Paula's slides for her presentation on Outcomes Measures in Cancer given at the C2E2 Rounds Conference at the University of British Columbia on July 5th, 2017.

1. Paula Lorgelly
Deputy Director, OHE
Visiting Professor, Division of Cancer Studies, King’s College London
C2E2 Rounds
5th July 2017
Outcome Measures in Cancer:
Do disease specific instruments offer
greater sensitivity than generic
instruments?

2. Outcome Measures in Cancer: Do disease specific instruments offer greater
sensitivity than generic instruments?
Acknowledgements
• Cancer 2015 is funded by the Victorian Cancer Agency
Translational Research Program, Australia
• The cancer patients who agreed to participate and
hospitals from which they were recruited
• Cancer 2015 investigators, specifically Stephen Fox,
David Thomas and John Parisot
• Brett Doble, Monash PhD student (now Oxford)
• Richard Norman, Curtin University

3. Outcome Measures in Cancer: Do disease specific instruments offer greater
sensitivity than generic instruments?
Background – Generic MAUIs
• Cost utility analyses require preference-based measures
of outcome to generate QALYs
• Norm has been to employ generic preference based
measures (multi attribute utility instruments, MAUIs)
• EQ-5D or SF-6D
• Criticisms (both health economists and clinicians) that
these are not sensitive to certain disease specific
improvements

4. Outcome Measures in Cancer: Do disease specific instruments offer greater
sensitivity than generic instruments?
Background – Condition Specific MAUIs
• How do we introduce sensitivity to disease?
• Could map from a condition specific non-preference-
based measure to a generic preference-based measure
• Could use a bolt-on to a generic measure
• Could elicit patient preferences using the generic
measure
• Growing trend to develop condition-specific preference-
based measures (CSPBM)

5. Outcome Measures in Cancer: Do disease specific instruments offer greater
sensitivity than generic instruments?
Background - CSPBM
• Two approaches
• developing CS measures from scratch or
• modifying an existing non-preference based measures
• CSPBMs use is limited within HTA, but instruments/
algorithms are increasing
• Research is required to aid adoption/value considerations
• evidence of validity, responsiveness and sensitivity

6. Outcome Measures in Cancer: Do disease specific instruments offer greater
sensitivity than generic instruments?
CSPBM in oncology
• EORTC-8D (Rowen et al, 2011)
• QLU-C10D (King et al, 2016)
• Both map responses from the EORTC QLQ-C30 a generic
measure of quality of life for cancer patients
• EORTC = European Organisation for Research and
Treatment of Cancer

7. Outcome Measures in Cancer: Do disease specific instruments offer greater
sensitivity than generic instruments?
Which to choose?

8. Outcome Measures in Cancer: Do disease specific instruments offer greater
sensitivity than generic instruments?
Objective
• To compare and contrast the EQ-5D-3L, the EORTC-8D
and the QLU-C10D
• To understand the sensitivity of each to different sites and
stages of cancer and the effect of variations in patient
functioning on each outcome measure over time
• What do we already know?
• Lorgelly et al., 2017, Quality of Life Research
• Evidence of convergent validity and content validity but
limited agreement between EORTC-8D and EQ-5D-3L
• Variability in sensitivity between the baseline values
and the QALY estimations of each
• Researchers and decision makers advised to be cautious

9. Outcome Measures in Cancer: Do disease specific instruments offer greater
sensitivity than generic instruments?
EORTC-QLQ-C30 (version 3)
• 30 questions
• physical functioning
• role functioning
• emotional functioning
• social functioning
• cognitive functioning
• pain
• fatigue
• nausea and vomiting
• dyspnoea
• sleep
• appetite
• constipation
• diarrhoea
• financial impact
• global health
• 3 summary measures
• Physical functioning (0-100)
• Symptoms (0-100)
• Global QoL (0-100)

10. Outcome Measures in Cancer: Do disease specific instruments offer greater
sensitivity than generic instruments?
EORTC-8D
• Developed from EORTC-C30 using Rasch analysis and
factor analysis on dataset of multiple myeloma patients
• TTO valuation using ‘healthy’ individuals from the North
of England
• An algorithm takes responses to EORTC-C30 and gives a
utility score (10 questions in 8 domains)
• 81,920 unique health states
• Range 0.292-1.000 (UK specific algorithm)
• Physical functioning
• Role functioning
• Pain
• Emotional functioning
• Social functioning
• Fatigue
• Nausea
• Constipation & diarrhoea

