Cost-effectiveness of extracorporeal cardiopulmonary resuscitation vs. conventional cardiopulmonary resuscitation in out-of-hospital cardiac arrest: a pre-planned, trial-based economic evaluation.

AIMS: When out-of-hospital cardiac arrest (OHCA) becomes refractory, extracorporeal cardiopulmonary resuscitation (ECPR) is a potential option to restore circulation and improve the patient's outcome. However, ECPR requires specific materials and highly skilled personnel, and it is unclear whether increased survival and health-related quality of life (HRQOL) justify these costs. METHODS AND RESULTS: This cost-effectiveness study was part of the INCEPTION study, a multi-centre, pragmatic randomized trial comparing hospital-based ECPR to conventional CPR (CCPR) in patients with refractory OHCA in 10 cardiosurgical centres in the Netherlands. We analysed healthcare costs in the first year and measured HRQOL using the EQ-5D-5L at 1, 3, 6, and 12 months. Incremental cost-effectiveness ratios (ICERs), cost-effectiveness planes, and acceptability curves were calculated. Sensitivity analyses were performed for per-protocol and as-treated subgroups as well as imputed productivity loss in deceased patients. In total, 132 patients were enrolled: 62 in the CCPR and 70 in the ECPR group. The difference in mean costs after 1 year was €5109 (95% confidence interval -7264 to 15 764). Mean quality-adjusted life year (QALY) after 1 year was 0.15 in the ECPR group and 0.11 in the CCPR group, resulting in an ICER of €121 643 per additional QALY gained. The acceptability curve shows that at a willingness-to-pay threshold of €80.000, the probability of ECPR being cost-effective compared with CCPR is 36%. Sensitivity analysis showed increasing ICER in the per-protocol and as-treated groups and lower probabilities of acceptance. CONCLUSION: Hospital-based ECPR in refractory OHCA has a low probability of being cost-effective in a trial-based economic evaluation.

The estimation of a preference-based single index for the IBS-QoL by mapping to the EQ-5D-5L in patients with irritable bowel syndrome.

PURPOSE: The Irritable Bowel Syndrome Quality of Life (IBS-QoL) questionnaire is a commonly used and validated IBS-specific QoL instrument. However, this questionnaire is in contrast to the EQ-5D-5L, not preference-based and as such does not allow calculation of QALYs. The objective of this study was to describe the convergent- and known-group validity of both questionnaires and to develop a mapping algorithm from EQ-5D-5L which enable IBS-QoL scores to be transformed into utility scores for use in economic evaluations. METHODS: We used data from two multicenter randomized clinical trials, which represented the estimation and external validation dataset. The convergent validity was investigated by examining correlations between the EQ-5D-5L and IBS-QoL and the known-group validity by calculating effect sizes. Ordinary least squares (OLS), censored least absolute deviations (CLAD), and mixture models were used in this mapping approach. RESULTS: 283 IBS patients were included (n = 189 vs. n = 84). Mean IBS-QoL score was 71.13 (SD 15.66) and mean EQ-5D-5L utility score was 0.73 (SD 0.19). The overall sensitivity of the IBS-QoL and EQ-5D-5L to discriminate between patient and disease characteristics was similar. CLAD model 4, containing the total IBS-QoL score and squared IBS-SSS (IBS severity scoring system), was chosen as the most appropriate model to transform IBS-QoL scores into EQ-5D-5L utility scores. CONCLUSION: This study reports the development of an algorithm where the condition-specific questionnaire IBS-QoL can be used to calculate utility values for use in economic evaluations. Including a clinical measure, IBS-SSS, in the model improved the performance of the algorithm.

Positive Health dialogue tool and value-based healthcare: a qualitative exploratory study during residents' outpatient consultations.

