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Development and application of statistical methods for prognosis research

Snell, Kym Iris Erika (2015)
Ph.D. thesis, University of Birmingham.

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A pivotal component of prognosis research is the prediction of future outcome risk. This thesis applies, develops and evaluates novel statistical methods for development and validation of risk prediction (prognostic) models. In the first part, a literature review of published prediction models shows that the Cox model remains the most common approach for developing a model using survival data; however, this avoids modelling the baseline hazard and therefore restricts individualised predictions. Flexible parametric survival models are shown to address this by flexibly modelling the baseline hazard, thereby enabling individualised risk predictions over time. Clinical application reveals discrepant mortality rates for different hip replacement procedures, and identifies common issues when developing models using clinical trial data.

In the second part, univariate and multivariate random-effects meta-analyses are proposed to summarise a model’s performance across multiple validation studies. The multivariate approach accounts for correlation in multiple statistics (e.g. C-statistic and calibration slope), and allows joint predictions about expected model performance in applied settings. This allows competing implementation strategies (e.g. regarding baseline hazard choice) to be compared and ranked. A simulation study also provides recommendations for the scales on which to combine performance statistics to best satisfy the between-study normality assumption in random-effects meta-analysis.

Type of Work:Ph.D. thesis.
Supervisor(s):Riley, Richard and Billingham, Lucinda
School/Faculty:Colleges (2008 onwards) > College of Medical & Dental Sciences
Department:School of Health and Population Sciences
Additional Information:

Publication resulting from research:
McMinn, DJW, Snell, KIE, Daniel, J, Treacy, RBC, Pynsent, PB & Riley, RD 2012, 'Mortality and implant revision rates of hip arthroplasty in patients with osteoarthritis: registry based cohort study' British Medical Journal, vol 344, pp. e3319., 10.1136/bmj.e3319
This article is an Open Access article. Full-text is available via Research at Birmingham:, on the publisher's website, as well as in the e-version of this thesis.

Subjects:RA0421 Public health. Hygiene. Preventive Medicine
Institution:University of Birmingham
ID Code:6259
This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder.
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