Evidence Of Cost-effectiveness Research Articles

Trial protocol for SiroSkin: a randomised double-blind placebo-controlled trial of topical sirolimus in chemoprevention of facial squamous cell carcinomas in solid organ transplant recipients

BackgroundKeratinocyte carcinomas such as basal cell carcinomas and squamous cell carcinomas are a major burden affecting morbidity and mortality in solid organ transplant recipients (SOTRs). Best treatment includes frequent skin checks for early detection and surgery for high incidence of skin cancers.Sirolimus is an immunosuppressive drug which may reduce the burden of skin cancer but may be poorly tolerated when given orally. Topical sirolimus has been proven effective at reducing the burden of skin cancers in animal models, and its safety has long been established in children with tuberous sclerosis. A recent 12-week phase II trial of topical sirolimus suggested it was safe and effective at reducing the early signs of skin cancer in the absence of major side effects. The aim of the SiroSkin trial is to determine whether topical sirolimus can fill a major gap in current therapies by reducing the onset and number of new skin cancers thus reducing burden of disease and cost-effectiveness.MethodsProtocol for a multi-centred phase III, participant- and clinician assessor-blinded, placebo-controlled randomised trial in SOTRs. A minimum 146 participants randomised 1:1 will be treated with 1% topical sirolimus versus placebo applied to the face on a regular basis for 24 weeks. Participation is 24 months in total—24 weeks of treatment and 18 months of follow-up. Outcomes include the number of keratinocyte carcinomas at 24 weeks of treatment compared to placebo and then at 12 and 24 months after initiation of treatment. Analysis will be as per protocol and intention to treat.DiscussionThe results of this trial will inform management strategies for skin cancers in SOTRs and provide evidence for cost-effectiveness.Trial registrationClinicaltrials.gov NCT05860881. Registered on June 15, 2023, and on anzctr.org.au (registration number NCT05860881).

A genuine need or nice to have? Understanding HTA representatives' perspectives on the use of patient preference data.

The roles and potential value of patient preference (PP) data in health technology assessment (HTA) remain to be fully realized despite an expanding literature and various efforts to establish their utility. This article reports lessons learned through a series of collaborative workshops with HTA representatives, organized by the Health Technology Assessment International's Patient Preferences Project Subcommittee. Five online workshops were conducted between June 2022 and June 2023, seeking to facilitate collaborative learning and reflection on ways that PP data can be integrated into HTA. Participants included nine HTA representatives from the United States, Canada, Australia, England, and the Netherlands. Workshops were recorded, transcribed, and thematically analyzed. Despite appreciating the value of PP data, participants were ambivalent about their use in HTA. Some felt that they were already getting the information they needed from the cost-effectiveness analysis or existing patient involvement processes. Others thought that PP data would be very helpful at the initial and final stage of the decision-making process and, particularly, in the following cases: (a) when technology has important non-health benefits; (b) when the clinical and/or cost-effectiveness evidence is marginal; and (c) when treatment is indicated for a large and heterogeneous population. Issues related to the validity and reliability of PP studies were frequently raised, with preference heterogeneity at the core of these concerns. Collaborating with HTA representatives in the "co-creation" of PP research can help address their concerns and facilitate mutual learning about how PP data can be used in HTA.

Evaluation of a complex intervention: the Latch On randomized controlled trial of multicomponent breastfeeding support for women with a raised body mass index.

Latch On's objective was to achieve improved breastfeeding rates in women with raised body mass indices using a multicomponent breastfeeding support intervention. A hybrid type 1 implementation-effectiveness trial with mixed-methods process and health economics analyses were conducted. Data collection included stakeholder questionnaires, interviews, focus groups, fidelity data, participant and health system costs. The intervention was delivered with fidelity but the high breastfeeding rates at 3months were not different between intervention and usual care. Participants receiving the minimum intervention dose were more likely to initiate breastfeeding (P=0.045) and be breastfeeding at hospital discharge (P=0.01) compared with participants below the threshold. Participant exit interview themes highlighted the importance of improving breastfeeding support to women, the effect of COVID-19 on the breastfeeding experience, and found that the intervention improved the experience of establishing breastfeeding. The intervention cost €157 per participant, with no other cost difference between groups. Process analysis found that follow-up breastfeeding services continued in half of sites after study completion. This low-cost intervention resulted in a more enjoyable breastfeeding experience for participants and changed practice in some study sites. The intervention dose received may impact effectiveness, but further research is needed to provide definitive evidence of clinical and cost effectiveness.