OBJECTIVE: To explore how residents experienced the application of the Positive Health dialogue tool (PH-tool) during outpatient consultations and its influence on the delivery of value-based healthcare (VBHC). DESIGN: Qualitative study using non-participant observations of outpatient consultations during which residents used the PH-tool, followed by longitudinal individual, semistructured interviews. To analyse the data from observations and interviews, observational form notes' summarisation and categorisation, and an iterative-inductive thematic approach was used. PARTICIPANTS: Eight residents-five from the ear, nose, and throat-department and three from the gastroenterology-hepatology-department-were selected through convenience sampling, accounting for 79 observations and 79 interviews. RESULTS: Residents had bivalent experiences with using the PH-tool. Residents discussed three main benefits: a gained insight into the individual patient's context and functioning, a changed dynamics in resident-patient communication, and an increased awareness regarding value in terms of patient-related outcomes and healthcare costs. Three barriers became apparent: doubts regarding the PH-tool's relevance and scope, boundaries of superspecialised medical professionals, and a lack of demarcation in clinical practice. CONCLUSION: The PH-tool use can be beneficial for residents during outpatient consultations with new patients and follow-up in cases of multidimensional problems, particularly in cases of chronic conditions and generalist care. In these situations, the tool yielded valuable patient information beyond physical health, helped foster patient engagement, and enabled tailoring the treatment plan to individual patients' needs. On the other hand, the PH-tool was not a good fit for simple problems, clearly demarcated help requests, periodic follow-up consultations, or verbose patients. In addition, it was not suitable for superspecialised care, because it yielded an abundance of general information. For particular patients and problems, using the PH-tool seems a promising strategy to increase VBHC delivery. Nevertheless, further research and detailing is needed to better align the PH-tool's broad intent and clinical practice.

A trial-based economic evaluation of peppermint oil for the treatment of irritable bowel syndrome.

BACKGROUND: Irritable Bowel Syndrome (IBS) is a prevalent, chronic gastrointestinal disorder that imposes a substantial socioeconomic burden. Peppermint oil is a frequently used treatment for IBS, but evidence about cost-effectiveness is lacking. OBJECTIVE: We aimed to assess cost-effectiveness of small-intestinal release peppermint oil versus placebo in IBS patients. METHODS: In a multicenter randomized placebo-controlled trial, cost-effectiveness was evaluated from a societal perspective. The incremental cost-effectiveness ratios (ICERs) were expressed as (1) incremental costs per Quality Adjusted Life Years (QALY), and (2) incremental costs per successfully treated patient, that is per abdominal pain responder (according to FDA definitions), both after an eight-week treatment period with placebo versus peppermint oil. Cost-utility and uncertainty were estimated using non-parametric bootstrapping. Sensitivity analyses were performed. RESULTS: The analysis comprised 126 patients (N = 64 placebo, N = 62 small-intestinal release peppermint oil). Peppermint oil was a dominant treatment compared to placebo in 46% of bootstrap replications. Peppermint oil was also more effective but at higher cost in 31% of replications. The net-benefit acceptability curve showed that peppermint oil has a 56% probability of being cost-effective at a conservative willingness-to-pay threshold of €10.000/QALY. Peppermint oil was also a dominant treatment per additional successfully treated patient according to FDA definitions, that is in 51% of replications. In this case, the acceptability curve showed an 89% probability of being cost-effective. CONCLUSIONS: In patients with IBS, small-intestinal release peppermint oil appears to be a cost-effective treatment although there is uncertainty surrounding the ICER. When using abdominal pain responder as outcome measure for the ICER, peppermint oil has a high probability of being cost-effective. The use of peppermint oil, which is a low-cost treatment, can be justified by the modest QALY gains and slightly higher proportion of abdominal pain responders. More research and long-term data are necessary to confirm the cost-effectiveness of peppermint oil. NCT02716285.

National mixed methods evaluation of the effects of removing legal barriers to full practice authority of Dutch nurse practitioners and physician assistants.

OBJECTIVE: To evaluate the effects of granting legal full practice authority (FPA) to nurse practitioners (NP) and physician assistants (PA) regarding the performance of specified reserved medical procedures and to support governmental decision-making. DESIGN: Nationwide mixed methods design with triangulation of quantitative (Pre-post test design) and qualitative data (expert interviews and focus groups). METHODS: Surveys focused on the performance of the procedures (monthly number, authorisation mode, consultations and procedural time) and legal cross-compliance requirements (adherence with protocols, competence). Interviews focused on competence, knowledge, skills, responsibilities, routine behaviour, NP/PA role, acceptance, organisational structure, collaboration, consultation, NP/PA positioning, adherence with protocols and resources. Data collection took place between 2011 and 2015. RESULTS: Quantitative data included 1251 NPs, 798 PAs and 504 physicians. Besides, expert interviews with 33 healthcare providers and 28 key stakeholders, and 5 focus groups (31 healthcare providers) were held.After obtaining FPA, the proportion of NPs and PAs performing reserved procedures increased from 77% to 85% and from 86% to 93%, respectively; the proportion of procedures performed on own authority increased from 63% to 76% for NPs and from 67% to 71% for PAs. The mean number of monthly contacts between NPs/PAs and physicians about procedures decreased (from 81 to 49 and from 107 to 54, respectively), as did the mean duration in minutes (from 9.9 to 8.6 and from 8.8 to 7.4, respectively). Utilisation of FPA was dependent on the setting, as scepticism of physicians and medical boards hampered full implementation. Legal cross-compliance requirements were mostly fulfilled. CONCLUSIONS: Informal practice was legalised. The opportunities to independently perform catheterisations, injections, prescribing, punctures and small surgical procedures were highly used. Care processes were organised more efficiently, services were performed by the most appropriate healthcare provider and conditions were met. This led to the recommendation to continue with FPA.

