Below I discuss my speculations on the possible reasons the recent UNITY senolyic trial might have failed
WOMAC or equivalent for other OA (osteoarthritis) joints has poor correlation with hard rejuvenation outcomes (as I discovered when I was systematically reviewing all therapies and trials for osteoarthritis for my osteoarthritis rejuvenation guide);
Nor is it a placebo-resistant outcome, and in fact is affected by many things other than placebo, from mineral baths, painkillers, supplements, weight loss etc (which is not clear they adjusted for in results or covered in inclusion/exclusion criteria).
Hard rejuvenation outcomes would be more like ROM (range of motion) and quantitative imaging markers (e.g. quantitative 3 Tesla MRI multiparametric arthrography).
I have been calling this year for there to be a discussion on what set of rejuvenation core outcomes measures in effectiveness trials (COMET), as per COMET initiative - http://www.comet-initiative.org/, there should be for 1) whole body rejuvenation indication (like TAME's primary outcome) and 2) rejuvenation for specific ageing caused conditions (like this unity trial).
I don't think this is the case but if FDA requires a 3 month WOMAC as a sole primary outcome in Phase 2/3 for KOA intra articular (IA) injection trials then I would consider using non-FDA regulators, or working with FDA to change this requirement.
You can analyse efficacy failure in Phase 2 trials through the PICOTS framework
P - Population
I - Intervention
C - Comparator
O - Outcome
T - Timecourse
S - Setting
In this case major risk of bias from incomplete followup or allocation concealment seem unlikely, but these are often things that ruin trials too and should be thought about in every trial.
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