Validity and measurement equivalence of EQ-5D-5L questionnaire among heart failure patients in Malaysia: a cohort study.

AIM: This study aimed to examine the validity of EQ-5D-5L among HFrEF patients in Malaysia, and to explore the measurement equivalence of three main language versions. METHODS: We surveyed HFrEF patients from two hospitals in Malaysia, using Malay, English or Chinese versions of EQ-5D-5L. EQ-5D-5L dimensional scores were converted to utility scores using the Malaysian value set. A confirmatory factor analysis longitudinal model was constructed. The utility and visual analog scale (VAS) scores were evaluated for validity (convergent, known-group, responsiveness), and measurement equivalence of the three language versions. RESULTS: 200 HFrEF patients (mean age = 61 years), predominantly male (74%) of Malay ethnicity (55%), completed the admission and discharge EQ-5D-5L questionnaire in Malay (49%), English (26%) or Chinese (25%) languages. 173 patients (86.5%) were followed up at 1-month post-discharge (1MPD). The standardized factor loadings and average variance extracted were ≥ 0.5 while composite reliability was ≥ 0.7, suggesting convergent validity. Patients with older age and higher New York Heart Association (NYHA) class reported significantly lower utility and VAS scores. The change in utility and VAS scores between admission and discharge was large, while the change between discharge and 1MPD was minimal. The minimal clinically important difference for utility and VAS scores was ±0.19 and ±11.01, respectively. Malay and English questionnaire were equivalent while the equivalence of Malay and Chinese questionnaire was inconclusive. LIMITATION: This study only sampled HFrEF patients from two teaching hospitals, thus limiting the generalizability of results to the entire heart failure population. CONCLUSION: EQ-5D-5L is a valid questionnaire to measure health-related quality of life and estimate utility values among HFrEF patients in Malaysia. The Malay and English versions of EQ-5D-5L appear equivalent for clinical and economic assessments.

EQ-5D is the most commonly used questionnaire to measure patients' health-related quality of life in clinical trials and health technology assessments. To increase confidence over clinical trial findings that heart failure interventions improve health-related quality of life and quality-adjusted life years (number of years alive with equivalence health-related quality of life), the questionnaire used to measure health-related quality of life needs to be validated in the specific population. Since EQ-5D-5L has not been validated in Malaysia's heart failure with reduced ejection fraction (HFrEF) population, this study evaluated the psychometric properties (validity) of EQ-5D-5L among HFrEF patients in Malaysia and the equivalence of different versions of languages (i.e. Malay, Chinese and English) of EQ-5D-5L in measuring the health-related quality of life. The findings suggested that EQ-5D-5L is a valid questionnaire to measure the health-related quality of life in HFrEF patients and estimate the quality-adjusted life years. The Malay and English versions of EQ-5D-5L appear to be equivalent for use in clinical trials and health technology assessments.

Measuring the impact of monoclonal antibody therapies.

Objective: Monoclonal antibody (Mab) treatments have significantly improved the quality and quantity of life, but they are some of the most expensive treatments, resulting in a degree of hesitancy to introduce new Mab agents. A system for estimating the effect of Mab drugs, in general, would optimally inform health strategy and fully realize how a single scientific discovery can deliver health benefits. We evaluated such a method with several well-established Mab regimens. Methods: We selected five different Mab regimens in oncology and rheumatology in England. We carried out two systematic literature reviews and meta-analyses to assess health outcomes (Health Assessment Questionnaire-Disability Index for rheumatoid arthritis; overall mortality for melanoma) from real-world data and compared them to the outcomes from randomized control trials (RCTs). We applied economic modeling to estimate the net monetary benefits for health outcomes for the estimated patient population size for each Mab regimen. Results: Meta-analyses of 27 eligible real-world data (RWD) sets and 26 randomized controlled trial (RCT) sets found close agreement between the observed and expected health outcomes. A Markov model showed the net positive monetary benefit in three Mab regimens and the negative benefit in two regimens. However, because of limited access to NHS data, the economic model made several assumptions about the number of treated patients and the cost of treatment to the NHS, the accuracy of which may affect the estimation of the net monetary benefit. Conclusion: RCT results reliably inform the real-world experience of Mab treatments. Calculation of the net monetary benefit by the algorithm described provides a valuable overall measure of the health impact, subject to the accuracy of data inputs. This study provides a compelling case for building a comprehensive, systematized, and accessible database and related analytics, on all Mab treatments within health services.

