By: Paul G. Kluetz, M.D., Associate Director of Patient Outcomes at the FDA Oncology Center of Excellence

Cancer therapies are typically evaluated based on their ability to control the growth of a tumor or extend life. Tumor response and survival data are strong trial endpoints that remain the mainstay of regulatory review, but cancer patients have other meaningful concerns as well, such as coping with treatment-related side effects that can impact their ability to function, as well as other aspects of their quality of life. In short, cancer therapies treat patients … not just their disease.

The Oncology Center of Excellence Patient-Focused Drug Development Program fosters collaboration between FDA Centers and external stakeholders involved in patient outcomes research in cancer populations. The program focuses on three key areas:

• Actively engaging with patients and advocacy groups
• Fostering research into measurement of the patient experience
• Generating science-based recommendations for regulatory policy

The overarching goal of the program is to identify rigorous methods to assess the patient experience that will complement existing survival and tumor information to better inform a cancer therapy’s effect on the patient.

Learning from Patient Experiences

One way patient experience has been quantified is through the use of patient-reported outcome data, collected from rigorously developed and reliable patient questionnaires. These questionnaires, which cover such topics as the patient’s symptoms and the burden of these symptoms on their everyday life, are now commonly used in clinical trials across therapeutic areas. The results are weighed as part of a regulatory approval and can be incorporated in a product label.

For example, the FDA has used patient-reported outcome information quantifying symptoms and/or function as evidence to support regulatory risk-benefit decisions in several hematology and oncology approvals. In one case, the data demonstrated improvements in symptoms such as pain, itching and night sweats in patients who took Jakafi (ruxolitinib) to treat a rare disease of the bone marrow called myelofibrosis. Another example is the approval of Hemlibra (emicizumab) for patients with hemophilia, where patient-reported outcome data showed improvements in patients’ joint pain, swelling and mobility.

In addition to providing evidence of efficacy, an important objective for patient-reported outcome measures is to inform safety and tolerability. An example is the use of a measure to describe patient perception of the impact of certain visual side effects (e.g. floaters, shimmering lights, difficulty seeing at night) from the targeted lung cancer therapy Xalkori (crizotinib). This important data provided detailed patient experience information that was included in the safety section of the FDA product label.

To accurately communicate patient experience data, it is critical that we develop standard approaches to measurement and analysis so that all those involved in clinical trials and drug development can familiarize themselves with interpreting results. Patient-report outcome measurement and analysis is past its infancy of the 1980s and 1990s but has yet to reach the maturity seen in other measures commonly used in oncology, such as measures of tumor shrinkage, with internationally agreed upon criteria.

Collaborating with Patients, Public and Private Sectors

The Oncology Center of Excellence is looking at several issues related to symptom and functional measurement, including standardized analytic and visualization methods for patient-reported outcome data in order to accurately interpret and communicate results. These efforts require clinical reviewers to work closely with statisticians and social scientists across different FDA Offices and Centers. In addition to internal collaboration, we proactively engage external groups to advance the measurement and analysis of patient-reported outcomes. The Patient-Focused Drug Development Program is actively participating along with members of the FDA’s Center for Drug Evaluation and Research’s (CDER) Office of Biostatistics and the National Cancer Institute in several national and international working groups and collaborations.

Outside of controlled clinical trials, obtaining data from patients through electronic patient-related outcome measures during routine treatment by their oncologist is a promising method to improve patient-clinician communication that can also generate structured real-world data. Recently, the Oncology Center for Excellence and the Division of Research of The Permanente Medical Group signed a research collaboration agreement to study the use of patient-reported outcome measurement of physical function in pancreatic cancer patients who are undergoing treatment and follow-up for their illness. Newly diagnosed pancreatic cancer patients are now being enrolled in a prospective natural history study at Kaiser Permanente Northern California called Pancreatic Cancer Patient Reported Outcomes Using the Electronic Medical Record (PanPROE). Through the PanPROE study, Kaiser and FDA investigators hope to learn more about the measurement of patients’ perceptions of physical functioning throughout their pancreatic cancer treatment journey.

In another initiative, the Oncology Center of Excellence Patient-Focused Drug Development Program collaborated with colleagues across the FDA, the National Institutes of Health, and the Department of Health and Human Services, on a journal publication to address concerns raised by trial sponsors regarding the use of patient-reported outcome measures to assess safety and tolerability in clinical trials. The article explores issues related to clinical monitoring, safety reporting and clinical site inspections.

Fostering Continued Engagement

To continue advancing our efforts to increase the rigor of patient-reported outcome measures in cancer trials, the FDA hosted its 3rd public workshop in June 2018, in collaboration with the American Society for Clinical Oncology. The Clinical Outcome Assessments in Cancer Clinical Trials workshop provided a public forum to discuss efforts to assess a core set of patient-reported outcomes and develop standardized analysis and presentation methods. The workshop included international regulators, payors, academics, patients, industry, and policy leaders. The next public workshop is scheduled for July 12, 2019.

The Oncology Center of Excellence Patient-Focused Drug Development Program fosters collaboration among the FDA Centers and external stakeholders involved in patient outcomes research in cancer populations. We look forward to our continued engagement with cancer patients and advocacy groups, and will encourage research into the measurement of patient experiences so that we can use this information to generate science-based recommendations for patient-centered regulatory policy.