Adverse drug events in cost-effectiveness analyses of interventions for diabetic conditions: a scoping review protocol.

OBJECTIVE: The objective of this review is to provide an overview of adverse drug events in cost-effectiveness analyses related to the pharmacological treatments of diabetes and diabetes-related complications. INTRODUCTION: The inclusion of adverse drug events in cost-effectiveness analyses is recognized in health technology assessments guidelines, but in practice, this is inconsistent. This inconsistency may affect the reliability of the evaluation and, therefore, indicate that the information provided for decision-making in health care is misleading. Reviewing if and how adverse drug events are incorporated in cost-effectiveness analyses is necessary to address this gap. INCLUSION CRITERIA: Studies including participants who are receiving pharmacological interventions for diabetes, diabetic retinopathy, or diabetic macular edema will be considered for inclusion. We will include sources that focus on cost-effectiveness analyses using modeling framework, and are published in English between 2011 and the present. Other types of analyses and other types of conditions will be excluded. METHODS: The information sources to be searched include MEDLINE, CINAHL, Scopus, Web of Science, the NHS Economic Evaluations Database, and the Health Technology Assessment Database. Studies in English will be considered for inclusion in the review. Potential sources will be assessed by 2 independent reviewers and imported into the JBI System for the Unified Management, Assessment and Review of Information. The results of the search and the study inclusion process will be reported in a Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram. A specific data extraction form will be used to extract and analyze the data. Results will be presented in tabular and graphic formats with a narrative summary, and will be discussed in the context of current literature and guidelines.

Cost-effectiveness of an educational intervention to reduce potentially inappropriate medication.

BACKGROUND: Educational interventions can reduce potentially inappropriate medication (PIM) use in older people. Their effectiveness has been measured mainly as changes in PIM use. In this economic evaluation, we analyse the impact of an educational intervention in terms of costs and quality-adjusted life years (QALYs). METHODS: The educational intervention consisted of activating and interactive training sessions for nursing staff and consulting physicians, and was compared with treatment as usual (TAU). Participants (n = 227) in a cluster randomised trial (cRCT) were residents living permanently in assisted living facilities (n = 20 wards). For economic evaluation, participants' healthcare service use costs and costs for the intervention were estimated for a 12 month period.Incremental cost-effectiveness ratios (ICERs) were estimated for QALYs per participant. Cost-effectiveness analysis was conducted from a healthcare perspective. A bootstrapped cost-effectiveness plane and one-way sensitivity analysis were undertaken to analyse the uncertainty surrounding the estimates. RESULTS: The educational intervention was estimated to be less costly and less effective in terms of QALYs than TAU at the 12 month follow-up [incremental costs -€1,629, confidence interval (CI) -€5,489 to €2,240; incremental effect -0.02, CI -0.06 to 0.02]. The base case ICER was >€80,000/QALY. CONCLUSION: The educational intervention was estimated to be less costly and less effective in terms of QALYs compared with TAU, but the results are subject to some uncertainties. Reduction in PIM use or benefits in quality of life did not seem to translate into improvements in QALYs. Our findings emphasise the need for better understanding of the impact of decreasing PIM use on health outcomes.

The long-term cost of childhood conduct problems: Finnish Nationwide 1981 Birth Cohort Study.

BACKGROUND: Commonly recognized childhood conduct problems often lead to costly problems in adulthood. This study aimed to evaluate the long-term cumulative cost of childhood conduct problems until the age of 30. The costs included inpatient care, nervous system medicine purchases, and criminal offences. METHODS: The study used population-based nationwide 1981 birth cohort data. Families and teachers assessed the conduct problems of the eight-year-olds based on Rutter questionnaires. We grouped 5,011 children into low-level of conduct problems (52%), intermediate-level of conduct problems (37%), and high-level of conduct problems (11%) groups, based on combined conduct symptoms scores. The analysis included the cohort data with the Care Register for Health Care, the Drug Prescription Register, and the Finnish Police Register. The cost valuation of service use applied national unit costs in 2016 prices. We used Wilcoxon rank-sum test to test the differences between groups and gender. RESULTS: During 1989-2011, average cumulative costs of the high-level (€44,348, p < .001) and the intermediate-level (€19,405, p < .001) of conduct problems groups were higher than the low-level of conduct problems group's (€10,547) costs. In all three groups, the boys' costs were higher than girls' costs. CONCLUSIONS: The costs associated with conduct problems in childhood are substantial, showing a clear need for cost-effective interventions. Implementation decisions of interventions benefit from long-term cost-effectiveness modelling studies. Costing studies, like this, provide cost and cost offset information for modelling studies.

