Christopher McCabe

Claire Hulme

David Cameron

Janet Dunn

Peter Hall

Richard Edlin

Rob Stein

Trials

PubMed

Crossref

ORAL PRESENTATION Open AccessEfficient design of a phase III trial of competingtests for personalised cancer treatment in theabsence of gold standard outcome data:challenges and potential solutionsPeter Hall1*, Christopher McCabe3, Claire Hulme1, Richard Edlin4, Janet Dunn2, David Cameron6, Rob Stein5From 2nd Clinical Trials Methodology Conference: Methodology MattersEdinburgh, UK. 18-19 November 2013IntroductionThe OPTIMAprelim pilot trial in early breast canceraims to select multi-parameter tests for inclusion in aphase III trial evaluating their use for patient selectionfor chemotherapy. Patients are randomised between uni-versal chemotherapy or test-directed chemotherapy.A key criterion for inclusion of a test as a comparator willbe the expected value of further research into its clinicaland cost-effectiveness.MethodsIn order to conduct a Value-of-Information (VoI) Analy-sis a probabilistic decision model was developed to evalu-ate the cost-effectiveness of a personalised treatmentstrategy based on each of the candidate tests from a UKNHS perspective. Concordance/discordance with Onco-type DX, the gold standard test, was used to modelexpected sensitivity and specificity of alternative tests.ResultsDecision analytic models of test guided cancer therapyrequire the explicit characterisation of test performancefor different test definitions and survival conditionalupon test result. In this example, modelling the requiredoutcome data, dependent on the modelled test result,was feasible although likely represents an underestimateof the true uncertainty. It was possible to describe rela-tive value of research on the test characteristics versusresearch on chemotherapy effectiveness across test-defined patient sub-groups. Modelling solutions whichconsider alternative test cut-points and time-dependentoutcomes are presented.ConclusionCharacterising the uncertainty and value of informationassociated with test performance parameters and theexpected outcomes conditional upon test results is feasi-ble on the basis of test concordance data, even with lim-ited current long term outcomes data.Authors’ details1University of Leeds, Leeds, UK. 2University of Warwick, Warwick, UK.3University of Alberta, Edmonton, Canada. 4University of Auckland, Auckland,New Zealand. 5University College London, London, UK. 6University ofEdinburgh, Edinburgh, UK.Published: 29 November 2013doi:10.1186/1745-6215-14-S1-O5Cite this article as: Hall et al.: Efficient design of a phase III trial ofcompeting tests for personalised cancer treatment in the absence ofgold standard outcome data: challenges and potential solutions. Trials2013 14(Suppl 1):O5.1University of Leeds, Leeds, UKFull list of author information is available at the end of the articleHall et al. Trials 2013, 14(Suppl 1):O5http://www.trialsjournal.com/content/14/S1/O5 TRIALS© 2013 Hall et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative CommonsAttribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction inany medium, provided the original work is properly cited.

Efficient design of a phase III trial of competing tests for personalised cancer treatment in the absence of gold standard outcome data: challenges and potential solutions

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ORAL PRESENTATION Open Access
Efficient design of a phase III trial of competing
tests for personalised cancer treatment in the
absence of gold standard outcome data:
challenges and potential solutions
Peter Hall1*, Christopher McCabe3, Claire Hulme1, Richard Edlin4, Janet Dunn2, David Cameron6, Rob Stein5
From 2nd Clinical Trials Methodology Conference: Methodology Matters
Edinburgh, UK. 18-19 November 2013
Introduction
The OPTIMAprelim pilot trial in early breast cancer
aims to select multi-parameter tests for inclusion in a
phase III trial evaluating their use for patient selection
for chemotherapy. Patients are randomised between uni-
versal chemotherapy or test-directed chemotherapy.
A key criterion for inclusion of a test as a comparator will
be the expected value of further research into its clinical
and cost-effectiveness.
Methods
In order to conduct a Value-of-Information (VoI) Analy-
sis a probabilistic decision model was developed to evalu-
ate the cost-effectiveness of a personalised treatment
strategy based on each of the candidate tests from a UK
NHS perspective. Concordance/discordance with Onco-
type DX, the gold standard test, was used to model
expected sensitivity and specificity of alternative tests.
Results
Decision analytic models of test guided cancer therapy
require the explicit characterisation of test performance
for different test definitions and survival conditional
upon test result. In this example, modelling the required
outcome data, dependent on the modelled test result,
was feasible although likely represents an underestimate
of the true uncertainty. It was possible to describe rela-
tive value of research on the test characteristics versus
research on chemotherapy effectiveness across test-
defined patient sub-groups. Modelling solutions which
consider alternative test cut-points and time-dependent
outcomes are presented.
Conclusion
Characterising the uncertainty and value of information
associated with test performance parameters and the
expected outcomes conditional upon test results is feasi-
ble on the basis of test concordance data, even with lim-
ited current long term outcomes data.
Authors’ details
1University of Leeds, Leeds, UK. 2University of Warwick, Warwick, UK.
3University of Alberta, Edmonton, Canada. 4University of Auckland, Auckland,
New Zealand. 5University College London, London, UK. 6University of
Edinburgh, Edinburgh, UK.
Published: 29 November 2013
doi:10.1186/1745-6215-14-S1-O5
Cite this article as: Hall et al.: Efficient design of a phase III trial of
competing tests for personalised cancer treatment in the absence of
gold standard outcome data: challenges and potential solutions. Trials
2013 14(Suppl 1):O5.
1University of Leeds, Leeds, UK
Full list of author information is available at the end of the article
Hall et al. Trials 2013, 14(Suppl 1):O5
http://www.trialsjournal.com/content/14/S1/O5 TRIALS
© 2013 Hall et al; licensee 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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Efficient design of a phase III trial of competing tests for personalised cancer treatment in the absence of gold standard outcome data: challenges and potential solutions

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