Real-World Cost-Effectiveness Analysis
Which Comparator Has The X-Factor?
1
X-Factor Competition
The Question
Real-world cost-effectiveness analysis,
which comparator?
Answers
The medical professional – Peter Huijgens\Aiko de Raaf
The decision maker – Jolanda de Boer
The health-economist – Ellen van Rooijen
X-Factor Competition
Peter Huijgens
Aiko de Raaf
Jolanda de Boer
Ellen van Rooijen
2
X-Factor Competition
Three answers
The audience will vote to decide the winner
The medical professional
The Question
Real-world cost-effectiveness analysis,
which comparator?
What is your answer?
3
The medical professional
REAL WORLD COST- EFFECTIVENESS
ANALYSIS
Aiko de Raaf
Peter Huijgens
11 nov 2014
8
Clinical use of anti cancer drugs
Phase Il
Preclinicall
Phase IVlIII
Phase IIIlIII
Phase IIl
4
Clinical use of anti cancer drugs
Mature?lIII
Development of CHOP and rituximab
in malignant lymphoma
CHOP28
GELA
R-CHOP21
CHOP21
NHL-B2
?
CHOP14
R-CHOP14
RiCOVER
It took 30 years of clinical trials to handle
CHOP in the most useful way
5
Path of care in oncology
pathology
MDO (1)
labs
treatment (1)
imaging
response
clinic
history
phys ex
ao
relapse
MDO (2)
guidelines
shared decision
guidelines
shared decision
treatment (2)
Introduction of new drugs in path of care
pathology
MDO (1)
labs
treatment (1)
imaging
response
clinic
history
phys ex
ao
relapse
MDO (2)
guidelines
shared decision
guidelines
shared decision
treatment (2)
6
Oncological care
Standards
Guidelines
Breast cancer
Colorectal cancer
Prostate cancer
Hematol. cancers
a.o.
Public
Policy
Care
Advance expertise
Coordinate efforts
Change behaviour
Holy grail ?
Salver or plate in Perceval
1150 ac
Dante Gabriel Rossetti
1850 ac
7
www.iknl.nl
www.linkedin.com/company/iknl
twitter.com/iknl
[email protected] | 0650743943
The decision maker
The Question
Real-world cost-effectiveness analysis,
which comparator?
What is your answer?
8
Real world costeffectiveness analysis:
The answer of the payer
Jolanda de Boer
National Health Care Institute
Reimbursement decisions
Important questions for reimbursement decisions:
• Has the new treatment an added value in
comparison to the “golden standard”?
• Is the incremental cost-benefit ratio acceptable?
• Budget impact?
• Social value?
24
9
European network for Health Technology Assessment | JA2 2012-2015 | www.eunethta.eu
Use of technology in health care
Health Technology Life-cycle
HTA
Early scientific
advice
Regulators and
HTA
Time line of innovation
Additional
data
collection
Relative
efficacy
Market
Postmarket Safety and
Authorization
Effectiveness Assessment
25
25
European network for Health Technology Assessment | JA2 2012-2015 |
www.eunethta.eu
Interest in real life data
• reimbursement decision are often based on
uncertainty
• collecting real life data can help to develop
evidence in daily practice
• adherence to guidelines can also be reflected
26
10
Usefullness of real life data
•
as input of cost-effectiveness/cost-utility analysis
•
the opportunity to validate modeling assumptions.
•
makes it possible to evaluate the changing environment: When
there’s a lot of dynamic in the therapeutic field the comparator can
change over time
•
to compare results on relative effectiveness to the relative efficacy
from the (randomized) clinical trials
•
additional outcomes like adherence, compliance parameters and
sometimes more long-term clinical events
27
Real world data in reimbursement decisions
• Conditional reimbursement: gathering additional
evidence in case of
• questions about appropriate use
• uncertain cost-effectiveness
•
Only usefull when it helps to solve the evidence
gap
28
11
Challenges of real life data
Also need for data about the comparator!
Methodological: no randomisation, bias, confounding,
small groups, missing data, difference in patient
characteristics
Registries: manpower effort and budget
29
Is there a comparator with the ultimate X-Factor?
