THE DEPRESSION INVENTORY DEVELOPMENT SCALE: Assessment of Psychometric Properties Using Classical and Modern Measurement Theory in a CAN-BIND Trial.

Objective: The goal of the Depression Inventory Development (DID) project is to develop a comprehensive and psychometrically sound rating scale for major depressive disorder (MDD) that reflects current diagnostic criteria and conceptualizations of depression. We report here the evaluation of the current DID item bank using Classical Test Theory (CTT), Item Response Theory (IRT) and Rasch Measurement Theory (RMT). Methods: The present study was part of a larger multisite, open-label study conducted by the Canadian Biomarker Integration Network in Depression (ClinicalTrials.gov: NCT01655706). Trained raters administered the 32 DID items at each of two visits (MDD: baseline, n=211 and Week 8, n=177; healthy participants: baseline, n=112 and Week 8, n=104). The DID's "grid" structure operationalizes intensity and frequency of each item, with clear symptom definitions and a structured interview guide, with the current iteration assessing symptoms related to anhedonia, cognition, fatigue, general malaise, motivation, anxiety, negative thinking, pain, and appetite. Participants were also administered the Montgomery- Åsberg Depression Rating Scale (MADRS) and Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR) that allowed DID items to be evaluated against existing "benchmark" items. CTT was used to assess data quality/reliability (i.e., missing data, skewness, scoring frequency, internal consistency), IRT to assess individual item performance by modelling an item's ability to discriminate levels of depressive severity (as assessed by the MADRS), and RMT to assess how the items perform together as a scale to capture a range of depressive severity (item targeting). These analyses together provided empirical evidence to base decisions on which DID items to remove, modify, or advance. Results: Of the 32 DID items evaluated, eight items were identified by CTT as problematic, displaying low variability in the range of responses, floor effects, and/or skewness; and four items were identified by IRT to show poor discriminative properties that would limit their clinical utility. Five additional items were deemed to be redundant. The remaining 15 DID items all fit the Rasch model, with person and item difficulty estimates indicating satisfactory item targeting, with lower precision in participants with mild levels of depression. These 15 DID items also showed good internal consistency (alpha=0.95 and inter-item correlations ranging from r=0.49 to r=0.84) and all items were sensitive to change following antidepressant treatment (baseline vs. Week 8). RMT revealed problematic item targeting for the MADRS and QIDSSR, including an absence of MADRS items targeting participants with mild/moderate depression and an absence of QIDS-SR items targeting participants with mild or severe depression. Conclusion: The present study applied CTT, IRT, and RMT to assess the measurement properties of the DID items and identify those that should be advanced, modified, or removed. Of the 32 items evaluated, 15 items showed good measurement properties. These items (along with previously evaluated items) will provide the basis for validation of a penultimate DID scale assessing anhedonia, cognitive slowing, concentration, executive function, recent memory, drive, emotional fatigue, guilt, self-esteem, hopelessness, tension, rumination, irritability, reduced appetite, insomnia, sadness, worry, suicidality, and depressed mood. The strategies adopted by the DID process provide a framework for rating scale development and validation.

The Depression Inventory Development Workgroup: A Collaborative, Empirically Driven Initiative to Develop a New Assessment Tool for Major Depressive Disorder.

The Depression Inventory Development project is an initiative of the International Society for CNS Drug Development whose goal is to develop a comprehensive and psychometrically sound measurement tool to be utilized as a primary endpoint in clinical trials for major depressive disorder. Using an iterative process between field testing and psychometric analysis and drawing upon expertise of international researchers in depression, the Depression Inventory Development team has established an empirically driven and collaborative protocol for the creation of items to assess symptoms in major depressive disorder. Depression-relevant symptom clusters were identified based on expert clinical and patient input. In addition, as an aid for symptom identification and item construction, the psychometric properties of existing clinical scales (assessing depression and related indications) were evaluated using blinded datasets from pharmaceutical antidepressant drug trials. A series of field tests in patients with major depressive disorder provided the team with data to inform the iterative process of scale development. We report here an overview of the Depression Inventory Development initiative, including results of the third iteration of items assessing symptoms related to anhedonia, cognition, fatigue, general malaise, motivation, anxiety, negative thinking, pain and appetite. The strategies adopted from the Depression Inventory Development program, as an empirically driven and collaborative process for scale development, have provided the foundation to develop and validate measurement tools in other therapeutic areas as well.

