Antenatal cardiotocography in primary midwife-led care: a budget impact analysis.

OBJECTIVES: In many countries, the healthcare sector is dealing with important challenges such as increased demand for healthcare services, capacity problems in hospitals and rising healthcare costs. Therefore, one of the aims of the Dutch government is to move care from in-hospital to out-of-hospital care settings. An example of an innovation where care is moved from a more specialised setting to a less specialised setting is the performance of an antenatal cardiotocography (aCTG) in primary midwife-led care. The aim of this study was to assess the budget impact of implementing aCTG for healthy pregnant women in midwife-led care compared with usual obstetrician-led care in the Netherlands. METHODS: A budget impact analysis was conducted to estimate the actual costs and reimbursement of aCTG performed in midwife-led care and obstetrician-led care (ie, base-case analysis) from the Dutch healthcare perspective. Epidemiological and healthcare utilisation data describing both care pathways were obtained from a prospective cohort, survey and national databases. Different implementation rates of aCTG in midwife-led care were explored. A probabilistic sensitivity analysis was conducted to estimate the uncertainty surrounding the budget impact estimates. RESULTS: Shifting aCTG from obstetrician-led care to midwife-led-care would increase actual costs with €311 763 (97.5% CI €188 574 to €426 072) and €1 247 052 (97.5% CI €754 296 to €1 704 290) for implementation rates of 25% and 100%, respectively, while it would decrease reimbursement with -€7 538 335 (97.5% CI -€10 302 306 to -€4 559 661) and -€30 153 342 (97.5% CI -€41 209 225 to -€18 238 645) for implementation rates of 25% and 100%, respectively. The sensitivity analysis results were consistent with those of the main analysis. CONCLUSIONS: From the Dutch healthcare perspective, we estimated that implementing aCTG in midwife-led care may increase the associated actual costs. At the same time, it might lower the healthcare reimbursement.

Cost-effectiveness of the FindMyApps eHealth intervention vs. digital care as usual: results from a randomised controlled trial.

OBJECTIVES: Despite growing interest, the cost-effectiveness of eHealth interventions for supporting quality of life of people with dementia and their caregivers remains unclear. This study evaluated the cost-effectiveness of the FindMyApps intervention, compared to digital care-as-usual. FindMyApps aims to help people with dementia and their caregivers find and learn to use tablet apps that may support social participation and self-management of people with dementia and sense of competence of caregivers. METHOD: A randomised controlled trial (Netherlands Trial Register NL8157) was conducted, including people with mild cognitive impairment (MCI) or mild dementia and their informal caregivers (FindMyApps n = 76, digital care-as-usual n = 74). Outcomes for people with MCI/dementia were Quality-Adjusted Life-Years (QALYs), calculated from EQ-5D-5L data and the Dutch tariff for utility scores, social participation (Maastricht Social Participation Profile) and quality of life (Adult Social Care Outcomes Toolkit), and for caregivers, QALYs and sense of competence (Short Sense of Competence Questionnaire). Societal costs were calculated using data collected with the RUD-lite instrument and the Dutch costing guideline. Multiple imputation was employed to fill in missing cost and effect data. Bootstrapped multilevel models were used to estimate incremental total societal costs and incremental effects between groups which were then used to calculate Incremental Cost-Effectiveness Ratios (ICERs). Cost-effectiveness acceptability curves were estimated. RESULTS: In the FindMyApps group, caregiver SSCQ scores were significantly higher compared to care-as-usual, n = 150, mean difference = 0.75, 95% CI [0.14, 1.38]. Other outcomes did not significantly differ between groups. Total societal costs for people with dementia were not significantly different, n = 150, mean difference = €-774, 95%CI [-2.643, .,079]. Total societal costs for caregivers were significantly lower in the FindMyApps group compared to care-as-usual, n = 150, mean difference = € -392, 95% CI [-1.254, -26], largely due to lower supportive care costs, mean difference = €-252, 95% CI [-1.009, 42]. For all outcomes, the probability that FindMyApps was cost-effective at a willingness-to-pay threshold of €0 per point of improvement was 0.72 for people with dementia and 0.93 for caregivers. CONCLUSION: FindMyApps is a cost-effective intervention for supporting caregivers' sense of competence. Further implementation of FindMyApps is warranted.

