Maximizing Adherence and Gaining New Information For Your Chronic Obstructive Pulmonary Disease (MAGNIFY COPD): Study Protocol for the Pragmatic, Cluster Randomized Trial Evaluating the Impact of Dual Bronchodilator with Add-On Sensor and Electronic Monitoring on Clinical Outcomes

Figures & data

Figure 1 MAGNIFY trial design.

Note: It is assumed that 82 practices in each arm will complete the study.

Abbreviation: EMR, electronic medical record.

Table 1 Definitions of Population Sets

Population Set	Definition
Primary population	ASA site: Group of patients who satisfy inclusion criteria at baseline, and accepted the intervention package Control site: Group of patients who satisfy inclusion criteria at baseline and are willing to use intervention package (based on COPD review questionnaire data collected at the end of the study)
Secondary population	ASA site: Group of patients satisfying selection criteria (i.e. adherence to current mono/dual therapy ≤50%) and who were offered the intervention package (regardless of their acceptance) Control site: Group of patients satisfying selection criteria (i.e. adherence to current mono/dual therapy ≤50%) and continuing with routine clinical care (LABA/LAMA, LABA, LAMA, LABA/ICS, LABA/LAMA/ICS)
Exploratory population	ASA site: Group of patients satisfying selection criteria (i.e. adherence to current mono/dual therapy ≤50%) and who accept or do not accept the technology

Abbreviations: ASA, adherence support arm; COPD, chronic obstructive pulmonary disease; ICS, inhaled corticosteroids; LABA, long-acting beta-2 agonists; LAMA, long-acting muscarinic antagonists.

Table 2 Potential Sources of Bias and Measures to Address Bias

Potential Source of Bias	Measures Taken to Address Bias
Index date
Date of initiation on the adherence package is used as the index date in the ASA patients, but there is no equivalent index date in the control arm. The median time from cluster randomization to the package initiation (i.e. delay) across all adherence support group sites will be determined and this delay value will be added to the time each control practice was cluster randomized, to obtain the follow-up period start date (“index date”) for patients at control sites. This approach ensures that the baseline is time-matched between the two arms, but may cause bias because in the control arm the index date is not defined on a patient-level as it is in the ASA	Sensitivity analyses will be conducted using: (a) the first COPD maintenance treatment after practice randomization as the index date in the control arm, and (b) the first primary care practitioner consultation after practice randomization as index dates in the control arm
Treatment failures
Stepping up maintenance therapy is often considered as a treatment failure in clinical studies. However, if any maintenance therapy step up was considered a treatment failure, there would be potential bias for more treatment failures in the control arm due to patients on monotherapy being stepped up to LABA/LAMA or ICS/LABA (both in line with current treatment recommendations), while in the ASA initiation on the package (LABA/LAMA) at baseline of a patient previously on monotherapy cannot be considered a treatment failure	Only step up to triple therapy will be considered treatment failure in the primary analysis. However, a sensitivity analysis will be conducted using a modified definition of the primary outcome where any step up is considered a treatment failure
Impact on prescribing decisions
Participation in the trial may drive LABA/LAMA prescribing decisions at participating sites	Only sites that are actively prescribing LABA/LAMA will be included in the trial. LABA/LAMA is recommended for patients with COPD by the current treatment guidelines

Abbreviations: ASA, adherence support arm; COPD, chronic obstructive pulmonary disease; ICS, inhaled corticosteroids; LABA, long-acting beta-2 agonists; LAMA, long-acting muscarinic antagonists.