Functional outcome and cost-effectiveness of pulsed electromagnetic fields in the treatment of acute scaphoid fractures: a cost-utility analysis.

BACKGROUND: Physical forces have been widely used to stimulate bone growth in fracture repair. Addition of bone growth stimulation to the conservative treatment regime is more costly than standard health care. However, it might lead to cost-savings due to a reduction of the total amount of working days lost. This economic evaluation was performed to assess the cost-effectiveness of Pulsed Electromagnetic Fields (PEMF) compared to standard health care in the treatment of acute scaphoid fractures. METHODS: An economic evaluation was carried out from a societal perspective, alongside a double-blind, randomized, placebo-controlled, multicenter trial involving five centres in The Netherlands. One hundred and two patients with a clinically and radiographically proven fracture of the scaphoid were included in the study and randomly allocated to either active bone growth stimulation or standard health care, using a placebo. All costs (medical costs and costs due to productivity loss) were measured during one year follow up. Functional outcome and general health related quality of life were assessed by the EuroQol-5D and PRWHE (patient rated wrist and hand evaluation) questionnaires. Utility scores were derived from the EuroQol-5D. RESULTS: The average total number of working days lost was lower in the active PEMF group (9.82 days) compared to the placebo group (12.91 days) (p = 0.651). Total medical costs of the intervention group (€1594) were significantly higher compared to the standard health care (€875). The total amount of mean QALY's (quality-adjusted life year) for the active PEMF group was 0.84 and 0.85 for the control group. The cost-effectiveness plane shows that the majority of all cost-effectiveness ratios fall into the quadrant where PEMF is not only less effective in terms of QALY's but also more costly. CONCLUSION: This study demonstrates that the desired effects in terms of cost-effectiveness are not met. When comparing the effects of PEMF to standard health care in terms of QALY's, PEMF cannot be considered a cost-effective treatment for acute fractures of the scaphoid bone. TRIAL REGISTRATION: Netherlands Trial Register (NTR): NTR2064.

Erythrocytapheresis versus phlebotomy in the initial treatment of HFE hemochromatosis patients: results from a randomized trial.

BACKGROUND: Standard treatment of newly diagnosed HFE hemochromatosis patients is phlebotomy. Erythrocytapheresis provides a new therapeutic modality that can remove up to three times more red blood cells per single procedure and could thus have a clinical and economic benefit. STUDY DESIGN AND METHODS: To compare the number of treatment procedures between erythrocytapheresis and phlebotomy needed to reach the serum ferritin (SF) target level of 50 µg/L, a two-treatment-arms, randomized trial was conducted in which 38 newly diagnosed patients homozygous for C282Y were randomly assigned in a 1:1 ratio to undergo either erythrocytapheresis or phlebotomy. A 50% decrease in the number of treatment procedures for erythrocytapheresis compared to phlebotomy was chosen as the relevant difference to detect. RESULTS: Univariate analysis showed a significantly lower mean number of treatment procedures in the erythrocytapheresis group (9 vs. 27; ratio, 0.33; 95% confidence interval [CI], 0.25-0.45; Mann-Whitney p < 0.001). After adjustments for the two important influential factors initial SF level and body weight, the reduction ratio was still significant (0.43; 95% CI, 0.35-0.52; p < 0.001). Cost analysis showed no significant difference in treatment costs between both procedures. The costs resulting from productivity loss were significantly lower for the erythrocytapheresis group. CONCLUSION: Erythrocytapheresis is highly effective treatment to reduce iron overload and from a societal perspective might potentially also be a cost-saving therapy.

Assessing the public's preference for surgical treatment of primary basal cell carcinoma: a discrete-choice experiment in the south of the Netherlands.

