Leona Hakkaart

Cost-consequence analysis of remifentanil-based analgo-sedation vs. conventional analgesia and sedation for patients on mechanical ventilation in the Netherlands

IntroductionHospitals are increasingly forced to consider the economics of technology use. We estimated the incremental cost-consequences of remifentanil-based analgo-sedation (RS) vs. conventional analgesia and sedation (CS) in patients requiring mechanical ventilation (MV) in the intensive care unit (ICU), using a modelling approach.MethodsA Markov model was developed to describe patient flow in the ICU. The hourly probabilities to move from one state to another were derived from UltiSAFE, a Dutch clinical study involving ICU patients with an expected MV-time of two to three days requiring analgesia and sedation. Study medication was either: CS (morphine or fentanyl combined with propofol, midazolam or lorazepam) or: RS (remifentanil, combined with propofol when required). Study drug costs were derived from the trial, whereas all other ICU costs were estimated separately in a Dutch micro-costing study. All costs were measured from the hospital perspective (price level of 2006). Patients were followed in the model for 28 days. We also studied the sub-population where weaning had started within 72 hours.ResultsThe average total 28-day costs were €15,626 with RS versus €17,100 with CS, meaning a difference in costs of €1474 (95% CI -2163, 5110). The average length-of-stay (LOS) in the ICU was 7.6 days in the RS group versus 8.5 days in the CS group (difference 1.0, 95% CI -0.7, 2.6), while the average MV time was 5.0 days for RS versus 6.0 days for CS. Similar differences were found in the subgroup analysis.ConclusionsCompared to CS, RS significantly decreases the overall costs in the ICU.Trial RegistrationClinicaltrials.gov NCT00158873.

Orphan drugs expenditure in the Netherlands in the period 2006–2012

BackgroundThe relatively low budget impact of orphan drugs is often used as an argument in reimbursement decisions. However, overall, the budget impact of orphan drugs can still be substantial. In this study, we assess the uptake and budget impact of orphan drugs in the Netherlands.MethodsWe examined the number of orphan drugs, the number of patients and budget impact of orphan drugs in the Netherlands in the period 2006 to 2012, both for inpatient and outpatient orphan drugs. Budget impact was provided in absolute numbers and relative to total pharmaceutical spending.ResultsThe number of orphan drugs and patients treated increased substantially over the period studied. Overall, budget impact increased substantially over a period of six years, both in absolute terms (326% increase) as well as relative to total pharmaceutical spending (278% increase). Growth rates decreased over time. In 2012, 17% of available drugs had an individual budget impact of more than €10 million per year.ConclusionsIndividual budget impact of orphan drugs is often limited, although exceptions exist. However, in total, the budget impact of orphan drugs is considerable and has grown substantially over the years. This could potentially influence reimbursement decisions for orphan drugs in the future.

Systematic review of available evidence on 11 high-priced inpatient orphan drugs

BackgroundAttention for Evidence Based Medicine (EBM) is growing, but evidence for orphan drugs is argued to be limited and inferior. This study systematically reviews the available evidence on clinical effectiveness, cost-effectiveness and budget impact for orphan drugs.MethodsA systematic review was performed in PubMed, Embase, NHS EED and HTA databases for 11 inpatient orphan drugs listed on the Dutch policy rule on orphan drugs. For included studies, we determined the type of study and various study characteristics.ResultsA total of 338 studies met all inclusion criteria. Almost all studies (96%) focused on clinical effectiveness of the drug. Of these studies, most studies were case studies (41%) or observational studies (39%). However, for all orphan diseases at least one experimental or quasi-experimental study was found, and a randomized clinical trial was available for 60% of the orphan drugs. Eight studies described the cost-effectiveness of an orphan drug; an equal number described an orphan drug’s budget impact.ConclusionsDespite the often heard claim that RCTs are not feasible for orphan drugs, we found that an RCT was available in 60% of orphan drugs investigated. Cost-effectiveness and budget impact analyses for orphan drugs are seldom published.

