Economic Evaluations of Digital Health Interventions for Patients With Heart Failure: Systematic Review.

BACKGROUND: Digital health interventions (DHIs) have shown promising results in enhancing the management of heart failure (HF). Although health care interventions are increasingly being delivered digitally, with growing evidence on the potential cost-effectiveness of adopting them, there has been little effort to collate and synthesize the findings. OBJECTIVE: This study's objective was to systematically review the economic evaluations that assess the adoption of DHIs in the management and treatment of HF. METHODS: A systematic review was conducted using 3 electronic databases: PubMed, EBSCOhost, and Scopus. Articles reporting full economic evaluations of DHIs for patients with HF published up to July 2023 were eligible for inclusion. Study characteristics, design (both trial based and model based), input parameters, and main results were extracted from full-text articles. Data synthesis was conducted based on the technologies used for delivering DHIs in the management of patients with HF, and the findings were analyzed narratively. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed for this systematic review. The reporting quality of the included studies was evaluated using the CHEERS (Consolidated Health Economic Evaluation Reporting Standards) guidelines. RESULTS: Overall, 27 economic evaluations were included in the review. The economic evaluations were based on models (13/27, 48%), trials (13/27, 48%), or a combination approach (1/27, 4%). The devices evaluated included noninvasive remote monitoring devices (eg, home telemonitoring using digital tablets or specific medical devices that enable transmission of physiological data), telephone support, mobile apps and wearables, remote monitoring follow-up in patients with implantable medical devices, and videoconferencing systems. Most of the studies (24/27, 89%) used cost-utility analysis. The majority of the studies (25/27, 93%) were conducted in high-income countries, particularly European countries (16/27, 59%) such as the United Kingdom and the Netherlands. Mobile apps and wearables, remote monitoring follow-up in patients with implantable medical devices, and videoconferencing systems yielded cost-effective results or even emerged as dominant strategies. However, conflicting results were observed, particularly in noninvasive remote monitoring devices and telephone support. In 15% (4/27) of the studies, these DHIs were found to be less costly and more effective than the comparators (ie, dominant), while 33% (9/27) reported them to be more costly but more effective with incremental cost-effectiveness ratios below the respective willingness-to-pay thresholds (ie, cost-effective). Furthermore, in 11% (3/27) of the studies, noninvasive remote monitoring devices and telephone support were either above the willingness-to-pay thresholds or more costly than, yet as effective as, the comparators (ie, not cost-effective). In terms of reporting quality, the studies were classified as good (20/27, 74%), moderate (6/27, 22%), or excellent (1/27, 4%). CONCLUSIONS: Despite the conflicting results, the main findings indicated that, overall, DHIs were more cost-effective than non-DHI alternatives. TRIAL REGISTRATION: PROSPERO CRD42023388241; https://tinyurl.com/2p9axpmc.

A Systematic Literature Review of Gaps and Challenges in Value Assessment of Biosimilars: An ISPOR Special Interest Group Report.

OBJECTIVES: This study aims to provide an overview of the gaps and challenges in the value assessment of biosimilars and to identify potential approaches to address them. METHODS: A multidisciplinary, international team of biosimilar experts identified gaps and challenges. A systematic review was conducted of the peer-reviewed literature in PubMed, EMBASE, Web of Science Core Collection, EBSCOhost Business Source Complete; and of the gray literature. Preliminary results were presented at ISPOR conferences and this article benefited from 2 review rounds among ISPOR Biosimilar Special Interest Group members. RESULTS: Given that a biosimilar is highly similar to its reference biologic, health technology assessment agencies should accept the comparability exercise approved by regulatory authorities and, thus, conduct a price comparison when biosimilar reimbursement is requested for the same indication as the reference biologic. If the reference biologic is not reimbursed or is not the standard of care, a full economic evaluation of the biosimilar versus a relevant comparator needs to be conducted. To date, little consideration has been given to specific challenges, such as how biosimilar value assessment can account for the nocebo effect, potential differences between biologic-naive and biologic-experienced patients, the availability of intravenous and subcutaneous administration forms or different administration devices for the same active compound, value-added services, and the contribution of biosimilars for generating health gain at the population level. CONCLUSIONS: There is a need to gather further insights in the methodology of value assessment for biosimilars, and health technology assessment agencies need to develop more elaborate guidance on biosimilar value assessment in specific circumstances.

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.

Genetic-Guided Pharmacotherapy for Atrial Fibrillation: A Systematic and Critical Review of Economic Evaluations.

