Objectives To identify non-inferiority trials within a cohort where the experimental therapy is the same as the active control comparator but at a reduced intensity and determine if these non-inferiority trials of reduced intensity therapies have less favourable results than other non-inferiority trials in the cohort. Such a finding would provide suggestive evidence of biocreep in these trials. Design This metaresearch study used a cohort of non-inferiority trials published in the five highest impact general medical journals during a 5-year period. Data relating to the characteristics and results of the trials were abstracted. Primary outcome measures Proportions of trials with a declaration of superiority, non-inferiority and point estimates favouring the experimental therapy and mean absolute risk differences for trials with outcomes expressed as a proportion. Results Our search yielded 163 trials reporting 182 non-inferiority comparisons; 36 comparisons from 31 trials were between the same therapy at reduced and full intensity. Compared with trials not evaluating reduced intensity therapies, fewer comparisons of reduced intensity therapies demonstrated a favourable result (non-inferiority or superiority) (58.3%vs82.2%; P=0.002) and fewer demonstrated superiority (2.8%vs18.5%; P=0.019). Likewise, point estimates for reduced intensity therapies more often favoured active control than those for other trials (77.8%vs39.7%; P<0.001) as did mean absolute risk differences (+2.5% vs 0.7%; P=0.018). Conclusions Non-inferiority trials comparing a therapy at reduced intensity to the same therapy at full intensity showed reduced effects compared with other non-inferiority trials. This suggests these trials may have a high rate of type 1 errors and biocreep, with significant implications for the design and interpretation of future non-inferiority trials.
%0 Journal Article
%1 Aberegg2018
%A Aberegg, Scott K
%A Hersh, Andrew M
%A Samore, Matthew H
%D 2018
%I BMJ Open
%J BMJ Open
%K AndrewMHersh EquivalenceTrialsasTopic* Humans MEDLINE MatthewHSamore NCBI NIH NLM NationalCenterforBiotechnologyInformation NationalInstitutesofHealth NationalLibraryofMedicine PMC5855198 PlaceboEffect Placebos PubMedAbstract ResearchDesign/standards* ScottKAberegg TreatmentOutcome doi:10.1136/bmjopen-2017-019494 pmid:29500210
%N 3
%P e019494
%R 10.1136/bmjopen-2017-019494
%T Do non-inferiority trials of reduced intensity therapies show reduced effects? A descriptive analysis
%U https://pubmed.ncbi.nlm.nih.gov/29500210/ https://bmjopen.bmj.com/lookup/doi/10.1136/bmjopen-2017-019494
%V 8
%X Objectives To identify non-inferiority trials within a cohort where the experimental therapy is the same as the active control comparator but at a reduced intensity and determine if these non-inferiority trials of reduced intensity therapies have less favourable results than other non-inferiority trials in the cohort. Such a finding would provide suggestive evidence of biocreep in these trials. Design This metaresearch study used a cohort of non-inferiority trials published in the five highest impact general medical journals during a 5-year period. Data relating to the characteristics and results of the trials were abstracted. Primary outcome measures Proportions of trials with a declaration of superiority, non-inferiority and point estimates favouring the experimental therapy and mean absolute risk differences for trials with outcomes expressed as a proportion. Results Our search yielded 163 trials reporting 182 non-inferiority comparisons; 36 comparisons from 31 trials were between the same therapy at reduced and full intensity. Compared with trials not evaluating reduced intensity therapies, fewer comparisons of reduced intensity therapies demonstrated a favourable result (non-inferiority or superiority) (58.3%vs82.2%; P=0.002) and fewer demonstrated superiority (2.8%vs18.5%; P=0.019). Likewise, point estimates for reduced intensity therapies more often favoured active control than those for other trials (77.8%vs39.7%; P<0.001) as did mean absolute risk differences (+2.5% vs 0.7%; P=0.018). Conclusions Non-inferiority trials comparing a therapy at reduced intensity to the same therapy at full intensity showed reduced effects compared with other non-inferiority trials. This suggests these trials may have a high rate of type 1 errors and biocreep, with significant implications for the design and interpretation of future non-inferiority trials.
@article{Aberegg2018,
abstract = {Objectives To identify non-inferiority trials within a cohort where the experimental therapy is the same as the active control comparator but at a reduced intensity and determine if these non-inferiority trials of reduced intensity therapies have less favourable results than other non-inferiority trials in the cohort. Such a finding would provide suggestive evidence of biocreep in these trials. Design This metaresearch study used a cohort of non-inferiority trials published in the five highest impact general medical journals during a 5-year period. Data relating to the characteristics and results of the trials were abstracted. Primary outcome measures Proportions of trials with a declaration of superiority, non-inferiority and point estimates favouring the experimental therapy and mean absolute risk differences for trials with outcomes expressed as a proportion. Results Our search yielded 163 trials reporting 182 non-inferiority comparisons; 36 comparisons from 31 trials were between the same therapy at reduced and full intensity. Compared with trials not evaluating reduced intensity therapies, fewer comparisons of reduced intensity therapies demonstrated a favourable result (non-inferiority or superiority) (58.3%vs82.2%; P=0.002) and fewer demonstrated superiority (2.8%vs18.5%; P=0.019). Likewise, point estimates for reduced intensity therapies more often favoured active control than those for other trials (77.8%vs39.7%; P<0.001) as did mean absolute risk differences (+2.5% vs 0.7%; P=0.018). Conclusions Non-inferiority trials comparing a therapy at reduced intensity to the same therapy at full intensity showed reduced effects compared with other non-inferiority trials. This suggests these trials may have a high rate of type 1 errors and biocreep, with significant implications for the design and interpretation of future non-inferiority trials.},
added-at = {2023-02-03T11:44:35.000+0100},
author = {Aberegg, Scott K and Hersh, Andrew M and Samore, Matthew H},
biburl = {https://www.bibsonomy.org/bibtex/2c3d02e5be76c9adc84d4d5d836f3c10f/jepcastel},
doi = {10.1136/bmjopen-2017-019494},
interhash = {dd6d8fbc83ccfe6c381b06dc6c09ce76},
intrahash = {c3d02e5be76c9adc84d4d5d836f3c10f},
issn = {2044-6055},
journal = {BMJ Open},
keywords = {AndrewMHersh EquivalenceTrialsasTopic* Humans MEDLINE MatthewHSamore NCBI NIH NLM NationalCenterforBiotechnologyInformation NationalInstitutesofHealth NationalLibraryofMedicine PMC5855198 PlaceboEffect Placebos PubMedAbstract ResearchDesign/standards* ScottKAberegg TreatmentOutcome doi:10.1136/bmjopen-2017-019494 pmid:29500210},
month = {3},
note = {Tests d'equivalència; Biocreep},
number = 3,
pages = {e019494},
pmid = {29500210},
publisher = {BMJ Open},
timestamp = {2023-02-03T11:44:35.000+0100},
title = {Do non-inferiority trials of reduced intensity therapies show reduced effects? A descriptive analysis},
url = {https://pubmed.ncbi.nlm.nih.gov/29500210/ https://bmjopen.bmj.com/lookup/doi/10.1136/bmjopen-2017-019494},
volume = 8,
year = 2018
}