Article
Misinterpreting survival functions in cancer studies
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Published: | March 20, 2019 |
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Outline
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Background/research question: Proper interpretation of survival data of clinical cancer studies may be difficult, and pitfalls related to the nature of Kaplan-Meier analyses might end up in mistaken inferences. The purpose of the present work is to raise awareness of those pitfalls and to prevent errors in future studies.
Methods: While evaluating a randomized controlled trial [1], [2], we came across some issues possibly associated with misinterpreting survival data [3], [4]. We thoroughly reviewed the reporting of survival analyses, statistical approaches, baseline characteristics, and choice of primary end point. The reported data were derived from people with high-risk neuroblastoma. Thus, the trial focused on survival. We reenacted survival functions by deducing the data of various treatment groups from pictured survival functions to estimate the respective hazard ratios.
Results: Opposed to the conclusion of the trial, we did not identify a significant difference between treatment groups with respect to overall survival. With respect to event-free survival, we focused on comparable treatment groups and we did not identify a significant difference between treatment groups, thereby again opposing the conclusion of the trial. The identified problems included assumed crossing of survival curves without real crossing, statistical approach changed in follow-up, different pretreatment between groups, and event-free survival used as primary outcome.
Conclusions: The present work exemplifies statistical issues that wer apparently difficult to dectect and that are possibly associated with misinterpreting survival functions.
References
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- Matthay KK, Reynolds CP, Seeger RC, et al. Long-term results for children with high-risk neuroblastoma treated on a randomized trial of myeloablative therapy followed by 13-cis-retinoic acid: a children’s oncology group study. J Clin Oncol. 2009;27(7):1007-13.
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- Peinemann F, van Dalen EC, Tushabe DA, Berthold F. Retinoic acid post consolidation therapy for high-risk neuroblastoma patients treated with autologous hematopoietic stem cell transplantation. Cochrane Database Syst Rev. 2015;1:CD010685.
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- Peinemann F, Labeit AM. Issues possibly associated with misinterpreting survival data: A method study. J Evid Based Med. 2018 Aug;11(3):208-215. DOI: 10.1111/jebm.12301