Development and content validity of a patient reported outcomes measure to assess symptoms of major depressive disorder

<p>Abstract</p> <p>Background</p> <p>Although many symptoms of Major Depressive Disorder (MDD) are assessed through patient-report, there are currently no patient-reported outcome (PRO) instruments that incorporate documented evidence of patient input in PRO instrument development. A review of existing PROs used in MDD suggested the need to conduct qualitative research with patients with MDD to better understand their experience of MDD and develop an evaluative instrument with content validity. The aim of this study was to develop a disease-specific questionnaire to assess symptoms important and relevant to adult MDD patients.</p> <p>Methods</p> <p>The questionnaire development involved qualitative interviews for concept elicitation, instrument development, and cognitive interviews to support content validity. For concept elicitation, ten MDD severity-specific focus group interviews with thirty-eight patients having clinician-confirmed diagnoses of MDD were conducted in January 2009. A semi-structured discussion guide was used to elicit patients' spontaneous descriptions of MDD symptoms. Verbatim transcripts of focus groups were coded and analyzed to develop a conceptual framework to describe MDD. A PRO instrument was developed by operationalizing concepts elicited in the conceptual framework. Cognitive interviews were carried out in patients (n = 20) to refine and test the content validity of the instrument in terms of item relevance and comprehension, instructions, recall period, and response categories.</p> <p>Results</p> <p>Concept elicitation focus groups identified thirty-five unique concepts falling into several domains: i) emotional, ii) cognitive, iii) motivation, iv) work, v) sleep, vi) appetite, vii) social, viii) activities of daily living, ix) tired/fatigue, x) body pain, and xi) suicidality. Concept saturation, the point at which no new relevant information emerges in later interviews, was achieved for each of the concepts. Based on the qualitative findings, the PRO instrument developed had 15 daily and 20 weekly items. The cognitive interviews confirmed that the instructions, item content, and response scales were understood by the patients.</p> <p>Conclusions</p> <p>Rigorous qualitative research resulted in the development of a PRO measure for MDD with supported content validity. The MDD PRO can assist in understanding and assessing MDD symptoms from patients' perspectives as well as evaluating treatment benefit of new targeted therapies.</p

PRO development: rigorous qualitative research as the crucial foundation

Recently published articles have described criteria to assess qualitative research in the health field in general, but very few articles have delineated qualitative methods to be used in the development of Patient-Reported Outcomes (PROs). In fact, how PROs are developed with subject input through focus groups and interviews has been given relatively short shrift in the PRO literature when compared to the plethora of quantitative articles on the psychometric properties of PROs. If documented at all, most PRO validation articles give little for the reader to evaluate the content validity of the measures and the credibility and trustworthiness of the methods used to develop them. Increasingly, however, scientists and authorities want to be assured that PRO items and scales have meaning and relevance to subjects. This article was developed by an international, interdisciplinary group of psychologists, psychometricians, regulatory experts, a physician, and a sociologist. It presents rigorous and appropriate qualitative research methods for developing PROs with content validity. The approach described combines an overarching phenomenological theoretical framework with grounded theory data collection and analysis methods to yield PRO items and scales that have content validity

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

The Political Culture of Medical Technology Assessment (Nih, Boundary Spanner, Organization).

This dissertation explores how medical technology assessment goes forward within the National Institutes of Health (NIH). The underlying assumption is that organizations involved in the implementation of policy are affected by the environment within which they operate. This study employs a political culture model to examine the symbolic environment surrounding the issue of the Federal role vis-a-vis the conduct and transfer of biomedical research and the effect that environment has on the production of Consensus Development Conferences at the NIH. It then employs an organizational process model to examine the relationship between political culture and organizational behavior. A content analysis of the popular and medical press identifies key frames, or interpretive packages in the political culture of medical technology assessment. These frames entail policy prescriptions concerning medical technologies. A content analysis of the Consensus Statements produced at Consensus Development Conferences reveals that issues and recommendations associated with certain frames are more likely to be represented in these statements. An organizational analysis of the decision-making process leading to the development of Consensus Development Conferences examines how OMAR (an administrative unit within the NIH) filters the use of these frames to affect the outcome of conferences in ways that protect NIH's resources and legitimacy. The data collected in this study suggest the importance of analyzing policy within its broader cultural, social, political and economic context. Specifically, the findings support the notion of a link between political culture and policy choice. The issues and recommendations concerning medical technologies in consensus statements reflected the prominence of various frames, or interpretive packages, in the political culture of medical technology assessment. As the prominence of interpretive packages changed over time, the issues raised in consensus statements narrowed reflecting this change. Organizational shaping led to the exclusion and deemphasis of questions which focus on the economic, ethical, or social implications of the use of medical technologies.Ph.D.Social workUniversity of Michiganhttp://deepblue.lib.umich.edu/bitstream/2027.42/160362/1/8502868.pd

