Ethical implications of cluster-randomized trials
Ethical implications of cluster-randomized trials
Research informed consent not necessary
IRBs mostly are familiar with research that enrolls individuals, and their attention is paid to the individual informed consent. But there are other types of human subjects research, including cluster-randomized trials, which require IRBs to focus on interventions at a wider level, an expert says.
Examples would be putting fluoride in a community's water or doing a community intervention for people at risk for HIV infection, says James E. Sabin, MD, director of the ethics program at Harvard Pilgrim Health Care in Boston, MA, and a clinical professor in the departments of population medicine and psychiatry at Harvard Medical School in Boston.
"The idea with cluster-randomized trials is to compare drug effectiveness in cases where there is a wide area of medical practice," Sabin explains. "The medications in use are widely accepted, but we don't know their relative comparative effectiveness."
Sabin and co-researchers examined the ethics of cluster-randomized trials in a paper published in the Hastings Center Report.1
Subjects in such a trial would not be randomized in the typical way. Instead they would be selected by their region or doctor. For example, if two or more medications were being compared for treating one disease, then it's likely physicians would have certain preferences, with one doctor choosing drug A and another drug B. Even in regions of the country, most doctors might choose one drug over another, Sabin says.
"The two agents might be in a state of clinical equipoise, and the expert community would have no conclusion about which was better," he says.
So the idea would be to have doctors, perhaps clustered in a region, who favor drug A to collect data on their patients, and doctors, favoring drug B, likewise would collect data on their patients' outcomes. The two clusters of patients then would be compared to see which treatment showed greater efficacy.
Individual informed consent would not be necessary, but a cluster-representation mechanism could provide consent for entry of a cluster into a cluster-randomized trial.1
IRBs reviewing such a study would require consideration of the views of patients and physicians, health insurance plan agents, and others. The IRB would assess whether there is a true state of equipoise for the drugs whose effectiveness is compared and whether the study is designed in a way to produce useful and scientifically-valid findings.1
Since these two drugs are equally safe and effective in the opinion of the medical community, individual patients would not need to be given informed consent, Sabin says.
The study would be designed so that individual patients could opt for the alternate drug if they so chose, and this opt-out provision is key to the conclusion that informed consent is not required, he adds.
"Both drugs are commonly used and are justifiable in the context of the study," Sabin says.
Physicians make flip-of-the-coin sort of decisions about prescriptions routinely, he notes.
"Sometimes a clinician will say, 'I've used drug A the last five times and so I want to use drug B and see how it works,' or the patient or doctor saw an advertisement and want to try drug B," Sabin says.
In a cluster-randomized trial, the goal is to compare clusters where a significant majority of patients were given one drug over the other.
Reference
- Sabin JE, Mazor K, Meterko V, et al. Comparing drug effectiveness at health plans: the ethics of cluster randomized trials. Hastings Center Report. 2008;38(5):39-48.
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