How Should Patient-Reported Outcomes Be Used in Drug Development?

Given the evolving health care environment and an increased focus on comparative effectiveness research, it is important, and, in some cases, essential, to consider integrating patient-reported outcomes (PROs) into both research and clinical care in hematology. During the 57th American Society of Hematology Meeting and Exposition, experts discussed the advances in measurement of PROs, the integration of PROs in drug development, and their use in clinical care.

Patient-Reported Outcomes

“You really have to take on the patient’s experience with treatment and factors like disease symptoms, side effect burden, and tolerability. It’s not a one size fits all treatment scenario,” said David Cella, PhD, professor, department of medical social sciences, Feinberg School of Medicine, Northwestern University, and associate director, prevention and control research, Robert H. Lurie Comprehensive Cancer Center.

One ongoing initiative focused on patient outcomes is the National Institutes of Health’s PROMIS, which was established in 2004. Dr Cella, a pioneer in the field of PRO measures and a PROMIS principal investigator, described the system’s capabilities. “PROMIS is domain specific, not disease specific,” he said. PROMIS aims to provide clinicians and researchers access to efficient, precise, and valid measures of patient-reported health status across 7 domains for physical (physical function, pain interference, fatigue, sleep disturbance); mental (depression, anxiety); and social health (ability to participate in social roles and activities). “There is a lot of value in asking questions symptomatically,” said Dr Cella.

In hematology-oncology, for example, PROMIS measures can be used as primary or secondary endpoints in clinical studies of effectiveness of treatment. PROMIS has constructed item banks—a collection of questions measuring the same thing that can be administered in short forms or through computerized adaptive testing. The PROMIS metric is a T-score that has a mean of 50 and a standard deviation of 10, and the scores are referenced to the US general population.

Future direction of PROMIS includes developing and testing disease-specific branches of PROMIS. One of those branches is the Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me). This system documents effects of sickle cell disease on adult functioning and well-being; helps characterize the efficacy of therapies tested in randomized; controlled trials; and helps evaluate the comparative effectiveness of therapies.

PROs and Drug Development

Virginia E. Kwitkowski, MS, ACNP-BC, associate director labeling, division of hematology products, FDA, discussed the importance of PROs in drug development. “Patients are the primary recipients of treatment and it is crucial to recognize the value of the patient’s perception of change and response to any treatment,” she said, adding that patients, prescribers, regulators, and payers are the stakeholders who want PRO data.

While the patient perspective is important, how one measures it is challenging. In 2009, the FDA finalized guidance for good measurement principles specifically for PROs when they are intended to be used as support for labeling claims. Kwitkowski said that PROs can provide important answers for drug development. For example, Does the drug provide superior improvement in disease-related symptoms of functional deficits? How does the patient feel and function while on therapy? However, in hematology-oncology, PROs provide some limitations. Historically, PROs were assessed with static-global health-related quality of life (HRQOL) instruments, and randomized, blinded trials are rare in this setting. “Because of these limitations, the FDA thought a modular PRO approach may offer a more adaptable and sensitive assessment in the clinical trial context where the objective is defining the safety and efficacy of therapy,” she said.

HRQOL is a common PRO strategy, therefore, the FDA’s modular approach recommends focus on 3 core concepts of disease, treatment, and physical symptoms that are important contributions to HRQOL. This provides a more flexible and well-defined assessment that may be more sensitive to a drug’s effect.

A key component across drug trials is the systematic assessment of treatment-related toxicities. One new program that appears promising to assess symptomatic treatment side effects is the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE), which is funded by the National Cancer Institute. PRO-CTCAE is an electronic patient-reported system for monitoring and reporting symptomatic adverse events that patient’s may experience during treatment. “The status quo for clinician-reported safety data can be improved by inclusion of patient-reported toxicities in hematology-oncology clinical trials,” Kwitkowski said. “FDA staff are actively working with stakeholders to evaluate opportunities for integration of PRO-CTCAE in registration trials with potential for inclusion of descriptive data in product labeling.”

PROs in Clinical Practice

Implementing PROs in clinical practice is complex and complicated, but is feasible according to Julie A. Panepinto, MD, MSPH, professor, department of pediatrics, division of hematology/oncology, Medical College of Wisconsin. PROs can help with decision support such as the impact of the disease and/or therapy on functioning and well-being.

Studies have examined the use of electronic PRO systems to demonstrate real-time feasibility, said Dr Panepinto, highlighting a study by Jensen and colleagues (Jensen RE, Synder CF, Abernethry AP, et al. Review of electronic patient-reported outcomes systems used in cancer clinical care. J Oncol Pract. 2014;10[4]:e215-e122) that looked at 33 electronic PRO systems implemented in cancer clinical practice. The study showed that 44% of systems integrated PRO results into the electronic medical record, 96% of systems provided PRO result summaries to providers, and 63% of systems provided results to patients. The researchers concluded that PRO data continues to be increasingly important to health care. “Systems can be programmed to have numerous features that facilitate integration of PRO assessment and routine monitoring into clinical care,” they said.

PROs in performance improvement is also gaining increased attention because of the focus on value of health care. “For health care systems, it [PROs] can help track and report health care delivery systems’ performance and, more importantly, it can help improve outcomes of population and contribute to better overall health and quality of care,” Dr Panepinto said.—Eileen Koutnik-Fotopoulos