Introduction to PROs in Clinical Care & Research
PROs in Clinical Care
Snyder, C. F., et al. Implementing patient-reported outcomes assessment in clinical practice: a review of the options and considerations. Qual Life Res. 2012; 21(8): 1305-1314. PMID: 22048932.
ABSTRACT: PURPOSE: While clinical care is frequently directed at making patients “feel better,” patients’ reports on their functioning and well-being (patient-reported outcomes [PROs]) are rarely collected in routine clinical practice. The International Society for Quality of Life Research (ISOQOL) has developed a User’s Guide for Implementing Patient-Reported Outcomes Assessment in Clinical Practice. This paper summarizes the key issues from the User’s Guide. METHODS: Using the literature, an ISOQOL team outlined considerations for using PROs in clinical practice; options for designing the intervention; and strengths, weaknesses, and resource requirements associated with each option. RESULTS: Implementing routine PRO assessment involves a number of methodological and practical decisions, including (1) identifying the goals for collecting PROs in clinical practice, (2) selecting the patients, setting, and timing of assessments, (3) determining which questionnaire(s) to use, (4) choosing a mode for administering and scoring the questionnaire, (5) designing processes for reporting results, (6) identifying aids to facilitate score interpretation, (7) developing strategies for responding to issues identified by the questionnaires, and (8) evaluating the impact of the PRO intervention on the practice. CONCLUSIONS: Integrating PROs in clinical practice has the potential to enhance patient-centered care. The online version of the User’s Guide will be updated periodically.
Bennett, AV, Jensen RE, Basch E. Electronic patient-reported outcome systems in oncology clinical practice. CA Cancer J Clin. 2012; 62(5): 337-347. PMID: 22811342.
Patient-reported outcome (PRO) questionnaires assess topics a patient can report about his or her own health. This includes symptoms (eg, nausea, fatigue, diarrhea, pain, or frequent urination), physical functioning (eg, difficulty climbing stairs or difficulty fastening buttons), and mental health (eg, anxiety, fear, or worry). Electronic PRO (ePRO) systems are used in oncology clinical care because of 1) their ability to enhance clinical care by flagging important symptoms and saving clinicians time; 2) the availability of standardized methods for creating and implementing PROs in clinics; and 3) the existence of user-friendly platforms for patient self-reporting like tablet computers and automated telephone surveys. Many ePRO systems can provide actionable links to clinical care such as summary reports in a patient’s electronic medical record and real-time e-mail alerts to providers when patients report acute needs. This review presents 5 examples of ePRO systems currently in use in oncology practice. These systems support multiple clinical activities, including assessment of symptoms and toxicities related to chemotherapy and radiation, postoperative surveillance, and symptom management during palliative care and hospice. Patient self-reporting is possible both at clinical visits and between visits over the Internet or by telephone. The implementation of an ePRO system requires significant resources and expertise, as well as user training. ePRO systems enable regular monitoring of patient symptoms, function, and needs, and can enhance the efficiency and quality of care as well as communication with patients.
Jensen, RE et al. Review of electronic patient-reported outcomes systems used in cancer clinical care. J Oncol Pract. 2014; 10(4): e215-222. PMID: 24301843.
PURPOSE: The use of electronic patient-reported outcomes (PRO) systems is increasing in cancer clinical care settings. This review comprehensively identifies existing PRO systems and explores how systems differ in the administration of PRO assessments, the integration of information into the clinic workflow and electronic health record (EHR) systems, and the reporting of PRO information. METHODS: Electronic PRO (e-PRO) systems were identified through a semistructured review of published studies, gray literature, and expert identification. System developers were contacted to provide detailed e-PRO system characteristics and clinical implementation information using a structured review form. RESULTS: A total of 33 unique systems implemented in cancer clinical practice were identified. Of these, 81% provided detailed information about system characteristics. Two system classifications were established: treatment-centered systems designed for patient monitoring during active cancer treatment (n = 8) and patient-centered systems following patients across treatment and survivorship periods (n = 19). There was little consensus on administration, integration, or result reporting between these system types. Patient-centered systems were more likely to provide user-friendly features such as at-home assessments, integration into larger electronic system networks (eg, EHRs), and more robust score reporting options. Well-established systems were more likely to have features that increased assessment flexibility (eg, location, automated reminders) and better clinical integration. CONCLUSION: The number of e-PRO systems has increased. Systems can be programmed to have numerous features that facilitate integration of PRO assessment and routine monitoring into clinical care. Important barriers to system usability and widespread adoption include assessment flexibility, clinical integration, and high-quality data collection and reporting.