Thresholds for the value judgement of health technologies in the United Arab Emirates: a consensus approach through voting sessions

BackgroundIn the evolving healthcare landscape of the United Arab Emirates (UAE), establishing cost-effectiveness thresholds (CETs) is pivotal to informing decision-makers about the value of health technologies.ObjectiveThis study aimed to establish...

A Narrative Review of the Clinical, Humanistic, and Economic Value of Pembrolizumab-Based Immunotherapy for the Treatment of Breast and Gynecologic Cancers.

Breast and gynecologic cancers are common across the world and are associated with substantial societal and economic burden. Pembrolizumab was among the first immune checkpoint inhibitors targeting programmed cell death protein1 to be approved for the treatment of patients with triple-negative breast cancer, cervical cancer, and endometrial cancer. Recent clinical trials have established pembrolizumab regimens as a standard of care treatment for these tumor types. Clinical data are further supported by patient-reported outcome, cost-effectiveness, and real-world evidence. Pembrolizumab monotherapy and combination regimens do not negatively influence health-related quality of life and are cost-effective relative to comparators. Ongoing phase3 studies with pembrolizumab will expand the current understanding of its use in breast and gynecologic cancers. Several of these studies are in patients with early-stage disease with the hope of curing patients. The main objective of this review is to summarize the clinical, humanistic, and economic value of pembrolizumab in these settings and to describe the future challenges for patients, caregivers, clinicians, and payers.

Remote monitoring of rheumatoid arthritis (REMORA): study protocol for a stepped wedge cluster randomized trial and process evaluation of an integrated symptom tracking intervention

BackgroundManagement of rheumatoid arthritis (RA) relies on symptoms reported by patients during infrequent outpatient clinic visits. These reports are often incomplete and inaccurate due to poor recall, leading to suboptimal treatment decisions and outcomes. Asking people to track symptoms in-between visits and integrating the data into clinical pathways may improve this. However, knowledge on how to implement this into practice and its impact on services and outcomes remains scarce in RA. Therefore, we evaluate the comparative effectiveness and cost-effectiveness of integrated symptom tracking in people with RA over and above usual care, while generating insights on factors for successful implementation.MethodsIn this superiority stepped wedge cluster-randomized controlled trial with continuous recruitment short exposure design, 16 rheumatology outpatient departments (clusters) recruit a total of 732 people with active RA. They initially offer clinic visits according to standard of care before switching in pairs to visits with integrated symptom tracking. Clusters switch in randomized order every 3 weeks. Integrated symptom tracking consists of (1) a mobile app for patients to track their symptoms daily and other RA aspects weekly/monthly, and (2) an interactive dashboard visualizing the app data, which healthcare professionals access from their electronic health record system. Clinic visits happen according to usual practice, with tracked symptom data only reviewed during visits. Our primary outcome is a difference in marginal mean disease activity score at 12 ± 3 months between standard of care and integrated symptom tracking, after accounting for baseline values, cluster, and other covariates. Secondary outcomes include patient-reported disease activity, quality of life and quality-adjusted life-years, medication/resource use, consultation and decision-making experience, self-management, and illness perception. We also conduct interviews and observations as part of a parallel process evaluation to gather information on implementation.DiscussionOur trial will generate high-quality evidence of comparative and cost-effectiveness of integrated symptom tracking compared to standard of care in people with RA, with our process evaluation delivering knowledge on successful implementation. This optimizes the chances of integrated symptom tracking being adopted more widely if we find it is (cost-) effective.Trial registrationRegistered 4-Jun-2024 on https://www.isrctn.com/, ISRCTN51539448.Trial open science framework repositoryhttps://osf.io/sj9ha/.

Exploring the Broader Benefits of Obesity Prevention Community-based Interventions From the Perspective of Multiple Stakeholders.

