Effective Patient Reported Outcomes

By: Elida Ramberge
IntroductionReliable patient reports in clinical research have been a long sought-after goal. In response to the increasing focus on these reports in clinical trials the Food and Drug Administration (FDA) issued its "Guidance for Industry Patient Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims" (Guidance) in February 2006, which began the dialogue regarding standards for these reports. The Guidance serves as a description of how the FDA evaluates the effectiveness of a Patient Reported Outcome (PRO) in collection of clinical trial endpoint data. Laurie Burke provides the FDA's views on PROs: The goal of using PRO measures is to provide better information to doctors and patients so that the best treatment for patients can be determined, says Laurie Burke, R.Ph., M.P.H., director of the FDA's study endpoints and label development team in the Office of New Drugs. "It's all about the patients."Definition of A Patient Reported OutcomeIt is useful to briefly review what constitutes a PRO before examining how the guidance document influences the design, deployment and implementation of processes that aim to collect information directly from participants in clinical research. PRO instruments run the gamut from discrete inquiry, e.g., pain, to domains of functioning, e.g., physical, psychological or social. In its most fundamental form a PRO is the patient's measurement/assessment of health status free of the interpretation by anyone else, including physicians and clinicians. It is generally accepted that PROs are desirable when the endpoint being examined is known only to the patient; when the patient's perspective of treatment effectiveness may be unique; and when the assessment format is more reliable when administered more formally. "The use of PRO instruments is part of a general movement toward the idea that the patient, properly queried, is the best source of information about how he or she feels," says Robert Temple, MD director of the Food and Drug Administration's Office of Medical Policy.How PRO's Differ From Other Clinical AssessmentsAs the best source of information about how he or she feels, the patient's role in the conduct of the study shifts the importance of some assessments from the physician or clinician to the patient. This shift represents a role transformation that recognizes the value of patient reports, which transformation is sometimes not readily embraced by physicians or clinical staff. The difficulty comprehending the shift was exemplified during a recent Kronos HelpDesk call when a study coordinator asked how it could be possible that a patient was able to assess their disease state. The question was not born of a disdain for the patient's ability to assess their disease, but rather a lack of education about how the patients role in the study as the authority on primary endpoint data. The Guidance makes scant mention of the education necessary for patients who are being asked to record the most important data in the study - endpoint data. Unlike the expectation that clinical site training include a review of Good Clinical Practices, patients do not receive similar training. Training commensurate with the task of diary/outcome data entry is necessary to ensure the validity of the data being entered by patients. Herein lies the impetus for this discussion. Although the Guidance notes its purpose as explanation of "how the FDA evaluates such instruments for their usefulness in measuring and characterizing the benefit of medical product treatment" the shift in the respective roles of the patient and the physician or clinician does not receive the attention by way of elaboration or guidance necessary to ensure the validity of data being recorded. Beyond recommending that "Sponsors should consider the method of data collection …associated with instrument administration, including instructions to interviewers, instructions for self-administration, instructions for supervising self-administration, case report forms or examples of electronic PRO instrument,.." the Guidance lacks the specificity for administration procedures necessary to engage patients as integral to study conduct. Anecdotal information derived from this clinician's experience has demonstrated that implementation processes/procedures have a direct affect on how a PRO is administered. The example offered involves the administration of the SASSI (Substance Abuse Subtle Screening Inventory). The inherent nature of a behavioral health PRO of experience/assessment makes this PRO most dependent on patient reports with the least objective endpoint data to support claims. During administration of the SASSI, patients inquired about the verbiage of questions. The validity of the results depended on the administrator's understanding that adding information by way of explaining the question invalidated the response because the subject was no longer responding to the question - the patient would have been responding to the question as interpreted by the administrator. Reliability of data is affected by variability in administration, however, the Guidance does not offer recommendations to minimize this effect. Recommended Additions to the Guidance1.Lay out in greater detail how the role shift affects implementation of the studya. Engage patients as participants in study conduct - explain what the study hopes to accomplishb. Educate patients in the importance of their role and the data they enter to the study's outcome c. Elaborate on how they will fulfill the expectation of recording their datad. Recommend reviewing instrument in detaile. Provide audio-visual aide that reaffirms process discussed2. Elaborate on the education necessary to demonstrate to the Investigational Site and the patient their respective roles in the study3. Provide off-site support for patients who need assistance complying with the requirements to report outcomesIt is this clinician's experience that patients are anxious to comply with their responsibility in a clinical trial, even though they are sometimes forgetful when completing diaries or other outcome instruments. Electronic data capture reminders that are built-in, provide patients with the necessary tools to meet their responsibility. It behooves the clinical research community to provide these tools as the return will be better data as patients engage in a more thoughtful process when entering information about their experience during a clinical study. ABOUT KRONOS COMMUNICATED DATA: Since 1993, Kronos has provided outstanding professional services and products for clinical research. Specializing in the innovative, electronic data capture of patients' and subjects' feedback in studies, the experienced staff at Kronos has been key to the success of many over the years. It is also an SBA Certified Woman-Owned-Business which is helpful when government funding is being used. For information matching your study requirements, contact KCDI at 888-538-1690 or kronos@kronosdata.com