Government Researchers Changed Endpoint During Remdesivir Trial

Vials of investigational COVID-19 treatment drug remdesivir are capped at a Gilead Sciences facility in La Verne, Calif., on March 18, 2020. Gilead Sciences via Reuters

Researchers changed the primary endpoint for a clinical trial testing remdesivir against COVID-19, a shift that provoked concerns among some scientists.

The endpoint is the main result measured at the end of a study. The endpoint for the remdesivir trial was originally focused on counting how many patients died after two weeks. After the trial began, it was changed to “time to recovery,” or how quickly patients were discharged after receiving the experimental drug.

Remdesivir is produced by California-based Gilead Sciences. The clinical trial was run by the National Institute of Allergy and Infectious Diseases (NIAID).

“Little was known regarding the natural course of COVID-19 when the trial was initially designed, and the initial endpoint chosen specified a single time point for evaluation, namely day 14,” a spokesperson for the agency told The Epoch Times.

“However, with the growing knowledge during the epidemic, we learned that COVID-19 had a more protracted course than previously known. Further concerns were raised about the reliance on a single time point for evaluating treatment effects.”

The Gilead Sciences headquarters in Foster City, Calif., on April 29, 2020. Justin Sullivan/Getty Images

Statisticians modeled to see what would happen if “the right day” wasn’t picked for assessing the trial. Models showed that meaningful effects could be missed.

“Time to recovery avoids this issue, and the change in primary endpoint seemed appropriate given the evolving clinical data. This change in primary endpoint was made without any knowledge of data from ACTT, before any interim data was available,” the spokesperson said. ACTT is an acronym for the Adaptive COVID-19 Treatment Trial.

Under the new endpoint, the trial found remdesivir helped patients recover faster when compared to the control group.

“What it has proven is that a drug can block this virus,” Dr. Anthony Fauci, the head of NIAID, told reporters at the White House.

Results indicate the group that received the drug had a lower mortality rate, but the number hasn’t yet reached statistical significance.

The change was announced on the trial listing last month but received renewed attention after NIAID championed remdesivir last week. Researchers said the trial proved the drug worked against COVID-19, the disease caused by the CCP (Chinese Communist Party) virus, commonly known as the novel coronavirus.

A vial of the drug Remdesivir held by a researcher at a facility in Hamburg, Germany, on April 8, 2020. Ulrich Perey/Pool/AFP via Getty Images

The positive results prompted the Food and Drug Administration to approve emergency use of remdesivir against COVID-19. Unlike other drugs being tested against the new disease, remdesivir hasn’t received official approval for any use in normal conditions anywhere in the world against any illness.

The change in endpoint, though, drew concern from some scientists.

“I think that they thought they weren’t going to win, and they wanted to change it to something they could win on,'' Steven Nissen, a Cleveland Clinic cardiologist who has led drug trials, told The Washington Post. “I prefer the original outcome. It’s harder. It’s a more meaningful endpoint.

“Getting out of the hospital early is useful, but it’s not a game-changer,” he added.

The move has been described as unusual, but does happen. Dr. Todd Lee, a clinician-scientist at McGill University, said the change “makes sense.”

There were also calls for the data to be released and questions about why it hasn’t been.

Dr. Anthony Fauci, left, director of the National Institute of Allergy and Infectious Diseases, speaks next to response coordinator for the White House coronavirus task force Dr. Deborah Birx, during a meeting in the Oval Office of the White House on April 29, 2020. Mandel Ngan/AFP via Getty Images

The full results still haven’t been published. The NIAID spokesperson said there’s no firm date yet for the release. Fauci said the results are undergoing peer review.

“As much as people respect and admire and trust Dr. Fauci, they’d prefer not to take his word for it that this is promising, but to see the data themselves,” Holly Fernandez Lynch, a medical ethics professor at the University of Pennsylvania, told Quartz. “Even Tony Fauci needs peer review.”

NIAID announced the data several days earlier than it normally would have because of ethical considerations, Fauci said.

“Whenever you have clear cut evidence that a drug works, you have an ethical obligation to immediately let the people who are in the placebo group know so that they can have access,” he said.

Fauci dismissed results from another study that published full results the same day.

Chinese researchers found remdesivir wasn’t linked to a difference in time to clinical improvement. They also found signs of clinical improvement in patients given the drug earlier in the illness.