COVID Vaccine Clinical Trials Require Fast Decisions, But No Shortcuts

As the Trump administration revs up its Operation Warp Speed initiative to acceler­ate access to COVID-19 vaccines and thera­peutics, biopharmaceutical companies and federal agencies continue to work over­time to test and develop safe and effective preventives for patients around the world. Research is underway on more than 175 vaccine candidates across a wide range of technologies, as sponsors and scientists look to have “multiple shots on goal,” along with “multiple goals to shoot at,” in the race to identify effective products in the coming months. 

This proliferation of vaccine research pro­grams, however, highlights the importance of carrying out clinical trials that utilize simi­lar protocols and endpoints able to produce comparable results. Peter Marks, director of the Center for Biologics Evaluation and Research (CBER), acknowledges the need for regulators to move quickly, while also being sure to “check all the boxes” so that research yields clear evidence that a vac­cine is safe and effective. FDA is “willing to take certain calculated risks to get into Phase I” and to accept novel trial designs, particularly with vaccine platforms that have been used before, Marks noted in a webinar sponsored by the Duke Margolis Center for Health Policy May 13. But he also recognizes that FDA has to con­vince people that we’re “not taking short­cuts here.” 

Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases (NIAID), similarly emphasizes the need to as­sess different candidates in ways that com­plement each other in order to get definitive answers about whether a vaccine works or not. Without complete clinical trials, re­searchers may get a signal that “strongly indicates” a response, but “doesn’t nail it down,” Fauci warned. 

These experts further advised sponsors to utilize clinical research networks in loca­tions with high incidences of COVID-19 cases to be able to assess efficacy efficiently. Sponsors need to “go where the cases are-not the traditional sites,” said Marks, acknowledging unhappily that widespread infection rates should facilitate getting data quickly. At the same time, sponsors should “space out” trials to different locations to avoid bias, while also utilizing endpoints that are similar enough to be able to compare results from different studies. 

Despite anticipated pressure to permit expanded or emergency access to any promising vaccine, Marks doesn’t envision authorizing such use during Phase III trials for fear of undermining efforts to obtain definitive data. Some early use may be ap­proved for health professionals and at-risk patients during the few months between when a clinical trial ends and the sponsor completes the analysis needed to support a biologics licensing application, so long as such access doesn’t short-circuit clinical assessment. 

The tight timeframes for developing and then distributing any successful vaccines means that companies cannot wait for final clinical test results to begin preparing large-scale manufacturing operations and to ad­dress supply chain issues critical for deliver­ing products globally. Consequently, instead of spending several years testing vaccine candidates and then ramping up produc­tion based on successful findings, industry and government agencies “have to proceed at risk,” Fauci acknowledges, and invest in operations before they have a product that would be used. 

While the medical community sees many patients recovering from COVID by mount­ing a strong immune response to the virus, Marks acknowledges that scientists still have only a limited understanding of what will constitute long-term, definitive protec­tion. He admits to having “great concerns” about a second pandemic wave this fall and winter and will be very pleased to have a vaccine with strong efficacy data by then. A preventive that could get to herd immunity “would be really nice,” he commented. But regulators and researchers expect to move forward with any vaccine that indicates it can help get the pandemic under control, even without clear assurances for long-term success.