Cost-effectiveness of physical activity intervention in children - results based on the Physical Activity and Nutrition in Children (PANIC) study.

BACKGROUND: We assessed the cost-effectiveness of a 2-year physical activity (PA) intervention combining family-based PA counselling and after-school exercise clubs in primary-school children compared to no intervention from an extended service payer's perspective. METHODS: The participants included 506 children (245 girls, 261 boys) allocated to an intervention group (306 children, 60 %) and a control group (200 children, 40 %). The children and their parents in the intervention group had six PA counselling visits, and the children also had the opportunity to participate in after-school exercise clubs. The control group received verbal and written advice on health-improving PA at baseline. A change in total PA over two years was used as the outcome measure. Intervention costs included those related to the family-based PA counselling, the after-school exercise clubs, and the parents' taking time off to travel to and participate in the counselling. The cost-effectiveness analyses were performed using the intention-to-treat principle. The costs per increased PA hour (incremental cost-effectiveness ratio, ICER) were based on net monetary benefit (NMB) regression adjusted for baseline PA and background variables. The results are presented with NMB and cost-effectiveness acceptability curves. RESULTS: Over two years, total PA increased on average by 108 h in the intervention group (95 % confidence interval [CI] from 95 to 121, p < 0.001) and decreased by 65.5 h (95 % CI from 81.7 to 48.3, p < 0.001) in the control group, the difference being 173.7 h. the incremental effectiveness was 87 (173/2) hours. For two years, the intervention costs were €619 without parents' time use costs and €860 with these costs. The costs per increased PA hour were €6.21 without and €8.62 with these costs. The willingness to pay required for 95 % probability of cost-effectiveness was €14 and €19 with these costs. The sensitivity analyses revealed that the ICER without assuming this linear change in PA were €3.10 and €4.31. CONCLUSIONS: The PA intervention would be cost-effective compared to no intervention among children if the service payer's willingness-to-pay for a 1-hour increase in PA is €8.62 with parents' time costs. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01803776. Registered 4 March 2013 - Retrospectively registered, https://clinicaltrials.gov/ct2/results?cond=&term=01803776&cntry=&state=&city=&dist= .

Cost-effectiveness of dexamethasone and triamcinolone for the treatment of diabetic macular oedema in Finland: A Markov-model.

PURPOSE: Diabetic macular oedema (DMO), a complication of diabetes, causes vision loss and blindness. Corticosteroids are usually used as a second-line treatment. The aim of this study was to analyse the cost-effectiveness of dexamethasone implants compared to cheaper and more frequently applied triamcinolone injections. METHODS: Markov-modelling, which incorporated both eyes, was used for economic evaluation. The model consisted of five health states based on visual acuity, illustrating the progression of DMO. A cycle length of five months was chosen for dexamethasone and four months for triamcinolone. Time horizons of two and five years were applied. Transition probabilities and health state utilities were sourced from previous studies. The perspective used in this analysis was the hospital perspective. The health care costs were acquired from Kuopio University Hospital in Finland. RESULTS: In this cost-effectiveness analysis, the incremental cost-effectiveness ratio ICER with 3% discount rate was €56 591/QALY for a two-year follow-up and -€1 110 942/QALY for a five-year follow-up. In order to consider dexamethasone as cost-effective over a 2-year time horizon, the WTP needs to be around €55 000/QALY. Over the five-year follow-up, triamcinolone is clearly a dominant treatment. Sensitivity analyses support the cost-effectiveness of dexamethasone over a 2-year time horizon. CONCLUSIONS: Since the sensitivity analyses support the results, dexamethasone would be a cost-effective treatment during the first two years with WTP threshold around €55 000/QALY, and triamcinolone would be a convenient treatment after that. This recommendation is in line with the guidelines of EURETINA.

Self-certification versus physician certification of sick leave for reducing sickness absence and associated costs.

