Approaches to interim analysis of cancer randomised clinical trials with time to event endpoints: A survey from the Italian National Monitoring Centre for Clinical Trials
Open accessAbstract
BACKGROUND: Although interim analysis approaches in clinical trials are widely known, information on current practice of planned monitoring is still scarce. Reports of studies rarely include details on the strategies for both data monitoring and interim analysis. The aim of this project is to investigate the forms of monitoring used in cancer clinical trials and in particular to gather information on the role of interim analyses in the data monitoring process of a clinical trial. This study focused on the prevalence of different types of interim analyses and data monitoring in cancer clinical trials. METHODS: Source of investigation were the protocols of cancer clinical trials included in the Italian registry of clinical trials from 2000 to 2005. Evaluation was restricted to protocols of randomised studies with a time to event endpoint, such as overall survival (OS) or progression free survival (PFS). A template data extraction form was developed and tested in a pilot phase. Selection of relevant protocols and data extraction were performed independently by two evaluators, with differences in the data assessment resolved by consensus with a third reviewer, referring back to the original protocol. Information was obtained on a) general characteristics of the protocol b) disease localization and patient setting; c) study design d) interim analyses; e) DSMC. RESULTS: The analysis of the collected protocols reveals that 70.7% of the protocols incorporate statistical interim analysis plans, but only 56% have also a DSMC and be considered adequately planned. The most concerning cases are related to lack of any form of monitoring (20.0% of the protocols), and the planning of interim analysis, without DSMC (14.7%). CONCLUSION: The results indicate that there is still insufficient attention paid to the implementation of interim analysis.
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Such analyses were reported in 71% (106/150) of cancer trial protocols with time-to-event outcomes in Italy from 2000 to 2005; among 86 protocols with plans for efficacy interim analyses, 100% reported the timing of the analyses, 90% specified the overall reason for stopping, and 94% detailed the statistical approach.
“Such analyses were also reported in 71% (106/150) of cancer trial protocols with time-to-event outcomes in Italy from 2000 to 2005461; among 86 protocols with plans for efficacy interim analyses, 100% reported the timing of the analyses, 90% specified the overall reason for stopping (eg, superiority, futility), and 94% detailed the statistical approach.461”
From SPIRIT 2025 explanation and elaboration: updated guideline for protocols of randomised trials (2025) · cites this paper as [461]
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- Authors
- Floriani, I., Rotmensz, N., Albertazzi, E., Torri, V., De Rosa, M., Tomino, C., & de Braud, F.
- Affiliations
- Mario Negri Institute for Pharmacological Research (IT)
- European Institute of Oncology (IT)
- Italian Medicines Agency (IT)
- Corresponding author
- Floriani, Irene
- Venue
- Trials
- Published
- 2008-07-25
- Volume
- 9
- Issue
- 1
- Pages
- 46-46
- ISSN
- 1745-6215 (ISSN-L)
- PMC
- PMC2533282
- OpenAlex
- W2144554939
- Cited by
- 8
- References
- 15
- Citations by year
- 2025: 2 · 2021: 1 · 2019: 1 · 2017: 1 · 2013: 2
- FWCI
- 0.32
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Trials (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Topics
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
- Social Sciences › Decision Sciences › Statistics, Probability and Uncertainty › Meta-analysis and systematic reviews
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Ethics in Clinical Research
- Keywords
- interim analysis, data monitoring committees, cancer clinical trials, time-to-event outcomes, overall survival, progression-free survival, statistical monitoring, protocol review
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