Community-based interventions (CBIs) show promise as effective and cost-effective obesity prevention initiatives. CBIs are typically complex interventions, including multiple settings, strategies and stakeholders. Cost-effectiveness evidence, however, generally only considers a narrow range of costs and benefits associated with anthropometric outcomes. While it is recognised that the complexity of CBIs may result in broader non-health societal and community benefits, the identification, measurement, and quantification of these outcomes is limited. This study aimed to understand the perspectives of stakeholders on the broader benefits of CBIs and their measurement, as well as perceptions of CBI cost-effectiveness. Purposive sampling was used to recruit participants from three stakeholder groups (lead researchers, funders, and community stakeholders of CBIs). Online semi-structured interviews were conducted, taking a constructivist approach. Coding, theme development and analysis were based on published guidance for thematic analysis. Twenty-six stakeholders participated in the interviews (12 lead researchers; 7 funders; 6 community stakeholders). Six key themes emerged; (1) Impacts of CBIs (health impacts and broader impacts); (2) Broader benefits were important to stakeholders; (3) Measurement of benefits are challenging; (4) CBIs were considered cost-effective; (5) Framing CBIs for community engagement (6) Making equitable impacts and sustaining changes-successes and challenges. Across all stakeholders, broader benefits, particularly the establishment of networks and partnerships within communities, were seen as important outcomes of CBIs. Participants viewed the CBI approach to obesity prevention as cost-effective, however, there were challenges in measuring, quantifying and valuing broader benefits. Development of tools to measure and quantify broader benefits would allow for more comprehensive evaluation of the cost-effectiveness of CBIs for obesity prevention.

Debate: How much should nonspecialists be involved in mental health care when resources are limited? A perspective from low- and middle-income countries.

Millions of children and young people (CYP) in low- and middle-income countries (LMICs) have no access to mental health care. This huge treatment gap is primarily due to limited availability of trained mental health professionals. We propose task-sharing as a scalable strategy to expand access to child and adolescent mental health (CAMH) interventions in LMICs. Task-sharing involves using the few mental health specialists in LMICs to train and supervise nonspecialists to provided CAMH interventions. There is strong evidence of clinical and cost effectiveness of task-shared mental health interventions for adults in LMICs and promising evidence for CYP. To succeed, task-shared programmes need to be embedded in a balanced system-wide care setting that includes stakeholder involvement. The existing mental health specialists may require additional training in leadership, supervision, mentoring, service design and evaluation in order to meet the additional expectations of managing task-sharing programmes. The nonspecialists to be trained would need assurances about workload, ongoing supervision, clinical back up for cases that exceed their expertise, certification for their training and career progression. CAMH task-sharing offers good promise for increasing CYP's access to mental health interventions in LMICs. However, planners need to be aware of the important practical, ethical and contextual considerations necessary for success and sustainability.

Continuous Diffused Oxygen Therapy for Wound Healing

What Is the Issue? Wounds are prevalent across health care settings, costing Canada an estimated $12 billion per year in wound care. Chronic wounds (wounds that do not heal in the typical amount of time, which can depend on the size and type of wound) can have a significant impact on a patient’s quality of life and health. Healing tissue has a high need for oxygen. Oxygen can be delivered in several ways, including topical oxygen therapy, which delivers oxygen directly to the wound. One type of topical oxygen therapy is continuously diffused oxygen (CDO) therapy, which uses a device that takes oxygen from the air and then delivers pure, humidified oxygen to the wound. We previously completed a Rapid Review on CDO therapy for wounds in 2020. This review aimed to determine if new evidence has since been published on this topic. What Did We Do? To inform decisions about CDO therapy for wound healing, we sought to identify and summarize literature comparing the clinical effectiveness and cost-effectiveness of CDO therapy versus conventional wound care. We also attempted to identify evidence-based recommendations for the use of CDO therapy. We searched key resources, including journal citation databases, and conducted a focused internet search for relevant evidence published since 2019. One reviewer screened articles for inclusion based on predefined criteria, critically appraised the included studies, and narratively summarized the findings. What Did We Find? CDO therapy appears to be clinically effective for treating patients with diabetic foot ulcers, particularly chronic or hard-to-heal ulcers that have not responded to standard care. Rates of adverse events were comparable between patients receiving CDO and patients receiving standard care. Two cost-effectiveness studies reported that CDO is likely to be cost-effective compared to standard care for patients with chronic, hard-to-heal diabetic foot ulcers. We identified fewer studies for other types of wounds. Preliminary evidence suggests that CDO therapy may be helpful for patients with other types of wounds that are chronic or have not responded to standard care. Reporting on adverse events was limited. Limited evidence suggests that patients receiving CDO therapy had better outcomes if their wound was debrided more frequently as well as if they received CDO therapy for a longer time. The evidence-based guidelines recommend the use of topical oxygen therapy (of which CDO is a subtype) for treating diabetic foot ulcers that have failed to heal with standard care. One guideline suggested that topical oxygen therapy may be considered for other types of non-neoplastic, hard-to-heal wounds. We did not find cost-effectiveness evidence for wounds other than diabetic foot ulcers that met the inclusion criteria for our report. We also did not identify any clinical effectiveness or cost-effectiveness evidence, or any guidelines regarding the use of CDO to treat First Nations, Inuit, and Métis patients, that met the inclusion criteria for our report. What Does This Mean? CDO therapy may be beneficial and more cost-effective than standard care for patients with hard-to-heal, chronic diabetic foot ulcers that have not responded to standard care. Evidence-based guidelines also recommend the use of CDO therapy for this patient population. The clinical effectiveness and cost-effectiveness of CDO therapy for other types of wounds is still unclear. It is also unclear if there is an optimal way to provide CDO (e.g., oxygen flow rate, debridement, length of treatment). We identified limited evidence that reported on patient ethnicity. Considering that some groups, including First Nations, Inuit, and Métis Peoples, have higher rates of diabetes than the overall population in Canada — which may lead to higher rates of diabetic foot ulcers — decision-makers involved in implementing CDO therapy should consider ways to ensure equitable access for all patients who may need this treatment.

