Reconciling Protection with Scientific Progress

In this issue, three articles and one of the essays contribute to an emerging discourse that challenges the core assumptions, concepts, and principles of research ethics. Some of these contributions are useful. We must be wary, however, that in refining and clarifying the concepts of research ethics we do not undermine the protections for human subjects.

Lynn Jansen examines the implications of the "antiexploitation norm" that Frank Miller and Howard Brody had proposed previously in these pages as a partial replacement for another research norm that they thought seriously confused, that of "clinical equipoise." Jansen shows that "bad deal trials"—trials not in the best interest of at least some research subjects—would be unethical under the norm of clinical equipoise but not necessarily under the antiexploitation norm. One option for reconciling the bad deal trial with the antiexploitation norm is a compulsory lottery for research participation. Jansen notes, however, that this approach would require modifying or abandoning the ethical requirement for informed consent.

David Orentlicher's proposal for compulsory research participation would not require modifying or abandoning informed consent or clinical equipoise. However, he proposes that physician-researchers could require their patients to participate in studies that compare two or more standard therapies; patients who refuse would have to find another physician. As precedent for the proposal, Orentlicher claims that most pediatric cancer patients and all cancer patients who go to the National Institutes of Health Clinical Center are required to participate in a clinical trial as a condition of receiving medical care for their illness. Here he confuses research with treatment (having already confused "patients" with research "subjects/participants"). Individuals go to the NIH and other specialized cancer centers for the purpose of receiving an investigational treatment as a subject in a clinical trial, not for getting "medical care" as a "patient."

More serious are the ethics of compulsory research participation. The recent controversy over the safety of several COX-2 prescription drugs reveals that just because an intervention is "standard" or "established" does not mean it is risk-free. Clinical trials do not necessarily identify all of a treatment's side effects; nor do they definitively determine that treatments are effective. Moreover, in the absence of a national, comprehensive drug safety system that monitors adverse effects of "standard" and "established" therapies, it is an empirical question whether comparing these types of therapies in a clinical trial does not place participants at greater risk of harm than had they not participated. An individual whose physician-researcher prescribed standard therapy X might be harmed by receiving standard therapy Y if assigned to that intervention in a clinical trial.

Orentlicher's claim that his compulsory participation scheme is not coercive illustrates the point that Hawkins and Emanuel make about the need for conceptual clarity when talking about coercion. If a physician-researcher threatened to withhold necessary, standard treatment unless a patient joined a clinical trial, it "would clearly be coercion," they say. But many other problems and transgressions should not be confused with coercion. They rightly point out that "the use of a word has extremely important practical implications: how one understands a problem shapes what one does about it." It's curious, therefore, that the definition they opt for allows them to reject many claims of coercion involving human subjects. There may be other ways to conceptualize the term that permit a broader application than Hawkins and Emanuel accept.

The phrase "minimal risk research" has also been problematic. Wendler contends that the standard typically used to define "minimal risk" does not adequately protect children and cognitively impaired adults who cannot consent to participate in nonbeneficial studies. His "charitable participation standard" would not allow certain risks of daily life to be present in these types of studies. Yet Wendler seems willing to permit riskier research to go forward within foreign communities. Wendler contends that as long as communities are assured of receiving "fair benefits," then individuals are not exploited by being enrolled in riskier, nonbeneficial studies that other societies would not tolerate.

At issue throughout these proposals is whether they bring greater clarity to faster scientific progress at the expense of...