Methods and impact of engagement in research, from theory to practice and back again: early findings from the Patient-Centered Outcomes Research Institute.

PURPOSE: Since 2012, PCORI has been funding patient-centered comparative effectiveness research with a requirement for engaging patients and other stakeholders in the research, a requirement that is unique among the US funders of clinical research. This paper presents PCORI's evaluation framework for assessing the short- and long-term impacts of engagement; describes engagement in PCORI projects (types of stakeholders engaged, when in the research process they are engaged and how they are engaged, contributions of their engagement); and identifies the effects of engagement on study design, processes, and outcomes selection, as reported by both PCORI-funded investigators and patient and other stakeholder research partners. METHODS: Detailed quantitative and qualitative information collected annually from investigators and their partners was analyzed via descriptive statistics and cross-sectional qualitative content and thematic analysis, and compared against the outcomes expected from the evaluation framework and its underlying conceptual model. RESULTS: The data support the role of engaged research partners in refinements to the research questions, selection of interventions to compare, choice of study outcomes and how they are measured, contributions to strategies for recruitment, and ensuring studies are patient-centered. CONCLUSIONS: The evaluation framework and the underlying conceptual model are supported by results to date. PCORI will continue to assess the effects of engagement as the funded projects progress toward completion, dissemination, and uptake into clinical decision making.

Challenges of Developing an Observable Parent-Reported Measure: A Qualitative Study of Functional Impact of ADHD in Children.

BACKGROUND: Informant-reported outcome measures, usually completed by parents, are often administered in pediatric clinical trials with the intention of collecting data to support claims in a medical product label. Recently, there has been an emphasis on limiting these measures to observable content, as recommended in the US Food and Drug Administration guidance on patient-reported outcomes. This qualitative study explores the concept of observability using the example of childhood attention deficit/hyperactivity disorder (ADHD). METHODS: Concept elicitation interviews were conducted with children (aged 6-12 years) diagnosed with ADHD and parents of children with ADHD to identify concepts for a potential parent-reported measure of functional impact of childhood ADHD. The observability of each concept was considered. RESULTS: Of the 30 parents (90% females; mean age = 42.0 years), 24 had a child who was also interviewed (87.5% males; mean age = 9.6 years). Areas of functional impact reported by parents and/or children included the following: 1) functioning within the home/family, 2) academic performance, 3) school behavior, 4) social functioning, 5) emotional functioning, and 6) decreased self-efficacy. Parents cited many examples of direct observation at home, but opportunities for observation of some important areas of impact (e.g., school behavior and peer relationships) were limited. CONCLUSIONS: Findings illustrate the substantial functional impairment associated with childhood ADHD while highlighting the challenges of developing informant-reported outcome measures limited to observable content. Because ADHD has an impact on children's functioning in a wide range of contexts, a parent-report measure that includes only observable content may fail to capture important aspects of functional impairment. Approaches for addressing this observability challenge are discussed.

Opioid-Induced Constipation Among Patients with Chronic Noncancer Pain in the United States, Canada, Germany, and the United Kingdom: Laxative Use, Response, and Symptom Burden Over Time.

PURPOSE: Estimate rate of laxative inadequate response (LIR) over time among patients with chronic noncancer pain with opioid-induced constipation (OIC). METHODS: A prospective longitudinal study was conducted in United States, Canada, Germany, and United Kingdom. Patients on opioid therapy for ≥4 weeks for chronic noncancer pain and OIC completed an Internet-based survey at Baseline and Weeks 2, 4, 6, 8, 12, 16, 20, and 24. 1xLIR was defined as sufficient laxative use (≥1 laxative ≥ 4 times in past 2 weeks) and inadequate response (<3 bowel movements or ≥ 1 constipation symptom rated Moderate or greater). 2xLIR was sufficient laxative use of ≥2 laxatives from different drug classes and inadequate response. Descriptive statistics and logistic regressions were performed. RESULTS: 489 patients (62% female; 85% white) completed Baseline; 27% reported no laxative use; 25% had insufficient laxative use; 48% had sufficient laxative use. During follow-up, 21-28% of patients had no or insufficient laxative use. Prevalence of 1xLIR was 93% at Baseline and ranged from 59-81% across follow-up; 26% met criteria for 2xLIR (follow-up range: 11-20%). CONCLUSIONS: OIC among noncancer pain patients is a persistent and significant condition with varying utilization and response to laxatives thus increasing the ongoing burden of chronic pain. © 2014 Wiley Periodicals, Inc.