OBJECTIVES: This study aimed to examine the extent and quality of evidence from economic evaluations (EEs) of genetic-guided pharmacotherapy (PGx) for atrial fibrillation (AF) and to identify variables influential in changing base-case conclusions. METHODS: From systematic searches, we included EEs of existing PGx testing to guide pharmacotherapy for AF, without restrictions on population characteristics or language. Articles excluded were genetic tests used to guide device-based therapy or focused on animals. RESULTS: We found 18 EEs (46 comparisons), all model-based cost-utility analysis with or without cost-effectiveness analysis mostly from health system's perspectives, of PGx testing to determine coumadin/direct-acting anticoagulant (DOAC) dosing (14 of 18), to stratify patients into coumadin/DOACs (3 of 18), or to increase patients' adherence to coumadin (1 of 18) versus non-PGx. Most PGx to determine coumadin dosing found PGx more costly and more effective than standard or clinical coumadin dosing (19 of 24 comparisons) but less costly and less effective than standard DOAC dosing (14 of 14 comparisons). The remaining comparisons were too few to observe any trend. Of 61 variables influential in changing base-case conclusions, effectiveness of PGx testing was the most common (37%), accounted for in the models using time-based or medication-based approaches or relative risk. The cost of PGx testing has decreased and plateaued over time. CONCLUSIONS: EEs to date only partially inform decisions on selecting optimal PGx testing for AF, because most evidence focuses on PGx testing to determine coumadin dosing, but less on other purposes. Future EE may refer to the list of influential variables and the approaches used to account for the effect of PGx testing to inform data collection and study design.

Genetic-guided pharmacotherapy for venous thromboembolism: a systematic and critical review of economic evaluations.

Despite the known contributions of genes, genetic-guided pharmacotherapy has not been routinely implemented for venous thromboembolism (VTE). To examine evidence on cost-effectiveness of genetic-guided pharmacotherapy for VTE, we searched six databases, websites of four HTA agencies and citations, with independent double-reviewers in screening, data extraction, and quality rating. The ten eligible studies, all model-based, examined heterogeneous interventions and comparators. Findings varied widely; testing was cost-saving in two base-cases, cost-effective in four, not cost-effective in three, dominated in one. Of 22 model variables that changed decisions about cost-effectiveness, effectiveness/relative effectiveness of the intervention was the most frequent, albeit of poor quality. Studies consistently lacked details on the provision of interventions and comparators as well as on model development and validation. Besides improving the reporting of interventions, comparators, and methodological details, future economic evaluations should examine strategies recommended in guidelines and testing key model variables for decision uncertainty, to advise clinical implementations.

Psychological Resilience as an Emergent Characteristic for Well-Being: A Pragmatic View.

Currently, there is no clear agreement on the definition and conceptualization for psychological resilience (PR) in old age. Adopting a pragmatic view, this article elucidates the definition and conceptualization of PR by (1) extracting existing PR concepts that are relevant to aging, and (2) elucidating the contributing and delimiting factors for developing and sustaining PR as guided by the biopsychosocial framework. In addition, a comprehensive review of the tools used to measure PR was conducted to examine how scholars have conceptualized PR. Consequently, the renewed understanding defines PR as an emergent construct which is malleable, enduring, and can be developed and sustained by a dynamic interplay of biological, psychological, spiritual, and social factors. Correlates in terms of physical and mental well-being in the context of aging are identified.

Validity and reliability of the ten-item Connor-Davidson Resilience Scale (CD-RISC10) instrument in patients with axial spondyloarthritis (axSpA) in Singapore.

We aimed to assess the validity and reliability of the ten-item Connor-Davidson Resilience Scale (CD-RISC10) in patients with axial spondyloarthritis (axSpA) in Singapore. We used cross-sectional data from 108 patients with axSpA recruited from a dedicated axSpA clinic in a Singapore tertiary referral hospital from 2017 to 2018. Analyses were guided by the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) framework. Face validity was assessed through cognitive debriefing interviews (CDIs). Internal consistency was assessed through Cronbach's alpha. Test-retest reliability was assessed through intraclass correlation (ICC). Measurement error was assessed through smallest detectable change (SDC). Construct validity was assessed through six a priori hypotheses through correlation of the CD-RISC10 score with other patient-reported outcome measures. Structural validity was assessed using confirmatory factor analysis (CFA). Fit indices evaluated were root-mean-square error of approximation (RMSEA), comparative fit index (CFI), Tucker-Lewis index (TFI), and standardized root-mean-squared residual (SRMR). Ten patients completed the CDIs and face validity was supported. Among 108 patients (median age: 37(21-77), 81.5% males, 93.5% Chinese), the CD-RISC10 demonstrated good internal consistency (Cronbach's alpha = 0.94), and excellent test-retest reliability [ICC = 0.964 (95% CI 0.937-0.980)]. SDC was calculated as 1.88. Construct validity was established by meeting five out of the six a priori hypotheses. Structural validity was supported as CFA confirmed a one-factor model, with adequate fit statistics after adding three covariances (RMSEA = 0.077; CFI = 0.975; TLI = 0.964; SRMR = 0.036). This study supports the CD-RISC10 as a valid and reliable measure of resilience for use in patients with axSpA.

