How to compare instrumental variable and conventional regression analyses using negative controls and bias plots

Neil M. Davies, Kyla H. Thomas, Amy E. Taylor, Gemma M.J. Taylor, Richard M. Martin, Marcus R. Munafò, Frank Windmeijer

Research output: Contribution to journalArticle

8 Citations (Scopus)
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There is increasing interest in the use of instrumental variable analysis to overcome unmeasured confounding in observational pharmacoepidemiological studies. This is partly because instrumental variable analyses are potentially less biased than conventional regression analyses. However, instrumental variable analyses are less precise, and regulators and clinicians find it difficult to interpret conflicting evidence from instrumental variable compared with conventional regression analyses. In this paper, we describe three techniques to assess which approach (instrumental variable versus conventional regression analyses) is least biased. These techniques are negative control outcomes, negative control populations and tests of covariate balance. We illustrate these methods using an analysis of the effects of smoking cessation therapies (varenicline) prescribed in primary care.

Original languageEnglish
Pages (from-to)2067-2077
Number of pages11
JournalInternational Journal of Epidemiology
Issue number6
Early online date7 Apr 2017
Publication statusPublished - 1 Dec 2017


  • Causal inference
  • Instrumental variables
  • Negative controls
  • Pharmacoepidemiology

ASJC Scopus subject areas

  • Epidemiology

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