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This article touches upon many of the concepts we have been thinking about over the last few years. How do we evaluate vaccines/therapeutics during public health emergencies? RCTs are tricky but important! A few key points... 1/8 https://www.nytimes.com/2020/08/04/health/trump-plasma.html
There is genuine uncertainty about the value of convalescent sera for treating severely ill patients. This is best addressed by randomized controlled trials. But patients are unwilling to enroll in trials because they can receive sera through expanded access programs. 2/8
"A spokeswoman for the FDA said that the expanded access program was meant to bridge the gap until trials could get underway and “was never intended to substitute for randomized clinical trials, which are critically important for the demonstration of efficacy.”" 3/8
But the result is a set of underpowered trials, some in former hotspots like NYC. Others just unable to recruit people to be randomized. Discussions are now turning to post hoc pooling of data from ongoing trials, but this is not ideal. 4/8 https://med.nyu.edu/departments-institutes/population-health/divisions-sections-centers/biostatistics/research/continuous-monitoring-pooled-international-trials-convalescent-plasma-covid19-hospitalized-patients
Our group had at one point discussed the role of this type of meta-analysis, but obviously it is not as good as having planned in advance to pool data. Endpoints/populations may be defined differently. There is no coordinated analysis plan. 5/8 https://www.nejm.org/doi/full/10.1056/NEJMsb1905390
Now there is discussion about the FDA preparing an emergency authorization to make the treatment even easier to use (per the NYT), despite lack of efficacy data. This would only further undermine our ability to determine whether it works at all. A perpetual state of limbo. 6/8
At the start of an emergency, randomized clinical trials always appear too slow and cumbersome, but we could have (or nearly have) definitive evidence by now if we had a coordinated effort, similar to the UK recovery trial. 7/8 https://www.washingtonpost.com/outlook/coronavirus-hydroxychloroquine-trials-research/2020/04/10/fa003ada-7a7a-11ea-a130-df573469f094_story.html
The "what do you have to lose?" approach of treating with whatever we have is short-sighted. Besides the time, money, and resources wasted on ineffective treatments (people are literally donating blood), some treatments could even be harmful. RCTs are our best path forward. 8/end
