In the US, the Food and Drug Administration (FDA) reviews and approves prescription drugs before they can be marketed and made available for use by patients outside of clinical trials. For approved drugs, the FDA publishes review materials, but for drugs that are not approved or receive approval via the supplemental new drug or new biologic pathway (sNDA or sBLA), review materials are not made public. However, if the FDA convenes an advisory committee, a public meeting during which an independent panel of experts evaluates the evidence, some details about the FDA review will be publicly shared, and members of the public have an opportunity to comment on the product.
At these meetings — whether for new, not-yet-available, products or supplemental indications for those already in use — committee members may hear from patients, their family members, and clinicians with direct experience of the product. Comments from patients, including patients enrolled in clinical trials for new products, can offer committee members insights into patients’ experiences with the product, preferences for acceptable benefit-risk profiles, and unmet needs. The inclusion of patients, many of whom advocate for approval of the product,Reference Gusmano 1 speaks to a tension between asking advisory committee members to make a recommendation based on clinical evidence and the role of experiential testimonies in those recommendations.
In their article, Zhang et al. analyze advisory committee decisions on sNDA and sBLA submissions for new indications. Their analysis highlights the important role advisory committees serve to create transparency into regulatory decision making.Reference Zhang 2 The authors highlight the feature of sNDA/sBLA advisory committees that members can draw on their own or otherwise reported clinical experience with the products, which are already available for other indications. They find that this experience influences members’ judgments of acceptable safety profiles of the products. 3
The Role of Stakeholder and Patient Engagement
Given that committee members often rely on their own or reported experience with a product alongside clinical evidence, to what extent are patient testimonies representative of broader patient experiences, and how should they shape committee and FDA decisions? Transparency at the meetings promotes the legitimacy of regulatory decision making as a democratic value. This is especially important when decisions are contested — whether due to differing views on an acceptable benefit-risk tradeoffs or the sufficiency of evidence for approval. Patient engagement is an important element of a fair and legitimate FDA approval process, as inconsistent or insufficient stakeholder engagement can undermine public trust in the FDA.Reference Daniels 4 Yet while advisory committee meetings serve as a key public forum in the US regulatory process, the influence of patient testimony on committee votes — and the role it should play — remains unclear.Reference Daval, Kesselheim and Sarpatwari 5
Over the past decade, the stakes surrounding FDA advisory committees have risen substantially, and patient involvement has become more consequential. Public attention on advisory committees has increased as the FDA has indicated receptiveness to approving drugs with more limited data, which amplifies uncertainty about the drugs’ efficacy and safety.Reference Andreoletti and Blasimme 6 Advisory committees are particularly contentious when there is tension between weak clinical evidence and strong patient testimonies about the unmet medical need that they face.Reference Lynch 7 High-profile meetings, including those on COVID-19 vaccines, new Alzheimer’s disease drugs, and sickle cell gene therapies, have made front-page news.Reference Jewett 8 One witness during the advisory committee meeting for a controversial treatment for Duchenne muscular dystrophy noted, “Everyone was visibly moved by the audience and their testimony, and that is not going to go unnoticed,” when discussing the likelihood of a positive vote.Reference Silverman 9 In that case, the committee was divided on whether to approve the product, voting 7–3 against, with 3 abstentions; nevertheless, the FDA ultimately approved the drug.Reference Bendicksen 10
A 2012 survey of Advisory Committee members found that 72% reported being never or rarely influenced by patient testimony, while 28% acknowledged being open to its influence.Reference McIntyre, Pappas and DiBasi 11 This difference in opinion raises questions of epistemic justice concerning whose testimonies and evidence interpretations have legitimacy. Advisory Committee members, FDA regulators, and the patients/patient advocates who speak are not elected officials. Yet their actions and decisions profoundly impact current and future patients. The proper role of public and patient involvement in regulatory decision making remains an ongoing bioethical and political debate. While this involvement is widely recognized as an essential component of decision making in a democratic society,Reference Conley 12 there remains little clarity on how to effectively engage patient stakeholders or reconcile the diverse perspectives that they bring. The need for clear, structured approaches to patient engagement in the FDA decision-making process endures as a notable gap in both scholarship and practice-oriented guidance. Existing studies of advisory committee decision-making answer some questions but leave others unresolved. Although the advisory committee format is well-established, it remains an open question what role this input both should and does play in shaping regulatory decisions.