Evaluation of the Sexual Desire Relationship Distress Scale (SDRDS) in women with hypoactive sexual desire disorder.

INTRODUCTION: The Sexual Desire Relationship Distress Scale (SDRDS) was developed to address the need for a patient-reported outcome (PRO) measure of sexual distress associated with hypoactive sexual desire disorder (HSDD). The SDRDS is a 17-item PRO that includes items related to personal distress and distress related to relationship with partner. AIM: The aim of this article was to evaluate the psychometric properties of the SDRDS among women with HSDD. METHODS: Pre- and post-menopausal women with HSDD or with no sexual dysfunction completed the SDRDS, Sexual Activity Questions, Female Sexual Distress Scale-Revised (FSDS-R), and desire domain of the Female Sexual Function Index (FSFI) at baseline and 2 and 4 weeks later. MAIN OUTCOME MEASURES: The main outcome measures of this article were item performance, internal consistency, test-retest reliability, construct validity, known groups validity, and responsiveness of the SDRDS. RESULTS: Data from 260 women were analyzed: 101 in each of the pre- and post-menopausal HSDD groups and 29 in each of the pre- and post-menopausal control groups. No differences emerged between pre- and post-menopausal women. Least-squares mean (±standard errors [SE]) SDRDS score was higher in women with HSDD than in women with no sexual dysfunction (43.1 ± 0.9 vs. 6.1 ± 1.7; P < 0.0001), supporting known groups validity. Individual item scores correlated with total scores (r = 0.7-0.9; P < 0.0001). Internal consistency was high, with a Cronbach's alpha of 0.973 at baseline. Test-retest reliability was good, with an intraclass correlation coefficient of 0.89. SDRDS scores correlated strongly with other measures of sexual distress and sexual function including the FSDS-R and FSFI desire domain items. Preliminary analyses suggested that the SDRDS was sensitive to changes in clinical status. CONCLUSIONS: The SDRDS provides a comprehensive and reliable assessment of distress due to decreased sexual desire in women with HSDD and may be a useful measure of treatment effects in clinical trials in women with this condition.

Validation of the UFS-QOL-hysterectomy questionnaire: modifying an existing measure for comparative effectiveness research.

OBJECTIVE: The Uterine Fibroid Symptom and Quality of Life (UFS-QOL) questionnaire, a validated patient-reported outcome measure of fibroid symptoms and health-related quality of life, was modified for use posthysterectomy. This study was conducted to psychometrically validate the UFS-QOL-Hysterectomy questionnaire for potential use in comparative effectiveness research to evaluate uterine fibroid treatments. METHODS: This multicenter prospective study enrolled premenopausal women aged 30 to 50 years with uterine fibroids who were scheduled for hysterectomy, myomectomy, or uterine fibroid embolization. All participants completed the UFS-QOL questionnaire and short form 36 health survey at baseline prior to treatment and 6 and 12 months postprocedure. Women with hysterectomy completed the UFS-QOL-Hysterectomy questionnaire during follow-up visits. Internal consistency reliability, discriminant and concurrent validity, and responsiveness were assessed. RESULTS: A total of 274 women were enrolled (107 uterine fibroid embolization, 61 myomectomy, and 106 hysterectomy) and 89 (83%), 55 (90%), and 91 (86%), respectively, completed the 12-month follow-up. The mean age was 43.2 (uterine fibroid embolization), 40.6 (myomectomy), and 44.5 (hysterectomy) years; 53%, 43%, and 37%, respectively, were black. Cronbach's alphas for the UFS-QOL-Hysterectomy questionnaire at 6 months ranged from 0.70 to 0.96 and from 0.66 to 0.95 at 12 months. Effect sizes ranged from 1.23 to 2.55, indicating that the UFS-QOL-Hysterectomy questionnaire was highly responsive. CONCLUSIONS: The UFS-QOL-Hysterectomy questionnaire is a valid and reliable patient-reported outcome measure of uterine fibroid treatment with hysterectomy and can be used in conjunction with the UFS-QOL questionnaire to compare patient-reported outcomes across treatments.

Further validation of the uterine fibroid symptom and quality-of-life questionnaire.

