%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 }