This protocol is part of the RCT DUPLICATE initiative, a project which is replicating 30+
randomized clinical trial designs using non-randomized healthcare data and comparing the results
from the trials and non-randomized studies. The goal is to better understand when and how
questions on drug effects can be validly answered with such data and used to inform regulatory,
clinical or other decision-making.
This protocol focused on a phase 3 trial comparing Budesonide + Formoterol versus Budesonide
alone for asthma. The trial evaluated whether one drug was better than another at first-serious
asthma related events (a composite of adjudicated death, intubation, and hospitalization). We will
replicate the trial design based on methods reported in the main trial publication.
The objective of this protocol is to emulate the design of the published randomized clinical trial
(RCT): “A 6 month safety study comparing Symbicort with inhaled corticosteroid only is asthmatic
adults and adolescents. NCT01444430. We will focus on the parallel comparison of budesonide
+ formoterol versus budesonide alone for 26-weeks.
The study will include all patients who contributed to CPRD data between May 2000 to June 2018
and had an established clinical history of asthma diagnosis any time prior to initiation of exposure
or referent drug. We will implement a new-user active-comparator design, where new use will be defined as no recorded use of the exposure medication or comparator medication in the 180 days prior to exposure or comparator treatment initiation. Propensity score 1-1 calliper matching will be applied at the beginning of follow-up to balance the investigator-specified covariates across treatment groups. Follow-up will begin 1 day after initiation of
Budesonide + Formoterol versus Budesonide alone. The outcome will be measured as first serious asthma-related event (a composite of adjudicated death, intubation, and hospitalization). All the patients will be
followed-up during the treatment period of 26-weeks. The primary analysis will evaluate the survival function with 95% confidence intervals after PS adjustment.
This replication is part of the RCT DUPLICATE study. The goal of this project is to utilize
real-world data to replicate phase 3 or phase 4 RCTs and compare findings. The project aims to
assess reasons for success and failure to replicate RCTs using real-world data and help lay a
groundwork for regulators to gain confidence in decision making if an RCT can be duplicated by
real-world data study.
First serious-asthma related events defined as composite of asthma-related deaths, intubations,
and hospitalizations. Follow-up and measurement of the outcome will begin 1 day after initiation
of Budesonide + Formoterol versus Budesonide alone. See attached excel file for formal CPRD
definition.
Samy Suissa - Chief Investigator - Sir Mortimer B Davis Jewish General Hospital
Samy Suissa - Corresponding Applicant - Sir Mortimer B Davis Jewish General Hospital
Richard Wyss - Collaborator - Harvard Medical School
Shirley Wang - Collaborator - Harvard University
Sophie Dell'Aniello - Collaborator - McGill University
Sophie Dell'Aniello - Collaborator - McGill University
HES Admitted Patient Care;ONS Death Registration Data