Boyd, Kathleen Anne (2012) Employing early decision analytic modelling to inform economic ...

354 Pages·2012·2.96 MB·English

Boyd, Kathleen Anne (2012) Employing early decision analytic
modelling to inform economic evaluation in health care: theory &
practice. PhD thesis

http://theses.gla.ac.uk/3685/

Copyright and moral rights for this thesis are retained by the author

A copy can be downloaded for personal non-commercial research or
study, without prior permission or charge

This thesis cannot be reproduced or quoted extensively from without first
obtaining permission in writing from the Author

The content must not be changed in any way or sold commercially in any
format or medium without the formal permission of the Author

When referring to this work, full bibliographic details including the
author, title, awarding institution and date of the thesis must be given.

Glasgow Theses Service
http://theses.gla.ac.uk/
[email protected]
Employing early decision analytic modelling to inform
economic evaluation in health care: theory & practice

Kathleen Anne Boyd
MSc Economic & Health Economics, BA (Honours) Economics

Submitted in fulfilment of the requirements for the degree of
Doctor of Philosophy

Health Economics and Health Technology Assessment
Institute of Health & Wellbeing
University of Glasgow

October 2012
II
Abstract
Decision analytic modelling (DAM) is a mathematical technique which is used to
structure and synthesise evidence in order to inform decision making, given
uncertainty. Decision models are an ideal tool for undertaking economic
evaluations as they enable a wide range of data on costs and effects to be
synthesised within the model in order to derive cost-effectiveness outcomes.
The iterative framework for economic appraisal has been proposed as good
practice for undertaking economic evaluations (1), and DAM plays a key role
within this framework. In particular there is a role for early stage DAM prior to
primary research, to provide an indication of the potential cost-effectiveness
of a new health technology (2) given current evidence, and the use of value of
information (VOI) techniques to help inform further research priority setting. In
practice, support and funding for early stage DAM and full exploitation of VOI
techniques is rare.
The aim of this thesis is to examine the role for early decision analytic
modelling in informing research priorities and the design of future studies in a
health care setting. This thesis explores the feasibility, merits and drawbacks
of undertaking early DAM and considers potential reasons as to why it has not
been more widely implemented.
This thesis demonstrates the value and importance of early DAM; in both an
‘ideal’ setting and also in a less desirable, time-constrained setting. Applying
early DAM and VOI techniques enables researchers to provide relevant
conclusions and recommendations to decision makers, who can make informed
decisions as to whether a new intervention should be adopted (or rejected), or
whether further information is required to help make the decision; as opposed
to making decisions based on subjective reasoning. There is considerable merit
with employing early DAM for health care research, such as reduced
uncertainty, reduction of costs and efficiency gains, however, some drawbacks
exist in terms of whether it is always viable to fully exploit VOI analyses, which
may hinder widespread support both inside and out-with the health economics
community.
III
Table of Contents
Abstract.................................................................................... II
Table of Contents ........................................................................III
List of Tables..............................................................................VI
List of Figures...........................................................................VIII
Contributions.............................................................................. X
Publications and Presentations........................................................XII
Acknowledgements..................................................................... XIII
Author’s Declaration...................................................................XIV
Abbreviations ............................................................................XV

1 Introduction...........................................................................1
1.1 Rationale.........................................................................1
1.2 Economic evaluation in health care .........................................3
1.2.1 Modelling...................................................................6
1.2.2 Trial based .................................................................7
1.2.3 DAM in economic evaluation using an iterative approach.........10
1.3 Thesis outline .................................................................12

2 DAM for economic evaluation in health care...................................15
2.1 Introduction ...................................................................15
2.2 Economic evaluation in health care .......................................18
2.3 Decision Analytic Modelling.................................................20
2.3.1 Specifying the problem.................................................20
2.3.2 Defining boundaries.....................................................21
2.3.3 Structuring the problem................................................22
2.3.4 Synthesising evidence ..................................................23
2.3.5 Handling Uncertainty...................................................25
2.4 Assessing parameter uncertainty...........................................27
2.4.1 Distributional forms.....................................................28
2.4.2 Fitting parameters to distributions...................................30
2.4.3 Illustrating parameter uncertainty ...................................33
2.5 Decision uncertainty: CEAC .................................................36
2.6 Value of Information.........................................................40
2.6.1 EVPI per decision/patient..............................................41
2.6.2 EVPI population level...................................................42
2.6.3 EVPI for parameters (EVPPI)...........................................45
2.7 EVSI.............................................................................49
2.8 ENBS............................................................................52
2.9 An Iterative Approach to Economic Evaluation...........................54
2.9.1 Stages of the iterative approach......................................56
2.9.2 Benefits of the Iterative Approach ...................................61
2.10 Summary.......................................................................67

