Monday, September 19, 2016

Deciding Vote in FDA Advisory Committee Recommendation to Remove Black Box Warning for Chantix is Cast by Pharmaceutical Company President; FDA Review Process is Badly Tainted

Last Wednesday, a pair of FDA advisory committees - meeting jointly - voted 10-9 to recommend that the FDA remove the black box warning for Chantix (varenicline). Currently, the black box warns about the potential for severe psychiatric side effects of Chantix, including depression and suicidal ideation. The recommendation is not binding, and the FDA is free to follow or ignore the advisory panel's vote.

According to an article at MedPage Today: "a few of those who voted to remove the warning said the study supplied the evidence needed to make them comfortable using Varenicline to address a major public health problem. 'The risk-benefit ratio is as clear as anything I have ever seen,' said David Pickar, MD, a Johns Hopkins Medical School psychiatry professor who said he works with psychiatric patients. Looking at his fellow committee members, Pickar added: 'For you, these are adverse events, but the benefit to these patients could be substantial in the most fundamental thing, which is being alive.'"

The Rest of the Story

What this article and similar ones are not telling you is that the advisory committee member mentioned above - who cast the deciding vote - is, believe it or not, the president of a pharmaceutical company!

In a whopping conflict of interest that is apparently not disclosed in the article, it turns out that Dr. Pickar, according to his own web site, is "Founder and President of Gabriel Sciences, a company whose mission is advancing the development of a novel treatment for schizophrenia." Prior to that, he was "Co-Founder of Comprehensive Neuroscience, Inc., a clinical trials and medical communication company where he served as a Director, Executive Vice-President and Chief Science Officer." On top of that, he "is the inventor on two US patents."

Dr. Pickar's curriculum vitae confirms that he is the founder and president of a pharmaceutical company (Gabriel Sciences). Prior to that (going back to 2001), he was the founder and president of Potomac Pharma, Inc., a biopharmaceutical company which has transferred assets to Gabriel Sciences. Thus, it appears that Dr. Pickar has been a pharmaceutical company president for the past 15 years.  Dr. Pickar's patents appear to be related to strategies for the pharmacological treatment of schizophrenia. The patents were licensed exclusively to Potomac Pharma, Inc.

I have previously pointed out the problems inherent in having advisory panel members who have personal conflicts of interest with Big Pharma, but here you actually have a pharmaceutical company president serving on the advisory panel!

I view this as an enormous conflict of interest. This pharmaceutical company president, whose company specializes in research and development of psychopharmacologic drugs, is serving on an FDA advisory board to evaluate psychopharmacologic drugs! The name of the advisory committee is the "Psychopharmacologic Drugs Advisory Committee." I can't think of a more pertinent conflict of interest. If you are going to allow this type of a conflict, then you might as well throw conflict of interest policies out the window completely and just let the CEO's of various pharmaceutical companies serve as the advisory committee. I do not understand how the FDA can possibly allow this type of a conflict of interest.

Even in decisions regarding drugs that are not used for treatment of psychiatric illnesses - such as Chantix - the conflict is still present because the way that the FDA deals with one drug is relevant to how it deals with other drugs. In this case, the decision sets a precedent that could benefit drugs that are subsequently developed by Gabriel Sciences. For one thing, the decision accepts the principle that it is acceptable to have conflicted investigators conducting clinical trials on drugs, even when their financial conflict of interest is with the company that manufactures the very drug being tested.

As I reported last week, investigators at 32 of the 139 study sites involved in the recent study of adverse psychiatric effects related to Chantix had a financial conflict of interest by virtue of having received more than $25,000 in the past five years in speaking fees related to the promotion of Chantix or other Pfizer products. To be very clear, at my institution, investigators with such a conflict of interest would not be permitted to conduct such research.

I should point out that I am not criticizing Dr. Pickar here. My criticism is directed at the agency for allowing members of its advisory committees to have these kind of conflicts. 

The rest of the story is that in my view, the FDA is in violation of the regulations issued by the Office of Government Ethics related to conflicts of interest among FDA advisory committee members (5 CFR part 2640), which state that financial conflicts are disqualifying for committee membership unless a waiver is granted and that to grant a waiver, it must be determined that "the disqualifying financial interest is not so substantial that it is likely to affect the integrity of an employee's services to the government." In this case, the FDA is clearly in violation of these regulations.

By the way, the statement that Dr. Pickar made, as quoted by MedPage Today, is not relevant to the issue of whether or not the black box warning should be maintained. He was quoted as stating: "The risk-benefit ratio is as clear as anything I have ever seen. For you, these are adverse events, but the benefit to these patients could be substantial in the most fundamental thing, which is being alive." These expressed concerns are relevant to the question of whether Chantix should remain on the market, but the decision about whether or not to require a black box warning should not be based on the risk-benefit ratio of the drug, but on the evidence related to the drug's adverse effects.

In my view, there needs to be a serious review of the FDA's adherence to federal conflict of interest regulations because it appears that the agency is blatantly violating these rules and that the public is being placed at potential risk because of it.

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