The cost-effectiveness of preventing, diagnosing, and treating postpartum haemorrhage: A systematic review of economic evaluations.

Postpartum haemorrhage (PPH) is an obstetric emergency. While PPH-related deaths are relatively rare in high-resource settings, PPH continues to be the leading cause of maternal mortality in limited-resource settings. We undertook a systematic review to identify, assess, and synthesise cost-effectiveness evidence on postpartum interventions to prevent, diagnose, or treat PPH. This systematic review was prospectively registered on PROSPERO (CRD42023438424). We searched Medline, Embase, NHS Economic Evaluation Database (NHS EED), EconLit, CINAHL, Emcare, Web of Science, and Global Index Medicus between 22 June 2023 and 11 July 2024 with no date or language limitations. Full economic evaluations of any postpartum intervention for prevention, detection, or management of PPH were eligible. Study screening, data extraction, and quality assessments (using the CHEC-E tool) were undertaken independently by at least 2 reviewers. We developed narrative syntheses of available evidence for each intervention. From 3,993 citations, 56 studies were included: 33 studies of preventative interventions, 1 study assessed a diagnostic method, 17 studies of treatment interventions, 1 study comparing prevention and treatment, and 4 studies assessed care bundles. Twenty-four studies were conducted in high-income countries, 22 in upper or lower middle-income countries, 3 in low-income countries, and 7 studies involved countries of multiple income levels. Study settings, methods, and findings varied considerably. Interventions with the most consistent findings were the use of tranexamic acid for PPH treatment and using care bundles. In both cases, multiple studies predicted these interventions would either result in better health outcomes and cost savings, or better health outcomes at acceptable costs. Limitations for this review include that no ideal setting was chosen, and therefore, a transferability assessment was not undertaken. In addition, some sources of study uncertainty, such as effectiveness parameters, were interrogated to a greater degree than other sources of uncertainty. In this systematic review, we extracted, critically appraised, and summarised the cost-effectiveness evidence from 56 studies across 16 different interventions for the prevention, diagnosis, and treatment of PPH. Both the use of tranexamic acid as part of PPH treatment, and the use of comprehensive PPH bundles for prevention, diagnosis, and treatment have supportive cost-effectiveness evidence across a range of settings. More studies utilizing best practice principles are required to make stronger conclusions on which interventions provide the best value. Several high-priority interventions recommended by World Health Organization (WHO) such as administering additional uterotonics, non-pneumatic anti-shock garment, or uterine balloon tamponade (UBT) for PPH management require robust economic evaluations across high-, middle-, and low-resource settings.

The effectiveness, cost-effectiveness and policy processes of regulatory, voluntary and partnership policies to improve food environments: an evidence synthesis.

