The GLORIA adherence subproject: problems and randomization mistakes

Linda Hartman,Ed N Griep,L Thomas Klausch,Jaap M Van Laar,Rui M A Pinto,Esmeralda Molenaar,Marieke J H Voshaar,Cornelia F Allaart,Yvonne P M Ruiterman,Willem F Lems,Hennie G Raterman,Jan Maarten Van Woerkom,Marc R Kok,Maarten Boers,João Redol

doi:10.36850/e6

Abstract

Medication adherence, which is the extent to which patients take their medication as prescribed, is essential in treating chronic inflammatory diseases such as rheumatoid arthritis (RA). Therefore, we nested a subproject in the two-year multicenter Glucocorticoid Low-dose Outcome in Rheumatoid Arthritis (GLORIA) trial to add a low-dose prednisolone (5 mg/day) or placebo to the standard care in older people (≥65 years) with RA. Adherence was measured with an electronic monitoring cap that recorded bottle openings in all patients. In the subproject, we performed an adherence intervention with an advanced cap that could communicate with an application on the smart device via Bluetooth. We randomized patients with a smart device to receive or not to receive adherence reminders on the smart device for three months. Multiple problems emerged that precluded an answer to the research question: sample size (overly optimistic estimates of older patients with a smart device), logistic issues (availability of smartcaps, data extraction), randomization and treatment allocation errors (despite training of personnel), and low quality of the data in the intervention group (hardware failure, discovered too late because data was read in batches). For future trials planning to include a subproject, we recommend keeping it simple, starting with a field test before the actual study starts, and monitoring data from the beginning of the study.

Highlights

Medication adherence, which is the extent to which patients take their medication as prescribed (Brown & Bussell, 2011), is essential to treat chronic inflammatory diseases, such as rheumatoid arthritis (RA; Jungst et al, 2019)
In the two-year multicenter Glucocorticoid Low-dose Outcome in Rheumatoid Arthritis (GLORIA) trial, a low-dose prednisolone (5 mg/day) or placebo was added to the standard care in older people (65+ years) with RA
In a subproject nested within the trial, we assessed the efficacy of an adherence intervention for the patients with a smart device

Summary

Introduction

Medication adherence, which is the extent to which patients take their medication as prescribed (Brown & Bussell, 2011), is essential to treat chronic inflammatory diseases, such as rheumatoid arthritis (RA; Jungst et al, 2019). Almost half of patients with chronic diseases are non-adherent (Jungst et al, 2019; Kini, 2018). Non-adherence substantially increases the risk of a disease flare in RA (Jungst et al, 2019). We measured adherence with electronic monitoring and pill count in all patients (Hartman et al, 2021). In a subproject nested within the trial, we assessed the efficacy of an adherence intervention for the patients with a smart device

Methods

Findings

Discussion

Conclusion