Evaluating the risks and benefits of phase II and III cancer clinical trials: a look at Institutional Review Board members in the Netherlands.

13 T he Declaration of Helsinki and other national and international regulations oblige Institutional Review Boards (IRBs) to weigh the risks of medical research against its benefits, and to assess the ratio between the two. In the Netherlands, the Medical Research Involving Human Subjects Act (WMO) states that a review committee may only approve a research study when " it is reasonable to expect that the risk to and burden for the subject will be in proportion to the potential value of the research. " 1 In order for a study to be approved, this risk-benefit ratio must, in the IRB's opinion, be " favorable, " " in balance, " or " proportional. " This assumes that IRBs are sufficiently aware of which risks the medical research community and society, in general, find acceptable in relation to which benefits. The extent to which this assumption is justified in practice is open to question , especially considering the vague description of this requirement in the various regulations. The requirement for a favorable risk-benefit ratio further presupposes that IRBs know what is important to research participants with respect to their protection. Whether this assumption is justified is also unknown. For example, there are indications that patients' experiences of recruitment to early phase cancer trials and their perceptions of the informed consent process reflect a lack of understanding of the trial in which they are taking part. 2 This may be due, in part to vagueness, inconsistency, and overstatement of benefit in the consent forms for these trials. 3 The absence of clear criteria for assessing the risk-benefit ratio has been identified as a weak link in the IRB review process. 4 Previous studies have indicated that IRB members find risk-benefit ratio assessments to be one of the most difficult tasks involved in reviewing research protocols. 5 For example, van Luijn et al., found that phase II cancer protocols provide too little information relating to the evaluation of cost-benefit and scientific issues; that IRB members felt less than fully competent in carrying out such evaluations; that only a small minority of IRB members weigh risks and benefits against each other in a systematic way, rather than intuitively; and that one-third of IRB members did not determine the risk-benefit ratio themselves , but rather preferred to leave that to the individuals being recruited for the studies. 6 The results of another study indicated that …