BACKGROUND: From the societal and employers' perspectives, sickness absence has a large economic impact. Internationally, there is variation in sickness certification practices. However, in most countries a physician's certificate of illness or reduced work ability is needed at some point of sickness absence. In many countries, there is a time period of varying length called the 'self-certification period' at the beginning of sickness absence. During that time a worker is not obliged to provide his or her employer a medical certificate and it is usually enough that the employee notifies his or her supervisor when taken ill. Self-certification can be introduced at organisational, regional, or national level. OBJECTIVES: To evaluate the effects of introducing, abolishing, or changing the period of self-certification of sickness absence on: the total or average duration (number of sickness absence days) of short-term sickness absence periods; the frequency of short-term sickness absence periods; the associated costs (of sickness absence and (occupational) health care); and social climate, supervisor involvement, and workload or presenteeism (see Figure 1). SEARCH METHODS: We conducted a systematic literature search to identify all potentially eligible published and unpublished studies. We adapted the search strategy developed for MEDLINE for use in the other electronic databases. We also searched for unpublished trials on ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP). We used Google Scholar for exploratory searches. SELECTION CRITERIA: We considered randomised controlled trials (RCTs), controlled before-after (CBA) studies, and interrupted time-series (ITS) studies for inclusion. We included studies carried out with individual employees or insured workers. We also included studies in which participants were addressed at the aggregate level of organisations, companies, municipalities, healthcare settings, or general populations. We included studies evaluating the effects of introducing, abolishing, or changing the period of self-certification of sickness absence. DATA COLLECTION AND ANALYSIS: We conducted a systematic literature search up to 14 June 2018. We calculated missing data from other data reported by the authors. We intended to perform a random-effects meta-analysis, but the studies were too different to enable meta-analysis. MAIN RESULTS: We screened 6091 records for inclusion. Five studies fulfilled our inclusion criteria: one is an RCT and four are CBA studies. One study from Sweden changed the period of self-certification in 1985 in two districts for all insured inhabitants. Three studies from Norway conducted between 2001 and 2014 changed the period of self-certification in municipalities for all or part of the workers. One study from 1969 introduced self-certification for all manual workers of an oil refinery in the UK.Longer compared to shorter self-certificationfor reducing sickness absence in workersOutcome: average duration of sickness absence periodsExtending the period of self-certification from one week to two weeks produced a higher mean duration of sickness absence periods: mean difference in change values between the intervention and control group (MDchange) was 0.67 days/period up to 29 days (95% confidence interval (95% CI) 0.55 to 0.79; 1 RCT; low-certainty evidence).The introduction of self-certification for a maximum of three days produced a lower mean duration of sickness absence up to three days (MDchange -0.32 days/period, 95% CI -0.39 to -0.25; 1 CBA study; very low-certainty evidence). The authors of a different study reported that prolonging self-certification from ≤ 3 days to ≤ 365 days did not lead to a change, but they did not provide numerical data (very low-certainty evidence). OUTCOME: number of sickness absence periods per workerExtending the period of self-certification from one week to two weeks resulted in no difference in the number of sickness absence periods in one RCT, but the authors did not report numerical data (low-certainty evidence).The introduction of self-certification for a maximum of three days produced a higher mean number of sickness absence periods lasting up to three days (MDchange 0.48 periods, 95% CI 0.33 to 0.63) in one CBA study (very low-certainty evidence).Extending the period of self-certification from three days to up to a year decreased the number of periods in one CBA study, but the authors did not report data (very low-certainty evidence). OUTCOME: average lost work time per 100 person-yearsExtending the period of self-certification from one week to two weeks resulted in an inferred increase in lost work time in one RCT (very low-certainty evidence).Extending the period of self-certification (introduction of self-certification for a maximum of three days (from zero to three days) and from three days to five days, respectively) resulted in more work time lost due to sickness absence periods lasting up to three days in two CBA studies that could not be pooled (MDchange 0.54 days/person-year, 95% CI 0.47 to 0.61; and MDchange 1.38 days/person-year, 95% CI 1.16 to 1.60; very low-certainty evidence).Extending the period of self-certification from three days up to 50 days led to 0.65 days less lost work time in one CBA study, based on absence periods lasting between four and 16 days. Extending the period of self-certification from three days up to 365 days resulted in less work time lost due to sickness absence periods longer than 16 days (MDchange -2.84 days, 95% CI -3.35 to -2.33; 1 CBA study; very low-certainty evidence). OUTCOME: costs of sickness absence and physician certificationOne RCT reported that the higher costs of sickness absence benefits incurred by extending the period of self-certification far outweighed the possible reduction in costs of fewer physician appointments by almost six to one (low-certainty evidence).In summary, we found very low-certainty evidence that introducing self-certification of sickness absence or prolonging the self-certification period has inconsistent effects on the mean number of sickness absence days, the number of sickness absence periods, and on lost work time due to sickness absence periods. AUTHORS' CONCLUSIONS: There is low- to very low-certainty evidence of inconsistent effects of changing the period of self-certification on the duration or frequency of short-term sickness absence periods or the amount of work time lost due to sickness absence. Because the evidence is of low or very low certainty, more and better studies are needed.

