Patient Reported Outcomes (PROs) in Clinical Trials: Is ‘In-Trial’ Guidance Lacking? A Systematic Review

Abstract

BackgroundPatient reported outcomes (PROs) are increasingly assessed in clinical trials, and guidelines are available to inform the design and reporting of such trials. However, researchers involved in PRO data collection report that specific guidance on ‘in-trial’ activity (recruitment, data collection and data inputting) and the management of ‘concerning’ PRO data (i.e., data which raises concern for the well-being of the trial participant) appears to be lacking. The purpose of this review was to determine the extent and nature of published guidelines addressing these areas.Methods and FindingsSystematic review of 1,362 articles identified 18 eligible papers containing ‘in-trial’ guidelines. Two independent authors undertook a qualitative content analysis of the selected papers. Guidelines presented in each of the articles were coded according to an a priori defined coding frame, which demonstrated reliability (pooled Kappa 0.86–0.97), and validity (<2% residual category coding). The majority of guidelines present were concerned with ‘pre-trial’ activities (72%), for example, outcome measure selection and study design issues, or ‘post-trial’ activities (16%) such as data analysis, reporting and interpretation. ‘In-trial’ guidelines represented 9.2% of all guidance across the papers reviewed, with content primarily focused on compliance, quality control, proxy assessment and reporting of data collection. There were no guidelines surrounding the management of concerning PRO data.ConclusionsThe findings highlight there are minimal in-trial guidelines in publication regarding PRO data collection and management in clinical trials. No guidance appears to exist for researchers involved with the handling of concerning PRO data. Guidelines are needed, which support researchers to manage all PRO data appropriately and which facilitate unbiased data collection.

Content Validity of the Lee Chronic Graft-versus-Host Disease Symptom Scale as Assessed by Cognitive Interviews

“…The Lee cGVHD Symptom Scale was not intended for cognitively impaired patients, children less than 12 years old, or for proxy-reporting of symptoms. In trial guidance has been published to address situations when study participants have a PRO endpoint due for collection and they have cognitive impairment [20]. …”

Systematic collection of patient reported outcome research data: A checklist for clinical research professionals

“…Procedures should also describe who will contact the study participant and the timeframe permitted for follow-up to avoid recall bias. Determine quality control activities [19] in the protocol development phase, such as building in windows for data collection that anticipates both routine and unexpected patient and clinical factors that are typically experienced by the target population, is useful. Gralla and Thatcher emphasize that researchers should carefully consider the potential for subject attrition and what impact it might have on missing data since it introduces bias during analysis and interpretation of the findings of study endpoints [41].…”

International Society for Quality of Life Research commentary on the draft European Medicines Agency reflection paper on the use of patient-reported outcome (PRO) measures in oncology studies

“…In particular, they highlight the importance of: a strong rationale, supporting both PRO collection itself and the timing of assessment; comprehensive training of trial staff and patients involved in PRO measurement; implementation of methods to maximize compliance; and the formulation of a detailed, PROspecific, statistical analysis plan addressing special issues such as multiplicity and missing data. This approach is welcome: both experience and empirical research suggest that a failure to incorporate these design features during trial planning may result in PRO data that are uninformative or inappropriate for evaluating the harms and benefits of the intervention under study [4,5]. The EMA recommendations also align with those presented in other contemporary PRO guidance documents, including those produced by the Center for Medical Technology Policy [6] and the US Food and Drug Administration (FDA) [7].…”