4 ms·

You sound like you understand this process well, so dumb question: why is the Phase 3 process so rigid? Wouldn't it make more sense to simply have multiple inc

You sound like you understand this process well, so dumb question: why is the Phase 3 process so rigid? Wouldn't it make more sense to simply have multiple inclusion criteria, (e.g. broad, more targeted, and same as Phase 2) and collect enough data in the front to be able to discriminate the patient at an individual level? That way if Phase 3 for 'broad' criteria fail, you can still demonstrate the drug works for a more strict population and maybe actually release it with that on the label? This also avoids data mining (where you keep looking for subsets until one seems to pass your significance criterion) since you came up with the criteria ahead of time.

danieltillett 8y ago
The reason why is that you can’t make any money just selling to the sub-population in many cases. Yes you are right that you can design the trial to identify the sub-population that the drug works in. Sometimes drug companies do do this, but if they are going to go down this path they normally run a tighter Phase 3 trial and then try to expand post-approval by running more trials. It is all a cost/benefit analysis taking into account the patent life and lots of other commercial factors. The point I was making is that a high failure rate at Phase 3 is to be expected given the marketing needs of the company. A Phase 3 trial is not just a scientific exercise in proving a drug works, it is a complex balancing act where commercial concerns are critical.
lekanwang 8y ago
You'll need more patients, which is expensive. But yes, you're actually right -- sponsors do run stratified phase 3 trials where subsets of patients are measured independently per pre-approved statistical analysis plan. The rub is that your patient population and your trial design needs to be sufficiently statistically powered to do that kind of analysis. The required number of patients quickly increases for the number of stratifications/subsets you're trying to prove an indication for, and patients are extremely expensive, so sponsors generally try to run the smallest trial possible while still being adequately statistically powered. This is generally why in Phase IIs, sponsors will stratify by exploratory biomarkers, where there may not be sufficient statistical power per stratification, but can give them some idea for what to include in the IIIs.

danieltillett 8y ago

The reason why is that you can’t make any money just selling to the sub-population in many cases. Yes you are right that you can design the trial to identify the sub-population that the drug works in. Sometimes drug companies do do this, but if they are going to go down this path they normally run a tighter Phase 3 trial and then try to expand post-approval by running more trials. It is all a cost/benefit analysis taking into account the patent life and lots of other commercial factors. The point I was making is that a high failure rate at Phase 3 is to be expected given the marketing needs of the company. A Phase 3 trial is not just a scientific exercise in proving a drug works, it is a complex balancing act where commercial concerns are critical.

lekanwang 8y ago

You'll need more patients, which is expensive. But yes, you're actually right -- sponsors do run stratified phase 3 trials where subsets of patients are measured independently per pre-approved statistical analysis plan. The rub is that your patient population and your trial design needs to be sufficiently statistically powered to do that kind of analysis. The required number of patients quickly increases for the number of stratifications/subsets you're trying to prove an indication for, and patients are extremely expensive, so sponsors generally try to run the smallest trial possible while still being adequately statistically powered. This is generally why in Phase IIs, sponsors will stratify by exploratory biomarkers, where there may not be sufficient statistical power per stratification, but can give them some idea for what to include in the IIIs.