Impact of a telemonitoring intervention in patients with chronic heart failure in Germany: A difference-in-difference matching approach using real-world data.

INTRODUCTION: The aim of this study was to evaluate the effects of a non-invasive telemonitoring intervention on mortality, healthcare costs, and hospital and pharmaceutical utilisation in patients with chronic heart failure (CHF) of a large statutory health insurer in Germany. METHODS: In a retrospective observational cohort study using real-world data, we assessed differences between 635 patients who received a telemonitoring intervention versus 635 receiving usual care covering 36 months after intervention. We used propensity score matching on a set of 102 parameters collected in the 24-month pre-intervention period to correct for observed differences, as well as difference-in-difference (DiD) estimators to account for unobserved differences. We analysed the effect of the intervention for up to three years on (i) all-cause mortality; (ii) costs (i.e. inpatient stays, ambulatory care, pharmaceuticals, and medical aids and appliances); and (iii) healthcare utilisation (i.e. length and number of hospital stays, number of prescriptions). RESULTS: DiD estimates suggest lower inpatient costs of the telemonitoring group of up to €1160 (95% confidence interval (CI): -2253 to -69) in year three. Ambulatory care costs increased significantly in all three years up to €316 (95% CI: 1267 to 505) per year. Telemonitoring had a positive effect on survival (hazard ratio = 0.71; 95% CI: 0.51 to 0.99) and increased the number of prescriptions for diuretics. Effects were more prominent for patients with severe CHF. DISCUSSION: The study suggests that the telemonitoring intervention led to a significant decrease in mortality and a shift in costs from the inpatient to the ambulatory care sector 36 months after intervention.

Spillover effects and other determinants of medical device uptake in the presence of a medical guideline: An analysis of drug-eluting stents in Germany and Italy.

We investigated the role of spillover effects among hospitals in the diffusion of drug-eluting stents (DES) in Germany and Italy during a period in which the relevant medical guideline clearly recommended their use over bare-metal stents. We used administrative data of hospitalized patients treated with ST-elevation myocardial infarction from 2012 to 2016 to estimate spatial panel models allowing for global spillover effects. We used an inverse-distance weights matrix to capture the geographical proximity between neighboring hospitals and assigned a lower weight to more distant neighbors. For both countries, we found significant positive spatial autocorrelation in most years based on the global Moran's I test, and a significant, positive spatial lag parameter across model specifications, indicating positive spillover effects among neighboring hospitals. We found that private for-profit hospital ownership and hospital competition in Germany and the number of inpatient cases with circulatory system diseases in Italy were other significant determinants of DES adoption. Our results underline the importance of spillover effects among peers for the diffusion of medical devices even in the presence of a positive guideline recommendation. Policymakers might therefore consider promoting various forms of exchange and collaboration among medical staff and hospitals to ensure the appropriate use of medical technologies.

Variation in the utilization of medical devices across Germany, Italy, and the Netherlands: A multilevel approach.

Variation in healthcare utilization has been discussed extensively, with many studies showing that variation exists, but fewer studies investigating the underlying factors. In our study, we used a logistic multilevel-model at the patient, hospital, and regional levels to investigate (i) the levels to which variation could be attributed and (ii) the hospital and regional factors associated with treatment decisions. To do so, we used hospital discharge records for the years 2012-2016 in Germany and Italy and for 2014-2016 in the Netherlands combined with hospital and regional characteristics in nine case studies. We used a theoretical framework to categorize these case studies into effective, preference-sensitive, and supply-sensitive care. Our results suggest that most variation in the treatment decision can be attributed to the hospital level (e.g., case volume), whereas only a minor part is explained by regional characteristics. Italy had the highest share attributable to the regional level, whereas the Netherlands had the lowest. We observed less variation for procedures in the effective-care category compared to the preference- and supply-sensitive categories. Although our results were heterogeneous, we identified patterns in line with the theoretical framework for treatment categories, underlining the need to address variation differently depending on the category in question.

