Adjusting for switches to multiple treatments: Should switches be handled separately or combined?

Treatment switching is common in randomised controlled trials (RCTs). Participants may switch onto a variety of different treatments, all of which may have different treatment effects. Adjustment analyses that target hypothetical estimands - estimating outcomes that would have been observed in the absence of treatment switching - have focused primarily on a single type of switch.

Is inverse probability of censoring weighting a safer choice than per-protocol analysis in clinical trials?

Deviation from the treatment strategy under investigation occurs in many clinical trials. We term this intervention deviation. Per-protocol analyses are widely adopted to estimate a hypothetical estimand without the occurrence of intervention deviation.

Use of transportability methods for real-world evidence generation: a review of current applications.

To evaluate how transportability methods are currently used for real-world evidence (RWE) generation to inform good practices and support adoption and acceptance of these methods in the RWE context. We conducted a targeted literature review to identify studies that transported an effect estimate of the clinical effectiveness or safety of a biomedical exposure to a target real-world population. Records were identified from PubMed-indexed articles published any time before 25 July 2023 (inclusive).

Investigating Stability in Subgroup Identification for Stratified Medicine.

Subgroup analysis may be used to investigate treatment effect heterogeneity among subsets of the study population defined by baseline characteristics. Several methodologies have been proposed in recent years and with these, statistical issues such as multiplicity, complexity, and selection bias have been widely discussed. Some methods adjust for one or more of these issues; however, few of them discuss or consider the stability of the subgroup assignments.

Quantifying the benefit-risk trade-off for individual patients in a clinical trial: principles and antithrombotic case study.

Background: A treatment's overall favorable benefit-risk profile does not imply that every individual patient will benefit from the treatment.

Objectives: To describe a statistical methodology for quantifying the benefit-risk trade-off in individual patients.

Methods: The method requires a large randomized controlled trial containing a primary efficacy outcome and a primary safety outcome, for instance, the Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events-Thrombolysis in Myocardial Infarction 50 placebo-controlled trial of vorapaxar in 17 779 patients following myocardial infarction.