Trial-based economic evaluations are increasingly being conducted to support healthcare decision-making. When analysing trial-based economic evaluation data, different methodological challenges may ...be encountered, including (i) missing data, (ii) correlated costs and effects, (iii) baseline imbalances and (iv) skewness of costs and/or effects. Despite the broad range of methods available to account for these methodological challenges in effectiveness studies, they may not always be directly applicable in trial-based economic evaluations where costs and effects are analysed jointly, and more than one methodological challenge typically needs to be addressed simultaneously. The use of inappropriate methods can bias results and conclusions regarding the cost-effectiveness of healthcare interventions. Eventually, such low-quality evidence can hamper healthcare decision-making, which may in turn result in a waste of already scarce healthcare resources. Therefore, this tutorial aims to provide step-by-step guidance on how to combine appropriate statistical methods for handling the abovementioned methodological challenges using a ready-to-use R script. The theoretical background of the described methods is provided, and their application is illustrated using a simulated trial-based economic evaluation.
Neck and shoulder complaints are common in primary care physiotherapy. These patients experience pain and disability, resulting in high societal costs due to, for example, healthcare use and work ...absence. Content and intensity of physiotherapy care can be matched to a patient's risk of persistent disabling pain. Mode of care delivery can be matched to the patient's suitability for blended care (integrating eHealth with physiotherapy sessions). It is hypothesized that combining these two approaches to stratified care (referred to from this point as Stratified Blended Approach) will improve the effectiveness and cost-effectiveness of physiotherapy for patients with neck and/or shoulder complaints compared to usual physiotherapy.
This paper presents the protocol of a multicenter, pragmatic, two-arm, parallel-group, cluster randomized controlled trial. A total of 92 physiotherapists will be recruited from Dutch primary care physiotherapy practices. Physiotherapy practices will be randomized to the Stratified Blended Approach arm or usual physiotherapy arm by a computer-generated random sequence table using SPSS (1:1 allocation). Number of physiotherapists (1 or > 1) will be used as a stratification variable. A total of 238 adults consulting with neck and/or shoulder complaints will be recruited to the trial by the physiotherapy practices. In the Stratified Blended Approach arm, physiotherapists will match I) the content and intensity of physiotherapy care to the patient's risk of persistent disabling pain, categorized as low, medium or high (using the Keele STarT MSK Tool) and II) the mode of care delivery to the patient's suitability and willingness to receive blended care. The control arm will receive physiotherapy as usual. Neither physiotherapists nor patients in the control arm will be informed about the Stratified Blended Approach arm. The primary outcome is region-specific pain and disability (combined score of Shoulder Pain and Disability Index & Neck Pain and Disability Scale) over 9 months. Effectiveness will be compared using linear mixed models. An economic evaluation will be performed from the societal and healthcare perspective.
The trial will be the first to provide evidence on the effectiveness and cost-effectiveness of the Stratified Blended Approach compared with usual physiotherapy in patients with neck and/or shoulder complaints.
Netherlands Trial Register: NL8249 . Officially registered since 27 December 2019. Date of first enrollment: 30 September 2020. Study status: ongoing, data collection.
The Transmural Trauma Care Model (TTCM) is a refined post-clinical rehabilitation approach, in which a multidisciplinary hospital-based team guides a network of primary care physical therapists in ...the treatment of trauma patients. The objective of this study was to assess the effectiveness of the TTCM compared to regular care.
A controlled-before-and-after study was performed in a level 1 trauma center. The TTCM includes four elements: 1) a multidisciplinary team at the outpatient clinic, 2) coordination and individual goal setting for each patient by this team, 3) a network of primary care physical therapists, 4) E-health support for transmural communication. Intervention group patients were prospectively followed (3, 6 and 9 months). The control group consisted of 4 clusters of patients who either had their first consultation at the outpatient clinic 0, 3, 6 or 9 months ago. Outcomes included generic- and disease-specific health-related quality of life (HR-QOL), pain, functional status, patient satisfaction, and perceived recovery. Between-group comparisons were made using linear regression analyses. The recovery pattern of intervention group patients was identified using longitudinal data analysis methods.
A total of 83 participants were included in the intervention group. In the control group, 202 participants were included (68 in the baseline cluster, 26 in the 3-month cluster, 51 in the 6-month cluster, 57 in the 9-month cluster). Between-group differences were statistically significant in favor of the intervention group for disease-specific HR-QOL at 9 months, pain at 6 and 9 months, functional status at 6 and 9 months, patient satisfaction at 3, 6 and 9 months, and perceived recovery at 6 months. No significant differences were found between groups for generic HR-QOL at any time point. Generic HR-QOL, disease-specific HR-QOL, pain, and functional status significantly improved in a linear fashion among intervention group patients during the nine-month follow-up period.
