Evaluation of person-level heterogeneity of treatment effects in published multiperson N-of-1 studies: systematic review and reanalysis

BMJ Open. 2018 May 26;8(5):e017641. doi: 10.1136/bmjopen-2017-017641.

Abstract

Objective: Individual patients with the same condition may respond differently to similar treatments. Our aim is to summarise the reporting of person-level heterogeneity of treatment effects (HTE) in multiperson N-of-1 studies and to examine the evidence for person-level HTE through reanalysis.

Study design: Systematic review and reanalysis of multiperson N-of-1 studies.

Data sources: Medline, Cochrane Controlled Trials, EMBASE, Web of Science and review of references through August 2017 for N-of-1 studies published in English.

Study selection: N-of-1 studies of pharmacological interventions with at least two subjects.

Data synthesis: Citation screening and data extractions were performed in duplicate. We performed statistical reanalysis testing for person-level HTE on all studies presenting person-level data.

Results: We identified 62 multiperson N-of-1 studies with at least two subjects. Statistical tests examining HTE were described in only 13 (21%), of which only two (3%) tested person-level HTE. Only 25 studies (40%) provided person-level data sufficient to reanalyse person-level HTE. Reanalysis using a fixed effect linear model identified statistically significant person-level HTE in 8 of the 13 studies (62%) reporting person-level treatment effects and in 8 of the 14 studies (57%) reporting person-level outcomes.

Conclusions: Our analysis suggests that person-level HTE is common and often substantial. Reviewed studies had incomplete information on person-level treatment effects and their variation. Improved assessment and reporting of person-level treatment effects in multiperson N-of-1 studies are needed.

Keywords: N-of-1 studies; heterogeneity of treatment effect; perseonalized medicine; systematic review.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Clinical Trials as Topic*
  • Cross-Over Studies*
  • Evidence-Based Medicine / methods*
  • Humans
  • Models, Statistical
  • Therapeutics / statistics & numerical data
  • Treatment Outcome