BACKGROUND: Basal cell carcinoma (BCC) is a slowly growing nonmelanoma type of skin cancer that often is located on the face. Different therapies are available to treat BCC, of which surgical excision (SE) and Mohs micrographic surgery (MMS) are the most frequently used surgical procedures. OBJECTIVES: To examine which attributes of a surgical treatment the general public values as important and to determine the incremental willingness to pay for MMS versus SE. METHODS: A discrete-choice experiment (DCE) was conducted among members of the general public to examine which attributes of a surgical treatment for primary BCC are valued as important. In addition, based on the attributes included in the experiment, the willingness to pay for MMS versus SE was determined. RESULTS: Respondents (N=312) preferred a treatment with a lower recurrence rate, shorter surgery time, shorter travelling time, shorter waiting time, no risk for re-excision, and lower cost. The incremental willingness to pay for MMS was 847 euro ($1,203). CONCLUSIONS: Results from this DCE indicate that, when outcome and process attributes are considered from a societal perspective, MMS is preferred over SE for primary BCC. The authors have indicated no significant interest with commercial supporters.

Does the inclusion of a cost attribute result in different preferences for the surgical treatment of primary basal cell carcinoma?: a comparison of two discrete-choice experiments.

BACKGROUND: Nowadays, an increasing number of discrete-choice experiments (DCEs) incorporate cost as an attribute. However, the inclusion of a cost attribute, particularly within collectively funded healthcare systems, can be challenging because health services or goods are generally not traded in a market situation and individuals are not used to paying for a service or a good at the point of consumption. OBJECTIVE: To examine whether the inclusion of a cost attribute in a DCE results in different preferences regarding a surgical treatment for primary basal cell carcinoma (BCC) compared with a DCE without a cost attribute. METHODS: A randomized study was performed in which the impact of a cost attribute on the general public's preferences for a surgical treatment (Mohs micrographic surgery [MMS] or standard excision [SE]) to remove BCC was examined. This was done by comparing the outcomes of two DCEs, one with a cost attribute (DCE_cost) and one without (DCE_nocost). Six attributes (recurrence, re-excision, travel time, surgical time, waiting time for surgical results, costs) and their levels were selected, based on results of a clinical trial, a cost-effectiveness study, a review and a focus group of patients who had recently received treatment for BCC. Outcomes of both DCEs were compared in terms of theoretical validity, relative importance of the attributes and the rank order of preferences. RESULTS: A total of 615 respondents (n = 303 for DCE_nocost; n = 312 for DCE_cost) were interviewed by telephone. This gave an overall response rate of 38%. Respondents in DCE_nocost preferred a surgical treatment with a lower probability of recurrence, lower surgery time, lower waiting time and no risk for a re-excision. Respondents in DCE_cost showed the same preferences, but also preferred a treatment with less travel time and lower costs. Overall, respondents in both DCEs showed the same preference for a surgical treatment: MMS was preferred over SE. CONCLUSION: Results suggest that, in this population, the inclusion of a cost attribute in a DCE leads to the same preference regarding a surgical treatment to remove BCC as a DCE without a cost attribute. However, further research in different settings is needed to confirm these findings.

Transferability of model-based economic evaluations: the case of trastuzumab for the adjuvant treatment of HER2-positive early breast cancer in the Netherlands.

INTRODUCTION: Geographic transferability of model-based cost-effectiveness results may facilitate and shorten the reimbursement process of new pharmaceuticals. This study provides a real world example of transferring a cost-effectiveness study of trastuzumab for the adjuvant treatment of HER2-positive early breast cancer from the United Kingdom to The Netherlands. METHODS: Three successive steps were taken. Step 1: Collect available information with regard to the original model, and assess transferability using existing checklists. Step 2: Adapt transferability-limiting factors. Step 3: Obtain a country-specific estimate of cost-effectiveness. RESULTS: The structure of the UK model was transferable, although some of the model inputs needed adaptation. From a health-care perspective, the Dutch estimate amounted to euro5828/quality-adjusted life-year gained. From a societal perspective, the incremental cost-effectiveness ratio was dominant. CONCLUSION: Transferability of a model-based UK-study in three steps proved to be an efficient method to provide an early indication of the cost-effectiveness of trastuzumab and has led to the provisional reimbursement of the treatment.

Surgical excision versus Mohs' micrographic surgery for primary and recurrent basal-cell carcinoma of the face: a prospective randomised controlled trial with 5-years' follow-up.

