Covid vaccine trials: what went well and what went wrong?
Covid vaccines are widely seen as a medical and regulatory success story.
This blog takes a look at what went well, flags some ongoing controversies, and highlights concerns about the weak transparency of some vaccine trials.
Note: This blog is part of a series presenting the findings of a recent report by Health Action International and TranspariMED. Previous blogs discussed Covid research waste, the weaknesses of the global clinical trial registry system, and trials of non-pharmaceutical interventions.
What went well?
The strong design and implementation of Covid vaccine trials – at least those run in Europe and the United States – supported the extremely rapid development of vaccines that substantially reduced deaths and hospitalisations, saved countless lives, and eventually enabled normal life to resume in many wealthy countries.
Regulators set clear success benchmarks for potential Covid vaccines at an early stage, contributing to the overall high quality of vaccine trials.
Early in the pandemic, the European Medicines Agency and other major regulators, including the U.S. Food and Drug Administration, defined the evidence and efficacy bars that new vaccines would have to clear to be allowed onto their markets.
What opportunities were missed?
Some aspects of the Covid vaccine research agenda are still being hotly debated.
Contentious issues include whether vaccine development and rollout could have been significantly accelerated through challenge trials (in which vaccinated volunteers would be deliberately exposed to the virus), and whether and when some population groups – notably pregnant women and children – should have been included in trials.
In addition, the launch of head-to-head trials directly comparing multiple vaccines at an early stage could have reduced uncertainties about comparative efficacy.
Similarly, when the Delta variant started rapidly spreading in the UK, lack of trial data on different dosing intervals created considerable uncertainty about whether to shorten the timespan between the first and second vaccine shots.
Mixed picture on transparency
The pandemic highlighted significant differences between regulatory transparency standards and corporate transparency practices between countries, and the consequences of global regulatory fragmentation.
As of May 2022, a total of 38 different vaccines are on the market worldwide; most of these have been approved by a very small number of countries only.
In Europe and the United States, the transparency of landmark pivotal trials was high overall.
This was largely due to pre-existing regulatory requirements, combined with strong political, public and scientific pressure for transparency.
For example, after Moderna and Pfizer voluntarily publish their trial protocols, AstraZeneca followed suit two days later. The outcomes of their landmark trials were rapidly published in academic journals.
Outside Europe and North America, significant transparency gaps were reported.
A report by Transparency International that reviewed 86 clinical trials of 20 Covid vaccines in development or on the market found significant transparency gaps in many trials (as of March 2021). Full protocols were available for only 12% of all trials. Transparency levels appeared to be low overall outside the North Atlantic region.
A subsequent academic study that assessed a wider range of transparency elements (published in August 2021) also found “varied transparency” at the level of individual trials, pharmaceutical companies, and regulatory agencies.
The study warned that the Chinese Sinovac and Sinopharm vaccines accounted for the majority of vaccines administered in Asia, South America, and Africa, but that disclosures of their trial results had “largely been limited to government media reports and press releases”.
The study also noted that only the European Medicines Agency, Health Canada and the Japanese regulator had disclosed Clinical Study Reports, and flagged strong variations in companies’ stated willingness to share Individual Participant Data.
Can we improve transparency globally?
Around half of the vaccine doses administered worldwide to date were trialled and produced in non-traditional pharmaceutical hubs including China, India and Russia.
Arguably, clinical trial transparency in vaccine exporting countries has now shifted from being a purely domestic issue to becoming a global health issue.
The European Medicines Agency should open a dialogue on developing global common minimum transparency standards both for regulatory documents and for pivotal clinical trial data within the International Coalition of Medicines Regulatory Authorities, while seeking to widen the body’s membership to include all emerging medical research and export hubs.
Download the full report
The full report by Health Action International and TranspariMED from which this blog was extracted can be downloaded below.
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