A team of researchers from The Netherlands report that members of Institutional Review Boards (or ethical committees) use a variety of ways to identify, estimate and evaluate the risks and benefits associated with phase two clinical cancer trials, and their approach often depends on their own professional background.
However, Professor Neil Aaronson, Head of the Division of Psychosocial Research and Epidemiology at The Netherlands Cancer Institute in Amsterdam and senior author of the paper, says this is not necessarily a problem because the ethical committees reach collective decisions on whether or not to grant approval to clinical trials, and the different experiences of the individual members may actually strengthen the decision-making process. "Undoubtedly the whole is more than the sum of its parts," he said.
The study, carried out by Dr Heleen van Luijn of the Institute for Ethics at the Vrije University in Amsterdam, involved interviews with 53 members of Institutional Review Boards (IRBs) from six research hospitals and specialist cancer centres in The Netherlands. The IRB members were asked about their attitudes, beliefs and experiences in evaluating the risk/benefit ratios of phase two clinical trials. In particular, they focused on: how members identified the risks and benefits of trials; how much information they needed to make a risk/benefit assessment and whether such information is usually available in phase two clinical trial protocols; how they perceive their own competence in making risk/benefit assessments; and how they evaluate specific risks and benefits of the trials to participating patients, future cancer patients and to medical science in general.
The team found that all of the IRB members identified the potential for developing more effective cancer therapies as the primary benefit to future patients and to medical science from the phase two clinical trials. But there was far more variability in the way individual members weighed up the other pros and cons of the trials for participating patients – only 12% of members weighed up risks and benefits systematically, and when asked what decisive factors influenced their assessment of a trial, 34% of members said they did not make a risk/benefit calculation.
Prof Aaronson said: "Most of the decision strategies followed do not reflect a process of weighing risks and benefits against each other in a systematic way, but rather involve gaining an overall impression (20% of members), considering what alternative treatments are available (15%), or considering whether one would be willing to undergo the trial-based treatment oneself or would advise a family member to do so (10%). Twelve per cent said weighing risks and benefits was a task for the committee as a whole, rather than for individual members and 17% said they left it up to the patients to decide whether the risks of the trial outweighed the benefits. This last finding is somewhat disconcerting in light of the evidence that patients are often unable to understand fully the information provided to them about the clinical trials in which they are invited to participate."
The study has flagged up issues surrounding the information supplied to IRBs and the members' perception of their competence in evaluating trials. Although the majority of members said that trial protocols contain enough information about the types of risks and benefits of a trial, a substantial percentage (between 25% and 60%) reported that too little information is available about more specific issues such as the likelihood, magnitude and duration of such risks and benefits. A substantial minority of members (15% to 40%) reported feeling less than fully competent to evaluate risks, and this was particularly the case for the non-physician members of the committees.
However, Prof Aaronson commented: "This does not necessarily suggest a problem. The decision regarding the acceptability of a trial in risk-benefit terms is made by the IRBs as a whole. The non-physician members are relatively dependent on the judgement of their medical colleagues when it comes to clinical issues being discussed. However, they can contribute significantly to the process by commenting on the practical, ethical and legal aspects of trials. Additionally, it is often the case that, given the heterogeneous composition of IRBs, the clinicians are forced to explain clinical issues in terms that are understandable to non-physicians. This may bring certain issues to light that need clarification, for instance in the written information provided to patients.
"Training for IRB members would undoubtedly be useful but, in general, it is my impression that the collective expertise and experience of IRB members is what really counts. The different methods used by IRB members to evaluate the risks and benefits are not mutually exclusive, and reflect the rather complex nature of this task."
The researchers conclude that IRB members view phase two clinical trials primarily as a vehicle for testing new therapies that may be of benefit to future patients and to medical science in general. Dr Luijn said: "While this is in line with the goals and objectives of the vast majority of phase two trials, it may not reflect the expectations of patients themselves, who often choose to participate in such trials in the hope that the treatment will prove to be clinically effective. This underscores the need to provide potential patients with sufficient information to make informed decisions, and to ensure that such decisions are appropriately motivated."
The researchers say that, although their study was restricted to members of IRBs from The Netherlands, they believe the results of this study are relevant to other countries because ethical committees in other European countries and in North America are quite similar in respect of their basic structure, objectives and procedures for protocol review.
* Assessment of the risk/benefit ratio of phase two cancer clinical trials by Institutional Review Board (IRB) members. Annals of Oncology. H.E.M. van Luijn, A.W. Musschenga, R.B. Keus, W.M. Robinson & N.K. Aaronson. Vol 13. No. 8. pp 1307-1313.
Journal
Annals of Oncology