Active-comparator design and new-user design in observational studies

Nat Rev Rheumatol. 2015 Jul;11(7):437-41. doi: 10.1038/nrrheum.2015.30. Epub 2015 Mar 24.


Over the past decade, an increasing number of observational studies have examined the effectiveness or safety of treatments for rheumatoid arthritis. Unlike randomized controlled trials (RCTs), however, observational studies of drug effects have methodological limitations such as confounding by indication. Active-comparator designs and new-user designs can help mitigate such biases in observational studies and improve the validity of their findings by making them more closely approximate RCTs. In an active-comparator study, the drug of interest is compared with another agent commonly used for the same indication, rather than with no treatment (a 'non-user' group). This principle helps to ensure that treatment groups have similar treatment indications, attenuating both measured and unmeasured differences in patient characteristics. The new-user study includes a cohort of patients from the time of treatment initiation, enabling assessment of patients' pretreatment characteristics and capture of all events occurring during follow-up. These two principles should be considered when designing or reviewing observational studies of drug effects.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Arthritis, Rheumatoid / drug therapy
  • Bias
  • Confounding Factors, Epidemiologic
  • Humans
  • Observational Studies as Topic / methods*
  • Randomized Controlled Trials as Topic