Transcript Collecting Real World Evidence: HTA*s perspective

Collecting Real World Evidence:
HTA’s perspective
Dr. Kelvin Chan, MD FRCPC MSc (Clin Epi) MSc (Biostats)
Clinical Lead, Provincial Drug Reimbursement Programs, CCO
Co-Director, Canadian Centre for Applied Research in Cancer Control
Medical Oncologist, Sunnybrook Odette Cancer Centre
Advancing Health Economics, Services, Policy and Ethics
Contents
• What types of uncertainty do HTA committees encounter in
their deliberations?
• How often does pCODR Expert Review Committee (pERC)
request collecting evidence to reduce uncertainty?
• What types of information can be potentially obtained by
collecting real world evidence (RWE)?
Disclaimer
• Member of HTAs
• pCODR Expert Review Committee
• Committee to Evaluate Drugs
• Ontario Steering Committee of Cancer Drugs
• Personal opinion
• Does not represent the views of U of Toronto, pCODR, CED,
OSCCD, CCO, Ministry etc.
• Information from publicly available source
Ontario Cancer Plan IV (2015-2019)
Health Technology Assessment (HTA)
Committee’s Recommendations
Recent Example
Things that HTA committees consider before
making a recommendation to fund (or not to fund)
In general, HTA committees (pCODR, CED, OSCCD)
consider the following inputs:
•Clinical benefit (from clinical trial data)
– Efficacy (survival) data
– Safety data
– Quality of Life (QOL) data
•Patient values
•Cost-effectiveness and budget impact
•Adoption feasibility
Uncertainty in clinical data
• Uncertainty in clinical data
– Survival data
• Missing or limited
• Surrogate of overall survival
• Non-comparative
• Short term data
– Safety data
• Missing data/Late data
– Quality of life data
• Missing data (numerous examples)
Non-Comparative Data
Romidepsin in Peripheral T-Cell Lymphoma
“It was noted that due to the limitations of relying on non-comparative, non-randomized evidence and
the heavy reliance on extrapolation of overall survival data, there was substantial uncertainty in the
magnitude of the net clinical benefit associated with romidepsin.”
- pCODR Expert Review Committee Final Recommendation
Adapted from Piekarz et al. BLOOD 2011
Adapted from Coiffier et al. JCO 2012
Missing Quality of Life Data
Vismodegib in Basal Cell Carcinoma
“… quality of life and functional outcomes are very important in this population. Patients with BCC
who are inappropriate for surgery may experience severe disfigurement, leading to extreme social
isolation and decreased quality of life.”
- pCODR Expert Review Committee Final Recommendation
• Survival is main a concern for patients with locally advanced or
metastatic disease
• Disease progression may lead to facial disfigurement, and thus a
decreased QoL
• This study presents no QoL data, however researchers connected a
response and decreased tumour size to an improvement in overall
QoL
Adapted from Sekulic et al. NEJM 2012
Economic evidence:
Estimation or “guess-timation”
• Cost-effectiveness analysis and budget
impact analysis
• Model structure and methods
– Comparator and long term clinical efficacy
• Uncertainty in the inputs of the model
– Number of patients
– Duration of drug treatments
– Resource utilization
• Underestimation of ICER (sometimes 1-2 fold
difference)
• Underestimation of BIA
Short Term Survival Data
Pembrolizumab in Unresectable Metastatic Melanoma
“In the absence of longer term data, pERC was unable to accept this assumption of prolonged benefit and agreed
with the EGP’s use of alternative data sources to extrapolate survival in both settings.”
- pCODR Expert Review Committee Final Recommendation
Adapted from Robert et al. NEJM 2015
Loss in “Translation”: Uncertainty about
Translating clinical trial evidence to the real world
• Trial patients are different from real world patients
– e.g. age, co-morbidities, performance status, diffusion
– Intensive monitoring on trial
• Different practice patterns in the real world
– Duration of treatment (treatment until progression vs.
discontinuation before progression)
– Dose intensity of treatment in the trials vs. in the real world
– Management of side-effects (e.g. febrile neutropenia are
managed mostly as in-patient in Ontario)
• Sequencing of subsequent lines of available therapy
– Different from what was available on the trial
• Changes in drug price over time (e.g. generics)
– Drop in price in the older drugs will make the new drug less costeffective
EXPERIENCE OF pCODR EXPERT
REVIEW COMMITTEE (pERC)
Requesting Real World Evidence
• pCODR 60 reviews (Up to Feb 2016)
• Total of 21 pCODR reviews requested Real World
Evidence
• 13 pCODR reviews explicitly requested Real World
Evidence
• 10 pCODR reviews potentially requested Real World
Evidence
Potential RWE Request:
Unclear if pERC requested RWE, but it could be beneficial
Next Steps for Real World Evidence Collection
Inform magnitude of clinical benefit and cost-effectiveness or the true cost-effectiveness
Define the potential clinical benefit or magnitude of clinical benefit
Define the population or disease
Inform duration of treatment
Inform duration of treatment and cost-effectiveness
Inform sequencing of available therapies
7
10
23 requests for RWE for
21 studies
1
2
2
1
Breakdown of pCODR Reviews
60 Final Recommendations
Positive Recommendation
Conditional Recommendation
Negative Recommendation
(4 requested RWE)
10
11
(17 requested RWE)
39
Temporal Trends in RWE Requests
60 pERC Final Recommendations
Number of Recommendations
24
Negative Recommendations
Without RWE Request
With RWE Request
18
12
6
0
2012
2013
2014
2015
Final Recommendation Issue Year
2016
Breakdown by Tumour Site
60 pERC Final Recommendations
Number of Recommendations
24
Negative Recommendations
Without RWE Request
With RWE Request
18
12
6
0
Heme
Melanoma
GI
GU
Lung
Tumour Site
Breast
Other
Gyne
Breakdown by Study Characteristics: 21 Studies
Primary Endpoint of Final Recommendations Requesting
RWE
Number of Studies
10
8
6
4
2
0
DSV (Decrease in Spleen Volume), MCyR (Major Cytogenetic Response), MaHR (Major Haematological Response)
WHAT REAL WORLD EVIDENCE CAN WE
COLLECT?
Potential Deliverables (effectiveness, safety,
quality of life, cost-effectiveness)
Potential Deliverables (verify economic models)
Discussions
• HTA committees commonly make best possible
recommendations based on substantial uncertainties
• pCODR ERC commonly requests for the collection for further
evidence to reduce uncertainties
– How can further evidence be collected?
• Routinely collected data (population-based admin data)
• Evidence building program (prospective collection of data)
• Real world experiments (real world pragmatic randomized trials)
– Who will use this evidence once collected?
• Practitioners and patients – informed treatment decisions
• Policy decision-makers and payers
• Re-HTA (recommendation-makers)