PUBLIC NEEDS REASSURANCES ON HOW VACCINES ARE VETTED

We believe that the public’s confidence in, and adoption of, COVID-19 vaccines — two of which the U.S. Food and Drug Administration approved last month — can be enhanced by increasing public knowledge about how scientific peer review, regulation and surveillance work together to ensure the safety and efficacy of vaccines. A September report by a consortium of Northeastern, Harvard, Rutgers and Northwestern universities about public trust in institutions and vaccine acceptance demonstrated that acceptance depends on the level of trust in scientists and researchers, so increasing trust should be a top public health priority. The report also noted that concerns about vaccine safety reduce uptake and therefore effectiveness of vaccines.

Journalists often mention that study findings cannot be considered definitive until they are peer-reviewed or until regulatory review has taken place, but these processes are quite distinct and serve different purposes. Publication in leading journals, review by regulatory authorities such as the FDA or the European Medicines Agency, and disease surveillance by public health agencies — such as the Centers for Disease Control and Prevention and the World Health Organization — serve as pillars that jointly support development of policies for containing outbreaks.

Dependence on multiple pillars is a common approach for defending the public interest from adverse consequences of processes that involve a complex web — often multinational — of actors and organizations. For example, neither credit rating agencies nor biomedical journals — whose publication decisions rely on peer review — can serve as final arbiters of truth. In both cases, reviewers generally have limited access to important underlying data and internal processes.

Rating agencies such as Standard & Poor’s, Moody’s and Fitch, charged with the evaluation of creditworthi

ness, rely on organizations acting in good faith with their data. Even provided with access, neither peer reviewers nor raters have the resources or capacity to assure data quality control or redo analyses. Like peer reviewing, credit rating must work in tandem with regulators like the U.S. Securities and Exchange Commission and non-governmental organizations such as the Financial Industry Regulatory Authority to promote the stability of the financial systems we depend on.

Peer review of a scientific article provides important validation of the scientific appropriateness of design, monitoring and analysis of study data as well as of the logic that support scientific claims. But it is regulatory review that provides validation not only of data but also of manufacturing standards for the new product; this process requires resources well beyond what peer-reviewed journals can customarily provide. Regulatory review at the FDA is conducted by highly trained multidisciplinary teams of professionals — aided by advisory panels that provide important independent opinions. But this process is not the final step. Large COVID-19 vaccine studies, for example, have sample sizes of 30,000 or more, but billions of people around the globe will need to be vaccinated.

Detection of very rare events requires much larger post-review studies — which can be mandated by the FDA. Furthermore, assessment of the real-world impact of licensure of a new treatment is greatly benefited by CDC surveillance, which provides near realtime information on morbidity and mortality trends before and after approval. Examples include the success of human papillomavirus vaccine in reducing cervical cancer and the finding that, because of herd effects (i.e. high levels of immunity across a population), board implementation of pneumococcal vaccines yields even greater effectiveness than was observed in clinical trials as well.

Maintaining the highest level of scientific innovation (for example, the extraordinary speed of COVID-19 vaccine development) and the highest standards for approval of new treatments requires public engagement. This is why FDA livestreams advisory panel meetings. Community representation in the clinical research process currently exists at many levels — institutional review boards, a community advisory board for National Institutes of Health funded trials, public comment at FDA panel meeting — but even broader community engagement is now required.

Bridging the increasingly sharp division of the citizenry into scientific/technical elites and disaffected others is a tall order — but we believe making the citizenry aware of the increasing opportunities for active engagement may be a useful first step. As we prepare for new leadership in Washington, D.C., and for implementation of new modalities to prevent and to treat COVID-19, the time is now to create the broad coalitions needed to bring the pandemic to the swiftest possible end.