Placebo tribulations

In his commentary, Charles Weijer poses interesting and challenging questions regarding placebo-controlled clinical drug trials.1 However, it is unfortunate that he chooses to make negative and unsubstantiated assertions about for-profit research ethics boards (REBs), lumping them all together.

He states that the failures of university teaching hospital REBs are attributed to “lack of clarity … regarding the need for adherence to the Tri-Council Policy Statement” while for-profit REBs are assailed because of “obvious conflicts of interest doing ethics reviews.” Why is the latter an “obvious” conflict of interest? Getting paid for work does not necessarily compromise judgement.

We would suggest that the members of most for-profit REBs are guided, or should be, by the same ethical standards as are the members of university teaching hospital REBs. For example, the members of the latter are subject to the same conflicts of interest because university teaching hospitals receive “overhead” funds whenever a study is done at that institution. Moreover, the voting members of university teaching hospital REBs regularly review studies submitted by their colleagues and thus potentially have more conflicts of interest than do the members of for-profit REBs. Our institutional review board (IRB) is totally independent, without a research arm, and is well positioned to pass judgement on the merits of a particular study. We are completely independent of outside pressures and able to consider the safety of the patient foremost, providing the study has scientific merit.

We would like to point out that our IRB rejected an unethical study involving an angiotensin-converting enzyme (ACE) inhibitor versus an angiotensin-II blocker versus placebo in diabetics with proteinurea, although 7 Canadian university teaching hospital boards approved it. Only 1 university teaching hospital REB rejected it. What's even more worrisome is that this particular study had been running for more than 2 years before it was sent to us, and each of the approving university teaching hospital REBs had extended the approval. None shut it down despite incontrovertible evidence of the ACE inhibitor's nephroprotective effect during the continuing review period.

We also restricted approval of a study with a new thrombolytic agent to 3 months due to safety concerns, although a university teaching hospital REB approved it for 1 year. Why did we restrict it? Because we knew of an exsanguinating hemorrhage with the study compound that occurred at the hospital REB's sister hospital. The bleeding could not be stopped, and the case was discussed during the university's cardiology department rounds. Despite this occurrence, the REB apparently did not review their approval or require changes to the consent form, despite information from their own investigators that the study drug might cause life-threatening bleeding.

How do we know about the hospital REBs' decisions? Because in each instance we were told by the sponsor or the principal coordinating investigator when we refused to approve these studies that “you are the only one to refuse!”

In several other cases, we have rejected unethical studies that other REBs have not (see the complete letter at www.cmaj.ca).

Weijer should also consider the well-publicized ethical problems at prestigious US academic institutions such as Duke, Virginia Commonwealth, Johns Hopkins, Pennsylvania and the Fred Hutchinson Cancer Institute, not omitting the sad Poisson breast cancer trial at the University of Montreal.

In the US, the FDA inspects both the private and university teaching hospital REBs. Yet, all the above major problems found by Food and Drug Administration or Office for Human Research Protections inspections have been at academic institutions.

Legitimate differences of opinion will always exist in a free society. Improving the protection of human research subjects is everyone's concern and responsibility — whether a particular study is vetted by an REB in the university/public study sector or private sector.

Jack Corman President Morris A. Blajchman Alternate Chairman Allan Knight Chairman IRB Services Aurora, Ont.