Costs of care trajectories of people with dementia compared with matched controls. Longitudinal analysis of linked health and administrative data.

OBJECTIVES: To provide insight into the health and social care costs during the disease trajectory in persons with dementia and the impact of institutionalization and death on healthcare costs compared with matched persons without dementia. METHODS: Electronic health record data from family physicians were linked with national administrative databases to estimate costs of primary care, medication, secondary care, mental care, home care and institutional care for people with dementia and matched persons from the year before the recorded dementia diagnosis until death or a maximum of 4 years after the diagnosis. RESULTS: Total mean health and social care costs among persons with dementia increased substantially during the disease trajectory, mainly due to institutional care costs. For people who remained living in the community, mean health and social care costs are higher for people with dementia than for those without dementia, while for those who are admitted to a long-term care facility, mean health and social care costs are higher for people without dementia than for those with dementia. CONCLUSIONS: The steep rise in health and social care costs across the dementia care trajectory is mainly due to increasing costs for institutional care. For those remaining in the community, home care costs and hospital care costs were the main cost drivers. Future research should adopt a societal perspective to investigate the influence of including social costs.

Optimizing and Implementing a Community-Based Group Fall Prevention Program: A Mixed Methods Study.

Falls and fall-related injuries among older adults are associated with decreased health. Therefore, fall prevention programs (FPPs) are increasingly important. However, the translation of such complex programs into clinical practice lacks insight into factors that influence implementation. Therefore, the aim of this study was to identify how to optimize and further implement a widely used group-based FPP in the Netherlands among participants, therapists and stakeholders using a mixed methods study. FPP participants and therapists filled out a questionnaire about their experiences with the FPP. Moreover, three focus groups were conducted with FPP participants, one with therapists and one with other stakeholders. Data were analysed according to the thematic analysis approach of Braun and Clarke. Overall, 93% of the 104 FPP participants were satisfied with the FPP and 86% (n = 12) of the therapists would recommend the FPP to older adults with balance or mobility difficulties. Moreover, six themes were identified regarding further implementation: (1) recruiting and motivating older adults to participate; (2) structure and content of the program; (3) awareness, confidence and physical effects; (4) training with peers; (5) funding and costs; and (6) long-term continuation. This study resulted in practical recommendations for optimizing and further implementing FPPs in practice.

Don't be late! Postponing cognitive decline and preventing early unemployment in people with multiple sclerosis: a study protocol.

BACKGROUND: Up to 65% of people with multiple sclerosis (PwMS) develop cognitive deficits, which hampers their ability to work, participating in day-to-day life and ultimately reducing quality of life (QoL). Early cognitive symptoms are often less tangible to PwMS and their direct environment and are noticed only when symptoms and work functioning problems become more advanced, i.e., when (brain) damage is already advanced. Treatment of symptoms at a late stage can lead to cognitive impairment and unemployment, highlighting the need for preventative interventions in PwMS. AIMS: This study aims to evaluate the (cost-) effectiveness of two innovative preventative interventions, aimed at postponing cognitive decline and work functioning problems, compared to enhanced usual care in improving health-related QoL (HRQoL). METHODS: Randomised controlled trial including 270 PwMS with mild cognitive impairment, who have paid employment ≥ 12 h per week and are able to participate in physical exercise (Expanded Disability Status Scale < 6.0). Participants are randomised across three study arms: 1) 'strengthening the brain' - a lifestyle intervention combining personal fitness, mental coaching, dietary advice, and cognitive training; 2) 'strengthening the mind' - a work-focused intervention combining the capability approach and the participatory approach in one-on-one coaching by trained work coaches who have MS themselves; 3) Control group-receiving general information about cognitive impairment in MS and receiving care as usual. Intervention duration is four months, with short-term and long-term follow-up measurements at 10 and 16 months, respectively. The primary outcome measure of the Don't be late! intervention study will be HRQoL as measured with the 36-item Short Form. Secondary outcomes include cognition, work related outcomes, physical functioning, structural and functional brain changes, psychological functioning, and societal costs. Semi-structured interviews and focus groups with stakeholders will be organised to qualitatively reflect on the process and outcome of the interventions. DISCUSSION: This study seeks to prevent (further) cognitive decline and job loss due to MS by introducing tailor-made interventions at an early stage of cognitive symptoms, thereby maintaining or improving HRQoL. Qualitative analyses will be performed to allow successful implementation into clinical practice. TRIAL REGISTRATION: Retrospectively registered at ClinicalTrials.gov with reference number NCT06068582 on 10 October 2023.