YES
Choice of the comparator (standard or usual treatment for a
certain indication) has to be based on
• evidence-based guidelines or if not available
• the opinion of medical specialists
Motivate and substantiate when there are changes in the choice
for the comparative treatment.
BUT…
30
12
Is there a patient with the real X-factor?
In data from daily practice there is no guarantee that
you find patients with the real X-factor:
• patients are often not comparable: there is a
reason to give a specific therapy
Use of other sources is often necessary
It’s important to clearly describe these sources and
motivate why these are chosen
31
The health-economist
The Question
Real-world cost-effectiveness analysis,
which comparator?
What is your answer?
13
Real world cost-effectiveness analysis:
The answer of the health-economist
Ellen van Rooijen
Introduction
• Previous presentations
• Medical professional perspective:
– Economic analysis only at a late stage
• Decisions maker’s perspective
– Follow the (medical) guideline
• The health-economist answer to the question:
– Which comparator has the ultimate X-factor?
14
Incremental cost-effectiveness analysis
• Incremental effectiveness is essential
– But to compare apples and oranges will only
yield nonsense
Incremental cost-effectiveness analysis
• Incremental effectiveness is essential
– But to compare apples and oranges will only
yield nonsense
• Essential in the selection of a comparator for a
real-world incremental cost-effectiveness
analysis is therefore:
– A comparable patient
• But what defines a comparable patient?
15
The ‘comparable patient’ in RWD
Treatment A
Treatment B
P-values
73
62
<0.01
0-1
76.3
92.4
>1
23.7
7.6
< 5 ng/ml
93.2
80.8
≥ 5 ng/ml
6.8
19.2
Age (yrs)
Comorbidity (%)
<0.01
CEA-level (%)
<0.01
The ‘comparable patient’ in RWD
Treatment variation by line
Percentage of patients treated
70
bortezomib
lenalidomide
60
thalidomide
50
adriamycin
40
vincristine
melphalan
30
HDM
prednisone
20
dexamethasone
cyclophosphamide
10
DLI
0
Line 2
(n=139)
Line 3
(n=90)
Line 4
(n=55)
Line 5
(n=20)
Line 6
(n=8)
Treatment line
SCT
interferon alpha
experimental
Franken MG, Gaultney JG, Blommestein HM, Huijgens PC, et al. Policymaker, please consider
your needs carefully: Does outcomes research of bortezomib in relapsed or refractory multiple
myeloma reduce policymaker uncertainty? Value Health. 2014 Mar;17(2):245-53.
16
The ‘comparable patient’ in RWD
First-line treatment NSCLC with EGFR-TK-inhibitors
Are patient registries the solution?
• Patient registries can solve many issues with RWD
– A registry may contain comparable patients treated in
the same time-frame
– A registry may contain comparable patients in the form
of historical controls
• But registries will not always hold the answer
• And registries are not (yet) omni-present
• When a comparable patient cannot be found in RWD a
combination of RWD and trial data can offer a solution.
17
Are patient registries the solution?
• Combining the external validity of RWD with the internal
validity of RCT data
Treatment A Treatment B
RWD
N=110
N=281
RCT
N=675
N=672
van Gils CW, de Groot S, Redekop WK, Koopman M, Punt CJ, Uyl-de Groot CA. Real-world
cost-effectiveness of oxaliplatin in stage III colon cancer: a synthesis of clinical trial and daily
practice evidence. Pharmacoeconomics. 2013 Aug;31(8):703-18.
Conclusion
• The ultimate X-factor of a comparator
– A collection of patients comparable to the treated
patients
• A comparable patient can come from different sources:
– A disease registry
– A historical control
– A combination of RWD and RCT data
• Slogan:
– The best comparator chosen from multiple sources
18
X-Factor Competition
Questions and discussion
19
X-Factor Competition
Three answers
The medical professional :
“Registries are the holy grail”
The decision maker :
“Ask the medical professional”
The Health-economist:
“The best comparator from multiple sources”
X-Factor Competition
Three answers
The medical professional :
“Registries are the holy grail”
The decision maker :
“Ask the medical professional”
The Health-economist:
“The best comparator from multiple sources”
20
21