Biostatistician Natalie Dean and Epidemiologist Marc Lipsitch, key international experts in vaccine studies, just published an article in Science today explaining how to interpret "vaccine efficacy" for the COVID-19 trials.
Here are some of their key points (some of which I discussed in previous blog post):
Vaccines have two benefits: direct effects, preventing infection in the vaccinated individual, and indirect effects, slowing societal spread which protects many in the community from exposure.
Phases 3 studies (as the interim analysis reported this week for BioNtech/Pfizer vaccine) are designed to assess individual level efficacy and safety, focusing on testing for differences in symptomatic infections confirmed by rigorous testing between placebo and vaccine arms.
Two limitations of these studies:
They are not powered for subgroup analyses, so cannot tell if they work equally well in all age and risk groups, and for mild, moderate or severe disease. These studies will provide initial estimates, but may not be large enough in each subgroup to get definitive answers.
Even if they reduce infections, it is not possible from these studies to assess whether it reduces infections. For example, it is possible the vaccine prevents symptoms so the case is not detected, but the individual may still be an asymptomatic spreader.
When the vaccine is approved, all subjects may move to active vaccine, which is good for them but also limits the strong information we can gain because of the placebo-controlled design, especially for subgroup analyses.
Post-approval observation studies will be needed to answer these additional questions, as well as to assess any late emerging side effects. The problem with these observational study is that it is difficult to identify true causal effects of the vaccine because of factors that might be different in the vaccine and control groups.
Special designs can be used to assess infectiveness using viral testing.
The article also mentions some innovative new designs and approaches that can be used for these follow-up studies, and these two researchers are likely to be key innovators in those efforts.
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