This study provides preliminary evidence that the TTCM is effective in improving patient related outcome measures, such as disease-specific HR-QOL, pain and functional status. A multicenter, and ideally randomized controlled trial, is required to confirm these results.
The trial is registered at the Dutch Trial Register (NTR5474). Registered 12 October 2015. Retrospectively registered.
Mental disorders are associated with high costs for productivity loss, sickness absence and unemployment. A participatory supportive return to work (RTW) program was developed in order to improve RTW ...among workers without an employment contract, sick-listed due to a common mental disorder. The program contained a participatory approach, integrated care and direct placement in a competitive job. The aim of this study was to evaluate the cost-effectiveness and cost-utility of this new program, compared to usual care. In addition, its return on investment was evaluated.
An economic evaluation was conducted alongside a 12-month randomized controlled trial. A total of 186 participants was randomly allocated to the new program (n = 94) or to usual care (n = 92). Effect measures were the duration until sustainable RTW in competitive employment and quality-adjusted life years (QALYs) gained. Costs included intervention costs, medical costs and absenteeism costs. Registered data of the Dutch Social Security Agency were used to assess the duration until sustainable RTW, intervention costs and absenteeism costs. QALYs and medical costs were assessed using three- or six-monthly questionnaires. Missing data were imputed using multiple imputations. Cost-effectiveness analysis and cost-utility analysis were conducted from the societal perspective. A return on investment analysis was conducted from the social insurer's perspective. Various sensitivity analyses were performed to assess the robustness of the results.
The new program had no significant effect on the duration until sustainable RTW and QALYs gained. Intervention costs and medical costs were significantly higher in the intervention group. From the societal perspective, the maximum probability of cost-effectiveness for duration until sustainable RTW was 0.64 at a willingness to pay of about €10 000/day, and 0.27 for QALYs gained, regardless of the willingness to pay. From the social insurer's perspective, the probability of financial return was 0.18.
From the societal perspective, the new program was neither cost-effective in improving sustainable RTW nor in gaining QALYs. From the social insurer's perspective, the program did not result in a positive financial return. Therefore, the present study provided no evidence to support its implementation.
The trial was listed at the Dutch Trial Register (NTR) under NTR3563 on August 7, 2012.
Pressure ulcers (PUs) on the buttocks are among the most common secondary complications in individuals with chronic spinal cord injury (SCI). PUs can result from sitting for extended periods, disuse ...atrophy, increased sitting pressure and reduced circulation. Compared with usual care, activation of paralysed muscles using electrical stimulation (ES) has been shown to markedly increase paralysed muscle mass, improve circulation of skin and muscle and improve sitting pressure distribution. ES might therefore be a useful method to reduce PU incidence.
A multicentre randomized controlled trial (SCI PREVOLT) will be conducted with an economic and process evaluation alongside. One hundred participants with a SCI in the chronic phase and a minimal incidence of 1 PU in the last 5 years will be recruited from rehabilitation centres across the Netherlands. Participants will be stratified by centre and age and randomized to the intervention or control group. The intervention group will use ES at least 1 h/day during at least 4 times a week for 1 year next to usual care. The control group will only receive usual care. The primary outcome is the incidence of PUs, measured by a blinded person assessing the presence or absence of a PU on the buttocks on a photo made by the participant or his/her caregiver. The incidence of a PU will be evaluated every 2 weeks. Secondary outcomes include interface pressure distribution, blood flow in the profunda femoris artery, muscle thickness of the hamstrings and gluteal muscles and questionnaires about different dimensions of life, e.g. participation and quality of life. Secondary outcomes will be measured at baseline and 3, 6, 9 and 12 months after randomization.
This study will assess if electrical stimulation is a (cost-)effective method to prevent PUs and reduce the risk factors of getting PUs. If ES is effective and cost-effective compared with usual care, ES could be implemented in daily treatment of individuals with a SCI.
Netherlands Trials Register NTR NL9469 . Registered on 26 May 2021.
To examine whether physical therapy (PT) is cost-effective compared with arthroscopic partial meniscectomy (APM) in patients with a non-obstructive meniscal tear, we performed a full trial-based ...economic evaluation from a societal perspective. In a secondary analysis-this paper-we examined whether PT is non-inferior to APM.
We recruited patients aged 45-70 years with a non-obstructive meniscal tear in nine Dutch hospitals. Resource use was measured using web-based questionnaires. Measures of effectiveness included knee function using the International Knee Documentation Committee (IKDC) and quality-adjusted life-years (QALYs). Follow-up was 24 months. Uncertainty was assessed using bootstrapping techniques. The non-inferiority margins for societal costs, the IKDC and QALYs, were €670, 8 points and 0.057 points, respectively.
