Psychometric validation of symptom severity measures in irritable bowel syndrome with constipation.

BACKGROUND: Historically, measures of symptom severity of irritable bowel syndrome with constipation (IBS-C) in clinical trials have not met the evidence requirements described in the FDA guidance on patient-reported outcomes (PROs), which describes the evidentiary requirements and review criteria for patient-reported outcome measures intended to support product approval or labelling claims. AIM: Data from two phase 3 trials (N = 1608) of linaclotide for the treatment of IBS-C were analysed to evaluate the psychometric properties of patient-reported outcome measures assessing changes in the severity of abdominal and bowel symptoms. METHODS: A set of patient-reported outcome assessments addressing abdominal and bowel symptoms, the IBS-C Symptom Severity Measures, were administered daily using interactive voice response system technology. Intraclass correlation coefficients (ICCs), Pearson correlations, factor analyses, F-tests and effect sizes were computed to evaluate the reliability, construct validity, discriminating ability and responsiveness of the IBS-C Symptom Severity Measures in a clinical trial context. RESULTS: The IBS-C Symptom Severity Measures showed highly satisfactory test-retest reliability (ICCs ranging from 0.79 to 0.95) and construct validity. Factor analyses indicated one factor for abdominal symptoms and another for bowel symptoms. Known-groups F-tests comparing subgroups based on various responder definitions were statistically significant and in the expected direction, substantiating the discriminating ability of the IBS-C Symptom Severity Measures. Responsiveness statistics (ranging from 0.6 to 2.1) demonstrated these measures are also capable of detecting change. CONCLUSIONS: The psychometric analysis results strongly support the reliability, construct validity, discriminating ability and responsiveness of the IBS-C Symptom Severity Measures and substantiate the conclusion of linaclotide treatment benefit.

An evaluation of the FDA responder endpoint for IBS-C clinical trials: analysis of data from linaclotide Phase 3 clinical trials.

BACKGROUND: Our objective was to evaluate the performance of the Food and Drug Administration (FDA) Responder Endpoint for clinical trials in IBS-C, using data from two large Phase 3 clinical trials of linaclotide. The FDA interim endpoint requires that, for 50% of trial weeks, patients report ≥30% decrease in Abdominal Pain at its worst and (in the same week) an increase in Complete Spontaneous Bowel Movements (CSBMs) of ≥1 from baseline. METHODS: Anchor-based methodology was used to estimate thresholds of clinically meaningful change using symptom-specific patient rating of change questions (PRCQs) and symptom severity questions. The diagnostic accuracy of the FDA Responder Endpoint was assessed using sensitivity/specificity-based methods. KEY RESULTS: Using anchor-based methods, the estimates of the clinically meaningful improvement thresholds for Abdominal Pain ranged from 25.9% to 32.4% and thresholds for increase in weekly CSBM rate ranged from 1.4 to 1.6 CSBMs per week. Compared with the symptom-specific PRCQs for patient rating of relief, the FDA Responder Endpoint has a sensitivity of 60.7%, a specificity of 93.5%, and an accuracy of 82.0%. Changing the number of weeks required to be a responder or the percentage improvement in the Abdominal Pain criteria did not result in notable improvement in the accuracy of the FDA Responder Endpoint. CONCLUSIONS & INFERENCES: The FDA Responder Endpoint for IBS-C clinical trials represents clinically meaningful improvements in IBS-C symptoms for patients with excellent specificity and reasonable sensitivity.

Prevalence and impact of antidepressant-associated sexual dysfunction in three European countries: replication in a cross-sectional patient survey.

Sexual dysfunction is a common but often unrecognized side effect of many antidepressants. Building upon the results of a previous investigation, this study aimed to assess the prevalence and impact of antidepressant-associated sexual dysfunction (AASD) in three European countries. A cross-sectional survey of 704 adults in Germany, Spain, and The Netherlands was used in the study. All participants had recently started taking a selective serotonin reuptake inhibitor or serotonin- noradrenaline reuptake inhibitor. Information about other medications and conditions known to impair sexual functioning was gathered, and changes in sexual functioning and the impact of such changes were assessed. The SF-12 and Arizona Sexual Experience Scale (ASEX) were administered to measure health status and sexual functioning. AASD was defined using ASEX scores and information regarding changes in sexual functioning. ASEX scores generally exceeded the threshold defining sexual dysfunction: 67.2% in the German, 79.4% in the Spanish, and 73.3% in the Dutch samples. The prevalence of AASD was conservatively estimated to be between 37.1% (German sample) and 61.5% (Spanish sample). Overall, 46.4% of male and 52.1% of female participants were classified with AASD. Patients classified with AASD reported significantly worse quality of life (QoL), self-esteem, mood, and relationships with partners, compared with non-AASD patients. There were significant differences between patients with and without AASD in SF-12 Mental Component scores, with AASD patients displaying poorer mental well-being. Sexual dysfunction is a frequent occurrence during antidepressant treatment, and is associated with reduced QoL and self-esteem, and negative effects on mood and relationships.