OBJECTIVE: To further examine the reliability, validity and responsiveness of the uterine fibroid symptom and quality-of-life (UFS-QOL) questionnaire among women with and without uterine fibroids. METHODS: A multicenter, non-randomized, prospective study was conducted with women undergoing treatment for uterine fibroids (fibroid treatment group [FTG]) and normal controls (normal control group [NCG]). Women in the FTG were recruited when they were scheduled for treatment; women in the NCG were recruited during their annual exam. Participants completed the UFS-QOL and a short form 36 health survey (SF-36) at enrollment and at 6 and 12 months. Descriptive statistics, Cronbach's alpha, Spearman's correlations, t tests, and general linear models were used to analyze the internal consistency and test-retest reliability, concurrent and discriminant validity, and responsiveness of the UFS-QOL. RESULTS: There were 89 NCG and 234 FTG women who completed the study. Mean age was 43.1 years for FTG and 40.8 for NCG (P < 0.001). The FTG reported significantly greater symptom severity and worse health-related quality of life (HRQL) than the NCG (all UFS-QOL subscales P < 0.001). The UFS-QOL subscales were significantly correlated in the expected direction and magnitude with each SF-36 subscale in the FTG, indicating acceptable concurrent validity. Cronbach's alphas were 0.73 to 0.97, reflecting adequate internal consistency. Each UFS-QOL subscale was responsive to changes after treatment in the FTG with effect sizes ranging between 1.1 and -2.35. The UFS-QOL remained stable in the NCG during the 1 year follow-up. CONCLUSION: The UFS-QOL is a valid and reliable measure to assess symptoms and HRQL in women with uterine fibroids and is highly responsive to treatment-related changes.

The ability of the general male public to assess their suitability to take 50-mg sildenafil: an assessment of the comprehension of patient information materials via internet survey.

INTRODUCTION: Erectile dysfunction (ED) is the most common male sexual dysfunction and has a negative impact on masculinity and self-esteem. Phosphodiesterase type 5 inhibitors, including sildenafil, are the first-line treatment option for ED. Providing appropriate information regarding suitability for using sildenafil is important. AIM: The purpose of this study was to assess whether a broad spectrum of men could appropriately evaluate their suitability for 50-mg sildenafil after reviewing patient information materials. MAIN OUTCOME MEASURES: Patient information (Pack) on appropriate use of 50-mg sildenafil and patient information leaflet (PIL), a Web survey including demographics, self-assessed suitability for sildenafil use, and suitability screener. METHODS: A randomly selected, population-representative Web-based panel of males in the UK was recruited for this study. Eligible men answered a brief sociodemographic questionnaire and then were presented with the Pack. If a participant desired additional information, he could also review the PIL. The participants then rated the Pack and PIL (if reviewed), self-assessed their suitability for sildenafil use, and completed a previously validated screener for suitability. RESULTS: A total of 1,275 men aged 40 and above were included in these analyses; the mean age was 57.8 ± 9.9 years. A total of 1,054 men reported ED; 517 men (40.5%) deemed themselves suitable for sildenafil; 504 men (39.6%) deemed themselves unsuitable; and 254 (19.9%) were unsure. The concordance rate between screener-assessed suitability and self-assessed suitability was 70.9% (95% confidence interval [CI] = 68.1-73.7%). When accounting for men who would not take sildenafil even though they were suitable or would seek additional information from a healthcare professional prior to using sildenafil, the concordance rate was 84.2% (95% CI = 82.2-86.2%). CONCLUSION: The results of this study suggest that men in the general population are capable of using written sildenafil patient education materials to accurately assess their suitability for treatment with 50-mg sildenafil.

Validation of the urinary sensation scale (USS).

AIM: The purpose of this study was to assess the validity of the Urinary Sensation Scale (USS) in men with overactive bladder and voiding symptoms (OAB-LUTS) and women with overactive bladder (OAB). METHODS: Data from two OAB clinical trials of tolterodine were used. The USS, a 5-point scale, assesses the amount of urinary urgency associated with each urination. Three methods to calculate the USS are: mean urgency (Mean USS); mode urgency (Mode USS); and sum urgency (sum USS). The validity and responsiveness of the scoring methods was assessed using Spearman's correlations, general linear models, and effect sizes. RESULTS: Data from 650 men (Study 1) and 413 women (Study 2) were analyzed. Mean age was 65.2 (men) and 47.8 (women); 70% were Caucasian in both studies. Correlations of USS scores with bladder diary variables were small to moderate and higher among Sum USS than Mean USS (r=0.02-0.64). Correlations among the USS and patient-reported outcomes (PROs) were again small to moderate and higher with Sum USS (r=0.05-0.41). Both the Mean USS and Sum USS significantly discriminated (all P<0.001) among all bladder diary variables (except nocturia and UUI in men) when grouped as improved/not improved as well as by the PROs. Effect sizes for men and women, respectively, were -0.52 and -1.09 for Mean USS and -0.72 and -1.36 for Sum USS. CONCLUSION: The USS is a valid and highly responsive measure of urinary urgency in men with OAB-LUTS and women with OAB.

