Moderna, in bid for transparency, discloses detailed plan of coronavirus vaccine trial.

Moderna on Thursday took the unusual step of making public the detailed study plan for the company's large coronavirus vaccine trial, becoming the first developer in late-stage testing to do so amid calls for greater transparency by researchers and public health experts.

The so-called study protocol, a lengthy document that's typically closely kept while testing is ongoing, gives outside observers a better sense of how the trial is being run. Most importantly, the plans help clarify how — and when — an independent committee in charge of reviewing data from the study would determine whether the vaccine is safe and effective.

"We want to ensure that what we know is shared with the public, with the media, with clinicians who aren't part of the company so we can develop confidence," said Stéphane Bancel, Moderna's CEO, in an interview.

"Submitting the protocol online is another step," he added. "We want the world to know they can trust us."

Trust has been in short supply, however. As Moderna and fellow coronavirus frontrunnners Pfizer and AstraZeneca have raced through early-stage testing, scrutiny of the companies and their clinical programs has ratcheted up. All three are now studying their experimental shots in late-stage trials involving tens of thousands of volunteers each.

Their rapid progress has brought concerns that they, or regulators, may rush to declare a vaccine ready for use before having sufficient data in hand to prove their shots are safe and effective. In the U.S., the question is intensely political, as President Donald Trump has said a vaccine could be available before election day on Nov. 3.

Government officials, including the head of the Trump administration's vaccine initiative, have indicated that's unlikely, although Pfizer anticipates the first results from its Phase 3 trial could come by the end of October.

Moderna expects an initial readout from its late-stage study a little later, likely in the latter half of November, Bancel said. The company recently slowed enrollment to ensure it recruits a more diverse group of trial volunteers.

But that timeline could still slip, should infection rates in the U.S. decline further. Moderna's trial, as with the others, measures vaccine effectiveness by comparing the number of COVID-19 cases in vaccinated participants to those who received placebo, meaning the study's outcome is dependent on infections occurring.

Moderna had previously said that an independent data monitoring committee would compare the vaccine to placebo at two interim time points, when 53 and 106 cases were confirmed. The principal comparison will take place after 151 cases.

The trial protocol shared by the biotech Thursday fills in some missing details on how the committee will conduct those analyses.

Summary statistical plans included in the protocol, for instance, indicate the vaccine would need to be more than 70% effective for the trial to be considered positive at the first interim data check. The trial would not be stopped early in the event of a positive interim analysis, according to the protocol.

The protocol also reveals statistical assumptions Moderna made to design its study, such as what percentage of participants will develop COVID-19, as well as how the data monitoring committee will convene and report its recommendations to a study oversight group. That group consists of representatives from the company and two government agencies that have helped fund and test its vaccine. 

Disclosure of the protocol is a "gesture of good faith," said Walid Gellad, an associate professor at the University of Pittsburgh and a director of the Center for Pharmaceutical Policy and Prescribing there, in an interview. 

"Everyone is on edge," he added. "[Disclosure] is more symbolic than a necessity but in this kind of environment I think it can help."

Moderna's decision to share the protocol comes a week after it and eight other vaccine developers vowed they would not ask for authorization or approval of their shots until they had safety and efficacy data from a Phase 3 trial that met regulators' standards.

Bancel said positive interim data from Moderna's trial would meet the bar for requesting an emergency authorization — a special type of clearance granted during a public health crisis — but not for a full approval.

The unconventional vow, which was also made by Pfizer and AstraZeneca, was aimed at shoring up public confidence. One day later, however, AstraZeneca disclosed it had paused vaccinations in all of its trials to assess an unexplained illness in one participant in the U.K.

The report, and AstraZeneca's limited communication of further details, renewed fears that rarer and more serious side effects may be missed in hurried testing. Typically, vaccine trials run for several years to ensure safety is well documented, a luxury developers and regulators don't have during the pandemic.

Author:Ned Pagliarulo

Published: https://www.biopharmadive.com/news/moderna-coronavirus-vaccine-study-protocol-november/585386/