The Clavien–Dindo classification (CDC) is the most widely used tool for reporting postoperative complications in randomized clinical trials (RCTs) in pancreatic surgery1. Although the CDC provides a standardized framework, there is still noticeable variability in how major complications (MCs) are defined. Different thresholds (CDC ≥ II in one versus CDC ≥ IIIb in another study) raise concerns regarding the comparability of RCTs. Such inconsistency in the definition of MCs represents a critical scientific issue, because it undermines the quality of systematic reviews, meta-analyses, and clinical guidelines. This systematic review investigated differences in the definition of MCs in RCTs in pancreatic surgery when applying the CDC.
This systematic review was conducted according to the Cochrane Handbook for Systematic Reviews and Interventions and is reported following the PRISMA guidelines. A literature search was performed using the Evidence Map of Pancreatic Surgery platform (https://map.eviglance.com/maps/8?view=map) up to 27 October 2024. The inclusion criterion was the definition of MCs according to the CDC. The exclusion criteria were the absence of a definition of MCs in the methods, missing reporting of MCs in the results, articles not written in English, and studies published before the CDC was introduced (that is, before 2004). The following details were extracted: study authors, publication year, sample size, definition of MCs, primary endpoint, and the number of patients. Data were analysed using SPSS® (version 29; IBM, Armonk, NY, USA).
Of 1066 studies on pancreatic surgery, 366 were identified as RCTs by the Evidence Map of Pancreatic Surgery platform. Sixty-six studies defined MCs according to the CDC and were included in the analysis (Table S1). Most studies (52, 78.8%) defined MCs as CDC ≥ III. Five studies (7.6%) defined MCs as only CDC III–IV. Four studies (6.1%) defined MCs as CDC ≥ IIIb, and one study (1.5%) defined MCs as CDC > IIIb. CDC ≥ II and CDC II–IV were both used twice (3.0%) to define MCs (Table S1).
There were 20 different ways of reporting postoperative complications according to the CDC. Most studies (24, 36.4%) reported only CDC ≥ III. Nine studies (13.6%) reported postoperative complications without distinguishing CDC IIIa from CDC IIIb or CDC IVa from CDC IVb. Only 12 (18.2%) of the 66 included studies reported all CDC grades. The remaining studies (23, 34.8%) were distributed across the 17 observed CDC variations for reporting postoperative complications (Fig. 1).
Fig. 1.
Observed variations in CDC reporting in the 66 studies included in the analysis
*MCs were defined in the methods without reporting of MCs or any CD grades in the results. CDC, Clavien–Dindo classification; CD, Clavien–Dindo; MCs, major complications.
The MC variations showed inconsistency across the included RCTs. Despite the rigorous methodology described, most studies developed different definitions of MCs and unique approaches to report postoperative complications. This raised reasonable concern about how results of RCTs are being interpreted.
MCs are a valid clinical outcome because they are linked to severe complications that affect healthcare quality and cost2,3. However, inconsistencies in the definition of MCs undermine objective and reproducible data interpretation. The failure to objectively determine whether an intervention reduces the rate of postoperative complications hampers improvements in patient care and increases healthcare costs4,5. The next issue was the incomplete reporting of CDC grades. The tendency to report postoperative complications using different CDC modifications often made it difficult to distinguish between CDC IIIa and CDC IIIb, or CDC IVa and CDC IVb, because they were frequently reported together. The inability to differentiate between the CDC grades hinders the interpretation of outcomes and data synthesis.
Consistent reporting of postoperative complications in RCTs is crucial for providing evidence-based guidance. Adopting a universal definition of MCs can enhance objectivity.
Supplementary Material
Contributor Information
Amila Cizmic, Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Laetitia Hampe, Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Philipp A Wise, Department of Neuroradiology at the Neurology Center, Heidelberg University Hospital, Heidelberg, Germany.
Pascal Probst, Department of Surgery, Cantonal Hospital Thurgau, Frauenfeld, Switzerland.
Markus K Muller, Department of Surgery, Cantonal Hospital Thurgau, Frauenfeld, Switzerland.
Christoph Kuemmerli, Department of Surgery, Clarunis University Digestive Health Care Center, Basel, Switzerland.
Philip C Müller, Department of Surgery, Clarunis University Digestive Health Care Center, Basel, Switzerland.
Jan Bardenhagen, Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Anna Nießen, Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Faik G Uzunoglu, Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Jakob Izbicki, Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Thilo Hackert, Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Felix Nickel, Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Funding
The authors have no funding to declare.
Author contributions
Amila Cizmic (Data curation, Formal analysis, Writing—original draft), Laetitia Hampe (Data curation, Writing—original draft), Philipp A. Wise (Formal analysis, Investigation), Pascal Probst (Methodology, Supervision), Markus Müller (Methodology, Supervision), Christoph Kuemmerli (Validation, Visualization), Philip Müller (Investigation, Methodology), Jan Bardenhagen (Formal analysis, Visualization), Anna Nießen (Supervision, Validation), Faik G. Uzunoglu (Formal analysis, Methodology), Jakob Izbicki (Supervision, Writing—review & editing), Thilo Hackert (Validation, Writing—review & editing), and Felix Nickel (CRediT contribution not specified)
Disclosure
The authors declare no conflict of interest.
Supplementary material
Data availability
All data used is provided in the manuscript or as Supplementary material.
References
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Supplementary Materials
Data Availability Statement
All data used is provided in the manuscript or as Supplementary material.