BACKGROUND: Basal-cell carcinoma (BCC) is the most common form of skin cancer and its incidence is still rising worldwide. Surgery is the most frequently used treatment for BCC, but large randomised controlled trials with 5-year follow-up to compare treatment modalities are rare. We did a prospective randomised controlled trial to compare the effectiveness of surgical excision with Mohs' micrographic surgery (MMS) for the treatment of primary and recurrent facial BCC. METHODS: Between Oct 5, 1999, and Feb 27, 2002, 408 primary BCCs (pBCCs) and 204 recurrent BCCs (rBCCs) in patients from seven hospitals in the Netherlands were randomly assigned to surgical excision or MMS. Randomisation and allocation was done separately for both groups by a computer-generated allocation scheme. Tumours had a follow-up of 5 years. Analyses were done on an intention-to-treat basis. The primary outcome was recurrence of carcinoma, diagnosed clinically by visual inspection with histological confirmation. Secondary outcomes were determinants of failure and cost-effectiveness. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN65009900. FINDINGS: Of the 397 pBCCs that were treated, 127 pBCCs in 113 patients were lost to follow-up. Of the 11 recurrences that occurred in patients with pBCC, seven (4.1%) occurred in patients treated with surgical excision and four (2.5%) occurred in patients treated with MMS (log-rank test chi(2) 0.718, p=0.397). Of the 202 rBCCs that were treated, 56 BCCs in 52 patients were lost to follow-up. Two BCCs (2.4%) in two patients treated with MMS recurred, versus ten BCCs (12.1%) in ten patients treated with surgical excision (log-rank test chi(2) 5.958, p=0.015). The difference in the number of recurrences between treatments was not significant for pBCC, but significantly favoured MMS in rBCC. In pBCC, Cox-regression analysis showed no significant effects from risk factors measured in the study. In rBCC, aggressive histological subtype was a significant risk factor for recurrence in the Cox-regression analysis. For pBCC, total treatment costs were euro1248 for MMS and euro990 for surgical excision, whereas for rBCC, treatment costs were euro1284 and euro1043, respectively. Dividing the difference in costs between MMS and surgical excision by their difference in effectiveness leads to an incremental cost-effectiveness ratio of euro23 454 for pBCC and euro3171 for rBCC. INTERPRETATION: MMS is preferred over surgical excision for the treatment of facial rBCC, on the basis of significantly fewer recurrences after MMS than after surgical excision. However, because there was no significant difference in recurrence of pBCC between treatment groups, treatment with surgical excision is probably sufficient in most cases of pBCC.

Cost-effectiveness of Mohs Micrographic Surgery vs Surgical Excision for Basal Cell Carcinoma of the Face.

OBJECTIVE: To assess the cost-effectiveness of Mohs micrographic surgery (MMS) compared with the surgical excision for both primary and recurrent basal cell carcinoma (BCC). DESIGN: A cost-effectiveness study performed alongside a prospective randomized clinical trial in which MMS was compared with surgical excision. SETTING: The study was carried out from 1999 to 2002 at the dermatology outpatient clinic of the University Hospital Maastricht, Maastricht, The Netherlands. PARTICIPANTS: A total of 408 primary (374 patients) and 204 recurrent (191 patients) cases of facial BCC were included. MAIN OUTCOME MEASURES: The mean total treatment costs of MMS and surgical excision for both primary and recurrent BCC and the incremental cost-effectiveness ratio, calculated as the difference in costs between MMS and surgical excision divided by their difference in effectiveness. The resulting ratio is defined as the incremental costs of MMS compared with surgical excision to prevent 1 additional recurrence. RESULTS: Compared with surgical excision, the total treatment costs of MMS are significantly higher (cost difference: primary BCC, 254 euros; 95% confidence interval, 181-324 euros; recurrent BCC, 249 euros; 95% confidence interval, 175-323 euros). For primary BCC, the incremental cost-effectiveness ratio was 29,231 euros, while the ratio for recurrent BCC amounted to 8094 euros. The acceptability curves showed that for these ratios, the probability of MMS being more cost-effective than surgical excision never reached 50%. CONCLUSIONS: At present, it does not seem cost-effective to introduce MMS on a large scale for both primary and recurrent BCC. However, because a 5-year period is normally required to determine definite recurrence rates, it is possible that MMS may become a cost-effective treatment for recurrent BCC.