Dietary factors are among the largest and costliest drivers of chronic diseases in England. As a response, the government implements a range of population interventions to promote healthy diets by targeting food environments. This study aimed to conduct a systematic review of the effectiveness, cost-effectiveness and policy process of real-world evaluations of national and state policies on improving food environments, with a focus on whether they were regulatory, voluntary or partnership approaches. Fourteen relevant English-language databases were searched in November 2020 for studies published between 2010 and 2020. Six separate evidence reviews were conducted to assess the evidence of effectiveness, cost-effectiveness and policy processes of policies to improve food environments. A total of 483 primary research evaluations and 14 evidence syntheses were included. The study reveals considerable geographic, methodological and other imbalances across the literature, with, for example, 81% of publications focusing only on 12 countries. The systematic reviews also reveal the effectiveness and cost-effectiveness of reviewed regulatory approaches designed to improve health, consumer behaviour and food environment outcomes while public-private partnerships and voluntary approaches to improve diets via reformulation, advertising and promotion restrictions or other changes to the environment were limited in their effectiveness and cost-effectiveness. The study also revealed key enabling and impeding factors across regulatory, voluntary and public-private partnership approaches. From the available evidence reviewed, this study finds that regulatory approaches appear most effective at improving the food environment, and voluntary agreements and partnerships have limited effectiveness. These findings should be carefully considered in future public health policy development, as should the findings of geographic imbalance in the evidence and inadequate representation of equity dimensions across the policy evaluations. We find that food policies are at times driven by factors other than the evidence and shaped by compromise and pragmatism. Food policy should be first and foremost designed and driven by the evidence of greatest effectiveness to improve food environments for healthier diets. This was a complex evidence synthesis due to its scope and some policy evaluations may have been missed as the literature searches did not include specific policy names. The literature was limited to studies published in English from 2010 to 2020, potentially missing studies of interest. Priorities include the need for guidance for appraising risk of bias and quality of non-clinical studies, for reporting policy characteristics in evaluations, for supporting evaluations of real-world policies equitably across geographic regions, for capturing equity dimensions in policy evaluations, and for guideline development for quality and risk of bias of policy evaluations. This study is registered as PROSPERO CRD42020170963. This awardproject was funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme (NIHR award ref: NIHR128607)and is published in full in Public Health Research; Vol. 12, No. 8. See the NIHR Funding and Awards website for further awardinformation.

Scoping Review of Economic Analyses of Rare Kidney Diseases

IntroductionRare kidney diseases (RKD) place a substantial economic burden on patients and health systems, the extent of which is unknown and may be systematically underestimated by health economic techniques. We aimed to investigate the economic burden and cost-effectiveness evidence base for RKD. MethodsWe conducted a systematic scoping review to identify economic evaluations, health technology assessments and cost-of-illness studies relating to RKD published since 2012. Results161 published studies, including 66 cost of illness studies, 95 economic evaluations and 72 grey literature reports were included. Most published literature originated from high-income nations, particularly the USA (81 studies), and focused on a handful of diseases, notably renal cell carcinomas (70) and systemic lupus erythematosus (36). Limited evidence was identified from lower-income settings and there were few studies of genetic conditions, which make up most RKD. Some studies demonstrated the cost-effectiveness of existing treatments, however, there were limited considerations of broader economic impacts on patients that may be important to those with RKD. Included health technology assessments highlighted difficulties in obtaining high-quality clinical evidence for treatments in very small patient populations, and often considered equity issues and other patient impacts qualitatively alongside clinical and economic evidence in their recommendations. ConclusionsWe found large gaps in the economic evidence base for RKD and limited adaption of methods to account for the uniqueness of these diseases. There may be significant scope for innovation in building an investment case for RKD treatments, as well as in decision-making processes to inform investment decisions.

Cost effectiveness of a GP delivered medication review to reduce polypharmacy and potentially inappropriate prescribing in older patients with multimorbidity in Irish primary care: the SPPiRE cluster randomised controlled trial.

Evidence on the cost effectiveness of deprescribing in multimorbidity is limited. To investigate the cost effectiveness of a general practitioner (GP) delivered, individualised medication review to reduce polypharmacy and potentially inappropriate prescribing in older patients with multimorbidity in Irish primary care. Within trial economic evaluation, from a healthcare perspective and based on a cluster randomised controlled trial with a 6month follow up and 403 patients (208 Intervention and 195 Control) recruited between April 2017 and December 2019. Intervention GPs used the SPPiRE website which contained educational materials and a template to support a web-based individualised medication review. Control GPs delivered usual care. Incremental costs, quality adjusted life years (QALYs) generated using the EQ-5D-5L instrument, and expected cost effectiveness were estimated using multilevel modelling and multiple imputation techniques. Uncertainty was explored using parametric, deterministic and probabilistic methods. On average, the SPPiRE intervention was dominant over usual care, with non-statistically significant mean cost savings of €410 (95% confidence interval (CI): - 2211, 1409) and mean health gains of 0.014 QALYs (95% CI - 0.011, 0.039). At cost effectiveness threshold values of €20,000 and €45,000 per QALY, the probability of SPPiRE being cost effective was 0.993 and 0.988. Results were sensitive to missing data and data collection period. The study observed a pattern towards dominance for the SPPiRE intervention, with high expected cost effectiveness. Notably, observed differences in costs and outcomes were consistent with chance, and missing data and related uncertainty was non trivial. The cost effectiveness evidence may be considered promising but equivocal. ISRCTN: 12752680, 20th October 2016.

