The iMTA Productivity Cost Questionnaire: A Standardized Instrument for Measuring and Valuing Health-Related Productivity Losses.

BACKGROUND: Productivity losses often contribute significantly to the total costs in economic evaluations adopting a societal perspective. Currently, no consensus exists on the measurement and valuation of productivity losses. OBJECTIVE: We aimed to develop a standardized instrument for measuring and valuing productivity losses. METHODS: A group of researchers with extensive experience in measuring and valuing productivity losses designed an instrument suitable for self-completion, building on preknowledge and evidence on validity. The instrument was designed to cover all domains of productivity losses, thus allowing quantification and valuation of all productivity losses. A feasibility study was performed to check the questionnaire's consistency and intelligibility. RESULTS: The iMTA Productivity Cost Questionnaire (iPCQ) includes three modules measuring productivity losses of paid work due to 1) absenteeism and 2) presenteeism and productivity losses related to 3) unpaid work. Questions for measuring absenteeism and presenteeism were derived from existing validated questionnaires. Because validated measures of losses of unpaid work are scarce, the questions of this module were newly developed. To enhance the instrument's feasibility, simple language was used. The feasibility study included 195 respondents (response rate 80%) older than 18 years. Seven percent (n = 13) identified problems while filling in the iPCQ, including problems with the questionnaire's instructions and routing (n = 6) and wording (n = 2). Five respondents experienced difficulties in estimating the time that would be needed for other people to make up for lost unpaid work. CONCLUSIONS: Most modules of the iPCQ are based on validated questions derived from previously available instruments. The instrument is understandable for most of the general public.

Ivacaftor for the treatment of patients with cystic fibrosis and the G551D mutation: a systematic review and cost-effectiveness analysis.

BACKGROUND: Ivacaftor (Kalydeco(®), Vertex Pharmaceuticals) is the first of a new class of drugs that target the underlying protein defect in cystic fibrosis (CF). It is aimed at patients with the G551D (glycine to aspartate change in nucleotide 1784 in exon 11) mutation; 5.7% of patients with CF in the UK have this mutation. OBJECTIVES: To review the clinical effectiveness and cost-effectiveness of ivacaftor for the treatment of CF in patients aged ≥ 6 years who have the G551D mutation. METHODS: Ten databases, including MEDLINE and EMBASE, were searched from inception to July 2012. Studies that evaluated ivacaftor for the treatment of adults and children (≥ 6 years) with at least one G551D mutation were eligible. There were insufficient data to conduct a formal meta-analysis. The manufacturer of ivacaftor, Vertex Pharmaceuticals, submitted a deterministic patient-level simulation model for the assessment of the lifetime cost-effectiveness of ivacaftor. We modified the model where values were not UK-specific or not recent, or where better estimates could be found. The only change to the model structure was the addition of lung transplantations. We changed utility values, annual decline in percentage predicted forced expiratory volume in 1 second (FEV1), and the baseline exacerbation rate, and used data from the CF Registry to estimate the relation between costs, age and percentage predicted FEV1. Estimates of treatment effect of ivacaftor came from the clinical effectiveness review. We modelled three scenarios for the longer-term effects of ivacaftor. We also modelled an 'optimistic' scenario for patients aged < 12 years with little lung damage. We conducted a budget impact analysis to estimate the total cost to the NHS of introducing ivacaftor in England. RESULTS: Three studies were included: a randomised controlled trial (RCT) in adults (n = 167) (≥ 12 years), a RCT in children (n = 26) (6-11 years), and an open-label extension study of the two RCTs. Both RCTs reported significantly greater changes from baseline in all measures of lung function in patients receiving ivacaftor than in those receiving placebo. The mean difference in change in percentage predicted FEV1 was 10.5 [95% confidence interval (CI) 8.5 to 12.5] percentage points in the adults' study and 10.0 (95% CI 4.5 to 15.5) percentage points in the children's study at 48 weeks. Improvements in lung function were seen across all subgroups investigated (age, sex, study region and lung function). There were significantly greater improvements in the ivacaftor group than in the placebo group for all outcomes assessed (exacerbations, quality of life, sweat chloride and weight) with the exception of quality of life in children. Improvements were maintained in the open-label trial. Adverse events were mainly minor and comparable across treatment groups. Both RCTs reported more withdrawals in the placebo group than in the ivacaftor group. The incremental cost-effectiveness ratio varied between £335,000 and £1,274,000 per quality-adjusted life-year gained. The total additional lifetime costs for all eligible CF patients in England ranged from £438M to £479M; the lifetime cost for standard care only was £72M. CONCLUSIONS: The available evidence suggests that ivacaftor is a clinically effective treatment for patients with CF and the G551D mutation; the high cost of ivacaftor may prove an obstacle in the uptake of this treatment. The main priority for further research is the long-term effectiveness of ivacaftor. STUDY REGISTRATION: This study is registered as PROSPERO CRD42012002516. SOURCE OF FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Determinants of health care use in chronic fatigue syndrome patients: a cross-sectional study.

