Measuring Health and Broader Well-Being Benefits in the Context of Opiate Dependence: The Psychometric Performance of the ICECAP-A and the EQ-5D-5L

BACKGROUND: Measuring outcomes in economic evaluations of social care interventions is challenging because both health and well-being benefits are evident. The ICEpop CAPability instrument for adults (ICECAP-A) and the five-level EuroQol five-dimensional questionnaire (EQ-5D-5L) are measures potentially suitable for the economic evaluation of treatments for substance use disorders. Evidence for their validity in this context is, however, lacking. OBJECTIVES: To assess the construct validity of the ICECAP-A and the EQ-5D-5L in terms of convergent and discriminative validity and sensitivity to change on the basis of standard clinical measures (Clinical Outcomes in Routine Evaluation-Outcome Measure, Treatment Outcomes Profile, Interpersonal Support Evaluation List, Leeds Dependence Questionnaire, and Social Satisfaction Questionnaire). METHODS: A secondary analysis of pilot trial data for heroin users in opiate substitution treatment was conducted. Baseline convergence with clinical measures was assessed using the Pearson correlation coefficient. Discriminative validity was assessed using one-way analysis of variance and stepwise regressions. Sensitivity to changes in clinical indicators was assessed at 3 and 12 months using the standardized response mean statistic and parametric and nonparametric testing. RESULTS: Both measures had the same level of construct validity, except for clinical indicators of well-being, for which the ICECAP-A performed better. The ICECAP-A was sensitive to changes in both health and well-being indicators. The EQ-5D-5L had lower levels of sensitivity to change, and a ceiling effect (27%), particularly evident in the dimensions of self-care (89%), mobility (75%), and usual activities (72%). CONCLUSIONS: The findings support the construct validity of both measures, but the ICECAP-A gives more attention to broader impacts and is more sensitive to change. The ICECAP-A shows promise in evaluating treatments for substance use disorders for which recovery is the desired outcome

Clinical Outcomes and Survival Following Treatment of Metastatic Castrate-Refractory Prostate Cancer With Docetaxel Alone or With Strontium-89, Zoledronic Acid, or Both

Importance Bony metastatic castrate-refractory prostate cancer (CRPC) has a poor prognosis and high morbidity. Zoledronic acid (ZA) is commonly combined with docetaxel in practice but lacks evidence that combining is effective, and strontium-89 (Sr89) is generally used palliatively in patients unfit for chemotherapy. Phase 2 analysis of the TRAPEZE trial confirmed combining the agents was safe and feasible, and the objectives of phase 3 include assessment of the treatments on survival. Objective To determine clinical effectiveness and cost-effectiveness of combining docetaxel, ZA, and Sr89, all having palliative benefits and used in bony metastatic CRPC to control bone symptoms and, for docetaxel, to prolong survival. Design, Setting, and Participants The TRAPEZE trial is a 2 × 2 factorial trial comparing docetaxel alone or with ZA, Sr89, or both. A cohort of 757 participants were recruited between February 2005 and February 2012 from hospitals in the United Kingdom. Overall, 169 participants (45%) had received palliative radiotherapy, and the median (IQR) prostate-specific antigen level was 146 (51-354). Follow-ups were performed for at least 12 months. Interventions Up to 10 cycles of docetaxel alone; docetaxel with ZA; docetaxel with a single Sr89 dose after 6 cycles; or docetaxel with both ZA and Sr89. Main Outcomes and Measures Primary outcomes included clinical progression-free survival (CPFS) (pain progression, skeletal-related events [SREs], or death) and cost-effectiveness. Secondary outcomes included SRE-free interval, pain progression–free interval, total SREs, and overall survival (OS). Results Overall, of 757 participants, 349 (46%) completed docetaxel treatment. Median (IQR) age was 68 (63-73) years. Clinical progression-free survival did not reach statistical significance for either Sr89 or ZA. Cox regression analysis adjusted for all stratification variables showed benefit of Sr89 on CPFS (hazard ratio [HR], 0.85; 95% CI, 0.73-0.99; P = .03) and confirmed no effect of ZA (HR, 0.98; 95% CI, 0.85-1.14; P = .81); ZA had a significant effect on SRE-free interval (HR, 0.78; 95% CI, 0.65-0.95; P = .01). For OS, there was no effect of either Sr89 (HR, 0.92; 95% CI, 0.79-1.08; P = 0.34) or ZA (HR, 0.99; 95% CI, 0.84-1.16; P = 0.91). Conclusions and Relevance Strontium-89 combined with docetaxel improved CPFS but did not improve OS, SRE-free interval, or total SREs; ZA did not improve CPFS or OS but did significantly improve median SRE-free interval and reduced total SREs by around one-third, suggesting a role as postchemotherapy maintenance therapy

