Most important is the nature of the intervention itself. As described above, the intervention involves the placement of a specialist into a practice to help physicians follow treatment guidelines. Although the study might require the specialist not to directly contact nonintervention patients if patients were randomized MAPK inhibitor within a single practice, it is a likely – indeed hoped for – outcome of the study that the experience of the physician in working with the specialist in the long-term

treatment of depression with intervention patients will “spill Inhibitors,research,lifescience,medical over” and affect the physician’s care of his or her patients. Another option would be to randomize physicians within a single practice. This strategy might work if the physicians worked largely independently from each other, but, especially in smaller

practices, the threat of contamination seems high. Potential bias resulting from contamination in either Inhibitors,research,lifescience,medical scenario would dilute any effect of the intervention and be very difficult to correct in the analysis. In contrast, randomizing practices leads to two biases Inhibitors,research,lifescience,medical that are resolvable at the analysis stage: (i) bias created by treating the patient as the unit of analysis while the practice is the unit of randomization; and (ii) indication or selection bias rising from patient treatment that is not blinded to the diagnosis of depression. Both types of potential bias can be addressed using data-analytic strategies, the former by using random effects for patients and practices and the latter using instrumental variable modeling.52 A strength of PROSPECT is the involvement of several primary care practices with no prior history of Inhibitors,research,lifescience,medical academic

research. The willingness of the physicians Inhibitors,research,lifescience,medical to participate is all the more noteworthy given the increased time demands on them and their staff in the past few years. These constraints pose an additional challenge to studies such as PROSPECT trying to fit literally into the office space and schedule. PROSPECT investigators have worked closely with the physicians, administrators, and office managers at each practice tailoring procedures PDK4 to minimize office burden while facilitating access to data and space needed for the study methodology described below. At all practices, physicians met with investigators to review procedures, approve the PROSPECT patient recruitment letter, and receive a packet of baseline physician assessments. A separate inservice training was held for office support staff to review study procedures and discuss strategies for responding to patient phone calls concerning the study. Patients To study the effect of the intervention, PROSPECT collects longitudinal data on patients both from practices in which the guideline management intervention is implemented and the comparison enhanced care practices.