Different Weights of the Evidence-Based Medicine Triad in Regulatory, Health Technology Assessment, and Clinical Decision Making

Abstract

Evidence-based medicine (EBM) is defined as a systematic approach to clinical problem solving by the integration of best research evidence with real-world clinical expertise and patient values. Since those early days, decision requirements expanded from patient-centric clinical decision making to a population-based view including regulatory health technology assessments (HTAs). Regulatory bodies mainly rely on the totality of research evidence, which includes preclinical and all available clinical data. HTA bodies primarily focus on clinical data with a strong preference for comparative data from randomized controlled clinical trials (RCTs). Conversely, bedside clinical decisions are largely driven by real-world clinical expertise, which takes into account the individual patients’ preferences, as well as the availability of supportive research evidence. While the focus on research evidence is a typical feature of the early part of the adoption curve for innovative technologies, HTA decision makers need to ensure that clinical expertise is also appropriately included in their decisions, in order to avoid beneficial medications from being not available to patients.

A comprehensive review of economic evaluations of therapeutic drug monitoring interventions for cancer treatments

“…Many short term non-randomised studies used to inform the economic evaluations show reductions in AEs that are likely to be patient-relevant and reduction hospital resource use. However, economic evaluations relying on less robust evidence may be less persuasive to decision-makers as health technology assessment bodies have a strong preference for direct evidence from RCTs [40]. Due to the difficulties conducting RCTs for TDM interventions in oncology [41], good quality observational studies may provide robust estimates on the effectiveness of TDM [42].…”

“Market withdrawals” of medicines in Germany after AMNOG: a comparison of HTA ratings and clinical guideline recommendations

“…Twenty-one (95%) of those medicines received a ‘no additional benefit’ rating by the G-BA, a sharp contrast to the average of 43% of ‘no additional benefit ratings’ in all G-BA appraisals [10]. As both benefit appraisals and clinical guidelines rely on the principles of evidence-based medicine [26], those discrepancies are striking, raising the question of how these diverging evaluations of the same medicine fit together. The respective analysis reveals a couple of key features:An obvious heterogeneity between guideline recommendations and G-BA appraisals occurred in diabetes.…”

Challenges for Optimizing Real-World Evidence in Alzheimer’s Disease: The ROADMAP Project

“…Incorporating the assessment of AD-related outcomes into real-world settings requires consensus between stakeholders. RWE helps to inform regulators (on treatment patterns, effectiveness, and risk); payers, Health Technology Assessment (HTA) bodies, and healthcare providers (HCPs; on economic value/resource utilization, clinical effectiveness relative to current standard-of-care treatments, and patient-relevant outcomes, including quality of life [QoL]); industry (on product effectiveness and safety, research and development, pricing, and manufacturing); and scientists (on mechanisms and diagnostic/treatment pathways) to accelerate decision-making on new and existing treatments [8– 10].…”