Basch, E et al. Symptom monitoring with patient-reported outcomes during routine cancer treatment: A randomized controlled trial. J Clin Oncol. 2016; 34(6): 557-565. PMID: 26644527.
ABSTRACT: PURPOSE: There is growing interest to enhance symptom monitoring during routine cancer care using patient-reported outcomes, but evidence of impact on clinical outcomes is limited. METHODS: We randomly assigned patients receiving routine outpatient chemotherapy for advanced solid tumors at Memorial Sloan Kettering Cancer Center to report 12 common symptoms via tablet computers or to receive usual care consisting of symptom monitoring at the discretion of clinicians. Those with home computers received weekly e-mail prompts to report between visits. Treating physicians received symptom printouts at visits, and nurses received e-mail alerts when participants reported severe or worsening symptoms. The primary outcome was change in health-related quality of life (HRQL) at 6 months compared with baseline, measured by the EuroQol EQ-5D Index. Secondary endpoints included emergency room (ER) visits, hospitalizations, and survival. RESULTS: Among 766 patients allocated, HRQL improved among more participants in the intervention group than usual care (34% v 18%) and worsened among fewer (38% v 53%; P
PROs in Research
FDA. Patient-reported outcome measures: Use in medical development to support labeling claims. 2009. From http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM193282.pdf.
This guidance describes how the Food and Drug Administration (FDA) reviews and evaluates existing, modified, or newly created patient-reported outcome (PRO) instruments used to support claims in approved medical product labeling.
Basch E, et al. Recommendations for incorporating patient-reported outcomes into clinical comparative effectiveness research in adult oncology. J Clin Oncol. 2012; 30(34): 4249-55. PMID: 23071244.
ABSTRACT: Examining the patient’s subjective experience in prospective clinical comparative effectiveness research (CER) of oncology treatments or process interventions is essential for informing decision making. Patient-reported outcome (PRO) measures are the standard tools for directly eliciting the patient experience. There are currently no widely accepted standards for developing or implementing PRO measures in CER. Recommendations for the design and implementation of PRO measures in CER were developed via a standardized process including multistakeholder interviews, a technical working group, and public comments. Key recommendations are to include assessment of patient-reported symptoms as well as health-related quality of life in all prospective clinical CER studies in adult oncology; to identify symptoms relevant to a particular study population and context based on literature review and/or qualitative and quantitative methods; to assure that PRO measures used are valid, reliable, and sensitive in a comparable population (measures particularly recommended include EORTC QLQ-C30, FACT, MDASI, PRO-CTCAE, and PROMIS); to collect PRO data electronically whenever possible; to employ methods that minimize missing patient reports and include a plan for analyzing and reporting missing PRO data; to report the proportion of responders and cumulative distribution of responses in addition to mean changes in scores; and to publish results of PRO analyses simultaneously with other clinical outcomes. Twelve core symptoms are recommended for consideration in studies in advanced or metastatic cancers. Adherence to methodologic standards for the selection, implementation, and analysis/reporting of PRO measures will lead to an understanding of the patient experience that informs better decisions by patients, providers, regulators, and payers.
Gnanasakthy, A et al. Patient-Reported Outcomes Labeling for Products Approved by the Office of Hematology and Oncology Products of the US Food and Drug Administration (2010-2014). J Clin Oncol. 2016; e-pub ahead of print. PMID: 27069082.
