Difference In Quality-adjusted Life-years Research Articles

Robot-assisted Versus Open Radical Cystectomy in Bladder Cancer: An Economic Evaluation Alongside a Multicentre Comparative Effectiveness Study

BackgroundOpen radical cystectomy (ORC) is regarded as the standard treatment for muscle-invasive bladder cancer, but robot-assisted radical cystectomy (RARC) is increasingly used in practice. A recent study showed that RARC resulted in slightly fewer minor but slightly more major complications, although the difference was not statistically significant. Some differences were found in secondary outcomes favouring either RARC or ORC. RARC use is expected to increase in coming years, which fuels the debate about whether RARC provides value for money. ObjectiveTo assess the cost-effectiveness of RARC compared to ORC in bladder cancer. Design, setting, and participantsThis economic evaluation was performed alongside a prospective multicentre comparative effectiveness study. We included 348 bladder cancer patients (ORC, n = 168; RARC, n = 180) from 19 Dutch hospitals. Outcome measurements and statistical analysisOver 1 yr, we assessed the incremental cost per quality-adjusted life year (QALY) gained from both healthcare and societal perspectives. We used single imputation nested in the bootstrap percentile method to assess missing data and uncertainty, and inverse probability of treatment weighting to control for potential bias. Deterministic sensitivity analyses were performed to explore the impact of various parameters on the cost difference. Results and limitationsThe mean healthcare cost per patient was €17 141 (95% confidence interval [CI] €15 791–€18 720) for ORC and €21 266 (95% CI €19 163–€23 650) for RARC. The mean societal cost per patient was €18 926 (95% CI €17 431–€22 642) for ORC and €24 896 (95% CI €21 925–€31 888) for RARC. On average, RARC patients gained 0.79 QALYs (95% CI 0.74–0.85) compared to 0.81 QALYs (95% CI 0.77–0.85) for ORC patients, resulting in a mean QALY difference of −0.02 (95% CI −0.05 to 0.02). Using a cost-effectiveness threshold of €80 000, RARC was cost-effective in 0.6% and 0.2% of the replications for the healthcare and societal perspectives, respectively. ConclusionsRARC shows no difference in terms of QALYs, but is more expensive than ORC. Hence, RARC does not seem to provide value for money in comparison to ORC. Patient summaryThis study assessed the relation between costs and effects of robot-assisted surgery compared to open surgery for removal of the bladder in 348 Dutch patients with bladder cancer. We found that after 1 year, the two approaches were similarly effective according to a measure called quality-adjusted life years, but robot-assisted surgery was much more expensive.This trial was prospectively registered in the Netherlands Trial Register as NTR5362 (https://www.trialregister.nl/trial/5214).

Newborn screening for inherited metabolic diseases using tandem mass spectrometry in China: Outcome and cost-utility analysis.

Few studies in China have focused on the economic evaluation of newborn screening (NBS) for inherited metabolic disorders (IMDs) by tandem mass spectrometry (MS/MS). This study assesses the total costs, benefits, benefit-cost ratio (BCR), cost-utility ratio (CUR) and incremental cost-utility ratio (ICUR) of NBS using MS/MS compared to the non-screened group. The NBS outcomes of newborns who underwent MS/MS screening for IMDs in 2009-2018 were retrospectively reviewed. Records were extracted from a screening management system at the NBS Center of Zhejiang province. A cost-benefit analysis of screening was conducted, assessing screening costs for each subject, and direct and indirect treatment costs for IMDs detected by screening. The putative benefit of clinical outcomes related to early diagnosis was assumed to be improvement in quality of life and prolonged life expectancy in the screened group, as compared to the non-screened group. Of the 3,040,815 newborns screened, 735 (2.86%) cases were diagnosed through gene sequence analysis. The most frequently occurring types of IMD were amino acid disorders (n = 276), then fatty acid oxidation disorders (n = 248), followed by organic acidaemias (n = 211). The difference in quality-adjusted life-years (QALYs) ranged from 0.78 to 15.4 in the screened group. The CUR was CNY¥ 116,183.89/QALY in the screened group and CNY¥ 3,078,823.65/QALY in the non-screened group. The ICUR was CNY¥ -768,428.76/QALY, and the BCR was 6.09. NBS using MS/MS can be considered cost-effective in China. The nationwide promotion of NBS using MS/MS deserves priority consideration and sufficient publicity.

Cost-effectiveness of a self-management and comprehensive training intervention in patients with type 2 diabetes up to 5 years of diagnosis in a specialized hospital in Mexico City

IntroductionTo assess the cost-effectiveness of a multidisciplinary and comprehensive innovative diabetes care program (CAIPaDi) versus usual treatment in public health institutions.Research design and methodsUsing a cost-effectiveness analysis, we compared the...