The ability of men to assess their suitability to take a phosphodiesterase type 5 inhibitor: an assessment of the comprehension of patient information materials.

INTRODUCTION: Erectile dysfunction is a treatable condition that affects a large proportion of men. Most men do not seek medical help for their ED because of embarrassment or social stigma that may lead some men to self-treat. AIM: To evaluate men's ability to self-assess their suitability for 50 mg sildenafil use after reviewing patient information materials. MAIN OUTCOME MEASURES: Patient rating of patient information materials, self-assessment of suitability for sildenafil use, and clinician assessment of sildenafil suitability. METHODS: Men in the UK were recruited through newspaper, radio, and internet advertisements. Eligible men reviewed the 50 mg sildenafil patient information materials (packaging materials and patient information leaflet) at the in-person visit and then completed a survey to rate the materials and self-assess their suitability for sildenafil use. A clinician, blinded to the participant's ED status and self-assessed sildenafil suitability, then conducted a one-on-one interview to assess the participant's ED status and suitability for sildenafil treatment. The primary analysis was the concordance of self-assessed suitability versus clinician-assessed suitability. RESULTS: The initial study phase included 113 generally healthy men, mean age 40.2 ± 13.1 years. The second phase included 70 men with comorbid prostate or cardiac conditions, mean age 60.7 ± 7.8 years. The 183 men rated the patient information materials as easy to understand; few participants reported problems understanding the materials, and many participants learned new information. The concordance rate between clinician-assessed suitability and self-assessed suitability was 73.9% (95% confidence interval [CI] = 66.7-81.2%). When accounting for men who would not take sildenafil even though they were suitable or would seek additional information from a healthcare professional prior to using sildenafil, the concordance rate was 90.1% (95% CI = 85.8-94.4%). CONCLUSION: The results of this UK study suggest that men are capable of using written sildenafil patient education materials to accurately assess their suitability for treatment with 50 mg sildenafil.

Psychometric validation of the overactive bladder satisfaction with treatment questionnaire (OAB-SAT-q).

AIMS: Valid and reliable questionnaires must be used to accurately assess patients' satisfaction with overactive bladder (OAB) treatment. This study evaluated the reliability and validity of the OAB Satisfaction with Treatment Questionnaire (OAB-SAT-q). METHODS: This was a secondary analysis of clinical study data of patients randomized to darifenacin or darifenacin plus Behavioral Modification Program. Patients completed the Overactive Bladder Questionnaire (OAB-q) and a 3-day bladder diary at Baseline and Week 12 and the OAB-SAT-q at Week 12. Internal consistency reliability was assessed by Cronbach's alpha. Concurrent validity was assessed through correlations with OAB-q change scores and adverse events (AEs). Discriminant validity was assessed among subgroups using general linear models. RESULTS: Analyses utilized a per-protocol population (completion of OAB-q at Baseline and OAB-q and OAB-SAT-q at Week 12) (n = 375). Exploratory factor analysis of the OAB-SAT-q revealed three 3-item subscales (Satisfaction, Side Effects, Endorsement) and two single items (Convenience, Preference). Cronbach's alphas = 0.84-0.95. Subscale-to-subscale correlations = 0.10-0.67 (all P < 0.01 except Side Effects and Convenience). The Side Effects subscale significantly correlated with number of treatment-related AEs (r = 0.27; P < 0.01) and discriminated between patients with/without dry mouth and patients with/without constipation. The Satisfaction and Endorsement subscales discriminated between patients who worsened or had no change in micturition frequency and urinary urgency and patients who had a reduction of >3 episodes (all P < 0.001). The OAB-SAT-q does not appear to discriminate by incontinence episodes. CONCLUSION: The OAB-SAT-q demonstrated good psychometric properties in this initial evaluation-including internal consistency reliability and concurrent and discriminant validity-and appears to be a useful assessment of OAB treatment satisfaction. Neurourol. Urodynam. 28:416-422, 2009. (c) 2008 Wiley-Liss, Inc.

Psychometric equivalence of the OAB-q in Danish, German, Polish, Swedish, and Turkish.

