COVID vaccination studies: plan now to pool data, or be bogged down in confusion


Natalie Dean at Nature: “More and more COVID-19 vaccines are rolling out safely around the world; just last month, the United States authorized one produced by Johnson & Johnson. But there is still much to be learnt. How long does protection last? How much does it vary by age? How well do vaccines work against various circulating variants, and how well will they work against future ones? Do vaccinated people transmit less of the virus?

Answers to these questions will help regulators to set the best policies. Now is the time to make sure that those answers are as reliable as possible, and I worry that we are not laying the essential groundwork. Our current trajectory has us on course for confusion: we must plan ahead to pool data.

Many questions remain after vaccines are approved. Randomized trials generate the best evidence to answer targeted questions, such as how effective booster doses are. But for others, randomized trials will become too difficult as more and more people are vaccinated. To fill in our knowledge gaps, observational studies of the millions of vaccinated people worldwide will be essential….

Perhaps most importantly, we must coordinate now on plans to combine data. We must take measures to counter the long-standing siloed approach to research. Investigators should be discouraged from setting up single-site studies and encouraged to contribute to a larger effort. Funding agencies should favour studies with plans for collaborating or for sharing de-identified individual-level data.

Even when studies do not officially pool data, they should make their designs compatible with others. That means up-front discussions about standardization and data-quality thresholds. Ideally, this will lead to a minimum common set of variables to be collected, which the WHO has already hammered out for COVID-19 clinical outcomes. Categories include clinical severity (such as all infections, symptomatic disease or critical/fatal disease) and patient characteristics, such as comorbidities. This will help researchers to conduct meta-analyses of even narrow subgroups. Efforts are under way to develop reporting guidelines for test-negative studies, but these will be most successful when there is broad engagement.

There are many important questions that will be addressed only by observational studies, and data that can be combined are much more powerful than lone results. We need to plan these studies with as much care and intentionality as we would for randomized trials….(More)”.