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This study aimed to conduct a scoping review of randomized controlled trials (RCTs) and investigate which work productivity loss outcomes were measured in these RCTs, how each outcome was measured and analyzed, and how the results for each outcome were presented. A systematic search was conducted from January 2010 to April 2020 from 2 databases: PubMed and Cochrane Central Register of Controlled Trials. Data on country, study population, disease focus, sample size, work productivity loss outcomes measured (absenteeism, presenteeism, employment status changes), and methods used to measure, report, and analyze each work productivity loss outcome were extracted and analyzed. We found 435 studies measuring absenteeism or presenteeism, of which 155 studies (35.6%) measured both absenteeism and presenteeism and were included in our final review. Only 9 studies also measured employment status changes. The most used questionnaire was the Work Productivity and Activity Impairment Questionnaire. The analysis of absenteeism and presenteeism data was mostly done using regression models (n = 98, n = 98, respectively) for which a normal distribution was assumed (n = 77, n = 89, respectively). Absenteeism results were most often presented in time whereas presenteeism was commonly presented using a percent scale or score. There is a lack of consensus on how to measure, analyze, and present work productivity loss outcomes in RCTs published in the past 10 years. The diversity of measurement, analysis, and presentation methods used in RCTs may make comparability challenging. There is a need for guidelines providing recommendations to standardize the comprehensiveness and the appropriateness of methods used to measure, analyze, and report work productivity loss in RCTs. • Increasingly, randomized controlled trials (RCTs) are incorporating work productivity loss as a patient-centered outcome. Previous literature has focused on assessing measurement properties of various questionnaires used to measure work productivity loss. Nevertheless, little is known about current research practices in terms of which work productivity loss outcomes are measured (absenteeism, presenteeism, and employment status changes) and how they are measured, analyzed, and presented in RCTs among broader populations including employees, patients, and caregivers. • We found 435 studies measuring absenteeism or presenteeism. Among them, 155 (35.6%) measured both, and only 9 studies also measured employment status changes. The most used questionnaire was the Work Productivity and Activity Impairment Questionnaire. Despite their skewed distribution with many zeros, absenteeism and presenteeism were commonly analyzed with models that assume they follow a normal distribution. Absenteeism results were most often presented in time, whereas presenteeism was commonly presented using a percent scale or score. • RCTs are measuring work productivity loss as a patient-centered outcome or a cost component for economic evaluations. The results of RCTs and economic evaluations are critical in informing healthcare decision makers for their funding decisions. Our review suggests that most RCTs partially measured work productivity loss and may not analyze the data with statistically appropriate methods, which may result in reporting underestimated loss and biased treatment effects. The diverse methods used in RCTs make comparability challenging. [ABSTRACT FROM AUTHOR]

Objectives: To model the cost-effectiveness of the TYRX Absorbable Antibacterial Envelope when used in patients at increased risk of cardiac implantable electronic device (CIED) infection in the context of 3 European healthcare systems: Germany, Italy, and England.Methods: A decision tree model with a lifetime horizon was populated using data from the Worldwide Randomized Antibiotic Envelope Infection Prevention Trial, a large multicenter randomized controlled trial. Use of the antibacterial envelope adjunctive to standard of care was compared to standard of care infection prevention alone. Patients in the model were divided into subgroups based on presence of factors known to increase infection risk.Results: The antibacterial envelope had the most favorable cost-effectiveness profile when patients had previously experienced CIED infection, had a history of immunosuppressive therapy, or had a Prevention of Arrhythmia Device Infection Trial (PADIT) score indicating high risk of infection (scores ≥6) at cost-effectiveness thresholds of €50 000 in Germany (assumed in the absence of an official threshold), €40 000 in Italy, and £30 000 in England. Probabilistic sensitivity analysis indicated that the antibacterial envelope was likely to be cost-effective in patients with other risk factors (including replacement of high power CIEDs, generator replacement with lead modification, and PADIT scores indicating intermediate risk of infection) when used with some device types and in some countries.Conclusions: The absorbable antibacterial envelope was associated with cost-effectiveness ratios below European benchmarks in selected patients at increased risk of infection, suggesting the envelope provides value for European healthcare systems by reducing CIED infections. [ABSTRACT FROM AUTHOR]