OBJECTIVE: Patient-reported outcomes (PROs) are measures of patients' health status provided directly by patients and when utilized in clinical trials, multiple language versions may be needed. The overactive bladder questionnaire (OAB-q), a self-administered PRO assessing symptom bother and health-related quality of life (HRQL) in patients with OAB, was developed in US English and has been translated into more than 40 languages. This analysis evaluated the psychometric equivalence of five language versions of the OAB-q. METHODS: The Disease Management Study (DMS) was a multicenter, double-blind, placebo-controlled, parallel group, randomized study in adults with OAB. Participants completed the OAB-q, 3-day micturition diaries, and the patient's perception of bladder condition (PPBC) at baseline and weeks 1 and 12 of treatment. RESULTS: Data from 398 patients from five countries were analyzed: Denmark (N = 71), Germany (N = 127), Poland (N = 60), Sweden (N = 94), and Turkey (N = 46). Participants were a mean of 57.4 years old; 31% were male; and almost all were Caucasian. Cronbach alphas for the OAB-q symptom bother subscale = 0.71 to 0.83 and 0.82 to 0.94 for the HRQL subscales (concern, coping, sleep, and social) across all five languages. OAB-q subscales were significantly correlated with PPBC in all languages. Mean baseline to week 12 change scores = -21.4 to -30.3 for symptom bother and 5.2 to 36.0 for the HRQL subscales. Effect sizes for the symptom bother subscale = 0.92 to 2.79 and 0.21 to 1.30 for the HRQL subscales. CONCLUSION: OAB-q language versions of Danish, German, Polish, Swedish, and Turkish demonstrated acceptable psychometric characteristics, including internal consistency reliability, construct validity, and responsiveness.

Gastrointestinal (GI)-Specific patient reported outcomes instruments differentiate between renal transplant patients with or without GI symptoms: results from a South American cohort.

BACKGROUND: Immunosuppressive therapies have burdensome side effects which may lead to sub-therapeutic dosing and non-compliance. Patients on different immunosuppressant regimens may feel less bothered by Gastrointestinal (GI) side effects or report better health-related quality of life (HRQL). We evaluated the reliability and validity of two GI-specific outcome instruments (Gastrointestinal Symptom Rating Scale (GSRS; higher scores = increased severity) and Gastrointestinal Quality of Life Index (GIQLI; higher scores = better GI-specific HRQL)) in renal transplant patients in South America. METHODS: Data from 5 South American centers participating in an international, longitudinal, observational study were analyzed. Patients were > or = 1 month post transplant and on mycophenolate mofetil (MMF) and a calcineurin inhibitor. Patients completed the GSRS, GIQLI, and Psychological General Well-Being (PGWB; higher scores = better HRQL) Index at baseline and at 4-6 weeks. Internal consistency, test-retest reliability and construct and discriminant validity were assessed. RESULTS: Sixty-two participants were enrolled. Mean age was 42 years; mean time since transplant was 3.3 years; 57% were male; 65% received a deceased organ transplant and 68%had GI events. The GSRS and GIQLI demonstrated high internal consistency (Cronbach's alphas 0.72-0.96). Test-retest reliability was adequate (intraclass correlation coefficient > 0.6) for all GIQLI subscales and all GSRS subscales except Diarrhea and Reflux syndrome. Correlations between the GSRS and PGWB were moderate (range: -0.21 to -0.53, all p < 0.001 except 6 correlations with p < 0.05); correlations between the GIQLI and PGWB were higher (range: 0.36 to 0.71 p < 0.001), indicating good construct validity. The GSRS and GIQLI demonstrated good discriminant validity, as they clinically and statistically distinguished between patients with and without GI complaints and among patients with varying GI complication severity. Patients with GI complaints reported higher GSRS scores than patients without complaints (all p < 0.001). GIQLI scores were lower in patients with GI complaints than patients without complaints (all p < 0.001). The GSRS and GIQLI differentiated among patients with four GI severity levels (overall Kruskall-Wallis test p < 0.001, except for one scale). The GSRS and GIQLI are acceptable for use in South American renal transplant patients. These two instruments demonstrate adequate reliability and validity. Patients with GI complaints reported poor HRQL and strategies are needed to improve patients' HRQL.

Impact of uterine fibroid symptoms on health-related quality of life of US women: evidence from a cross-sectional survey.

