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NEW article in @ClinTrialsJ: "An Ethics Framework for Consolidating and Prioritizing COVID-19 Clinical Trials," with @gelinas_luke, @BarbaraBierer, @ChandrosHull, @SteveJoffe, David Magnus, @profmohapatra, Rich Sharp, @KayteSB, Jeremy Sugarman, @BWilfond & @HollyLynchez 
There is a plethora of COVID-19 therapeutics that could be trialed. But health systems & academic medical centers have limited research capacity, especially during surges, since clinical care & research can compete for the same resources. From April 2020: https://www.businessinsider.in/science/news/there-are-already-72-drugs-in-human-trials-for-coronavirus-in-the-us-with-hundreds-more-on-the-way-a-top-drug-regulator-warns-we-could-run-out-of-researchers-to-test-them-all-/articleshow/75333967.cms
There are also (thankfully!) finite patients who are eligible—& willing—to participate in any given trial. Most trials prohibit co-enrollment in others, so trials with overlapping inclusion/exclusion criteria will tend to compete for the same patient-participants.
This suggests a need to consolidate & prioritize trials to avoid duplication, ensure trials meet enrollment targets/are powered, & ensure the "best" trials go first. Ideally, this would occur upstream at the funding/manufacturing stages & at the regional & (inter)national levels.
For a variety of reasons, that largely hasn't happened in many places, including (especially) in the U.S. Even with upstream consolidation & prioritization of sponsored research, there will still be competition among an institution's "local" investigator-initiated trials.
As a result, individual health systems/AMCs have had to decide themselves which COVID-19 trials to field, and when (and to some extent will always have this burden). Yet existing institutional processes (IRB, scientific review) look at studies one-by-one, not comparatively.
How has relying on 1st-come, 1st-served, business-as-usual gone? Of the 1551 COVID-19 studies registered on http://CT.gov as of May 2020, only 29.1% could potentially yield 2011 OCEBM level 2 evidence (highest level of individual study evidence) https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2768882
By June 2020, of all participants enrolled in 1 of 1200 COVID-19 trials registered on http://CT.gov , 35% were enrolled in a study of (hydroxy)chloroquine. And across all COVID-19 trials, 39% sought to or did enroll 100 or fewer participants. https://www.statnews.com/2020/07/06/data-show-panic-and-disorganization-dominate-the-study-of-covid-19-drugs/
By January 2021, the number of COVID-19 trials had doubled, but with little reason to think things had improved. Here's @califf001 & @DeborahZarin on Jan. 4 ( https://califf001.medium.com/complete-rapid-reporting-of-clinical-trials-a-necessary-component-of-the-pandemic-response-aa158eb1a1cb):
And here's @DrWoodcockFDA's 1/13 sober assessment: most COVID-19 studies had little hope of yielding actionable info; if we'd been more focused & disciplined in how we set up our global trial infrastructure, we'd be further along. (remarks start at 4:12) https://vimeo.com/502342017
In the absence of better global trial infrastructure, many individual institutions deluged w/COVID-19 research proposals quickly stood up committees to sort through it all. But little guidance was available. Several of us who serve on these committees tried to develop some.
To help guide individual institutions ethically consolidate and prioritize COVID-19 trials—and thereby help ensure that the most socially valuable research isn't crowded out by duplicative, unpowered & otherwise uninformative trials—we propose this 3-stage process:
Each trial must meet all 4 Threshold Criteria that—save for consolidating similar trials—are familiar to research ethics. Stage 2 entails an assessment of the institution's capacity to simultaneously field all trials meeting threshold criteria.
Trials proceed to Stage 3 for prioritization if the institution lacks research capacity (including sufficient eligible patients) to field them all at once. Study-Specific criteria overlap Threshold Criteria but at this stage are comparative.
If we only considering study-specific criteria, we might end up with trials that are individually strong but collectively omit important research questions or patient groups patients. Hence, Portfolio Diversity Criteria.
Finally, we provide some recommendation about committee staffing and procedures. What we propose isn't perfect, of course, & it doesn't solve all problems. But we have to start somewhere. We very much welcome others to build on our work.
The value of consolidating & prioritizing clinical trials—& other kinds of research—isn't unique to the pandemic (indeed, we hope our guidance will inform oversight of non-COVID-19 research). But the pandemic has made uniquely clear that we have a problem. https://news.bloomberglaw.com/pharma-and-life-sciences/reams-of-useless-covid-data-drive-reckoning-on-clinical-trials
Published version ($): https://journals.sagepub.com/doi/full/10.1177/1740774520988669
Ungated accepted version: http://www.michellenmeyer.com/uploads/2/2/2/2/22222570/meyer_et_al-prioritizing_covid-19_research-accepted_version.pdf (will be updated with the PMC version, when available)
Thanks to my co-authors & to the other members of @GeisingerRsrch's COVID-19 Research Oversight Committee! /fin
Ungated accepted version: http://www.michellenmeyer.com/uploads/2/2/2/2/22222570/meyer_et_al-prioritizing_covid-19_research-accepted_version.pdf (will be updated with the PMC version, when available)
Thanks to my co-authors & to the other members of @GeisingerRsrch's COVID-19 Research Oversight Committee! /fin
