(Reuters) – Pfizer Inc. is betting that its coronavirus vaccine candidate will show clear evidence of efficacy early in its clinical trial, according to the company and internal documents reviewed by Reuters that describe how the trial is run.
In recent weeks, Pfizer has said that they should know by the end of October whether the vaccine, developed together with Germany̵
President Donald Trump, who is seeking re-election, has said that a vaccine to fight the coronavirus pandemic is possible before the vote in the United States on November 3, which raises concerns about political interference. Researchers have questioned whether drug manufacturers will have enough evidence to succeed at that time.
Pfizer’s clinical trial protocol describes the company, researchers, and regulators how the drug manufacturer can demonstrate that its vaccine meets efficacy and safety standards established by the U.S. Food and Drug Administration.
A company’s protocol is submitted to the FDA for review and monitored by an independent panel of experts called a Data and Safety Monitoring Board.
The protocol requires an initial assessment of the vaccine’s performance of the surveillance card after 32 participants in the study have been infected with the new coronavirus. To date, more than 29,000 people have signed up for the trial, which started in July, some received the vaccine and others received a placebo.
The FDA has said that a coronavirus vaccine must be at least 50 percent more effective than placebo in a large-scale study to be considered for approval. However, a smaller sample of infections in a clinical trial changes the calculation of how that standard is met, according to researchers.
Pfizer’s vaccine would need to be at least 76.9% effective to show that it works based on 32 infections, according to its protocol. This would mean that a maximum of six of these cases of coronavirus would have occurred among people who received the vaccine, the documents showed.
If the drug manufacturer’s vaccine does not meet the 76.9% efficacy target in this initial interim analysis, it would meet stricter statistical significance thresholds during subsequent interim assessments, said biostatisticians who reviewed the protocol.
Pfizer said its interim analyzes were designed to show conclusive evidence “as quickly as possible in the midst of the devastating pandemic if our vaccine meets the stringent standards set by the FDA.” Pfizer would not say whether it would use an interim analysis as a basis for seeking approval.
The FDA declined to comment on whether it would consider such information sufficient for approval.
Interim assays are usually used by computer and safety monitoring cards to determine if an experimental drug works safely and effectively enough to continue a trial, or if it should be stopped if a safety problem occurs.
But if a vaccine meets the FDA’s criteria in an interim analysis without any serious safety concerns, it may make sense to use it as a basis for authorization to quell a pandemic that has killed about 940,000 people worldwide, says Thomas Lumley, president of biostatistics. at the University of Auckland in New Zealand.
Moderna Inc, another leader in the vaccine race, told Reuters it would seek FDA approval to use its vaccine in high-risk groups if an interim assessment of its trials showed that its vaccine was at least 70 percent effective.
Modern, which published its minutes on Thursday, said its first interim analysis of 53 infections is likely to come in November.
Some vaccine experts have said that drug manufacturers should wait to reach their final analyzes of more than 150 cases before applying for FDA approval. They note the rate at which vaccines are being developed for COVID-19 and compress what can be a decades-long process into months.
Relying on the more limited interim analyzes may exaggerate the effectiveness of a vaccine simply because not enough test subjects became ill, they have said. Going faster through the testing process also means that a drug manufacturer can miss potential side effects that can occur if the trials are given more time.
“These interim analyzes are a flashing sign of shortcuts,” said Eric Topol, director of the Scripps Research Translational Institute in La Jolla, California. “You lack security issues and you may well exaggerate the benefits.”
In addition to Pfizer and Moderna, Reuters reviewed the clinical trial protocols for vaccine candidates developed by AstraZeneca Plc and Johnson & Johnson.
AstraZeneca launched its first interim analysis when approximately 40 coronavirus infections were reported among participants. Its US trial is currently pending after a patient became ill.
J & J’s first analysis would begin with 20 infections, according to the minutes of their large-scale trial that began on September 21.
AstraZeneca and J&J declined to comment.
Reporting by Marisa Taylor in Washington and Dan Levine in San Francisco; Edited by Michele Gershberg and Will Dunham