PCV20 Cost-Effectiveness of a Tacrolimus-Mycophenolate Mofetil Regimen for Organ Rejection Prophylaxis in Heart Transplant Recipients in Colombia

Evidence of the cost-effectiveness of the calcineurin inhibitor tacrolimus is required to guide its inclusion in the Colombian National Benefit Plan as a treatment for organ rejection prophylaxis in heart transplant recipients. A model was developed to estimate the cost-effectiveness of tacrolimus-mycophenolate mofetil (TAC-MMF) versus cyclosporine-mycophenolate mofetil (CYC-MMF) for organ rejection prophylaxis in heart transplant recipients in Colombia. A Markov model with monthly cycle length was constructed to estimate costs and quality-adjusted life years (QALY) for each treatment alternative over a 15-year time horizon from the perspective of the Colombian third-party payer. The following states were considered: alive with a functioning graft, history of acute graft rejection, cardiac allograft vasculopathy, and death. The costs were estimated using the Social Security (Instituto del Seguro Social) Rates Manual and reports of the Medicine Price Information System, and the resources and cost-generating events were identified using a base case constructed with clinical experts. The rejection rate for each treatment alternative was taken from a previously undertaken meta-analysis. Information on vasculopathy and mortality was taken from observational studies with follow-up times beyond 1 month, and was later adjusted to probabilistic distributions to obtain a monthly probability of developing the outcome. The TAC-MMF regimen represented a 0.236 difference in QALY and a cost difference of US −$18,337 versus CYC-MMF over the 15-year time horizon (US $1 = Colombian peso ∼3763, November 2020), which makes the former a dominant intervention. The main differentiators of the treatment alternatives in the model were acute rejection rate, cardiac allograft vasculopathy, and treatment cost. In this regard, the cost of CYC treatment was higher than the cost of TAC treatment. Under the model assumptions, the TAC-MMF regimen could be a dominant option over the CYC-MMF regimen for organ rejection prophylaxis in heart transplant recipients in Colombia.

Cost-Effectiveness of Domiciliary High Flow Nasal Cannula Treatment in COPD Patients with Chronic Respiratory Failure.

PurposeTo evaluate the cost-effectiveness of long-term domiciliary high flow nasal cannula (HFNC) treatment in COPD patients with chronic respiratory failure.Patients and MethodsA cohort of 200 COPD patients were equally randomized into usual care ± HFNC and followed for 12 months. The outcome of the analysis was the incremental cost per quality-adjusted life-year (QALY) gained, and the analysis was conducted from a healthcare sector perspective. Data on the patients’ health-related quality of life (HRQoL), gathered throughout the trial using the St. George’s Respiratory Questionnaire (SGRQ), was converted into EQ-5D-3L health state utility values. Costs were estimated using Danish registers and valued in British pounds (£) at price level 2019. Scenario analyses and probabilistic sensitivity analyses were conducted to assess the uncertainty of the results.ResultsThe adjusted mean difference in QALYs between the HFNC group and the control group was 0.059 (95% CI: 0.017; 0.101), and the adjusted mean difference in total costs was £212 (95% CI: −1572; 1995). The analysis resulted in an incremental cost-effectiveness ratio (ICER) of £3605 per QALY gained. At threshold values of £20.000–30.000 per QALY gained, the intervention had an 83–92% probability of being cost-effective. The scenario analyses all revealed ICERs below the set threshold value and demonstrated the robustness of the main result.ConclusionThis is the first cost-effectiveness study on domiciliary HFNC in Europe. The findings demonstrate that long-term domiciliary HFNC treatment is very likely to be a cost-effective addition to usual care for COPD patients with chronic respiratory failure. The results must be interpreted in light of the uncertainty associated with the indirect estimation of health state utilities.

Reverse Total Shoulder Arthroplasty Versus Hemiarthroplasty for the Treatment of Proximal Humerus Fractures: A Model-Based Cost-Effectiveness Analysis.

Compared with hemiarthroplasty (HA), reverse total shoulder arthroplasty (RTSA) may provide greater cost and health-related benefits for patients with complex three- and four-part proximal humeral fractures. This study set out to compare RTSA versus HA for the incremental cost per incremental improvement in quality adjusted life years (QALYs) for a hypothetical cohort of patients with proximal humerus fractures. Parameters and characteristics for a hypothetical cohort of elderly patients with proximal humerus fractures were collected through the literature. A cohort-level Markov decision model was constructed. Incremental cost-effectiveness ratios representing the difference in cost divided by the difference in QALYs were calculated, and scenario, one-way, and probabilistic analysis were conducted. RTSA was associated with lower cost and greater effectiveness compared with HA. The predicted cost difference corresponded to a saving of $99,626 per 100 individuals treated, and the predicted difference in QALY was 16.8 per 100 individuals treated. Results were sensitive to the discount rate, the health-related quality of life assigned to health states, and the cost of the surgical procedures. In probabilistic analysis, 77.1% of iterations were cost-effective at a threshold willingness-to-pay for a QALY of $100,000 US dollars. Findings suggest that RTSA may be a cost-effective alternative to HA for treating elderly patients requiring surgery for proximal humerus fractures. The model and corresponding code are available on request to the corresponding author. Level III.

Cost-Effectiveness of Dopamine Agonists and Monoamine Oxidase B Inhibitors in Early Parkinson's Disease.

