Chapter 9: Article 4
In Ch2: Part 2, I introduced you to David Graham, the FDA whistleblower. Remember his interview, where he explained the FDA structural make-up is biased favouring pharmaceutical company interests. He stated (emphasis mine):
As currently configured, the FDA is not able to adequately protect the American public. It's more interested in protecting the interests of industry. It views industry as its client, and the client is someone whose interest you represent. Unfortunately, that is the way the FDA is currently structured. Within the Center for Drug Evaluation and Research about 80 percent of the resources are geared towards the approval of new drugs and 20 percent is for everything else. Drug safety is about five percent. The "gorilla in the living room" is new drugs and approval. Congress has not only created that structure, they have also worsened that structure through the PDUFA, the Prescription Drug User Fee Act, by which drug companies pay money to the FDA so they will review and approve its drug.
...The Prescription Drug User Fee Act came into play in 1992. It was passed by Congress as a way of providing the FDA with more funds so that it could hire more physicians and other scientists to review drug applications. For industry, every day a drug is held up from being marketed, represents a loss of one to two million dollars of profit. The incentive is to review and approve the drugs as quickly as possible, and not stand in the way of profit-making. The FDA cooperates with that mandate.
Ten years after this interview, in 2015, a New York Times article explained that then FDA Commissioner, Dr. Robert Califf, inferred during a lecture that he gave that regulation actually hinders innovation. And, in a 2017 Los Angelos Times article, it explains how then FDA Commissioner, Dr. Scott Gottlieb wants to speed up the FDA drug approval process.
Graham explained that flawed FDA regulations helped produce the Vioxx catastrophe, and those deficient regulations have not been changed to prevent future catastrophes. Furthermore, in the opinion of two FDA commissioners (who have recently led this agency), the flawed regulations are now viewed as too time consuming and as a barrier to innovation. Based on that, it's reasonable to assume that any changes made within the FDA, under the leadership of these men, have likely also been in the drug industry's favour.
In addition to FDA's structural practices that prioritize industry interest ahead of public interests, there is an additional layer of influence, where industry money flows to FDA appointed advisors. A letter that was recently submitted directly to the Secretary of HHS identifies the conflicts of interests held by FDA appointed advisors. The letter was prepared by the non-profit organization ICAN, it explains:
HHS Licenses & Recommends Vaccines. With regard to the FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC), which effectively decides whether to license a vaccine, in 2000 the U.S. House Committee on Government Reform (the Committee) “determined that conflict of interest rules employed by the FDA and the CDC have been weak, enforcement has been lax, and committee members with substantial ties to pharmaceutical companies have been given waivers to participate in committee proceedings.” The Committee concluded of the VRBPAC: “The overwhelming majority of members, both voting members and consultants, have substantial ties to the pharmaceutical industry.”
Let's look at one of those investigations that ICAN referred to. This government led investigation was completed on June 15, 2000 by the Committee on Government Reform. They prepared a report that was titled Conflicts of Interest in Vaccine Policy Making. The report identifies the following problems within the FDA (underline emphasis mine):
To provide focus to the discussion, this report examines the deliberations of the two committees on one specific vaccine -- the Rotavirus vaccine. Approved for use by the FDA on August 31, 1998, the Rotavirus vaccine was pulled from the market 13 months later after serious adverse reactions to the vaccine emerged. Financial disclosure forms and waivers granted to committee members who participated in these meetings were analyzed, along with their votes and actions taken during the meetings.
...Vaccines and Related Biological Products Advisory Committee [VRBPAC]
...In short, the VRBPAC advises the FDA on whether or not to license new vaccines for commercial use.
...The Government Reform Committee's investigation of the VRBPAC's Rotashield vaccine approval meeting raised several concerns:
Unanimous vote despite concerns raised: At the VRBPAC meeting, several members raised concerns about adverse effects that occurred at the rotavirus clinical trials. These included: intussusception, infant's failure to thrive, and febrile reactions among others. A statement by Dr. Fleming, a temporary voting member, summarizes the statements of many of the other voting members. He stated: "And as a result, I would ask the FDA to work with the sponsor to further quantitate what these serious side effects are -- specifically the adverse effects, driven in particular by febrile illness -- is inducing hospitalizations and what is that level of access. I still don't feel like I have a good grasp of that at this point." He proceeded to vote for the approval recommendation.
Potential conflicts of interest of VRBPAC members: Four out of five members had conflicts of interest that necessitated waivers. Perhaps one of the major problems contributing to the overall influence of the pharmaceutical industry over the vaccine approval and recommendation process may be the loose standards that are used by the [FDA] in determining whether a conflict actually exists. (Exhibit 53). In many cases, significant conflicts of interest are not deemed to be conflicts at all...