Lenvatinib plus pembrolizumab for untreated advanced renal cell carcinoma: a systematic review and cost-effectiveness analysis.

Renal cell carcinoma is the most common type of kidney cancer, comprising approximately 85% of all renal malignancies. Patients with advanced renal cell carcinoma are the focus of this National Institute for Health and Care Excellence multiple technology appraisal. A patient's risk of disease progression depends on a number of prognostic risk factors; patients are categorised as having intermediate/poor risk or favourable risk of disease progression. The objectives of this multiple technology appraisal were to appraise the clinical effectiveness and cost-effectiveness of lenvatinib plus pembrolizumab versus relevant comparators listed in the final scope issued by the National Institute for Health and Care Excellence: sunitinib, pazopanib, tivozanib, cabozantinib and nivolumab plus ipilimumab. The assessment group carried out clinical and economic systematic reviews and assessed the clinical and cost-effectiveness evidence submitted by Eisai, Hatfield, Hertfordshire, UK (the manufacturer of lenvatinib) and Merck Sharp & Dohme, Whitehouse Station, NJ, USA (the manufacturer of pembrolizumab). The assessment group carried out fixed-effects network meta-analyses using a Bayesian framework to generate evidence for clinical effectiveness. As convergence issues occurred due to sparse data, random-effects network meta-analysis results were unusable. The assessment group did not develop a de novo economic model, but instead modified the partitioned survival model provided by Merck Sharp & Dohme. The assessment group clinical systematic review identified one relevant randomised controlled trial (CLEAR trial). The CLEAR trial is a good-quality, phase III, multicentre, open-label trial that provided evidence for the efficacy and safety of lenvatinib plus pembrolizumab compared with sunitinib. The assessment group progression-free survival network meta-analysis results for all three risk groups should not be used to infer any statistically significant difference (or lack of statistically significant difference) for any of the treatment comparisons owing to within-trial proportional hazards violations or uncertainty regarding the validity of the proportional hazards assumption. The assessment group overall survival network meta-analysis results for the intermediate-/poor-risk subgroup suggested that there was a numerical, but not statistically significant, improvement in the overall survival for patients treated with lenvatinib plus pembrolizumab compared with patients treated with cabozantinib or nivolumab plus ipilimumab. Because of within-trial proportional hazards violations or uncertainty regarding the validity of the proportional hazards assumption, the assessment group overall survival network meta-analysis results for the favourable-risk subgroup and the all-risk population should not be used to infer any statistically significant difference (or lack of statistically significant difference) for any of the treatment comparisons. Only one cost-effectiveness study was included in the assessment group review of cost-effectiveness evidence. The study was limited to the all-risk population, undertaken from the perspective of the US healthcare system and included comparators that are not recommended by the National Institute for Health and Care Excellence for patients with untreated advanced renal cell carcinoma. Therefore, the extent to which resource use and results are generalisable to the NHS is unclear. The assessment group cost-effectiveness results from the modified partitioned survival model focused on the intermediate-/poor-risk and favourable-risk subgroups. The assessment group cost-effectiveness results, generated using list prices for all drugs, showed that, for all comparisons in the favourable-risk subgroup, treatment with lenvatinib plus pembrolizumab costs more and generated fewer benefits than all other treatments available to NHS patients. For the intermediate-/poor-risk subgroup, treatment with lenvatinib plus pembrolizumab costs more and generated more benefits than treatment with cabozantinib and nivolumab plus ipilimumab. Good-quality clinical effectiveness evidence for the comparison of lenvatinib plus pembrolizumab with sunitinib is available from the CLEAR trial. For most of the assessment group Bayesian hazard ratio network meta-analysis comparisons, it is difficult to reach conclusions due to within-trial proportional hazards violations or uncertainty regarding the validity of the proportional hazards assumption. However, the data (clinical effectiveness and cost-effectiveness) used to populate the economic model are relevant to NHS clinical practice and can be used to inform National Institute for Health and Care Excellence decision-making. The assessment group cost-effectiveness results, generated using list prices for all drugs, show that lenvatinib plus pembrolizumab is less cost-effective than all other treatment options. This study is registered as PROSPERO CRD4202128587. This award was funded by the National Institute for Health and Care Research (NIHR) Evidence Synthesis Programme (NIHR award ref: NIHR134985) and is published in full in Health Technology Assessment; Vol. 28, No. 49. See the NIHR Funding and Awards website for further award information.