Objectives: Continuous chemotherapy has been used to treat patients with metastatic esophageal squamous cell carcinoma (mESCC), despite weak evidence supporting a clinical benefit, associated side effects for the patients, and unjustified medical costs. In the French setting, we conducted a cost-utility analysis alongside the randomized E-DIS trial (NCT01248299), which compared first-line fluorouracil/platinum-based chemotherapy continuation (CT-CONT) to CT discontinuation (CT-DISC) in progressive-free patients after an initial 6-week treatment phase.Methods: A partitioned survival analysis was performed using patient-level data collected during the trial for survival outcomes, quality of life (EQ-5D-3L), and medical costs. The mean quality-adjusted life-years (QALYs) and medical costs were estimated over an 18-month period to assess the incremental net monetary benefit and incremental cost-effectiveness ratio. Uncertainty was handled using the nonparametric bootstrap and univariate analysis. Sixty-seven patients with mESCC were randomized and included in the cost-utility analysis.Results: On average, CT-CONT slightly decreased the number of QALYs (-0.038) and increased the cost per patient (+ €1177). At a willingness-to-pay threshold of €50 000/QALY, the incremental net monetary benefit was negative (-€3077 [95% confidence interval: -6564; 4359]), and the incremental cost-effectiveness ratio was -30 958€/QALY (CT-CONT dominated). The probability of the CT-CONT treatment option being cost-effective at a willingness-to-pay threshold of €50 000/QALY, compared to CT-DISC, was 29%.Conclusions: CT-DISC may be considered as an alternative therapeutic option to CT-CONT in patients with mESCC who have stable disease after an initial chemotherapy treatment phase. A continuous chemotherapy could indeed reduce the number of QALYs because of the disutility associated with the continuous treatment. [ABSTRACT FROM AUTHOR]

Objectives: We applied principles for conducting economic evaluations of factorial trials to a trial-based economic evaluation of a cluster-randomized 2 × 2 × 2 factorial trial. We assessed the cost-effectiveness of atorvastatin, omega-3 fish oil, and an action-planning leaflet, alone and in combination, from a UK National Health Service perspective.Methods: The Atorvastatin in Factorial With Omega EE90 Risk Reduction in Diabetes (AFORRD) Trial randomized 800 patients with type 2 diabetes to atorvastatin, omega-3, or their respective placebos and randomized general practices to receive a leaflet-based action-planning intervention designed to improve compliance or standard care. The trial was conducted at 59 UK general practices. Sixteen-week outcomes for each trial participant were extrapolated for 70 years using the United Kingdom Prospective Diabetes Study Outcomes Model v2.01. We analyzed the trial as a 2 × 2 factorial trial (ignoring interactions between action-planning leaflet and medication), as a 2 × 2 × 2 factorial trial (considering all interactions), and ignoring all interactions.Results: We observed several qualitative interactions for costs and quality-adjusted life-years (QALYs) that changed treatment rankings. However, different approaches to analyzing the factorial design did not change the conclusions. There was a ≥99% chance that atorvastatin is cost-effective and omega-3 is not, at a £20 000/QALY threshold.Conclusions: Atorvastatin monotherapy was the most cost-effective combination of the 3 trial interventions at a £20 000/QALY threshold. Omega-3 fish oil was not cost-effective, while there was insufficient evidence to draw firm conclusions about action planning. Recently-developed methods for analyzing factorial trials and combining parameter and sampling uncertainty were extended to estimate cost-effectiveness acceptability curves within a 2x2x2 factorial design with model-based extrapolation. [ABSTRACT FROM AUTHOR]

Objective To report the cost-effectiveness of a tailored handheld computerized procedural preparation and distraction intervention (Ditto) used during pediatric burn wound care in comparison to standard practice. Methods An economic evaluation was performed alongside a randomized controlled trial of 75 children aged 4 to 13 years who presented with a burn to the Royal Children’s Hospital, Brisbane, Australia. Participants were randomized to either the Ditto intervention (n = 35) or standard practice (n = 40) to measure the effect of the intervention on days taken for burns to re-epithelialize. Direct medical, direct nonmedical, and indirect cost data during burn re-epithelialization were extracted from the randomized controlled trial data and combined with scar management cost data obtained retrospectively from medical charts. Nonparametric bootstrapping was used to estimate statistical uncertainty in cost and effect differences and cost-effectiveness ratios. Results On average, the Ditto intervention reduced the time to re-epithelialize by 3 days at AU$194 less cost for each patient compared with standard practice. The incremental cost-effectiveness plane showed that 78% of the simulated results were within the more effective and less costly quadrant and 22% were in the more effective and more costly quadrant, suggesting a 78% probability that the Ditto intervention dominates standard practice (i.e., cost-saving). At a willingness-to-pay threshold of AU$120, there is a 95% probability that the Ditto intervention is cost-effective (or cost-saving) against standard care. Conclusions This economic evaluation showed the Ditto intervention to be highly cost-effective against standard practice at a minimal cost for the significant benefits gained, supporting the implementation of the Ditto intervention during burn wound care. [ABSTRACT FROM AUTHOR]

