What are ethical considerations for a trial with a pre-study washout period?

Question:

Question edited from the original:  We are working with a sponsor on the design and conduct of a double-blind placebo-controlled study of an investigational new drug for Alzheimer’s disease. The study design includes a one-month washout period prior to the trial. Does this study design raise ethical issues for the IRB?

– Director, Clinical Research Organization

Answer:

To approve research involving human subjects, IRBs are required to determine that seven regulatory criteria are met. One of the seven criterion for the approval of human research says that “the risks to subjects are reasonable in relation to anticipated benefits, if any, to subjects, and the importance of the knowledge that may be expected to result.”

To approve any study that includes a pre-study washout period or taking participants off their current medications for the duration of the study, the sponsor would need to be able to demonstrate that the risks of stopping the medication are reasonable. 

There may be some circumstances where this is not difficult to demonstrate, for example, if the regimen that the potential participant is taking is not working very well for them; if they are experiencing have a lot of side effects with their current regimen;  or the duration of the study is short, so the time that time off their medication is limited. 

But if someone is on a stable regimen of treatment and their symptoms relatively well controlled, it may be difficult to make the ethical argument that they should stop that treatment to start an experimental therapy with unknown safety and efficacy.  It is even harder to make the ethical argument that they should stop a treatment that works well enough for them to go on a placebo for an extended period.

With Alzheimer’s disease, the sponsor may be able to make these arguments.  There are medications that are approved for Alzheimer’s that may not do much to alleviate the symptoms of AD. If the sponsor can provide data to show that participants are unlikely to be worse off their medications than they are on the medications, and there is a good rationale for why the new drug can’t be tested on a background of current therapy, the IRB may find this argument acceptable.