Patient-Centered Initiatives at the FDA

A Conversation With Vishal Bhatnagar, MD, Bellinda King-Kallimanis, PhD, Janice Kim, PharmD, and Paul G. Kluetz, MD

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OCE Insights is a periodic column developed for The ASCO Post by members of the Oncology Center of Excellence (OCE) at the U.S. Food and Drug Administration (FDA). In this first installment, Vishal Bhatnagar, MD, Acting Associate Director of Patient Outcomes; Bellinda King-Kallimanis, PhD, Senior Staff Fellow; Janice Kim, PharmD, Regulatory Health Project Manager; and Paul G. Kluetz, MD, Deputy Director at the OCE, explore a variety of patient-focused policy initiatives aimed at understanding and reporting the patient experience in clinical trials and real-world settings.

Vishal Bhatnagar, MD

Vishal Bhatnagar, MD

Bellinda King-Kallimanis, PhD

Bellinda King-Kallimanis, PhD

Janice Kim, PharmD

Janice Kim, PharmD

Paul G. Kluetz, MD

Paul G. Kluetz, MD







Patient-Focused Drug Development

What is the role of the OCE’s patient-focused drug development (PFDD) program?

The OCE currently has a number of important initiatives. Our PFDD program is centered around patient outcomes research in cancer populations. We are interested in improving the measurement of clinical outcomes—symptom and functional outcomes assessed through measures such as patient-reported outcomes, or “PROs”—as well as identifying ways to make trials more patient-friendly across the drug development cycle.

Although we have focused on improving methods around collection, analysis, and interpretation of PRO data, the PFDD program has a larger purpose, which includes efforts to broaden eligibility criteria, identify patient-friendly language, leverage digital health tools, and explore additional research topics. A few initiatives we are working on include the creation of patient-friendly definitions for clinical trial terms, standardizing analytic methods for PRO data, and exploring methods to measure both physical function and summary measures of overall side effect impact. We are actively working with domestic and international members of the patient advocacy, academic, policy, and industry communities to advance progress in these areas.

Recent Activities

What are some recent developments from this team?

In July, we held our fourth annual Clinical Outcome Assessments in Cancer Clinical Trials workshop, which was cosponsored with ASCO. At this meeting, we explored the use of physical function as an outcome measure, advancing the standardization of data collection, measurement tools, endpoints, analysis, and visualization with respect to regulatory decision-making in oncology.

We are also working on drafting guidance documents on the use of patient-reported outcomes in cancer trials. The first guidance document provides our current thinking regarding the use of PRO to assess symptomatic side effects. The second puts forth a core set of clinical outcomes to measure in cancer trials and includes information on trial design considerations, including assessment frequency.

We hope that our recent and future work will help the field move forward, lead to higher-quality clinical outcome data in regulatory submissions, and, in turn, provide interpretable information for patients and practitioners about disease symptoms, symptomatic adverse events, and physical function in cancer trials.

Patient-Reported Data in Cancer Trials

Are patient-reported outcomesbeing collected in oncology clinical trials?

Yes, patient-reported symptoms and function have long been captured in cancer clinical trials to both complement standard safety and efficacy data for regulatory review as well as support global health technology assessment. There are several reasons why there is an increase in interest regarding clinical assessments such as PROs. In December 2016, the 21st Century Cures Act tasked the FDA with taking submitted patient-experience data into account in the benefit-risk determination for regulatory submissions. In addition, sponsors are interested in opportunities to differentiate their product among an increasing number of therapeutic options.

We are interested in improving the measurement of clinical outcomes … as well as identifying ways to make trials more patient-friendly across the drug development cycle.
— Paul G. Kluetz, MD

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The collection of PRO data in cancer trials has also benefited from new measurement systems developed at the National Institutes of Health, such as the patient-reported outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) and the Patient-Reported Outcomes Measurement Information System (PROMIS). Even in early-phase oncology trials, patient-reported outcomes data can complement standard safety data, identifying tolerability issues that could affect adherence, an important issue with oral anticancer medications.

Impact on Drug Review

How has the inclusion of PRO assessments affected the review of oncology drugs?

The FDA is using patient-reported outcomes data quantifying symptoms and/or function to support regulatory decisions when the data are of sufficient quality. We have used PRO data to support disease symptom improvement (ie, efficacy) as well as to describe important tolerability considerations with cancer drugs. Because of the richness of the PRO data, they can be analyzed in many ways.

To aid our review, we have generated a standard set of analyses and have sent companies a document outlining how to analyze and submit their patient-reported outcomes data so that they can be most useful for the FDA clinical and statistical reviewers. Because the data are being presented in the same way across trials, it becomes easier for reviewers to find the key takeaways.

An example of how patient-reported outcomes data were used in drug review, approval, and labeling was the use of a measure to describe patient perception of the impact of certain visual side effects (eg, floaters, shimmering lights, difficulty seeing at night) from the targeted lung cancer therapy crizotinib. This patient experience information was included in the safety section of the FDA product label.

Patient-Reported Data in Professional Presentations

How should clinicians, academics, patients, and caregivers approach patient-reported outcomesdata presented in journal publications or academic conferences?

Patients spend a lot of time completing PRO surveys in cancer trials, and we are supportive of the increased publication of patient-reported outcomes data in academic journals and presented at conferences. Although we are pleased to see these data entering the mainstream oncology landscape, their presentation is heterogeneous and occasionally misleading.

We urge sound methodologic approaches, good data quality, and nonmisleading analysis. Most importantly, these data need to be interpretable and usable for patients and providers. Our vision is that PRO results can be conveyed in a standard, rigorous fashion to facilitate familiarity among those who are interested in interpretable information on symptoms and function from cancer trials.

Looking Ahead

What are some priorities for the OCE PFDD program in the next year?

The field has made considerable process in standard approaches to measurement and analysis of patient-reported outcomes data. The next step is to collaborate with patients, advocates, and drug developers on appropriate visualizations to communicate symptomatic adverse event and physical function data in a way that is clear and interpretable.

Although patient-reported symptomatic adverse event data from key symptoms are usually collected as part of registrational trials, this information is often difficult for the public to access. One of our short-term goals is to facilitate access to patient-reported symptomatic adverse event data to supplement the known safety data from the product label. We will be working on visualization techniques and seeking feedback from stakeholders in the next year. We are also beginning work on identifying standard analytic methods and visualizations for patient-reported physical function. 

DISCLOSURE: Drs. Bhatnagar, King-Kallimanis, Kim, and Kluetz reported no conflicts of interest.