Data Standards and ePRO Systems: A Road Less Travelled?

The potential benefits arising from the standardization of processes and approaches to clinical trial data acquisition and submission are manifold, with speed, efficiency, enhanced data quality, reduced risk to trial execution, and support to regulatory reviewability being arguably the most compelling. The Clinical Data Interchange Standards Consortium (CDISC) has had a remarkable impact on medical product development, and yet we see opportunities for further benefits derivable from CDISC standards implementation in the context of electronic patient-reported outcome (ePRO) systems and electronic clinical outcome (eCOA) systems more broadly.

FDA and Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) have required data to be submitted in CDISC format for some time.^1,2 The European Medicines Agency announced in October 2022 its intention to explore the value of having access to raw patient-level data in a standardized format, namely study data tabulation model and analysis data model formats via a proof-of-concept pilot.³ This suggests that a similar expectation around CDISC standard usage for submission data is on the horizon.

Though ePRO systems have been integral components of clinical trials for almost as long as CDISC has existed, there may be a presumption that CDISC standards are fully embedded by default in ePRO dataset creation, but this is not the case. Therefore, to satisfy FDA and PMDA requirements, extensive data mapping is necessary to enable regulatory review. This manual effort typically falls to the sponsor’s in-house or external analytic functions, and has a negative impact on resources, data quality, and ultimately the time to potential regulatory approval. It is evident that while CDISC standards have matured extensively over the last 20 years, those applicable to ePRO and other types of eCOA data have not matured similarly; COA data acquired electronically shouldn’t be treated any differently from that derived from paper sources.

To help address this issue and foster better alignment between standards at source to those at submission, a multi-stakeholder initiative was launched by Critical Path Institute’s eCOA Consortium and Patient-Reported Outcome (PRO) Consortium with key representation from analytic experts and CDISC itself, as well as consultative input from FDA.

The resulting paper⁴ examines the prevalent issues around ePRO dataset content and structure and illustrates the critical need to embed CDISC standards throughout the ePRO data continuum. The paper examines the importance of “having the end in mind” when designing ePRO systems, and the implications of not involving key stakeholders in the earliest stages of ePRO system development. Among other best practice recommendations, the initiative also incorporated surveys of eCOA providers and sponsors on typical approaches to ePRO dataset definition. It is apparent from the initiative that ownership of this very necessary alignment sits on both sides of the sponsor-provider relationship.

Beyond the regulatory requirements driving this need to realign on how we arrive at submission-ready datasets, a key concept at the heart of this work was of ePRO data lineage, which adoption of CDISC standards supports but is impaired when any manual processing is involved. Full traceability of data from capture through to reporting and submission should be a central expectation.

Best practice recommendations around eCOA data changes have long been desired, and the eCOA Consortium, PRO Consortium, and eClinical Forum will have a collaborative paper on this topic published later in 2023. A further project between the eCOA Consortium and PRO Consortium examining the various components of eCOA data management is well into its scoping phase and targets a full project launch this summer.

Authored on behalf of Critical Path Institute’s eCOA Consortium by Scottie Kern, Executive Director.

References

1. FDA, Providing Regulatory Submissions in Electronic Format - Standardized Study Data (June 2021). https://www.fda.gov/media/82716/download
2. Pharmaceuticals and Medical Devices Agency, Electronic Data Promotion Group (August 2016). https://www.pmda.go.jp/files/000215100.pdf
3. European Medicines Agency, Information About the Raw Data Proof-of-Concept Pilot for Industry (October 2022). https://www.ema.europa.eu/en/documents/other/information-about-raw-data-proofconcept-pilot-industry_en.pdf
4. Hudgens, S.; Kern, S; Barsdorf, A.I.; et al. Best Practice Recommendations for Electronic Patient-Reported Outcome (ePRO) Dataset Structure and Standardization to Support Drug Development. Value in Health. February 25, 2023, https://doi.org/10.1016/j.jval.2023.02.011