Cost-effectiveness of treating wet age-related macular degeneration at the Kuopio University Hospital in Finland based on a two-eye Markov transition model.

PURPOSE: Wet age-related macular degeneration (AMD) is the leading cause of blindness worldwide, which can be treated with regular intraocular anti-vascular endothelial growth factor (VEGF) injections. In this study, we wanted to evaluate whether less frequent injections of aflibercept would make it more cost-effective when compared with ranibizumab and low priced bevacizumab. METHODS: We used a two-eye model to simulate the progression and the treatment of the disease. We selected an 8-year period, 3-month cycles and five health states based on the visual acuity of the better-seeing eye. The transition probabilities and utilities attached to the health states were gathered from previous studies. We conducted the analysis from the hospital perspective and we used the health care costs obtained from Kuopio University Hospital. The costs of intraocular adverse events were taken into account. RESULTS: The incremental cost-effectiveness ratio (ICER) with 3% discount rate (€/QALY) for aflibercept compared with monthly bevacizumab was 1 801 228 and when compared with ranibizumab given as needed, the ICER was minus 3 716 943. The sensitivity analysis showed that a change of 20% of the estimated model parameters or a longer follow-up period did not influence these conclusions. CONCLUSION: A two-eye Markov transition model was developed to analyse the cost-effectiveness of wet AMD treatment, as quality of life years (QALYs) are largely based on the visual acuity of the better-seeing eye. Monthly injected bevacizumab was the most cost-effective treatment and monthly ranibizumab the least effective.

Cost-effectiveness of population-level physical activity interventions: a systematic review.

OBJECTIVE: This systematic review synthesizes the evidence on the cost-effectiveness of population-level interventions to promote physical activity. DATA SOURCE: A systematic literature search was conducted between May and August 2013 in four databases: PubMed, Scopus, Web of Science, and SPORTDiscus. STUDY INCLUSION AND EXCLUSION CRITERIA: Only primary and preventive interventions aimed at promoting and maintaining physical activity in wide population groups were included. An economic evaluation of both effectiveness and cost was required. Secondary interventions and interventions targeting selected population groups or focusing on single individuals were excluded. DATA EXTRACTION: Interventions were searched for in six different categories: (1) environment, (2) built environment, (3) sports clubs and enhanced access, (4) schools, (5) mass media and community-based, and (6) workplace. DATA SYNTHESIS: The systematic search yielded 2058 articles, of which 10 articles met the selection criteria. The costs of interventions were converted to costs per person per day in 2012 U.S. dollars. The physical activity results were calculated as metabolic equivalent of task hours (MET-hours, or MET-h) gained per person per day. Cost-effectiveness ratios were presented as dollars per MET-hours gained. The intervention scale and the budget impact of interventions were taken into account. RESULTS: The most efficient interventions to increase physical activity were community rail-trails ($.006/MET-h), pedometers ($.014/MET-h), and school health education programs ($.056/MET-h). CONCLUSION: Improving opportunities for walking and biking seems to increase physical activity cost-effectively. However, it is necessary to be careful in generalizing the results because of the small number of studies. This review provides important information for decision makers.

Market competition, ownership, payment systems and the performance of health care providers - a panel study among Finnish occupational health services providers.

