The US Food and Drug Administration (FDA) recently finalized a guidance document outlining the agency’s thinking on Submitting Patient-Reported Outcome Data Cancer Clinical Trials. This guidance lays out technical specifications to facilitate FDA review of marketing applications including patient reported outcome (PRO) data used to evaluate either safety and tolerability of a product or the clinical benefit of a product. A separate guidance document, Core Patient-Reported Outcomes in Cancer Clinical Trials, should be referred to when selecting PROs for a trial.

The guidance outlines specifics with respect to SDTM, ADaM, and summary tables and figures that should be considered by the programming and biostatistical teams.

SDTM Technical Notes:

• PRO data should be submitted within the QS domain
• Recommendations on how to handle missing data
• Information to be included within the Trial Summary (TS) dataset

ADaM Technical Notes:

• In addition to individual and summary scores, recommendation to also retain data collection mode (e.g. paper-based, handheld device), data collector (e.g., patient independently, not independently), and language.
• Recommendations on how to handle missing data
• Instructions on how to handle phantom records within ADQS. Phantom records are handled differently depending on whether the PRO is to support safety and tolerability or clinical benefit.
• Information, and examples, on how to derive PARCAT to ensure transparency on which items are utilized to derive subscale and summary scores.

Tables and Listings Technical Notes:

• In addition to the analysis tables for the PRO the FDA requests the following tables and figures be presented within the CSR. Thoughtful examples are provided for all tables and figures within the document to ease implementation.
  • Patient disposition to clarify which subjects the PRO was expected
  • Data completeness of the PRO
  • Distribution of responses
  • Distribution of change in responses from baseline

The guidance illustrates the importance of choosing a PRO vendor that is capable of capturing the recommended content and framework as source data if possible. This will reduce the need for time-consuming and potentially error prone data manipulation in SDTM and ADaM.

Do you have questions on implementation of CDISC standards with respect to PROs? Contact us to talk to one of our Data Standards Specialists.

Heather Kopetskie, Senior Director, Biostatistics, has worked at Rho for more than 19 years. Ms. Kopetskie provides leadership and oversight for the biostatistics department and utilizes her experience to guide sponsors on the design and analysis of clinical trials. Her experience spans many therapeutic areas with an emphasis on solid organ and cell transplantation along with rare disease (orphan) products. Ms. Kopetskie has supported both federally funded projects and biotech/pharmaceutical companies. She has served as the biostatistical functional lead for the Immune Tolerance Network (ITN) Statistical and Data Coordinating Center and the Clinical Trials in Organ Transplantation (CTOT) Statistical and Clinical Coordinating Center overseeing more than 30 studies in the areas of allergy, immunology, and transplantation.

Charity Quick, Senior Director, Statistical Programming & Data Standards, has directed and supported statistical programming teams in more than 100 clinical studies across all development phases for more than 17 years. This includes analytical programming of ISS and/or ISE development in more than 15 marketing applications. Ms. Quick uses her deep industry experience and CDISC knowledge to develop strategic high-performing global programming and data standards teams to bring technical expertise and efficiencies to sponsor projects of all sizes. Her experience with data standards integration and reporting from study start to submission spans a variety of therapeutic areas with a focus on pain, CNS, and OA.