Effectiveness and cost-effectiveness of a multimodal, physiotherapist-led, vocational intervention in people with inflammatory arthritis: study protocol of the Physiotherapy WORKs trial.

BACKGROUND: Although reduced work ability is a substantial problem among people with inflammatory arthritis (IA), work ability is an underexposed area in clinical practice. Evidence on vocational interventions in IA is limited, but favourable results of delivery by a physiotherapist (PT) warrant the need for further research. Therefore, we aim to evaluate the (cost-)effectiveness of a multimodal, PT-led, vocational intervention in (self-)employed people with IA compared to usual care. METHODS: This randomized controlled trial will include 140 people with rheumatoid arthritis (RA) or axial spondyloarthritis (axSpA) who are (self-)employed and have reduced work ability (Work Ability Index - Single Item Scale (WAS) ≤ 7/10) and/or RA/axSpA related sick leave (≤ 6 months). Participants will be randomized 1:1 to the intervention or control condition (usual care). The intervention, delivered by primary care PTs, will be personalized to each patient, consisting of 10 to 21 sessions over 12 months. The intervention will be multimodal, comprising of 1) exercise therapy and a physical activity plan, 2) education/self-management support, 3) work-roadmap to guide participants in finding relevant other care, with optionally 4) online self-management course and 5) workplace examination. Assessments will be performed at baseline and after 3, 6, and 12 months. The primary outcome measure of effectiveness is work ability, as measured with the WAS at 12 months. For the cost-effectiveness analysis, the EuroQol (EQ-5D-5L), self-reported healthcare use, sick leave and productivity while at work will be used to estimate the trial based cost-utility from a societal perspective. A process evaluation, including assessments of adherence and treatment fidelity, will be undertaken using the registrations of the PTs and semi-structured interviews at 12 months follow-up in a random sample of the intervention group. DISCUSSION: The results of this study will provide insights in the (cost-)effectiveness of a multimodal, PT-led, vocational intervention in people with IA and a reduced work ability. TRIAL REGISTRATION: This study is registered in the International Clinical Trial Registry Platform (ICTRP) under number NL9343.

Diagnostic and societal impact of implementing the syncope guidelines of the European Society of Cardiology (SYNERGY study).

BACKGROUND: Syncope management is fraught with unnecessary tests and frequent failure to establish a diagnosis. We evaluated the potential of implementing the 2018 European Society of Cardiology (ESC) Syncope Guidelines regarding diagnostic yield, accuracy and costs. METHODS: A multicentre pre-post study in five Dutch hospitals comparing two groups of syncope patients visiting the emergency department: one before intervention (usual care; from March 2017 to February 2019) and one afterwards (from October 2017 to September 2019). The intervention consisted of the simultaneous implementation of the ESC Syncope Guidelines with quick referral routes to a syncope unit when indicated. The primary objective was to compare diagnostic accuracy using logistic regression analysis accounting for the study site. Secondary outcome measures included diagnostic yield, syncope-related healthcare and societal costs. One-year follow-up data were used to define a gold standard reference diagnosis by applying ESC criteria or, if not possible, evaluation by an expert committee. We determined the accuracy by comparing the treating physician's diagnosis with the reference diagnosis. RESULTS: We included 521 patients (usual care, n = 275; syncope guidelines intervention, n = 246). The syncope guidelines intervention resulted in a higher diagnostic accuracy in the syncope guidelines group than in the usual care group (86% vs.69%; risk ratio 1.15; 95% CI 1.07 to 1.23) and a higher diagnostic yield (89% vs. 76%, 95% CI of the difference 6 to 19%). Syncope-related healthcare costs did not differ between the groups, yet the syncope guideline implementation resulted in lower total syncope-related societal costs compared to usual care (saving €908 per patient; 95% CI €34 to €1782). CONCLUSIONS: ESC Syncope Guidelines implementation in the emergency department with quick referral routes to a syncope unit improved diagnostic yield and accuracy and lowered societal costs. TRIAL REGISTRATION: Netherlands Trial Register, NTR6268.