The Political Culture of Social Welfare Policy

http://deepblue.lib.umich.edu/bitstream/2027.42/51014/1/242.pd

An Assessment of Clinically Important Differences on the Worst Pain Severity Item of the Modified Brief Pain Inventory in Patients with Diabetic Peripheral Neuropathic Pain

Objectives. Using patient global impression of change (PGIC) as an anchor, an approximately 30% reduction on an 11-point numeric pain intensity rating scale (PI-NRS) is considered a clinically important difference (CID) in pain. Our objective was to define the CID for another pain measure, the worst pain severity (WPS) item of the modified Brief Pain Inventory (m-BPI). Methods. In this post hoc analysis of a double-blind, placebo-controlled, phase 2 study, 452 randomized patients with diabetic peripheral neuropathic pain (DPNP) were followed over 5 weeks, with m-BPI data collected weekly and PGIC at treatment conclusion. Receiver operating characteristic (ROC) curves (via logistic regression) were used to determine the changes in the m-BPI-WPS score that best predicted ordinal clinical improvement thresholds (i.e., “minimally improved” or better) on the PGIC. Results. Similar to the PI-NRS, a change of −3 (raw) or −33.3% from the baseline on the m-BPI-WPS optimized prediction for the “much improved” or better PGIC threshold and represents a CID. There was a high correspondence between observed and predicted PGIC categories at each PGIC threshold (ROC AUCs were 0.78–0.82). Conclusions. Worst pain on the m-BPI may be used to assess clinically important improvements in DPNP studies. Findings require validation in larger studies

Qualitative modification and development of patient- and caregiver-reported outcome measures for iron chelation therapy

Abstract Background Compliance, palatability, gastrointestinal (GI) symptom, and treatment satisfaction patient- and observer-reported outcome (PRO, ObsRO) measures were developed/modified for patients with transfusion-dependent anemias or myelodysplastic syndrome (MDS) requiring iron chelation therapy (ICT). Methods This qualitative cross-sectional observational study used grounded theory data collection and analysis methods and followed PRO/ObsRO development industry guidance. Patients and caregivers of patients with transfusion-dependent anemias or MDS were individually interviewed face-to-face to cognitively debrief the Compliance, Palatability, GI Symptom Diary, and Modified Satisfaction with Iron Chelation Therapy (SICT) instruments presented electronically. Interviews were conducted in sets. Interviews began open-endedly to spontaneously elicit ICT experiences. Item modifications were debriefed during the later interviews. Interviews were audio recorded, transcribed, and coded. Data was analyzed using ATLAS.ti qualitative research software. Results Twenty-one interviews were completed (Set 1: 5 patients, 6 caregivers; Set 2: 6 patients, 4 caregivers) in 6 US cities. Mean age was 43 years for patients and 9 years for children of caregivers. Conditions requiring ICT use across groups included transfusion-dependent anemias (85.7%) and MDS (14.3%). Concepts spontaneously reported were consistent with instruments debriefed. Interview analysis resulted in PRO and ObsRO versions of each instrument: Compliance (2 items), Palatability (4 items), GI Symptom Diary (6 items), and Modified SICT (PRO = 13, ObsRO = 17 items). Conclusion Qualitative research data from cognitive interviews supports the content validity and relevance of the instruments developed/modified. Quantitative validation of these PRO and ObsRO measures is needed testing for validity, reliability, and responsiveness for future research use with new formulations of oral ICT