3 Early DAM: a case of good practice..............................................68
3.1 Introduction ...................................................................68
3.1.1 The decision problem...................................................68
3.2 Methods........................................................................71
3.2.1 Overview..................................................................71
IV
3.2.2 Existing evidence........................................................72
3.3 Model design and development.............................................75
3.3.1 The diagnostic pathway................................................75
3.3.2 Model 1: Primary rectal & colon cancer .............................82
3.3.3 Model 2: Recurrent colorectal cancer................................96
3.3.4 Model 3: Metastatic cancer...........................................107
3.4 Model Parameterisation and population .................................117
3.4.1 Model 1: Primary rectal and colon...................................117
3.4.2 Model 2: Recurrent disease...........................................131
3.4.3 Model 3: Metastatic disease ..........................................143
3.5 Deterministic Results........................................................154
3.5.1 Primary colorectal cancer results....................................154
3.5.2 Recurrent colorectal cancer results.................................163
3.5.3 Metastatic colorectal cancer results ................................167
3.6 Summary......................................................................169
3.6.1 Primary CRC.............................................................172
3.6.2 Recurrent CRC..........................................................175
3.6.3 Metastatic CRC .........................................................177
3.6.4 Next steps in the analysis.............................................177

4 Setting research priorities.......................................................179
4.1 Introduction ..................................................................179
4.1.1 Identifying the decision problem ....................................179
4.2 Probabilistic results .........................................................182
4.2.1 Primary CRC results....................................................182
4.2.2 Recurrent CRC results .................................................189
4.2.3 Metastatic results ......................................................192
4.3 Decision Uncertainty........................................................194
4.3.1 Primary CRC decision uncertainty ...................................195
4.3.2 Recurrent CRC decision uncertainty.................................200
4.3.3 Metastatic decision uncertainty......................................202
4.4 Value in further research: EVPI & EVPPI .................................204
4.4.1 Primary CRC: Value of Information..................................204
4.4.2 Recurrent CRC..........................................................211
4.4.3 Metastatic...............................................................221
4.5 Discussion.....................................................................226
4.5.1 Primary results..........................................................226
4.5.2 Recurrent results.......................................................228
4.5.3 Metastatic results ......................................................229
4.5.4 Model conclusions......................................................230
4.5.5 Early DAM & VOI........................................................231

5 Designing clinical trials with economic evaluations .........................236
5.1 Case study: fFN testing for pre-term labour.............................238
5.1.1 A pre-trial model for fFN testing.....................................240
5.1.2 Decision Tree ...........................................................241
5.1.3 Pre-trial model predictions...........................................246
5.2 Sample Size calculations....................................................250
5.2.1 Superiority Sample Size ...............................................250
5.2.2 Net Monetary Benefit Sample Size...................................254
5.2.3 Non-inferiority approach..............................................260
V
5.3 Discussion.....................................................................264

6 Designing trials following an iterative approach .............................269
6.1 Re-analysis of the fFN case study.........................................270
6.1.1 Probabilistic analysis of fFN model..................................270
6.1.2 EVSI for the fFN case study...........................................278
6.1.3 EVSI Results .............................................................280
6.2 Practicalities with employing the EVSI approach.......................289
6.2.1 Interpretation of the EVSI process...................................289
6.2.2 Computation............................................................297
6.3 Conclusion ....................................................................301

7 Summary & Conclusions..........................................................303
7.1 Introduction ..................................................................303
7.2 Overview......................................................................304
7.2.1 Chapter 1................................................................304
7.2.2 Chapter 2................................................................304
7.2.3 Chapter 3................................................................305
7.2.4 Chapter 4................................................................306
7.2.5 Chapter 5................................................................308
7.2.6 Chapter 6................................................................308
7.3 Practical limitations for early DAM & VOI................................310
7.4 Areas for further research..................................................312
7.4.1 Fully exploiting VOI within an iterative context...................312
7.4.2 Exploring uncertainty in sample size calculations.................312
7.4.3 A simple guide to undertaking EVSI..................................313
7.5 Conclusions...................................................................314

