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Posted On: 08/19/2020 2:39:39 PM
Post# of 154062
Here's the thing: Very often (in about 50%) larger Phase 3 trials, even with same endpoints as in Phase 2 don't replicate the results! Which is why only in rare cases regulators approve on Phase 2, and even then require a further study to confirm the findings...
https://www.acsh.org/news/2020/06/11/clinical...area-14845
In fact, in some large indications like MS and Alzheimer's, FDA usually requires TWO pivotal Phase 3 trials with 300 patients to definitely show success.
Here is a great case study showing drugs with great Phase 2 results that failed in Phase 3:
https://www.google.com/url?sa=t&source=we..._U1YH6GSh7
In fact, NP's description of the purpose of Phase 2 trials is not entirely accurate: as a rule, Phase 2 trials establish safety and efficacy (and sometimes serve to find the right dose) in a smaller population, and if successful, warrant a Phase 3 which serves to confirm those findings in a larger population... In diseases where it is not yet understood what a meaningful clinical endpoint looks like, NP's statement is more accurate...
In any case, even if FDA decides to grant EUA, they will, due to our small sample size, mostly likely ask for a confirmatory study, purely out of statistical reasons.
To put it differently: when tested in a smaller population (Phase 1+2), it is much more likely - due to mere chance/a statistical error - that a drug seems to work although it does in fact nothing, which is why you do larger Phase 3 studies, because in a big population such a statistical error can be ruled out with much higher confidence... That's the reason so many drugs fail going from Phase 1 to Phase 2 and Phase 3...
https://www.acsh.org/news/2020/06/11/clinical...area-14845
In fact, in some large indications like MS and Alzheimer's, FDA usually requires TWO pivotal Phase 3 trials with 300 patients to definitely show success.
Here is a great case study showing drugs with great Phase 2 results that failed in Phase 3:
https://www.google.com/url?sa=t&source=we..._U1YH6GSh7
In fact, NP's description of the purpose of Phase 2 trials is not entirely accurate: as a rule, Phase 2 trials establish safety and efficacy (and sometimes serve to find the right dose) in a smaller population, and if successful, warrant a Phase 3 which serves to confirm those findings in a larger population... In diseases where it is not yet understood what a meaningful clinical endpoint looks like, NP's statement is more accurate...
In any case, even if FDA decides to grant EUA, they will, due to our small sample size, mostly likely ask for a confirmatory study, purely out of statistical reasons.
To put it differently: when tested in a smaller population (Phase 1+2), it is much more likely - due to mere chance/a statistical error - that a drug seems to work although it does in fact nothing, which is why you do larger Phase 3 studies, because in a big population such a statistical error can be ruled out with much higher confidence... That's the reason so many drugs fail going from Phase 1 to Phase 2 and Phase 3...
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