3+3 Design [Design Issues]

posted by Ohlbe – France, 2020-01-07 12:25 (1060 d 10:47 ago) – Posting: # 21063
Views: 2,483

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❝ Further, in next cohort suppose 1 patient is withdrawn or have some AE then its compulsory to add 3 more patients to inline with multiplication of 3?


If a patient is withdrawn due to a DLT, see my first paragraph.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 If he is withdrawn for another reason: you really have to be extra-sure it is really totally unrelated to a DLT.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:

UA Flag
Activity
 Admin contact
22,423 posts in 4,694 threads, 1,600 registered users;
11 visitors (0 registered, 11 guests [including 9 identified bots]).
Forum time: 23:13 CET (Europe/Vienna)

The rise of biometry in this 20th century,
like that of geometry in the 3rd century before Christ,
seems to mark out one of the great ages or critical periods
in the advance of the human understanding.    R.A. Fisher

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