The PD MED study reported small but persistent benefits in patient-rated mobility scores and quality of life from initiating therapy with levodopa compared with levodopa-sparing therapies in early Parkinson's disease (PD). The objective was to estimate the cost-effectiveness of levodopa-sparing therapy (dopamine agonists or monoamine oxidase type B inhibitors compared with levodopa alone. PD MED is a pragmatic, open-label randomized, controlled trial in which patients newly diagnosed with PD were randomly assigned between levodopa-sparing therapy (dopamine agonists or monoamine oxidase type B inhibitors ) and levodopa alone. Mean quality-adjusted life-years and costs were calculated for each participant. Differences in mean quality-adjusted life-years and costs between levodopa and levodopa-sparing therapies and between dopamine agonists and monoamine oxidase type B inhibitors were estimated using linear regression. Over a mean observation period of 4 years, levodopa was associated with significantly higher quality-adjusted life-years (difference, 0.18; 95% CI, 0.05-0.30; P < 0.01) and lower mean costs (£3390; £2671-£4109; P < 0.01) than levodopa-sparing therapies, the difference in costs driven by the higher costs of levodopa-sparing therapies. There were no significant differences in the costs of inpatient, social care, and institutional care between arms. There was no significant difference in quality-adjusted life-years between those allocated dopamine agonists and monoamine oxidase type B inhibitors (0.02; -0.17 to 0.13 in favor of dopamine agonists; P=0.81); however costs were significantly lower for those allocated monoamine oxidase type B inhibitors (£2321; £1628-£3015; P < 0.01) because of the higher costs of dopamine agonists. There were no significant differences between arms for other costs. Initial treatment with levodopa is highly cost-effective compared with levodopa-sparing therapies. Monoamine oxidase type B inhibitors, as initial levodopa-sparing therapy was more cost-effective, with similar quality-adjusted life-years but lower costs than dopamine agonists. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Endoscopic urethrotomy versus open urethroplasty for men with bulbar urethral stricture: the OPEN randomised trial cost-effectiveness analysis

BackgroundBulbar urethral stricture is a common cause for urinary symptoms in men and its two main treatment options both have drawbacks with little evidence on their relative cost-effectiveness. Current guidelines on the management of recurrent bulbar urethral stricture have been predominantly based on expert opinion and panel consensus.ObjectiveTo assess the relative cost-effectiveness of open urethroplasty and endoscopic urethrotomy as treatment for recurrent urethral stricture in men.MethodsSet in the UK National Health Service with recruitment from 38 hospital sites, a randomised controlled trial of open urethroplasty and endoscopic urethrotomy with 6-monthly follow-up over 24 months was conducted. Two hundred and twenty-two men requiring operative treatment for recurrence of bulbar urethral stricture and having had at least one previous intervention for stricture were recruited. Effectiveness was measured by quality- adjusted life years (QALYs) derived from EQ-5D 5L. Cost-effectiveness was measured by the incremental cost per QALY gained over 24 months using a within trial analysis and a Markov model with a 10-year time horizon.ResultsIn the within trial, urethroplasty cost on average more than urethrotomy (cost difference: £2148 [95% CI 689, 3606]) and resulted in a similar number of QALYs on average (QALY difference: − 0.01 [95% CI − 0.17, 0.14)] over 24 months. The Markov model produced similar results. Sensitivity analyses using multiple imputation, suggested that the results were robust, despite observed missing data.ConclusionsBased on current practice and evidence, urethrotomy is a cost-effective treatment compared with urethroplasty.KeypointsUrethrotomy and urethroplasty both led to symptom improvement for men with bulbar urethral stricture—a common cause for urinary symptoms in men; Urethroplasty appeared unlikely to offer good value for money compared to urethrotomy based on current evidence.Trial registration: ISRCTN: 98009168 (date: 29 November 2012) and it is also in the UK NIHR Portfolio (reference 13507).Trial protocol: The latest version (1.8) of the full protocol is available at: www.journalslibrary.nihr.ac.uk/programmes/hta/105723/#/ and a published version is also available: Stephenson R, Carnell S, Johnson N, Brown R, Wilkinson J, Mundy A, et al. Open urethroplasty versus endoscopic urethrotomy—clarifying the management of men with recurrent urethral stricture (the OPEN trial): study protocol for a randomised controlled trial. Trials 2015;16:600. https://doi.org/10.1186/s13063-015-1120-4.Trial main clinical results publication: Goulao B, Carnell S, Shen J, MacLennan G, Norrie J, Cook J, et al. Surgical Treatment for Recurrent Bulbar Urethral Stricture: A Randomised Open-label Superiority Trial of Open Urethroplasty Versus Endoscopic Urethrotomy (the OPEN Trial), European Urology, Volume 78, Issue 4, 2020, Pages 572–580.

Comparative Cost and Effectiveness of a New Algorithm for Early Lyme Disease Diagnosis: Evaluation in US, Germany, and Italy.

