In late 2022, Aetion announced the launch of the Aetion Coalition to Advance Real‐World Evidence through Randomized Controlled Trial Emulation (CARE) Initiative: Oncology. This first-of-its-kind, cross-industry collaboration brings together multiple stakeholders who will, together, explore instances where real-world evidence (RWE) and randomized controlled trials (RCTs) yield different or similar results, with an initial focus on oncology.
To learn more about the CARE Initiative and its framework for systematically emulating trials in oncology, we sat down with Aetion’s Inish O’Doherty and Dave Merola for a brief Q&A on the Initiative’s stated methods and goals, as outlined in an article published in Clinical Pharmacology and Therapeutics.
Q: Can you tell us a little bit about the CARE initiative and the work it will undertake?
Inish: The CARE initiative is a demonstration project that will emulate oncology clinical trials using real-world data (RWD). Through this process, we can better understand the strengths and limitations of real-world evidence and determine when and why RWE and RCTs might yield similar or different results. Furthermore, this project can help identify strategies that address some of the concerns associated with real-world studies (e.g., missing data). To illustrate when RWD can provide reliable evidence on drug effectiveness, we seek to conduct several RWD-based studies that emulate RCTs in oncology using a systematic, protocol-driven approach. The results can then help inform clinical, scientific, and regulatory stakeholders on the applications of RWD in the context of product labeling expansion, drug safety, and comparative effectiveness in oncology.
Q: Why oncology?
Dave: Oncology is a space well-suited for RWE. Cancer is a serious and life-threatening disease and many forms of cancer do not have adequate treatments available. As a result, it can be difficult or unethical to conduct a traditional placebo-controlled clinical trial that provide sufficient evidence of effectiveness to support a product application. Reaching a better understanding of how RWE can augment more traditional evidence generation activities could have a substantial impact for patients. At the same time, the management of cancers is clinically complex, which sets a high bar for the oncology RWD used for trial emulation. Our collaboration with six oncology data providers will ensure that findings from the CARE initiative will guide advancements in oncology RWD.
Q: Can you talk about the importance of a cross-industry collaborative approach?
Inish: The cross-functional approach allows us to leverage a wealth of different experience and approaches, ensuring that this will be an impactful and rigorous project. We are pleased to work with a great set of collaborators, including pharmaceutical companies (AbbVie, Amgen, AstraZeneca, Bayer, Gilead, Janssen, Pfizer), clinical researchers from academic medical centers (Baylor College of Medicine, Brigham and Women’s Hospital and Harvard Medical School), data providers (ConcertAI, COTA, Loopback Analytics, Tempus, TriNetX, and xCures), and standard-setting organizations (the Duke-Margolis Center for Health Policy, Friends of Cancer Research, Reagan-Udall Foundation). Each participant brings a unique viewpoint on cancer care, data, and evidence generation that will continue to be helpful in determining which trials to emulate, the most appropriate emulation strategy, and the most balanced interpretation of the emulation results.
Q: What are you hoping to learn from this initiative? How does this add something new compared to the other trial emulation efforts?
Dave: Other emulation efforts, such as RCT-DUPLICATE, have demonstrated how RWE studies can meaningfully supplement RCT evidence. CARE seeks to build on that work by extending this framework for emulating RCTs to include oncology clinical trials and EHR-based data resources that have been emerging on the marketplace. Additionally, our hope is that this study will provide a sense of the overall availability and reliability of RWD resources, as well as illuminate which data attributes are most important to account for in studies of a particular tumor type.
Q: This is a massive undertaking, how will the work get done?
Inish: The CARE Initiative will be a true team effort that relies on the deep expertise and unique perspectives of our partners. We carefully designed processes to ensure efficient, objective, and impactful work, and then refined our approaches based on learnings from our pilot emulation. For each of the emulation studies, we will carefully detail the study’s design, feasibility analyses, power analyses, eligibility criteria in a protocol using the HARPER template. To further ensure both transparency and reproducibility, the protocols will be pre-registered on clinicaltrials.gov before execution.
For additional information, please visit the Aetion CARE Initiative homepage here.