A Longitudinal Evaluation of the Preferences of Patients With Advanced Cancer for Quality of Life and Survival in Malaysia: A Discrete Choice Experiment.

OBJECTIVES: This study aims to quantify the preferences of patients with advanced cancer for quality of life (QoL) outcomes versus survival extension in Malaysia. The secondary aim of this study is to explore the change in preferences over time. METHODS: A discrete choice experiment was developed to include 7 attributes valued in cancer management: physical, psychological and social functioning, pain control, survival, place of death, and cost. Patients were recruited via convenience sampling from 2 Malaysian public hospitals. The survey questionnaire was administered to patients within 6 months of their cancer diagnosis with a follow-up 3 months later. Conditional logit regression was used to estimate the preference weight, relative attribute importance, and willingness to pay. RESULTS: One hundred valid responses were collected at baseline and 45 at follow-up. Respondents placed higher values on QoL improvements from severe to moderate or mild levels and to achieve home death over survival extension from 6 to 18 months. However, additional improvements (from moderate to mild) in some of the QoL outcomes were not valued as highly as life extension from 12 to 18 months, showing that it was vital for patients to avoid being in "severe" health dysfunction. Improving physical dysfunction from severe to mild yielded 3 times as much value as additional 1-year survival. After 3 months, the respondents' preferences changed significantly, with increased relative attribute importance of physical functioning, pain control, and cost. CONCLUSIONS: As QoL outcomes are valued more than survival, palliative care should be introduced as early as possible to alleviate suffering related to advanced cancer.

Development and validation of an interpretable machine learning scoring tool for estimating time to emergency readmissions.

Background: Emergency readmission poses an additional burden on both patients and healthcare systems. Risk stratification is the first step of transitional care interventions targeted at reducing readmission. To accurately predict the short- and intermediate-term risks of readmission and provide information for further temporal risk stratification, we developed and validated an interpretable machine learning risk scoring system. Methods: In this retrospective study, all emergency admission episodes from January 1st 2009 to December 31st 2016 at a tertiary hospital in Singapore were assessed. The primary outcome was time to emergency readmission within 90 days post discharge. The Score for Emergency ReAdmission Prediction (SERAP) tool was derived via an interpretable machine learning-based system for time-to-event outcomes. SERAP is six-variable survival score, and takes the number of emergency admissions last year, age, history of malignancy, history of renal diseases, serum creatinine level, and serum albumin level during index admission into consideration. Findings: A total of 293,589 ED admission episodes were finally included in the whole cohort. Among them, 203,748 episodes were included in the training cohort, 50,937 episodes in the validation cohort, and 38,904 in the testing cohort. Readmission within 90 days was documented in 80,213 (27.3%) episodes, with a median time to emergency readmission of 22 days (Interquartile range: 8-47). For different time points, the readmission rates observed in the whole cohort were 6.7% at 7 days, 10.6% at 14 days, 13.6% at 21 days, 16.4% at 30 days, and 23.0% at 60 days. In the testing cohort, the SERAP achieved an integrated area under the curve of 0.737 (95% confidence interval: 0.730-0.743). For a specific 30-day readmission prediction, SERAP outperformed the LACE index (Length of stay, Acuity of admission, Charlson comorbidity index, and Emergency department visits in past six months) and the HOSPITAL score (Hemoglobin at discharge, discharge from an Oncology service, Sodium level at discharge, Procedure during the index admission, Index Type of admission, number of Admissions during the last 12 months, and Length of stay). Besides 30-day readmission, SERAP can predict readmission rates at any time point during the 90-day period. Interpretation: Better performance in risk prediction was achieved by the SERAP than other existing scores, and accurate information about time to emergency readmission was generated for further temporal risk stratification and clinical decision-making. In the future, external validation studies are needed to evaluate the SERAP at different settings and assess their real-world performance. Funding: This study was supported by the Singapore National Medical Research Council under the PULSES Center Grant, and Duke-NUS Medical School.

A New Procedure to Assess When Estimates from the Cumulative Link Model Can Be Interpreted as Differences for Ordinal Scales in Quality of Life Studies.

