Change in financial limitations, income, and weekly spending.

Change in financial limitations, income, and weekly spending.</p

S1 Checklist -

(PDF)</p

S1 File -

(DOCX)</p

Distress due to financial difficulties.

Distress due to financial difficulties.</p

Logistic regression: Financial limitations analysis.

Logistic regression: Financial limitations analysis.</p

Change in spending.

Change in spending.</p

Comparison of financial limitations and field of studies.

Comparison of financial limitations and field of studies.</p

Logistic regression results for financial distress.

Logistic regression results for financial distress.</p

Stress level due to financial difficulties.

Stress level due to financial difficulties.</p

Estimation of treatment effects in early-phase randomized clinical trials involving external control data

There are good reasons to perform a randomized controlled trial (RCT) even in early phases of clinical development. However, the low sample sizes in those settings lead to high variability of the treatment effect estimate. The variability could be reduced by adding external control data if available. For the common setting of suitable subject-level control group data only available from one external (clinical trial or real-world) data source, we evaluate different analysis options for estimating the treatment effect via hazard ratios. The impact of the external control data is usually guided by the level of similarity with the current RCT data. Such level of similarity can be determined via outcome and/or baseline covariate data comparisons. We provide an overview over existing methods, propose a novel option for a combined assessment of outcome and baseline data, and compare a selected set of approaches in a simulation study under varying assumptions regarding observable and unobservable confounder distributions using a time-to-event model. Our various simulation scenarios also reflect the differences between external clinical trial and real-world data. Data combinations via simple outcome-based borrowing or simple propensity score weighting with baseline covariate data are not recommended. Analysis options which conflate outcome and baseline covariate data perform best in our simulation study.</p