Balanced representation: As previously discussed, the statutory requirement of balanced representation is one of the most controversial provisions of the FACA [Federal Advisory Committee Act]. The FDA has interpreted "balance" as diversity of geography, ethnicity, disciplines and gender. While it is questionable whether this standard guarantees the balance of points of view represented expressly required by the statute, it was interesting to see the high concentration of professors in pediatrics represented on the VRBPAC committee, particularly during the Rotashield discussion...The overwhelming majorityof members, both voting members and consultants, have substantial ties to the pharmaceutical industry.
Timing of the proceedings: A particularly troubling aspect of the deliberations on the Rotashield vaccine is the sequence of events. The ACIP Committee voted to recommend universal vaccinations of infants before the FDA licensure of the vaccine. Officials of the CDC acknowledge that they knew of no other instance where this has happened. As discussed before, during the December 12, 1997, VRBPAC vote to recommend the licensure of the Rotashield vaccine, a number of concerns were raised by some of the members with regard to the vaccine and its possible adverse effects. Although the VRBPAC unanimously approved the vaccine recommendation, some of the committee members votes were conditioned on the FDA's ability to successfully resolve the areas of concern. However, before the FDA final licensure of the Rotashield vaccine in August 1998, the ACIP committee - as will be discussed in the ACIP section of this report- had already voted to recommend the mandatory universal use of the vaccine. This is troubling, not only because the vaccine had not yet been approved by the FDA, but because there were several areas of concerns that may not have been successfully addressed by the FDA, at the time of the ACIP vote.
That investigation repeatedly mentioned the conflicts of interest held by many voting committee members within VRBPAC and ACIP. Although this investigation was completed in 2000, the problems identified then have not been resolved to date.
Also, an article published in Science Magazine looked at the committee members' voluntary disclosure documents. The voluntary disclosure required members to explain any conflicts of interest that they had. The FDA was supposed to use those documents to determine whether or not it was appropriate to appoint an applicant to be on the advisory committee. The article explains:
Science found that AstraZeneca and makers of rival drugs made payments to, or funded research by, several FDA advisers—including [Duke University cardiologist Christopher] Granger—in the year leading up to the 2009 meetings on [the drug] Seroquel. Granger calls full financial disclosure "crucially important" in order for FDA to assemble the best committee. "I certainly hope that I disclosed everything," he says. "If I hadn't, I would be horrified because that's antithetical to everything I believe in." After initially offering to share his disclosure forms, Granger did not respond to repeated requests for copies. In response to a Freedom of Information Act (FOIA) request, FDA says it could not locate his documents.
[Cardiologist Jonathan] Halperin [of the Icahn School of Medicine at Mount Sinai in New York] has a similar history. In addition to receiving funds from AstraZeneca and its competitors after he voted to approve the anticlotting drug Brilinta, Halperin was receiving unspecified payments or research support from rival firms during the 12 months before the meeting. He says he disclosed the payments to FDA and that it did not flag them as conflicts. Science requested copies of his disclosure materials, but Halperin did not provide them. Again, FDA says it could not locate Halperin's disclosures.
...Rheumatologist Daniel Solomon of Harvard Medical School in Boston chaired the Amjevita panel. Neither FDA nor Solomon disclosed publicly that about 3 months before that meeting, Amgen provided $232,000 for his study of etanercept (Enbrel), another arthritis drug made by Amgen, and 1 month before the meeting AbbVie provided $819,000 for a Solomon study of Humira.
..Solomon says he described the payments in an FDA disclosure, but he hadn't kept a copy. The agency rejected a FOIA request for the document, calling its release "a clearly unwarranted invasion of personal privacy."
Also reported in Science Magazine, an article explains a newly identified phenomenon called "pay-later" conflicts of interest, where FDA advisors are financially rewarded by pharmaceutical companies after voting to approve a drug. The summary of this investigation states:
An investigative report uncovers little recognized and unpoliced potential conflicts of interest among those who serve on FDA advisory panels that review drugs. Some members of such panels are later receiving significant payments from either the makers of drugs they previously reviewed, or from competitors. This is happening despite the FDA's established system to identify possible financial conflicts of interest among those recruited for the drug advisory panels. The investigation analyzed records on the federal Open Payments website between 2013 and 2016. Of 107 physician advisors who voted on FDA advisory committees during this time, 26 later took more than $100,000 from the makers of drugs, or from competing firms, in post-hoc earnings or research support.
CONTINUE to the next article in this series: Ch9: Part 5
Interview with David Graham - flawed FDA regulations Here
ICAN letter addressed to the Secretary of HHS Here
Investigation into FDA VRBPAC committee conflicts of interest Here
Investigative Report (Science Magazine) - pay-later conflicts of interest Here
Science Magazine article about pay-later conflicts of interest Here