BACKGROUND: Uterine fibroids (UF) are associated with significant health-related quality of life (HRQL) impact. This study examined the impact of UF symptoms on HRQL. METHODS: An online cross-sectional survey of 18 to 49 year old US women was conducted and collected demographics, UF prevalence, symptoms, and HRQL using the UFS-QOL. Descriptive statistics were used to examine the impact of symptom presence, severity, bothersomeness, and number of UF symptoms on HRQL. Analyses were weighted to match the US female population distribution. Multivariate regressions were performed with each subscale as a dependent variable to examine the impact of individual UF symptoms on HRQL. RESULTS: A total of 59,411 (15.5%) panel members completed the prevalence screener; 4848 met inclusion criteria; 955 had UF and no hysterectomy. Mean age was 40.3; 58% were white; 63% were married/civil union. Common UF symptoms were: lower back pain (65%), fatigue/weariness (63%), bloating (61%), pelvic pain/cramping during menses (63%), and heavy bleeding during menses (54%). Mean UFS-QoL subscale scores were significantly (p < .05) worse among women with a UF symptom versus women without the symptom. Women who rated their UF symptoms as severe had significantly (p < .001) worse UFS-QoL scores than women with mild or moderate symptoms. UFS-QoL subscale scores worsened as the number of symptoms increased. In the regressions, the presence of bleeding and non-bleeding symptoms were related to worse UFS-QoL subscale scores. CONCLUSION: HRQL among women with UF was significantly impacted by UF-related symptoms. Greater impact was observed as the number and severity of symptoms increased.

Validation of the 4 week recall version of the Uterine Fibroid Symptom and Health-related Quality of Life (UFS-QOL) Questionnaire.

OBJECTIVE: To assess the psychometric performance of the 4 week recall version of the Uterine Fibroid Symptom and Health-related Quality of Life Questionnaire (UFS-QoL), a patient measure of the severity of uterine fibroid (UF) symptoms and their impact on health-related quality of life (HRQL). METHODS: This was a retrospective analysis of phase 2a data from pre-menopausal women with heavy menstrual bleeding associated with UF. Participants completed the UFS-QoL at Baseline, Treatment Month 3, and Follow-up Month 3 and a daily diary with a Menstrual Bleeding Scale and the UF Daily Symptom Scale throughout the study duration. Descriptive statistics were performed on patient demographic characteristics; analyses were conducted to assess the internal consistency reliability, validity, and responsiveness of the UFS-QoL 4 week recall version. RESULTS: A total of 271 women were enrolled with a mean age of 41.8 years; 74% were black. The UFS-QoL demonstrated excellent internal consistency reliability, with Cronbach's alpha coefficient values >0.70 for each subscale at each study visit. Results indicated good concurrent validity with the UF Daily Symptom Scale items. The women with amenorrhea at Treatment Month 3 had significantly better scores on all UFS-QoL subscales and HRQL Total than women with menstrual bleeding, indicating acceptable discriminant validity. Mean subscale change scores from Baseline to Treatment Month 3 were 19.2 to 39.8. Effect sizes were moderate to large (0.53 to 1.86), demonstrating responsiveness to change. LIMITATIONS: As this study is a post hoc validation of the 4 week recall UFS-QOL, it is limited to the clinical trial data available and does not include a direct comparison to the 3 month recall version of UFS-QOL. CONCLUSIONS: The 4 week recall version of the UFS-QoL demonstrated good internal consistency reliability, concurrent validity, and responsiveness and is psychometrically comparable to the original 3 month recall UFS-QoL. CLINICAL TRIAL REGISTRATION: Data from a phase 2a, cohort design proof of concept study (trial M12-663); ClinicalTrials.gov identifier NCT01441635. Date of Registration: 6 September 2011.

Satisfaction with Therapy Among Patients with Chronic Noncancer Pain with Opioid-Induced Constipation.