Factors Associated With Initiation of Biologics in Patients With Axial Spondyloarthritis in an Urban Asian City: A PRESPOND Study.

OBJECTIVE: The aim of this study was to examine if patients' sociodemographic, clinical characteristics, and patient-reported outcomes were associated with biologics initiation in patients with axial spondyloarthritis in Singapore. METHODS: Data from a dedicated registry from a tertiary referral center in Singapore from January 2011 to July 2016 were used. Initiation of first biologics was the main outcome of interest. Logistic regression analyses were used to explore the association of various factors on biologics initiation. RESULTS: Of 189 eligible patients (aged 37.7 ± 13.3 years; 76.2% were males), 30 (15.9 %) were started on biologics during follow-up. In the multivariable analysis model, age (odds ratio [OR]; 0.93; 95% confidence interval [CI], 0.89-0.98; p < 0.01), mental component summary score of Short-Form 36 Health Survey (OR, 0.18; 95% CI, 0.03-0.89; p = 0.04), erythrocyte sedimentation rate (OR, 1.02; 95% CI, 1.00-1.04; p = 0.02), presence of peptic ulcer disease (OR, 10.4; 95% CI, 2.21-48.8; p < 0.01), and lack of good response to nonsteroidal anti-inflammatory drugs (OR, 4.44; 95% CI, 1.63-12.1; p < 0.01) were found to be associated with biologics initiation. CONCLUSIONS: Age, erythrocyte sedimentation rate, mental component summary score, comorbidities of peptic ulcer disease, and responsiveness to nonsteroidal anti-inflammatory drugs were associated with biologics initiation. It is essential that clinicians recognize these factors in order to optimize therapy.

Anti-hypertensive medications and injurious falls in an older population of low socioeconomic status: a nested case-control study.

BACKGROUND: This study aimed to determine whether the number of anti-hypertensive medication classes or any change in anti-hypertensive medication were associated with injurious fall among the community-dwelling older population of low socioeconomic status. METHODS: Using data from electronic medical records, we performed a nested case-control study among older Singapore residents (≥60) of low socioeconomic status (N = 210). Controls (n = 162) were matched to each case (n = 48) by age and gender. Variables with p < 0.10 in univariate analysis were included in multivariate analysis. We used conditional logistic regression to assess the associations of the number of anti-hypertensive medication classes and change in anti-hypertensive medication with injurious falls. We also performed stepwise regressions as sensitivity analyses. p < 0.05 was considered statistically significant. RESULTS: The mean (±SD) age of participants was 78.1 (± 8.33) years; 127 (60.4%) were female, 189 (90.0%) were Chinese. Those on ≥2 anti-hypertensive medication classes had an increased risk of experiencing an injurious fall compared to those not on any anti-hypertensive medication (OR = 5.45; CI:1.49-19.93; p = 0.01). Among those who were taking anti-hypertensive medication, those who had a change in the medication 180-day prior to injurious fall had a significantly increased risk of experiencing an injurious fall compared to those that did not report any change in anti-hypertensive medication (OR = 3.88; CI:1.23-12.19; p = 0.02). Sensitivity analyses generated consistent findings. CONCLUSION: Both ≥2 anti-hypertensive medication classes and change in anti-hypertensive medication were associated with an increased risk of experiencing an injurious fall among the older population of low socioeconomic status. Our findings could guide prescribers to exercise caution in the initiation of anti-hypertensive medications or in making medication changes, especially among the older population of low socioeconomic status.

Equity in access to health care in a rural population in Malaysia: A cross-sectional study.