Many health care reforms rely on competition although health care differs in many respects from the assumptions of perfect competition. Finnish occupational health services provide an opportunity to study empirically competition, ownership and payment systems and the performance of providers. In these markets employers (purchasers) choose the provider and prices are market determined. The price regulation of public providers was abolished in 1995. We had data on providers from 1992, 1995, 1997, 2000 and 2004. The unbalanced panel consisted of 1145 providers and 4059 observations. Our results show that in more competitive markets providers in general offered a higher share of medical care compared to preventive services. The association between unit prices and revenues and market environment varied according to the provider type. For-profit providers had lower prices and revenues in markets with numerous providers. The public providers in more competitive regions were more sensitive to react to the abolishment of their price regulation by raising their prices. Employer governed providers had weaker association between unit prices or revenues and competition. The market share of for-profit providers was negatively associated with productivity, which was the only sign of market spillovers we found in our study.

Public health care providers and market competition: the case of Finnish occupational health services.

BACKGROUND: As reforms in publicly funded health systems rely heavily on competition, it is important to know if and how public providers react to competition. In many European countries, it is empirically difficult to study public providers in different markets, but in Finnish occupational health services, both public and private for-profit and non-profit providers co-exist. We studied possible differences in public providers' performance (price, intensity of services, service mix-curative medical services/prevention, productivity and revenues) according to the competitiveness of the market. MATERIALS AND METHODS: The Finnish Institute of Occupational Health (FIOH) collected data on clients, services and personnel for 1992, 1995, 1997, 2000 and 2004 from occupational health services (OHS) providers. Employers defray the costs of OHS and apply for reimbursement from the Social Insurance Institution (SII). The SII data was merged with FIOH's questionnaire. The unbalanced panel consisted of about 230 public providers, totalling 1,164 observations. Local markets were constructed from several municipalities based on commuting practices and regional collaboration. Competitiveness of the market was measured by the number of providers and by the Herfindahl index. The effect of competition was studied by ordinary least square regression analysis and panel models. RESULTS: The more competitive the environment was for a public provider the higher were intensity, productivity and the share of medical care. Fixed panel models showed that these differences were not due to differences and changes in the competitiveness of the market. Instead, in more competitive markets public providers had higher unit prices and higher revenues.

Economic incentives as a policy tool to promote safety and health at work.

Incentives are regarded as a promising policy tool for promoting occupational safety and health (OSH). This article discusses the potential of different kinds of incentives in light of economic theory and evidence from research. When incentives are used as a policy tool, it implies the existance of an institution that has both the interest and the power to apply incentives to stakeholders, usually to employers. Governments can subsidize employers' investments in OSH with subsidies and tax structures. These incentives are successful only if the demand for OSH responds to the change in the price of OSH investments and if the suppliers of OSH are able to increase their production smoothly. Otherwise, the subsidy will only lead to higher prices for OSH goods. Both public and private insurance companies can differentiate insurance premiums according to claim behavior in the past (experience rating). There is evidence that this can effectively lower the frequency of claims, but not the severity of cases. This papers concludes that incentives do not directly lead to improvement. When incentives are introduced, their objective(s) should be clear and the end result (ie what the incentive aims to promote) should be known to be effective in achieving healthy and safe workplaces.

Transferring results of occupational safety and health cost-effectiveness studies from one country to another - a case study.

OBJECTIVES: There are a limited number of studies about the cost-effectiveness of occupational health and safety (OSH) interventions. Applying the results of a cost-effectiveness study from one country to another is hampered by differences in the organization of healthcare and social security. In order to find out how these problems can be overcome, we transferred the results of a Dutch occupational cost-effectiveness study to the Finnish situation and vice-versa. METHODS: We recalculated incremental cost-effectiveness ratios (ICER) for the target country based on resource use in the original study and the associated costs in the target country. We also allocated the costs to the employer, the employee, and tax-payers. RESULTS: We found that the ICER did not differ very much from those in the original studies. However, the different healthcare funding structure led to a more unfavorable ICER for employers in the Netherlands. Both interventions represented a cost saving for tax-payers and employees. Employers had to invest euro10-54 to avert one day of sick leave. CONCLUSIONS: We conclude that results of cost-effectiveness studies can be transferred from one country to another, but many adjustments are needed. An extensive description of the intervention, a detailed list of resource use, allocation of costs to various parties, and detailed knowledge of the healthcare systems in the original studies are necessary to enable calculations.

