Volume 14 Supplement 1

2nd Clinical Trials Methodology Conference: Methodology Matters

Open Access

Challenges in the development of prognostic models utilising clinical trials data

  • Kym Snell1,
  • Lucinda Billingham1, 2,
  • Deborah Stocken3 and
  • Richard Riley1
Trials201314(Suppl 1):P115

https://doi.org/10.1186/1745-6215-14-S1-P115

Published: 29 November 2013

Aims

Prognostic models are statistical models that predict the risk of a future clinical outcome for individuals, and they are increasingly being developed using existing data from clinical trials. In this presentation we consider the challenges of this approach.

Methods

Using data from two clinical trials in advanced stage pancreatic cancer, a prognostic model was developed using Royston-Parmar (R-P) flexible parametric survival models. R-P models use restricted cubic splines to model the baseline hazard function for time-to-event data and thereby allows absolute risk to be predicted for individuals. This contrasts the Cox regression approach which does not explicitly model the baseline hazard function.

Results

We identified 6 key issues when using the trials' data to develop the prognostic model. These included dealing with multiple trials, handling multiple treatment groups with potentially different baseline hazard functions, and suitably using the data for model validation.

Informed judgement is needed to tackle these issues, and the baseline hazard function is pivotal to this. R-P models allow the baseline hazard to be displayed for all trials and all treatment groups. This aids decisions about whether to combine trials and treatment groups in the model development, and enables internal validation of predicted survival probabilities compared to observed probabilities from Kaplan-Meier plots.

Conclusion

Clinical trials data is a rich source of existing data for prognostic model development, but it also provides many challenges. By modelling the baseline hazard, researchers can gain insight into how to tackle these issues.

Authors’ Affiliations

(1)
MRC Midland Hub for Trials Methodology Research, University of Birmingham
(2)
Cancer Research UK Clinical Trials Unit, University of Birmingham
(3)
Newcastle Clinical Trials Unit, Institute of Health and Society, Newcastle University

Copyright

© Snell et al; licensee BioMed Central Ltd. 2013

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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