Appendix 1: Literature Search Histories ............................................315

Reference List...........................................................................322
VI
List of Tables
Table 2-1: Typical parameters and their distributional forms in a DAM.........31

Table 3-1: Staging colorectal cancer using AJCC and TNM classifications......69
Table 3-2: Model type and analysis undertaken ....................................72
Table 3-3: Economics literature search..............................................74
Table 3-4: Diagnostic test accuracy ..................................................77
Table 3-5: Inappropriate treatments for inaccurate staging......................95
Table 3-6: Inappropriate treatments for inaccurate diagnosis ..................106
Table 3-7: Inappropriate treatments for inaccurate diagnosis ..................116
Table 3-8: Primary CRC model prevalence parameter estimates ...............118
Table 3-9: Primary colon & rectal cancer DTA parameter estimates...........120
Table 3-10: Primary colon & rectal cancer Treatment parameter estimates .123
Table 3-11: Primary colorectal cancer Survival parameter estimates..........124
Table 3-12: Primary colon & rectal cancer Utility parameter estimates.......126
Table 3-13: Primary CRC model costs...............................................128
Table 3-14: Recurrent CRC model prevalence parameter estimates ...........132
Table 3-15: Recurrent CRC model Diagnostic Test Accuracy estimates........135
Table 3-16: Recurrent CRC model Optimal Treatment estimates...............137
Table 3-17: Recurrent CRC model Survival estimates.............................138
Table 3-18: Recurrent CRC Utility parameter estimates .........................139
Table 3-19: Recurrent CRC model costs.............................................141
Table 3-20: Metastatic CRC model Prevalence parameters......................143
Table 3-21: Metastatic CRC model Diagnostic Test Accuracy parameters .....147
Table 3-22: Metastatic CRC model Treatment Parameters.......................148
Table 3-23: Metastatic CRC model Survival Parameters..........................149
Table 3-24: Metastatic CRC model Utility Parameters............................150
Table 3-25: Metastatic CRC model costs............................................152
Table 3-26: Primary rectal cancer – cost per correct diagnosis .................155
Table 3-27: Primary rectal cancer – DTA outcomes under different strategies
............................................................................................156
Table 3-28: Primary rectal cancer – cost per QALY gain..........................158
Table 3-29: Primary colon cancer – cost per correct diagnosis..................159
Table 3-30: Primary colon cancer – cost per QALY gain ..........................160
Table 3-31: Primary rectal cancer scenario – cost per QALY.....................161
Table 3-32: Primary colon cancer scenario – cost per QALY .....................162
Table 3-33: Recurrent rectal cancer – cost per correct diagnosis...............163
Table 3-34: Recurrent rectal cancer – cost per QALY gain.......................164
Table 3-35: Recurrent colon cancer – cost per correct diagnosis ...............165
Table 3-36: Recurrent colon cancer – cost per QALY gain........................165
Table 3-37: Metastatic cancer – cost per correct diagnosis......................167
Table 3-38: Metastatic cancer – cost per QALY gain ..............................168

Table 4-1: EVPPI parameter groups and parameters..............................214
Table 4-2: EVPPI parameter groups and parameters..............................223

Table 5-1: Model parameters.........................................................245
Table 5-2: Model predictions .........................................................246
Table 5-3: Scenario model predictions..............................................249
VII
Table 5-4: Sample size calculation parameters....................................251
Table 5-5: Superiority sample sizes for each endpoint ...........................252
Table 5-6: NMB sample sizes under different power specifications.............258
Table 5-7: NMB sample sizes under alternative monetary thresholds (λ)......259
Table 5-8: Non-inferiority sample size under different power specifications.263

Table 6-1: fFN model predictions....................................................271
Table 6-2: fFN Parameters for probabilistic model................................272
Table 6-3: Net Benefits from posterior calculation ...............................279
Table 6-4: EVSI calculations for a range of sample sizes.........................281
Table 6-5: Sample sizes under different approaches .............................287
Table 6-6: EVSI results for 1 and 10,000 binomial draws.........................291
Table 6-7: Alternative methods for calculating posterior net benefits in EVSI294
Table 6-8: Calculating ENB for EVSI in a non-linear model.......................296
Table 6-9: Duration to run linear simulation with alternative number of priors
............................................................................................299
VIII
List of Figures
Figure 2-1: The cost-effectiveness plane............................................34
Figure 2-2: CEAC for Treatment versus Control.....................................38
Figure 2-3: The iterative approach to economic appraisal........................56

