Reference Model for Economic Evaluation: Industry Perspective
Christopher LeibmanVP, HEOR – Global Market Access
Biogen
Disclosure and Acknowledgements C. Leibman is an employee of Biogen
Views and opinions are Leibman’s, not Biogen’s
Acknowledgements: Michele Potashman, Ravi Singh, Samantha Budd Haeberlein, Eric Hall, Tom Koenig, Robin Thompson
Outline IPECAD 2011 - Let’s see how far we’ve come…
IPECAD 2015 – Situation and near-term– Key attributes for a ‘reference’ model
IPECAD circa 2020+– Preparation for transformation
Conceptual Framework Focused on AD, not pAD
McLaughlin T, Feldman H, Fillit H, Sano M, Schmitt F, Aisen P, Leibman C, Mucha L, Ryan JM, Sullivan SD, Spackman DS, Neumann PJ, Cohen J, Stern Y. Alzheimer’s & Dementia 6(2010) 482-493.
AD Models: Moving Towards Models 2.0 Much of this has been driven by:
– Lack of good data (measures, trial length)
– Limited inclusion of broader measures that might incorporate impacts of multiple symptoms into clinical trials
Future Models– More realistic and compelling evaluations of various interventions
– Better characterization of the disease – conceptual framework
– Better assess the full range of costs and benefits across interventions
– Better evaluate the incremental costs and benefits
Cohen JT, Neumann PJ. Alzheimer’s & Dementia 4(2008) 212-222.Green C. Pharmacoeconomics 2007; 25(9): 735-750.
AD: Alzheimer’s Disease
IPECAD 2015: ‘Reference’ Reality in AD Where have ‘reference models’ been successful
Attributes for reference success:– Population characterization stability – clear definitions
– Robust/Agreed data on disease progression (and costs)
– Evidence expectations clear – aligned endpoints / staging
– Stable period of clinical practice and clear treatment pathways
– Recent assessments to draft from:• Previous model variation has been honed - ‘survival of the fittest’
• Fit for near-term purpose – recent series of evaluations lead to anticipation of upcoming evaluations
• Consortium interests align (nice to have – but not required)
IPECAD 2015: ‘Reference’ Reality in AD Where have ‘reference models’ been successful
Attributes for reference success:– Population characterization stability – clear definitions
– Robust/Agreed data on disease progression (and costs)
– Evidence expectations clear – aligned endpoints / staging
– Stable period of clinical practice and clear treatment pathways
– Recent assessments to draft from:• Previous model variation has been honed - ‘survival of the fittest’
• Fit for near-term purpose – recent series of evaluations lead to anticipation of upcoming evaluations
• Consortium interests align (nice to have – but not required)
Population Continuum Evolving
~1.6M ~2.3M ~1.4M
5.3 M - Diagnosed with Alzheimer’s disease in the US
Cognitive and functional decline fulfilling dementia
SevereSevereModerateModerateMildMild
US Census Bureau 2014, * Jansen et al JAMA 2015, ⱡ Roberts et al Clin Geriatr Med 2013, Petersen et al Curr Alz Res 2009, Mitchell et al Acta Psych Scand 2009# Petersen et al Neurol 2012, Whitwell et al Arch Neurol 2012, Plassman et al Ann Int Med 2008, Manly et al Arch Neurol 2005
Population Continuum Evolving10-15%ⱡ Conversion/year
MCI due to AD / Prodromal
MCI due to AD / ProdromalAt risk PopulationAt risk Population
~1.6M ~2.3M ~1.4M ~13M ~3.8M
27%* of over 65’s - US at risk population
~8%# of over 65’s - US amnestic MCI pop.
