Visualizing the target estimand in comparative effectiveness studies with multiple treatments.

Comparative effectiveness research using real-world data often involves pairwise propensity score matching to adjust for confounding bias. We show that corresponding treatment effect estimates may have limited external validity, and propose two visualization tools to clarify the target estimand. We conduct a simulation study to demonstrate, with bivariate ellipses and joy plots, that differences in covariate distributions across treatment groups may affect the external validity of treatment effect estimates.

Comparing tocilizumab biosimilar BAT1806/BIIB800 with reference tocilizumab in patients with moderate-to-severe rheumatoid arthritis with an inadequate response to methotrexate: a phase 3, randomised, multicentre, double-blind, active-controlled clinical trial.

Background: Biosimilars provide an opportunity to address unmet medical need by expanding access to biological treatments. This study aimed to show equivalent efficacy, and comparable safety, immunogenicity, and pharmacokinetic profiles of a proposed tocilizumab biosimilar BAT1806/BIIB800, to reference tocilizumab, in participants with rheumatoid arthritis with an inadequate response to methotrexate.

Methods: This phase 3, multicentre, randomised, double-blind, active-controlled, equivalence study comprised a 24-week initial treatment period (results reported here) and a 24-week secondary treatment period.

Estimation of treatment effects in short-term depression studies. An evaluation based on the ICH E9(R1) estimands framework.

Estimands aim to incorporate intercurrent events in design, data collection and estimation of treatment effects in clinical trials. Our aim was to understand what estimands may correspond to efficacy analyses commonly employed in clinical trials conducted before publication of ICH E9(R1). We re-analysed six clinical trials evaluating a new anti-depression treatment.

Applicability and added value of novel methods to improve drug development in rare diseases.

Background: The ASTERIX project developed a number of novel methods suited to study small populations. The objective of this exercise was to evaluate the applicability and added value of novel methods to improve drug development in small populations, using real world drug development programmes as reported in European Public Assessment Reports.

Methods: The applicability and added value of thirteen novel methods developed within ASTERIX were evaluated using data from 26 European Public Assessment Reports (EPARs) for orphan medicinal products, representative of rare medical conditions as predefined through six clusters.

Measurement error is often neglected in medical literature: a systematic review.

Objectives: In medical research, covariates (e.g., exposure and confounder variables) are often measured with error.