PurposeThis Lyme disease early detection economic model, for patients with suspected Lyme disease without erythema migrans (EM), compares outcomes of standard two-tier testing (sTTT), modified two-tier testing (mTTT) and the DiaSorin Lyme Detection Algorithm (LDA), a combination of both serology tests and Interferon-ɤ Release Assay.Patients and MethodsA patient-level simulation model was built to incorporate effectiveness estimation from a structured focused literature review, and health-care cost inputs for the United States, Germany, and Italy. Simulated clinical outcomes were 1) percent of patients with timely and correct diagnosis, 2) patients appropriately treated and exposed to antibiotics therapy, and 3) patients with late Lyme disease manifestations. Expected health outcomes were expressed in terms of differences in quality-adjusted life years (QALYs) due to disseminated Lyme disease and persisting symptoms, and economic outcomes were analyzed from a third-party payer perspective.ResultsThe DiaSorin LDA resulted in a better sensitivity compared to sTTT and mTTT, 84% vs 49% and 45%, respectively, in the base case (13% of infected patients in the tested population). Due to the improved diagnostic performance, the LDA-based strategy is expected to be more effective, providing mean incremental 0.024 QALYs per tested patient, or 0.19 per infected patient. Furthermore, from a third-party payer perspective, the adoption of the LDA-based strategy would reduce the expected health-care cost for suspected and confirmed Lyme disease by roughly 40%, ie about $410, €130, and €170 per tested patient in the United States, Germany, and Italy, respectively, compared to sTTT. The results are most sensitive to the infection rate in the tested population, with LDA maintaining a cost advantage for Lyme disease active infection rates ≥0.8-2.5%.ConclusionLDA early diagnostic testing and subsequent treatment of subjects with early Lyme disease without EM are expected to outperform traditional management strategies both clinically and economically in the US, Germany, and Italy.

Premedication prior to PEG-asparaginase is cost-effective in pediatric patients with acute lymphoblastic leukemia.

PEG-asparaginase is critical in pediatric acute lymphoblastic leukemia (ALL) therapy but is highly immunogenic. Severe allergic reactions lead to substitution of further PEG-asparaginase with Erwinia. Erwinia is associated with more frequent dosing, increased expense, and limited availability. Premedication may reduce rates of allergic reactions. This Markov model evaluated the cost-effectiveness of three strategies: premedication plus therapeutic drug monitoring (TDM), TDM alone, and no premedication or TDM. We modeled two scenarios: a standard-risk (SR) B-ALL patient receiving two asparaginase doses and a high-risk (HR) patient receiving seven asparaginase doses. The model incorporated costs of asparaginase, premedication, TDM and clinic visits, and lost parental wages associated with each additional Erwinia dose. We incorporated a five-year time horizon with a societal perspective. Outcomes were Erwinia substitutions avoided and differences in quality-adjusted life years (QALYs). Probabilistic and one-way sensitivity analyses evaluated model uncertainty. In both scenarios, premedication was the least costly strategy. In SR and HR scenarios, premedication with monitoring resulted in 8% and 7% fewer changes toErwiniacompared with monitoring alone and 3% and 2% fewer changes compared with no premedication/monitoring, respectively. Premedication resulted in the most QALYs gained in the SR patients. Individual variation of model inputs did not change premedication/monitoring favorability for either scenario. In probabilistic sensitivity analyses, premedication/monitoring was favored in >87% of iterations in both scenarios. Compared with other strategies, premedication use and asparaginase level monitoring in children with B-ALL is potentially cost-saving.

COST-EFFECTIVENESS ANALYSIS FOR THE USE OF INTERVENTIONAL DECENTRALIZED TELEMONITORING (IDTM) IN HYPERTENSION THERAPY

Objective: We calculate quality-adjusted life years (QALY) and incremental cost-effectiveness ratio (ICER) for the use of interventional decentralized telemonitoring (idTM) in hypertension therapy. Both values are key performance indicators for cost-benefit and cost-effectiveness analysis of medical interventions. The calculations compare blood pressure adjustment and the correlated reduction in risk of morbidity and mortality between idTM and standard therapy (ST). Prior studies have shown idTM to significantly reduce the time required to reach blood pressure targets as well as to reduce the variability of blood pressure values. IdTM also allows maintaining blood pressure on target for a longer duration than ST. Design and method: Our QALY evaluation only takes myocardial infarction (MI) and stroke, the two most prominent comorbidities of hypertension, into account. Thus, the achievable QALY are likely to be underestimated by this analysis. We assume a linear correlation between elevated blood pressure and the risk of morbidity and mortality. Data on prevalence and morbidity have been included from statistical and medical publications on the German population while data on life quality come from an EQ-5D-based study performed in the US. Results: We calculate the ICER for both for the difference in QALY and blood pressure reduction in mmHg. The latter allows evaluating the cost-effectiveness of idTM independent of specific comorbidities. Conclusions: Even though idTM adds cost to the treatment of hypertension, we find that the resulting improvement of blood pressure significantly improves QALY and ICER over ST. Therefore, idTM in hypertension therapy is a promising concept both from a medical and cost-effectiveness point of view. Especially in the context of the upcoming evaluation of digital health applications (DiGA) by the German Federal Institute for Drugs and Medical Devices (BfArM), this is a crucial result. Furthermore, the results suggest idTM as a sensible candidate for addition as an element of standard care in Germany.