Cost-effectiveness of behavioral activation compared to treatment as usual for depressed older adults in primary care: A cluster randomized controlled trial.

INTRODUCTION: Depression in older adults is associated with decreased quality of life and increased utilization of healthcare services. Behavioral activation (BA) is an effective treatment for late-life depression, but the cost-effectiveness compared to treatment as usual (TAU) is unknown. METHODS: An economic evaluation was performed alongside a cluster randomized controlled multicenter trial including 161 older adults (≥65 years) with moderate to severe depressive symptoms (PHQ-9 ≥ 10). Outcome measures were depression (response on the QIDS-SR), quality-adjusted life-years (QALYs) and societal costs. Missing data were imputed using multiple imputation. Cost and effect differences were estimated using bivariate linear regression models, and statistical uncertainty was estimated with bootstrapping. Cost-effectiveness acceptability curves showed the probability of cost-effectiveness at different ceiling ratios. RESULTS: Societal costs were statistically non-significantly lower in BA compared to TAU (mean difference (MD) -€485, 95 % CI -3861 to 2792). There were no significant differences in response on the QIDS-SR (MD 0.085, 95 % CI -0.015 to 0.19), and QALYs (MD 0.026, 95 % CI -0.0037 to 0.055). On average, BA was dominant over TAU (i.e., more effective and less expensive), although the probability of dominance was only 0.60 from the societal perspective and 0.85 from the health care perspective for both QIDS-SR response and QALYs. DISCUSSION: Although the results suggest that BA is dominant over TAU, there was considerable uncertainty surrounding the cost-effectiveness estimates which precludes firm conclusions.

Cost-effectiveness of twice-weekly versus once-weekly sessions of cognitive-behavioural therapy and interpersonal psychotherapy for depression at 12 months after start of treatment: randomised controlled trial.

BACKGROUND: Cost-effective treatments are needed to reduce the burden of depression. One way to improve the cost-effectiveness of psychotherapy might be to increase session frequency, but keep the total number of sessions constant. AIM: To evaluate the cost-effectiveness of twice-weekly compared with once-weekly psychotherapy sessions after 12 months, from a societal perspective. METHOD: An economic evaluation was conducted alongside a randomised controlled trial comparing twice-weekly versus once-weekly sessions of psychotherapy (cognitive-behavioural therapy or interpersonal psychotherapy) for depression. Missing data were handled by multiple imputation. Statistical uncertainty was estimated with bootstrapping and presented with cost-effectiveness acceptability curves. RESULTS: Differences between the two groups in depressive symptoms, physical and social functioning, and quality-adjusted life-years (QALY) at 12-month follow-up were small and not statistically significant. Total societal costs in the twice-weekly session group were higher, albeit not statistically significantly so, than in the once-weekly session group (mean difference €2065, 95% CI -686 to 5146). The probability that twice-weekly sessions are cost-effective compared with once-weekly sessions was 0.40 at a ceiling ratio of €1000 per point improvement in Beck Depression Inventory-II score, 0.32 at a ceiling ratio of €50 000 per QALY gained, 0.23 at a ceiling ratio of €1000 per point improvement in physical functioning score and 0.62 at a ceiling ratio of €1000 per point improvement in social functioning score. CONCLUSIONS: Based on the current results, twice-weekly sessions of psychotherapy for depression are not cost-effective over the long term compared with once-weekly sessions.