OBJECTIVE: To examine the extent of equity in access to health care, their determinants and reasons of unmet need of a rural population in Malaysia. DESIGN: Exploratory cross-sectional survey administered by trained interviewers among participants of a health screening program. SETTING: A rural plantation estate in the West Coast of Peninsular Malaysia. PARTICIPANTS: One hundred and thirty out of 142 adults above 18 years old who attended the program. MAIN OUTCOME MEASURE: Percentages of respondents reporting realised access and unmet need to health care, determinants of both access indicators and reasons for unmet need. Realised access associated with need but not predisposing or enabling factors and unmet need not associated with any variables were considered equitable. RESULTS: A total of 88 (67.7%) respondents had visited a doctor (realised access) in the past 6 months and 24.8% (n = 31) experienced unmet need in the past 12 months. Using logistic regression, realised access was associated with presence of chronic disease (OR 6.97, P < 0.001), whereas unmet need was associated with low education level (OR 6.50, P < 0.05), 'poor' or 'fair' self-assessed health status (OR 6.03, P < 0.05) and highest income group (> RM 2000 per month) (OR 51.27, P < 0.05). Personal choice (67.7%) was more commonly expressed than barriers (54.8%) as reasons for unmet need. CONCLUSIONS: The study found equity in realised access and inequity in unmet need among the rural population, the latter associated with education level, subjective health status and income. Despite not being generalisable, the findings highlight the need for a national level study on equity in access before the country reforms its health system.

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.

Impact of hospital mergers on staff job satisfaction: a quantitative study.

BACKGROUND: Hospital mergers began in the UK in the late 1990s to deal with underperformance. Despite their prevalence, there is a lack of research on how such organizational changes affect the staff morale. This study aims to assess the impact of NHS hospital mergers between financial years 2009/10 and 2011/12 on staff job satisfaction and to identify factors contributing to satisfaction. METHODS: Data on staff job satisfaction were obtained from the annual NHS Staff Survey. A list of mergers was compiled using data provided by the Cooperation and Competition Panel and the Department of Health. Other sources of data included the NHS Hospital Estates and Facilities Statistics, the NHS 'Quarter' publication, official reports from health service regulators, individual hospitals' annual accounts, data from the NHS Information Centre and the NHS Recurrent Revenue Allocations Exposition Book. Only full mergers of acute and mental health hospitals were analyzed. Propensity scores were generated using observable factors likely to affect merger decision to select three comparable hospitals for every constituent hospital in a merger to act as a control group. A difference-in-difference was estimated between baseline (3 years before merger approval) and each subsequent year up to 4 years post-merger, controlling for work environment, drivers of job satisfaction, data year, type of hospital and occupation group. RESULTS: There were nine mergers during the study period. Only job satisfaction scores 1 to 2 years before (0.03 to 0.04 point) and 1 year after merger approval (0.06 point) were higher (P < 0.01) than baseline. Robustness testing produced consistent findings. Assuming other conditions were equal, an increase in autonomy, staff support, perceived quality and job clarity ratings would increase job satisfaction scores. Higher job satisfaction scores were also associated with being classified as medical, dental, management or administrative staff and working in a mental health trust. CONCLUSION: Hospital mergers have a small, transient positive impact on staff job satisfaction in the year immediately before and after merger approval. Continuous staff support and management of staff expectations throughout a merger may help to increase staff job satisfaction during the challenging period of merger.

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.

Genetic-Guided Pharmacotherapy for Coronary Artery Disease: A Systematic and Critical Review of Economic Evaluations.

BACKGROUND: Genetic-guided pharmacotherapy (PGx) is not recommended in clinical guidelines for coronary artery disease (CAD). We aimed to examine the extent and quality of evidence from economic evaluations of PGx in CAD and to identify variables influential in changing conclusions on cost-effectiveness. METHODS AND RESULTS: From systematic searches across 6 databases, 2 independent reviewers screened, included, and rated the methodological quality of economic evaluations of PGx testing to guide pharmacotherapy for patients with CAD. Of 35 economic evaluations included, most were model-based cost-utility analyses alone, or alongside cost-effectiveness analyses of PGx testing to stratify patients into antiplatelets (25/35), statins (2/35), pain killers (1/35), or angiotensin-converting enzyme inhibitors (1/35) to predict CAD risk (8/35) or to determine the coumadin doses (1/35). To stratify patients into antiplatelets (96/151 comparisons with complete findings of PGx versus non-PGx), PGx was more effective and more costly than non-PGx clopidogrel (28/43) but less costly than non-PGx prasugrel (10/15) and less costly and less effective than non-PGx ticagrelor (22/25). To predict CAD risk (51/151 comparisons), PGx using genetic risk scores was more effective and less costly than clinical risk score (13/17) but more costly than no risk score (16/19) or no treatment (9/9). The remaining comparisons were too few to observe any trend. Mortality risk was the most common variable (47/294) changing conclusions. CONCLUSIONS: Economic evaluations to date found PGx to stratify patients with CAD into antiplatelets or to predict CAD risk to be cost-effective, but findings varied based on the non-PGx comparators, underscoring the importance of considering local practice in deciding whether to adopt PGx.

