Development of the Incontinence Utility Index: estimating population-based utilities associated with urinary problems from the Incontinence Quality of Life Questionnaire and Neurogenic Module

BACKGROUND: Generic utility instruments may not fully capture the impact and consequences of urinary problems. Condition-specific preference-based measures, developed from previously validated disease-specific patient-reported outcomes instruments, may add relevant information for economic evaluations. The aim of this study was to develop a condition-specific preference-based measure, the Incontinence Utility Index (IUI), for valuing health states associated with urinary problems. METHODS: A two-step process was implemented. First, an abbreviated health state classification system was developed from the Incontinence Quality of Life Questionnaire (I-QOL) and Neurogenic Module by applying Rasch modelling, classical psychometrical testing and expert criteria to data from two pivotal trials comprised of neurogenic detrusor overactivity (NDO) patients. Criterion, convergent validity and concordance with the original instrument was assessed in the abbreviated version. Then, a multi-attribute utility function (MAUF) was estimated from a representative sample of the UK non-institutionalized adult general population. Visual analogue and time-trade off (TTO) evaluations were applied in the elicitation process. Predictive validity of the MAUF was tested comparing estimated and direct utility scores. RESULTS: The abbreviated health state classification system generated from the NDO sample contained 5 attributes with 3 levels of response and had adequate psychometrical properties: significant differences in scores according to the reduction in the frequency of urinary incontinence episodes [UIE] (p < 0.001); Spearman correlation coefficient with number of daily UIE = −0.43; p < 0.01 and Intraclass Correlation Coefficient (ICC, 95% CI) with the original version = 0.90 (0.89-0.91; p < 0.001). Next, 442 participants were interviewed (398 cases were valid, generating 2,388 TTO evaluations) to estimate the social preferences for derived health states. Mean age was 44.75 years (interquartile range 33.5-55.5) and 60.1% were female. An overall algorithm for the IUI was estimated and transformed onto a dead = 0.00 and full health = 1.00 scale. Model fits were acceptable (R-squared = 0.923 and 0.978). Predictive validity was adequate: ICC (95% CI) = 0.928 (0.648-0.985) and Mean of Absolute Differences = 0.038. CONCLUSIONS: The newly developed IUI is a preference-based measure for urinary problems related to NDO that provides general population-based utility scores with adequate predictive validity. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00461292, NCT00311376. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12955-014-0147-7) contains supplementary material, which is available to authorized users

Chronic recurrent ankle sprain: A randomized clinical trial studying the impact of two treatment protocols

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Development and validation of the Ulcerative Colitis patient-reported outcomes signs and symptoms (UC-pro/SS) diary

Abstract Background The clinical course of ulcerative colitis (UC) and the effects of treatment are assessed through patient-reported signs and symptoms (S&S), and endoscopic evidence of inflammation. The Ulcerative Colitis Patient-Reported Outcomes Signs and Symptoms (UC-PRO/SS) measure was developed to standardize the quantification of gastrointestinal S&S of UC in clinical trials through direct report from patient ratings. Design The UC-PRO/SS was developed by collecting data from concept elicitation (focus groups, and individual interviews), then refined through a process of cognitive interviews of 57 UC patients. Measurement properties, including item-level statistics, scaling structure, reliability, and validity, were evaluated in an observational, four-week study of adults with mild to severe UC (N = 200). Results Findings from qualitative focus groups and interviews identified nine symptom items covering bowel and abdominal symptoms. The final UC-PRO/SS daily diary includes two scales: Bowel S&S (six items) and Abdominal Symptoms (three items), each scored separately. Each scale showed evidence of adequate reliability (α = 80 and 0.66, respectively); reproducibility (intraclass correlation coefficient = 0.81, 0.71) and validity, including moderate-to-high correlations with the Partial Mayo Score (0.79; 0.45) and Inflammatory Bowel Disease Questionnaire (IBDQ) total score (− 0.70; − 0.61). Scores discriminated by level of disease severity, as defined by the Partial Mayo Score, Patient Global Rating, and Clinician Global Rating (p < 0.0001). Conclusions Results suggest that the UC-PRO/SS is a reliable and valid measure of gastrointestinal symptom severity in UC patients. Additional longitudinal data are needed to evaluate the ability of the UC-PRO/SS scores to detect responsiveness and inform the selection of responder definitions.https://deepblue.lib.umich.edu/bitstream/2027.42/143869/1/41687_2018_Article_49.pd

A randomized controlled phase III study of VB-111 combined with bevacizumab vs bevacizumab monotherapy in patients with recurrent glioblastoma (GLOBE)

