Health Letter, February 2023
By Michael Carome, M.D.
If you’re not outraged,
you’re not paying attention!
Read what Public Citizen has to say about the biggest blunders and outrageous offenses in the world of public health, published monthly in Health Letter.
A scathing report issued by the U.S. House of Representatives’ Committees on Oversight and Reform and on Energy and Commerce on Dec. 29, 2022, affirmed allegations raised by Public Citizen’s Health Research Group two years earlier about the inappropriately close collaboration between drugmaker Biogen and the Food and Drug Administration (FDA) during the analysis of data from the key clinical trials of the Alzheimer’s disease drug aducanumab (ADUHELM).
In one of the worst decisions in its history, the FDA in June 2021 approved aducanumab for the treatment of Alzheimer’s disease. The FDA took this action despite the nearly unanimous conclusion of an advisory committee convened by the agency in November 2020 that there was inadequate evidence that the drug is effective for slowing cognitive decline in patients with Alzheimer’s disease.
In December 2020 and June 2021, Public Citizen urged the U.S. Department of Health and Human Services’ Office of Inspector General (OIG) to investigate the unprecedented and inappropriately close collaboration between Biogen and the FDA. This close collaboration before and after the submission of the company’s marketing application for aducanumab dangerously compromised the integrity of the FDA’s review and decision-making for the drug. An OIG investigation into this matter was finally initiated in August 2021 and is ongoing.
Separately, the House Committees on Oversight and Reform and on Energy and Commerce in June 2021 launched a joint investigation into the FDA’s review and approval of aducanumab. According to their December 2022 report, the committees found that the FDA’s review and approval process for aducanumab was “rife with irregularities.”
The House committees’ review of more than 500,000 FDA and Biogen documents disturbingly revealed that agency staff and the drugmaker engaged in at least 115 meetings, calls and substantive email exchanges — including at least 40 FDA-Biogen “working group” meetings — over a one-year period starting in July 2019. The FDA’s own internal review characterized the extent of collaboration between the FDA and Biogen as “atypical” and “exceed[ing] the norms in some respects.” Moreover, of the more than 40 FDA-Biogen working group meetings, not all were properly documented in accordance with internal FDA procedures. The committees also identified numerous calls and email exchanges of the working group that were not memorialized in FDA records.
Predictably, the FDA’s own internal review concluded that the agency’s interactions with Biogen prior to the company’s submission of the marketing application for aducanumab were “appropriate,” which highlights the fact that the agency is incapable of objectively investigating its own misconduct.
The House committees also found that the FDA and Biogen inappropriately collaborated in the preparation of a joint briefing document for the November 2020 FDA advisory committee meeting. The committees reported that, according to FDA officials, a joint advisory committee meeting briefing document had only been previously utilized by the agency nine times and only for cancer drugs. This is because the FDA has generally taken the position that such advisory committee briefing materials from the FDA and drug companies should be “independent and separate documents.”
Documents obtained by the committees showed that the FDA review team for aducanumab and Biogen staff worked closely for several months to prepare “text for Biogen’s sections of the briefing document” for the November 2020 advisory committee meeting. Under this approach, the agency provided direct guidance to Biogen on drafting the company’s own sections of the briefing document. Importantly, the joint briefing document did not give equal weight to divergent views and concerns about the analyses of data from the clinical trials of aducanumab that were raised by the agency’s statistical experts. The FDA’s own internal review found that the use of a joint briefing document in this case was inappropriate given the substantial disagreement between FDA reviewers on key substantive issues.
The House committees concluded the following:
The findings in this report raise serious concerns about FDA’s lapses in protocol and Biogen’s disregard of efficacy and access in the approval process for Aduhelm. The findings also justify experts’ and stakeholders’ concerns about FDA’s accelerated approval of Aduhelm. The criticism surrounding Aduhelm’s approval may have been avoided had FDA adhered to its own guidance and internal practices. FDA must take swift action to ensure that its processes for reviewing future Alzheimer’s disease treatments do not lead to the same doubts about the integrity of FDA’s review.
In dismissive comments about the House committees’ report, FDA Commissioner Robert Califf told a STAT reporter, “There were no surprises in the report. The language is inflammatory, I think, on purpose, because that’s what oversight committees do.” He also said that practices, such as preparing joint advisory committee briefing documents with drugmakers, will not go away because of the fallout from aducanumab. Such statements signal that Califf is not a leader who will push back against the regulatory capture by the pharmaceutical and other regulated industries that has corrupted the FDA.
Public trust in the FDA can only be restored by firing the senior FDA officials who have fostered a culture that encouraged the inappropriately close collaboration between the agency and Biogen and undermined the integrity of the agency’s drug review process.