What phases of the drug development framework can epidemiological studies emulate?

Area of Science:

• Epidemiology
• Clinical Trial Design

Background:

• Target trial emulation is a framework for causal inference.
• It aims to mitigate bias in observational studies by mimicking randomized controlled trials.
• Understanding which trial phases are suitable for emulation is crucial.

Purpose of the Study:

• To explore the applicability of target trial emulation across different phases of clinical research.
• To differentiate the goals and estimands of early-phase versus late-phase target trials.
• To discuss the trade-offs between validity and applicability in causal inference.

Main Methods:

• Conceptual analysis of target trial emulation.
• Comparison of early-phase (Phase 2 or earlier) and late-phase (Phase 3 or 4) trial objectives.
• Discussion of natural experiments within the target trial emulation framework.

Main Results:

• Late-phase target trials aim for precise causal estimates of interventions as implemented.
• Early-phase target trials provide proof-of-concept on intervention effects, but may not reflect practical application.
• Natural experiments, when emulated as early-phase trials, may yield valid but less applicable findings.

Conclusions:

• Target trial emulation can protect against various biases, though not confounding.
• The choice between early-phase and late-phase emulation depends on the research question and desired estimand.
• Prioritizing validity over applicability is often preferable in causal inference, especially when dealing with natural experiments.