Are large clinical trials in orthopaedic trauma justified?

on behalf of the FLOW Investigators

Research output: Contribution to journalArticle

Abstract

Background: The objective of this analysis is to evaluate the necessity of large clinical trials using FLOW trial data. Methods: The FLOW pilot study and definitive trial were factorial trials evaluating the effect of different irrigation solutions and pressures on re-operation. To explore treatment effects over time, we analyzed data from the pilot and definitive trial in increments of 250 patients until the final sample size of 2447 patients was reached. At each increment we calculated the relative risk (RR) and associated 95% confidence interval (CI) for the treatment effect, and compared the results that would have been reported at the smaller enrolments with those seen in the final, adequately powered study. Results: The pilot study analysis of 89 patients and initial incremental enrolments in the FLOW definitive trial favored low pressure compared to high pressure (RR: 1.50, 95% CI: 0.75-3.04; RR: 1.39, 95% CI: 0.60-3.23, respectively), which is in contradiction to the final enrolment, which found no difference between high and low pressure (RR: 1.04, 95% CI: 0.81-1.33). In the soap versus saline comparison, the FLOW pilot study suggested that re-operation rate was similar in both the soap and saline groups (RR: 0.98, 95% CI: 0.50-1.92), whereas the FLOW definitive trial found that the re-operation rate was higher in the soap treatment arm (RR: 1.28, 95% CI: 1.04-1.57). Conclusions: Our findings suggest that studies with smaller sample sizes would have led to erroneous conclusions in the management of open fracture wounds. Trial registration: NCT01069315 (FLOW Pilot Study) Date of Registration: February 17, 2010, NCT00788398 (FLOW Definitive Trial) Date of Registration: November 10, 2008.

Original languageEnglish (US)
Article number2029
JournalBMC Musculoskeletal Disorders
Volume19
Issue number1
DOIs
StatePublished - Apr 20 2018

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Orthopedics
Clinical Trials
Confidence Intervals
Soaps
Wounds and Injuries
Pressure
Sample Size
Open Fractures
Therapeutics

Keywords

  • FLOW trial
  • Large trials
  • Orthopaedic trial
  • Sample size

ASJC Scopus subject areas

  • Rheumatology
  • Orthopedics and Sports Medicine

Cite this

Are large clinical trials in orthopaedic trauma justified? / on behalf of the FLOW Investigators.

In: BMC Musculoskeletal Disorders, Vol. 19, No. 1, 2029, 20.04.2018.

Research output: Contribution to journalArticle

on behalf of the FLOW Investigators. / Are large clinical trials in orthopaedic trauma justified?. In: BMC Musculoskeletal Disorders. 2018 ; Vol. 19, No. 1.
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title = "Are large clinical trials in orthopaedic trauma justified?",
abstract = "Background: The objective of this analysis is to evaluate the necessity of large clinical trials using FLOW trial data. Methods: The FLOW pilot study and definitive trial were factorial trials evaluating the effect of different irrigation solutions and pressures on re-operation. To explore treatment effects over time, we analyzed data from the pilot and definitive trial in increments of 250 patients until the final sample size of 2447 patients was reached. At each increment we calculated the relative risk (RR) and associated 95{\%} confidence interval (CI) for the treatment effect, and compared the results that would have been reported at the smaller enrolments with those seen in the final, adequately powered study. Results: The pilot study analysis of 89 patients and initial incremental enrolments in the FLOW definitive trial favored low pressure compared to high pressure (RR: 1.50, 95{\%} CI: 0.75-3.04; RR: 1.39, 95{\%} CI: 0.60-3.23, respectively), which is in contradiction to the final enrolment, which found no difference between high and low pressure (RR: 1.04, 95{\%} CI: 0.81-1.33). In the soap versus saline comparison, the FLOW pilot study suggested that re-operation rate was similar in both the soap and saline groups (RR: 0.98, 95{\%} CI: 0.50-1.92), whereas the FLOW definitive trial found that the re-operation rate was higher in the soap treatment arm (RR: 1.28, 95{\%} CI: 1.04-1.57). Conclusions: Our findings suggest that studies with smaller sample sizes would have led to erroneous conclusions in the management of open fracture wounds. Trial registration: NCT01069315 (FLOW Pilot Study) Date of Registration: February 17, 2010, NCT00788398 (FLOW Definitive Trial) Date of Registration: November 10, 2008.",
keywords = "FLOW trial, Large trials, Orthopaedic trial, Sample size",
author = "{on behalf of the FLOW Investigators} and Sheila Sprague and Paul Tornetta and Slobogean, {Gerard P.} and O'Hara, {Nathan N.} and Paula McKay and Brad Petrisor and Jeray, {Kyle J.} and Schemitsch, {Emil H.} and David Sanders and Mohit Bhandari and Guyatt, {Gordon H.} and Stephen Walter and Jeff Anglen and Michael Bosse and Susan Liew and Parag Sancheti and Kerry Tai and Diane Heels-Ansdell and Lisa Buckingham and Aravin Duraikannan and Tanner, {Stephanie L.} and Snider, {Rebecca G.} and Douglas Altman and Rajiv Gandhi and Markus Bischoff and {Della Rocca}, {Gregory J.} and Bill Ristevski and Krishan Rajaratnam and Dale Williams and Matthew Denkers and Drew Bednar and John Sadler and Desmond Kwok and Brian Drew and Ivan Wong and Kim Madden and Hall, {Jeremy A.} and McKee, {Michael D.} and Henry Ahn and Daniel Whelan and James Waddell and Timothy Daniels and Earl Bogoch and Aaron Nauth and Vicente, {Milena R.} and Hidy, {Jennifer T.} and Lawendy, {Abdel Rahman} and Karl Shively and Brian Mullis and Janos Ertl",
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AU - on behalf of the FLOW Investigators

AU - Sprague, Sheila

AU - Tornetta, Paul

AU - Slobogean, Gerard P.