The YEARS algorithm for suspected pulmonary embolism: shorter visit time and reduced costs at the emergency department.

Essentials The YEARS algorithm was designed to simplify the diagnostic workup of suspected pulmonary embolism. We compared emergency ward turnaround time of YEARS and the conventional algorithm. YEARS was associated with a significantly shorter emergency department visit time of ˜60 minutes. Treatment of pulmonary embolism was initiated 53 minutes earlier with the YEARS algorithm SUMMARY: Background Recently, the safety of the YEARS algorithm, designed to simplify the diagnostic work-up of pulmonary embolism (PE), was demonstrated. We hypothesize that by design, YEARS would be associated with a shorter diagnostic emergency department (ED) visit time due to simultaneous assessment of pre-test probability and D-dimer level and reduction in number of CT scans. Aim To investigate whether implementation of the YEARS diagnostic algorithm is associated with a shorter ED visit time compared with the conventional algorithm and to evaluate the associated cost savings. Methods We selected consecutive outpatients with suspected PE from our hospital included in the YEARS study and ADJUST-PE study. Different time-points of the diagnostic process were extracted from the to-the-minute accurate electronic patients' chart system of the ED. Further, the costs of the ED visits were estimated for both algorithms. Results All predefined diagnostic turnaround times were significantly shorter after implementation of YEARS: patients were discharged earlier from the ED; 54 min (95% CI, 37-70) for patients managed without computed tomography pulmonary angiography (CTPA) and 60 min (95% CI, 44-76) for the complete study population. Importantly, patients diagnosed with PE by CTPA received the first dose of anticoagulants 53 min (95% CI, 22-82) faster than those managed according to the conventional algorithm. Total costs were reduced by on average €123 per visit. Conclusion YEARS was shown to be associated with a shorter ED visit time compared with the conventional diagnostic algorithm, leading to faster start of treatment in the case of confirmed PE and savings on ED resources.

Systematic review of the clinical and economic value of gene expression profiles for invasive early breast cancer available in Europe.

Gene expression profiles with prognostic capacities have shown good performance in multiple clinical trials. However, with multiple assays available and numerous types of validation studies performed, the added value for daily clinical practice is still unclear. In Europe, the MammaPrint, OncotypeDX, PAM50/Prosigna and Endopredict assays are commercially available. In this systematic review, we aim to assess these assays on four important criteria: Assay development and methodology, clinical validation, clinical utility and economic value. We performed a literature search covering PubMed, Embase, Web of Science and Cochrane, for studies related to one or more of the four selected assays. We identified 147 papers for inclusion in this review. MammaPrint and OncotypeDX both have evidence available, including level IA clinical trial results for both assays. Both assays provide prognostic information. Predictive value has only been shown for OncotypeDX. In the clinical utility studies, a higher reduction in chemotherapy was achieved by OncotypeDX, although the number of available studies differ considerably between tests. On average, economic evaluations estimate that genomic testing results in a moderate increase in total costs, but that these costs are acceptable in relation to the expected improved patient outcome. PAM50/prosigna and EndoPredict showed comparable prognostic capacities, but with less economical and clinical utility studies. Furthermore, for these assays no level IA trial data are available yet. In summary, all assays have shown excellent prognostic capacities. The differences in the quantity and quality of evidence are discussed. Future studies shall focus on the selection of appropriate subgroups for testing and long-term outcome of validation trials, in order to determine the place of these assays in daily clinical practice.

Multicentre randomized clinical trial to investigate the cost-effectiveness of an allogeneic single-donor fibrin sealant after coronary artery bypass grafting (FIBER Study).