We randomly assigned 321 patients to PT (n=162) or APM (n=159). PT was associated with significantly lower costs after 24 months compared with APM (-€1803; 95% CI -€3008 to -€838). The probability of PT being cost-effective compared with APM was 1.00 at a willingness to pay of €0/unit of effect for the IKDC (knee function) and QALYs (quality of life) and decreased with increasing values of willingness to pay. The probability that PT is non-inferior to APM was 0.97 for all non-inferiority margins for the IKDC and 0.89 for QALYs.
The probability of PT being cost-effective compared with APM was relatively high at reasonable values of willingness to pay for the IKDC and QALYs. Also, PT had a relatively high probability of being non-inferior to APM for both outcomes. This warrants further deimplementation of APM in patients with non-obstructive meniscal tears.
NCT01850719 and NTR3908.
Objectives
The aim of this study was to assess the performance and impact of multilevel modelling (MLM) compared with ordinary least squares (OLS) regression in trial-based economic evaluations with ...clustered data.
Methods
Three thousand datasets with balanced and unbalanced clusters were simulated with correlation coefficients between costs and effects of − 0.5, 0, and 0.5, and intraclass correlation coefficients (ICCs) varying between 0.05 and 0.30. Each scenario was analyzed using both MLM and OLS. Statistical uncertainty around MLM and OLS estimates was estimated using bootstrapping. Performance measures were estimated and compared between approaches, including bias, root mean squared error (RMSE) and coverage probability. Cost and effect differences, and their corresponding confidence intervals and standard errors, incremental cost-effectiveness ratios, incremental net-monetary benefits and cost-effectiveness acceptability curves were compared.
Results
Cost-effectiveness outcomes were similar between OLS and MLM. MLM produced larger statistical uncertainty and coverage probabilities closer to nominal levels than OLS. The higher the ICC, the larger the effect on statistical uncertainty between MLM and OLS. Significant cost-effectiveness outcomes as estimated by OLS became non-significant when estimated by MLM. At all ICCs, MLM resulted in lower probabilities of cost effectiveness than OLS, and this difference became larger with increasing ICCs. Performance measures and cost-effectiveness outcomes were similar across scenarios with varying correlation coefficients between costs and effects.
Conclusions
Although OLS produced similar cost-effectiveness outcomes, it substantially underestimated the amount of variation in the data compared with MLM. To prevent suboptimal conclusions and a possible waste of scarce resources, it is important to use MLM in trial-based economic evaluations when data are clustered.
The prevalence of knee osteoarthritis is increasing worldwide. Obesity is an important modifiable risk factor for both the incidence and progression of knee osteoarthritis. Consequently, ...international guidelines recommend all patients with knee osteoarthritis who are overweight receive support to lose weight. However, few overweight patients with this condition receive care to support weight loss. Telephone-based interventions are one potential solution to provide scalable care to the many patients with knee osteoarthritis. The objective of this study is to evaluate, from a societal perspective, the cost-utility and cost-effectiveness of a telephone-based weight management and healthy lifestyle service for patients with knee osteoarthritis, who are overweight or obese.
An economic evaluation was undertaken alongside a pragmatic randomised controlled trial. Between May 19 and June 30, 2015, 120 patients with knee osteoarthritis were randomly assigned to an intervention or usual care control group in a 1:1 ratio. Participants in the intervention group received a referral to an existing non-disease specific 6-month telephone-based weight management and healthy lifestyle service. Quality-adjusted life years (QALYs) was the utility measure and knee pain intensity, disability, weight, and body mass index (BMI) were the clinical measures of effect. Costs included intervention costs, healthcare utilisation costs (healthcare services and medication use) and absenteeism costs due to knee pain. Data was collected at baseline, 6 weeks and 26 weeks. The primary cost-effectiveness analysis was performed from the societal perspective.
Mean cost differences between groups (intervention minus control) were $493 (95%CI: -3513 to 5363) for healthcare costs, $-32 (95%CI: -73 to 13) for medication costs, and $125 (95%CI: -151 to 486) for absenteeism costs. The total mean difference in societal costs was $1197 (95%CI: -2887 to 6106). For QALYs and all clinical measures of effect, the probability of the intervention being cost-effective compared with usual care was less than 0.36 at all willingness-to-pay values.
From a societal perspective, telephone-based weight loss support, provided using an existing non-disease specific 6-month weight management and healthy lifestyle service was not cost-effective in comparison with usual care for overweight and obese patients with knee osteoarthritis.
