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As you consider the #COVID19 #vaccine debates about 1 vs 2 doses, timing of 2nd dose & dosing w/ 2 diff vaccines, keep in mind there is no "right" answer & there are gaps in the evidence such that we may not know which is the "right" answer for a long time. Why not? A 
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Well, while individually-randomized clinical trials give great evidence to understand vaccine efficacy, they cannot tell us which is the most effective COVID19 #vaccination strategy. This should not be a surprise-none of the COVID19 trials evaluated any vaccination strategies.2/
As a result, the phase 3 trial data from #pfizer #moderna #oxford #COVID19 #vaccines alone cannot single-handedly identify how we should vaccinate populations. Optimal vaccination strategies depend on population-level factors such as context-specific disease epi & logistics. 3/
We (population-based public health researchers. i.e. epidemiologists) specialize in designing phase 4 studies that go beyond phase 3 trials by assess the effectiveness of multiple vaccination strategies in populations using cohorts and other methods. 4/
We ask questions like what is the most effective way to optimize the benefits of vaccination in this population at this time given what is known about vaccine efficacy (incl efficacy against multiple outcomes, differences in efficacy by age, efficacy waning over time)? 5/
We gather evidence to determine the impact of targeting different age groups or targeting based on transmission etc. These phase 4 studies are crucial because they complement evidence from phase 3 trials and answer the next important question-how should we use this vaccine? 6/
My group & many others focus on this population-level public health research. How can we maximize the effectiveness & thus the benefits of vaccines via optimal vaccination strategies? Why do we do this research when clinical trials tell us if a vaccine is safe & effective? 7/
Because individually-randomized clinical trials incl the #COVID19 vaccine trials assess the average individual-level benefit of vaccination. Such a trial might tell us that 2 doses given 21 days apart maximizes the immune response & duration of immunity among individuals. 8/
These clinical trial results are critical, which is why FDA & other regulators use trials to assess whether a vaccine is safe & effective enough to be given to individuals. They ensure that the evidence demonstrates that the vaccine protects (and does not harm) individuals. 9/
What does this tell us about how to protect populations? Surprisingly little! There are dozens of decisions that need to be made about HOW a vaccine that is safe and effective on an individual-level SHOULD be used to control a disease at the population-level. 10/
In normal times, we (epidemiologists & population-based researchers) would launch studies to ask these questions & inform evidence-based vaccination strategies. These studies take time & if we’ve learned anything during the pandemic it is that time is of the essence. 11/
No doubt these studies WILL be done, but decisions will need to be made before results are available.
So, how should we approach these debates? 12/
So, how should we approach these debates? 12/
First, be clear about what the evidence says about maximizing individual-level efficacy AND acknowledge that that evidence alone is insufficient to assess pop-level effectiveness for any strategy, especially if the proposed one deviates from the doses/timing/age in the trial. 13/
Second, acknowledge the decisions that need to be made-urgently-and identify which of those decisions are:
1) supported directly by evidence
2) extrapolated from related evidence, and
3) made in the absence of evidence based on assumptions.
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1) supported directly by evidence
2) extrapolated from related evidence, and
3) made in the absence of evidence based on assumptions.
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These distinctions are CRITICALLY important because the scope of evidence available & the assumptions we make WILL change over time as we gather more knowledge, so we must be explicit about how these decisions are being made now & which elements might change in the future. 15/
Third, communicate these decisions transparently & clearly. It is a major disservice to all to suggest scientific evidence exists to support a decision that was made based purely on lack of resources or on logistical feasibility. Of course there are trade-offs. 16/
Communicate how those trade-offs are prioritized from the start or risk losing credibility and trust - we cannot afford losing trust and faith in the process at this stage. 17/
And, finally, accelerate the implementation of phase 4 studies of #COVID19 #vaccines so we can revise guidelines & recommendations as soon as possible. All decisions not fully based on evidence are a gamble. If we don’t collect these data, we will never know... 18/
Which gambles paid off and which should be revised immediately. We can’t afford gambling for longer than necessary. Too many lives/livelihoods are at stake. Too many have been lost already. 19/
If you follow me, you’ll see this is why I often say that the same resources-billions $$$-that have been devoted to vaccine development need to be devoted to vaccination research. There remains so much we don’t know about how to use vaccines effectively at population-level. 20/
Thanks for reading this far. Hope this clarifies some of the very real challenges w/ making decisions about optimal population-level vaccination strategies when we only have evidence about individual-level vaccine efficacy. 21/
And I hope you’ll keep this in mind & ask questions if others claim certainty about decisions for which there is no comprehensive evidence at present. Let’s gather the evidence needed now as we move ahead so we don't risk wasting the best chance we have to end the #pandemic. /end