A systematic review of occupational safety and health business cases.

OBJECTIVE: Business cases are commonly developed as means to rationalize investment. We systematically reviewed 26 reported cases on occupational safety and health (OSH) interventions to assess if health and productivity arguments make a good business case. METHODS: To be included in the review, studies had to analyze the costs and benefits, including productivity, of an OSH intervention at the enterprise level. We searched Medline and Embase for studies and used Google search in addition. Two reviewers independently selected studies and extracted data. The intervention profitability was calculated in euros (euro in 2008) as the first year's benefits minus the total intervention costs per worker. The payback period was calculated as the intervention costs divided by the first year's benefits. RESULTS: We found three ex-ante and 23 ex-post cases. In 20 cases, the study design was a before-after comparison without a control group. Generally a 100% reduction of injuries or sickness absence was assumed. In two cases, productivity and quality increases were very large. The main benefit was avoided sick leave. Depreciation or discounting was applied only in a minority of cases. The intervention profitability was negative in seven studies, up to euro 500 per employee in 12 studies and more than euro 500 per employee in seven studies. The payback period was less than half a year for 19 studies. Only a few studies included sensitivity analyses. CONCLUSIONS: Few ex-ante business cases for management decisions on OSH are reported. Guidelines for reporting and evaluation are needed. Business cases need more sound assumptions on the effectiveness of interventions and should incorporate greater uncertainty into their design. Ex-post evaluation should be based preferably on study designs that control for trends at a time different from that of the intervention.

Does the company's economic performance affect access to occupational health services?

BACKGROUND: In Finland like in many other countries, employers are legally obliged to organize occupational health services (OHS) for their employees. Because employers bear the costs of OHS it could be that in spite of the legal requirement OHS expenditure is more determined by economic performance of the company than by law. Therefore, we explored whether economic performance was associated with the companies' expenditure on occupational health services. METHODS: We used a prospective design to predict expenditure on OHS in 2001 by a company's economic performance in 1999. Data were provided by Statistics Finland and expressed by key indicators for profitability, solidity and liquidity and by the Social Insurance Institution as employers' reimbursement applications for OHS costs. The data could be linked at the company level. Regression analysis was used to study associations adjusted for various confounders. RESULTS: Nineteen percent of the companies (N = 6 155) did not apply for reimbursement of OHS costs in 2001. The profitability of the company represented by operating margin in 1999 and adjusted for type of industry was not significantly related to the company's probability to apply for reimbursement of the costs in 2001 (OR = 1.00, 95%CI: 0.99 to 1.01). Profitability measured as operating profit in 1999 and adjusted for type of industry was not significantly related to costs for curative medical services (Beta -0.001, 95%CI: -0.00 to 0.11) nor to OHS cost of prevention in 2001 (Beta -0.001, 95%CI: -0.00 to 0.00). CONCLUSION: We did not find a relation between the company's economic performance and expenditure on OHS in Finland. We suppose that this is due to legislation obliging employers to provide OHS and the reimbursement system both being strong incentives for employers.

Promoting prevention with economic arguments - the case of Finnish occupational health services.

BACKGROUND: Both social and ethical arguments have been used to support preventive occupational health services (OHS). During the 1990s it became more common to support political argumentation for occupational health and safety by converting the consequences of ill health at work into monetary units. In addition, OHS has been promoted as a profitable investment for companies, and this aspect has been used by OHS providers in their marketing. Our intention was to study whether preventive occupational health services positively influence a company's economic performance. METHODS: We combined the financial statements provided by Statistics Finland and employers' reimbursement applications for occupational health services (OHS) costs to the Social Insurance Institution. The data covered the years 1997, 1999 and 2001 and over 6000 companies. We applied linear regression analysis to assess whether preventive OHS had a positive influence on the companies' economic performance after two or four years. RESULTS: Resources invested in preventive OHS were not positively related to a company's economic performance. In fact, the total cost of preventive OHS per turnover was negatively correlated to economic performance. CONCLUSION: Even if OHS has no effect on the economic performance of companies, it may have other effects more specific to OHS. Therefore, we recommend that the evaluation of prevention in OHS should move towards outcome measures, such as sickness absence, disability pension and productivity, when applicable, both in occupational health service research and in practice at workplaces.