BACKGROUND: Reduction of blood transfusion in cardiac surgery is an important target. The aim of this study was to investigate the cost-effectiveness of the use of CryoSeal®, an allogeneic single-donor fibrin sealant, in patients undergoing coronary artery bypass grafting (CABG). METHODS: This randomized clinical study involved seven cardiac surgery centres in the Netherlands. Patients undergoing elective isolated CABG with the use of at least one internal thoracic artery (ITA) graft were assigned randomly to receive either CryoSeal® (5 ml per ITA bed) or no CryoSeal®. Primary efficacy endpoints were units of transfused red blood cells, fresh frozen plasma and platelet concentrates, and duration of intensive care unit stay. Secondary efficacy endpoints were 48-h blood loss, reoperation for bleeding, mediastinitis, 30-day mortality and duration of hospital stay. RESULTS: Between March 2009 and January 2012, 1445 patients were randomized. The intention-to-treat (ITT) population comprised 1436 patients; the per-protocol (PP) population 1292. In both the ITT and the PP analysis, no significant difference between the treatment groups was observed for any of the primary and secondary efficacy endpoints. In addition, no significant difference between the groups was seen in the proportion of transfused patients. Estimated CryoSeal® costs were €822 (95 per cent c.i. €808 to €836) per patient, which translated to €72,000 per avoided transfusion (unbounded 95 per cent c.i.). CONCLUSION: The use of the fibrin sealant CryoSeal® did not result in health benefits. Combined with the high cost per avoided transfusion, this study does not support the implementation of routine CryoSeal® use in elective isolated CABG. REGISTRATION NUMBER: NTR1386 ( http://www.trialregister.nl).

Healthcare costs and loss of productivity in patients with trapeziometacarpal osteoarthritis.

The objective of this study was to analyse healthcare and productivity costs in patients with trapeziometacarpal osteoarthritis. We included 161 patients who received surgery or steroid injection and calculated their healthcare costs in Euro (€) over 1 year. Patients filled out the Work Productivity and Activity Impairment Questionnaire to assess loss of productivity at baseline, and after 3, and 12 months. In the surgical group, loss of productivity among employed patients first increased and then decreased (50%, 64%, and 25% at 0, 3, and 12 months). Productivity was more stable over time in the injection group (52%, 38%, and 48%). In the surgical group, estimated total annual healthcare and productivity costs were €5770 and €5548, respectively. In the injection group, healthcare and productivity costs were €348 and €3503. These findings highlight the need for assessing productivity costs to get a comprehensive view of the costs associated with a treatment.Level of Evidence III.

Cost-effectiveness of 3-year vs 1-year adjuvant therapy with imatinib in patients with high risk of gastrointestinal stromal tumour recurrence in the Netherlands; a modelling study alongside the SSGXVIII/AIO trial.

BACKGROUND: Surgical resection of gastrointestinal stromal tumour (GIST) is rarely curative in patients at high risk of tumour recurrence and therefore 1 year of post-surgery adjuvant imatinib therapy has been recommended in this sub-group. Recently, adjuvant imatinib therapy administered for 3 years has been demonstrated to further increase recurrence-free survival and overall survival. The goal of this study was to assess the economic value of extending the duration of adjuvant imatinib therapy in high-risk patients in the Netherlands. METHODS: A multistate Markov model was developed to simulate how patients' clinical status after GIST excision evolves over time until death. The model structure encompassed four primary health states: free of recurrence, first GIST recurrence, second GIST recurrence, and death. Transition probabilities between the health states, data on medical care costs, and quality-of-life were obtained from published sources and from expert opinion. RESULTS: The expected number of life years (or quality-adjusted life years, QALYs) was higher in the 3-year group than in the 1-year group, 8.91 (6.55) and 7.04 (5.18) years, respectively. In the 3-year and 1-year group, the expected total costs amounted to €120,195 and €79,361, of which, €74,631 (62%) and €27,619 (35%) were adjuvant therapy drug costs, respectively. The difference in health benefits, that is 1.87 life years or 1.37 QALYs, and costs, €40,835, resulted in incremental cost-effectiveness ratios (ICER) of €21,865 per life year gained, and €29,872 per QALY gained. LIMITATIONS: A limitation of the study was inherently related to the uncertainty around the predictions of RFS. Scenario analyses were conducted to test the sensitivity of different RFS predictions on the results. CONCLUSIONS: Delayed recurrence due to treatment with longer-term adjuvant imatinib therapy represents a cost-effective treatment option with an ICER below the generally accepted threshold in the Netherlands.

