4 ms·

After looking at the first few examples I skimmed the summary header, ALL of the (examples of) phase 3 failures include lack of efficacy (some also lack of safe

After looking at the first few examples I skimmed the summary header, ALL of the (examples of) phase 3 failures include lack of efficacy (some also lack of safety) as the main failure. Since medial trails are very expensive and time consuming, I can't help but wonder if identifying this would have been possible from prior phases, possibly with better study design of at least the phase 2 version of the study.

jcranmer 8y ago
The problem is that we don't have any reliable means to predict in vivo efficacy. Recognizing failed attempts earlier means substantial reductions to the cost of drugs (i.e., cost savings on the order of hundreds of millions of dollars), so there is very strong financial incentive to stop projects that will fail phase 3 as early as possible. Pretty much every pharmaceutical company has as its "what we'll start doing better" goal as killing off failures earlier. That nothing has appreciably changed in this regard suggests that the fix is beyond our current capabilities--human biology is simply too complicated and too confusing for us to reliably predict at this point.
Fomite 8y ago
Figuring this out is a "and now I am rich beyond avarice" scale problem.
aaavl2821 8y ago
The most commonly cited study of success rates across trials lists Phase 3 probability of success, in aggregate, at 70% [0] Phase 2 success rate is 34%. Phase 3 studies are more expensive than Phase 2, but the higher failure rate in Phase 2 makes Phase 2 failure the largest driver of the cost of drug development. Because predicting Phase 2 success from earlier stage data is a daunting task, the industry has started tackling this issue by "failing faster / cheaper", getting to Phase 2 data quickly and cheaply, to reduce the cost of Phase 2 failure. However, companies don't want to fail -- so they sometimes design Phase 1/2 proof of concept studies to increase chance of success rather than increase truth finding. This may end up causing the Phase 3 failure rate to increase, though there isnt yet data to prove this. The IDO-PD1 failure from Merck / Incyte could be interpreted as an example of this phenomenon I wrote a blog post that in part discusses ways companies are trying to reduce cost of Phase 2 failure: https://newbio.tech/blog/bio_startup_ideas.html https://newbio.tech/blog/bio_startup_ideas.html [0] https://www.ncbi.nlm.nih.gov/pubmed/20168317 https://www.ncbi.nlm.nih.gov/pubmed/20168317
comex 8y ago
Actually, 1 out of the 22 (Olanzapine Pamoate) only had lack of safety, not lack of efficacy. It went on to be approved with a “Risk Evaluation and Mitigation Strategy”.

jcranmer 8y ago

The problem is that we don't have any reliable means to predict in vivo efficacy. Recognizing failed attempts earlier means substantial reductions to the cost of drugs (i.e., cost savings on the order of hundreds of millions of dollars), so there is very strong financial incentive to stop projects that will fail phase 3 as early as possible. Pretty much every pharmaceutical company has as its "what we'll start doing better" goal as killing off failures earlier. That nothing has appreciably changed in this regard suggests that the fix is beyond our current capabilities--human biology is simply too complicated and too confusing for us to reliably predict at this point.

Fomite 8y ago

Figuring this out is a "and now I am rich beyond avarice" scale problem.

aaavl2821 8y ago

The most commonly cited study of success rates across trials lists Phase 3 probability of success, in aggregate, at 70% [0] Phase 2 success rate is 34%. Phase 3 studies are more expensive than Phase 2, but the higher failure rate in Phase 2 makes Phase 2 failure the largest driver of the cost of drug development. Because predicting Phase 2 success from earlier stage data is a daunting task, the industry has started tackling this issue by "failing faster / cheaper", getting to Phase 2 data quickly and cheaply, to reduce the cost of Phase 2 failure. However, companies don't want to fail -- so they sometimes design Phase 1/2 proof of concept studies to increase chance of success rather than increase truth finding. This may end up causing the Phase 3 failure rate to increase, though there isnt yet data to prove this. The IDO-PD1 failure from Merck / Incyte could be interpreted as an example of this phenomenon I wrote a blog post that in part discusses ways companies are trying to reduce cost of Phase 2 failure: https://newbio.tech/blog/bio_startup_ideas.html https://newbio.tech/blog/bio_startup_ideas.html [0] https://www.ncbi.nlm.nih.gov/pubmed/20168317 https://www.ncbi.nlm.nih.gov/pubmed/20168317

comex 8y ago

Actually, 1 out of the 22 (Olanzapine Pamoate) only had lack of safety, not lack of efficacy. It went on to be approved with a “Risk Evaluation and Mitigation Strategy”.