No head-to-head trial? simulate the missing arms.

Area of Science:

• Health economics
• Clinical trial methodology
• Comparative effectiveness research

Background:

• Payer coverage decisions increasingly require evidence comparing new interventions against existing ones, not just placebo.
• Head-to-head trials are the gold standard for comparative effectiveness but are rarely conducted.
• Lack of direct comparative data hinders informed decision-making for healthcare interventions.

Purpose of the Study:

• To introduce and describe the simulated treatment comparison (STC) methodology.
• To demonstrate how STC can generate simulated head-to-head trial data from existing single-arm trials.
• To highlight STC's utility in informing payers and economic models in the absence of direct comparative evidence.

Main Methods:

• STC replicates an index trial's design, including patient enrollment, randomization, and follow-up, using predictive equations derived from the index trial data.
• Separate comparator data are used to calibrate these equations, simulating the addition of 'missing arms' to the index trial.
• The calibrated simulation estimates the outcomes that would have been observed in a direct head-to-head comparison.

Main Results:

• The STC approach successfully generates simulated head-to-head trial results, addressing discrepancies between source trials.
• It provides valuable inputs for health economic models, aiding decision-makers.
• The method allows for the estimation of comparative effectiveness across diverse settings and populations.

Conclusions:

• Simulated treatment comparison (STC) offers a robust method for deriving comparative effectiveness evidence when direct trial data are unavailable.
• STC can inform healthcare policy and economic evaluations, bridging the gap until head-to-head trials are conducted.
• This approach also serves as a platform for testing trial design features to optimize future head-to-head studies.