The Prevention of Delirium system of care for older patients admitted to hospital for emergency care: the POD research programme including feasibility RCT

The Prevention of Delirium system of care for older patients admitted to hospital for emergency care: the POD research programme including feasibility RCT

A Self-Help App for Syrian Refugees With Posttraumatic Stress (Sanadak): Randomized Controlled Trial.

BackgroundSyrian refugees residing in Germany often develop posttraumatic stress as a result of the Syrian civil war, their escape, and postmigration stressors. At the same time, there is a lack of adequate treatment options. The smartphone-based app Sanadak was developed to provide cognitive behavioral therapy–based self-help in the Arabic language for Syrian refugees with posttraumatic stress.ObjectiveThe aim of this study was to evaluate the effectiveness and cost-effectiveness of the app.MethodsIn a randomized controlled trial, eligible individuals were randomly allocated to the intervention group (IG; app use) or control group (CG; psychoeducational reading material). Data were collected during structured face-to-face interviews at 3 assessments (preintervention/baseline, postintervention/after 4 weeks, follow-up/after 4 months). Using adjusted mixed-effects linear regression models, changes in posttraumatic stress and secondary outcomes were investigated as intention-to-treat (ITT) and per-protocol (PP) analysis. Cost-effectiveness was evaluated based on adjusted mean total costs, quality-adjusted life years (QALYs), and cost-effectiveness acceptability curves using the net benefit approach.ResultsOf 170 screened individuals (aged 18 to 65 years), 133 were eligible and randomized to the IG (n=65) and CG (n=68). Although there was a pre-post reduction in posttraumatic stress, ITT showed no significant differences between the IG and CG after 4 weeks (Posttraumatic Diagnostic Scale for DSM-5, Diff –0.90, 95% CI –0.24 to 0.47; P=.52) and after 4 months (Diff –0.39, 95% CI –3.24 to 2.46; P=.79). The same was true for PP. Regarding secondary outcomes, ITT indicated a treatment effect for self-stigma: after 4 weeks (Self-Stigma of Mental Illness Scale/SSMIS–stereotype agreement: d=0.86, 95% CI 0.46 to 1.25; stereotype application: d=0.60, 95% CI 0.22 to 0.99) and after 4 months (d=0.52, 95% CI 0.12 to 0.92; d=0.50, 95% CI 0.10 to 0.90), the IG showed significantly lower values in self-stigma than the CG. ITT showed no significant group differences in total costs and QALYs. The probability of cost-effectiveness was 81% for a willingness-to-pay of €0 per additional QALY but decreased with increasing willingness-to-pay.ConclusionsSanadak was not more effective in reducing mild to moderate posttraumatic stress in Syrian refugees than the control condition nor was it likely to be cost-effective. Therefore, Sanadak is not suitable as a standalone treatment. However, as the app usability was very good, no harms detected, and stigma significantly reduced, Sanadak has potential as a bridging aid within a stepped and collaborative care approach.Trial RegistrationGerman Clinical Trials Register DRKS00013782; https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00013782International Registered Report Identifier (IRRID)RR2-10.1186/s12888-019-2110-y

Health Economic Evaluation of Patients with Colorectal Liver Metastases Randomized to ALPPS or TSH - Analysis from the LIGRO Trial

Introduction: Two-staged hepatectomy (TSH), is an established method in advanced colorectal liver metastases (CRLM). Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has emerged providing improved resection rate and survival. The health care costs and health outcomes, combining health related quality of life (HRQoL) and survival into quality-adjusted life years (QALYs), of ALPPS and TSH have not previously been evaluated and compared. Methods: This is a pre-planned, health economic evaluation from the LIGRO trial. One hundred patients with CRLM and standardized FLR < 30 % were randomized to ALPPS or TSH. Costs and QALYs were compared from treatment start up to 2 years. Costs are estimated from resource use, including all surgical interventions, length of stay after interventions, diagnostic procedures and chemotherapy and applying Swedish unit costs. QALYs were estimated by combining survival and HRQoL data, the latter being assessed with EQ-5D 3L. Estimated costs and QALYs for each treatment strategy were combined into an incremental cost-effectiveness ratio (ICER). Non-parametric bootstrapping was used to assess the joint distribution of incremental costs and QALYs. Results: The mean cost difference between ALPPS and TSH was 12662€, (95% CI -10728-36051, p=0.283). Corresponding mean difference in life years and QALYs was 0.1296 (95% CI -0.12-0.38, p=0.314) and 0.1285 (95% CI -0.11-0.36, p=0.28), respectively. The ICER was 93186 and 92414 for QALYs and life-years as outcomes, respectively. Conclusion: Based on the two-year data, the cost-effectiveness of ALPPS is uncertain. Further research, exploring cost and health outcomes beyond 2 year is needed.

Assessing the Impact of EQ-5D Country-specific Value Sets on Cost-utility Outcomes.

