title: PRO data collection in clinical trials using mixed modes: report of the ISPOR PRO mixed modes good research practices task force.
abstract: The objective of this report was to address the use and mixing of data collection modes within and between trials in which patient-reported outcome (PRO) end points are intended to be used to support medical product labeling. The report first addresses the factors that should be considered when selecting a mode or modes of PRO data collection in a clinical trial, which is often when mixing is first considered. Next, a summary of how to "faithfully" migrate instruments is presented followed by a section on qualitative and quantitative study designs used to evaluate measurement equivalence of the new and original modes of data collection. Finally, the report discusses a number of issues that must be taken into account when mixing modes is deemed necessary or unavoidable within or between trials, including considerations of the risk of mixing at different levels within a clinical trial program and mixing between different types of platforms. In the absence of documented evidence of measurement equivalence, it is strongly recommended that a quantitative equivalence study be conducted before mixing modes in a trial to ensure that sufficient equivalence can be demonstrated to have confidence in pooling PRO data collected by the different modes. However, we also strongly discourage the mixing of paper and electronic field-based instruments and suggest that mixing of electronic modes be considered for clinical trials and only after equivalence has been established. If proceeding with mixing modes, it is important to implement data collection carefully in the trial itself in a planned manner at the country level or higher and minimize ad hoc mixing by sites or individual subjects. Finally, when mixing occurs, it must be addressed in the statistical analysis plan for the trial and the ability to pool the data must be evaluated to then evaluate treatment effects with mixed modes data. A successful mixed modes trial requires a "faithful migration," measurement equivalence established between modes, and carefully planned implementation to minimize the risk of increased measurement error impacting the power of the trial to detect a treatment effect.
authors.affiliation: Outcomes Research, Evidera, Inc., Bethesda, MD, USA. Electronic address: sonya.eremenco@evidera.com.
authors.forename: Sonya
authors.initials: S
authors.lastname: Eremenco
authors.affiliation: Patient-Reported Outcome Consortium, Critical Path Institute, Tucson, AZ, USA.
authors.forename: Stephen Joel
authors.initials: SJ
authors.lastname: Coons
authors.affiliation: Endpoint Strategy, Quintiles, Hawthorne, NY, USA.
authors.forename: Jean
authors.initials: J
authors.lastname: Paty
authors.affiliation: Outcomes Research, Evidera, Inc., Bethesda, MD, USA.
authors.forename: Karin
authors.initials: K
authors.lastname: Coyne
authors.affiliation: Department of Health Policy and Management, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Antonia V
authors.initials: AV
authors.lastname: Bennett
authors.affiliation: Consultant, Nottingham, UK.
authors.forename: Damian
authors.initials: D
authors.lastname: McEntegart
mesh_terms: D026683:Advisory Committees; D002986:Clinical Trials as Topic / Q000379:methods*; D003625:Data Collection / Q000379:methods*; D006801:Humans; D017063:Outcome Assessment, Health Care / Q000379:methods*; D012107:Research Design; D057566:Self Report
keywords: ePRO; electronic PRO; equivalence; mixed modes