ACTRN12615000490572 , registered 18th May 2015.
Transforaminal epidural injections with steroids (TESI) are used increasingly for patients with sciatica. However, their safety, effectiveness, and cost-effectiveness are still a matter of debate. ...This a priori statistical analysis plan describes the methodology of the analysis for the STAR trial that assesses the (cost-)effectiveness of TESI during the acute stage of sciatica (< 8 weeks).
The STAR trial is a multicentre, randomized controlled, prospective trial (RCT) investigating the (cost-)effectiveness of TESI by making a three-group comparison among patients with acute sciatica due to a herniated lumbar disc (< 8 weeks): (1) TESI combined with levobupivacaine added to oral pain medication (intervention group 1) versus oral pain medication alone (control group), (2) intervention group 1 versus transforaminal epidural injection with levobupivacaine and saline solution added to oral pain medication (intervention group 2), and (3) intervention group 2 versus control group. Co-primary outcomes were physical functioning (Roland Morris Disability Questionnaire), pain intensity (10-point numerical rating scale), and global perceived recovery (7-point Likert scale, dichotomized into 'recovered' and 'not recovered'). For all three comparisons, we defined the following minimal clinically relevant between-group differences: two points for pain intensity (range 0-10), four points for physical functioning (range 0-24) and a 20% difference in recovery rate. Secondary outcomes are health-related quality of life (EQ-5D-5L) and patient satisfaction (7-point Likert scale) and surgery rate. We also collected resource use data to perform an economic evaluation. Analyses will be conducted by intention-to-treat with p < 0.05 (two-tailed) for all three comparisons. Effects will be estimated using mixed models by maximum likelihood. For each comparison, mean differences, or difference in proportions, between groups will be tested per time point and an overall mean difference, or difference in proportions, between groups during the complete duration of follow-up (6 months) will be estimated. In the economic evaluation, Multivariate Imputation by Chained Equations will be used to handle missing data. Cost and effect differences will be estimated using seemingly unrelated regression, and uncertainty will be estimated using bootstrapping techniques.
This statistical analysis plan provides detailed information on the intended analysis of the STAR trial, which aims to deliver evidence about the (cost-)effectiveness of TESI during the acute phase of sciatica (< 8 weeks).
Dutch National trial register NTR4457 (6 March 2014).
Abstract Question Is referral for early rehabilitation after lumbar disc surgery effective and cost-effective compared to no referral? Design Multicentre, randomised, controlled trial, and economic ...evaluation with concealed allocation and intention-to-treat-analysis. Participants Adults who underwent discectomy for a herniated lumbar disc, confirmed by magnetic resonance imaging, and signs of nerve root compression corresponding to the herniation level. Intervention Early rehabilitation (exercise therapy) for 6 to 8 weeks, versus no referral, immediately after discharge. Outcome measures In line with the recommended core outcome set, the co-primary outcomes were: functional status (Oswestry Disability Index); leg and back pain (numerical rating scale 0 to 10); global perceived recovery (7-point Likert scale); and general physical and mental health (SF12), assessed 3, 6, 9, 12 and 26 weeks after surgery. The outcomes for the economic evaluation were quality of life and costs, measured at 6, 12 and 26 weeks after surgery. Results There were no clinically relevant or statistically significant overall mean differences between rehabilitation and control for any outcome adjusted for baseline characteristics: global perceived recovery (OR 1.0, 95% CI 0.6 to 1.7), functional status (MD 1.5, 95% CI –3.6 to 6.7), leg pain (MD 0.1, 95% CI –0.7 to 0.8), back pain (MD 0.3, 95% CI –0.3 to 0.9), physical health (MD –3.5, 95% CI –11.3 to 4.3), and mental health (MD –4.1, 95% CI –9.4 to 1.3). After 26 weeks, there were no significant differences in quality-adjusted life years (MD 0.01, 95% CI –0.02 to 0.04 points) and societal costs (MD –€527, 95% CI –2846 to 1506). The maximum probability for the intervention to be cost-effective was 0.75 at a willingness-to-pay of €32 000/quality-adjusted life year. Conclusion Early rehabilitation after lumbar disc surgery was neither more effective nor more cost-effective than no referral. Trial registration Netherlands Trial Register NTR3156. Oosterhuis T, Ostelo RW, van Dongen JM, Peul WC, de Boer MR, Bosmans JE, Vleggeert-Lankamp CL, Arts MP, van Tulder MW (2017) Early rehabilitation after lumbar disc surgery is not effective or cost-effective compared to no referral: a randomised trial and economic evaluation. Journal of Physiotherapy XX: XX–XX
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