Validity of Surrogate Endpoints and Their Impact on Coverage Recommendations: A Retrospective Analysis across International Health Technology Assessment Agencies.

BACKGROUND: Surrogate endpoints (i.e., intermediate endpoints intended to predict for patient-centered outcomes) are increasingly common. However, little is known about how surrogate evidence is handled in the context of health technology assessment (HTA). OBJECTIVES: 1) To map methodologies for the validation of surrogate endpoints and 2) to determine their impact on acceptability of surrogates and coverage decisions made by HTA agencies. METHODS: We sought HTA reports where evaluation relied on a surrogate from 8 HTA agencies. We extracted data on the methods applied for surrogate validation. We assessed the level of agreement between agencies and fitted mixed-effects logistic regression models to test the impact of validation approaches on the agency's acceptability of the surrogate endpoint and their coverage recommendation. RESULTS: Of the 124 included reports, 61 (49%) discussed the level of evidence to support the relationship between the surrogate and the patient-centered endpoint, 27 (22%) reported a correlation coefficient/association measure, and 40 (32%) quantified the expected effect on the patient-centered outcome. Overall, the surrogate endpoint was deemed acceptable in 49 (40%) reports (k-coefficient 0.10, P = 0.004). Any consideration of the level of evidence was associated with accepting the surrogate endpoint as valid (odds ratio [OR], 4.60; 95% confidence interval [CI], 1.60-13.18, P = 0.005). However, we did not find strong evidence of an association between accepting the surrogate endpoint and agency coverage recommendation (OR, 0.71; 95% CI, 0.23-2.20; P = 0.55). CONCLUSIONS: Handling of surrogate endpoint evidence in reports varied greatly across HTA agencies, with inconsistent consideration of the level of evidence and statistical validation. Our findings call for careful reconsideration of the issue of surrogacy and the need for harmonization of practices across international HTA agencies.

Surrogate Endpoints in Health Technology Assessment: An International Review of Methodological Guidelines.

In the drive towards faster patient access to treatments, health technology assessment (HTA) agencies are increasingly faced with reliance on evidence from surrogate endpoints, leading to increased decision uncertainty. This study undertook an updated survey of methodological guidance for using surrogate endpoints across international HTA agencies. We reviewed HTA and economic evaluation methods guidance from European, Australian and Canadian HTA agencies. We considered how guidelines addressed the methods for handling surrogate endpoints, including (1) level of evidence, (2) methods of validation, and (3) thresholds of acceptability. Across the 73 HTA agencies surveyed, 29 (40%) had methodological guidelines that made specific reference to consideration of surrogate outcomes. Of the 45 methods documents analysed, the majority [27 (60%)] were non-technology specific, 15 (33%) focused on pharmaceuticals and three (7%) on medical devices. The principles of the European network for Health Technology Assessment (EUnetHTA) guidelines published in 2015 on the handling of surrogate endpoints appear to have been adopted by many European HTA agencies, i.e. preference for final patient-relevant outcomes and reliance on surrogate endpoints with biological plausibility and epidemiological evidence of the association between the surrogate and final endpoint. Only a small number of HTA agencies (UK National Institute for Care and Excellence; the German Institute for Medical Documentation and Information and Institute for Quality and Efficiency in Health Care; the Australian Pharmaceutical Benefits Advisory Committee; and the Canadian Agency for Drugs and Technologies in Health) have developed more detailed prescriptive criteria for the acceptance of surrogate endpoints, e.g. meta-analyses of randomised controlled trials showing strong association between the treatment effect on the surrogate and final outcomes. As the decision uncertainty associated with reliance on surrogate endpoints carries a risk to patients and society, there is a need for HTA agencies to develop more detailed methodological guidance for consistent selection and evaluation of health technologies that lack definitive final patient-relevant outcome evidence at the time of the assessment.