NIH takes exception to AstraZeneca data

Very Unclear

At midnight on March 23, the National Institutes of Health (NIH) (specifically, an NIH subunit called National Institute of Allergy and Infectious Diseases [NIAID]) released this statement:

“Late Monday, the Data and Safety Monitoring Board (DSMB) notified NIAID, BARDA, and AstraZeneca that it was concerned by information released by AstraZeneca on initial data from its COVID-19 vaccine clinical trial. The DSMB expressed concern that AstraZeneca may have included outdated information from that trial, which may have provided an incomplete view of the efficacy data. We urge the company to work with the DSMB to review the efficacy data and ensure the most accurate, up-to-date efficacy data be made public as quickly as possible.

Authorization and guidelines for use of the vaccine in the United States will be determined by the Food and Drug Administration and Centers for Disease Control and Prevention after thorough review of the data by independent advisory committees.”

Katelyn Jetelina, who publishes the blog Your Local Epidemiologist (YLE), shared the opinion that it is ”HIGHLY unusual for the Data Safety and Monitoring Board (DSMB) and a vaccine sponsor (AstraZeneca) to publicly (or privately in that matter) disagree. We (scientists and the general public) don’t have access to the raw data, so I’m not entirely sure what’s going on, but this is concerning, especially given AstraZeneca’s rocky history throughout the pandemic.”

In a blog in September, YLE explained that, “Depending on the risk of a study, a scientist must get approval from 1 or 2 external review boards. These boards are made up of people that aren’t connected, in any way, with the study. Meaning… they aren’t affected by the success of a study (professionally or financially). This ensures that studies are ‘double checked’ for safety without the influence of conflicts of interest. This is an essential process in science. The two boards are…

Institutional Review Board. Every study needs this BEFORE a study starts. It’s usually made up of people with an ethics background or specialists in the field. Scientists HAVE to get this stamp of approval before they can start.

Data Safety Monitoring Board (DSMB). Only ‘risky’ studies need this. This board is typically made up of 4-10 people and are ethicists, statisticians, medical specialists, and even community members. This board checks for safety DURING the study. They make the rules on when to stop a trial. They also meet on a regular basis, have access to the data throughout the trial, and knows who got the placebo and who didn’t.”

Both of these boards were involved with the AstraZeneca Phase III trial. On September 8, the #2 board (DSMB) decided to pause the study. It can pause OR stop a study for three reasons:

Overwhelming positive effect of a drug (stop the study, so the placebo participants can start getting the effective drug)

A negative effect of a drug (adverse event, serious side effect, hospitalization or death)

Futility (the study can’t complete what it promised OR it isn’t working as well or better than existing approved drugs). This is what happened with a couple of the hydroxychloroquine studies that ended early.”

The DSMB stopped the AstraZeneca trial because of reason #2. A participant had a serious adverse event or serious side effect while enrolled in the study. This could OR could not mean the vaccine caused the side effect. The DSMB needed more time to carefully investigate what happened and whether it was, in fact, related to the vaccine. After the investigation, there could be a recommendation to stop the Phase III trial altogether or continue the trial.

However, it turned out that the participant who prompted the global shutdown of AstraZeneca’s Phase 3 Covid-19 vaccine trials was a woman in the United Kingdom who had neurological symptoms consistent with a rare but serious spinal inflammatory disorder called transverse myelitis, according to AstraZeneca’s chief executive, Pascal Soriot. The woman’s diagnosis improved, and she was released from the hospital. She had been injected with the company’s Covid-19 vaccine and not a placebo. The AstraZeneca clinical trial was halted once previously in July after a participant experienced neurological symptoms. That participant was diagnosed with multiple sclerosis, considered  to be unrelated to the Covid-19 vaccine treatment.

In December the first full peer-reviewed results of phase 3 trials of the COVID-19 vaccine developed by AstraZeneca and Oxford University were reported to be safe and up to 90% effective in preventing infection, supporting regulatory submissions for emergency use. However, it has not yet been cleared for use in the United States.