Bioequivalence and Bioavailability Forum

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❝ Further, in next cohort suppose 1 patient is withdrawn or have some AE then its compulsory to add 3 more patients to inline with multiplication of 3?

If a patient is withdrawn due to a DLT, see my first paragraph.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 If he is withdrawn for another reason: you really have to be extra-sure it is really totally unrelated to a DLT.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