To assess the impact of EQ-5D country-specific value sets on cost-utility outcomes. Data from 2 randomized controlled trials on low back pain (LBP) and depression were used. 3L value sets were identified from the EuroQol Web site. A nonparametric crosswalk was employed for each tariff to obtain the likely 5L values. Differences in quality-adjusted life years (QALYs) between countries were tested using paired t tests, with United Kingdom as reference. Cost-utility outcomes were estimated for both studies and both EQ-5D versions, including differences in QALYs and cost-effectiveness acceptability curves. For the 3L, QALYs ranged between 0.650 (Taiwan) and 0.892 (United States) in the LBP study and between 0.619 (Taiwan) and 0.879 (United States) in the depression study. In both studies, most country-specific QALY estimates differed statistically significantly from that of the United Kingdom. Incremental cost-effectiveness ratios ranged between &OV0556;2044/QALY (Taiwan) and &OV0556;5897/QALY (Zimbabwe) in the LBP study and between &OV0556;38,287/QALY (Singapore) and &OV0556;96,550/QALY (Japan) in the depression study. At the NICE threshold of &OV0556;23,300/QALY (≈£20,000/QALY), the intervention's probability of being cost-effective versus control ranged between 0.751 (Zimbabwe) and 0.952 (Taiwan) and between 0.230 (Canada) and 0.396 (Singapore) in the LBP study and depression study, respectively. Similar results were found for the 5L, with extensive differences in ICERs and moderate differences in the probability of cost-effectiveness. This study indicates that the use of different EQ-5D country-specific value sets impacts on cost-utility outcomes. Therefore, to account for the fact that health state preferences are affected by sociocultural differences, relevant country-specific value sets should be used.

Cost Effectiveness of Caplacizumab in Acquired Thrombotic Thrombocytopenic Purpura

Introduction: Acquired thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease characterized by thrombotic microangiopathy leading to end-organ damage. The standard of care (SOC) treatment is therapeutic plasma exchange (TPE) alongside immunomodulation with steroids, with increasing use of rituximab +/- other immunomodulatory agents. The addition of caplacizumab, a nanobody targeting von Willebrand factor, was shown to accelerate platelet count recovery, reduce TPE treatments and hospital length of stay, decrease exacerbations and increase relapses in TTP patients treated in the TITAN and HERCULES trials. Given the efficacy of caplacizumab in the TITAN and HERCULES trials, we conducted a cost effectiveness analysis (CEA) of caplacizumab in acquired TTP, representing the first-ever CEA in TTP. Methods: We built decision tree models to evaluate the cost effectiveness of SOC plus caplacizumab versus SOC in acquired TTP based on the results of each of the phase II TITAN trial at 12-month follow-up and the phase III HERCULES trial at 1-month follow-up. Costs were assessed from the health system perspective. For each trial, the SOC cost was calculated as the sum of TPE sessions, hospital length-of-stay (LOS), intensive care unit (ICU) stay, and rituximab use, while the cost of the SOC plus caplacizumab arm included the SOC cost plus the list price of caplacizumab (USD $270,000 per TTP episode). Effectiveness was calculated in quality-adjusted life years (QALY). Cost effectiveness of each treatment arm was calculated as the ratio of cost divided by QALYs. The incremental cost effectiveness ratio (ICER) of adding caplacizumab to SOC was calculated as the difference between the costs of the two treatment arms divided by the difference in QALYs; the ICER was then compared against the 2019 US willingness-to-pay (WTP) threshold of $195,300 USD as a measure of overall cost effectiveness. To avoid potential confounding factors that might inadvertently bias our analysis against the addition of caplacizumab, all values used in our models were selected to maximize cost in the SOC arm and minimize cost in the SOC plus caplacizumab arm in the two clinical trials. We also created a Markov model comparing cost effectiveness of SOC plus caplacizumab versus SOC in acquired TTP with a 5-year time horizon. We performed one-way sensitivity analyses for all models varying parameters including LOS, ICU stay, number of TPE sessions, rituximab use, utilities of the well and diseases states, and caplacizumab cost. Results: In the decision tree models, caplacizumab use yielded a higher cost of treatment compared to SOC alone in both trials (TITAN: $325,647 for caplacizumab plus SOC, versus $89,750 for SOC; HERCULES: $323,547 for caplacizumab plus SOC, versus $83,634 for SOC). An improvement in QALYs with the addition of caplacizumab was noted as compared to SOC in both trials (0.07 in TITAN and 0.26 in HERCULES). The ICER for adding caplacizumab to SOC versus SOC alone was $3.7 million in the TITAN trial and $0.9 million in the HERCULES trial, well above the US WTP threshold. The 5-year horizon Markov model yielded higher cost of caplacizumab treatment compared to SOC alone ($551,878 versus $151,947) and an improvement in QALYs (3.19 versus 2.92). The ICER for adding caplacizumab to SOC was $1.5 million (95% confidence interval $1.25-$1.72 million) with SOC favored in 100% of 10,000 Monte Carlo simulations in a probabilistic sensitivity analysis. Among all parameters, decreasing the cost of caplacizumab had the greatest impact on decreasing the ICERs in all models. The price of caplacizumab treatment for one TTP episode to meet the 2019 US WTP would have to be $46,424 and $80,848 in the TITAN and HERCULES decision tree models, respectively, and $65,106 in a Markov model with a 5-year horizon. Conclusion: The addition of caplacizumab to SOC treatment is not cost effective at its current drug pricing. As our models are designed to maximize the cost effectiveness of caplacizumab, it is very likely that the actual costs incurred by this medication will be much higher than what we report here. Compared to CEA studies of other orphan drugs that, unlike caplacizumab, alter long-term disease course, the costs incurred by caplacizumab treatment in acquired TTP are at the higher end of the spectrum. Additional studies utilizing longer-term follow-up data are warranted to assess the full impact of caplacizumab on the cost of treating TTP. Figure Disclosures No relevant conflicts of interest to declare.

