “I believe PDUFA and special interest groups have allowed Congress to be lulled into a false sense of security. When things don’t ‘go their way,’ a company or its representatives will call and harass office directors to approve their product. In addition, PDUFA is like money laundering. Companies give money to Congress to fund regulatory decisions. This is clearly a conflict of interest.”

And in another comment, a CDER scientist suggested that post-marketing safety regulations could be stricter in terms of sponsor’s reporting responsibilities. “We continue to receive very incomplete post-marketing reports of serious events that do not have any follow-up,” the scientist said.