Response

We appreciate Coyne highlighting several of our original points, including the fundamental importance of the research question and the strikingly small body of relevant randomized controlled trials (RCTs). We agree that each included RCT had limitations. We concur that dissemination into routine care requires additional carefully formulated research. Two primary points of disagreement with Coyne remain. First, we contend that including collaborative care RCTs and trials with relatively small samples was well reasoned. Our goal (p. 991) was to examine the efficacy of RCTs testing various therapeutic approaches rather than specific psychotherapies. Collaborative care (CC) interventions are well suited for primary care ( 1 ) and are gaining traction in oncology ( 2 ). Secondary processes in CC, such as education about depression, are common components of psychotherapy ( 3 ). In the three CC trials, patients were randomly assigned to CC or usual care. We emphasized (p. 1000) that patients do not invariably receive psychotherapy in a CC model but rather can receive psychotherapy, medication, or both. Most CC patients received psychotherapy, with or without medication. Having treatment options better represents the naturalistic context and fosters successful dissemination to practice. Moreover, attending to patients’ preferences for depression treatment can yield positive outcomes ( 4 , 5 ). It is notable, however, that problem-solving therapy (all delivered within CC) had statistically significantly less impact on depressive symptoms than did cognitive behavioral therapy. Allowing RCTs with relatively small sample sizes, which coincides with our inclusion of pharmacologic studies and the well-documented knowledge of substantial attrition in pharmacologic RCTs for major depressive disorder ( 6 ), reflects a decision about which active debate exists in the meta-analytic literature ( 7 ). Our use of Hedges’ g , which corrects for small sample bias, and findings from our elected safeguards of examining publication bias, the fail-safe N , and whether the psychotherapeutic RCT effects varied as a function of trial attrition all suggest a stable overall effect size. A second disagreement regards a statistical decision. As we stated (p. 992), because interventions were distinct, we calculated two separate effect sizes for trials containing two intervention groups, which violates the assumption of independent effect sizes. We conducted sensitivity analyses to address this issue; separate analyses including only the largest or the smallest effect size from those studies did not substantially influence the findings (p. 999). Do the limitations of existing RCTs, as illuminated in our original article, and our analytic decisions render the meta-analytic findings unreliable or invalid? Our adoption of conservative analytic approaches and methodologic and quantitative safeguards leads us to affirm the finding of “reliable positive effects” of psychotherapeutic and pharmacologic interventions for adults with cancer and elevated depressive symptoms. Rather than offering a definitive verdict, this meta-analysis provides a foundation of evidence from which to build. Enhancing intervention efficacy and efficiency is urgent in light of the burden of depression and the exigencies of a changing health-care environment. Ideally, Hart et al. and Coyne will motivate researchers to apply rigorous standards for conducting RCTs and applying evidence-based interventions to address depression in individuals confronting cancer.

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