BACKGROUND: Chronic fatigue syndrome (CFS) is associated with a high use of health care services. To reduce the related costs for patients and society, it will be useful to know which factors determine CFS patients' amount of health care use. Little is known, however, about these factors. METHOD: The present study retrospectively performed a cross-sectional analysis to investigate the possible factors determining CFS patients' health care use. A total of 263 CFS patients, derived from two subgroups (149 from tertiary care and 114 from primary/secondary care), participated. Health care use was measured with a questionnaire asking details on consumption over the past 6 months. Fatigue severity and physical functioning were measured with the subscale Experienced Fatigue of the Checklist Individual Strength (CIS-20) and the subscale Physical Functioning of the SF-36, respectively. Multiple regression analysis, T-tests, and chi(2) tests were performed. RESULTS: The regression analysis revealed that, after controlling for patient characteristics (explaining 13%), fatigue factors added 4% predictive value and certain perpetuating factors of fatigue, including focus on bodily symptoms and attributions of fatigue, added another 5%. The analysis of subgroups revealed that, compared to the tertiary care population, fewer patients from primary/secondary care had visited a medical specialist (50% vs. 71%), used antidepressants (16% vs. 25%) and tranquilizers (3% vs. 18%), and had spent a night in hospital (7% vs. 10%). However, overall costs of health care between these subgroups did not differ. CONCLUSIONS: This study showed that illness duration, physical impairment due to fatigue, and psychological perpetuating factors of fatigue do determine the variance in CFS patients' health care use. These results give clear directions for treating CFS patients and managing health care for CFS.

Cost-utility of a disease management program for patients with asthma.

OBJECTIVES: The long-term cost-utility of a disease management program (DMP) for adults with asthma was assessed compared to usual care. METHODS: A DMP for patients with asthma has been developed and implemented in the region of Maastricht (The Netherlands). By integrating care, the program aims to continuously improve quality of care within existing budgets. A clinical trial was performed over a period of 15 months to collect data on costs and effects of the program and usual care. These data were used to inform a probabilistic decision-analytic model to estimate the 5-year impact of the program beyond follow-up. A societal perspective was adopted, with outcomes assessed in terms of costs per quality-adjusted life-year (QALY). RESULTS: The DMP is associated with a gain in QALYs compared to usual care (2.7+/-.2 versus 3.4+/-.8), at lower costs (3,302+/-314 euro versus 2,973+/-304 euro), thus leading to dominance. The probability that disease management is the more cost-effective strategy is 76 percent at a societal willingness to pay (WTP) for an additional QALY of 0 euro, reaching 95 percent probability at a WTP of 1,000 euro per additional QALY. CONCLUSIONS: Organizing health care according to the principles of disease management for adults with asthma has a high probability of being cost-effective and is associated with a gain in QALYs at lower costs.

A cost-effectiveness decision model for antiepileptic drug treatment in newly diagnosed epilepsy patients.

OBJECTIVE: To establish cost-effectiveness of antiepileptic drug (AED) treatment strategies of newly diagnosed patients with epilepsy. METHODS: A decision analysis was carried out comparing effectiveness and treatment cost of six treatment strategies comprising carbamazepine (CBZ), lamotrigine (LTG), and valproate (VPA) as first-line and second-line drugs. Three outcome groups were defined: complete success, partial success, and failure. Data on seizure control and failure due to adverse effects were derived from the literature. Data on resource use and costs were collected for each outcome group by means of a patient survey. RESULTS: Cost data were obtained from 71 patients. Cost increased from complete success to failure outcome groups. The probability of obtaining complete success varied from 64% (VPA-CBZ strategy) to 74% (LTG-VPA strategy). The strategy LTG-VPA was more effective than the least expensive strategy CBZ-VPA, but at higher costs per additional effectively treated patient. Probabilistic sensitivity analysis confirmed these findings to be robust. Subsequent analysis showed that changing inclusion criteria used in the selection of the studies from the literature had a major effect on cost-effectiveness ratios of the various strategies. The probability that LTG first-line therapy is the most cost-effective option remains small, even defining a high cost-effectiveness threshold. Nevertheless, LTG second-line strategies can be cost-effective depending on the willingness to pay for patient improvement. CONCLUSIONS: Only a few studies satisfied our inclusion criteria for employment in our decision model. Our model supports the use of conventional AEDs as first-line options for patients with newly diagnosed epilepsy. LTG second-line therapy is likely to be the most cost-effective option in case society is willing to pay more than Euro 6000 for an additional successfully treated patient. This study also illustrates that, with the data presently available, the outcome of decision analysis for AED treatment choice depends on the inclusion criteria used to select trials. Prospective real-life studies are needed in which first- and second-line treatment strategies are compared with respect to both effectiveness and costs.