Open urethroplasty versus endoscopic urethrotomy for recurrent urethral stricture in men: the OPEN RCT.

Men who suffer recurrence of bulbar urethral stricture have to decide between endoscopic urethrotomy and open urethroplasty to manage their urinary symptoms. Evidence of relative clinical effectiveness and cost-effectiveness is lacking. To assess benefit, harms and cost-effectiveness of open urethroplasty compared with endoscopic urethrotomy as treatment for recurrent urethral stricture in men. Parallel-group, open-label, patient-randomised trial of allocated intervention with 6-monthly follow-ups over 24 months. Target sample size was 210 participants providing outcome data. Participants, clinicians and local research staff could not be blinded to allocation. Central trial staff were blinded when needed. UK NHS with recruitment from 38 hospital sites. A total of 222 men requiring operative treatment for recurrence of bulbar urethral stricture who had received at least one previous intervention for stricture. A centralised randomisation system using random blocks allocated participants 1 : 1 to open urethroplasty (experimental group) or endoscopic urethrotomy (control group). The primary clinical outcome was control of urinary symptoms. Cost-effectiveness was assessed by cost per quality-adjusted life-year (QALY) gained over 24 months. The main secondary outcome was the need for reintervention for stricture recurrence. The mean difference in the area under the curve of repeated measurement of voiding symptoms scored from 0 (no symptoms) to 24 (severe symptoms) between the two groups was -0.36 [95% confidence interval (CI) -1.78 to 1.02; p = 0.6]. Mean voiding symptom scores improved between baseline and 24 months after randomisation from 13.4 [standard deviation (SD) 4.5] to 6 (SD 5.5) for urethroplasty group and from 13.2 (SD 4.7) to 6.4 (SD 5.3) for urethrotomy. Reintervention was less frequent and occurred earlier in the urethroplasty group (hazard ratio 0.52, 95% CI 0.31 to 0.89; p = 0.02). There were two postoperative complications requiring reinterventions in the group that received urethroplasty and five, including one death from pulmonary embolism, in the group that received urethrotomy. Over 24 months, urethroplasty cost on average more than urethrotomy (cost difference £2148, 95% CI £689 to £3606) and resulted in a similar number of QALYs (QALY difference -0.01, 95% CI -0.17 to 0.14). Therefore, based on current evidence, urethrotomy is considered to be cost-effective. We were able to include only 69 (63%) of the 109 men allocated to urethroplasty and 90 (80%) of the 113 men allocated to urethrotomy in the primary complete-case intention-to-treat analysis. The similar magnitude of symptom improvement seen for the two procedures over 24 months of follow-up shows that both provide effective symptom control. The lower likelihood of further intervention favours urethroplasty, but this had a higher cost over the 24 months of follow-up and was unlikely to be considered cost-effective. Formulate methods to incorporate short-term disutility data into cost-effectiveness analysis. Survey pathways of care for men with urethral stricture, including the use of enhanced recovery after urethroplasty. Establish a pragmatic follow-up schedule to allow national audit of outcomes following urethral surgery with linkage to NHS Hospital Episode Statistics. Current Controlled Trials ISRCTN98009168. This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 61. See the NIHR Journals Library website for further project information.

Cost-effectiveness of Population-Wide Genomic Screening for Hereditary Breast and Ovarian Cancer in the United States

