Question

A group of prominent nephrologists convened in Montréal to discuss a new immunosuppressant drug that was thought to reduce the incidence of organ rejection in solid organ transplant recipients. In a phase II trial, 150 transplant recipients received the drug and the incidence of rejection was 10% over one year of follow-up. To date, no phase III trials of the new drug have been conducted.

(a) One nephrologist thought the results were so stunningly positive that he argued guidelines should be drafted to make the new drug a first line treatment option. Do you agree? Why? [4]

(b) Another nephrologist told the group that she was currently trying the new drug on 10 patients. She offered to treat 10 other patients with the standard immunosuppressant drug and compare results. List four potential problems with this proposed study (just list – no need to discuss or elaborate). [4]

Answer 1

SOLUTION:-

(a) The ideal response would be to disagree.Phase ll (and earlier phase l) trials do not involve a comparison group. Consequently, it is too early to recommend that the new drug become a first-line treatment. The drug should be compared to an existing, standard immunosuppressant (or placebo) to examine whether the 10% rejection rate is better or worse than something else.

(b) The guiding ethical principal to justify an RCT is that there is general uncertainty in the medical community about teh efficacy of a treatment. In this case, general uncertainty exists: some nephrologists like the new drug, others do not, and others are neutral. Further study is required to give a clearer picture of the efficacy of the new drug.

From an ethical standpoint, the troubled physician would be justified in participating in the RCT (because there is general uncertainty in the medical community).

NB: The notion of clinical equipoise posits that there should be general uncertainty only in the "expert" medical community. However, defining an 'expert' and agreeing on who these people are might not be easy.