Often lost in the glitter of T1, however, is the nettlesome challenge of taking clinical findings and translating them into community practice. Such T2 research in many cases involves 'phase 4' studies: trials that test a drug that has already been licensed by regulatory authorities.
A few years ago, I organized a research ethics symposium at McGill on phase 1 and phase 4 studies, titled "Dirty Business?" because such studies are often perceived as the most ethically suspect (the former because of their risk-benefit balance, the latter because they are often drug promotion masquerading as science).
The current issue of Annals of Internal Medicine features an article "The ADVANTAGE Seeding Trial: A Review of Internal Documents" (August 19, 2008) where Kevin P. Hill and co-authors show that Merck ran and published the ADVANTAGE study primarily to promote Vioxx sales(gasp!) rather than to answer a question about the drug's performance.
In an editorial accompanying the article, editors Drummond Rennie and Harold Sox condemn such "seeding trials" and offer a series of recommendations for ending this abuse of study volunteers and health care professionals. Specifically, they urge physicians and IRBs to "ask... about the study hypothesis and whether it addresses a settled question... they should look for clues [that it does]: such as a sttudy with an open label design, no control group, a very large projected enrollment relative to the importance of the question, a short-term study of a chronic disease, a study of an already approved drug...."
Rennie and Sox couch the ethical problem with seeding trials as one of risk– "few physicians would knowingly enroll their patients in a study that placed them at risk in order to provide a company with a marketing advantage." But in my opinion, IRBs are reasonably good at sniffing out risk and harm. Where they underperform is in assessing value. In my experience, IRBs seem to take the attitude "if nobody is going to get hurt, what the heck?" Phase 4 studies are generally harmless– probably more so than typical medical practice. What is troubling about them is that they are often valueless and– in the case of seeding studies– deceptive as well. And current review procedures at IRBs, focused as they are on risks rather than ends, are ill equipped (and frankly unmotivated) to staunch such unethical conduct. (photo credit: nutmeg66 2007)