• Early Symptom Improvement as a Predictor of Antidepressant Response in Children and Adolescents Diagnosed with Depression: Translating Evidence from Randomized Controlled Trials to Community Practice

      Spence, O'Mareen; dosReis, Susan (2020)
      Statement of the Problem: A common problem among children and adolescents diagnosed with depression who receive care in community settings is that antidepressant regimen changes such as psychotropic augmentation may occur soon after starting treatment. This raises the question as to whether such changes are implemented among youth who would otherwise respond to the antidepressant. Thus, the overarching objectives of this dissertation were to 1) distinguish early in treatment children and adolescents who are likely to respond, and 2) empirically evaluate the association between predicted response and psychotropic augmentation or switching in real world settings. Summary of Methods: Using randomized clinical trial (RCT) data, this research applied a Bayesian approach to predict the likelihood of initial (12 week) and sustained (18 week) response to treatment as a function of early changes in depressive symptoms (i.e. mood, somatic, subjective and behavioral) and other demographic and clinical factors. An innovative application of combined sample multiple imputations (CSMI) was used to estimate the 12-week predicted probability of response among commercially insured adolescents who received care in real-world settings. Each adolescent received a probability of treatment response, which was then used to compare the odds of psychotropic augmentation or switch. Results: Early changes in mood and somatic symptoms within the first six weeks of treatment are primary predictors of initial (at 12 weeks) and sustained (at 18 weeks) response to an antidepressant. Baseline depression severity is an important prognostic factor for initial response, and additional, though minimal improvement, in somatic symptoms from weeks 6 to 12 is indicative of sustained response. In a highly selected cohort of adolescents receiving care in community settings, an augmentation or switch occurred similarly among adolescents with a high versus low likelihood of responding to fluoxetine. Conclusion: The results suggest that other factors beyond expected antidepressant response (or lack thereof) might influence current treatment practices. Our findings have clinical and public health implications that support measurement-based care in pediatric depression. Our application of CSMI highlights several key areas of consideration for future pharmacoepidemiologic research aimed at translating RCT evidence to real world data to better understand clinical practices patterns.
    • The economic impact of DUR interventions on the pharmacological management of asthma in children

      Raut, Monika Kumar; Stuart, Bruce C. (2001)
      The purpose of the dissertation was to assess the economic impact of a DUR intervention among children enrolled in the Pennsylvania Medicaid program who had overused SA beta2-agonist inhalation drugs. This research expanded on previous work, the base study, titled 'Pennsylvania Medicaid Retrospective Drug Utilization Review Program Improvement of the Pharmacological Management of Asthma in Children Enrolled in the Pennsylvania Medicaid Fee-for-Service Program' conducted by the Center on Drugs and Public Policy, University of Maryland and Pennsylvania Medical Society for the Commonwealth of Pennsylvania, Department of Public Welfare. This base study was descriptive in design and did not include a control group. The dissertation used scientifically controlled research methodologies to assess the base study results and evaluate whether a true DUR intervention effect existed. It used various multivariate techniques designed to control for non-intervention related influences. Four pre/post comparison series designs to address uncontrolled confounders such as regression to the mean, history, and maturation were used. These included (a) a self-controlled historical comparison group design, (b) a historical equivalent comparison group design, (c) a concurrent non-equivalent comparison group design, and (d) a regression discontinuity design. The self-controlled historical comparison group design was a single-group pre/post design that monitored trends in resource utilization among the intervention group in a year previous to the DUR claims review period. The historical equivalent comparison group design was a two-group design that compared the DUR intervention group to a comparison group identified by the same criteria as the intervention group in a year previous to the DUR claims review period. The concurrent non-equivalent comparison group design and the regression discontinuity design were two-group designs that utilized two different methods of analyses to compare the intervention group to a control group in the concurrent period. The end-points of interest were cost of asthma medications, asthma-related hospitalizations, and asthma-related emergency department visits. The study used Pennsylvania Medicaid administrative and prescription claims data for the period July 1997 to March 2000 residing at the CDPP. The robustness of each study design's findings to the base study results was analytically assessed. None of the four scientifically controlled study designs showed a significant positive DUR effect. The base study results were confounded by regression to the mean, history, and/or maturation.