Predictive Validity of Anesthesiologists' Quality of Clinical Supervision and Nurse Anesthetists' Work Habits Assessed by Their Associations With Operating Room Times.

At all Joint Commission-accredited hospitals, the anesthesia department chair must report quantitative assessments of anesthesiologists' and nurse anesthetists' (CRNAs') clinical performance at least annually. Most metrics lack evidence of usefulness, cost-effectiveness, reliability, or validity. Earlier studies showed that anesthesiologists' clinical supervision quality and CRNAs' work habits have content, convergent, discriminant, and construct validity. We evaluated predictive validity by testing for (expected) small but statistically significant associations between higher quality of supervision (work habits) and reduced probabilities of cases taking longer than estimated. Supervision quality of each anesthesiologist was evaluated daily by assigned trainees using the 9-item de Oliveira Filho scale. The work habits of each CRNA were evaluated daily by assigned anesthesiologists using a 6-item scale. Both are scored binary, 1 if all items are rated the maximum, 0 otherwise. From 40,718 supervision evaluations and 53,722 work habit evaluations over 8 fiscal years, 16 mixed-effects logistic regression models were estimated, with raters as fixed effects and ratees (anesthesiologists or CRNAs) as random effects. Empirical Bayes means in the logit scale were obtained for 561 anesthesiologist-years and 605 CRNA-years. The binary-dependent variable was whether the case took longer than estimated from the historical mean time for combinations of scheduled procedures and surgeons. From 264,060 cases, 8 mixed-effects logistic regression models were fitted, 1 per fiscal year, using ratees as random effects. Predictive validity was tested by pairing the 8 one-year analyses of clinical supervision, and the 8 one-year analyses of work habits, by ratee, with the 8 one-year analyses of whether OR time was longer than estimated. Bivariate errors in variable linear least squares linear regressions minimized total variances. Among anesthesiologists, 8.2% (46/561) had below-average supervision quality, and 17.7% (99/561), above-average. Among CRNAs, 6.3% (38/605) had below-average work habits, and 10.9% (66/605) above-average. Increases in the logits of the quality of clinical supervision were associated with decreases in the logits of the probabilities of cases taking longer than estimated, unitless slope = -0.0361 (SE, 0.0053), P < .00001. Increases in the logits of CRNAs' work habits were associated with decreases in the logits of probabilities of cases taking longer than estimated, slope = -0.0238 (SE, 0.0054), P < .00001. Predictive validity was confirmed, providing further evidence for using supervision and work habits scales for ongoing professional practice evaluations. Specifically, OR times were briefer when anesthesiologists supervised residents more closely, and when CRNAs had better work habits.

Systematic Review of Cellular, Acellular, and Matrix-like Products and Indirect Treatment Comparison Between Cellular/Acellular and Amniotic/Nonamniotic Grafts in the Management of Diabetic Foot Ulcers.

Significance: This Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-compliant review focuses on the efficacy of cellular, acellular, and matrix-like products (CAMPs) in the management of diabetic foot ulcers (DFUs) based on published randomized controlled trials (RCTs). Recent Advances: Although CAMPs have been incorporated into the clinical algorithm for chronic wounds, evidence is lacking to comparatively evaluate the efficacy of these products. Critical Issues: Level 1 RCT studies are the gold standard to evaluate the efficacy of different treatment approaches; however, due to differences in surgical techniques, patient demographics, and compliance, standard-of-care (SOC) outcomes in the wound care space can vary significantly between different RCTs, making it difficult to compare them against each other. Future Directions: To mitigate variability between different RCTs, wound closure outcomes can be reported as risk ratios (RRs). This review of all the currently published RCTs (with a similar trial design) in patients with DFU and RRs confirms that CAMPs adjunct to SOC result in statistically superior wound closure outcomes in DFUs, when compared with SOC alone, with a RR of 1.72 [1.56, 1.90], p < 0.00001. Enough evidence is still lacking to determine a statistical difference between broad categories of cellular/acellular and amniotic/nonamniotic CAMPs, and hence, decision makers should consider published head-to-head comparative studies, real-world evidence, and cost-effectiveness evidence between individual CAMPs to decide on which to use in practice.

Health-Economic Evaluation of Psychological Interventions for Anxiety Prevention: A Systematic Review.

