Inappropriate Study Population
Bartholmes et al. (1) interpret their study results as evidence of a benefit of pupillometry in cardiac anesthesia. However, a number of limitations restrict this interpretation. The pupillometry did not reduce the postoperative extubation time, which was the primary endpoint. However, this is neither mentioned in the Summary nor in the Discussion section s. The investigation was stopped early based on an interim analysis after the inclusion of only 57 patients. The early stopping of the trial resulted not only in a considerably lower number of study participants than the planned 200, as stated in the study registration (2), but also in study groups of very different sizes (n = 32 in the pupillary pain index [PPI] group versus n = 25 in the control group).
Stopping a study earlier than planned can substantially underestimate the treatment effect. CONSORT (Consolidated Standards of Reporting Trials) therefore recommends a detailed description of the prerequisites of a planned interim analysis in the study protocol, and the establishment of an independent data control committee that reviews and implements those prerequisites (3). Statistical criteria should be viewed as recommendation rather than requirement for an early stopping. Respective information is neither provided in the methodology section of the article nor in the study registration (2). If one follows the CONSORT recommendations, the early stopping of this study is scientifically insufficiently founded.
The mean values of the extubation times are within the definition limit for fast-track cardiac surgery of less than eight hours; however, the extubation times exceeded eight hours in approximately 5 of 32 patients (16%) in the PPI group, and approximately 7 of 25 patients (28%) in the control group, with maximum extubation times of 19.7 hours and 22.7 hours, respectively. In this regard, the study population appears to have been inappropriate for the research question addressed.
Prof. em. Dr. med. Hans-Joachim Priebe
|1.||Bartholmes F, Malewicz NM, Ebel M, Zahn PK, Meyer-Frießem CH: Pupillometric monitoring of nociception in cardiac anesthesia—a randomized controlled study. Dtsch Arztebl Int 2020; 117: 833–40 VOLLTEXT|
|2.||Studienbeschreibung: Postoperative Extubationszeit und Inzidenz postoperativer Übelkeit und Erbrechen bei kardiochirugischen Patienten abhängig von einer intraoperativ gesteuerten Analgesie mittels Pupillometrie. www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00012329 (last accessed on 21 January 2021).|
|3.||Moher D, Hopewell S, Schulz KF, et al.: CONSORT 2010 Explanation and elaboration: updated guidelines for reporting parallel group randomised trials. BMJ 2010; 340: c869 CrossRef MEDLINE PubMed Central|