BACKGROUND: Greater satisfaction with medication is associated with better adherence; however, specific to opioid-induced constipation (OIC), data on the relationship between medication satisfaction and efficacy are lacking. OBJECTIVE: To understand satisfaction with therapy among patients with chronic noncancer pain and OIC. METHODS: A prospective longitudinal study was conducted in the United States, Canada, Germany, and the United Kingdom using web-based patient surveys. Patients on daily opioid therapy for ≥ 74 weeks for the treatment of chronic noncancer pain with OIC were recruited from physician offices and completed a web-based survey at baseline and weeks 2, 4, 6, 8, 12, 16, 20, and 24. When completing each survey, patients selected the remedies used in the previous 2 weeks to relieve constipation; options included natural/behavioral therapies, over-the-counter (OTC) therapies, and prescription laxatives. Patients selected the amount of relief and satisfaction with each selected therapy. Descriptive statistics were calculated; Spearman's correlations were calculated for symptom relief and satisfaction. RESULTS: Mean age of the 489 patients who met the criteria for OIC and completed the baseline survey was 52.6 ± 11.6 years; 62% were female; 85% were white. Increasing levels of relief from constipation were associated with increasing levels of satisfaction for all agents; correlations were > 0.55 and statistically significant (P < 0.001). Among the patients who had used OTC therapies in the 2 weeks prior to baseline, 54% to 73% reported that they were somewhat or very satisfied with the therapy. Yet, of these satisfied patients, 28% to 63% experienced no or only slight relief from the therapy. Twenty percent to 79% of the patients who had used prescription laxatives in the 2 weeks prior to baseline reported being at least somewhat satisfied with the therapy. CONCLUSIONS: These results indicate that there is a high rate of inadequate response to laxatives for patients with OIC that persisted for the 6 months of this study. While increased relief from constipation was associated with increased satisfaction for all therapies, there remains a substantial number of patients who report satisfaction despite having only inadequate relief from OIC that merits further investigation.

Opioid-Induced Constipation among a Convenience Sample of Patients with Cancer Pain.

BACKGROUND: Little is known regarding the burden of opioid-induced constipation (OIC) among patients who suffer from cancer-related pain. METHODS: A prospective longitudinal study was conducted among cancer patients in the United Kingdom (UK), Canada, and Germany, which included medical record data abstraction, Internet-based patient surveys, and physician surveys. Patients on daily opioid therapy (≥30 mg for ≥4 weeks) for treatment of cancer pain with self-reported OIC were recruited. Response to laxatives was defined by classifying participants into categories of laxative use and evaluating the prevalence of inadequate response. Descriptive statistics were used to evaluate outcomes, including the patient assessment of constipation-symptom (PAC-SYM), patient assessment of constipation-quality of life, EuroQOL-5 dimensions, and global assessment of treatment benefit, satisfaction, and willingness to continue. RESULTS: Recruitment was difficult for this study with only 31 participants completing the baseline survey and meeting criteria for opioid use and OIC (26 UK, 1 Canada, and 4 Germany). Fifty-two percent (n = 16) of participants were male, and all were White. Breast (23%, n = 7), pancreatic (13%, n = 4), and multiple myeloma (13%, n = 4) were the most common cancers. Mean duration of chronic pain and opioid use were 2.3 and 1.3 years, respectively. Participants reported having a mean of 4.4 bowel movements/week in the 2 weeks prior to baseline, of which a mean of 0.9 were spontaneous. Most participants (90%, n = 28) were using at least 1 lifestyle approach to manage their constipation; 65% (n = 20) were taking ≥1 over-the-counter laxative; 19% (n = 6) were taking ≥1 prescription laxative; 23% (n = 7) reported no laxative use in the prior 2 weeks. Moderate-to-severe constipation symptoms on the PAC-SYM were common, and mean scores on health-related quality of life outcomes were comparable to chronic pain populations. CONCLUSION: In this primarily UK sample, there appears to be considerable unmet OIC treatment needs among cancer patients.

Laxative utilization over time in chronic pain patients with opioid-induced constipation.

AIM: To determine laxative utilization over time among chronic noncancer pain patients with opioid-induced constipation (OIC). SETTING: A prospective longitudinal study conducted in the USA, Canada, Germany and UK. METHODS: Patients on daily opioid therapy for treatment of chronic noncancer pain with OIC were recruited from clinics to complete a survey at Baseline and weeks 2, 4, 6, 8, 12, 16, 20 and 24. RESULTS: 489 patients completed baseline with 452 completing one or more follow-up visits. 128 (28%) were nonlaxative users, 112 (25%) were insufficient laxative users and 212 (47%) were sufficient laxative users. The consistent sufficient laxative users reported the most bowel movements per week. CONCLUSION: The majority of OIC patients do not take or only intermittently take laxatives.

An observational study of health-related quality of life and pain outcomes in chronic low back pain patients treated with fentanyl transdermal system.

