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I want to do a double- blind sham controlled clinical trial of a laser therapy for a skin disease. As the primary endpoint is change in inflammation between pre and post treatment/sham biopsies I expect the sham arm to have very little to no effect. I expect that the treatment will have moderate-high improvement- lets say 60%.

Because of cost issues, I would prefer the active treatment arm to be 20 patients. Can you tell me how many patients I need in the control arm? Can I get away with 10?

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Doing pre- and post-treatment biopsies in a sham-controlled group whom you expect (by your own admission) to enjoy no benefit seems grossly unethical. You would expose the sham subjects to pain and other potential harms from the biopsies, without any benefit. Could you not employ photographic and symptomatic assessments of this dermatologic condition?

Also, if this is a skin disease with multiple lesions, can you not use subjects as their own controls, by randomly exposing (or masking) some lesions on each subject? Thoughtful design could surely blind subjects to which among their lesions received active laser treatment.

Furthermore, would you not do better to investigate a dose-response curve? Does the proposed laser treatment have any potential harms? Can you select two doses (e.g., laser intensities or durations of treatment sessions) about which you and your colleagues have equipoise regarding the balance between harms (or burdens, due e.g. to lengthy or frequent treatment sessions) and efficacy?

Would the disease by any chance be hidradenitis suppurativa (HS)? (I am guessing this based on your tag 'obstetrics' and your interest in an inflammatory skin condition thought to be treatable by laser.) It would improve your question to identify whatever disease you are dealing with, providing a link to a lay explanation of it. Please also clarify whether the laser treatments are repeated, such that you have longitudinal assessments in this trial. In that case, ethics might demand adaptive design.

In closing, I would like to emphasize that you cannot consider your trial ethical unless you would willingly allow your mother or sister to be enrolled and randomly assigned to any of its arms.


Addendum: In follow-up to the brief exchange with Frank Harrell below, I offer the following open-access references (neither comprehensive nor even representative) that may prove useful to someone dipping a toe into clinical trial ethics.

  1. Sackett DL. Why randomized controlled trials fail but needn’t: 1. Failure to gain “coal-face” commitment and to use the uncertainty principle. CMAJ. 2000;162(9):1311-1314. Free full text

  2. Shapiro SH, Glass KC. Why Sackett’s analysis of randomized controlled trials fails, but needn’t. CMAJ. 2000;163(7):834-835. Free full text

  3. Sackett DL. Equipoise, a term whose time (if it ever came) has surely gone. CMAJ. 2000;163(7):835-836. Free full text

  4. Berry DA. Bayesian Statistics and the Efficiency and Ethics of Clinical Trials. Statist Sci. 2004;19(1):175-187. doi:10.1214/088342304000000044. Free full text

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    $\begingroup$ David there have been ethical sham surgical trials including neurosurgery, a sham broncosopic ablation study, and sham knee surgery studies. How do those differ? $\endgroup$ – Frank Harrell Jul 3 '17 at 2:52
  • $\begingroup$ Frank, thank you for highlighting these examples. In truly ethical sham trials, one must suppose that the surgery yields 'benefits' of the placebo sort—an expectation famously borne out in cases such as knee arthroscopy and mammary artery ligation. The OP has however announced outright an expectation that the sham group will derive "very little to no" benefit from the sham treatment. Accordingly, in light of the the biopsy's potential harms, the trial as described is unethical. This is especially true considering the alternative designs available, with their possibilities for strong inference. $\endgroup$ – David C. Norris Jul 3 '17 at 3:51
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    $\begingroup$ Thanks for the thoughts. I think it's worth much more discussion - wish there were a research ethics site as active as this stats site. Need to consider among other things the state of knowledge and what are acceptable risks as perceived by patients. $\endgroup$ – Frank Harrell Jul 3 '17 at 11:22
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    $\begingroup$ I agree heartily on the 'state of knowledge' point; at some time in human history, surely even discretizing a continuous outcome was ethical, simply because no well developed alternative existed. I also agree that a research ethics discussion site would have great value. In any case, I will expand on my answer above in light of our conversation, providing several related citations of general interest. $\endgroup$ – David C. Norris Jul 3 '17 at 12:18

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