This paper explains why informed consent for randomized comparative effectiveness research must include risks of standard care. Disclosures of such risks are both legally and ethically required and, for reasons discussed in the paper, should remain so.

Lantos and Feudtner argue that SUPPORT was an instance of CER and that CER differs from research involving unproven, experimental therapies because it exposes research subjects to the same risks patients regularly face in clinical practice. Like many defenders of SUPPORT, they formally acknowledge the study as research but want it to be thought of as clinical care. They develop an appealing argument, but it is misleading. Whatever doctors might have done in clinical practice, their choice of target range within (...) the study and for study participants was influenced by research aims. Just as in research involving unproven, experimental therapies, the care of patients in SUPPORT was altered for the goal of obtaining knowledge to help future patients. (shrink)

Ethical issues related to comparative effectiveness research, or research that compares existing standards of care, have recently received considerable attention. In this paper we focus on how Ethics Review Committees should evaluate the risks of comparative effectiveness research. We discuss what has been a prominent focus in the debate about comparative effectiveness research, namely that it is justified when “nothing is known” about the comparative effectiveness of the available alternatives. We argue that this focus may be misleading. Rather, we should (...) focus on the fact that some experts believe that the evidence points in favor of one intervention, whereas other experts believe that the evidence favors the alternative. We will then introduce a case that illustrates this point, and based on that, discuss how ERCs should deal with such cases of expert disagreement. We argue that ERCs have a duty to assess the range of expert opinions and based on that assessment arrive at a risk judgment about the study under consideration. We also argue that assessment of expert disagreement is important for the assignment of risk level to a clinical trial: what is the basis for expert opinions, how strong is the evidence appealed to by various experts, and how can clinical trial monitoring affect the possible increased risk of clinical trial participation. (shrink)

Regulators rely on clinical trials for drug approval and labeling decisions. Health systems and clinicians rely on the evidence from trials to determine treatment, and patients rely on it to decide which courses of care to undertake. Many of these stakeholders presume that the careful review of individual studies is enough to address the ethical and scientific questions that arise in clinical trials. In what follows, however, we demonstrate that explicit consideration of trial portfolios—series of trials that are interrelated by (...) a common set of objectives—is crucial. the ethical acceptability and evidentiary probity of individual trials can change depending on the characteristics of the portfolios in which they are embedded. Second, how trial portfolios are composed, how well they are coordinated, and how efficiently they use information determines the balance of risks and benefits they present as well as their different prospects for generating socially valuable information; these three factors also raise distinct questions of justice. (shrink)

The debate about the ethics of the Surfactant, Positive Pressure, and Oxygenation Randomized Trial (SUPPORT) often focuses on the assumptions made by the different parties involved, failing to note the lack of a necessary connection between those assumptions and the main criticism of the study—that the parents appear to have been poorly informed. The fact that the target ranges of oxygen saturation (SpO2) used in SUPPORT were within the range recommended as an appropriate “standard of care” does not mean that (...) the infants randomized to one of two restricted SpO2 ranges received the same treatment they would have received outside of the trial. The corresponding observation that randomization altered the potential harms to which an individual infant was exposed does not mean that the risks of being in SUPPORT were greater than or in addition to the risks associated with usual care. The argument that parents should have been better informed about these potential harms does not entail the (incorrect) assumption that neonatal clinicians make individualized treatment decisions rather than follow a standardized protocol when adjusting the level of oxygen a preterm infant receives. The fact that parents are unaware of the trade‐off clinicians make between these potential harms when establishing such a protocol does not justify the failure to adequately inform parents about the purpose of SUPPORT and the risks and harms that were involved. (shrink)

Two articles in this issue of the Hastings Center Report address the continuing controversy over the Surfactant, Positive Pressure, and Oxygenation Randomized Trial (SUPPORT). This controversy is part of a larger discussion about the appropriate regulatory framework for protecting human research participants in comparative effectiveness research (CER), a group of studies that aims to compare two “usual” or “standard” treatments in order to provide evidence of which treatment is most effective.