The tension between scientific validity and ethical concerns (November 17, 2006) Category: Placebo controlled trials

A question on the IRB Forum email discussion group (from RI) centered on the ethical concerns about using a placebo arm in a study involving control of pain. There are scientific reasons why a placebo control group are important, but is it ethical to ask research subjects to possibly endure some greater level of pain in order to achieve certain scientific goals?

If the amount of pain is minor, I would argue that an IRB's effort to protect the research subjects veer towards paternalism. Just make sure that the research subjects know what they are in for.

If there is the potential for substantial pain, then things become more complicated. There is no consensus in the scientific community about placebos, so you can find support for pretty much any position from "placebos are never acceptable when an active control is available" to "placebo surgery is an acceptable research option."

A good starting point for this debate is the  International Conference on Harmonization (ICH) report E-10 which discusses the use of placebos and various alternative designs in great detail. The big advantage of knowing ICH E-10 inside and out is that it is an authoritative summary of the most permissive perspective on placebos. So if ICH E-10 doesn't support the use of placebos, nothing will.

It is also important to recognize that there is some tension here between the use of a placebo (or scientific validity in a broader sense) the desire to avoid undue pain and suffering (ethical concerns in a broader sense). A research design  that is more attractive from one perspective is often less attractive from the other perspective.

That's not to say that the two concerns are mutually exclusive. A trial that raises ethical concerns with the IRB is likely to raise similar concerns with the patients, leading to a subsequent degradation of scientific validity when large numbers of patients drop out or refuse to join the study in the first place.

On the flip side of the coin, it is unethical to ask patients to sacrifice the time, to undergo painful procedures, or to assume a greater degree of risk if it is for a trial that has limited scientific merit.

So while scientific validity and ethical concerns will often seem to be in conflict, you can actually justify scientific validity from an ethical perspective and you can justify ethical concerns from a scientific validity perspective.

07/08/2008.