Informed consent for pragmatic trials--the integrated consent model.

Learning health care systems hold great promise for improving medical care by systematically integrating the delivery of medical services with clinical research. In such systems, the generation of knowledge would be “embedded into the core of the practice of medicine,” leading to “continual improvement in care.”1 But is the goal of systematically integrating knowledge generation with health care delivery compatible with current research-oversight procedures2-4 — for example, when a comparative-effectiveness study compares two standard-of-care interventions?5,6 In some pragmatic, randomized clinical trials comparing two commonly prescribed medications for an outpatient condition such as hypertension, the only material departure from clinical practice may be replacing the physician selection of treatment with a randomized selection.4,7 It seems unlikely that such a study can be seamlessly “embedded” in routine clinical care delivery if the traditional informed-consent process for research participation (with the usual complex, lengthy document) is required. But what are the alternatives? A recent Department of Health and Human Services invitation for public comment specifically asked, “Should an IRB [institutional review board] be allowed to waive informed consent for research involving randomization of subjects to one or more standard of care interventions?”5 One group has developed a sophisticated moral framework for evaluating the ethics of learning health care activities8 and argues, following others,9 that these principles yield a surprising result: in some pragmatic comparative-effectiveness trials, the fact of randomization need not be disclosed to patients, and thus no express informed consent for research participation is ethically necessary.10 We share the goals of the learning health care movement3 and are deeply concerned about unnecessary regulatory obstacles to important research11; however, we find the proposal to not disclose to patients the fact of randomization even in low-risk outpatient pragmatic trials (hereafter called the no-consent model) problematic for both ethical and practical reasons. We propose instead that the consent process itself should reflect the ideal of learning health care of integrating medical care and clinical research, and we propose an integrated consent model for some types of pragmatic, randomized clinical trials. Notably, such a model can reasonably be seen as compatible with existing regulations.