Quality control in multicentric clinical trials. An experience of the EORTC gynecological cancer cooperative group

Data Quality is a central requirement of scientific research and external m onitoring is essential in multicentric clinical trials (MCT). A quality con trol (QC) study was conducted in the main Institutions participating in EOR TC-GCCG Protocol number 55863 - randomised phase III trial of vindesine. ci splatin, bleomycin and mitomycin-C (BEMP) versus cisplatin (P) in dissemina ted 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 r eliability of the different centres in following the protocol was investiga ted by a questionnaire covering drug prescription, local facilities and the procedure for preparation and administration of chemotherapy. The 'treatme nt 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 record s. Eleven centres participating in the trial were visited by the same team of reviewers. Striking differences were noted in the chemotherapy administr ation procedures and between the type and quality of hospital files. Overal l. there was an acceptable level of data quality and protocol compliance. D ata accuracy was 81.8% (range: 65.6-97%) of the 4424 items checked. Incorre ct 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 da ta management but also in a lack of clarity of the protocol and/or CRFs wer e to blame. Training and supervision of data managers, precision in writing protocols, standardisation of some aspects of CRFs and the use of a checkl ist 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. (C) 2000 Published by Elsevier Science Ltd. All rights reserve d.