Usual care as the control group in clinical trials of nonpharmacologic interventions

Abstract

We discuss the pros and cons of including usual care as a control arm in clinical trials of nonpharmacologic interventions. Usual care is a term used to describe the full spectrum of patient care practices in which clinicians have the opportunity (which is not necessarily seized) to individualize care. The decision to use usual care as the control arm should be based on the nature of the research question and the uniformity of usual-care practices. The use of a usual-care arm in a two-arm trial should be considered for trials of investigational drugs or devices, for trials that propose to test interventions that lie well outside usual-care practices, or for trials where the research question per se is to compare a strategy against usual care. Examples of the latter include pragmatic effectiveness trials of clinical pathways or protocolized-care versus usual-care practices. Randomized intervention trials can be safely conducted and monitored using two treatments that lie within the range of usual-care practices if both approaches are considered prudent and good care for the target population.

Figures

Figure 1.

Hemoglobin thresholds for packed red blood cell (PRBC) transfusions for 254 intensive care unit clinicians varied from less than 6.5 g/dl to over 10.5 g/dl. C1 indicates the entire range of hemoglobin transfusion thresholds (de facto usual care). C2 indicates a narrower range of practices that might be considered prudent care. Different treatment decisions for the identical patient scenario is an example of clinically unexplained practice variation. The province and practice setting (academic or community) explained some of the variation in practice (practice styles). Clinician practices were different for an actively bleeding patient scenario (hatched bars) in comparison to three nonbleeding scenarios (open bars), indicating evidence of customization, although practices still varied widely. Severity of illness and age also influenced practice (data not shown), which is further evidence of customization. The entire range of practices represents de facto usual care. Within these practices lies what a consensus of the investigators likely determined to be prudent care and they proposed to randomize two strategies within these bounds (A vs. B) (15). This proposal was subjected to peer review (Canadian Clinical Trials Group and the Medical Research Council of Canada), and the participating institutional review boards that approved the study (15). Both approaches were judged not to be prudent care for bleeding patients, so such patients were excluded. Data from Reference .

Figure 2.

Clinician-selected tidal volumes before the initiation of study procedures are shown for the Exosurf trial (Aerosolized Surfactant for ARDS, conducted in nine countries, 63 hospitals, with 726 patients enrolled between 1992 and 1993) (11) and the Acute Respiratory Distress Syndrome Network (ARDSnet) lower tidal volume trial (conducted in the United States with 17 hospitals, and 861 patients enrolled between 1996 and 1999) (8). Arrow “A” represents the lower tidal volume group, selected after the completion of a phase II trial and the publication of another positive trial, and arrow “B” the tidal volume used in the traditional approach (32, 33). The Exosurf trial results were considered during the design of the ARDSnet trial. De facto usual care would be the entire range of clinician-selected tidal volumes. Note the shift in usual-care practices toward the use of lower tidal volumes during the trial, which may have represented adoption of lower tidal volumes in response to preclinical studies and expert opinion or the influence of the trial per se (Hawthorne effect). Hatched bars, Exosurf; solid bars, ARMA.