11. Outcome Measures in Cancer: Do disease specific instruments offer greater
sensitivity than generic instruments?
QLU-C10D
• Developed from EORTC-C30 using apriori inclusion/
exclusion with Confirmatory Factor Analysis and Rasch
analysis on a meta-dataset of 18 studies from 8 countries
• DCE with 16 choice sets of the general Australian public
• An algorithm takes responses to EORTC-C30 and gives a
utility score (13 questions in 10 domains)
• 410=1,048,576 unique health states
• Range -0.095-1.000 (Australian-specific algorithm)
• Physical functioning
• Role functioning
• Social functioning
• Emotional functioning
• Pain
• Fatigue
• Sleep
• Appetite
• Nausea
• Bowel problems

12. Outcome Measures in Cancer: Do disease specific instruments offer greater
sensitivity than generic instruments?
EQ-5D
• Originally referred to as the EuroQol-5D
• Five domains
• Three level and five level versions
• Dataset includes EQ-5D-3L (5L version subsequently
used)
• 3L, 35 = 243 unique health states
• Range -0.594-1.000 (UK MVH tariff)
• Mobility
• Self-care
• Usual activities
• Pain/Discomfort
• Anxiety/Depression

13. Outcome Measures in Cancer: Do disease specific instruments offer greater
sensitivity than generic instruments?
EQ-5D-3L
EORTC-8D
QLU-C10D
Maximal
theoretical
contributions
for each
dimension

14. Outcome Measures in Cancer: Do disease specific instruments offer greater
sensitivity than generic instruments?
Data
• Cancer 2015 is a large-scale longitudinal prospective
population-based cancer genomic cohort study
• Enrols treatment naïve cancer patients (all tumour sites
except leukaemia)
• Phase 1 targeted the enrolment of 1000 patients from 5
hospitals in Victoria
• Follow-up at 3, 6 and 12 months depending on severity
• Collection of tumour samples (blood), baseline
questionnaire of demographics, site and staging,
treatment (pharma, chemotherapy, radiotherapy,
surgery), EQ-5D-3L, and EORTC-QLQ-C30
• Also linked to administrative reimbursement data
• www.cancer2015.org

15. Outcome Measures in Cancer: Do disease specific instruments offer greater
sensitivity than generic instruments?
Summary of Patient Accrual
316
182
505
259
328
Patients Recruited by Hospital
Cabrini Institute
Warrnambool
Hospital
Peter MacCallum
Cancer Centre
Geelong Hospital
Royal Melbourne
Hospital
Cancer 2015 Dashboard as at 13-Aug-2014
Total Patients = 1590
GRAMPIANS
2%
LODDON
MALLEE
5%
BARWON
SOUTH
WEST
26%
GIPPSLAND
6%
HUME
4%
NORTHERN
& WESTERN
METRO 25%
EASTERN
METRO
11%
SOUTHERN
METRO 21%
OTHER 0%
VICTORIA
METRO

16. Outcome Measures in Cancer: Do disease specific instruments offer greater
sensitivity than generic instruments?
0
50
100
150
200
250
300
350
400
450
500
Breast
Prostate
Colorectal
Lung
Melanoma
HeadandNeck
Renal
Oesophagogastric
BoneandSoTissue
Cervical
CancerofUnknownPrimary
Other
CentralNervousSystem
Pancreac
Bladder
Ovarian
Thyroid
Endometrial
Tescular
Anal
Hepac
Biliary
Lymphoma
Not Specified
IV
III
II
I
0
Cancer histo-site & stage

17. Outcome Measures in Cancer: Do disease specific instruments offer greater
sensitivity than generic instruments?
Representativeness
Anal 0.17%
Biliary -0.89%
Bladder -0.05%
Bone and Soft Tissue -0.78%
Breast 6.13%
Cancer of Unknown Primary -0.14%
Central Nervous System 0.12%
Cervical 1.56%
Colorectal -2.23%
Endometrial -1.42%
Head and Neck 9.80%
Hepatic -0.59%
Lung 0.58%
Lymphoma -3.73%
Melanoma 1.57%
Oesophagogastric -0.45%
Other -5.57%
Ovarian -0.34%
Pancreatic -0.67%
Prostate -3.18%
Renal 1.04%
Testicular -0.07%
Thyroid -0.87%