Cost comparison of two implantable cardiac monitors in two different settings: Reveal XT in a catheterization laboratory vs. Reveal LINQ in a procedure room

AIMS Implantable cardiac monitors (ICMs) are used for long-term heart rhythm monitoring, e.g. to diagnose unexplained syncope or for detection of suspected atrial and ventricular arrhythmias. The newest ICM, Reveal LINQ™ (Medtronic Inc.), is miniaturized and inserted with a specific insertion tool kit. The procedure is therefore minimally invasive and can be moved from catheterization laboratory (cath lab) to a less resource intensive setting. This study aims to assess the change in procedure costs when performed outside the cath lab. METHODS AND RESULTS A bottom-up costing methodology was used. Data were collected from interviews with physicians, cath lab managers, and financial controllers. Hospitals in the Netherlands, France, and the UK were included in this study. The cost comparison of a Reveal XT implantation in a cath lab setting vs. a Reveal LINQ insertion outside a cath lab resulted in an estimated reduction of €662 for the UK, €682 for the Netherlands, and €781 for France. These cost savings were primarily realized through fewer staff, less equipment, and overhead costs. The net effect on savings depends on the price differential between these two technologies. The patient care pathway can be improved due to the possibility to move the procedure out of the cath lab. CONCLUSION Inserting the miniaturized version of the ICM is simpler and faster, and the procedure can take place outside the cath lab in a less resource intensive environment. Hospitals save resources when the higher price of the Reveal LINQ does not outweigh these savings.

A conceptual disease model for adult Pompe disease

BackgroundStudies in orphan diseases are, by nature, confronted with small patient populations, meaning that randomized controlled trials will have limited statistical power. In order to estimate the effectiveness of treatments in orphan diseases and extrapolate effects into the future, alternative models might be needed. The purpose of this study is to develop a conceptual disease model for Pompe disease in adults (an orphan disease). This conceptual model describes the associations between the most important levels of health concepts for Pompe disease in adults, from biological parameters via physiological parameters, symptoms and functional indicators to health perceptions and final health outcomes as measured in terms of health-related quality of life.MethodsThe structure of the Wilson-Cleary health outcomes model was used as a blueprint, and filled with clinically relevant aspects for Pompe disease based on literature and expert opinion. Multiple observations per patient from a Dutch cohort study in untreated patients were used to quantify the relationships between the different levels of health concepts in the model by means of regression analyses.ResultsEnzyme activity, muscle strength, respiratory function, fatigue, level of handicap, general health perceptions, mental and physical component scales and utility described the different levels of health concepts in the Wilson-Cleary model for Pompe disease. Regression analyses showed that functional status was affected by fatigue, muscle strength and respiratory function. Health perceptions were affected by handicap. In turn, self-reported quality of life was affected by health perceptions.ConclusionsWe conceptualized a disease model that incorporated the mechanisms believed to be responsible for impaired quality of life in Pompe disease. The model provides a comprehensive overview of various aspects of Pompe disease in adults, which can be useful for both clinicians and policymakers to support their multi-faceted decision making.

The search for relevant outcome measures for cost-utility analysis of systemic family interventions in adolescents with substance use disorder and delinquent behavior: a systematic literature review

PurposeSystemic family interventions have shown to be effective in adolescents with substance use disorder and delinquent behavior. The interventions target interactions between the adolescent and involved systems (i.e. youth, family, peers, neighbors, school, work, and society). Next to effectiveness considerations, economic aspects have gained attention. However, conventional generic quality of life measures used in health economic evaluations may not be able to capture the broad effects of systemic interventions. This study aims to identify existing outcome measures, which capture the broad effects of systemic family interventions, and allow use in a health economic framework.MethodsWe based our systematic review on clinical studies in the field. Our goal was to identify effectiveness studies of psychosocial interventions for adolescents with substance use disorder and delinquent behavior and to distill the instruments used in these studies to measure effects. Searched databases were PubMed, Education Resource Information Center (ERIC), Cochrane and Psychnet (PsycBOOKSc, PsycCRITIQUES, print). Identified instruments were ranked according to the number of systems covered (comprehensiveness). In addition, their use for health economic analyses was evaluated according to suitability characteristics such as brevity, accessibility, psychometric properties, etc.ResultsOne thousand three hundred seventy-eight articles were found and screened for eligibility. Eighty articles were selected, 8 instruments were identified covering 5 or more systems.ConclusionsThe systematic review identified instruments from the clinical field suitable to evaluate systemic family interventions in a health economic framework. None of them had preference-weights available. Hence, a next step could be to attach preference-weights to one of the identified instruments to allow health economic evaluations of systemic family interventions.