PURPOSE: To review the use of patient-reported outcome (PRO) data in medical product labeling granted by the US Food and Drug Administration (FDA) for new molecular entities and biologic license applications by the FDA Office of Hematology and Oncology Products (OHOP) between January 2010 and December 2014, to elucidate challenges faced by OHOP for approving PRO labeling, and to understand challenges faced by drug manufacturers to include PRO end points in oncology clinical trials. METHODS: FDA Drug Approval Reports by Month were reviewed to obtain the number of new molecular entities and biologic license applications approved from 2010 to 2014. Drugs approved by the FDA OHOP during this period were selected for further review, focusing on brand and generic name; approval date; applicant; indication; PRO labeling describing treatment benefit, measures, end point status, and significant results; FDA reviewer feedback on PRO end points; and study design of registration trials. First in class, priority review, fast track, orphan drug, or accelerated approval status was retrieved for selected oncology drugs from 2011 to 2014. Descriptive analyses were performed by using Microsoft Excel 2010. RESULTS: Of 160 drugs approved by the FDA (2010-2014), 40 were approved by OHOP. Three (7.5%) of the 40 received PRO-related labeling (abiraterone acetate, ruxolitinib phosphate, and crizotinib). Compared with nononcology drugs (2011-2014), oncology drugs were more likely to be orphan and first in class. The majority of oncology drug reviews by FDA were fast track, priority, or accelerated. CONCLUSION: Although symptoms and functional decrements are common among patients with cancer, PRO labeling is rare in the United States, likely because of logistical hurdles and oncology study design. Recent developments within the FDA OHOP to capture PROs in oncology studies for the purpose of product labeling are encouraging.
Gnanasakthy, A, Demuro, C, Boulton, C. Integration of patient-reported outcomes in multiregional confirmatory clinical trials. Contempt Clin Trials. 2013; 35(1): 62-69. PMID: 23415630.
INTRODUCTION: The increasing complexities of conducting multiregional trials and an evolving regulatory environment contribute to unprecedented new challenges for use of patient-reported outcome measures (PROMs)(1) within clinical trials. This paper presents these challenges and potential solutions. METHODS: Real-world examples and situations are reviewed from an industry and patient-reported outcome (PRO)(2) expert position. CONCLUSIONS: An increase in the pursuit of new therapeutic targets, changes to the regulatory environment, and business pressures to expand clinical trials to more countries have significantly increased the complexity of confirmatory clinical studies that incorporate PROMs. Decisions to participate in collaborative efforts for endpoint development or proceed independently are made in the context of competing priorities of drug development timelines, drug differentiation strategies, the need for patient-related value messages, and the depth of a sponsor pipeline within specific disease areas. Study logistics are critically important; factors such as concept cultural relevancy, respondent literacy level, and quality of cross-cultural adaptation of PROMs must be evaluated when integrating into confirmatory clinical trials. Awareness of the issues relating to PROs in multiregional studies will enable companies to better plan studies and interpret results.
Basch, E, Bennett, A. Patient-reported outcomes in clinical trials of rare diseases. Journal of General Internal Medicine. 2014; 29 (Suppl 3): S801-803. PMID: 25029974.
ABSTRACT: The science of measuring patient-reported outcomes (PROs) has advanced substantially in recent decades, allowing evaluation of how patients feel and function in clinical research. Assessment of the patient experience in populations with rare diseases can be successfully achieved using PRO measures when careful planning and rigorous methods are employed. A number of challenges exist when designing and implementing PRO analyses in rare disease contexts, including heterogeneity of outcomes, availability of suitable measures, recruitment, and selection of appropriate data collection methods. Strategies to address these exist and have been employed in past clinical research, particularly in pediatric populations. PRO assessments in rare disease clinical trials have been particularly successful through partnerships between investigators, PRO methodologists, and patient organizations. The overall goal of PRO measurement is to understand the patient experience and it provides an essential part of evaluating the impact of disease and treatment.