The IMPROVE trial: study protocol for a pragmatic cluster randomised controlled trial to assess the effectiveness of using lay health workers to improve uptake and completion of pulmonary rehabilitation in patients with chronic obstructive pulmonary disease.

BACKGROUND: Pulmonary rehabilitation (PR) is a programme of exercise and education and the most effective treatment for the symptoms and disability associated with chronic obstructive pulmonary disease. However, the benefits of PR are limited by poor uptake and completion. This trial will determine whether using trained volunteer lay health workers, called "PR buddies," improves uptake and completion of PR and is cost-effective. This trial protocol outlines the methods for evaluating effectiveness, cost-effectiveness, and acceptability. METHODS: The IMPROVE trial is a pragmatic, open, cluster randomised controlled trial planned in 38 PR services across England and Wales. PR services will be randomised to either intervention arm-offering support from PR buddies to patients with chronic obstructive pulmonary disease-or to usual care as the control arm. PR staff in trial sites randomised to the intervention arm will receive training in recruiting and training PR buddies. They will deliver training to volunteers, recruited from among people who have recently completed PR in their service. The 3-day PR-buddy training programme covers communication skills, confidentiality, boundaries of the PR-buddy role and behaviour change techniques to help patients overcome obstacles to attending PR. An internal pilot will test the implementation of the trial in eight sites (four intervention sites and four in control arm). The primary outcome of the trial is the uptake and completion of PR. A process evaluation will investigate the acceptability of the intervention to patients, PR staff and the volunteer PR buddies, and intervention fidelity. We will also conduct a cost-effectiveness analysis. DISCUSSION: Improving outcomes for chronic obstructive pulmonary disease and access to PR are priorities for the UK National Health Service (NHS) in its long-term plan. The trial hypothesis is that volunteer PR buddies, who are recruited and trained by local PR teams, are an effective and cost-effective way to improve the uptake and completion rates of PR. The trial is pragmatic, since it will test whether the intervention can be incorporated into NHS PR services. Information obtained in this trial may be used to influence policy on the use of PR buddies in PR and other similar services in the NHS. TRIAL REGISTRATION: ISRCTN12658458. Registered on 23/01/2023.

Continuous Positive Airway Pressure plus Mandibular Advancement Therapy (PAPMAT): study protocol for an adaptive randomised crossover trial comparing the benefits and costs of combining two established treatments for obstructive sleep apnoea.

BACKGROUND: Obstructive sleep apnoea (OSA) involves repeated breathing pauses during sleep due to upper airway obstruction. It causes excessive daytime sleepiness and has other health impacts. Continuous positive airway pressure (CPAP) therapy is effective first line treatment for moderate to severe OSA. Unfortunately, many patients have difficulty tolerating CPAP and pressure intolerance is probably an important contributing factor. Mandibular advancement devices (MAD) are an alternative to CPAP. They are worn in the mouth during sleep to reduce airway obstruction. There is some evidence that, when used in combination with CPAP, MADs improve airway anatomy enough to reduce the CPAP pressure required to treat OSA and that this combination therapy could improve CPAP adherence. METHODS: Consecutive patients starting on CPAP for moderate to severe OSA will be recruited at a regional NHS sleep service. Patients with high CPAP pressure requirements after initial titration, who satisfy all entry criteria and consent to participate, will undertake a 2-arm randomised crossover trial. The arms will be (i) standalone CPAP and (ii) CPAP + MAD therapy. Each arm will last 12 weeks, including 2 weeks acclimatisation. CPAP machines will be auto-titrating and with facility for data download, so the impact of MAD on CPAP pressure requirements and CPAP adherence can be easily measured. The primary outcome will be CPAP adherence. Secondary outcomes will include measures of OSA severity, patient-reported outcome measures including subjective daytime sleepiness, quality of life, and treatment preference at the trial exit and health service use. Cost-effectiveness analyses will be undertaken. DISCUSSION: If the intervention is shown to be effective and cost-effective in improving adherence in this standard CPAP-eligible OSA patient population it would be relatively straightforward to introduce into existing OSA treatment pathways, within the wider NHS and more widely. Both MAD and CPAP are already used by sleep services so their combination would require only minor adjustments to existing clinical pathways. It would be straightforward to disseminate the results of the study through regional, national, and international respiratory meetings. The health economics analysis would provide cost-effectiveness data to inform service planning and clinical guidelines through policy briefing papers, including those by NICE and SIGN. TRIAL REGISTRATION: PAPMAT was registered with ISRCTN prior to recruitment beginning (ISRCTN Registry 2021): https://www.isrctn.com/ISRCTN33966032 . Registered on 17th November 2021.