BACKGROUND: The analgesic effect of long-acting opioids, such as transdermal fentanyl, has been demonstrated in patients with cancer, neuropathic pain and chronic low back pain (CLBP). However, the broader effect of long-acting opioids on the patient's health-related quality of life (HRQoL) is less well known. OBJECTIVE: To evaluate HRQoL outcomes in CLBP patients treated with transdermal fentanyl. RESEARCH DESIGN AND METHODS: An observational study was conducted at 17 clinical centers in the US. Eligible patients had CLBP diagnosis for at least 3 months and were taking short-acting opioids chronically, and then initiated transdermal fentanyl treatment. Patients completed the Treatment Outcomes in Pain Survey (TOPS), which includes the SF-36 Health Survey, at baseline and > or = 9 weeks of treatment. The HRQoL burden of CLBP was determined by comparing CLBP patients' SF-36 scores to the general US population and low back pain patient norms. HRQoL outcomes were determined by comparing baseline and follow-up TOPS and SF-36 scores. Additionally, HRQoL outcomes were evaluated across patient groups stratified by changes in pain intensity ratings as measured by an 11-point numerical rating scale. RESULTS: At baseline CLBP patients (N = 131) scored one-to-two standard deviations (SD) below age and gender adjusted SF-36 general population norms (MANOVA F = 127.1, p < 0.0001) and significantly lower than low back pain norms (MANOVA F = 125.3, p < 0.0001). At follow-up, significant improvement (p < 0.05) was observed on six of the SF-36 scales and both SF-36 summary measures and five of the six TOPS pain-related scales. The magnitude of change in scores in effect size units among these scales ranged from 0.17 to 0.80, which are considered small to large effect size changes. HRQoL score improvement was greatest among patients experiencing the greatest pain relief. CONCLUSION: CLBP patients who chronically used short-acting opioids showed tremendous HRQoL burden. Favorable HRQoL outcomes were observed among patients who reported pain relief.

The state of patient-reported outcomes in atrial fibrillation : a review of current measures.

Atrial fibrillation (AF) is the most common cardiac arrhythmia, affecting approximately 2.2 million people in the US. The presentation of AF ranges from asymptomatic to severely symptomatic. When symptomatic, AF has been shown to have an adverse impact on health-related quality of life (HR-QOL) and to result in increased healthcare costs. The objective of this analysis was to review the current AF literature on patient-reported outcomes (PROs) in order to evaluate the impact of AF on PROs and the applicability of current PRO measures in assessing AF outcomes.HR-QOL and symptoms were the most frequently assessed PROs; however, the sensitivity of the majority of the questionnaires for detecting subtle change is not known. For highly symptomatic patients, interventional procedures reduce symptoms and improve HR-QOL; however, this is a small cohort of patients with AF. For the most part, PROs are equivalent between pharmacological treatments or are not known for the large percentage of patients treated pharmacologically with antiarrhythmic or rate-controlling drugs.PRO assessment in AF patients is an area that needs continued development. AF-specific PRO measures are needed to assess the full range of patient symptoms and treatment outcomes. The impact of paroxysmal AF versus permanent AF is not well delineated, and sex and nationality differences are not known. In addition, the impact of AF on daily activities and HR-QOL is not clearly described.

Validation of an overactive bladder awareness tool for use in primary care settings.

Overactive bladder (OAB)--a syndrome characterized by urinary urgency, with or without urge incontinence, urinary frequency and nocturia--is estimated to affect 10% to 20% of the US and European populations. This study was carried out to validate a patient-administered screening awareness tool to identify patients with bothersome OAB symptoms. Patients were recruited from 12 primary care and 1 gynecology practice during regularly scheduled appointments. Enrollees completed an 8-item questionnaire assessing the amount of "bother" they associated with OAB symptoms. Clinicians then asked the patients 4 questions regarding urinary frequency, urgency, nocturia, and incontinence. If the screening was positive for symptoms of OAB or if the patient provided positive responses to the urinary symptom questions, the clinician asked additional questions regarding lifestyle and coping behaviors. The clinician then diagnosed the patient, placing him or her in the "No OAB," "Possible OAB," or "Probable OAB" category. Multivariable logistic regressions controlling for age and sex were performed to assess the applicability of the tool for identifying patients with OAB. A total of 1,299 patients were enrolled, and 1,260 provided complete data. Patients were aged 51.6+/-17.0 years, 62% were female, most (89%) were Caucasian, 22% experienced urinary urgency, and 18% experienced urge incontinence. The prevalence of Probable OAB was 12%. The c-index of the model identifying patients with a diagnosis of Probable OAB was 0.96, with a sensitivity and specificity of 98.0 and 82.7. For OAB-V8 scores >or=8, the odds ratio for Probable OAB was 95.7 (95% CI: 29.3; 312.4). The OAB-V8 performed well in helping clinicians identify patients with bothersome OAB symptoms in a primary care setting and will assist clinicians in identifying patients who may benefit from treatment.