Ultrasound bladder wall thickness and detrusor overactivity:A multicentre test accuracy study

OBJECTIVE: Women with overactive bladder (OAB) often undergo urodynamics before invasive treatments are considered. Ultrasound measurement of bladder wall thickness (BWT) is a less invasive, less expensive and widely available test. It has the potential to diagnose the presence of detrusor overactivity (DO). We aimed to evaluate the accuracy of BWT in the diagnosis of DO. DESIGN: Prospective cohort study. SETTING: Twenty-two UK clinics (university and district general hospitals). METHODS: Consecutive eligible women with OAB symptoms had transvaginal ultrasound to estimate BWT (index test). The reference standard for the diagnosis of DO was urodynamic testing with multichannel subtracted cystometry. MAIN OUTCOME MEASURES: The sensitivity, specificity and likelihood ratios using a BWT threshold of ≥5 mm were used to indicate the presence of DO, and the area under the receiver operating characteristics (ROC) curve to give an overall estimate of BWT accuracy. RESULTS: Between March 2011 and 2013, 644/687 (94%) women recruited had both tests. The mean age was 52.7 years (standard deviation 13.9) and DO was diagnosed in 399/666 (60%) women. BWT had a sensitivity of 43% [95% confidence interval (CI) 38-48%], specificity of 62% (95% CI 55-68%), and likelihood ratios of 1.11 (95% CI 0.92-1.35) and 0.93 (95% CI 0.82-1.06) for positive and negative tests, respectively. The area under the ROC curve was 0.53 (95% CI 0.48-0.57). Extensive sensitivity analyses and subgroup analyses were carried out, but did not alter the interpretation. CONCLUSIONS: BWT is not a good replacement test for urodynamics in women with overactive bladder. TWEETABLE ABSTRACT: Bladder wall thickness is not a good replacement test for urodynamics in women with overactive bladder

Paving the path for implementation of clinical genomic sequencing globally - Are we ready?

Despite the emerging evidence in recent years, successful implementation of clinical genomic sequencing (CGS) remains limited and is challenged by a range of barriers. These include a lack of standardized practices, limited economic assessments for specific indications, limited meaningful patient engagement in health policy decision-making, and the associated costs and resource demand for implementation. Although CGS is gradually becoming more available and accessible worldwide, large variations and disparities remain, and reflections on the lessons learned for successful implementation are sparse. In this commentary, members of the Global Economics and Evaluation of Clinical Genomics Sequencing Working Group (GEECS) describe the global landscape of CGS in the context of health economics and policy and propose evidence-based solutions to address existing and future barriers to CGS implementation. The topics discussed are reflected as two overarching themes: (1) system readiness for CGS and (2) evidence, assessments, and approval processes. These themes highlight the need for health economics, public health, and infrastructure and operational considerations; a robust patient- and family-centered evidence base on CGS outcomes; and a comprehensive, collaborative, interdisciplinary approach

Comprehensive evaluation of a prospective Australian patient cohort with suspected genetic kidney disease undergoing clinical genomic testing: a study protocol