Healthcare costs of different treatment options for condylar fractures.

Objective: As treatment options for condylar fractures have comparable outcomes, getting insight into associated costs is a first step towards implementing value-based healthcare (VBH). Therefore, we described the actual costs of the different treatment options (surgical, conservative, and expectative treatment) for condylar fractures. We expected surgical treatment to be the most expensive treatment. Study design: This is a cost-of-illness study, based on estimates from the literature. Firstly, care pathways of all treatment options were described. Secondly, the costs per step were calculated based on the literature and Dutch guidelines for economic evaluations in health care. Results: The direct treatment costs of surgical treatment (€3721 to €4040) are three to five times higher than conservative treatment (€730 to €1332). When lost productivity costs during the recovery period are included, costs of surgical treatment remain 1.5 times higher (€9511 to €9830 for surgical treatment and €6224 to €6826 for conservative treatment). The costs of expectative treatment (€5436) are lower than both other treatments. Conclusion: The costs for surgical treatment are considerably higher than those for conservative or expectative treatment, mainly related to direct treatment cost. Future research should focus on the patients' perspective, to support implementation of VBH in treating condylar fractures.

Effects of a clinical decision support system and patient portal for preventing medication-related falls in older fallers: Protocol of a cluster randomized controlled trial with embedded process and economic evaluations (ADFICE_IT).

BACKGROUND: Falls are the leading cause of injury-related mortality and hospitalization among adults aged ≥ 65 years. An important modifiable fall-risk factor is use of fall-risk increasing drugs (FRIDs). However, deprescribing is not always attempted or performed successfully. The ADFICE_IT trial evaluates the combined use of a clinical decision support system (CDSS) and a patient portal for optimizing the deprescribing of FRIDs in older fallers. The intervention aims to optimize and enhance shared decision making (SDM) and consequently prevent injurious falls and reduce healthcare-related costs. METHODS: A multicenter, cluster-randomized controlled trial with process evaluation will be conducted among hospitals in the Netherlands. We aim to include 856 individuals aged ≥ 65 years that visit the falls clinic due to a fall. The intervention comprises the combined use of a CDSS and a patient portal. The CDSS provides guideline-based advice with regard to deprescribing and an individual fall-risk estimation, as calculated by an embedded prediction model. The patient portal provides educational information and a summary of the patient's consultation. Hospitals in the control arm will provide care-as-usual. Fall-calendars will be used for measuring the time to first injurious fall (primary outcome) and secondary fall outcomes during one year. Other measurements will be conducted at baseline, 3, 6, and 12 months and include quality of life, cost-effectiveness, feasibility, and shared decision-making measures. Data will be analyzed according to the intention-to-treat principle. Difference in time to injurious fall between the intervention and control group will be analyzed using multilevel Cox regression. DISCUSSION: The findings of this study will add valuable insights about how digital health informatics tools that target physicians and older adults can optimize deprescribing and support SDM. We expect the CDSS and patient portal to aid in deprescribing of FRIDs, resulting in a reduction in falls and related injuries. TRIAL REGISTRATION: ClinicalTrials.gov NCT05449470 (7-7-2022).

Conducting Trial-Based Economic Evaluations Using R: A Tutorial.

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.

Behavioural Activation versus Treatment as Usual for Depressed Older Adults in Primary Care: A Pragmatic Cluster-Randomised Controlled Trial.