Abstract: Background: Standard approaches to estimation of Markov models with data from randomized controlled trials tend either to make a judgment about which transition(s) treatments act on, or they assume that treatment has a separate effect on every transition. An alternative is to fit a series of models that assume that treatment acts on specific transitions. Investigators can then choose among alternative models using goodness-of-fit statistics. However, structural uncertainty about any chosen parameterization will remain and this may have implications for the resulting decision and the need for further research. Methods: We describe a Bayesian approach to model estimation, and model selection. Structural uncertainty about which parameterization to use is accounted for using model averaging and we developed a formula for calculating the expected value of perfect information (EVPI) in averaged models. Marginal posterior distributions are generated for each of the cost-effectiveness parameters using Markov Chain Monte Carlo simulation in WinBUGS, or Monte-Carlo simulation in Excel (Microsoft Corp., Redmond, WA). We illustrate the approach with an example of treatments for asthma using aggregate-level data from a connected network of four treatments compared in three pair-wise randomized controlled trials. Results: The standard errors of incremental net benefit using structured models is reduced by up to eight- or ninefold compared to the unstructured models, and the expected loss attaching to decision uncertainty by factors of several hundreds. Model averaging had considerable influence on the EVPI. Conclusions: Alternative structural assumptions can alter the treatment decision and have an overwhelming effect on model uncertainty and expected value of information. Structural uncertainty can be accounted for by model averaging, and the EVPI can be calculated for averaged models. [Copyright &y& Elsevier]

Abstract: Background: Very few randomized controlled trials (RCTs) have compared laparoscopic Nissen fundoplication (LNF) to proton pump inhibitors (PPI) medical management for patients with chronic gastroesophageal reflux disease (GERD). Larger RCTs have been relatively short in duration, and have reported mixed results regarding symptom control and effect on quality of life (QOL). Economic evaluations have reported conflicting results. Objectives: To determine the incremental cost-utility of LNF versus PPI for treating patients with chronic and controlled GERD over 3 years from the societal perspective. Methods: Economic evaluation was conducted alongside a RCT that enrolled 104 patients from October 2000 to September 2004. Primary study outcome was GERD symptoms (secondary outcomes included QOL and cost-utility). Resource utilization and QOL data collected at regular follow-up intervals determined incremental cost/QALY gained. Stochastic uncertainty was assessed using bootstrapping and methodologic assumptions were assessed using sensitivity analysis. Results: No statistically significant differences in GERD symptom scores, but LNF did result in fewer heartburn days and improved QOL. Costs were higher for LNF patients by $3205/patient over 3 years but QOL was also higher as measured by either QOL instrument. Based on total costs, incremental cost-utility of LNF was $29,404/QALY gained using the Health Utility Index 3. Cost-utility results were sensitive to the utility instrument used ($29,404/QALY for Health Utility Index 3, $31,117/QALY for the Short Form 6D, and $76,310/QALY for EuroQol 5D) and if current lower prices for PPIs were used in the analysis. Conclusions: Results varied depending on resource use/costs included in the analysis, the QOL instrument used, and the cost of PPIs; however, LNF was generally found to be a cost-effective treatment for patients with symptomatic controlled GERD requiring long-term management. [Copyright &y& Elsevier]

