The patient voice in cancer clinical research and clinical practice is becoming increasingly important. Patient-centered care strategies can positively impact patients’ trust in their doctors and their quality of care.1
The U.S. Food and Drug Administration’s (FDA) patient-focused drug development guidance series specifically addresses the value of patient feedback and experience. There has been an increase in the use of patient-reported outcomes (PROs) in oncology trials; however, despite the valuable information that this data provides, the inclusion of PROs in anti-cancer therapy labelling remains inconsistent and limited.2,3
Enhancing Clinical Outcome Assessment Measurement across Development Phases
There has been significant variation in clinical outcome assessment (COA) measurement strategy across cancer trials and the way PROs have been implemented, with concerns about instrument suitability, optimal timing of assessments, and capture of reasons for missing patient data flagged by the agency. To address these challenges, the FDA has provided comprehensive recommendations regarding the application of PROs in cancer trials, to help standardize and improve inference making using PRO data.4
Key recommendations from the FDA include:
- PRO instrument selection/adaptation: ensure specificity of measures to report across 5 core domains – disease-related symptoms, symptomatic adverse events (AEs), overall side effect impact summary measure, physical function, and role function.
- Frequency of PRO data collection: include optimal measurement frequency, departing from pre-cycle measurement to frequent within-cycle assessments to be completed at home by patients.
- Missing data mitigation: develop clear strategies to mitigate missing data and capture reasons for missing PRO data to enable intercurrent events to be correctly accounted for in statistical analyses.
Further, the importance and value of PRO data to measure aspects of tolerability in early phase/dose optimization studies is underlined by the FDA’s Project Optimus and their subsequent guidance on optimizing the dose of new oncological treatments.5
The patient perspective is a vital component of tolerability assessment, but PROs are to date seldom included in early phase studies. Physician assessment of patient AEs may be incomplete and underestimated compared to patients’ perspectives.6 Therefore, collection of patient-reported AEs to support information from clinicians on solicited AEs (e.g., using the Common Terminology Criteria for Adverse Events (CTCAE) measure) is needed.
The FDA encourages the use of the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) to accurately capture symptomatic AEs in cancer trials.
Signant Health has developed a solution to present patients with all 78 symptomatic AEs contained in the measure. Patients can select the relevant AEs from body-system groupings to enable rapid navigation and completion of the questionnaire items associated with those AEs experienced. This approach enables weekly completion in around 5 minutes, ensuring low patient burden and a comprehensive understanding of AEs experienced in early phase studies where less is known a priori about the side effect profile of the investigational treatment.
Patient-Reported Outcomes in Routine Oncology Care
Recently, integration of ePRO solutions for symptom monitoring in routine cancer care has been shown to lead to valuable patient benefits.7 The following benefits for cancer patients of oncology practices employing weekly symptom surveys were demonstrated:
- First emergency visit occurred later, with fewer visits overall.
- Deterioration of physical function, symptoms, and health-related quality of life quality-of-life was delayed.
- Patients expressed positive feedback relating to communication with their care teams and personal empowerment.
This ongoing symptom monitoring and real-time data access afforded by at-home electronic capture of PROs in cancer clinical care allows care teams to proactively intervene and manage side effects early and effectively, leading to better outcomes for patients.
Electronic solutions may also have the potential to provide instant feedback to patients in addition to care team interventions, for example providing approved individualized advice on strategies to mitigate specific AEs reported. They can also provide insight into treatment outcomes and help optimize treatment strategies based on patient feedback. PRO collection in clinical practice thus not only drives better symptom control but also helps tailor care decisions to individual patient needs.
Conclusion
The patient voice in cancer clinical trials provides important information, beyond traditional outcomes such as tumor response and survival, informing risk/benefit assessment.
Integrating the FDA’s recommendations into study designs increases the likelihood of PROs being included in label claims. Importantly, tolerability assessment without patient-reported AEs may be considered incomplete in the future and is likely to become a firm requirement by the FDA. Further, PROs in the context of clinical practice can improve symptom control and help to inform and adapt routine care and decision-making. Digital health tools and real-time patient data collection and monitoring are transforming cancer research and care. Thoughtful application of PROs in clinical trials and routine practice will be central for future advancements, ensuring that treatments align more closely with patient experiences and needs. Ongoing integration of technology and patient-centric approaches can improve outcomes and lead to a more responsive and individualized journey for cancer patients.
Greta van Schoor, PhD provides scientific expertise and guidance relating to the implementation of electronic clinical outcome assessments (eCOAs) and has a special focus on eDiary design and accessibility of eCOA best practices. She completed her PhD in Physiological Sciences at Stellenbosch University, which focused on the bacterial and inflammatory involvement in colorectal carcinogenesis, and has 3+ years’ experience in the clinical research industry. She has given scientific consultation for projects across a wide range of therapeutic areas, including oncology, infectious disease, dermatology, and gastroenterology.
Todd Everhart, MD, FACP, is the internal medicine leader at Signant. Dr. Everhart is board-certified in internal medicine and a fellow of the American College of Physicians with over 23 years of experience in the practice of medicine and over 12 years of experience in clinical development. Prior to joining Signant, Dr. Everhart held positions of Vice President, Medical Affairs and Vice President, Medical Informatics at Chiltern and Covance, and consulted independently in the areas of medical monitoring, medical data review, data analytics, and physician adoption of technology. He has worked in all phases of clinical development in numerous therapeutic areas including allergy & immunology, cardiovascular, hematology & oncology, infectious disease & HIV, neurology, ophthalmology, psychiatry, respiratory, and rheumatology.
Bill Byrom, PhD has over 30 years’ experience as a clinical development specialist, an eClinical product strategy leader, and an industry expert in clinical outcome assessments. He has authored 80+ publications and two industry textbooks on electronic patient-reported outcomes (ePRO), and his recent research includes the use of wearables and bring-you-own-device (BYOD) eCOA in clinical trials. At Signant he provides eCOA science expertise into customer projects and company strategy.
