The patient perspective on a particular therapy covers a wide range of information including patient feedback in the form of FDA correspondence, testimony at Advisory Committee meetings, patient opinions offered on social media, as well as qualitative measures collected by patient surveys and patient-reported outcome (PRO) tools. The assessment of PROs can complement those of clinical endpoints in cancer treatment, such as progression-free survival, overall survival, and toxicities to gain a broader assessment of a therapy’s overall benefit. In fact, PROs may help differentiate cancer treatments that otherwise have similar clinical benefit.
Aside from traditional clinical endpoints, the effect of a therapy on patient quality of life and symptoms are important measures of treatment success. Quality of life is often captured as PROs using validated instruments. Validated instruments undergo rigorous testing to confirm that what they measure is valid and responsive to change, rendering it a reliable indicator of the effect of treatment. Coupled with evidence of clinical benefit, e.g., improved survival, evidence of improved quality of life speaks directly to the patient perspective and carries significant weight to various healthcare stakeholders in addition to the patient.
When therapy is necessary in men with prostate cancer, radiotherapy offers comparable clinical benefit (e.g., cure rates) to prostatectomy, but rates of erectile dysfunction, urinary continence, and bowel function as a result of these therapies differ and are of great significance to patients. As patients weigh the potential for side effects; route of administration; and time, duration, and frequency of administration, the voice of the patient plays a pivotal role in treatment decisions. While hair loss is common during chemotherapy for breast cancer, some drugs and modes of administration are associated with higher rates of alopecia than others. Similarly, a patient’s perspective on avoiding hair loss is a strong influence on patient choice in breast cancer treatment.
Both the FDA and the European Medicines Agency (EMA) encourage the use of PROs in the drug development process for cancer therapies in order to provide additional context to clinical endpoints commonly evaluated by these agencies.[2, 3] The FDA considers assessment of signs and symptoms due to the cancer, often patient-reported, when evaluating evidence for cancer drug approvals. The American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology (ESMO) have each developed value frameworks for cancer treatments that highlight the role of PROs in evaluating value.[4, 5] In addition to considering clinical benefit and toxicity in its net health benefit (NHB) score, the ASCO Value Framework adds bonus points for patient-reported measures of quality of life and palliation. PROs are even considered in formulary decisions by payers. While PROs may not carry the same clout as clinical endpoints, PROs are considered complementary data and may be differentiators for payers when considering reimbursement.
Despite the extensive endorsements by regulatory agencies, professional societies, and payers, the implementation and success of PROs in the drug development process has been slow. One reason for this gradual progress is a lack of a standard approach to the measurement, collection, and analysis of PRO data. Manufacturers are, nevertheless, increasingly including PRO data as part of the regulatory submission package. A recent review of drug approvals from 2012 to 2016 found that out of 64 indications reviewed, the FDA did not approve any PRO labeling, despite PRO data being available in 45 of these submissions. The EMA, on the other hand, approved about one-third of these submissions to include PRO labeling. Without PRO labeling, which are developed by manufacturers with approval by the FDA and define the content available for legal promotion of the drug, PRO data cannot be a part of the marketing for the drug.
The FDA and EMA encourage the use of PROs in phase 3 trials as endpoints for drug approvals. However, as clinical trials are controlled environments where patient populations are highly selective, they may not reflect the demographic, clinical, or lived experience of real-world patients. As such, PRO data collected in trials can only provide insights into those highly selected populations. The use of PROs in observational research outside of the clinical trial setting may better characterize the patient perspective that can be generalized to the larger patient population. Nevertheless, there are challenges to collecting these data in a real-world setting.
Cancer patients tend to be an engaged patient population, showing interest in expressing their patient perspective and participating in PRO research if they are able. Identifying the correct patient population among whom to collect PRO data can be facilitated by collaborations with patient advocacy groups whose membership comprises patients with specific diagnoses. However, confirming certain clinical information about the patient (e.g., diagnostic criteria, date of metastatic disease, mutational and biomarker status, details around complex chemotherapy regimens) is limited when relying on self-reporting by participating patients. Connecting PRO data to their treating physicians, who would have these clinical data, has been met with little success in the past, in part due to the divergent priorities and incentives across these sources of data.
Cardinal Health is addressing the challenge of linking the clinical data necessary to establish the target patient population and PRO data through the creation of the Practice Research Network (PRN). The PRN consists of clinical practice sites with existing research infrastructure, including research coordinators who will screen and enroll eligible patients in RWE studies involving PROs. Once a patient is enrolled, clinical data will be abstracted from their medical record to provide the complement to the data collected from the patient perspective. Enrolled patients will complete questionnaires comprised of validated PRO instruments over the course of their treatment; at each routine office visit, clinical data will be abstracted from their medical record alongside the completion of their patient questionnaire.
While there are limited examples of PRO labeling in the U.S., the growing attention to the use of RWE in regulatory decision making is expected to see this change. The collection of PRO data outside of the clinical trial setting is an opportunity to incorporate the patient perspective in a patient population representative of those receiving care in the real-world setting, whether intended for label expansion by the FDA or to add to the clinical evidence for the broader group of healthcare stakeholders.