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 Comparison of the Content and Consistency of Methodological Quality and Transferability Checklists for Reviewing Model-Based Economic Evaluations.

OBJECTIVES: The aim of this study was to examine whether and how the content of six checklists (Caro, Consensus on Health Economic Criteria [CHEC]-Extended, European Network of Health Economic Databases [EURONHEED], National Institute for Health and Care Excellence [NICE], Philips, Welte) affect the consistency in findings on methodological quality and transferability, using 10 model-based economic evaluations of genetic-guided pharmacotherapy for venous thromboembolism. METHODS: Each checklist was categorised by domain (structure, data, consistency, etc.) and type of assessment (presence vs. appropriateness) and was applied to each study by two independent reviewers who agreed on ratings via consensus, and discussion with a third reviewer when necessary. Methodological quality scores and rankings were examined using Spearman correlation tests, with subgroup analyses for domains and types of assessment. We compared overall ratings of transferability qualitatively, including how content may affect what is considered 'transferable'. RESULTS: The checklists had similar proportions of items judging presence and appropriateness, but varying proportions of items across domains. For methodological quality, ranking consistencies were the highest between CHEC-Extended-Philips, Philips-NICE and NICE-Caro, with similar consistencies for domains and type of assessment. For transferability, NICE and Caro identified the same study, which scored high on EURONHEED, as transferable to the UK, while Welte, which considered methodological quality, identified none as transferable. CONCLUSIONS: We found that the choice of checklist can affect findings on study quality and decisions about whether study results are transferable, indicating that different checklists may shortlist different sets of studies in formulating policy recommendations, leading to different policy decisions. Our systematic approach for evaluating the content of methodological quality and transferability checklists of economic evaluations can be extended to other checklists.

Conjoint analyses of patients' preferences for primary care: a systematic review.

BACKGROUND: While patients' preferences in primary care have been examined in numerous conjoint analyses, there has been little systematic effort to synthesise the findings. This review aimed to identify, to organise and to assess the strength of evidence for the attributes and factors associated with preference heterogeneity in conjoint analyses for primary care outpatient visits. METHODS: We searched five bibliographic databases (PubMed, Embase, PsycINFO, Econlit and Scopus) from inception until 15 December 2021, complemented by hand-searching. We included conjoint analyses for primary care outpatient visits. Two reviewers independently screened papers for inclusion and assessed the quality of all included studies using the checklist by ISPOR Task Force for Conjoint Analysis. We categorized the attributes of primary care based on Primary Care Monitoring System framework and factors based on Andersen's Behavioural Model of Health Services Use. We then assessed the strength of evidence and direction of preference for the attributes of primary care, and factors affecting preference heterogeneity based on study quality and consistency in findings. RESULTS: Of 35 included studies, most (82.4%) were performed in high-income countries. Each study examined 3-8 attributes, mainly identified through literature reviews (n = 25). Only six examined visits for chronic conditions, with the rest on acute or non-specific / other conditions. Process attributes were more commonly examined than structure or outcome attributes. The three most commonly examined attributes were waiting time for appointment, out-of-pocket costs and ability to choose the providers they see. We identified 24/58 attributes with strong or moderate evidence of association with primary care uptake (e.g., various waiting times, out-of-pocket costs) and 4/43 factors with strong evidence of affecting preference heterogeneity (e.g., age, gender). CONCLUSIONS: We found 35 conjoint analyses examining 58 attributes of primary care and 43 factors that potentially affect the preference of these attributes. The attributes and factors, stratified into evidence levels based on study quality and consistency, can guide the design of research or policies to improve patients' uptake of primary care. We recommend future conjoint analyses to specify the types of visits and to define their attributes clearly, to facilitate consistent understanding among respondents and the design of interventions targeting them. Word Count: 346/350 words. TRIAL REGISTRATION: On Open Science Framework: https://osf.io/m7ts9.

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.