Meeting: 2015 ASCO Annual Meeting
Title: European Union (EU) vs. non-EU (NOEU) countries study compliance: the experience of the phase III FLORENCE study testing febuxostat in the Tumor Lysis Syndrome (TLS) prevention.



Background: Harmonization of clinical practice and standard of care allow multicenter pivotal trials to be successfully run both in EU and NOEU Countries, with patients recruitment increasing in favor of NOEU sites. Comparative data on the performance of EU vs. NOEU investigators in terms of compliance to study protocol and data collection are now offered by the FLORENCE study (a pivotal phase III study of Febuxostat vs. Allopurinol for TLS prevention in hematologic malignancies; NCT01724528) that included 75 European sites distributed in both EU (HR, CZ, DE, HU, IT, PL, RO, ES) and NOEU (RU, RS, UA) contributing with 193 and 152 randomized patients (0.35 and 0.44 patients/month/site), respectively. Methods: Compliance of sites to FLORENCE was evaluated by counting all protocol violations (APVs) and major protocol violations (MPVs) weighted for the number of randomized patients grouped by EU and NOEU sites. Distribution of APVs and MPVs was compared using a Chi Square test at 5% significant level. Additionally, distribution of the most affected MPVs subcategories, namely eligibility of randomized patients, errors in treatment intake, use of prohibited medications, compliance to stratification factors/safety data recording (SFSDR), compliance to scheduled Visits/Assessments (SVAs) and timely reporting of serious adverse events (weighted for the number of patients as per APVs and MPVs) was compared using a Fishers Exact test at 5% significant level. Results: APVs were 815, 32.4% in NOEU vs. 67.6% in EU sites (p = .0686). MPVs were 68, 17.7% in NOEU vs. 82.3% in EU (p < .0001), however the difference was due to only two MPVs subcategories, namely compliance to SFSDR (12.5% vs. 87.5% for NOEU and EU sites respectively; p = .0056) and to SVAs (4.2% vs. 95.8% for NOEU and EU sites respectively; p = .0001). Conclusions: Overall compliance to FLORENCE study was high with limited MPVs; NOEU sites had less MPVs affecting compliance to SFSDR and to SVAs, which may reflect difference in assigned site resources. The FLORENCE study provides the first evidence that NOEU and EU sites run a multicenter pivotal trial with high and almost comparable study compliance Clinical trial information: NCT01724528