3 ms·

The efficacy of most new drugs is barely feasible to detect at a small trial size, of the best guess for effective dose, comparing against only one other option

by mlyle 2y ago

The efficacy of most new drugs is barely feasible to detect at a small trial size, of the best guess for effective dose, comparing against only one other option (or nothing). Trying to microdose and test many things at once is going to make this signal vanish to nothing.

londons_explore 2y ago
The logical way to do it is to have doses starting really tiny, then doubling every ~week. Every week, patients are given a health survey, and if any effect is obvious in the results data (ie. patients given drug 43 have, on average, a 2 C increased core body temperature), then the dosage of that specific drug is either held fixed (since it is clear we have reached the 'has an effect' dosage), or removed entirely from the trial (if whatever the effect is is deemed likely to hide more valuable yet smaller data from other drugs)
- jdoe2020 2y ago
  Then your get dropout problems and by the time there is an effect you don't have the statistical power to detect it. You need 3-6 months on an AD, psychiatic, metabolic, or autoimmune drug to see a Real effect so that is how long you must wait to ramp the dose. It could take years to go from a conservative guaranteed nontoxic dose to an effective one. But in that time most patientss will have gotten tired of waiting and switched drugs, moved to a new city and dropped out of the trial, or die. Sure it could work for some things like antimicrobials or erectile dysfunction drugs that have a rapid response, but that isn't where most of the drug development is. It is in those categories I listed.
- mlyle 2y ago
  In addition to what the person has already said: An "obvious" effect is harder to spot than you think. Asking for statistical power to spot an effect in a week when you're trying a dozen compounds at once-- you'd need millions enrolled in this study, and they'd need to be very patient.

by mlyle 2y ago

londons_explore 2y ago

The logical way to do it is to have doses starting really tiny, then doubling every ~week. Every week, patients are given a health survey, and if any effect is obvious in the results data (ie. patients given drug 43 have, on average, a 2 C increased core body temperature), then the dosage of that specific drug is either held fixed (since it is clear we have reached the 'has an effect' dosage), or removed entirely from the trial (if whatever the effect is is deemed likely to hide more valuable yet smaller data from other drugs)

jdoe2020 2y ago
Then your get dropout problems and by the time there is an effect you don't have the statistical power to detect it. You need 3-6 months on an AD, psychiatic, metabolic, or autoimmune drug to see a Real effect so that is how long you must wait to ramp the dose. It could take years to go from a conservative guaranteed nontoxic dose to an effective one. But in that time most patientss will have gotten tired of waiting and switched drugs, moved to a new city and dropped out of the trial, or die. Sure it could work for some things like antimicrobials or erectile dysfunction drugs that have a rapid response, but that isn't where most of the drug development is. It is in those categories I listed.
mlyle 2y ago
In addition to what the person has already said: An "obvious" effect is harder to spot than you think. Asking for statistical power to spot an effect in a week when you're trying a dozen compounds at once-- you'd need millions enrolled in this study, and they'd need to be very patient.