The value of productivity: human-capital versus friction-cost method.

Many cost-of-illness studies have investigated the impact of rheumatoid arthritis on productivity, invariably concluding that productivity costs are high. Different methods exist to value productivity. The human-capital method takes the patient's perspective and counts any hour not worked as an hour lost. By contrast, the friction-cost method takes the employer's perspective, and only counts as lost those hours not worked until another employee takes over the patient's work. Both methods can produce widely different results. Productivity costs have the potential to compensate for the costs of expensive biological agents, but only in early-onset disease when patients still have jobs and if productivity is given full weight by using the human-capital method. If productivity is given less weight by excluding productivity costs or by using the friction-cost method, then currently, biological agents are probably too expensive.

Cost effectiveness and cost utility analysis of multidisciplinary care in patients with rheumatoid arthritis: a randomised comparison of clinical nurse specialist care, inpatient team care, and day patient team care.

OBJECTIVE: To assess the relative cost effectiveness of clinical nurse specialist care, inpatient team care, and day patient team care. METHODS: Incremental cost effectiveness analysis and cost utility analysis, alongside a prospective randomised controlled trial with two year follow up. Included were patients with rheumatoid arthritis (RA) with increasing difficulty in performing activities of daily living over the previous six weeks. Quality of life and utility were assessed by the Rheumatoid Arthritis Quality of Life questionnaire, the Short Form-6D, a transformed rating scale, and the time tradeoff. A cost-price analysis was conducted to estimate the costs of inpatient and day patient hospitalisations. Other healthcare and non-healthcare costs were estimated from cost questionnaires. RESULTS: 210 patients with RA (75% female, median age 59 years) were included. Aggregated over the two year follow up period, no significant differences were found on the quality of life and utility instruments. The costs of the initial treatment were estimated at euro 200 for clinical nurse specialist care, euro 5000 for inpatient team care, and euro 4100 for day patient team care. Other healthcare costs and non-healthcare costs were not significantly different. The total societal costs did not differ significantly between inpatients and day patients, but were significantly lower for the clinical nurse specialist patients by at least euro 5400. CONCLUSIONS: Compared with inpatient and day patient team care, clinical nurse specialist care was shown to provide equivalent quality of life and utility, at lower costs. Therefore, for patients with health conditions that allow for any of the three types of care, the preferred treatment from a health-economic perspective is the care provided by the clinical nurse specialist.

Cost-effectiveness analysis of colorectal cancer treatments.

A concise overview is provided of the methodology of cost-effectiveness analyses, followed by a survey of published CEAs of colorectal cancer treatments. To gain credibility, the methodology applied in CEAs must be further improved. Costs are rarely estimated from the societal perspective, and little is known about how colorectal patients value their treatment and health.

International differences in health care costs in Europe and the United States: Do these affect the cost-effectiveness of diagnostic strategies for pulmonary embolism?

The aim of this study was to assess whether potential differences in costs for diagnostic procedures and treatment of pulmonary embolism (PE) among European and U. S. hospitals alter the optimal cost-effective diagnostic strategy for PE. A standardized questionnaire was used to obtain cost data for the diagnosis and treatment of PE in participating European and U. S. hospitals. Costs for diagnostic tests and treatment of PE were then calculated in a standardized manner for all participating hospitals, from the hospital perspective. Costs were used in an existing cost-effectiveness analysis (CEA) model to determine the most cost-effective diagnostic strategy in participating hospitals. There were considerable differences in costs for diagnostic and therapeutic procedures for PE among the participating centers. These differences, however, did not affect the most cost-effective strategy based on incremental cost-effectiveness. In all hospitals the most cost-effective strategy appeared to be ultrasound followed by helical CT. International differences in cost of diagnostic and therapeutic procedures certainly exist and should be considered before applying a published CEA. Nevertheless, despite these cost differences, the diagnostic strategy for PE of ultrasound followed by helical CT appears most cost-effective.