PURPOSE: Assessing the clinical importance of an exposure effect on a quality of life (QoL) score often requires quantifying the effect in terms of a difference in scores. Using the linear regression model (LRM) for this purpose assumes the ordinal score is a proxy for an underlying continuous variable, but the analysis offers no assessment for the validity of the assumption. We propose an approach that assesses the proxy assumption and estimates the exposure effect by using the cumulative link model (CLM). PATIENTS AND METHODS: CLM is a well-established regression model that assumes an ordinal score is an ordered category generated from applying thresholds to a latent continuous variable. Our approach assesses the proxy assumption by testing whether these thresholds are equidistant. We compared the performance of CLM and LRM using simulated ordinal data and illustrated their application to the effect of time since diagnosis on five subscales of fatigue among breast cancer survivors measured using the Multidimensional Fatigue Inventory. RESULTS: CLM had good performance in estimating the difference in means with simulated ordinal data satisfying the proxy assumption, even when the outcome had only a few categories. When the proxy assumption was inadequate, both the CLM and LRM had biased estimates with poor coverage. The proxy assumption was appropriate for four of the five subscales in our real data application to fatigue scores, which highlighted the importance of assessing the proxy assumption to avoid reporting invalid estimates in terms of the difference in scores. CONCLUSION: The proxy assumption is critical to the interpretation of the exposure effect on the difference in mean QoL scores. CLM offers a valid test for the presence of an association, a method for assessing the proxy assumption, and when the assumption is adequate, an assessment for clinical significance using the difference in means.

Risk of malignancies in patients with spondyloarthritis treated with biologics compared with those treated with non-biologics: a systematic review and meta-analysis.

BACKGROUND: The aim of our study was to synthesize evidence on the occurrence of malignancy in spondyloarthritis (SpA), from randomized controlled trials (RCTs) comparing biologics with non-biologics and biologics to each other. METHODS: We systematically searched Medline, Cochrane Library, EMBASE, Scopus and ClinicalTrials.gov from inception until 31 October 2018. RCTs with ⩾24-week follow-up were included. We extracted data using standardized forms and assessed the risk of bias using the Cochrane Risk of Bias Tool. We performed pair-wise meta-analyses and network meta-analyses to compare the risk of malignancy for each biologics class and SpA type. We reported the Peto odds ratio (OR) of any malignancy along with 95% confidence intervals (95% CI). Bayesian posterior probabilities comparing risk of malignancy of each biologic class with non-biologics were computed as supplementary measures. RESULTS: Fifty-four trials were included; most (44/54) had follow-up <1 year. Among 14,245 patients, 63 developed a malignancy. While most Peto ORs were >1, they had wide 95% CI and p >0.05. The overall Peto OR comparing biologics with non-biologics was 1.42 (95% CI 0.80-2.53). Only interleukin-17 inhibitors in peripheral SpA had p <0.05 (Peto OR 2.77, 95% CI 1.07-7.13); the posterior probability that the risk was higher than non-biologics was 98%. Stratified analyses revealed no consistent trend by prior exposure to biologics, duration of follow-up, study quality, study-arm crossover, analytical approaches and type of malignancy. CONCLUSIONS: Our findings indicate no overall elevated risk of malignancy with biologics in SpA. As our meta-analyses are unable to conclude on the long-term risk, long-term pharmacovigilance of biologics in SpA may still be warranted.

The Association Between Psychological Resilience and Physical Function Among Older Adults With Hip Fracture Surgery.

OBJECTIVES: To examine the associations of prefracture psychological resilience and prefracture general mental health with physical function among older adults with hip fracture surgery. DESIGN: Single-center observational study. INTERVENTION: None. SETTING AND PARTICIPANTS: Patients aged ≥50 years who underwent first hip fracture surgery between January 2017 and December 2017 (N = 152). METHODS: We used data collected prospectively from the hospital's hip fracture registry. We performed generalized estimating equations to examine the associations of prefracture psychological resilience (10-item Connor-Davidson Resilience Scale) and prefracture general mental health (Short Form-36 mental health subscale) with physical function (Short Form-36 physical functioning subscale) at 4 time points-prefracture (based on recall), and 1.5, 3, and 6 months after surgery. RESULTS: Prefracture psychological resilience had an association with physical function; a 1-unit increase in psychological resilience score was associated with 1.15 units [95% confidence interval (CI) 0.71, 1.59] higher physical function score across 4 time points. In contrast, the association between general mental health and physical function varied over time; a 1-unit increase in general mental health score was associated with 0.42 units (95% CI 0.18, 0.66) higher physical function score at prefracture, 0.02 units (95% CI -0.18, 0.22) lower at 1.5 months, 0.23 units (95% CI -0.03, 0.49) higher at 3 months, and 0.39 units (95% CI 0.09, 0.68) higher at 6 months after surgery. CONCLUSIONS AND IMPLICATIONS: Psychological resilience is associated with physical function among older adults with hip fracture surgery, independent from general mental health. Our findings suggest the potential for interventions targeting psychological resilience for these patients and call for more studies on psychological factors affecting physical function recovery after hip fracture surgery.

