3+3 Design [Design Issues]

posted by Ohlbe – France, 2020-01-07 11:25  – Posting: # 21063
Views: 355

Dear Pharma_88,

» This is regarding 3+3 design for Phase-I trial.

Are you referring to Phase I trials in patients, mostly in oncology ? My experience in such trials is that you start each cohort with 3 patients, if you have 0 or 1 patient experiencing a dose-limiting toxicity (DLT) after e.g. 1 month you can enrol 3 more. Depending on the total number of DLT in these 6 patients you may then progress to the next dose level. If 2 or 3 of the first 3 patients have a DLT you stop there and you don't increase the dose to the next cohort. Is this what you have in mind ?

» My Question is that once the group/cohort is completed with 3 patients, whether same patients will be enrolled in next cohort or new patient will be enrolled?

In the design I have in mind, the group/cohort is completed with 3+3 patients, not just 3. And you enrol new patients in each cohort (if you only use the same patients who have a good tolerability, you have some bias).

» Further, in next cohort suppose 1 patient is withdrawn or have some AE then its compulsory to add 3 more patients to inline with multiplication of 3?

If a patient is withdrawn due to a DLT, see my first paragraph. The patient is not replaced. If he is withdrawn for another reason: you really have to be extra-sure it is really totally unrelated to a DLT. You may decide to replace that patient (meaning, only 1 extra-patient). Make sure this is properly defined in your protocol. I would not use 3 patients to replace just 1.

Regards
Ohlbe

Complete thread:

Activity
 Admin contact
20,250 posts in 4,262 threads, 1,398 registered users;
online 17 (0 registered, 17 guests [including 10 identified bots]).
Forum time (Europe/Vienna): 06:46 CET

No written law has ever been more binding than
unwritten custom supported by popular opinion.    Carrie Chapman Catt

The Bioequivalence and Bioavailability Forum is hosted by
BEBAC Ing. Helmut Schütz
HTML5