Background: Patient-reported outcomes (PROs) are the consequences of disease and/or its treatment as reported by the patient. The importance of PRO measures in clinical trials for new drugs, biological agents, and devices was underscored by the release of the US Food and Drug Administration's draft guidance for industry titled "Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims." The intent of the guidance was to describe how the FDA will evaluate the appropriateness and adequacy of PRO measures used as effectiveness end points in clinical trials. In response to the expressed need of ISPOR members for further clarification of several aspects of the draft guidance, ISPOR's Health Science Policy Council created three task forces, one of which was charged with addressing the implications of the draft guidance for the collection of PRO data using electronic data capture modes of administration (ePRO). The objective of this report is to present recommendations from ISPOR's ePRO Good Research Practices Task Force regarding the evidence necessary to support the comparability, or measurement equivalence, of ePROs to the paper-based PRO measures from which they were adapted.
Methods: The task force was composed of the leadership team of ISPOR's ePRO Working Group and members of another group (i.e., ePRO Consensus Development Working Group) that had already begun to develop recommendations regarding ePRO good research practices. The resulting task force membership reflected a broad array of backgrounds, perspectives, and expertise that enriched the development of this report. The prior work became the starting point for the Task Force report. A subset of the task force members became the writing team that prepared subsequent iterations of the report that were distributed to the full task force for review and feedback. In addition, review beyond the task force was sought and obtained. Along with a presentation and discussion period at an ISPOR meeting, a draft version of the full report was distributed to roughly 220 members of a reviewer group. The reviewer group comprised individuals who had responded to an emailed invitation to the full membership of ISPOR. This Task Force report reflects the extensive internal and external input received during the 16-month good research practices development process. RESULTS/RECOMMENDATIONS: An ePRO questionnaire that has been adapted from a paper-based questionnaire ought to produce data that are equivalent or superior (e.g., higher reliability) to the data produced from the original paper version. Measurement equivalence is a function of the comparability of the psychometric properties of the data obtained via the original and adapted administration mode. This comparability is driven by the amount of modification to the content and format of the original paper PRO questionnaire required during the migration process. The magnitude of a particular modification is defined with reference to its potential effect on the content, meaning, or interpretation of the measure's items and/or scales. Based on the magnitude of the modification, evidence for measurement equivalence can be generated through combinations of the following: cognitive debriefing/testing, usability testing, equivalence testing, or, if substantial modifications have been made, full psychometric testing. As long as only minor modifications were made to the measure during the migration process, a substantial body of existing evidence suggests that the psychometric properties of the original measure will still hold for the ePRO version. Hence, an evaluation limited to cognitive debriefing and usability testing only may be sufficient. However, where more substantive changes in the migration process has occurred, confirming that the adaptation to the ePRO format did not introduce significant response bias and that the two modes of administration produce essentially equivalent results is necessary. Recommendations regarding the study designs and statistical approaches for assessing measurement equivalence are provided.
Conclusions: The electronic administration of PRO measures offers many advantages over paper administration. We provide a general framework for decisions regarding the level of evidence needed to support modifications that are made to PRO measures when they are migrated from paper to ePRO devices. The key issues include: 1) the determination of the extent of modification required to administer the PRO on the ePRO device and 2) the selection and implementation of an effective strategy for testing the measurement equivalence of the two modes of administration. We hope that these good research practice recommendations provide a path forward for researchers interested in migrating PRO measures to electronic data collection platforms.