A systematic review of the association of obesity with the outcomes of inflammatory rheumatic diseases.

This was a systematic review of the literature on the association between obesity and the outcome of inflammatory rheumatic diseases. We conducted a literature search using PubMed®, Embase and PsycINFO®. Articles were classified into three categories based on the effects of obesity on the outcomes of inflammatory rheumatic diseases. The subject population, country, type of studies, number of patients, measurement of obesity and outcomes assessed were presented. Quality was appraised using Kmet et al's criteria. 4,331 articles were screened and 60 were relevant to the objective. Obesity had a negative, positive and neutral association with outcomes of inflammatory rheumatic diseases in 38 (63.3%) studies with 57,612 subjects, 11 (18.3%) studies with 3,866 subjects, and 11 (18.3%) studies with 3,834 subjects, respectively. In most studies, the disease population had been diagnosed with rheumatoid arthritis (RA). Tumour necrosis factor-α inhibitors were mostly associated with negative outcomes. More studies examining subjects outside Europe and North America and diseases other than RA are warranted.

The Role of Prefracture Health Status in Physical and Mental Function After Hip Fracture Surgery.

OBJECTIVES: To examine the associations of 3 measures of prefracture health status (physical function, mental function, and comorbidity count) with trajectories of physical and mental function at 1.5, 3, 6, and 12 months after hip fracture surgery. DESIGN: Single-center observational study. SETTING: Singapore General Hospital (an acute hospital). PARTICIPANTS: Patients aged ≥60 years who underwent first hip fracture surgery between June 2011 and July 2016 (N = 928). INTERVENTION: None. MEASUREMENTS: We used data collected prospectively from the hospital's hip fracture registry. We used the Short Form-36 (SF-36) Physical Component Summary (PCS) and Mental Component Summary (MCS) as indicators of physical and mental function, respectively, collected at admission and at 1.5, 3, 6, and 12 months after hip fracture surgery. Comorbidity count at admission was the sum from a list of 10 common diseases associated with poorer physical function. RESULTS: Prefracture physical function and prefracture mental function demonstrated time-varying associations (interaction P < .001 and P = .001, respectively) with postfracture physical function; the associations were small initially but increased in strength up to 6 months and stabilized thereafter. In contrast, the strength of the association between comorbidity count and postfracture physical function were time-invariant (-0.52, P = .027). The strength of the associations between all 3 measures of prefracture health status and postfracture mental function were also constant over time (0.09, P = .004, for physical function; 0.38, P < .001, for mental function; -0.70, P = .034, for comorbidity count). CONCLUSIONS/IMPLICATIONS: The time-varying associations between prefracture health status and postfracture physical function suggest that even for patients with good prefracture health status, initial recovery may be slow. Our findings can be useful to clinicians and therapists in their prognostic evaluations and in management of patients' expectation for recovery.

Is BRCA Mutation Testing Cost Effective for Early Stage Breast Cancer Patients Compared to Routine Clinical Surveillance? The Case of an Upper Middle-Income Country in Asia.

OBJECTIVE: Previous studies showed that offering BRCA mutation testing to population subgroups at high risk of harbouring the mutation may be cost effective, yet no evidence is available for low- or middle-income countries (LMIC) and in Asia. We estimated the cost effectiveness of BRCA mutation testing in early-stage breast cancer patients with high pre-test probability of harbouring the mutation in Malaysia, an LMIC in Asia. METHODS: We developed a decision analytic model to estimate the lifetime costs and quality-adjusted life-years (QALYs) accrued through BRCA mutation testing or routine clinical surveillance (RCS) for a hypothetical cohort of 1000 early-stage breast cancer patients aged 40 years. In the model, patients would decide whether to accept testing and to undertake risk-reducing mastectomy, oophorectomy, tamoxifen, combinations or neither. We calculated the incremental cost-effectiveness ratio (ICER) from the health system perspective. A series of sensitivity analyses were performed. RESULTS: In the base case, testing generated 11.2 QALYs over the lifetime and cost US$4815 per patient whereas RCS generated 11.1 QALYs and cost US$4574 per patient. The ICER of US$2725/QALY was below the cost-effective thresholds. The ICER was sensitive to the discounting of cost, cost of BRCA mutation testing and utility of being risk-free, but the ICERs remained below the thresholds. Probabilistic sensitivity analysis showed that at a threshold of US$9500/QALY, 99.9% of simulations favoured BRCA mutation testing over RCS. CONCLUSIONS: Offering BRCA mutation testing to early-stage breast cancer patients identified using a locally-validated risk-assessment tool may be cost effective compared to RCS in Malaysia.