Although evidence supports the effectiveness of psychological interventions for prevention of anxiety, little is known about their cost-effectiveness. The aim of this study was to conduct a systematic review of health-economic evaluations of psychological interventions for anxiety prevention. PubMed, PsycInfo, Web of Science, Embase, Cochrane Central Register of Controlled Trials, EconLit, National Health Service (NHS) Economic Evaluations Database, NHS Health Technology Assessment, and OpenGrey databases were searched electronically on December 23, 2022. Included studies focused on economic evaluations based on randomized controlled trials of psychological interventions to prevent anxiety. Study data were extracted, and the quality of the selected studies was assessed by using the Consensus on Health Economic Criteria and the Cochrane risk-of-bias tool. All included studies (N=5) had economic evaluations that were considered to be of good quality. In two studies, the interventions showed favorable cost-effectiveness compared with usual care groups. In one study, the intervention was not cost-effective. Findings from another study cast doubt on the cost-effectiveness of the intervention, and the cost-effectiveness of the intervention in the remaining study could not be established. Although the findings suggest some preliminary evidence of cost-effectiveness of psychological interventions for preventing anxiety, they were limited by the small number of included studies. Additional research on the cost-effectiveness of psychological interventions for anxiety in different countries and populations is required.

Aligning meta-regression analyses of cost-effectiveness evidence to policy makers' needs.

Aligning meta-regression analyses of cost-effectiveness evidence to policy makers' needs.

Cost-Effectiveness of Biosimilars vs Leflunomide in Patients With Rheumatoid Arthritis

Among patients with rheumatoid arthritis (RA) who had an inadequate response to methotrexate, a treatment sequence initiated with biosimilar disease-modifying antirheumatic drugs (DMARDs) provides better clinical efficacy compared with conventional synthetic DMARDs recommended by current treatment guidelines; but its cost-effectiveness evidence remains unclear. To evaluate the cost-effectiveness of the treatment sequence initiated with biosimilar DMARDs after failure with methotrexate vs leflunomide and inform formulary listing decisions. This economic evaluation's cost-effectiveness analysis was performed at a Hong Kong public institution using the Markov disease transition model to simulate the lifetime disease progression and cost for patients with RA, using monetary value in 2022. Scenario and sensitivity analyses were performed to test the internal validity of the modeling conclusion. Participants included patients diagnosed with RA from 2000 to 2021 who were retrieved retrospectively from local electronic medical records to generate model input parameters. Statistical analysis was performed from January 2023 to March 2024. The model assesses 3 competing treatment sequences initiated with biosimilar infliximab (CT-P13), biosimilar adalimumab (ABP-501), and leflunomide; all used in combination with methotrexate. Lifetime health care cost and quality-adjusted life-years (QALYs) of the simulated cohort. In total, 25 099 patients with RA were identified (mean [SD] age, 56 [17] years; 19 469 [72.7%] women). In the base-case analysis, the lifetime health care cost and QALYs for the treatment sequence initiated with leflunomide were US $154 632 and 14.82 QALYs, respectively; for biosimilar infliximab, they were US $152 326 and 15.35 QALYs, respectively; and for biosimilar adalimumab, they were US $145 419 and 15.55 QALYs, respectively. Both biosimilar sequences presented lower costs and greater QALYs than the leflunomide sequence. In the deterministic sensitivity analysis, the incremental cost-effectiveness ratio (US$/QALY) comparing biosimilar infliximab sequence vs leflunomide sequence and biosimilar adalimumab sequence vs leflunomide sequence ranged from -15 797 to -8615 and -9088 to 10 238, respectively, all below the predefined willingness-to-pay threshold (US $48 555/QALY gain). In the probabilistic sensitivity analysis, the probability of treatment sequence initiated with leflunomide, biosimilar infliximab, and biosmilar adalimumab being cost-effective out of 10 000 iterations was 0%, 9%, and 91%, respectively. In this economic evaluation study, the treatment sequences initiated with biosimilar DMARDs were cost-effective compared with the treatment sequence initiated with leflunomide in managing patients with RA who experienced failure with the initial methotrexate treatment. These results suggest the need to update clinical treatment guidelines for initiating biosimilars immediately after the failure of methotrexate for patients with RA.

HTA8 Identification of Cost-Effectiveness Evidence in UK NICE Single Technology Assessment Company Submissions: Databases, Sources and Currency of Searching

HTA8 Identification of Cost-Effectiveness Evidence in UK NICE Single Technology Assessment Company Submissions: Databases, Sources and Currency of Searching