title: Quality control in multicentric clinical trials. An experience of the EORTC Gynecological Cancer Cooperative Group.
abstract: Data Quality is a central requirement of scientific research and external monitoring is essential in multicentric clinical trials (MCT). A quality control (QC) study was conducted in the main Institutions participating in EORTC-GCCG Protocol number 55863 - randomised phase III trial of vindesine, cisplatin, bleomycin and mitomycin-C (BEMP) versus cisplatin (P) in disseminated squamous cell carcinoma of the uterine cervix - in order to assess the impact of variations in data quality on the conclusions of the trial. The reliability of the different centres in following the protocol was investigated by a questionnaire covering drug prescription, local facilities and the procedure for preparation and administration of chemotherapy. The 'treatment protocol adherence' was evaluated by recalculation of the ideal protocol dose and its comparison with the actual delivered dosage at each cycle of chemotherapy. 'Data quality control' was assessed by comparison of data on case report forms (CRFs) with the corresponding items in the medical records. Eleven centres participating in the trial were visited by the same team of reviewers. Striking differences were noted in the chemotherapy administration procedures and between the type and quality of hospital files. Overall, there was an acceptable level of data quality and protocol compliance. Data accuracy was 81.8% (range: 65. 6-97%) of the 4424 items checked. Incorrect data were found in 7.0% (2.3-14.5%), data were missing on the form in 3.6% of cases (0-12%) and data was on the form but not in the file in 7.6% of cases (0. 7-17.5%). Causes of inaccuracy were analysed. Both problems in data management but also in a lack of clarity of the protocol and/or CRFs were to blame. Training and supervision of data managers, precision in writing protocols, standardisation of some aspects of CRFs and the use of a checklist for chemotherapy data and treatment toxicities would have avoided many of these errors. The need for QC in all collaborative groups performing MCT is emphasised. A literature review on QC in MCT dealing with chemotherapy is included.
authors.affiliation: Department of Gynecologic Oncology, University of Brescia, Spedali Civili Brescia, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Favalli
authors.forename: J B
authors.initials: JB
authors.lastname: Vermorken
authors.forename: K
authors.initials: K
authors.lastname: Vantongelen
authors.forename: J
authors.initials: J
authors.lastname: Renard
authors.forename: A T
authors.initials: AT
authors.lastname: Van Oosterom
authors.forename: S
authors.initials: S
authors.lastname: Pecorelli
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001761:Bleomycin / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage; D002985:Clinical Protocols; D003625:Data Collection / Q000592:standards; D005260:Female; D006801:Humans; D016685:Mitomycin / Q000008:administration & dosage; D011786:Quality Control; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy*; D014751:Vindesine / Q000008:administration & dosage
chemical_list: D001761:Bleomycin; D016685:Mitomycin; D002945:Cisplatin; D014751:Vindesine