Are large clinical trials in orthopaedic trauma justified?

on behalf of the FLOW Investigators

doi:10.1186/s12891-018-2029-3

Are large clinical trials in orthopaedic trauma justified?

on behalf of the FLOW Investigators

Research output: Contribution to journal › Article › peer-review

5 Citations (Scopus)

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 language	English
Article number	124
Journal	BMC Musculoskeletal Disorders
Volume	19
Issue number	1
DOIs	https://doi.org/10.1186/s12891-018-2029-3
Publication status	Published - Apr 20 2018
Externally published	Yes

Bibliographical note

Funding Information:
The FLOW trial was supported by Research Grants from the Canadian Institutes of Health Research # MCT-93173, United States Army Institute of Surgical Research, Orthopaedic Trauma Research Program (OTRP) and Peer Reviewed Orthopaedic Research Program (PRORP), and Association Internationale pour l’Ostéosynthèse Dynamique (AIOD). Stryker Company provided Surgilav irrigators for the trial for clinical sites in Asia. Zimmer Company provided the Pulsavac irrigator at discounted rates to selected clinical sites in North America. Triad Medical donated the initial supply of castile soap for the study. No donor or funder had a role in the design or conduct of the FLOW study, data collection or analyses, or the preparation of this manuscript. The FLOW trial was supported by the Office of the Assistant Secretary of Defense for Health Affairs, through the Orthopaedic Trauma Research Program under Award No. W81XWH-08-1-0473 and the Peer Reviewed Orthopaedic Research Program under Award No. W81XWH-12-1-0530. Opinions, interpretations, conclusions and recommendations are those of the authors and are not necessarily endorsed by the Department of Defense.

Funding Information:
SS reports grants from the Canadian Institutes of Health Research, employment/salary from McMaster University, and employment/salary from Global Research Solutions outside the submitted work. PTIII reports other from Smith & Nephew and other from Lippincott Williams & Wilkins outside the submitted work. PM reports personal fees from Global Research Solutions outside the submitted work. BP reports grants from Stryker, outside the submitted work. KJJ reports personal fees from Zimmer, personal fees from Lilly USA, LLC, and personal fees from Pacira outside the submitted work. MB reports grants from Canadian Institutes of Health Research, other from Stryker, other from Zimmer, other from Triad Medical, grants from Office of the Assistant Secretary of Defense for Health Affairs through the Orthopaedic Trauma Research Program and the Peer Reviewed Orthopaedic Research Program, and grants from Association Internationale pour l’Osteosynthese Dynamique during the conduct of the study. He reports grants and personal fees from Stryker, personal fees from Smith & Nephew, grants and personal fees from Amgen, grants from DePuy, grants and personal fees from Eli Lilly, grants and personal fees from DJO Global Inc., personal fees from Zimmer, and personal fees from Ferring outside the submitted work. GPS, NNO, and DS have nothing to disclose.

Publisher Copyright:
© 2018 The Author(s).

ASJC Scopus Subject Areas

Rheumatology
Orthopedics and Sports Medicine

Access to Document

10.1186/s12891-018-2029-3

Cite this

@article{7645c6fe815b491a91c701ff88c90023,

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.",

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 Kevin Gurr and Richardson, {C. Glen} and William Oxner",

note = "Funding Information: The FLOW trial was supported by Research Grants from the Canadian Institutes of Health Research # MCT-93173, United States Army Institute of Surgical Research, Orthopaedic Trauma Research Program (OTRP) and Peer Reviewed Orthopaedic Research Program (PRORP), and Association Internationale pour l{\textquoteright}Ost{\'e}osynth{\`e}se Dynamique (AIOD). Stryker Company provided Surgilav irrigators for the trial for clinical sites in Asia. Zimmer Company provided the Pulsavac irrigator at discounted rates to selected clinical sites in North America. Triad Medical donated the initial supply of castile soap for the study. No donor or funder had a role in the design or conduct of the FLOW study, data collection or analyses, or the preparation of this manuscript. The FLOW trial was supported by the Office of the Assistant Secretary of Defense for Health Affairs, through the Orthopaedic Trauma Research Program under Award No. W81XWH-08-1-0473 and the Peer Reviewed Orthopaedic Research Program under Award No. W81XWH-12-1-0530. Opinions, interpretations, conclusions and recommendations are those of the authors and are not necessarily endorsed by the Department of Defense. Funding Information: SS reports grants from the Canadian Institutes of Health Research, employment/salary from McMaster University, and employment/salary from Global Research Solutions outside the submitted work. PTIII reports other from Smith & Nephew and other from Lippincott Williams & Wilkins outside the submitted work. PM reports personal fees from Global Research Solutions outside the submitted work. BP reports grants from Stryker, outside the submitted work. KJJ reports personal fees from Zimmer, personal fees from Lilly USA, LLC, and personal fees from Pacira outside the submitted work. MB reports grants from Canadian Institutes of Health Research, other from Stryker, other from Zimmer, other from Triad Medical, grants from Office of the Assistant Secretary of Defense for Health Affairs through the Orthopaedic Trauma Research Program and the Peer Reviewed Orthopaedic Research Program, and grants from Association Internationale pour l{\textquoteright}Osteosynthese Dynamique during the conduct of the study. He reports grants and personal fees from Stryker, personal fees from Smith & Nephew, grants and personal fees from Amgen, grants from DePuy, grants and personal fees from Eli Lilly, grants and personal fees from DJO Global Inc., personal fees from Zimmer, and personal fees from Ferring outside the submitted work. GPS, NNO, and DS have nothing to disclose. Publisher Copyright: {\textcopyright} 2018 The Author(s).",

year = "2018",

month = apr,

day = "20",

doi = "10.1186/s12891-018-2029-3",

language = "English",

volume = "19",

journal = "BMC Musculoskeletal Disorders",

issn = "1471-2474",