INTRODUCTION: Effective non-pharmacological treatment options for depression in older adults are lacking. OBJECTIVE: The effectiveness of behavioural activation (BA) by mental health nurses (MHNs) for depressed older adults in primary care compared with treatment as usual (TAU) was evaluated. METHODS: In this multicentre cluster-randomised controlled trial, 59 primary care centres (PCCs) were randomised to BA and TAU. Consenting older (≥65 years) adults (n = 161) with clinically relevant symptoms of depression (PHQ-9 ≥ 10) participated. Interventions were an 8-week individual MHN-led BA programme and unrestricted TAU in which general practitioners followed national guidelines. The primary outcome was self-reported depression (QIDS-SR16) at 9 weeks and 3, 6, 9, and 12-month follow-up. RESULTS: Data of 96 participants from 21 PCCs in BA and 65 participants from 16 PCCs in TAU, recruited between July 4, 2016, and September 21, 2020, were included in the intention-to-treat analyses. At post-treatment, BA participants reported significantly lower severity of depressive symptoms than TAU participants (QIDS-SR16 difference = -2.77, 95% CI = -4.19 to -1.35), p < 0.001; between-group effect size = 0.90; 95% CI = 0.42-1.38). This difference persisted up to the 3-month follow-up (QIDS-SR16 difference = -1.53, 95% CI = -2.81 to -0.26, p = 0.02; between-group effect size = 0.50; 95% CI = 0.07-0.92) but not up to the 12-month follow-up [QIDS-SR16 difference = -0.89 (-2.49 to 0.71)], p = 0.28; between-group effect size = 0.29 (95% CI = -0.82 to 0.24). CONCLUSIONS: BA led to a greater symptom reduction of depressive symptoms in older adults, compared to TAU in primary care, at post-treatment and 3-month follow-up, but not at 6- to 12-month follow-up.

Cost-effectiveness of general practitioner- versus surgeon-led colon cancer survivorship care: an economic evaluation alongside a randomised controlled trial.

PURPOSE: The aim of this study is to assess cost-effectiveness of general practitioner (GP) versus surgeon-led colon cancer survivorship care from a societal perspective. METHODS: We performed an economic evaluation alongside the I CARE study, which included 303 cancer patients (stages I-III) who were randomised to survivorship care by a GP or surgeon. Questionnaires were administered at baseline, 3-, 6-, 12-, 24- and 36-months. Costs included healthcare costs (measured by iMTA MCQ) and lost productivity costs (SF-HLQ). Disease-specific quality of life (QoL) was measured using EORTC QLQ-C30 summary score and general QoL using EQ-5D-3L quality-adjusted life years (QALYs). Missing data were imputed. Incremental cost-effectiveness ratios (ICERs) were calculated to relate costs to effects on QoL. Statistical uncertainty was estimated using bootstrapping. RESULTS: Total societal costs of GP-led care were significantly lower compared to surgeon-led care (mean difference of - €3895; 95% CI - €6113; - €1712). Lost productivity was the main contributor to the difference in societal costs (- €3305; 95% CI - €5028; - €1739). The difference in QLQ-C30 summary score over time between groups was 1.33 (95% CI - 0.049; 3.15). The ICER for QLQ-C30 was - 2073, indicating that GP-led care is dominant over surgeon-led care. The difference in QALYs was - 0.021 (95% CI - 0.083; 0.040) resulting in an ICER of 129,164. CONCLUSIONS: GP-led care is likely to be cost-effective for disease-specific QoL, but not for general QoL. IMPLICATIONS FOR CANCER SURVIVORS: With a growing number of cancer survivors, GP-led survivorship care could help to alleviate some of the burden on more expensive secondary healthcare services.

Mapping Oswestry Disability Index Responses to EQ-5D-3L Utility Values: Are Cost-Utility Results Valid?

