Real-world evidence in health technology assessment of high-risk medical devices: Fit for purpose?

Health technology assessment (HTA) of medical devices (MDs) increasingly rely on real-world evidence (RWE). The aim of this study was to evaluate the type and the quality of the evidence used to assess the (cost-)effectiveness of high risk MDs (Class III) by HTA agencies in Europe (four European HTA agencies and EUnetHTA), with particular focus on RWE. Data were extracted from HTA reports on the type of evidence demonstrating (cost-)effectiveness, and the quality of observational studies of comparative effectiveness using the Good Research for Comparative Effectiveness principles. 25 HTA reports were included that incorporated 28 observational studies of comparative effectiveness. Half of the studies (46%) took important confounding and/or effect modifying variables into account in the design and/or analyses. The most common way of including confounders and/or effect modifiers was through multivariable regression analysis. Other methods, such as propensity score matching, were rarely employed. Furthermore, meaningful analyses to test key assumptions were largely omitted. Resulting recommendations from HTA agencies on MDs is therefore (partially) based on evidence which is riddled with uncertainty. Considering the increasing importance of RWE it is important that the quality of observational studies of comparative effectiveness are systematically assessed when used in decision-making.

How real can we get in generating real world evidence? Exploring the opportunities of routinely collected administrative data for evaluation of medical devices.

Real-world data are considered a potentially valuable source of evidence for assessing medical technologies in clinical practice, but their widespread use is hampered by numerous challenges. Using the case of coronary stents in Italy, we investigate the potential of administrative databases for estimating costs and health outcomes associated with the use of medical devices in real world conditions. An administrative dataset was created ad hoc by merging hospital records from patients admitted between 2013 and 2019 for stent implantations with ambulatory records, pharmaceutical use data and vital statistics. Health outcomes were multifold: all-cause and cardiac mortality and myocardial infarction, within 30 days, 1, 2, 5 years. Costs were estimated from the National Health System perspective. We used multivariable Cox models and propensity score (PS) methods (PS matching; stratification on PS; inverse probability of treatment weighting using PS; PS adjustment). 257,907 coronary stents were implanted in 113,912 patients. For all health outcomes and follow-up times, and across all methods, patients receiving drug-eluting stents (DES) presented lower risk. For all-cause mortality, the DES patient advantage over bare-metal stent (BMS) patients declined over time but remained significant even at 5 years. For myocardial infarction, results remained quite stable. The DES group presented lower cumulative total costs (ranging from 3264 to 2363 Euros less depending on methods). Our results confirm the consolidated evidence of the benefits of DES compared to BMS. The consistency of results across methods suggests internal validity of the study, while highlighting strengths and limitations of each depending on research context. Administrative data yield great potential to perform comparative effectiveness and cost-effectiveness analysis of medical devices provided certain conditions are met.

Do existing real-world data sources generate suitable evidence for the HTA of medical devices in Europe? Mapping and critical appraisal.

AIM: Technological and computational advancements offer new tools for the collection and analysis of real-world data (RWD). Considering the substantial effort and resources devoted to collecting RWD, a greater return would be achieved if real-world evidence (RWE) was effectively used to support Health Technology Assessment (HTA) and decision making on medical technologies. A useful question is: To what extent are RWD suitable for generating RWE? METHODS: We mapped existing RWD sources in Europe for three case studies: hip and knee arthroplasty, transcatheter aortic valve implantation (TAVI) and mitral valve repair (TMVR), and robotic surgery procedures. We provided a comprehensive assessment of their content and appropriateness for conducting the HTA of medical devices. The identification of RWD sources was performed combining a systematic search on PubMed with gray literature scoping, covering fifteen European countries. RESULTS: We identified seventy-one RWD sources on arthroplasties; ninety-five on TAVI and TMVR; and seventy-seven on robotic procedures. The number, content, and integrity of the sources varied dramatically across countries. Most sources included at least one health outcome (97.5%), with mortality and rehospitalization/reoperation the most common; 80% of sources included resource outcomes, with length of stay the most common, and comparators were available in almost 70% of sources. CONCLUSIONS: RWD sources bear the potential for the HTA of medical devices. The main challenges are data accessibility, a lack of standardization of health and economic outcomes, and inadequate comparators. These findings are crucial to enabling the incorporation of RWD into decision making and represent a readily available tool for getting acquainted with existing information sources.

Socioeconomic inequalities across life and premature mortality from 1971 to 2016: findings from three British birth cohorts born in 1946, 1958 and 1970.

INTRODUCTION: Disadvantaged socioeconomic position (SEP) in early and adult life has been repeatedly associated with premature mortality. However, it is unclear whether these inequalities differ across time, nor if they are consistent across different SEP indicators. METHODS: British birth cohorts born in 1946, 1958 and 1970 were used, and multiple SEP indicators in early and adult life were examined. Deaths were identified via national statistics or notifications. Cox proportional hazard models were used to estimate associations between ridit scored SEP indicators and all-cause mortality risk-from 26 to 43 years (n=40 784), 26 to 58 years (n=35 431) and 26 to 70 years (n=5353). RESULTS: More disadvantaged SEP was associated with higher mortality risk-magnitudes of association were similar across cohort and each SEP indicator. For example, HRs (95% CI) from 26 to 43 years comparing lowest to highest paternal social class were 2.74 (1.02 to 7.32) in 1946c, 1.66 (1.03 to 2.69) in 1958c, and 1.94 (1.20 to 3.15) in 1970c. Paternal social class, adult social class and housing tenure were each independently associated with mortality risk. CONCLUSIONS: Socioeconomic circumstances in early and adult life show persisting associations with premature mortality from 1971 to 2016, reaffirming the need to address socioeconomic factors across life to reduce inequalities in survival to older age.

