The economic burden of stomas in the UK: a retrospective observational study of health records and hospital encounters.

BACKGROUND: Stomas divert waste from the small intestine (ileostomy), large intestine (colostomy) or ureters (urostomy), and complications are common. AIMS: This study evaluated healthcare resource utilisation (HCRU) and costs of stomas from a UK perspective. METHODS: This was a retrospective observational study of adults with new stomas (New Stoma Group) or new/existing stomas and >6 months of follow-up (Established Stoma Group) using health records linked with hospital encounters (January 2009-December 2018). Age- and sex-matched controls were identified for each stoma case (1:50). FINDINGS: Both the New (n=8533) and Established (n=9397) stoma groups had significantly higher HCRU (all P<0.0001) and associated costs (all P<0.01), driven by inpatient admissions. New Stoma Group: colostomy versus controls, £3227 versus £99 per person; ileostomy, £2576 versus £78 per person; and urostomy, £2850 versus £110 per person (all P<0.0001). Findings were similar in the Established Stoma Group. CONCLUSION: Stomas are associated with a substantial economic burden in the UK driven by hospital care. (Supplementary data tables can be obtained from the authors.).

Complications and Healthcare Costs Associated With the First Year Following Colostomy and Ileostomy Formation: A Retrospective Study.

PURPOSE: The purpose of this study was to evaluate clinical and economic outcomes during the first year following ostomy formation. DESIGN: Single-center retrospective audit. SUBJECTS AND SETTING: The sample comprised 200 patients who underwent surgery leading to ileostomy or colostomy at a large English National Health Service (NHS) Trust. METHODS: Clinical complications, medicine prescriptions, and interactions with healthcare services were reported over 12 months postsurgery, and interactions with the NHS were matched to the closest NHS unit cost to determine mean patient cost. RESULTS: The most common ostomy-related surgical site complications were high output (35.0%; n = 70), followed by moderate/severe peristomal skin complications (24.5%; n = 49) and bleeding (23.5%; n = 47). Ostomy management-related complications included general difficulties with ostomy management (50.0%; n = 100) and leakage-related mild peristomal skin issues (48.5%; n = 97). Clinical complication rates were highest in the first quarter following ostomy formation, except parastomal hernia, which increased in incidence over time. Ileostomy patients more frequently experienced high output, acute renal failure, and ostomy management-related complications and had increased length of inpatient admission. However, healthcare resource use was high in both groups, with a median of 13 inpatient admission days and 12 outpatient contacts overall within the first year. Mean cost per patient was £20,444.60 (US $26,018.41); 90.5% of these costs were attributed to ostomy-related factors. CONCLUSIONS: Patients are likely to experience at least one clinical complication following intestinal ostomy formation and have multiple interactions with the NHS. While a number of complications are more frequent in patients with ileostomies, both groups experienced considerable costs within the first year following surgery associated with ostomy management and recovery.

Cost-effectiveness analysis of HIV pre-exposure prophylaxis in Japan.

BACKGROUND: While global efforts have been made to prevent transmission of HIV, the epidemic persists. Men who have sex with men (MSM) are at high risk of infection. Despite evidence of its cost-effectiveness in other jurisdictions, pre-exposure prophylaxis (PrEP) for MSM is neither approved nor reimbursed in Japan. METHOD: The cost-effectiveness analysis compared the use of once daily PrEP versus no PrEP among MSM over a 30-year time horizon from a national healthcare perspective. Epidemiological estimates for each of the 47 prefectures informed the model. Costs included HIV/AIDS treatment, HIV and testing for sexually transmitted infections, monitoring tests and consults, and hospitalization costs. Analyses included health and cost outcomes, as well as the incremental cost-effectiveness ratio (ICER) reported as the cost per quality-adjusted life year (QALY) for all of Japan and each prefecture. Sensitivity analyses were performed. FINDINGS: The estimated proportion of HIV infections prevented with the use of PrEP ranged from 48% to 69% across Japan, over the time horizon. Cost savings due to lower monitoring costs and general medical costs were observed. Assuming 100% coverage, for Japan overall, daily use of PrEP costs less and was more effective; daily use of PrEP was cost-effective at a willingness to pay threshold of ¥5,000,000 per QALY in 32 of the 47 prefectures. Sensitivity analyses found that the ICER was most sensitive to the cost of PrEP. INTERPRETATION: Compared to no PrEP use, once daily PrEP is a cost-effective strategy in Japanese MSM, reducing the clinical and economic burden associated with HIV.