Average Out-of-Pocket Expenses Across Different Drug Categories and Commercial Third-Party Payers.

In this Trend Watch, we look at retail pharmacy prescriptions for branded and generic attention deficit hyperactivity disorder treatments, atypical antipsychotics, selective serotonin reuptake inhibitors, and serotonin and norepinephrine reuptake inhibitors and analyze the average out-of-pocket costs incurred by patients who are covered by commercial third-party prescription plans (i.e., as opposed to patients covered by Medicaid or patients with no prescription coverage). Overall, patient out-of-pocket costs in commercial third-party plans are lower for generic prescriptions than they are for brand prescriptions by at least $19.02. Comparisons across the drug classes reveal that the average co-pay for brands and generics, as well as the difference between brand and generic out-of-pocket costs, differ by drug category.

Trends in CNS prescribing following the economic slowdown.

We investigated total prescription and new prescription trends before and after the economic slowdown beginning in September 2008. Over the July to November timeframe, both total prescriptions and new prescriptions for sleep aids, benzodiazepines, and antidepressants increased. There appears to be a small spike in the number of total and new prescriptions following September 2008, although this increase was not enough to cause a statistically significant change in the overall rate of increase of prescriptions over time. Discussion of data is provided.

Symptoms of anxiety in depression: assessment of item performance of the Hamilton Anxiety Rating Scale in patients with depression.

BACKGROUND: Although diagnostically dissociable, anxiety is strongly co-morbid with depression. To examine further the clinical symptoms of anxiety in major depressive disorder (MDD), a non-parametric item response analysis on "blinded" data from four pharmaceutical company clinical trials was performed on the Hamilton Anxiety Rating Scale (HAMA) across levels of depressive severity. METHODS: The severity of depressive symptoms was assessed using the 17-item Hamilton Depression Rating Scale (HAMD). HAMA and HAMD measures were supplied for each patient on each of two post-screen visits (n=1,668 observations). Option characteristic curves were generated for all 14 HAMA items to determine the probability of scoring a particular option on the HAMA in relation to the total HAMD score. Additional analyses were conducted using Pearson's product-moment correlations. RESULTS: Results showed that anxiety-related symptomatology generally increased as a function of overall depressive severity, though there were clear differences between individual anxiety symptoms in their relationship with depressive severity. In particular, anxious mood, tension, insomnia, difficulties in concentration and memory, and depressed mood were found to discriminate over the full range of HAMD scores, increasing continuously with increases in depressive severity. By contrast, many somatic-related symptoms, including muscular, sensory, cardiovascular, respiratory, gastro-intestinal, and genito-urinary were manifested primarily at higher levels of depression and did not discriminate well at lower HAMD scores. CONCLUSIONS: These results demonstrate anxiety as a core feature of depression, and the relationship between anxiety-related symptoms and depression should be considered in the assessment of depression and evaluation of treatment strategies and outcome.

Culture and assessment of manic symptoms.

Cultural background may influence the perception of psychiatric symptoms. We examined the effects of cultural biases on the identification of manic symptoms using the Young Mania Rating Scale. Two video interviews, each with an American person with mania, were shown to psychiatrists from three countries (US, UK and India). Total scores on the scale differed significantly between the US and UK (P<0.001) and between India and UK (P<0.001) rater groups. Overall, differences between India and US rater groups were less marked (P=0.28). These differences suggest that cultural biases influence the interpretation of manic symptoms.

Improving clinical trials: American Society of Clinical Psychopharmacology recommendations.

The major purpose of this American Society of Clinical Psychopharmacology-sponsored meeting was to identify strategies for more efficiently detecting clinical drug effects, thus reducing the economic and scientific risks of investigating new chemical entities in psychiatric disorders. The meeting consisted of presentations and discussions by experts who repeatedly had difficulty pursuing scientific, public health--relevant goals. Many approaches to improving the detection of potentially beneficial agents were reviewed. In this article, we discuss technically feasible study improvements. The scope of inquiry included identifying means of shifting institutional and regulatory assumptions and processes, even to the point of seeking appropriate national incentives.