OBJECTIVES: To develop and validate approaches for mapping Oswestry Disability Index responses to 3-level version of EQ-5D utility values and to evaluate the impact of using mapped utility values on cost-utility results compared with published regression models. METHODS: Three response mapping approaches were developed in a random sample of 70% of 18 692 patients with low back pain: nonparametric approach (Non-p), nonparametric approach excluding logical inconsistencies (Non-peLI), and ordinal logistic regression (OLR). Performance was assessed in the remaining 30% using R-square (R2), root mean square error (RMSE), and mean absolute error (MAE). To evaluate whether MAEs and their 95% limits of agreement (LA) were clinically relevant, a minimally clinically important difference of 0.074 was used. Probabilities of cost-effectiveness estimated using observed and mapped utility values were compared in 2 economic evaluations. RESULTS: The Non-p performed the best (R2 = 0.43; RMSE = 0.22; MAE = 0.03; 95% LA = -0.40 to 0.47) compared with the Non-peLI (R2 = 0.07; RMSE = 0.29; MAE = -0.15; 95% LA = -0.63 to 0.34) and OLR (R2 = 0.22; RMSE = 0.26; MAE = 0.02; 95% LA = -0.49 to 0.53). MAEs were lower than the minimally clinically important difference for the Non-p and OLR but not for the Non-peLI. Differences in probabilities of cost-effectiveness ranged from 1% to 4% (Non-p), 0.1% to 9% (Non-peLI), and 0.1% to 20% (OLR). CONCLUSIONS: Results suggest that the developed response mapping approaches are not valid for estimating individual patients' 3-level version of EQ-5D utility values, and-depending on the approach-may considerably affect cost-utility results. The developed approaches did not perform better than previously published regression-based models and are therefore not recommended for use in economic evaluations.

The handling of missing data in trial-based economic evaluations: should data be multiply imputed prior to longitudinal linear mixed-model analyses?

INTRODUCTION: For the analysis of clinical effects, multiple imputation (MI) of missing data were shown to be unnecessary when using longitudinal linear mixed-models (LLM). It remains unclear whether this also applies to trial-based economic evaluations. Therefore, this study aimed to assess whether MI is required prior to LLM when analyzing longitudinal cost and effect data. METHODS: Two-thousand complete datasets were simulated containing five time points. Incomplete datasets were generated with 10, 25, and 50% missing data in follow-up costs and effects, assuming a Missing At Random (MAR) mechanism. Six different strategies were compared using empirical bias (EB), root-mean-squared error (RMSE), and coverage rate (CR). These strategies were: LLM alone (LLM) and MI with LLM (MI-LLM), and, as reference strategies, mean imputation with LLM (M-LLM), seemingly unrelated regression alone (SUR-CCA), MI with SUR (MI-SUR), and mean imputation with SUR (M-SUR). RESULTS: For costs and effects, LLM, MI-LLM, and MI-SUR performed better than M-LLM, SUR-CCA, and M-SUR, with smaller EBs and RMSEs as well as CRs closers to nominal levels. However, even though LLM, MI-LLM and MI-SUR performed equally well for effects, MI-LLM and MI-SUR were found to perform better than LLM for costs at 10 and 25% missing data. At 50% missing data, all strategies resulted in relatively high EBs and RMSEs for costs. CONCLUSION: LLM should be combined with MI when analyzing trial-based economic evaluation data. MI-SUR is more efficient and can also be used, but then an average intervention effect over time cannot be estimated.

Effectiveness and Cost-effectiveness of Minimal Ovarian Stimulation in-vitro Fertilization versus Conventional Ovarian Stimulation in Poor Responders: Economic Evaluation Alongside a Propensity Score Adjusted Prospective Observational Study.

OBJECTIVE: Information on the pregnancy rate after successive in-vitro fertilization (IVF) cycles and their associated costs is relevant for couples undergoing assisted reproduction treatments (ARTs). This study, therefore, sought to investigate the effectiveness and the cost-effectiveness of two ARTs, the minimal ovarian stimulation IVF (MS-IVF) compared to the conventional ovarian stimulation IVF (C-IVF) from the payer's perspective. METHODS: A 10-months follow-up prospective observational study was conducted in a sample of couples who sought ARTs in a private clinic in Southern Brazil. Women had to satisfy the Bologna Criteria and be older than 35 years. The effect outcome was pregnancy rate per initiated cycle. Medication costs were based on medical records. Costs and effect differences were estimated using seemingly unrelated regressions adjusted for the propensity score estimated based on women's characteristics. RESULTS: All 84 eligible women who agreed to participate received a total of 92 IVF cycles (MS-IVF, n=27[35 cycles]; C-IVF n=57[57 cycles]. The effect difference between MS-IVF and C-IVF was -5.1% (95%CI, -13.2 to 5.2). Medication costs of MS-IVF were significantly lower than C-IVF by €-1260 (95%CI, -1401 to -1118). The probabilities of MS-IVF being cost-effective compared to C-IVF ranged from 1 to 0.76 for willingness-to-pay of €0 to €15,000 per established pregnancy, respectively. CONCLUSIONS: Even though there were no positive effect differences between groups, MS-IVF might be cost-effective compared to C-IVF from the payer's perspective due to its relatively large cost savings compared to C-IVF. However, further investigation is needed to confirm these findings in a larger sample.