Measurement properties of patient reported outcome measures for spondyloarthritis: A systematic review.

OBJECTIVES: This systematic review aimed to identify studies investigating measurement properties of patient reported outcome measures (PROMs) for spondyloarthritis (SpA), and to evaluate their methodological quality and level of evidence relating to the measurement properties of PROMs. METHODS: This systematic review was guided by the preferred reporting items for systematic review and meta-analysis (PRISMA). Articles published before 30 June 2017 were retrieved from PubMed®, Embase®, and PsychINFO® (Ovid). Methodological quality and level of evidence were evaluated according to recommendations from the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN). RESULTS: We identified 60 unique PROMs from 125 studies in 39 countries. Twenty-one PROMs were validated for two or more SpA subtypes. The literature examined hypothesis testing (82.4%) most frequently followed by reliability (60.0%). A percentage of 77.7% and 42.7% of studies that assessed PROMs for hypothesis testing and reliability, respectively had "fair" or better methodological quality. Among the PROMs identified, 41.7% were studied in ankylosing spondylitis (AS) only and 23.3% were studied in psoriatic arthritis (PsA) only. The more extensively assessed PROMs included the ankylosing spondylitis quality of life (ASQoL) and bath ankylosing spondylitis functional index (BASFI) for ankylosing spondylitis, and the psoriatic arthritis quality of life questionnaire (VITACORA-19) for psoriatic arthritis. CONCLUSION: This study identified 60 unique PROMs through a systematic review and synthesized evidence of the measurement properties of the PROMs. There is a lack of validation of PROMs for use across SpA subtypes. Future studies may consider validating PROMs for use across different SpA subtypes.

Improving the effectiveness of service delivery in the public healthcare sector: the case of ophthalmology services in Malaysia.

BACKGROUND: Rising demand of ophthalmology care is increasingly straining Malaysia's public healthcare sector due to its limited human and financial resources. Improving the effectiveness of ophthalmology service delivery can promote national policy goals of population health improvement and system sustainability. This study examined the performance variation of public ophthalmology service in Malaysia, estimated the potential output gain and investigated several factors that might explain the differential performance. METHODS: Data for 2011 and 2012 on 36 ophthalmology centres operating in the Ministry of Health hospitals were used in this analysis. We first consulted a panel of ophthalmology service managers to understand the production of ophthalmology services and to verify the production model. We then assessed the relative performance of these centres using Data Envelopment Analysis (DEA). Efficiency scores (ES) were decomposed into technical, scale, and congestion component. Potential increase in service output was estimated. Sensitivity analysis of model changes was performed and stability of the result was assessed using bootstrap approach. Second stage Tobit regression was conducted to determine if hospital type, availability of day services and population characteristics were related to the DEA scores. RESULTS: In 2011, 33% of the ophthalmology centres were found to have ES > 1 (mean ES = 1.10). Potential output gains were 10% (SE ± 2.92), 7.4% (SE ± 2.06), 6.9% (SE ± 1.97) if the centres could overcome their technical, scale and congestion inefficiencies. More centres moved to the performance frontier in 2012 (mean ES = 1.07), with lower potential output gain. The model used has good stability. Robustness checks show that the DEA correctly identified low performing centres. Being in state hospital was significantly associated with better performance. CONCLUSIONS: Using DEA to benchmarking service performance of ophthalmology care could provide insights for policy makers and service managers to intuitively visualise the overall performance of resource use in an otherwise difficult to assess scenario. The considerable potential output gain estimated indicates that effort should be invested to understand what drove the performance variation and optimise them. Similar performance assessment should be undertaken for other healthcare services in the country in order to work towards a sustainable health system.