HIV remains an epidemic, and men who have sex with men (MSM) are at higher risk of infection. Pre-exposure prophylaxis (PrEP) is a preventive treatment that can reduce someone's risk of getting infected with HIV and has been shown to provide good value for money. PrEP, however, is neither approved nor reimbursed in Japan. In order to determine the value for money in Japan, an economic model was developed to estimate the number of HIV infections and AIDS cases that could be avoided, along with whether daily use of PrEP among MSM in Japan is cost effective. Findings showed that with use of daily PrEP, the proportion of HIV infections and AIDS cases prevented was 63% and 59%, respectively, across Japan. Over a 30-year time horizon, daily use of PrEP would cost the health system less and be more effective than no use of PrEP. Daily PrEP should therefore be considered for reimbursement in MSM in Japan, given its value for money.

Exploring the impact of excessive daytime sleepiness caused by obstructive sleep apnea on patient and partner quality of life: a time trade-off utility study in the UK general public.

STUDY OBJECTIVES: This study aimed to quantify the impact of excessive daytime sleepiness (EDS) on patient and patient's partner health-related quality of life in the form of utility values typically used in health economic evaluations. METHODS: A time trade-off study was conducted in a UK general population sample (representing a societal perspective) to elicit utility values, measured on a 0 to 1 scale, for health states with varying obstructive sleep apnea-associated EDS severity. In a time trade-off study, health states are described, and participants "trade off" time in a specific higher severity state for a shorter amount of time in full health. RESULTS: Overall, the sample consisted of 104 participants, who were interviewed and took part in the time trade-off exercise to elicit utility values for patient and partner residual EDS health states. The average utility score declined with increasing obstructive sleep apnea-associated EDS severity for both patient (no EDS, 0.926; mild EDS, 0.794; moderate EDS, 0.614; severe EDS, 0.546) and partner (no EDS, 0.955; mild EDS, 0.882; moderate EDS, 0.751; severe EDS, 0.670) health states. CONCLUSIONS: These results demonstrate the high impact that EDS in obstructive sleep apnea is estimated to have on patient and partner health-related quality of life. CITATION: Tolley K, Noble-Longster J, Mettam S, et al. Exploring the impact of excessive daytime sleepiness caused by obstructive sleep apnea on patient and partner quality of life: a time trade-off utility study in the UK general public. J Clin Sleep Med. 2022;18(9):2237-2246.

Examining the impact of haemophilia treatment on health-related quality of life.

INTRODUCTION: Haemophilia has substantial SD effects on health-related quality of life (HRQoL), particularly for people with severe haemophilia. How certain aspects of haemophilia influence HRQoL is not well understood. AIM: To develop predictive models of variables influencing HRQoL in people with severe haemophilia A or B. METHODS: We used data from 514 participants with haemophilia A or B who provided EQ-5D-3L responses in the 2015 CHESS study. Treatment was categorized as always been on-demand (POD), previously on prophylaxis and moved to on-demand regimen (SOD), on prophylaxis from diagnosis (PX), and prophylaxis, previously on-demand (PXOD). Target joints were defined as 'locations of chronic synovitis' as reported by the treating physician. Regression models were evaluated to assess the impact of demographic and clinical covariates on HRQoL scores. RESULTS: Significant covariates were generally consistent across models, with number of target joints, number of hospital admissions, and any haemophilia treatment regimen other than PX all independently negatively impacting estimated EQ-5D score. Higher level of treatment adherence (high vs. low/medium) and use of a prophylaxis treatment regimen had positive effects on estimated EQ-5D scores. Target joints were associated with a 0.04 decrement in EQ-5D score, and high versus low/medium adherence was associated with a 0.06 increment. PXOD, POD, and SOD treatment regimens were associated with decrements in predicted scores of 0.07, 0.09, and 0.08, respectively, versus PX. CONCLUSION: This study provides a model to estimate the impact of haemophilia interventions on HRQoL, to help assess the relative impact on patient-centric outcomes for this lifelong condition.