To what extent does the use of crosswalks instead of EQ-5D value sets impact reimbursement decisions?: a simulation study.

PURPOSE: Inconsistent results have been found on the impact of using crosswalks versus EQ-5D value sets on reimbursement decisions. We sought to further investigate this issue in a simulation study. METHODS: Trial-based economic evaluation data were simulated for different conditions (depression, low back pain, osteoarthritis, cancer), severity levels (mild, moderate, severe), and effect sizes (small, medium, large). For all 36 scenarios, utilities were calculated using 3L and 5L value sets and crosswalks (3L to 5L and 5L to 3L crosswalks) for the Netherlands, the United States, and Japan. Utilities, quality-adjusted life years (QALYs), incremental QALYs, incremental cost-effectiveness ratios (ICERs), and probabilities of cost-effectiveness (pCE) obtained from values sets and crosswalks were compared. RESULTS: Differences between value sets and crosswalks ranged from -0.33 to 0.13 for utilities, from -0.18 to 0.13 for QALYs, and from -0.01 to 0.08 for incremental QALYs, resulting in different ICERs. For small effect sizes, at a willingness-to-pay of €20,000/QALY, the largest pCE difference was found for moderate cancer between the Japanese 5L value set and 5L to 3L crosswalk (difference = 0.63). For medium effect sizes, the largest difference was found for mild cancer between the Japanese 3L value set and 3L to 5L crosswalk (difference = 0.06). For large effect sizes, the largest difference was found for mild osteoarthritis between the Japanese 3L value set and 3L to 5L crosswalk (difference = 0.08). CONCLUSION: The use of crosswalks instead of EQ-5D value sets can impact cost-utility outcomes to such an extent that this may influence reimbursement decisions.

Cost-effectiveness and return-on-investment of C-reactive protein point-of-care testing in comparison with usual care to reduce antibiotic prescribing for lower respiratory tract infections in nursing homes: a cluster randomised trial.

OBJECTIVES: C-reactive protein point-of-care testing (CRP POCT) is a promising diagnostic tool to guide antibiotic prescribing for lower respiratory tract infections (LRTI) in nursing home residents. This study aimed to evaluate cost-effectiveness and return-on-investment (ROI) of CRP POCT compared with usual care for nursing home residents with suspected LRTI from a healthcare perspective. DESIGN: Economic evaluation alongside a cluster randomised, controlled trial. SETTING: 11 Dutch nursing homes. PARTICIPANTS: 241 nursing home residents with a newly suspected LRTI. INTERVENTION: Nursing home access to CRP POCT (POCT-guided care) was compared with usual care without CRP POCT (usual care). MAIN OUTCOME MEASURES: The primary outcome measure for the cost-effectiveness analysis was antibiotic prescribing at initial consultation, and the secondary outcome was full recovery at 3 weeks. ROI analyses included intervention costs, and benefits related to antibiotic prescribing. Three ROI metrics were calculated: Net Benefits, Benefit-Cost-Ratio and Return-On-Investment. RESULTS: In POCT-guided care, total costs were on average €32 higher per patient, the proportion of avoided antibiotic prescribing was higher (0.47 vs 0.18; 0.30, 95% CI 0.17 to 0.42) and the proportion of fully recovered patients statistically non-significantly lower (0.86 vs 0.91; -0.05, 95% CI -0.14 to 0.05) compared with usual care. On average, an avoided antibiotic prescription was associated with an investment of €137 in POCT-guided care compared with usual care. Sensitivity analyses showed that results were relatively robust. Taking the ROI metrics together, the probability of financial return was 0.65. CONCLUSION: POCT-guided care effectively reduces antibiotic prescribing compared with usual care without significant effects on recovery rates, but requires an investment. Future studies should take into account potential beneficial effects of POCT-guided care on costs and health outcomes related to antibiotic resistance. TRIAL REGISTRATION NUMBER: NL5054.