18. Outcome Measures in Cancer: Do disease specific instruments offer greater
sensitivity than generic instruments?
Case history – Patient X
• Cohort baseline questionnaire: male, aged 60-64, lung
cancer, metro Victoria, presented asymptomatic/
incidental in July 2012, no previous history of Ca, no
familial history of Ca, no other chronic conditions, smoker
• Genomics panel: RB1 (retinoblastoma 1); FGFR3
(fibroblast growth factor receptor 3)
• Follow-up: Tx – surgery in July 2012, chemotherapy in
Aug 2012, radiotherapy Jan 2013
• QoL in July 2012: Functioning 91, Symptoms 10, Global
Health 100, VAS 95, EQ-5D 0.848
• QoL in Oct 2013: Functioning 49, Symptoms 54, Global
Health 33, VAS 60, EQ-5D 0.587

19. Outcome Measures in Cancer: Do disease specific instruments offer greater
sensitivity than generic instruments?
Case history cont.
• PBS activity: Atorvastatin and Ramipril since Nov 2011
(continued through anticancer treatment)
• Etoposide and Carboplatin in Sept 2012
• Mirtazapine in Oct 2012 and Diazepam in Nov 2012
• MBS activity: GP appointment in April 2012 (note no
activity prior to this)
• Pathology and Radiology in May 2012
• More path and diag-radio July to Nov 2012
• Psychologist in Nov 2012 and Feb 2013
• Radiology in Jan 2013
• VAED activity: July 2012 1 day stay for H61B (ICD- AM
C787), Aug-Nov 2012 18 separate day admissions for
R63Z (Z511)

20. Outcome Measures in Cancer: Do disease specific instruments offer greater
sensitivity than generic instruments?
Deceased
Cancer Dx
Cancer 2015
enrolment
GP visit
QoL QoL
Chemotherapy
Pathology
/radiology
Psychologist Psychologist
Radiotherapy
Statins and BP lowering meds

21. Outcome Measures in Cancer: Do disease specific instruments offer greater
sensitivity than generic instruments?
Methods
• Estimated generic and cancer-specific baseline utility
values for each respondent
• Similarly estimated utility values at each follow-up point
and then using area under curve estimated QALYs
• Simple comparison of values
• Regression analyses to test sensitivity to site and stage

22. Outcome Measures in Cancer: Do disease specific instruments offer greater
sensitivity than generic instruments?
Sample characteristics
• N = 1,663 patients with baseline health state
• Mean age 62 years
• 56% male
• 14% current smoker, 47% ex-smoker
• 40% have health insurance (indicator of high income)
• 74% had curative treatment intention, 19% had palliative
• 15% treated (recruited) in private hospital

23. Outcome Measures in Cancer: Do disease specific instruments offer greater
sensitivity than generic instruments?
Site of cancer
breast
prostate
headneck
colo
lung
bone
cervic
renal
CUP
oesoph
othersite

24. Outcome Measures in Cancer: Do disease specific instruments offer greater
sensitivity than generic instruments?
Stage of cancer
stage 0
stage 1
stage 2
stage 3
stage 4
stage 5
unable to stage

25. Outcome Measures in Cancer: Do disease specific instruments offer greater
sensitivity than generic instruments?
Health Status @ baseline
• EQ-5D-3L mean 0.749 (range: -0.594, 1)
• EORTC-8D mean 0.830 (range: 0.292, 1)
• QLU-C10D mean 0.736 (range: -0.022, 1)
• Correlation coefficient:
• EORTC-8D vs EQ-5D-3L = 0.746
• QLU-C10D vs EQ-5D-3L = 0.745
• EORTC-8D vs QLU-C10D = 0.947
• Interclass correlation coefficient (ICC) – measure of
agreement
• EORTC-8D vs EQ-5D-3L = 0.595 (moderate)
• QLU-C10D vs EQ-5D-3L = 0.739 (strong)
• EORTC-8D vs QLU-C10D = 0.770 (strong)