Genomic screening for hereditary breast and ovarian cancer (HBOC) in unselected women offers an opportunity to prevent cancer morbidity and mortality, but the potential clinical impact and cost-effectiveness of such screening have not been well studied. To estimate the lifetime incremental incidence of HBOC and the quality-adjusted life-years (QALYs), costs, and cost-effectiveness of HBOC genomic screening in an unselected population vs family history-based testing. In this study conducted from October 27, 2017, to May 3, 2020, a decision analytic Markov model was developed that included health states for precancer, for risk-reducing mastectomy (RRM) and risk-reducing salpingo-oophorectomy (RRSO), for earlier- and later-stage HBOC, after cancer, and for death. A complimentary cascade testing module was also developed to estimate outcomes in first-degree relatives. Age-specific RRM and RRSO uptake probabilities were estimated from the Geisinger MyCode Community Health Initiative and published sources. Parameters including RRM and RRSO effectiveness, variant-specific cancer risk, costs, and utilities were derived from published sources. Sensitivity and scenario analyses were conducted to evaluate model assumptions and uncertainty. Lifetime cancer incidence, QALYs, life-years, and direct medical costs for genomic screening in an unselected population vs family history-based testing only were calculated. The incremental cost-effectiveness ratio (ICER) was calculated as the difference in cost between strategies divided by the difference in QALYs between strategies. Earlier-stage and later-stage cancer cases prevented and total cancer cases prevented were also calculated. The model found that population screening of 30-year-old women was associated with 75 (95% credible range [CR], 60-90) fewer overall cancer cases and 288 QALYs (95% CR, 212-373 QALYs) gained per 100 000 women screened, at an incremental cost of $25 million (95% CR, $21 millon to $30 million) vs family history-based testing; the ICER was $87 700 (78% probability of being cost-effective at a threshold of $100 000 per QALY). In contrast, population screening of 45-year-old women was associated with 24 (95% CR, 18-29) fewer cancer cases and 97 QALYs (95% CR, 66-130 QALYs) gained per 100 000 women screened, at an incremental cost of $26 million (95% CR, $22 million to $30 million); the ICER was $268 200 (0% probability of being cost-effective at a threshold of $100 000 per QALY). A scenario analysis without cascade testing increased the ICER to $92 600 for 30-year-old women and $354 500 for 45-year-old women. A scenario analysis assuming a 5% absolute decrease in mammography screening in women without a variant was associated with the potential for net harm (-90 QALYs per 100 000 women screened; 95% CR, -180 to 10 QALYs). The results of this study suggest that population HBOC screening may be cost-effective among younger women but not among older women. Cascade testing of first-degree relatives added a modest improvement in clinical and economic value. The potential for harm conferred by inappropriate reduction in mammography among noncarriers should be quantified.

Reduction of routine use of radiography in patients with ankle fractures leads to lower costs and has no impact on clinical outcome: an economic evaluation

BackgroundTo evaluate the cost-effectiveness of a reduction in the number of routine radiographs in the follow-up of patients with ankle fractures.MethodsWe performed an economic evaluation alongside the multicentre, randomised WARRIOR trial. Participants were randomised to a reduced imaging follow-up protocol (i.e. radiographs at week 6 and 12 follow-up obtained on clinical indication) or usual care (i.e. routine radiography at weeks 6 and 12). The Olerud & Molander Ankle Score (OMAS) was used to assess ankle function and the EQ-5D-3L was used to estimate Quality-Adjusted Life Years (QALYs). Costs and resource use were assessed using self-reported questionnaires and medical records, and analysed from a societal perspective. Multiple imputation was used for missing data, and data were analysed using seemingly unrelated regression analysis and bootstrapping.ResultsIn total, 246 patients had data available for analysis (reduced imaging = 118; usual care = 128). Fewer radiographs were obtained in the reduced imaging group (median = 4) compared with the usual-care group (median = 5). Functional outcome was comparable in both groups. The difference in QALYs was − 0.008 (95% CI:-0.06 to 0.04) and the difference in OMAS was 0.73 (95% CI:-5.29 to 6.76). Imaging costs were lower in the reduced imaging group (−€48; 95% CI:- €72 to -€25). All other cost categories did not statistically differ between the groups. The probability of the reduced imaging protocol being cost-effectiveness was 0.45 at a wiliness-to-pay of €20,000 per QALY.ConclusionsReducing the number of routine follow-up radiographs has a low probability of being cost-effective compared with usual care. Functional outcome, health-related quality of life and societal costs were comparable in both groups, whereas imaging costs were marginally lower in the reduced imaging group. Given this, adherence to a reduced imaging follow-up protocol for those with routine ankle fractures can be followed without sacrificing quality of care, and may result in reduced costs.Trial registrationThe trial was registered on 26-05-2014 in the Netherlands Trial Registry, with reference number NL4477 (www.trialregister.nl/trial/4477).

The Prepare for Kidney Care Study: prepare for renal dialysis versus responsive management in advanced chronic kidney disease.

Shared decision making in advanced chronic kidney disease (CKD) requires unbiased information on survival and person-centred outcomes known to matter to patients: quality of life, symptom burden and support from family and healthcare professionals. To date, when deciding between dialysis and conservative care, patients have had to rely on evidence from small observational studies. Clinicians recognize that like is not being compared with like in these studies, and interpret the results differently. Furthermore, support differs considerably between renal units. What patients choose therefore depends on which renal unit they attend. To address this, a programme of work has been underway in the UK. After reports on survival and symptoms from a small number of renal units, a national, mixed-methods study—the Conservative Kidney Management Assessment of Practice Patterns Study—mapped out conservative care practices and attitudes in the UK. This led to the Prepare for Kidney Care study, a randomized controlled trial comparing preparation for dialysis versus preparation for conservative care. Although powered to detect a positivist 0.345 difference in quality-adjusted life years between the two treatments, this trial also takes a realist approach with a range of person-centred secondary outcomes and embedded qualitative research. To understand generalizability, it is nested in an observational cohort study, which is nested in a CKD registry. Challenges to recruitment and retention have been rapidly identified and addressed using an established embedded mixed methods approach—the QuinteT recruitment intervention. This review considers the background to and progress with recruitment to the trial.