In the evolving landscape of healthcare, the integration of real-world evidence (RWE) and randomized controlled trials (RCTs) in health technology assessments (HTAs)s is gaining momentum. This is further propelled by the European Union’s Regulation on Health Technology Assessment (HTAR) and the introduction of joint clinical assessments (JCAs), which started in 2025 for oncology drugs and advanced therapy medicinal products (ATMPs)[1]. Germany, known for its robust healthcare system and innovative approaches, is at the forefront of this integration. This blog post explores the significance of combining RWE and RCTs in HTAs and the implications for the future of healthcare in Germany.
Understanding RWE and RCTs
RWE refers to clinical evidence derived from the analysis of real-world data (RWD)[2]. This data is collected from various sources such as electronic health records, claims databases, patient registries, and even wearable devices. RWE provides insights into how treatments perform in routine clinical practice, outside the controlled environment of clinical trials.
RCTs are considered the gold standard in clinical research[3]. They involve randomly assigning participants to either the treatment group or the control group, ensuring that the results are not biased by external factors. RCTs provide high-quality evidence on the efficacy and safety of interventions.
The Role of HTA
HTA is a multidisciplinary process that evaluates the social, economic, organizational, and ethical issues of a health intervention or health technology[4]. The goal of HTA is to inform policy and decision-making in healthcare, ensuring that patients receive effective and efficient treatments.
The Integration of RWE and RCTs
The integration of RWE and RCTs in HTA (e.g. by using a synthetic control arm (SCA) as an external control in situations where recruiting a control group is difficult, such as in rare diseases or when ethical concerns arise) represents a paradigm shift in how healthcare interventions are evaluated. In our experience, there are a number of key benefits, including:
- Comprehensive evidence: Combining RWE with RCTs provides a more comprehensive understanding of a treatment’s effectiveness and safety. While RCTs offer strong internal validity, RWE adds external validity by showing how treatments work in real-world settings.
- Enhanced decision-making: Policymakers and healthcare providers can make more informed decisions by considering both controlled trial data and real-world outcomes. This leads to better resource allocation and improved patient care.
- Faster access to innovations: The integration of RWE can accelerate the assessment process, allowing innovative treatments to reach patients more quickly. This is particularly important in areas with unmet medical needs.
- Patient-centered care: RWE captures diverse patient populations and real-world clinical scenarios, ensuring that the assessment reflects the experiences of a broader range of patients. This supports the move toward more personalized and patient-centered care.
Germany’s Approach
The Gemeinsame Bundesausschuss (G-BA), Germany’s highest decision-making body of the joint self-government of physicians, dentists, hospitals and health insurance funds, in collaboration with the Institute for Quality and Efficiency in Health Care (IQWiG), utilizes high-quality registries to conduct added benefit assessments, especially in scenarios where there is limited evidence available at the time of market authorization. These registries provide valuable RWD that can complement clinical trial results.
The routine practice data collection known from the German AMNOG regulations (Anwendungsbegleitende Datenerhebung) is another example of how registries can bridge data gaps and provide further evidence for new benefit assessments[5].
Challenges and Future Directions
While the integration of RWE and RCTs in HTA offers numerous benefits, it also presents challenges. Ensuring the quality and reliability of RWE, addressing data privacy concerns, and developing standardized methodologies are critical areas that need attention.
Looking ahead, the continued collaboration between stakeholders, including regulators, healthcare providers, and researchers, will be essential. By leveraging the strengths of both RWE and RCTs, Germany can lead the way in creating a more dynamic and responsive healthcare system.
Conclusion
Making use of RWE as well as RCTs in support of HTA decision-making marks a significant advancement in healthcare evaluation. Germany’s commitment to this integration highlights its dedication to improving patient outcomes and fostering innovation. As we move forward, the synergy between RWE and RCTs will undoubtedly play a pivotal role in shaping the future of healthcare in Germany, Europe, and beyond.
What is your experience with assessing evidence from RWE and RCT? What issues have you faced with evidence synthesis? We would be interested in hearing your perspective.
[1] New EU rules on Health Technology Assessment open up a new era for patient access to innovation, European Commission. https://ec.europa.eu/commission/presscorner/detail/en/ip_25_226
[2] Real-World Evidence, FDA. https://www.fda.gov/science-research/science-and-research-special-topics/real-world-evidence
[3] Randomised controlled trials—the gold standard for effectiveness research, BJOG. 2018 Dec. https://pmc.ncbi.nlm.nih.gov/articles/PMC6235704/
[4] Health technology assessment, WHO. https://www.who.int/health-topics/health-technology-assessment#tab=tab_1
[5] Requirements for benefit assessment in Germany and England – overview and comparison, Health Econ Rev. 2014 Dec. https://pmc.ncbi.nlm.nih.gov/articles/PMC4884042/