5.3 M - Diagnosed with Alzheimer’s disease in the US
Amyloid positive, ‘cognition normal’
Cognitive and functional decline fulfilling dementia
Subjective memory decline
SevereSevereModerateModerateMildMild
Early AD
US Census Bureau 2014, * Jansen et al JAMA 2015, ⱡ Roberts et al Clin Geriatr Med 2013, Petersen et al Curr Alz Res 2009, Mitchell et al Acta Psych Scand 2009# Petersen et al Neurol 2012, Whitwell et al Arch Neurol 2012, Plassman et al Ann Int Med 2008, Manly et al Arch Neurol 2005
Targeting of the Disease Continuum
MCI due to AD / Prodromal
MCI due to AD / ProdromalAt risk PopulationAt risk Population
Amyloid positive, ‘cognition normal’
Cognitive and functional decline fulfilling dementia
Subjective memory decline
SevereSevereModerateModerateMildMild
Targeting of the Disease Continuum
MCI due to AD / Prodromal
MCI due to AD / ProdromalAt risk PopulationAt risk Population
Amyloid positive, ‘cognition normal’
Cognitive and functional decline fulfilling dementia
Subjective memory decline
SevereSevereModerateModerateMildMild
MCI/Mild MMSE 22-30, CDR 0.5 to 1.0
Mild MMSE 20-26
Asympt. MMSE 25-30,
CDR 0
MCI/Mild MMSE 21-28
MCI due to AD/portion of Mild MMSE 24-30, CDR 0.5
Mild (No MMSE)
MCI/Mild ≥ 20
Mild-Moderate (No MMSE)Prodromal (No MMSE)
*Prodromal and Mild definitions on MMSE overlap from 24-26
Early AD, CDR 0 to 0.5 (No MMSE)
Aβ plaque mAbAβ soluble mAb
BACE
Solanezumab
MK-8931
Aducanumab
Gantenerumab
AZD3293
JNJ-54861911
BAN-2401
E2609
Inve
stig
atio
nal C
ompo
unds
Evidence expectations clear?
Outcome of interest clarity
Economic flow by stage (population)
Patient and care-provider or support inclusion
Disease continuum and model construct: new stages, thresholds
Need for a fit for purpose evolution
IPECAD 2020…We can’t wait!AD starts many years prior to onset of symptoms
SevereSevereModerateModerateMildMildMCI due to AD / Prodromal
MCI due to AD / ProdromalAt risk PopulationAt risk Population
Jack, et al. Lancet Neurol (2013)
There is work to be done!
Population continuum and model structure versus…
Data challenges - Prioritization of gaps?
Population flexibility
Inclusion of other costs and benefits – appropriateness
Thinking with the future in mind:– Movement to non-symptomatic patients – use of surrogates
– Relevance of biomarkers – enrichment vs. outcomes
“Would you tell me, please, which way I should go from here?” Alice asked the Cheshire Cat.“That depends a good deal on where you want to get to,” said the Cat.
“I don’t much care where…” said Alice.
“Then it doesn’t matter which way you go”, said the Cat.
“…so long as I get somewhere”, Alice added as an explanation.
“Oh, you’re sure to do that,” said the Cat, “if you only walk long enough”.
Where do we go from here?
“Would you tell me, please, which way I should go from here?” Alice asked the Cheshire Cat.“That depends a good deal on where you want to get to,” said the Cat.
“I don’t much care where…” said Alice.
“Then it doesn’t matter which way you go”, said the Cat.
“…so long as I get somewhere”, Alice added as an explanation.
“Oh, you’re sure to do that,” said the Cat, “if you only walk long enough”.
Where do we go from here?
“Would you tell me, please, which way I should go from here?” Alice asked the Cheshire Cat.“That depends a good deal on where you want to get to,” said the Cat.
“I don’t much care where…” said Alice.
“Then it doesn’t matter which way you go”, said the Cat.
“…so long as I get somewhere”, Alice added as an explanation.
“Oh, you’re sure to do that,” said the Cat, “if you only walk long enough”.
Where do we go from here?
“Would you tell me, please, which way I should go from here?” Alice asked the Cheshire Cat.“That depends a good deal on where you want to get to,” said the Cat.
“I don’t much care where…” said Alice.
“Then it doesn’t matter which way you go”, said the Cat.
“…so long as I get somewhere”, Alice added as an explanation.
“Oh, you’re sure to do that,” said the Cat, “if you only walk long enough”.
Where do we go from here?
Theme 1: Outcome definition
Theme 2: Access to quality data
Theme 3: Use of data
Theme 4: Patient engagement
WP 2: Outcome definition and
mapping of RWE data sources
WP 3: Integrationstrategy of RWE
data
WP 4: Modelingand simulation
WP 5: HTA – EMA Integration
Set of target outcomes
Searchable web catalog of available data sources
Evaluation of suitability for use in natural history / effectiveness
Evaluation of suitability for combining data sources
Integration strategy (incl. demonstration)
Digital alternatives (incl. demonstration)
Statistical functions to predict outcomes
Drivers of outcome variation
Comparisons of methodologies to model archetypes
WP 1: Project management
WP 6: Training and CommunicationWP 7: Legal and Ethics
IMI: Real World Outcomes Across the AD Spectrum (ROADS) to Better Care Consortium