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Massive-scale platform trials coming up large AGAIN with toci RCT demonstrating survival advantage. The global impact of @NIHRresearch @agordonICU @Lennie333 @PeterHorby @MartinLandray continues to amaze and inspire 1/n
Value proposition for toci is different than dex. Appropriate ?s of scalability and applicability to LMICs. Health systems must grapple w decision to roll out a proven but expensive treatment. @srinmurthy99 2/n
Two potentially supply constraints we need to be proactive in addressing - the drug itself and money. Remember, we saw shortages in first wave in Italy @TheLancetRheum (my emphasis) 3/n
Can we facilitate access, save more lives, and reduce drug expenditures? Increase production? Reduce price? Re-orient distribution channels? All necessary but may be tough to do quickly in a pinch. Asymmetric gains may be hidden in dosing 4/n https://ascpt.onlinelibrary.wiley.com/doi/10.1002/cpt.1931
Toci dose in acute conditions like COVID and even CAR-T CRS is an OPEN QUESTION. We don’t know the minimum effective dose but very possible that it is a lot lower than 8mg/kg / 4mg/kg/ 400mg 5/n
In a pop. pre-selected for signs of hyper inflammation - the patients we might expect to need the *greatest* amount of toci - we failed to identify evidence of a dose-response relationship. In context of supply constraint this can be a GOOD thing 6/n https://onlinelibrary.wiley.com/doi/10.1002/cpt.2117
Yet another reason why the dose really, really matters. We have an open randomized dose-ranging study addressing the ?. Right now a single site but collaborators would be very welcome!! 7/n https://clinicaltrials.gov/ct2/show/NCT04479358
tl;dr Treatments are only effective if patients have access to them. Need to expand *effective* supply if not actual supply. Dosing matters. Controlled tinkering has big upside 8/fin