AU - O'Hara, Nathan N.

AU - McKay, Paula

AU - Petrisor, Brad

AU - Jeray, Kyle J.

AU - Schemitsch, Emil H.

AU - Sanders, David

AU - Bhandari, Mohit

AU - Guyatt, Gordon H.

AU - Walter, Stephen

AU - Anglen, Jeff

AU - Bosse, Michael

AU - Liew, Susan

AU - Sancheti, Parag

AU - Tai, Kerry

AU - Heels-Ansdell, Diane

AU - Buckingham, Lisa

AU - Duraikannan, Aravin

AU - Tanner, Stephanie L.

AU - Snider, Rebecca G.

AU - Altman, Douglas

AU - Gandhi, Rajiv

AU - Bischoff, Markus

AU - Della Rocca, Gregory J.

AU - Ristevski, Bill

AU - Rajaratnam, Krishan

AU - Williams, Dale

AU - Denkers, Matthew

AU - Bednar, Drew

AU - Sadler, John

AU - Kwok, Desmond

AU - Drew, Brian

AU - Wong, Ivan

AU - Madden, Kim

AU - Hall, Jeremy A.

AU - McKee, Michael D.

AU - Ahn, Henry

AU - Whelan, Daniel

AU - Waddell, James

AU - Daniels, Timothy

AU - Bogoch, Earl

AU - Nauth, Aaron

AU - Vicente, Milena R.

AU - Hidy, Jennifer T.

AU - Lawendy, Abdel Rahman

AU - Shively, Karl

AU - Mullis, Brian

AU - Ertl, Janos

PY - 2018/4/20

Y1 - 2018/4/20

N2 - Background: The objective of this analysis is to evaluate the necessity of large clinical trials using FLOW trial data. Methods: The FLOW pilot study and definitive trial were factorial trials evaluating the effect of different irrigation solutions and pressures on re-operation. To explore treatment effects over time, we analyzed data from the pilot and definitive trial in increments of 250 patients until the final sample size of 2447 patients was reached. At each increment we calculated the relative risk (RR) and associated 95% confidence interval (CI) for the treatment effect, and compared the results that would have been reported at the smaller enrolments with those seen in the final, adequately powered study. Results: The pilot study analysis of 89 patients and initial incremental enrolments in the FLOW definitive trial favored low pressure compared to high pressure (RR: 1.50, 95% CI: 0.75-3.04; RR: 1.39, 95% CI: 0.60-3.23, respectively), which is in contradiction to the final enrolment, which found no difference between high and low pressure (RR: 1.04, 95% CI: 0.81-1.33). In the soap versus saline comparison, the FLOW pilot study suggested that re-operation rate was similar in both the soap and saline groups (RR: 0.98, 95% CI: 0.50-1.92), whereas the FLOW definitive trial found that the re-operation rate was higher in the soap treatment arm (RR: 1.28, 95% CI: 1.04-1.57). Conclusions: Our findings suggest that studies with smaller sample sizes would have led to erroneous conclusions in the management of open fracture wounds. Trial registration: NCT01069315 (FLOW Pilot Study) Date of Registration: February 17, 2010, NCT00788398 (FLOW Definitive Trial) Date of Registration: November 10, 2008.

AB - Background: The objective of this analysis is to evaluate the necessity of large clinical trials using FLOW trial data. Methods: The FLOW pilot study and definitive trial were factorial trials evaluating the effect of different irrigation solutions and pressures on re-operation. To explore treatment effects over time, we analyzed data from the pilot and definitive trial in increments of 250 patients until the final sample size of 2447 patients was reached. At each increment we calculated the relative risk (RR) and associated 95% confidence interval (CI) for the treatment effect, and compared the results that would have been reported at the smaller enrolments with those seen in the final, adequately powered study. Results: The pilot study analysis of 89 patients and initial incremental enrolments in the FLOW definitive trial favored low pressure compared to high pressure (RR: 1.50, 95% CI: 0.75-3.04; RR: 1.39, 95% CI: 0.60-3.23, respectively), which is in contradiction to the final enrolment, which found no difference between high and low pressure (RR: 1.04, 95% CI: 0.81-1.33). In the soap versus saline comparison, the FLOW pilot study suggested that re-operation rate was similar in both the soap and saline groups (RR: 0.98, 95% CI: 0.50-1.92), whereas the FLOW definitive trial found that the re-operation rate was higher in the soap treatment arm (RR: 1.28, 95% CI: 1.04-1.57). Conclusions: Our findings suggest that studies with smaller sample sizes would have led to erroneous conclusions in the management of open fracture wounds. Trial registration: NCT01069315 (FLOW Pilot Study) Date of Registration: February 17, 2010, NCT00788398 (FLOW Definitive Trial) Date of Registration: November 10, 2008.

KW - FLOW trial

KW - Large trials

KW - Orthopaedic trial

KW - Sample size

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