Introduction: Recent advances in genomic technology have allowed better delineation of renal conditions, the identification of new kidney disease genes and subsequent targets for therapy. To date, however, the utility of genomic testing in a clinically ascertained, prospectively recruited kidney disease cohort remains unknown. The aim of this study is to explore the clinical utility and cost-effectiveness of genomic testing within a national cohort of patients with suspected genetic kidney disease who attend multidisciplinary renal genetics clinics. Methods and Analysis: This is a prospective observational cohort study performed at 16 centres throughout Australia. Patients will be included if they are referred to one of the multidisciplinary renal genetics clinics and are deemed likely to have a genetic basis to their kidney disease by the multidisciplinary renal genetics team. The expected cohort consists of 360 adult and paediatric patients recruited by December 2018 with ongoing validation cohort of 140 patients who will be recruited until June 2020. The primary outcome will be the proportion of patients who receive a molecular diagnosis via genomic testing (diagnostic rate) compared with usual care. Secondary outcomes will include change in clinical diagnosis following genomic testing, change in clinical management following genomic testing and the cost-effectiveness of genomic testing compared with usual care. Ethics and Dissemination: The project has received ethics approval from the Melbourne Health Human Research Ethics Committee as part of the Australian Genomics Health Alliance protocol: HREC/16/MH/251. All participants will provide written informed consent for data collection and to undergo clinically relevant genetic/genomic testing. The results of this study will be published in peer-reviewed journals and will also be presented at national and international conferences.Kushani Jayasinghe, Zornitza Stark, Chirag Patel, Amali Mallawaarachchi, Hugh McCarthy, Randall Faull, Aron Chakera, Madhivanan Sundaram, Matthew Jose, Peter Kerr, You Wu, Louise Wardrop, Ilias Goranitis, Stephanie Best, Melissa Martyn, Catherine Quinlan, Andrew J Mallet

Measuring the outcomes of long-term care for unpaid carers: Comparing the ASCOT-Carer, Carer Experience Scale and EQ-5D-3L

Background: The ASCOT-Carer and Carer Experience Scale are instruments designed to capture aspects of quality of life ‘beyond health’ for family carers. The aim of this study was to compare and validate these two carer care-related measures, with a secondary aim to compare both instruments to the three-level EQ-5D (EQ-5D-3L) measure of health-related quality of life. Methods: An interview survey was conducted with 387 carers of adults who used long-term care (also known as social care) support in England. Construct validity by hypothesis testing was assessed using Pearson correlation coefficient. Exploratory factor analysis was also applied to investigate the dimensionality of the combined items from the ASCOT-Carer and CES (as measures of carer quality of life ‘beyond health’) and the EQ-5D (as a measure of health-related quality of life). Results: In the construct validity analysis, hypothesised differences in correlations were observed with two exceptions. The exploratory factor analysis indicated that the ASCOT-Carer, CES and EQ-5D-3L items loaded onto three separate factors. The first factor comprised the seven ASCOT-Carer items plus two CES items (activities outside caring, support from friends and family). The second factor comprised three of the six CES items (fulfilment from caring, control over caring and getting on with the person you care for). The third factor included four of the five EQ-5D-3L items. Conclusion: The findings indicate that the ASCOT-Carer, CES and EQ-5D-3L capture separate constructs of social care-related quality of life (ASCOT-Carer) and carer experience (CES), which partially overlap in relation to activities outside caring and social support, and health-related quality of life (EQ-5D-3L). The ASCOT-Carer and CES are both promising measures for the evaluation of social care support for carers that capture aspects of quality of life ‘beyond health’. The choice of whether to use the ASCOT-Carer or CES depends on the study objectives

Economic evaluation alongside factorial trials: a systematic review of empirical studies

Although economic evaluations have been performed alongside factorial trials, there seems to be limited guidance/consensus on appropriate methods of analysis. Following Centre for Review and Dissemination guidance, a systematic review of published literature for all years was performed to explore how economic evaluation alongside factorial trials have been conducted and only full economic evaluations conducted alongside factorial trials were included. A total of 16 relevant studies were identified, and an assessment of these indicated that two methods: within-the-table and at-the-margins approaches were used for the analysis. With the exception of one study, all others did not consider interactions in costs and outcomes or give a detailed explanation of why a particular approach was adopted. The authors recommend that additional guidance is needed, and further research is required to evaluate the impact of alternative methods on policy recommendations and establish good practice methods for the economic analysis of factorial trials