Are we measuring what matters in health technology assessment of disease management? Systematic literature review.

OBJECTIVES: An overview was produced of indicators currently used to assess disease management programs and, based on these findings, provide a framework regarding sets of indicators that should be used when taking the aims and types of disease management programs into account. METHODS: A systematic literature review was performed. RESULTS: Thirty-six studies met the inclusion criteria. It appeared that a link between aims of disease management and evaluated structure, process, as well as outcome indicators does not exist in a substantial part of published studies on disease management of diabetes and asthma/chronic obstructive pulmonary disease, especially when efficiency of care is concerned. Furthermore, structure indicators are largely missing from the evaluations, although these are of major importance for the interpretation of outcomes for purposes of decision-making. Efficiency of disease management is mainly evaluated by means of process indicators; the use of outcome indicators is less common. Within a framework, structure, process, and outcome indicators for effectiveness and efficiency are recommended for each type of disease management program. CONCLUSIONS: The link between aims of disease management and evaluated structure, process, and outcome indicators does not exist in a substantial part of published studies on disease management. The added value of this study mainly lies in the development of a framework to guide the choice of indicators for health technology assessment of disease management.

Measuring productivity changes in economic evaluation: setting the research agenda.

Productivity costs related to illness may be relevant in assessing healthcare programmes for patients, as well as occupational interventions for workers. When performing an economic evaluation for both types of programmes, a sound methodology for measuring and valuing these productivity costs is essential. This article reviews research questions related to productivity and health, focusing on the costs of short-term absence from work, productivity costs without absence ('presenteeism') and possible compensation mechanisms and circumstances that may affect productivity costs. Furthermore, the important but under-explored relationship between productivity and QOL is analysed. Strategies for better answers on these research questions, such as developing more valid measurement instruments, are discussed. It is stressed that the analysis of productivity costs should not be restricted to the level of the individual patient and worker but extended to the level of teams of workers and firms. It may be advisable to explore several issues such as compensation mechanisms and efficiency losses in detail using employee questionnaires and consecutively applying the key elements in patient settings. It seems advisable to develop flexible, modular instruments for measuring and valuing absence from work, compensation mechanisms, efficiency loss and details of jobs and organisation in an integrative and consistent way. Further, it seems crucial to identify what determinants of jobs and organisations are the key factors in estimating productivity costs. This list of determinants could be mapped with a classification of jobs, to be used as a screener in patient questionnaires.

Pre-assessment to assess the match between cost-effectiveness results and decision makers' information needs: an illustration using two cases in rehabilitation medicine in The Netherlands.

OBJECTIVE: To determine if a pre-assessment can be used to establish whether cost-effectiveness results would meet the actual information needs of Dutch healthcare decision makers. METHODS: Two recent studies in rehabilitation medicine served as study material. Based on Wholey, a limited pre-assessment was performed in which the potential impact of cost-effectiveness analysis (CEA) results on intended users' decision making was assessed. Desk research and semi-structured interviews with several intended users of CEA results were performed. These included general practitioners, representatives of health insurance companies, the Health Care Insurance Board (CvZ), and medical guidelines committees. RESULTS: In day-to-day decision making of the interviewed decision makers, a cost-effectiveness criterion seemed to be of limited importance. Instead, results from clinical effectiveness studies and budget impact studies appeared to be sufficient. CvZ, however, preferred relative cost-effectiveness to be a criterion for inclusion in future reimbursement guidelines. In both cases the limited pre-assessments changed the expectations of the investigators regarding decision-making impact of an economic evaluation. CONCLUSION: This study revealed that the use of CEA results for Dutch micro- and meso-level healthcare decision making is not self-evident. The main purpose of CEA results is to support health policy making and planning at a macroeconomic level. Pre-assessment can be a valuable tool in designing a CEA to support the actual information needs of the decision makers.