Objective: To evaluate the cost-effectiveness of microwave endometrial ablation (MEA) and thermal balloon endometrial ablation (TBALL) for heavy menstrual bleeding. Methods: A cost-utility analysis performed alongside a pragmatic RCT in a single hospital within Scotland on women undergoing MEA and TBALL. Resource use data collected from all 314 trial participants were combined with study specific and published unit cost data to estimate a cost per patient. Quality-adjusted life-years (QALYs) were based on EQ-5D responses at baseline, 2 weeks, 6 and 12 months. The incremental cost per QALY of TBALL versus MEA was calculated and bootstrapping was performed to determine the likelihood that a treatment would be cost-effective at different threshold values for society's willingness to pay for a QALY. Results: The mean cost of TBALL (10 years equipment life, 100 uses annually) of reusable equipment was £181 (95% confidence interval [CI]£70–434) greater than MEA. There were no statistically significant differences between the total nonhealth costs and health benefits of the two arms. On average, MEA provided more QALYs after adjusting for baseline EQ-5D score (0.017; 95% CI 0.017–0.051). In terms of mean incremental cost per QALY, MEA was, on average, dominant (less costly and at least as effective) and there was over a 90% chance that MEA would be considered cost-effective at a £20,000 threshold of a cost per QALY. Conclusions: MEA is likely to be more cost-effective than TBALL at 1 year. Further longer-term follow-up is, however, needed. [ABSTRACT FROM AUTHOR]

Objectives: To estimate the cost-effectiveness of topical intranasal steroids for the treatment of otitis media with effusion (OME) in primary care from the perspective of the UK National Health Service. Methods: An economic evaluation was conducted based on evidence from the double-blind, randomized, placebo-controlled GPRF [General Practice Research Framework] Nasal Steroids for Otitis Media with Effusion (GNOME) trial. Participants comprised 217 children aged 4–11 years who had at least one episode of otitis media or related ear problem in the previous 12 months and had tympanometrically confirmed bilateral OME. Children were randomly allocated to receive either mometasone furoate 50 µg or placebo spray once daily into each nostril for 3 months. The main outcome measure was the incremental cost per quality-adjusted life-year (QALY) gained for topical steroids compared with placebo. The nonparametric bootstrap method was used to present cost-effectiveness acceptability curves at alternative willingness to pay thresholds. Results: Children receiving topical steroids accrued nonsignificantly higher costs (incremental cost/child: £11, 95% confidence interval [CI]: −£199 to £222) and nonsignificantly fewer QALYs (incremental QALY gain/child: −0.0166, 95% CI: −0.0652 to 0.0320) than those receiving placebo. Topical steroids had a 24.19% probability of being cost-effective at a £20,000 per QALY gained threshold, a 23.82% probability of being more effective and a 46.25% probability of being less costly. Sensitivity and subgroup analyses showed incremental costs and benefits to be highly sensitive to the methods used and the patient group considered, although differences between groups did not reach statistical significance in any analysis. Conclusions: Topical steroids are unlikely to be a cost-effective treatment for OME in general practice. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study is to design the optimal study comparing endovascular revascularization and supervised exercise training for patients with intermittent claudication and to demonstrate value of information (VOI) analysis of patient-level data from an economic randomized controlled trial to guide future research. Methods: We applied a net benefit framework to patient-level data on costs and quality-of-life of a previous randomized controlled trial. VOI analyses were performed using Monte Carlo simulation. We estimated the total expected value of perfect information (total EVPI), the total expected value of sample information (total EVSI), the partial expected value of perfect information (partial EVPI), and the partial expected value of sample information (partial EVSI). These VOI analyses identified the key parameters and the optimal sample size of future study designs. Sensitivity analyses were performed to explore the robustness of our assumptions about the population to benefit, the willingness-to-pay threshold, and the study costs. The VOI analyses are demonstrated in statistical software (R) and a spreadsheet (Excel) allowing other investigators to apply VOI analysis to their patient-level data. Results: The optimal study design for the treatment of intermittent claudication involves a randomized controlled trial collecting data on the quality-adjusted life expectancy and additional admission costs for 525 patients per treatment arm. The optimal sample size remained between 400 and 600 patients for a willingness-to-pay threshold between &U20AC;30,000 and &U20AC;100,000/quality-adjusted life-years, for even extreme assumptions about the study costs, and for a range of 3 to 7 years that future patients will benefit from the results of the proposed study. Conclusions: 1) The optimal study for patients with intermittent claudication collects data on two key parameters for 525 patients per trial arm; and 2) we have shown that value of information analysis provides an explicit framework to determine the optimal sample size and identify key parameters for the design of future clinical trials. [ABSTRACT FROM AUTHOR]