Faculty Bibliography

Longitudinal clinical trials in psychiatry have used various statistical methods to examine treatment effects. The validity of the inferences depends upon the different method's assumptions and whether a given study violates those assumptions. The objective of this paper was to elucidate these complex issues by comparing various methods for handling missing data (e.g., last observation carried forward [LOCF], completer analysis, propensity-adjusted multiple imputation) and for analyzing outcome (e.g., end-point analysis, repeated-measures analysis of variance [RM-ANOVA], mixed-effects models [MEMs]) using data from a multi-site randomized controlled trial in obsessive-compulsive disorder (OCD). The trial compared the effects of 12 weeks of exposure and ritual prevention (EX/RP), clomipramine (CMI), their combination (EX/RP&CMI) or pill placebo in 122 adults with OCD. The primary outcome measure was the Yale-Brown Obsessive Compulsive Scale. For most comparisons, inferences about the relative efficacy of the different treatments were impervious to different methods for handling missing data and analyzing outcome. However, when EX/RP was compared to CMI and when CMI was compared to placebo, traditional methods (e.g., LOCF, RM-ANOVA) led to different inferences than currently recommended alternatives (e.g., multiple imputation based on estimation-maximization algorithm, MEMs). Thus, inferences about treatment efficacy can be affected by statistical choices. This is most likely when there are small but potentially clinically meaningful treatment differences and when sample sizes are modest. The use of appropriate statistical methods in psychiatric trials can advance public health by ensuring that valid inferences are made about treatment efficacy

OBJECTIVE: The experiences of clinicians in regard to initial and long-term intention to use evidence-based treatments were examined in order to better understand factors involved in implementation of innovative treatments. METHODS: Ethnographic methods of participant observation and extended semistructured interviews with four trainers, six clinical supervisors, and 52 clinicians at five agencies in Honolulu and six in Boston were used to understand treatment implementation in the Clinic Treatment Project, a randomized effectiveness trial of evidence-based treatments for depression, anxiety, and conduct problems of children. Grounded-theory analytic methods were used to analyze field notes, interview transcripts, and meeting minutes. RESULTS: Three patterns in regard to long-term intention to implement the treatments were evident: application of the treatments with fidelity, abandonment of the treatments, and selective or partial application. These patterns were perceived to be associated with three preimplementation factors: lag time between initial training in the treatment protocol and treatment use in practice, clinician engagement with the project, and clinician-treatment fit. Four additional factors were proximal outcomes of the three determinants as well as first steps of implementation: clinicians' first impressions of the evidence-based treatments after initial use, competence in treatment use, clinician and researcher adaptability, and clinician-researcher interactions. CONCLUSIONS: Interactions between preimplementation factors and initial implementation experiences and between researchers and clinicians during the early implementation steps were related to intentions to sustain treatment.

Increased availability of research-supported, school-based prevention programs, coupled with the growing national policy emphasis on use of evidence-based practices, has contributed to a shift in research priorities from efficacy to implementation and dissemination. A critical issue in moving research to practice is ensuring high-quality implementation of both the intervention model and the support system for sustaining it. The paper describes a three-level framework for considering the implementation quality of school-based interventions. Future directions for research on implementation are discussed.

Developmental trajectories provide the empirical foundation for theories about change processes during development. However, the ability to distinguish among alternative trajectories depends on how frequently observations are sampled. This study used real behavioral data, with real patterns of variability, to examine the effects of sampling at different intervals on characterization of the underlying trajectory. Data were derived from a set of 32 infant motor skills indexed daily during the first 18 months. Larger sampling intervals (2-31 days) were simulated by systematically removing observations from the daily data and interpolating over the gaps. Infrequent sampling caused decreasing sensitivity to fluctuations in the daily data: Variable trajectories erroneously appeared as step functions, and estimates of onset ages were increasingly off target. Sensitivity to variation decreased as an inverse power function of sampling interval, resulting in severe degradation of the trajectory with intervals longer than 7 days. These findings suggest that sampling rates typically used by developmental researchers may be inadequate to accurately depict patterns of variability and the shape of developmental change. Inadequate sampling regimes therefore may seriously compromise theories of development.

