About this Research Topic
External control arms (ECAs) can be used to provide context or to provide a statistical comparison for single-arm studies. Single-arm studies may be conducted in situations where the treatment indication of interest is rare and enrollment of a control arm will be complicated and lengthy. These studies could include single-arm trials for new drug approval or long-term extension studies, where only the treatment arm is being followed for outcomes.
Methodological challenges can arise when using external treatment data as a control arm for decision-making, such as for regulatory or health technology assessment decisions. Challenges may include issues with the relevance and reliability of data used for ECAs, bias due to study design and analysis decisions, and poor performance of developed models. This journal edition seeks to provide examples of the impact of these methodological challenges on results and to explore how the challenges are addressed.
This Research Topic is seeking manuscripts with reviews, simulations, or real-world applications that answer methodological questions that arise when using external control arms for comparisons with or contextualization of single-arm studies. Comparisons can be between studies with patient-level or summary data.
Topics could include, but are not limited to:
o Effect of external control data relevancy and reliability on study findings
o Effect of missingness or misclassification of selection criteria variables in the external control data source on population comparability and results
o Best methods for selecting index dates for the external control arm
o Effect of differences in follow-up between the external control arm and the single-arm study
o Best methods for statistical comparisons between external control arms and single-arm trials
o Model validation
o Quantitative bias analysis of external control analysis results
o Special methodological considerations for external controls of long-term extension studies
Dr. Laura Hester is an employee of Janssen R&D, LLC, and owns stock in Johnson and Johnson.
Dr. Deborah Layton has received financial support for a consultancy from Ariello and AstraZeneca and is Director for PEPI Consultancy Limited, UK.
Dr. Asieh Golozar is employed by Odysseus Data Services.
Dr. Dalia Dawoud declares no competing interests with regard to the Research Topic subject.
Methodological challenges can arise when using external treatment data as a control arm for decision-making, such as for regulatory or health technology assessment decisions. Challenges may include issues with the relevance and reliability of data used for ECAs, bias due to study design and analysis decisions, and poor performance of developed models. This journal edition seeks to provide examples of the impact of these methodological challenges on results and to explore how the challenges are addressed.
This Research Topic is seeking manuscripts with reviews, simulations, or real-world applications that answer methodological questions that arise when using external control arms for comparisons with or contextualization of single-arm studies. Comparisons can be between studies with patient-level or summary data.
Topics could include, but are not limited to:
o Effect of external control data relevancy and reliability on study findings
o Effect of missingness or misclassification of selection criteria variables in the external control data source on population comparability and results
o Best methods for selecting index dates for the external control arm
o Effect of differences in follow-up between the external control arm and the single-arm study
o Best methods for statistical comparisons between external control arms and single-arm trials
o Model validation
o Quantitative bias analysis of external control analysis results
o Special methodological considerations for external controls of long-term extension studies
Dr. Laura Hester is an employee of Janssen R&D, LLC, and owns stock in Johnson and Johnson.
Dr. Deborah Layton has received financial support for a consultancy from Ariello and AstraZeneca and is Director for PEPI Consultancy Limited, UK.
Dr. Asieh Golozar is employed by Odysseus Data Services.
Dr. Dalia Dawoud declares no competing interests with regard to the Research Topic subject.
Keywords: external control arm, single arm trial, long-term extension studies, small populations, pharmacovigilance
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