Psychometric properties of the CAHPS 1.0 survey measures. Consumer Assessment of Health Plans Study.

OBJECTIVES: Consumer surveys are being used increasingly to assess the quality of care provided by health plans, physician groups, and clinicians. The purpose of the Consumer Assessment of Health Plans Study (CAHPS) is to develop an integrated and standardized set of surveys designed to collect reliable and valid information about health plan performance from consumers. This article reports psychometric results for the CAHPS 1.0 survey items in samples of individuals with Medicaid or private health insurance coverage. METHODS: Reliability estimates for CAHPS 1.0 measures were estimated in a sample of 5,878 persons on Medicaid and 11,393 persons with private health insurance. Correlations of the CAHPS global rating of the health plan with willingness to recommend the plan and intention to re-enroll were estimated in a sample of 313 persons on Medicaid. The association of the rating of the health plan with ratings using a 5-point Excellent-to-Poor response scale also was investigated in the latter sample and in a sample of 539 persons with private health insurance. RESULTS: The CAHPS measures appeared to have good reliability, particularly at the health-plan level. Responses from 300 consumers per health plan tend to yield estimates that are reliable enough for health plan comparisons, especially among the privately insured. The global health plan rating was significantly correlated with consumers' willingness to recommend the plan to family and friends and to their intention to re-enroll in the plan if given a choice. CONCLUSIONS: The CAHPS 1.0 survey instrument appears to have excellent psychometric properties.

Special issues addressed in the CAHPS survey of Medicare managed care beneficiaries. Consumer Assessment of Health Plans Study.

OBJECTIVES: This article describes the process through which the MMC survey was developed and examines issues in using this survey with Medicare beneficiaries that have implications for all CAHPS surveys. These include the ability of Medicare beneficiaries to use MMC navigational features, whether access measures are meaningful for this population, and whether beneficiaries' familiarity with managed care influences their health plan assessments. BACKGROUND: The Health Care Financing Administration (HCFA) is mandated to provide comparative plan information, based partly on consumer surveys, to Medicare beneficiaries. The Consumer Assessments of Health Plans Study (CAHPS) is an integrated set of tested, standardized surveys of health plan enrollees. To meet its goal, HCFA has invested in the development of a CAHPS survey of beneficiaries enrolled in Medicare Managed Care plans (MMC). METHODS: Cognitive interviews were completed with 31 Medicare beneficiaries. A field test also was conducted with beneficiaries to examine patterns of survey response. A sample of 956 eligible individuals was selected from six health plans. Using a combination of mail and telephone data collection, 663 (69%) questionnaires were completed. This article provides selective results from these tests. RESULTS: The use of screening questions, skip instructions, and tailored "not applicable" response options appeared to facilitate the response task. Some CAHPS access questions were not meaningful to Medicare beneficiaries. The data do not support the need to adjust for length of plan enrollment. CONCLUSION: Analyses suggested changes to improve the MMC survey and to make other CAHPS surveys consistent with these changes.

In situ microviscoelastic measurements by polarization-interferometric monitoring of indentation depth.

new type of computer-controlled instrument has been developed to measure microviscoelastic properties of thin materials. It can independently control and measure indentation loads and depths in situ revealing information about material creep and relaxation. Sample and indenter positions are measured with a specially designed polarization interferometer. Indenter loadings can be varied between 0.5 and 10 g and held constant to +/-41 mg. The resulting indentation depths can be measured in situ to +/-1.2 nm. The load required to maintain constant indentation depths from 0.1 to 5.0 microim can be measured in situ to +/-3.3 mg and the depth held constant to +/-15 nm.