Timeline for Are the arguments that placebo can be unethical mistaken?
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11 events
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| Mar 1, 2022 at 17:22 | comment | added | Todd D | @AdamO For patients in a trial, ethics can get muddy. For a new treatment that shows benefit at an interim analysis, is it unethical to continue to administer placebo? Most trialists argue that equipoise still exists for placebo or usual care despite a potential benefit of active treatment; this stance is largely motivated by issues of false positives at interim analysis and the need to continue the study until a conclusive result is reached to value the efforts of those persons who remain enrolled in the trial. | |
| Mar 1, 2022 at 17:13 | comment | added | gung - Reinstate Monica | If you look at Figure 2, you can see a range of outcomes are consistent with the hypothesis of non-inferiority, & good enough to move forward. Defining & justifying the non-inferiority margin can be tricky, & there are special problems such as biocreep & assay insensitivity. But the fact remains that you can just test new Tx vs existing Tx against a non-inferiority null when there is an accepted Tx. This approach is not terribly common, but neither is it rare (104 published last year). | |
| Mar 1, 2022 at 17:07 | comment | added | gung - Reinstate Monica | @AdamO, if there's a condition for which there is an accepted, effective treatment, the IRB isn't usually going to let you test a new treatment vs placebo, because the placebo patients are untreated for the condition. If you believe your new Tx is as good as the existing 1, you don't want to do a superiority trial, because you don't believe your Tx is superior. You could do an equivalence trial, but it isn't a problem if yours turns out to be better. So you just do a NI trial against the standard Tx. It doesn't have to be old + new Tx vs old + placebo, & it doesn't have to be equivalence. | |
| Mar 1, 2022 at 16:43 | comment | added | AdamO | @ToddD I would argue in your HIV trial, the argument for or against placebo has to do with participation bias, and ultimately the validity of the trial. This is ok if we mean ethics in a broader sense of policy and messaging, not a direct violation of the Helsinki declaration. I was moreover interested in the ethical treatment of patients in a trial. | |
| Mar 1, 2022 at 16:39 | comment | added | AdamO | @gung-ReinstateMonica reading the Wittes paper you link, I understand what she calls a "non-inferiority" trial refers specifically to a trial that's designed with a non-inferiority margin and powered to test the hypothesis of non-inferiority, irrespective of the actual treatments assigned. My understanding is the same as Todd D. One can still test superiority in a trial where patients randomly receive investigational treatment vs usual care, even without blinding in fact. | |
| Feb 26, 2022 at 3:15 | comment | added | gung - Reinstate Monica | I'm a biostatistician, I'm familiar w/ the medical literature. A is as good as B can include A is better than B. An entity promoting a new intervention of some kind would be perfectly happy if it turns out to be better than an existing approach. They only need to show it's not worse. Non-inferiority is not so exotic. It's covered in intro clinical trials texts such as Friedman et al, Fundamentals of Clinical Trials. A pubmed search finds 104 NI trials published last year. It may help you to read this explainer. | |
| Feb 25, 2022 at 19:47 | comment | added | Todd D | In the medical literature, studies that test whether A is as good as B are termed "equivalency trials." These are rarely performed due to the very large sample sizes required and a lack of interest in whether A is as good as B. Medical device studies are an exception to this rule; the Food and Drug Administration only requires that a new device be non-inferior or equivalent to an existing device. | |
| Feb 25, 2022 at 19:43 | comment | added | gung - Reinstate Monica | Non-inferiority can be used to show that A is 'just as good as' B. It doesn't have to be harm. | |
| Feb 25, 2022 at 19:32 | comment | added | Todd D | That is a reasonable group assignment, but non-inferiority refers to a statistical procedure where one only seeks to determine whether treatment A is more harmful than B (ie, A is not inferior to B on the basis of harm). | |
| Feb 25, 2022 at 19:29 | comment | added | gung - Reinstate Monica | It can also be usual care vs new treatment. Both arms get some Tx. This is called a "non-inferiority trial". | |
| Feb 25, 2022 at 19:25 | history | answered | Todd D | CC BY-SA 4.0 |