26. Outcome Measures in Cancer: Do disease specific instruments offer greater
sensitivity than generic instruments?
Histogram of baseline utility values

27. Outcome Measures in Cancer: Do disease specific instruments offer greater
sensitivity than generic instruments?
Coefficient values on site – regression
of baseline utility (breast is ref)

28. Outcome Measures in Cancer: Do disease specific instruments offer greater
sensitivity than generic instruments?
QALYs
• N = 1,142
• Mean follow-up = 435 days
• Follow-up max days = 1,146 (3.14 years)
• EQ-5D-3L meanQ = 0.862 (range: -0.108, 3.138)
• EORTC-8D meanQ = 0.911 (range: 0.001, 3.078)
• QLU-C10D meanQ = 0.821 (range: -0.000, 3.054)
• Correlation > 0.95
• Difference +ve for 8D while –ve for 10D (-0.049 & 0.042,
p<0.001)

29. Outcome Measures in Cancer: Do disease specific instruments offer greater
sensitivity than generic instruments?
Correlation in cancer QALY estimates

30. Outcome Measures in Cancer: Do disease specific instruments offer greater
sensitivity than generic instruments?
Regression for difference in QALYs

31. Outcome Measures in Cancer: Do disease specific instruments offer greater
sensitivity than generic instruments?
Discussion
• The three instruments produce different baseline values
but notably different QALY estimates
• Variation between EORTC-8D and QLU-C10D of
interest as use the same initial instrument, and
overlapping questions
• There would appear to be differences in the sensitivity of
each instrument to different sites and stages of cancer,
and the responsiveness of QALYs to identify severity of
disease and change in patient functioning
• Differences in baseline values are of interest as these
values would populate HTA decision models
• It is acknowledged that while the values are on the
same (theoretical) scale they accommodate different
ranges on that scale

32. Outcome Measures in Cancer: Do disease specific instruments offer greater
sensitivity than generic instruments?
Conclusion
• It is well known that generic preference-based measures
often produce different conclusions.
• This analysis suggests that the performance of the
cancer-specific measures, the EORTC-8D and the QLU-
C10D, differ considerably to that of the EQ-5D-3L

33. Outcome Measures in Cancer: Do disease specific instruments offer greater
sensitivity than generic instruments?
Further research
• Further research is required to understand the reasons
for the variability, particularly if recommendations for
reimbursement/adoption change in light of using one
instrument over another
• Further research is required to understand if the new
five-level version, the EQ-5D-5L, experiences similar
issues or is as hoped an improvement on the three-level

34. Outcome Measures in Cancer: Do disease specific instruments offer greater
sensitivity than generic instruments?
References
• King MT et al. “QLU-C10D: a health state classification system for a
multi-attribute utility measure based on the EORTC QLQ-C30.” Quality
of Life Research 25 (2016): 625-636.
• Rowen D et al. “Deriving a preference-based measure for cancer using
the EORTC QLQ-C30.” Value in Health 14 (2011): 721-731.
• Thomas DM et al. “Cancer 2015: a longitudinal whole-of-system study
of genomic cancer medicine.” Drug Discovery Today 20 (2015): 1429-
1432.
• Lorgelly et al. “Condition-specific or generic preference-based measures
in oncology? A comparison of the EORTC-8D and the EQ-5D-3L.”
Quality of Life Research, 26 (2017): 1163–1176.
• Lorgelly et al. “Realising the value of linked data to health economic
analyses of cancer care: a case study of cancer.” Pharmacoeconomics,
34 (2016): 139-154.

35. Outcome Measures in Cancer: Do disease specific instruments offer greater
sensitivity than generic instruments?
Questions?
Suggestions?
Comments?

36. Outcome Measures in Cancer: Do disease specific instruments offer greater
sensitivity than generic instruments?
To enquire about additional information and analyses, please contact
Paula Lorgelly at plorgelly@ohe.org
To keep up with the latest news and research, subscribe to our blog, OHE News
Follow us on Twitter @OHENews, LinkedIn and SlideShare
Office of Health Economics (OHE)
Southside, 7th Floor
105 Victoria Street
London SW1E 6QT
United Kingdom
+44 20 7747 8850
www.ohe.org
OHE’s publications may be downloaded free of charge from our website.