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The era of alternative designs to connect randomized clinical trials and real-world data

Nature Reviews Clinical Oncology volume 16, page 589 (2019)Cite this article

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In their Review published in the May 2019 issue of this journal (Real-world data: towards achieving the achievable in cancer care. Nat. Rev. Clin. Oncol. 16, 312–325 (2019))1, Booth et al. address challenges and future perspectives relating to the use of real-world data (RWD) in oncology. They describe the quality, and current and future applications of RWD, and the pitfalls of studies of comparative effectiveness using RWD. We acknowledge the authors’ efforts to provide this comprehensive overview and appreciate the future perspectives they present. In light of the authors’ appeal for increasing focus to be placed in the implementation of randomized clinical trials (RCTs) in real-world settings, herein we would like to address overlooked opportunities for using alternative trial designs to enhance the real-world nature of the data within RCTs. Owing to the length limitations of this Correspondence, we cannot define each modality but provide supporting references.

Pragmatic trial designs, such as registry-based RCTs (R-RCTs), have become of increasing interest globally as efficient and cost-effective tools that combine the advantages of a prospective RCT with the strengths of large-scale clinical registries. R-RCTs are characterized by low cost, enhanced generalizability of findings, rapid consecutive enrolment and the high potential for completeness in the follow-up management of participants, especially hard end points2,3. Although R-RCTs retain methodological limitations (for example, a dependence on the quality of the registry) and could face ethical challenges given the differences in national ethical guidelines3, such studies can be designed to efficiently address research questions about comparative effectiveness in real-world settings.

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Acknowledgements

The work of J.W.G.D. is fully supported by the Province of Utrecht, Netherlands.

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Authors and Affiliations

  1. Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands

    Jeroen W. G. Derksen & Miriam Koopman

  2. Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands

    Jeroen W. G. Derksen & Anne M. May

Authors
  1. Jeroen W. G. Derksen
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  2. Anne M. May
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Correspondence to Jeroen W. G. Derksen.

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Competing interests

M. K. is the principle investigator of the Prospective Dutch Colorectal Cancer (PLCRC) cohort. The PLCRC is sponsored by the Dutch Colorectal Cancer Group (DCCG). J.W.G.D. and A.M.M. declare no competing interests.

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Derksen, J.W.G., May, A.M. & Koopman, M. The era of alternative designs to connect randomized clinical trials and real-world data. Nat Rev Clin Oncol 16, 589 (2019). https://doi.org/10.1038/s41571-019-0250-0

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