Inequalities in avoidable hospitalisation in large urban areas: retrospective observational study in the metropolitan area of Milan.

OBJECTIVE: Significant inequalities in access to healthcare system exist between residents of world megacities, even if they have different healthcare systems. The aim of this study was to estimate avoidable hospitalisations in the metropolitan area of Milan (Italy) and explore inequalities in access to healthcare between patients and across their areas of residence. DESIGN: Retrospective observational study. SETTING: Public and accredited private hospitals in the metropolitan area of Milan. Data obtained from the hospital discharge database of the Italian Health Ministry. PARTICIPANTS: 472 579 patients hospitalised for ambulatory care sensitive conditions and resident in the metropolitan area of Milan from 2005 to 2016. OUTCOME MEASURE: Age-adjusted rates of avoidable hospitalisations; OR for hospital admissions with ambulatory care sensitive conditions. METHODS: Age-adjusted rates of avoidable hospitalisations in the metropolitan area of Milan were estimated from 2005 to 2016 using direct standardisation. For the hospitalised population, multilevel logistic regression model with patient random effects was used to identify patients, hospitals and municipalities' characteristics associated with risk of avoidable hospitalisation in the period 2012-2016. RESULTS: The rate of avoidable hospitalisation in Milan fell steadily between 2005 and 2016 from 16.6 to 10.5 per 1000. Among the hospitalised population, the odds of being hospitalised with an ambulatory care sensitive condition was higher for male (OR 1.42, 95% CI 1.36 to 1.48), older (OR 1.012, 95% CI 1.01 to 1.014), low-educated (elementary school vs degree OR 4.23, 95% CI 3.72 to 4.81) and single (vs married OR 2.08, 95% CI 2.01 to 2.16) patients with comorbidities (OR 1.47, 95% CI 1.38 to 1.56); avoidable admissions were more frequent in public non-teaching hospitals while municipality's characteristics did not appear to be correlated with hospitalisation for ambulatory care sensitive conditions. CONCLUSIONS: The health system in metropolitan Milan has experienced a reduction in avoidable hospitalisations between 2005 and 2016, quite homogeneously across its 134 municipalities. The study design allowed to explore inequalities among the hospitalised population for which we found specific sociodemographic disadvantages.

Impact of chemotherapy-induced nausea and vomiting on health-related quality of life and resource utilization: A systematic review.

BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) is a particularly distressing event for oncology patients. This review aims at analyzing the impact of CINV on Health-Related Quality of Life (QoL) and on the use of healthcare resources. METHODS: A systematic search was conducted according to the PRISMA statement on MEDLINE, EMBASE and NHS EED. RESULTS: Sixty-seven studies were included in the final selection. Despite the availability of numerous treatment options, CINV was found to have a strong impact on HRQoL of patients. Direct costs are particularly affected, but this result could be due to scarcity of studies assessing indirect costs. CONCLUSIONS: Evidence supports the notion that CINV continues to have a negative impact on HRQoL of patients, even for those receiving moderately emetic chemotherapy. Further studies need also to collect data on the cost of CINV, particularly indirect costs, to ensure that decisions on use of healthcare resources are better supported.

A Systematic Literature Review of Studies Analyzing Inequalities in Health Expectancy among the Older Population.

AIM: To collect, organize and appraise evidence of socioeconomic and demographic inequalities in health and mortality among the older population using a summary measure of population health: Health Expectancy. METHODS: A systematic literature review was conducted. Literature published in English before November 2014 was searched via two possible sources: three electronic databases (Web of Science, Medline and Embase), and references in selected articles. The search was developed combining terms referring to outcome, exposure and participants, consisting in health expectancy, socioeconomic and demographic groups, and older population, respectively. RESULTS: Of 256 references identified, 90 met the inclusion criteria. Six references were added after searching reference lists of included articles. Thirty-three studies were focused only on gender-based inequalities; the remaining sixty-three considered gender along with other exposures. Findings were organized according to two leading perspectives: the type of inequalities considered and the health indicators chosen to measure health expectancy. Evidence of gender-based differentials and a socioeconomic gradient were found in all studies. A remarkable heterogeneity in the choice of health indicators used to compute health expectancy emerged as well as a non-uniform way of defining same health conditions. CONCLUSIONS: Health expectancy is a useful and convenient measure to monitor and assess the quality of ageing and compare different groups and populations. This review showed a general agreement of results obtained in different studies with regard to the existence of inequalities associated with several factors, such as gender, education, behaviors, and race. However, the lack of a standardized definition of health expectancy limits its comparability across studies. The need of conceiving health expectancy as a comparable and repeatable measure was highlighted as fundamental to make it an informative instrument for policy makers.