Figure 3-1: Diagnostic pathway for a two test intervention ......................78
Figure 3-2: Decision tree for staging primary colorectal cancer .................83
Figure 3-3: Treatment pathways for primary rectal & colon cancers ...........88
Figure 3-4: Two-state survival model for each AJCC colorectal cancer stage..91
Figure 3-5: Overall survival for primary rectal cancer for each AJCC stage....92
Figure 3-6: Decision tree for staging recurrent colorectal cancer...............97
Figure 3-7: Treatment pathways for recurrent rectal & colon cancers ........100
Figure 3-8: Two-state survival model for each recurrence status...............103
Figure 3-9: Overall survival for patients suspected of recurrent rectal cancer
............................................................................................104
Figure 3-10: Decision tree for staging metastatic colorectal cancer ...........108
Figure 3-11: Treatment pathways for metastatic colorectal cancer............111
Figure 3-12: Two-stage survival model for metastatic disease status..........113
Figure 3-13: Overall survival for patients suspected of metastatic recurrence
............................................................................................114
Figure 3-14: Accuracy data of PET/CT in the detection of recurrent CRC.....134
Figure 3-15: Accuracy of PET/CT in detecting hepatic metastases.............145

Figure 4-1: The CE plane for PET/CT in primary rectal cancer..................183
Figure 4-2: The CE plane for PET/CT in primary colon cancer ..................185
Figure 4-3: The CE plane for cePET/CT in primary rectal cancer scenario....187
Figure 4-4: The CE plane for cePET/CT in primary colon cancer scenario.....188
Figure 4-5: The CE plane for PET/CT in recurrent rectal cancer................189
Figure 4-6: The CE plane for PET/CT in recurrent colon cancer ................190
Figure 4-7: The CE plane for metastatic cancer...................................192
Figure 4-8: The CEAC for primary rectal cancer...................................195
Figure 4-9: The CEAC for primary colon cancer....................................196
Figure 4-10: The CEAC for primary rectal scenario................................197
Figure 4-11: The CEAC for primary colon scenario ................................199
Figure 4-12: The CEAC for recurrent rectal cancer ...............................200
Figure 4-13: The CEAC for recurrent colon cancer................................201
Figure 4-14: The CEAC for metastatic cancer......................................202
Figure 4-15: EVPI for primary rectal cancer – population level..................206
Figure 4-16: EVPI for primary colon cancer – population level ..................207
Figure 4-17: EVPI for primary rectal cancer scenario – population level.......208
Figure 4-18: EVPI for primary colon cancer scenario – population level .......209
Figure 4-19: EVPI for recurrent rectal cancer – population level................212
Figure 4-20: EVPPI for recurrent rectal cancer – population level (λ=£30,000)
............................................................................................215
Figure 4-21: EVPI for recurrent colon cancer – population level................218
Figure 4-22: EVPPI for recurrent colon cancer – population level (λ=£30,000)220
Figure 4-23: EVPI for metastatic colorectal cancer - population................222
Figure 4-24: EVPPI for metastatic CRC – population level (λ=£30,000).........224
IX
Figure 5-1: Decision tree for diagnosing pre-term labour........................242
Figure 5-2: Cost-effectiveness plane for fFN model prediction .................247

Figure 6-1: The CE plane for Treatment (fFN test) versus Control (no test) ..273
Figure 6-2: The CEAC for fFN.........................................................274
Figure 6-3: EVPI for fFN – population level.........................................276
Figure 6-4: EVSI with varying sample size – per patient/decision...............282
Figure 6-5: EVSI with varying sample size – population level....................283
Figure 6-6: EVSI, Cost & ENBS for fFN trial.........................................285
Figure 6-7: Alternative EVSI, Cost & ENBS for an observational study..........286
Figure 6-8: EVSI curves under one and 10,000 binomial draws..................292
Figure 6-9: EVSI curves under alternative number of prior draws...............298