Survival analyses from the CENTAUR trial in amyotrophic lateral sclerosis: Evaluating the impact of treatment crossover on outcomes.

INTRODUCTION/AIMS: Trials incorporating placebo-to-active treatment crossover are encouraged in fatal conditions like amyotrophic lateral sclerosis (ALS) but may underestimate active treatment survival benefit. Here, we apply methods for modeling survival without crossover, including the rank-preserving structural failure time model (RPSFTM), to data from the CENTAUR trial of sodium phenylbutyrate and taurursodiol (PB and TURSO) in ALS incorporating both randomized placebo-controlled and open-label extension (OLE) phases. METHODS: Intent-to-treat (ITT) and RPSFTM survival analyses were performed with final data at a July 2020 cutoff date. Analyses of subgroups based on randomized treatment and OLE phase participation were also performed. RESULTS: Hazard ratios (95% confidence intervals) of death for PB and TURSO versus participants initially on placebo were 0.57 (0.35-0.92) on ITT analysis and 0.39 (0.17-0.88) in the primary on-treatment RPSFTM analysis (p = .023). Median ITT survival duration for PB and TURSO (25.8 mo) was 6.9 mo longer than placebo (18.9 mo) on ITT analysis and 10.6 mo longer than the median RPSFTM-adjusted survival duration for placebo (15.2 mo). Median survival duration was 18.8 mo longer in the PB and TURSO-randomized subgroup who continued into the OLE phase versus the placebo-randomized subgroup who did not continue into the OLE phase (p < .0001), although OLE phase selection bias may have potentially confounded these results. DISCUSSION: Similar to the prespecified ITT analysis, post hoc analyses adjusting for treatment crossover in CENTAUR showed a significant survival benefit for PB and TURSO. Such methods may provide clinical context for observed survival outcomes in future ALS crossover trials.

Examining patient and professional perspectives in the UK for gene therapy in haemophilia.

INTRODUCTION: With the development of gene therapy for people with haemophilia (PWH), it is important to understand how people impacted by haemophilia (PIH) and clinicians prioritise haemophilia treatment attributes to support informed treatment decisions. OBJECTIVE: To examine the treatment attribute preferences of PIH and clinical experts in the United Kingdom (UK) and to develop a profile of gene therapy characteristics fit for use in future discrete choice experiments (DCEs). METHODS: Semi-structured interviews were conducted with PIH (n = 14) and clinical experts (n = 6) who ranked pre-defined treatment attributes by importance. Framework analysis was conducted to identify key themes and treatment attributes; points were allocated based on the rankings. Synthesis of results by a multidisciplinary group informed development of a profile of gene therapy characteristics for use in future research. RESULTS: Key themes identified by PIH and clinical experts included patient relevant features and the importance of 'informed decision making'. The six top-ranked treatment attributes were 'effect on factor level' (79 points), 'uncertainty regarding long-term risks' (57 points), 'impact on daily life' (41 points), 'frequency of monitoring' (33 points), 'impact on ability to participate in physical activity' (29 points), and 'uncertainty regarding long-term benefits' (28 points). The final treatment characteristics were categorised as therapeutic option, treatment effectiveness, safety concerns, impact on self-management and quality of life (role limitations). CONCLUSION: We identified several gene therapy characteristics important to PIH and clinicians in the UK. These characteristics will be used in a future DCE to further investigate patient preferences for gene therapy.

Patient preferences and priorities for haemophilia gene therapy in the US: A discrete choice experiment.

INTRODUCTION: Gene therapy has shown promise in clinical trials for patients with haemophilia, but patient preference studies have focused on factor replacement treatments. AIM: We conducted a discrete choice experiment (DCE) to investigate the relative importance and differential preferences patients provide for gene therapy attributes. METHODS: We surveyed male adults with haemophilia in the United States recruited from patient panels including the National Hemophilia Foundation Community Voices in Research platform using an online survey over 4 months in 2020/21. Participants indicated preferences for gene therapy attributes including dosing frequency/durability, effect on annual bleeding, uncertainty related to side effects, impact on daily activities, impact on mental health, and post-treatment requirements. The relative importance of each attribute was analysed overall and for subgroups based on haemophilia type and severity. RESULTS: A total of 183 males with haemophilia A (n = 120) or B (n = 63) were included. Half (47%) had severe haemophilia; most (75%) were White. Overall, participants gave effect on bleeding rate the greatest relative importance (31%), followed by dose frequency/durability (26%), uncertainty regarding safety issues (17%), and impact on daily activities (11%). Dose frequency/durability had the greatest importance for those with haemophilia B (35%). CONCLUSION: People with haemophilia prioritised reduced bleeding and treatment burden; the former was more important in haemophilia A and the latter in haemophilia B, followed by safety and impact on daily life in this DCE of gene therapy attributes. These findings and differences can inform clinical and health policy decisions to improve health equity for people with haemophilia.

