Trial sequential analyses of meta-analyses of complications in laparoscopic vs. small-incision cholecystectomy: more randomized patients are needed.
OBJECTIVE
Conclusions based on meta-analyses of randomized trials carry a status of "truth." Methodological components may identify trials with systematic errors ("bias"). Trial sequential analysis (TSA) evaluates random errors in meta-analysis. We analyzed meta-analyses on laparoscopic vs. small-incision cholecystectomy regarding different outcome measures for the occurrence of type I errors.


METHODS
Using TSA, we calculated the required information size (IS) and the trial sequential monitoring boundaries regarding complications in our Cochrane review with meta-analyses of cholecystectomy. For each outcome, we calculated a low risk of bias heterogeneity-adjusted IS. As a sensitivity analysis, we calculated an a priori heterogeneity-adjusted IS.


RESULTS
According to the trial sequential analyses based on a low risk of bias heterogeneity-adjusted IS definitive evidence may be reached by conducting one more randomized trial. Information may be required on 582 and 119 additional randomized patients to evaluate the effect on severe complications and serious adverse events (SAEs), respectively.


CONCLUSIONS
Our results provide incentives to conduct a new trial with a low risk of bias focusing on a new composite outcome measure of SAEs to obtain conclusive evidence on which operative method to recommend.
Keus
Frederik
F
The Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Center for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. erickeus@hotmail.com
Wetterslev
Jørn
J
Gluud
Christian
C
Gooszen
Hein G
HG
van Laarhoven
Cornelis J H M
CJ
D015982:Bias; D001652:Bile Ducts / Q000293:injuries; D002763:Cholecystectomy / Q000009:adverse effects* / Q000379:methods; D017081:Cholecystectomy, Laparoscopic / Q000009:adverse effects; D041761:Cholecystolithiasis / Q000601:surgery*; D003627:Data Interpretation, Statistical; D019317:Evidence-Based Medicine / Q000379:methods; D006801:Humans; D007431:Intraoperative Complications; D015201:Meta-Analysis as Topic; D017063:Outcome Assessment, Health Care / Q000379:methods; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D018401:Sample Size