A scoping review of statistical methods for trial-based economic evaluations: The current state of play.

The statistical quality of trial-based economic evaluations is often suboptimal, while a comprehensive overview of available statistical methods is lacking. Therefore, this review summarized and critically appraised available statistical methods for trial-based economic evaluations. A literature search was performed to identify studies on statistical methods for dealing with baseline imbalances, skewed costs and/or effects, correlated costs and effects, clustered data, longitudinal data, missing data and censoring in trial-based economic evaluations. Data was extracted on the statistical methods described, their advantages, disadvantages, relative performance and recommendations of the study. Sixty-eight studies were included. Of them, 27 (40%) assessed methods for baseline imbalances, 39 (57%) assessed methods for skewed costs and/or effects, 27 (40%) assessed methods for correlated costs and effects, 18 (26%) assessed methods for clustered data, 7 (10%) assessed methods for longitudinal data, 26 (38%) assessed methods for missing data and 10 (15%) assessed methods for censoring. All identified methods were narratively described. This review provides a comprehensive overview of available statistical methods for dealing with the most common statistical complexities in trial-based economic evaluations. Herewith, it can provide valuable input for researchers when deciding which statistical methods to use in a trial-based economic evaluation.

Rivastigmine for ECT-induced cognitive adverse effects in late life depression (RECALL study): A multicenter, randomized, double blind, placebo-controlled, cross-over trial in patients with depression aged 55 years or older: Rationale, objectives and methods.

Background: Cognitive side-effects are an important reason for the limited use of electroconvulsive therapy (ECT). Cognitive side-effects are heterogeneous and occur frequently in older persons. To date, insight into these side-effects is hampered due to inconsistencies in study designs and small sample sizes. Among all cognitive side-effects, confusion and delirious states are especially troublesome for patients, relatives and clinicians. In particular inter-ictal delirium-like states are worrisome, since they may lead to premature treatment discontinuation. Besides a need for further insight into determinants of cognitive side-effects of ECT, there is a great need for treatment options. Methods and design: The Rivastigmine for ECT-induced Cognitive Adverse effects in Late Life depression (RECALL) study combines a multicenter, prospective cohort study on older patients with depression, treated with ECT, with an embedded randomized, placebo-controlled cross-over trial to examine the effect of rivastigmine on inter-ictal delirium. Patients are recruited in four centers across the Netherlands and Belgium. We aim to include 150 patients into the cohort study, in order to be able to subsequently include 30 patients into the trial. Patients are included in the trial when inter-ictal delirium, assessed by the Confusion Assessment method (CAM), or a drop in Mini Mental State Examination (MMSE) score of ≥4 during ECT, develops. In the cohort study, comprehensive measurements of ECT-related cognitive side-effects-and their putative determinants-are done at baseline and during the ECT-course. The primary outcome of the clinical trial is the effectiveness of rivastigmine on inter-ictal delirium-severity, assessed with a change in the Delirium Rating Scale-Revised-98. Secondary outcomes of the clinical trial are several ECT-characteristics and side-effects of rivastigmine. Discussion: This study is the first clinical trial with a focus on ECT-induced, inter-ictal delirium. The cohort provides the basis for recruitment of patients for the cross-over trial and additionally provides an excellent opportunity to unravel cognitive side-effects of ECT and identify putative determinants. This paper describes the rationale and study protocol. Clinical trial registration: EudraCT 2014-003385-24.