Using Real-World Data in the Health Technology Assessment of Pharmaceuticals: Strengths, Difficulties, and a Pragmatic Way Forward.

In the past decade, there have been increasing calls for greater use of real-world evidence (RWE) and data (RWD), with the explicit goal of enabling faster provision of effective medicines to patients in need. The push for decision makers to accept RWE is especially noticeable in the pursuit of regulatory approval, but RWE, particularly when used to estimate the relative effectiveness of interventions, is not always readily accepted by agencies responsible for reimbursement and pricing of new pharmaceuticals and, to a varying degree, is not accepted across jurisdictions. This lack of trust hampers the use of RWE despite a very large and growing literature base on the principles of how RWE should be used. In this article, we suggest an important part of the explanation of why this situation has arisen and make suggestions for its alleviation. Given that problems commonly arise that are particular to the question being asked and the data sources being used, general guidance on the principles of how to use RWD cannot cover all eventualities. Therefore, we are suggesting the creation of an archive, or repository, to record uses of RWD in support of decisions by funding bodies or their advisors. This article introduces a proposed, structured classification of decision types using RWE, around which evidence can be assembled in a curated source (RWD/RWE taxonomy) and thus facilitate judgments on when evidence is "good enough." This article is part of a series in a special issue of this journal that looks at the barriers to optimal use of RWE in health technology assessment and how to overcome them. We begin significantly to populate our "taxonomy" with examples in an accompanying article. We also propose recommendations for international standards of evaluating the acceptability of RWD governance practices.

The Real-World Evidence Workstream in EUreccA 2025: How the Task Was Addressed.

This is one of a series of articles that consider the barriers to optimal use of real-world evidence (RWE) in health technology assessment (HTA) as well as ways to overcome them. The work was carried out as part of EUreccA 2025 (European Initiative for New Reimbursement and Access Approaches 2025), in particular with the RWE workstream embodied within that collaboration. The starting premises of this workstream were as follows: (1) the acceptance of RWE by HTA agencies and payers in the assessment of drugs is suboptimal and variable between jurisdictions, and (2) if that were not the case, the path of new pharmaceuticals to patients could be quicker and less expensive. Elsewhere in this issue we set out the conclusions we had reached in the EUreccA RWE workstream. In this article, we set out the methodology used to conduct the totality of the EureccA 2025 RWE workstream effort, which led us to those conclusions. The main results, strengths, and limitations of the individual parts are discussed further in separate articles in this supplement. Through scoping work, we generated 4 key topics within which to identify and address the barriers to optimal RWE use in HTA. Through pragmatic literature searches, stakeholder engagement, and case studies, we suggest ways in which the problems identified may be addressed as a contribution to progress in this area.

Across-Country Variations of Real-World Data and Evidence for Drugs: A 5-European-Country Study.

OBJECTIVES: This study aimed to describe the role of real-world data (RWD) and real-world evidence (RWE) in health technology assessment (HTA) in 5 European countries and to identify the hurdles to the acceptance of RWE and suggest directions toward its more effective use. METHODS: Authors from France, Germany, Italy, and Sweden used a common template to extract evidence. For England, the Cancer Drugs Fund was described and analyzed as a particular model for the use of RWD to provide evidence for coverage decisions and managed entry agreements. RESULTS: In all countries except Germany, HTA bodies acknowledged the relevance of RWD/RWE to address postlaunch uncertainties. In Germany, evidence from randomized controlled trials remains the gold standard, and evidence based on RWD is generally rejected. Multiple sources of RWD exist, but the quality, the immediate relevance of existing sources, and their interoperability limit their adaptation to the specifics of a given drug. This leads to skepticism about the validity of the evidence. Timing is also a key issue: the production of evidence may not be synchronized with the HTA and pricing bodies' agendas. The Cancer Drugs Fund case emphasizes that a strong partnership among all stakeholders and a pragmatic use of existing data, alongside clinical evidence provided by companies, are key success factors. CONCLUSIONS: A continuous investment in national health information systems is a key issue for providing valid RWE. Processes and aids to guide the acceptability and usage of RWE derived from pairing between sources and questions are essential.

Data Governance for Real-World Data Management: A Proposal for a Checklist to Support Decision Making.

OBJECTIVES: Real-world data (RWD) and real-world evidence (RWE) can provide extensive information on healthcare for use in health technology assessment and decision making. Nevertheless, there is a lack of consensus surrounding the appropriate data governance (DG) practices for RWD/RWE. Data sharing is also a large concern, especially considering evolving data protection regulations. Our objective is to propose recommendations for international standards of evaluating the acceptability of RWD governance practices. METHODS: After reviewing the literature, we created a checklist targeting DG practices for RWD/RWE. We then carried out a 3-round Delphi panel, including European policy makers, health technology assessment experts, and hospital managers. The consensus for each statement was measured and the checklist adjusted accordingly. RESULTS: The literature review identified the main topics regarding RWD/RWE DG practices: data privacy and security, data management and linkage, data access management, and the generation and use of RWE. Members of the Delphi panel (21 experts/25 invited) were presented a total of 24 statements related to each of the topics. Experts demonstrated a progressive level of consensus and importance ratings in all topics and to most statements. We suggest a refined checklist in which the statements rated less important or with less consensus have been removed. CONCLUSIONS: This study suggests how the DG of RWD/RWE could be qualitatively evaluated. We propose checklists that could be used by all RWD/RWE users to help ensure the quality and integrity of RWD/RWE governance and complement data protection law.

