Tighten trial, manufacturing oversight and regulatory scrutiny
AstraZeneca has since disclosed that the separate regimens were a result of a manufacturing error—some vaccine vials used on subjects simply didn’t have the right concentration—which makes the manufacturing and trial administration oversight seem to be of questionable quality.
In light of the dosing error in its Covid-19 vaccine trial studies, AstraZeneca has done well—as per multiple news reports—to announce that it will run new global trials with the lower-dose regimen of the vaccine developed with Oxford University. The company has drawn a lot of flak over its early readouts from the trial. While 2,741 participants were part of a half-dose-subsequent-full-dose regimen (with 90% efficacy reported), 8,895 were part of a two-full-doses regimen (with 62% efficacy); given the two regimens were different, the company announcing a composite 70% efficacy isn’t strictly kosher, many scientists have opined.
AstraZeneca has since disclosed that the separate regimens were a result of a manufacturing error—some vaccine vials used on subjects simply didn’t have the right concentration—which makes the manufacturing and trial administration oversight seem to be of questionable quality. Even as the company had tried to gloss over the unintended dosing regimen and its higher efficacy by terming it “serendipity” when it should have addressed the confusion—why has a lower-dose regimen reported better efficacy, are there other such ‘unintended elements’ in the trial design, etc—the head of the Operation Warp Speed programme in the US pointed out that the low-dose trial that reported higher efficacy had been conducted with participants below 55 years of age. Bear in mind Covid-19 vaccine rollout planning in most nations views the elderly as a priority group, given their higher risk of mortality and severe morbidity from the disease. Some others have questioned the variations in the trials in different countries—for instance, while, in the UK, the placebo group received a meningococcal vaccine, in Brazil, it received a saline placebo.
With these revelations clouding AstraZeneca’s claims, the world would do well to treat this as a cautionary tale—on hyping of early, non-peer-reviewed results made public through press releases/statements, and the fact that the rush for a vaccine, thanks to which many aspects of traditional vaccine development and trials have been junked, calls for far greater regulatory scrutiny with regards to the checkpoints that have been retained. Else, even if AstraZeneca’s serendipity eventually proves a lucky break, there is always the possibility that similar regulatory and internal oversight lapses in the case of other candidates could lead to undesirable consequences. A new global trial offers Oxford-AstraZeneca researchers the chance to make sense of the rather baffling results—some top scientists are already wondering if the results underscore the importance of priming the immune system before getting it to commence the production of antibodies at scale—and the company the opportunity to mend the dent to its repute. Beyond that, it could also encourage other vaccine developers to re-examine their trials for any missed route to push up efficacy gains.