3+3 Design [Design Issues]

posted by Pharma_88 – India, 2020-01-08 10:55 (1542 d 01:07 ago) – Posting: # 21065
Views: 2,755

❝ 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 ?


yes. Same design.

❝ 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).


Yes. but intial cohort (means first one) is started with 3 patients only. subsequent cohort will have 3+3 patients. Right?

❝ ❝ Further, in next cohort suppose 1 patient is withdrawn or have some AE then its compulsory to add 3 more patients to inline with multiplication of 3?


❝ If a patient is withdrawn due to a DLT, see my first paragraph.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 If he is withdrawn for another reason: you really have to be extra-sure it is really totally unrelated to a DLT.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


So, in this case, total 4 patients are required to enroll (1 for replacement and 3 others). Correct?


Edit: Full quote removed. Please delete everything from the text of the original poster which is not necessary in understanding your answer; see also this post! [Ohlbe]

Complete thread:

UA Flag
Activity
 Admin contact
22,957 posts in 4,819 threads, 1,636 registered users;
129 visitors (0 registered, 129 guests [including 15 identified bots]).
Forum time: 12:02 CET (Europe/Vienna)

With four parameters I can fit an elephant,
and with five I can make him wiggle his trunk.    John von Neumann

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