F Trotta1, G Apolone2, S Garattini2, G Tafuri3. 1. Italian Medicines Agency (AIFA), Rome. 2. Mario Negri Institute for Pharmacological Research, Milan, Italy. 3. Italian Medicines Agency (AIFA), Rome; Utrecht University, Utrecht Institute for Pharmaceutical Sciences, Utrecht, The Netherlands. Electronic address: g.tafuri@aifa.gov.it.
Abstract
BACKGROUND: The aim of this study is to assess the use of interim analyses in randomised controlled trials (RCTs) testing new anticancer drugs, focussing on oncological clinical trials stopped early for benefit. MATERIALS AND METHODS: All published clinical trials stopped early for benefit and published in the last 11 years, regarding anticancer drugs and containing an interim analysis, were assessed. RESULTS: Twenty-five RCTs were analysed. The evaluation of efficacy was protocol planned through time-related primary end points, >40% of them overall survival. In 95% of studies, at the interim analysis, efficacy was evaluated using the same end point as planned for the final analysis. As a consequence of early stopping after the interim analysis, approximately 3300 patients/events across all studies were spared. More than 78% of the RCTs published in the last 3 years were used for registration purposes. CONCLUSION: Though criticism of the poor quality of oncological trials seems out of place, unfortunately early termination raises new concerns. The relation between sparing patients and saving time and trial costs indicates that there is a market-driven intent. We believe that only untruncated trials can provide a full level of evidence which can be translated into clinical practice without further confirmative trials.
BACKGROUND: The aim of this study is to assess the use of interim analyses in randomised controlled trials (RCTs) testing new anticancer drugs, focussing on oncological clinical trials stopped early for benefit. MATERIALS AND METHODS: All published clinical trials stopped early for benefit and published in the last 11 years, regarding anticancer drugs and containing an interim analysis, were assessed. RESULTS: Twenty-five RCTs were analysed. The evaluation of efficacy was protocol planned through time-related primary end points, >40% of them overall survival. In 95% of studies, at the interim analysis, efficacy was evaluated using the same end point as planned for the final analysis. As a consequence of early stopping after the interim analysis, approximately 3300 patients/events across all studies were spared. More than 78% of the RCTs published in the last 3 years were used for registration purposes. CONCLUSION: Though criticism of the poor quality of oncological trials seems out of place, unfortunately early termination raises new concerns. The relation between sparing patients and saving time and trial costs indicates that there is a market-driven intent. We believe that only untruncated trials can provide a full level of evidence which can be translated into clinical practice without further confirmative trials.
Authors: Matthias Briel; Melanie Lane; Victor M Montori; Dirk Bassler; Paul Glasziou; German Malaga; Elie A Akl; Ignacio Ferreira-Gonzalez; Pablo Alonso-Coello; Gerard Urrutia; Regina Kunz; Carolina Ruiz Culebro; Suzana Alves da Silva; David N Flynn; Mohamed B Elamin; Brigitte Strahm; M Hassan Murad; Benjamin Djulbegovic; Neill K J Adhikari; Edward J Mills; Femida Gwadry-Sridhar; Haresh Kirpalani; Heloisa P Soares; Nisrin O Abu Elnour; John J You; Paul J Karanicolas; Heiner C Bucher; Julianna F Lampropulos; Alain J Nordmann; Karen E A Burns; Sohail M Mulla; Heike Raatz; Amit Sood; Jagdeep Kaur; Clare R Bankhead; Rebecca J Mullan; Kara A Nerenberg; Per Olav Vandvik; Fernando Coto-Yglesias; Holger Schünemann; Fabio Tuche; Pedro Paulo M Chrispim; Deborah J Cook; Kristina Lutz; Christine M Ribic; Noah Vale; Patricia J Erwin; Rafael Perera; Qi Zhou; Diane Heels-Ansdell; Tim Ramsay; Stephen D Walter; Gordon H Guyatt Journal: Trials Date: 2009-07-06 Impact factor: 2.279