Use of daily electronic patient-reported outcome (PRO) diaries in randomized controlled trials for rheumatoid arthritis: rationale and implementation

Clifton O Bingham 3rd, Carol L Gaich, Amy M DeLozier, Kathryn D Engstrom, April N Naegeli, Stephanie de Bono, Pixy Banerjee, Peter C Taylor, Clifton O Bingham 3rd, Carol L Gaich, Amy M DeLozier, Kathryn D Engstrom, April N Naegeli, Stephanie de Bono, Pixy Banerjee, Peter C Taylor

Abstract

Background: Rheumatoid arthritis (RA) is associated with significantly diminished health-related quality of life. Patient-reported outcomes (PROs) are considered important in RA; however, some symptoms such as morning joint stiffness (MJS) and fatigue that are considered important by patients are not captured by the American College of Rheumatology "core set" measures for RA trials. The US Food and Drug Administration has endorsed electronic capture of clinical trial data including PROs, and electronic PRO (ePRO) systems may lead to more accurate and complete data capture, improved compliance, and patient acceptance compared with paper-based methods. Our objective was to assess the implementation of ePRO measures of Duration and Severity of MJS, Severity of Worst Tiredness, and Severity of Worst Joint Pain in baricitinib RA-BEAM and RA-BUILD phase 3 randomized clinical trials (RCTs).

Methods: A daily electronic diary (handheld device; Invivodata®, Inc.) was utilized to capture PRO data in the RCTs. Three "reporting window" options were incorporated to accommodate differences in patients' routine daily schedules, and alarms were programmed for each reporting window. Duration of MJS was recorded in "hours and minutes," and Severity of MJS, Worst Tiredness, and Worst Joint Pain were captured on a 0 to 10 rating scale, with a higher score indicating more severe symptoms. The patients and site staff were trained to use the daily electronic diary.

Results: Patients with moderately to severely active RA used the daily electronic diary in the RA-BEAM study (N = 1305) and RA-BUILD study (N = 684). The average compliance, calculated as total days completed by patients compared with total days expected to complete the diary, through Week 12 was high (RA-BEAM 94% patients; RA-BUILD 93% patients), potentially attributable to appropriate training, clarity of instructions, simple user interface, and electronic device design. Identified process challenges included non-timely issuance of the device, low battery, inadequate training of patients before data collection, inappropriate diary set-up, and first response entry 1 day after the baseline visit.

Conclusions: High compliance rates support the use of the daily electronic PRO diary in large RCTs. Despite the anticipated issues, the daily electronic diary is expected to reduce recall bias and improve the quality of PRO data collection.

Trial registration: RA-BEAM ( NCT01710358 ) and RA-BUILD ( NCT01721057 ).

Keywords: Daily electronic diary; Patient-reported outcome; Rheumatoid arthritis; ePRO.

Conflict of interest statement

Ethics approval and consent to participate

The study was conducted in accordance with ethical principles of the Declaration of Helsinki and Good Clinical Practice guidelines. Written informed consent was obtained from the human participants involved in the study.

Consent for publication

Not applicable.

Competing interests

CB has served as a consultant to Eli Lilly and Company. PT has served as a consultant to Eli Lilly and Company and received research grant funding from Lilly. CG, AD, KE, SB, and AN are employees of Eli Lilly and Company, USA, and PB is an employee of Eli Lilly Services India Pvt. Ltd. CG, KE, SB, AN, and PB hold stock/stock options at Eli Lilly and Company.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Questions to evaluate the four gated measures through daily electronic diary

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