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

Gowri Raman, Ethan M. Balk, Lana Lai, Jennifer Shi, Jeffrey Chan, Jennifer S. Lutz, Robert W. Dubois, Richard L Kravitz, David M. Kent

Research output: Contribution to journalReview article

2 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere017641
JournalBMJ Open
Volume8
Issue number5
DOIs
StatePublished - May 1 2018
Externally publishedYes

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Therapeutics
Information Storage and Retrieval
Linear Models
Pharmacology

Keywords

  • heterogeneity of treatment effect
  • N-of-1 studies
  • perseonalized medicine
  • systematic review

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Evaluation of person-level heterogeneity of treatment effects in published multiperson N-of-1 studies : Systematic review and reanalysis. / Raman, Gowri; Balk, Ethan M.; Lai, Lana; Shi, Jennifer; Chan, Jeffrey; Lutz, Jennifer S.; Dubois, Robert W.; Kravitz, Richard L; Kent, David M.

In: BMJ Open, Vol. 8, No. 5, e017641, 01.05.2018.

Research output: Contribution to journalReview article

Raman, Gowri ; Balk, Ethan M. ; Lai, Lana ; Shi, Jennifer ; Chan, Jeffrey ; Lutz, Jennifer S. ; Dubois, Robert W. ; Kravitz, Richard L ; Kent, David M. / Evaluation of person-level heterogeneity of treatment effects in published multiperson N-of-1 studies : Systematic review and reanalysis. In: BMJ Open. 2018 ; Vol. 8, No. 5.
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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.",
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AU - Balk, Ethan M.

AU - Lai, Lana

AU - Shi, Jennifer

AU - Chan, Jeffrey

AU - Lutz, Jennifer S.

AU - Dubois, Robert W.

AU - Kravitz, Richard L

AU - Kent, David M.

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N2 - 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.

AB - 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.

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