The need for ethical guidance for the use of patient-reported outcomes in research and clinical practice

To the Editor—Patient-reported outcomes (PROs) are increasingly being used in clinical research to provide evidence of the benefits and risk of therapy from a patient perspective. PRO data from clinical trials can inform regulatory approvals and drug labeling, clinical guideline development and health policy¹. Approximately one third of clinical trials include PROs collected through the use of patient questionnaires². Beyond trials, PRO data are also increasingly captured in observational research and routine clinical care to provide information on the burden of disease and real-world evidence of treatment safety and effectiveness³, for audit and benchmarking¹, and to monitor the status of patients and provide timely care tailored to individual needs. For instance, a study demonstrated that systematic web-based collection of information on symptoms led to improved health-related quality of life, survival and quality-adjusted survival, and fewer visits to the emergency room and hospitalization, among patients receiving chemotherapy for advanced solid tumors⁴. Patients value PRO trial results, as they can enhance clinician–patient communication about treatment options, which helps patients to feel more empowered in shared decision-making around their care⁵.

Despite the benefits of incorporating PROs in research and routine practice, several ethical challenges can hinder the uptake and benefit to patients of PRO data. The PRO content of trial protocols and reporting of PRO results are often suboptimal, missing data rates are high, and delay of the publication of PRO data is commonplace. A recent study evaluating 228 studies from the National Institute of Health Research Cancer Portfolio demonstrated that 50,000 patients were involved in studies that failed to publish the PRO data collected, which is considered unethical⁶.

PRO data collection is associated with a number of ethical considerations that must be addressed. An ethical consideration is defined as one that requires a choice based on moral considerations drawing on established principles, theories and values, that might have implications for the person’s or society’s welfare. The differing use of PROs in research and routine care settings, and review and/or use of data by clinical teams, may lead to uncertainties for patients about why data are being collected and data privacy—how their data are being viewed and used. Research indicates that in some instances, PRO measures may not reflect the perspectives of vulnerable groups or older people, which challenges bioethical principles and threatens the scientific validity of results⁷. The burden on patients associated with the completion of multiple questionnaires is also a concern. Of particular note is the lack of guidance on how staff should manage situations in which PRO data reveal ‘concerning’ levels of psychological distress or physical symptoms that may require an immediate response⁸. Evidence suggests research staff are handling such data inconsistently, which may lead to inequitable patient care, co-intervention bias and confusion.

Furthermore, PROs could be used for long-term follow-up to assess the impact of the coronavirus SARS-CoV-2 on patients’ quality of life and alert clinicians of potential life-threating symptoms⁹. The increased use of telehealth will also heighten the use of PRO data to monitor patients’ symptoms. Therefore, there is a need to ensure that this is done in an ethical way that protects patients’ safety and data.

To address these challenges, the PRO Ethics Steering Group, composed of PRO methodologists, patient partners and ethicists, is developing international, consensus-based guidelines for use by researchers and patient partners in preparing ethics submissions and for use by research ethics committees and institutional review boards in the assessment of PRO research. The guidelines will focus specifically on ethical considerations of PRO research and data collection in clinical practice, using methodological guideline development of the EQUATOR (Enhancing Quality and Transparency of Health Research) Network¹⁰. The development process will include a literature review, a modified Delphi exercise and an international consensus meeting involving members of research ethics committees, experts in research ethics, patient partners, trialists and PRO researchers. Given the dearth of guidance currently available, the authors plan to hold the Delphi exercise and consensus meeting with a view to publishing the guideline in 2021.