Budget Impact Analysis of Gemtuzumab Ozogamicin for the Treatment of CD33-Positive Acute Myeloid Leukemia.

BACKGROUND: Gemtuzumab ozogamicin (GO) was approved in 2017 in the US for the treatment of adults with newly diagnosed CD33-positive (CD33+) acute myeloid leukemia (AML), and adults and pediatric patients with CD33+ relapsed/refractory (R/R) AML. OBJECTIVE: The aim of this study was to estimate the budgetary impact of introducing GO to a 1-million-member US health plan over a 5-year period. METHODS: We developed models to estimate the impact of introducing GO in combination with conventional induction chemotherapy or as monotherapy for newly diagnosed AML, and as monotherapy for R/R AML. Models were built using data on drug costs and treatment-related outcomes obtained from published clinical trials and other publicly available sources. Results were reported on a per member/per year and per member/per month (PMPM) basis. RESULTS: Base-case results of the newly diagnosed model indicated that the addition of GO in the combination setting reduced the overall budget of a 1-million-member health plan. The estimated net cost (US$) savings ranged from $72,969 ($0.006 PMPM) in year 1 to $745,426 ($0.062 PMPM) in year 5. In the monotherapy setting, GO was associated with increased net costs ranging from $4118 (0.0003 PMPM) in year 1 to $31,885 ($0.003 PMPM) in year 5. Base-case results of the R/R AML model demonstrated increased net costs that ranged from $17,326 ($0.001 PMPM) in year 1 to $46,163 ($0.004 PMPM) in year 5. Scenario analyses in all settings indicated the budget impact was not overly sensitive to the selected input assumptions, with the exception of the scenario considering only the pharmacy budget impact in the combination setting. CONCLUSIONS: The introduction of GO for newly diagnosed and R/R AML would have a minimal impact on the budget of a US health plan and could result in cost savings in the combination therapy setting for newly diagnosed AML.

Systematic review, network meta-analysis and economic evaluation of biological therapy for the management of active psoriatic arthritis.

BACKGROUND: An updated economic evaluation was conducted to compare the cost-effectiveness of the four tumour necrosis factor (TNF)-α inhibitors adalimumab, etanercept, golimumab and infliximab in active, progressive psoriatic arthritis (PsA) where response to standard treatment has been inadequate. METHODS: A systematic review was conducted to identify relevant, recently published studies and the new trial data were synthesised, via a Bayesian network meta-analysis (NMA), to estimate the relative efficacy of the TNF-α inhibitors in terms of Psoriatic Arthritis Response Criteria (PsARC) response, Health Assessment Questionnaire (HAQ) scores and Psoriasis Area and Severity Index (PASI). A previously developed economic model was updated with the new meta-analysis results and current cost data. The model was adapted to delineate patients by PASI 50%, 75% and 90% response rates to differentiate between psoriasis outcomes. RESULTS: All four licensed TNF-α inhibitors were significantly more effective than placebo in achieving PsARC response in patients with active PsA. Adalimumab, etanercept and infliximab were significantly more effective than placebo in improving HAQ scores in patients who had achieved a PsARC response and in improving HAQ scores in PsARC non-responders. In an analysis using 1,000 model simulations, on average etanercept was the most cost-effective treatment and, at the National Institute for Health and Care Excellence willingness-to-pay threshold of between £20,000 to £30,000, etanercept is the preferred option. CONCLUSIONS: The economic analysis agrees with the conclusions from the previous models, in that biologics are shown to be cost-effective for treating patients with active PsA compared with the conventional management strategy. In particular, etanercept is cost-effective compared with the other biologic treatments.