Questions grow about Vax AstraZeneca-Oxford coronavirus trials – POLITICO

Drugmaker AstraZeneca is pushing back after experts questioned the quality of the company’s coronavirus vaccine testing.

A company spokesperson said Thursday that clinical trials of their vaccines were “conducted to the highest standards.” This included oversight by a data and security watchdog who found “the analysis … [showed] protection against COVID-19 occurring 14 days or more after receiving two doses of the vaccine. ”

The company will also submit the data to a peer-reviewed journal in the coming weeks, the spokesperson added.

Researchers have raised concerns since AstraZeneca and its partner, the University of Oxford, announced on Monday that their jab was around 70% effective. The news was particularly welcome as this vaccine could be cheaper and easier to deploy in low- and middle-income countries than others, but left experts to question the firm’s findings.

The assessment released on Monday was based on data from two groups: one included nearly 9,000 people who received two full doses of the vaccine, which produced an efficacy rate of 62%, while a smaller group of 2741 received a half dose followed by a full dose. , which produced an efficiency of 90%.

Experts say this is a problem. For starters, the group that initially received a half-dose of the vaccine in the UK did so by accident, the company first told Reuters.

The problem prompted the US government to investigate. Researchers like Moncef Slaoui, the outgoing leader of Operation Warp Speed ​​in the United States, have questioned whether the 90% effectiveness rate could be linked to the absence of anyone over 55 in the the second test group.

AstraZeneca and Oxford are insisting regulators were made aware of the error – which occurred when manufacturing was ramped up to produce large quantities for testing – and agreed to continue testing this group. The CEO of the company also told Bloomberg that he plans to launch a global trial testing the half-dose.

But some researchers remain concerned.

“These allegations are concerning,” said Eleanor Riley, professor of infectious diseases at the University of Edinburgh, adding that these questions need to be answered “clearly and completely.”

Uncertainty around testing reveals flaws in a system in which companies report their results in press releases to greedy audiences and fluctuating financial markets. These self-reported efficacy rates could withstand the scrutiny of regulators and gain their approval for use – but errors in testing could cost public confidence.

“Trust is everything when it comes to vaccines and we must not do anything that can undermine that trust anyway,” said Riley.

Paul Hunter, professor of medicine at the University of East Anglia, was among those who raised questions. He said in a statement that regulators need to review the final results before anyone can be sure of the half-dose diet’s claims of effectiveness. He added that the subgroup analyzes “are always fraught with difficulties”.

The accidental difference in dosing regimens was also one of the potential issues highlighted by Sheila Bird, a biostatistics researcher at the Medical Research Council at the University of Cambridge.

“It’s a considerable complication because [the half-dose/full dose protocol] happened by mistake, not [by] design, ”she told POLITICO in an email Thursday.

It was this and other outstanding questions about the lawsuit that led Bird to refrain from commenting initially on Monday. In her email, she pointed out too little information about the dosing regimens; on the number of people randomized in each group; and how this “error” affected the analysis.

“The answers await the sight of the written paper,” she wrote.

Not all researchers were so critical. This system is not “ideal”, wrote Stephen Evans, professor of pharmacoepidemiology at the London School of Hygiene & Tropical Medicine. But he argued that the pandemic has added a new emergency.

“In general, this applies to all COVID vaccine trials,” he wrote. “This is not the ‘normal’ process of authorizing a new vaccine – but we are in the midst of a pandemic where no vaccine was available for this disease.”

For its part, AstraZeneca did not respond to questions Thursday on whether data from all participants in various clinical trials would be sent for peer review, or just the subgroups mentioned in the press release from Monday. He also declined to respond to claims that the company was selecting data to achieve the 70% efficiency rate, which were detailed in a lengthy Wired article this week.

Do it quickly at the expense of quality?

Among the issues cited by the Wired story was an inconsistent dosage throughout the testing. The control groups also did not receive the same blows, he noted.

These questions stem from the company’s statement that it did not report data from a large-scale Phase 3 trial, but did report on a few subgroups of different trials around the world. This could potentially leave out half of the trial participants in Brazil, noted the Wired article, written by Hilda Bastian, a health consumer advocate.

Perhaps most important is the fact that the data could have been ‘handpicked’ because AstraZeneca did not initially indicate which subgroups they would report for their trial meta-analysis and when, writes Bastian.

The 70 percent effectiveness reports are “unknowable,” she wrote. “We only have numbers on these two patterns, unlike everyone else in the trials – and how they arrived at those percentages is not explained.”

“There are some problems with dosing error,” Joy Leahy, Statistical Ambassador for the Royal Statistical Society, wrote in a statement. Statistically, the more regiments are tested, the more likely it is to produce “particularly high efficiency, just because of chance and random variation.”

Hunter is among those who see “arguments for” subgroup analyzes. But he also questioned whether the AstraZeneca / Oxford trial was “sufficiently fueled for subgroup analysis” since it does not appear to be part of the trial design plan.

But many experts called for patience, noting that more data will come.

Gillies O’Bryan-Tear, director of policy and communications at the Faculty of Pharmaceutical Medicine, said the study still enrolled up to 60,000 people in trials around the world. “Given the efficiency we have seen so far [in both full and partial dose groups] … It is almost certain that robust efficacy… will be demonstrated in both groups, well above the benchmark 50 [percent] which was posed as an obstacle, ”he said.

Even those affected know that these issues will soon be in the hands of regulators, Bastian noted. But she added: “If anything less than this standard is accepted for this vaccine, it will be easy to stoke the already widespread fears about corner cuts. A loss of confidence would affect more than just this vaccine alone. “

This story has been updated.

This article is part of POLITICOPremium Police Service: Pro HealthCare. Whether it’s drug prices, EMAs, vaccines, pharmaceuticals and more, our expert journalists keep you up to date on the topics driving the healthcare policy agenda. E-mail [email protected] for a free trial.