Patient-Reported Outcome (PRO) Data in Oncology Trials – Part 1: Regulations

Sarah Gary and Rinah Yamamoto | |

In recent years, regulatory agencies such as the FDA and EMA have increasingly promoted the use of patient-reported outcomes (PRO) data in the development and approval of cancer products. While the standard primary endpoint for oncology trials is focused on survival and overall response, more recently regulatory agencies are also placing weight on the importance of PRO-based secondary endpoints that are indicative of clinical benefit in terms of patient symptoms and overall quality of life. In addition, elevating PRO data within the endpoint hierarchy and including PRO-based label claims is a mechanism to help differentiate a cancer product.

This review focuses on the latest guidance from the FDA and EMA regulatory agencies recommending the use of PROs in oncology trials.

Regulators expect PRO data when evaluating cancer products

What Regulators Want

Regulatory agencies have been placing more and more focus on capturing the patient experience when developing drugs. In 2018, the FDA, EMA, and Health Canada released a policy review on “Incorporating the patient experience into regulatory decision making in the USA, Europe, and Canada” focused on clinical development of cancer therapeutics.1 This joint policy review shows a global alignment among regulatory agencies on the importance of PROs in oncology drug development.

  • FDA: The FDA’s initial focus for oncology product PRO-based labeling is on PRO ─ measures of disease and treatment related symptoms ─ and physical function, but highlight that other aspects of the patient experience, such as health-related quality of life (HRQL), are also important to measure and will be taken into account as part of the full picture.
  • EMA: The EMA discusses both PROs and HRQL and has published a reflection paper on the use of HRQL in the evaluation of medicinal products, as well as in 2016 released “Appendix 2 to the guideline on the evaluation of anticancer medicinal products in man: The use of patient-reported outcome (PRO) measures in oncology”.2

Focus on the Patient

In December 2018, the FDA released an update to their guidance “Clinical Trials Endpoints for the Approval of Cancer Drugs and Biologics”.3 The guidance states: “[…] cancer drug approval should be based on more direct evidence of clinical benefit, such as improvement in survival, improvement in a patient’s quality of life, improved physical functioning, or improved tumor-related symptoms.”

Notable updates to the FDA oncology guidance include the emphasis on collecting cancer patient and caregiver experience data and reference to their recent guidance on Patient-Focused Drug Development which encourages the use of patient input when developing drugs.4 Symptom improvement/palliation was added as a specific endpoint that is a direct measure of clinical benefit, in addition to time to progression of cancer symptoms. Endpoints for labeling should be based on proximal cancer-specific symptoms and physical function rather than more distal HRQL.

Avoid Missing Data

The guidance also emphasizes the importance of minimizing missing data: “Missing data and infrequent assessments can complicate the evaluation of symptom data particularly for time to deterioration analyses. Procedures should be put in place to maximize completion rate during trial conduct […]”. Electronic data capture or electronic patient reported outcomes (ePRO) is one mechanism to reduce missing data, reduce patient burden and to allow for more frequent collection.


Taken together, regulatory agencies are placing more focus on the secondary outcome PRO data in addition to survival and overall response when evaluating the clinical benefit of oncology products. Missing data and infrequent collection should be avoided when collecting symptom data, and electronic data capture can help achieve this goal.


Sarah Tressel Gary, PhD and Rinah Yamamoto, PhD are Senior Scientific Advisors at ERT.



    1. Kluetz PG et al. Incorporating the patient experience into regulatory decision making in the USA, Europe, and Canada. Lancet Oncol. 2018 May;19(5):e267-e274
    2. EMA. Reflection paper on the regulatory guidance for the use of health-related quality of life (HRQL) measures in the evaluation of medicinal products. EMA, 2005; EMA. Appendix 2 to the guideline on the evaluation of anticancer medicinal products in man: The use of patient-reported outcome (PRO) measures in oncology. EMA, 2016
    3. FDA. Clinical Trials Endpoints for the Approval of Cancer drugs and Biologics: Guidance for Industry. FDA, 2018
    4. FDA. Patient-Focused Drug Development: Collecting Comprehensive and Representative Input: Guidance for Industry, Food and Drug Administration Staff, and Other Stakeholders (Draft Guidance). FDA, 2018