Staying on track means learning from past outbreaks
This is an important time for clinical trials. Researchers and hospitals are rushing to determine the effectiveness of treatments and vaccines for Covid-19. At the same time, many trials on other medicines are being stopped, suspended, or transferred to remote systems (with medicines and monitoring equipment delivered at home combined with digital consultation).
And while we have begun to see (sometimes confusing) results from a gaggle of preliminary studies looking to evaluate existing or experimental drugs against Covid-19, the picture will only become clear with large scale, high powered efforts such as the Solidarity trial being coordinated by the World Health Organization (WHO).
As Derek Lowe points out in his latest column, those trials will take time to reach a level of evidence sufficient to justify administering a vaccine to millions (or even billions) of people worldwide. But it’s not just the scale of the trials that presents challenges. The trials’ design needs careful planning to ensure that they don’t overburden already-stretched healthcare systems.
While the WHO’s Solidarity trial is rigorously testing four of the most promising treatment options, there is also an opportunity to establish trials that are specifically designed to respond to a rapidly evolving emergency such as Covid-19. That means trials that can adapt their protocols as new information and treatment options become available, without adversely affecting the integrity of the data.
On this front there are lessons to be learned from the past, including the recent Ebola outbreak. Adapting trials on-the-hoof makes it easier to wrongly conclude treatments are effective when they aren’t. And if a treatment does show definite effects, then there needs to be facility for it to be integrated into the baseline care of other patients, on ethical grounds alone. Some of these issues can be broached by adopting design based on Bayesian statistics, and statisticians at the US Food and Drug Administration (among many others) have put in significant effort to develop guidance for designing trials in this way.
It’s also important that the results of these trials are made available quickly, and in open and transparent ways. This will help avoid issues that were seen with Roche’s influenza drug Tamiflu (oseltamivir). The company is accused of withholding data showing the drug to be less effective than originally claimed, which led various countries to stockpile the drug and prescribe it more widely than perhaps was justified during outbreaks of more virulent flu strains.
These are significant challenges, especially with the time and resource constraints of a pandemic. But, with sufficient cooperation, I believe it can be done.