When clinical practice appears to diverge from evidence-based medicine, is the clinician departing from science, or are the data not applying to practice? The challenge of developing clinical research data to inform treatment strategies for the inconstant course of psychiatric illness was recently considered by Susan Murphy, PhD, of the University of Michigan's Institute for Social Research, with colleagues from the MCATS (Methodology for Constructing Adaptive Treatment Strategies) network, and John Rush, MD, of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) investigators group.1
The NIMH-funded STAR*D trial is the largest and longest study ever conducted to evaluate depression treatment, and it was designed to better reflect conditions of practice than have traditional clinical trials. While researchers traditionally evaluate specific treatments in selected populations over short periods, clinicians treat a varied population of patients with different treatment responses, comorbid illnesses, and concurrent medications and symptoms that wax and wane over time. Treatment strategies must be adaptive, then, for the dynamics of illness and such factors as the emergence of comorbid conditions, adverse drug reactions and interactions, and how the patient adheres to treatment regimens.
The STAR*D study design of sequenced treatments "reflects what is done in clinical practice," according to the NIMH, in a statement issued in November, "because it allowed study participants to choose the treatments most acceptable to them and limited the randomization of each participant only to his or her range of acceptable treatment strategies."
The STAR*D study investigators described this as "equipoise-stratified randomization," with subjects and clinicians determining whether certain sets of options would be unacceptable.2
"One of the imperatives guiding the development of STAR*D," the investigators related, "was to preserve the integral role participants typically play in negotiating treatment decisions in clinical settings. As medical practice has evolved and public access to information regarding treatment of mental illness has grown, clinicians have increasingly recognized the value of patient participation when decisions need to be made."3
This aspect of the STAR*D design has its detractors, however. In an editorial in the November 2006 issue of The American Journal of Psychiatry, Craig Nelson, MD, indicated, "The greatest disappointment of the study—depending on your perspective—was that patients were not randomly assigned to all treatments at level 2, and as a result comparisons between treatment strategies were limited."4
This contention notwithstanding, there is widespread support for this effort to conduct clinical research with patients and conditions more reflective of clinical practice and to assess treatment strategies for the varied and changing circumstances encountered in practice.
1. Murphy SA, Oslin DW, Rush JA, et al. Methodological challenges in constructing effective treatment sequences for chronic psychiatric disorders. Neuropsychopharmacology. 2007;32:257-262.
2. Alpert JE, Biggs MM, Davis L, et al. Enrolling research subjects from clinical practice: ethical and procedural issues in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial. Psychiatry Res. 2006;141: 193-200.
3. Fava M, Rush AJ, Trivedi MH, et al. Background and rationale for the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. Psychiatr Clin North Am. 2003;26:457-494.
4. Nelson JC. The STAR*D study: a four-course meal that leaves us wanting more. Am J Psychiatry. 2006;163: 1864-1866.
5. Dawson R, Lavori PW. Placebo-free designs for evaluating new mental health treatments: the use of adaptive treatment strategies. Stat Med. 2004;23:3249-3262.
6. Murphy SA. An experimental design for the development of adaptive treatment strategies. Stat Med. 2005; 24:1455-1481.