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

• Published in: BMJ open Vol. 8; no. 5; p. e017641
• Main Authors: Raman, Gowri, Balk, Ethan M, Lai, Lana, Shi, Jennifer, Chan, Jeffrey, Lutz, Jennifer S, Dubois, Robert W, Kravitz, Richard L, Kent, David M
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group LTD 01.05.2018; BMJ Publishing Group
• Subjects: Drug therapy; Evidence-based medicine; Patient-Centred Medicine; Patients; Precision medicine; Systematic review; systematic review; perseonalized medicine; N-of-1 studies; heterogeneity of treatment effect
• ISSN: 2044-6055; 2044-6055
• DOI: 10.1136/bmjopen-2017-017641

ObjectiveIndividual 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 designSystematic review and reanalysis of multiperson N-of-1 studies.Data sourcesMedline, Cochrane Controlled Trials, EMBASE, Web of Science and review of references through August 2017 for N-of-1 studies published in English.Study selectionN-of-1 studies of pharmacological interventions with at least two subjects.Data synthesisCitation screening and data extractions were performed in duplicate. We performed statistical reanalysis testing for person-level HTE on all studies presenting person-level data.ResultsWe 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.ConclusionsOur 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.