Randomized controlled trials are not always the solution

This commentary refers to ‘Quality and transparency of evidence for implantable cardiovascular medical devices assessed by the CORE-MD consortium’, by G.C.M. Siontis et al., https://doi.org/10.1093/eurheartj/ehad567 and the discussion piece ‘Randomised controlled trials remain underutilized’, by G.C.M. Siontis et al., https://doi.org/10.1093/eurheartj/ehad806. The recent article authored by Siontis et al.1 has made considerable contributions to the ongoing debate concerning the pre-market clinical evaluation of implantable medical devices in Europe, with a particular focus on the cardiovascular domain. The study encompassed seven different classes of devices over a span of 20 years, providing comprehensive details regarding study design, patient demographics, interventions, and primary outcomes. This information was critically evaluated in relation to the timing of the corresponding CE-mark approval, offering valuable insights that can shape the design of clinical investigations for novel devices. However, it is important to acknowledge certain reservations about the conclusions drawn in the article: Firstly, a randomized controlled trial (RCT) design is not always a feasible or ethical option. While RCTs remain a cornerstone of evidence-based medicine, they may present practical and ethical challenges in the context of medical device evaluations, especially in the case of vulnerable populations like children.2 As an alternative, prospective cohort studies and adaptive design trials have gained prominence due to their capacity to enhance result generalizability and explore individual variations and causal mechanisms.3,4 Secondly, gaining access to the European market and maintaining is not straightforward. While historically, the medical device domain was less regulated than the pharmaceutical industry, significant progress has been made. Even under the Medical Device Directive, manufacturers had to adhere to stringent requirements outlined by European Union legislation and international standards to obtain a “certificate of conformity” from a notified body. International Organization for Standardization (ISO) standards, such as ISO 5910 and ISO 5841-2, define the clinical requirements of specific medical device categories. Furthermore, the Medical Device Regulation (MDR) introduced expert panel assessments for high-risk devices, and notified bodies are subject to thorough scrutiny by national competent authorities. Lastly, the timeline for publishing an RCT in a medical journal is typically lengthy. A study from 2014 revealed that the median timeline for publishing an RCT was nearly 2 years,5 and this timeline has likely remained relatively unchanged in the past decade. Moreover, translating the results of a clinical investigation into a scientific publication demands substantial effort. Consequently, publishing the results of a pre-market study before obtaining the CE mark is extremely challenging. Alternative approaches such as presenting findings at international conferences or investigator meetings during the studies could be then used. Additionally, current MDR requirements emphasize transparency through the summary of the clinical investigation report and the summary of safety and clinical performance. In conclusion, while Siontis et al.’s recent article sheds crucial light on pre-market clinical evaluation complexities for implantable medical devices, the landscape encompasses ethical considerations, regulatory frameworks, and the need for diverse study designs. Striking a balance between accurate evaluation and timely access to innovative medical technologies remains a challenge, emphasizing the importance of refining our approaches to ensure patient safety and optimal healthcare outcomes. We welcome an open debate on this matter and commend Siontis et al. for initiating this discussion. We encourage all stakeholders to actively participate in this discourse. All authors declare no disclosure of interest for this contribution.