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Generalizability and effect measure modification in sibling comparison studies.

Arvid Sjölander1, Sara Öberg2, Thomas Frisell3

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Sibling comparison studies control for family factors but may lack generalizability. A new marginal between-within model addresses this by improving exposure effect estimation in these studies.

Keywords:
BiasCausal inferenceEffect measure modificationSibling comparison study

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Area of Science:

  • Epidemiology
  • Biostatistics
  • Genetics

Background:

  • Sibling comparison studies control for unmeasured familial confounding.
  • Concerns exist regarding the generalizability (external validity) of these studies due to implicit selection of covariate-discordant families.

Purpose of the Study:

  • To formally discuss the implicit restriction to covariate-discordant families in sibling comparison studies.
  • To analyze how this restriction impacts generalizability.
  • To present a solution for estimating marginal exposure effects.

Main Methods:

  • Formal discussion of selection bias in sibling comparison studies.
  • Development and application of a marginal between-within model.
  • Simulation study to illustrate theoretical findings.

Main Results:

  • The restriction to covariate-discordant families can impair generalizability.
  • Generalizability issues can arise even in covariate-discordant families (e.g., continuous exposure).
  • The marginal between-within model effectively estimates marginal exposure effects.

Conclusions:

  • Sibling comparison studies require careful consideration of generalizability.
  • The marginal between-within model offers a robust method for addressing generalizability concerns.
  • This approach enhances the validity of findings from sibling comparison studies.