BACKGROUND: Ofranergene obadenovec (VB-111) is an anticancer viral therapy that demonstrated in a phase II study a survival benefit for patients with recurrent glioblastoma (rGBM) who were primed with VB-111 monotherapy that was continued after progression with concomitant bevacizumab. METHODS: This pivotal phase III randomized, controlled trial compared the efficacy and safety of upfront combination of VB-111 and bevacizumab versus bevacizumab monotherapy. Patients were randomized 1:1 to receive VB-111 1013 viral particles every 8 weeks in combination with bevacizumab 10 mg/kg every 2 weeks (combination arm) or bevacizumab monotherapy (control arm). The primary endpoint was overall survival (OS), and secondary endpoints were objective response rate (ORR) by Response Assessment in Neuro-Oncology (RANO) criteria and progression-free survival (PFS). RESULTS: Enrolled were 256 patients at 57 sites. Median exposure to VB-111 was 4 months. The study did not meet its primary or secondary goals. Median OS was 6.8 versus 7.9 months in the combination versus control arm (hazard ratio, 1.20; 95% CI: 0.91-1.59; P = 0.19) and ORR was 27.3% versus 21.9% (P = 0.26). A higher rate of grades 3-5 adverse events was reported in the combination arm (67% vs 40%), mainly attributed to a higher rate of CNS and flu-like/fever events. Trends for improved survival with combination treatment were seen in the subgroup of patients with smaller tumors and in patients who had a posttreatment febrile reaction. CONCLUSIONS: In this study, upfront concomitant administration of VB-111 and bevacizumab failed to improve outcomes in rGBM. Change of treatment regimen, with the lack of VB-111 monotherapy priming, may explain the differences from the favorable phase II results. CLINICAL TRIALS REGISTRATION: NCT02511405

Estimating background rates of Guillain-Barré Syndrome in Ontario in order to respond to safety concerns during pandemic H1N1/09 immunization campaign

Abstract Background The province of Ontario, Canada initiated mass immunization clinics with adjuvanted pandemic H1N1 influenza vaccine in October 2009. Due to the scale of the campaign, temporal associations with Guillain-Barré syndrome (GBS) and vaccination were expected. The objectives of this analysis were to estimate the number of background GBS cases expected to occur in the projected vaccinated population and to estimate the number of additional GBS cases which would be expected if an association with vaccination existed. The number of influenza-associated GBS cases was also determined. Methods Baseline incidence rates of GBS were determined from published Canadian studies and applied to projected vaccine coverage data to estimate the expected number of GBS cases in the vaccinated population. Assuming an association with vaccine existed, the number of additional cases of GBS expected was determined by applying the rates observed during the 1976 Swine Flu and 1992/1994 seasonal influenza campaigns in the United States. The number of influenza-associated GBS cases expected to occur during the vaccination campaign was determined based on risk estimates of GBS after influenza infection and provincial influenza infection rates using a combination of laboratory-confirmed cases and data from a seroprevalence study. Results The overall provincial vaccine coverage was estimated to be between 32% and 38%. Assuming 38% coverage, between 6 and 13 background cases of GBS were expected within this projected vaccinated cohort (assuming 32% coverage yielded between 5-11 background cases). An additional 6 or 42 cases would be expected if an association between GBS and influenza vaccine was observed (assuming 32% coverage yielded 5 or 35 additional cases); while up to 31 influenza-associated GBS cases could be expected to occur. In comparison, during the same period, only 7 cases of GBS were reported among vaccinated persons. Conclusions Our analyses do not suggest an increased number of GBS cases due to the vaccine. Awareness of expected rates of GBS is crucial when assessing adverse events following influenza immunization. Furthermore, since individuals with influenza infection are also at risk of developing GBS, they must be considered in such analyses, particularly if the vaccine campaign and disease are occurring concurrently

Development and validation of the Crohn’s disease patient-reported outcomes signs and symptoms (CD-PRO/SS) diary

Abstract Background The clinical course of Crohn’s disease (CD) and the effect of its treatment are monitored through patient-reported signs and symptoms (S&S), and endoscopic evidence of inflammation. The Crohn’s Disease Patient-reported Outcomes Signs and Symptoms (CD-PRO/SS) measure was developed to standardize the quantification of gastrointestinal S&S of CD through direct report from patient ratings. Methods The CD-PRO/SS was developed based on data from concept elicitation (focus groups, interviews; n = 29), then refined through cognitive interviews of CD patients (n = 20). Measurement properties, including item-level statistics, scaling structure, reliability, and validity, were examined using secondary analyses of baseline and two-week clinical trial data of adults with moderate-to-severe CD (n = 238). Results Findings from qualitative interviews identified nine S&S items covering bowel and abdominal symptoms. The final CD-PRO/SS daily diary includes two scales: Bowel S&S (three items) and Abdominal Symptoms (three items), each scored separately. Each scale showed evidence of adequate reliability (α = 0.74 and 0.67, respectively); reproducibility (intraclass correlation coefficient > 0.80), and validity, with the last including moderate correlations with the Inflammatory Bowel Disease Questionnaire bowel symptom score and select items (ranging from r = 0.43–0.54). Scores distinguished patients categorized by patient global ratings of disease severity (p < 0.0001). Conclusions Results suggest the CD-PRO/SS is a reliable and valid measure of gastrointestinal symptom severity in CD patients. Additional longitudinal data are needed to evaluate the ability of the CD-PRO/SS scores to detect responsiveness and inform the selection of responder definitions.https://deepblue.lib.umich.edu/bitstream/2027.42/143542/1/41687_2018_Article_44.pd