Structure and Content of a Taxonomy to Support the Use of Real-World Evidence by Health Technology Assessment Practitioners and Healthcare Decision Makers.

This is one of a series of articles that consider the barriers to optimal use of real-world evidence (RWE) in health technology assessment and how to overcome them. The work was performed as part of EUreccA 2025, in particular with the RWE workstream embodied within that collaboration. Elsewhere in this issue we described the reasoning and process that led us to develop practical tools to support RWE use, including this taxonomy and explained the methods used to do so. The taxonomy classifies questions that are typically addressed using real-world data in health technology assessment and the data sources typically used to address these questions. In this article, we describe the taxonomy itself. For as many of the pairings as possible, we have provided links to advice and methods on how to address the associated question using those data. We have also provided links to examples of RWE use in practical decision making to answer the questions posed. Our work is not complete, but we believe it is sufficient to demonstrate the value of such a taxonomy and information source if it is completed and curated as a "wiki" by the community that would use it.

Clinical-effectiveness of self-management interventions in chronic obstructive pulmonary disease: An overview of reviews.

Self-management (SM) is defined as the provision of interventions to increase patients' skills and confidence, empowering the individual to take an active part in their disease management. There is uncertainty regarding the optimal format and the short- and long-term benefits of chronic obstructive pulmonary disease (COPD) SM interventions in adults. Therefore, a high-quality overview of reviews was updated to examine their clinical effectiveness. Sixteen reviews were identified, interventions were broadly classified as education or action plans, complex interventions with an SM focus, pulmonary rehabilitation (PR), telehealth and outreach nursing. Systematic review and meta-analysis quality and the risk of bias of underlying primary studies were assessed. Strong evidence was found that PR is associated with significant improvements in health-related quality of life (HRQoL). Limited to moderate evidence for complex interventions (SM focus) with limited evidence for education, action plans, telehealth interventions and outreach nursing for HRQoL was found. There was strong evidence that education is associated with a significant reduction in COPD-related hospital admissions, moderate to strong evidence that telehealth interventions and moderate evidence that complex interventions (SM focus) are associated with reduced health care utilization. These findings from a large body of evidence suggesting that SM, through education or as a component of PR, confers significant health gains in people with COPD in terms of HRQoL. SM supported by telehealth confers significant reductions in healthcare utilization, including hospitalization and emergency department visits.

Robot-assisted radical prostatectomy compared with open and laparoscopic approaches: a systematic review and meta-analysis.

Medline and Embase were searched for studies comparing robot-assisted radical prostatectomy with open prostatectomy and conventional laparoscopic prostatectomy. Random effects meta-analysis was used to calculate a pooled estimate of effect. The 95% prediction intervals are also reported. One randomized study and 50 observational studies were identified. The results show that compared with open surgery, robot-assisted surgery is associated with fewer positive surgical margins for pT2 tumors (relative risk 0.63, 95% confidence interval 0.49-0.81, P < 0.001) and improved outcomes for sexual function at 12 months (relative risk 1.60, 95% confidence interval 1.33-1.93, P = <0.001), and, to a lesser extent, urinary function at 12 months (relative risk 1.06, 95% confidence interval 1.02-1.11, P < 0.01). Compared with conventional laparoscopic prostatectomy, robot-assisted surgery is associated with a slight increase in urinary function at 12 months (relative risk 1.09, 95% confidence interval 1.02 to 1.17, P = 0.013). The overall methodological quality of the included studies was low, with high levels of heterogeneity. The use of prediction intervals as an aid to decision making in regard to the introduction of this technology is examined. Clinically significant improvements in positive surgical margins rates for pT2 tumors and sexual function at 12 months associated with robot-assisted surgery in comparison with open surgery should be interpreted with caution given the limitations of the evidence. Differences between robot-assisted and conventional laparoscopic surgery are minimal.

Acromion-fixation of glenoid components in total shoulder arthroplasty.

Successful design of components for total shoulder arthroplasty has proven to be challenging. This is because of the difficulties in maintaining fixation of the component that inserts into the scapula; i.e., the glenoid component. Glenoid components that are fixated to both the glenoid and acromion (a long process extending medially on the dorsal aspect of the scapula) have the possible advantage of greater stability over those that are fixated to the glenoid alone. In this study, a finite element analysis is used to investigate whether or not acromion fixation is advantageous for glenoid components. Full muscle loading and joint reaction forces are included in the finite element model. Reflective photoelasticity of five scapulae is used to obtain experimental data to compare with results from the finite element analysis, and it confirms the structural behaviour of the finite element model. When implanted with an acromion-fixated prosthesis, it is found that high unphysiological stresses occur in the scapula bone, and that stresses in the fixation are not reduced. Very high stresses are predicted in that part of the prosthesis which connects the acromion to the glenoid. It is found that the very high stresses are partly in response to the muscle and joint reaction forces acting at the acromion. It is concluded that, because of the relatively high forces acting at the acromion, fixation to it may not be the way forward in glenoid component design.