OBJECTIVE: To assess combined antidepressant and cognitive enhancer treatment in elderly patients presenting with depression plus cognitive impairment. METHODS: Twenty-three elderly (>50 years old) depressed, cognitively impaired (DEP-CI) patients participated in a pilot study. We evaluated whether, after 8 weeks of open antidepressant treatment, donepezil HCl (Aricept) would afford added cognitive benefit compared to placebo in a randomized 12-week trial. A subsample continued in an 8-month extension phase of open treatment with donepezil. Neuropsychological testing (NPT) was performed and antidepressant response monitored at baseline and the 8, 20, and 52-week time points. RESULTS: At 8-weeks, the antidepressant response rate was 61% (14/23). Improvement in SRT immediate recall (SRT-IR; e.g. episodic verbal memory) was observed in responders compared to non-responders. During the 12-week, placebo-controlled, donepezil add-on trial, patients on donepezil showed further improvement in SRT-IR versus patients on placebo. In the open extension phase, patients who continued open donepezil treatment (n = 6) maintained improvement in memory and tended to show an advantage over patients who never received donepezil and were evaluated at the 52-week time point (n = 6). There were no observed significant donepezil effects on non-memory cognitive domains. CONCLUSION: These preliminary findings suggest that addition of a cholinesterase inhibitor (AChEI) following antidepressant medication treatment in elderly Dep-CI patients may improve cognition, and support the need for a confirmatory, larger randomized placebo-controlled trial.

Behaviors characteristic of ADHD are common among preschool children, and as such, their clinical significance is oftentimes difficult to ascertain. Thus a focus on impairment is essential in determining the clinical significance of these behaviors. In order to explore the impact of impairment criteria on rates of diagnoses in inattentive/hyperactive children aged 36 through 60-months-old, we first developed, and psychometrically evaluated, the Children's Problem Checklist (CPC) which was designed to assess psychosocial impairment associated with ADHD in a community sample of preschoolers (n = 394), and found its reliability and validity to be acceptable. We then examined the impact of the inclusion of various CPC-determined impairment criteria, over and above symptom criteria measured by the ADHD-RS-IV, using various cut points ranging from the 75th to 90th percentile of our community sample. This reduced the number of children meeting criteria for ADHD by 46-77%. These findings are discussed in terms of the importance of using impairment criteria, rather than just severity of inattention, impulsivity and hyperactivity, when diagnosing ADHD in preschool children.

PURPOSE/OBJECTIVE:Community-based testing may identify young adults in the general population with sexually transmitted chlamydial infection. To develop selective screening guidelines appropriate for community settings, the authors conducted a cross-sectional analysis of the National Longitudinal Study of Adolescent Health Wave III (April 2, 2001, to May 9, 2002). METHODS:Separately for women and men, we developed three predictive models by using unconditional multiple logistic regression for survey data. To account for racial/ethnic disparity in prevalence, initial models included identical predictor characteristics plus information on 1) respondent's race/ethnicity; or 2) respondent's most recent partner's race/ethnicity; or 3) no information on race/ethnicity. RESULTS:Chlamydia trachomatis diagnosis was available for 10,928 (88.6%) of the sexually experienced respondents. A combination of five characteristics for women and six characteristics for men identified approximately 80% of infections when testing </=50% of the population. Information regarding race/ethnicity dramatically affected algorithm performance. CONCLUSION/CONCLUSIONS:The use of race/ethnicity in any screening algorithm is problematic and controversial, but the model without race information missed many diagnoses in the minority groups. Universal screening in high-prevalence regions and selective screening in low-prevalence regions may be one method of reaching the affected populations while avoiding the stigma of guidelines incorporating race/ethnicity.

OBJECTIVE: Predictability is a fundamental modulator of anxiety in that the ability to predict aversive events mitigates anxious responses. In panic disorder, persistent symptoms of anxiety are caused by anticipation of the next uncued (unpredictable) panic attack. The authors tested the hypothesis that elevated anxious reactivity, specifically toward unpredictable aversive events, is a psychophysiological correlate of panic disorder. METHOD: Participants were exposed to one condition in which predictable aversive stimuli were signaled by a cue, a second condition in which aversive stimuli were administered unpredictably, and a third condition in which no aversive stimuli were anticipated. Startle was used to assess anxious responses to cues and contexts. RESULTS: Relative to healthy comparison subjects, patients with panic disorder displayed equivalent levels of fear-potentiated startle to the threat cue but elevated startle potentiation in the context of the unpredictable condition. CONCLUSIONS: Patients with panic disorder are overly sensitive to unpredictable aversive events. This vulnerability could be either a premorbid trait marker of the disorder or an acquired condition caused by the experience of uncued panic attacks. As a premorbid trait, vulnerability to unpredictability could be etiologically related to panic disorder by sensitizing an individual to danger, ultimately leading to intense fear/alarm responses to mild threats. As an acquired characteristic, such vulnerability could contribute to the maintenance and worsening of panic disorder symptoms by increasing anticipatory anxiety.