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5/2/2006 1
Expensive Drugs for Rare Diseases
Janet Martin, BScPhm, RPh, PharmD
High Impact Technology Evaluation Centre (HiTEC)
London Health Sciences Centre, ON
Experience from the decision-making front
I. What is an orphan drug?II. What decisions have been made?III. Do they deserve special status?IV. What opportunities remain?
Experience from the decision-making front
I. What is an orphan drug?II. What decisions have been made?III. Do they deserve special status?IV. What opportunities remain?
My perspective: Hospital HTA Producer + User, MOH Provincial Formulary Committee
An old adage . . .
When you hear hoofbeats . . .
Zebras!
‘OrphanOrphan’’ Drugs in CanadaDrugs in Canada
What is an What is an ‘‘orphanorphan’’??
Drug for a rare disease that is debilitating or Drug for a rare disease that is debilitating or lifelife--threatening (<1/1000)threatening (<1/1000)
6000 rare diseases have been defined (most 6000 rare diseases have been defined (most are of genetic origin)are of genetic origin)
~3 million Canadians will suffer from a rare ~3 million Canadians will suffer from a rare disease, condition, or syndrome in their lifetime disease, condition, or syndrome in their lifetime
Unknown = Unloved?Unknown = Unloved?
Few Customers = No Industry IncentiveFew Customers = No Industry Incentive
‘OrphanOrphan’’ Drugs in CanadaDrugs in Canada
Examples of Examples of ‘‘orphanorphan’’ drugsdrugs
CerezymeCerezyme
MyozymeMyozyme
AldurazymeAldurazyme
FabrazymeFabrazyme
GleevecGleevec
Many more in the pipelineMany more in the pipeline……
International Orphan Drug Policies
Incentives to drug companies include:– Market exclusivity – Reduction of licensing fees– Assistance with marketing applications– Direct access to centralized procedure for
marketing authorization– Provision of specific research grants (US)
In Canada, no specific ‘Orphan Drug’ policy exists
Media Frenzy
CMAJ 2006;174(2):189
Cost informs the decision
Cost is one consideration,But never the only consideration
Expensive DrugsRare Diseases
True Heart-Rending Stories
Two Examples:1. Dominic*
2. Darla*
*Details have been modified to respect confidentiality
Expensive Drugs for Rare Diseases
I. Patient PerspectiveII. Hospital PerspectiveIII. Ministry of Health Perspective
Expensive Drugs for Rare Diseases
I. Patient PerspectiveII. Hospital PerspectiveIII. Ministry of Health Perspective
Dominic: Fabry’s Disease
FabryFabry’’ss DiseaseDisease
PainPain
Renal DysfunctionRenal Dysfunction
Cardiovascular DiseaseCardiovascular Disease
Premature DeathPremature Death
Treatment = SupportiveTreatment = Supportive
Darla: Hurler’s Syndrome (MPS I)
HurlerHurler’’s Syndromes Syndrome
Respiratory DysfunctionRespiratory Dysfunction
Musculoskeletal DeformityMusculoskeletal Deformity
Cardiovascular DiseaseCardiovascular Disease
NeurologicNeurologic DeclineDecline
Premature DeathPremature Death
Treatment = Supportive +/Treatment = Supportive +/-- BMTBMT
Expensive Drugs for Rare Diseases
I. Patient PerspectiveII. Hospital PerspectiveIII. Ministry of Health Perspective
Hospital Action: Rapid HTPA
What are the Benefits (Triple E)?What are the Risks (Triple E)?
Risks worth the Benefits (B:R)? What are the Tradeoffs (HTPA)?
AldurazymeAldurazyme: Benefits : Benefits
EvidenceEvidence
ClinicallyClinically--Important Benefits: None foundImportant Benefits: None found
Surrogate Outcomes: FEV, 6Surrogate Outcomes: FEV, 6--minute walk testminute walk test
Economics:Economics: (None)(None)
Downstream hospitalization costDownstream hospitalization cost--savings (?)savings (?)
EthicsEthics
Equity: Rule of RescueEquity: Rule of Rescue
Politically Politically ‘‘positivepositive’’; Media assuaging; Media assuaging
AldurazymeAldurazyme: Risks: Risks
Evidence:Evidence:
ClinicallyClinically--Important Risks: Infusion reactionImportant Risks: Infusion reaction
Surrogate Outcomes: InfusionSurrogate Outcomes: Infusion--related related reactions (NNH = 6), usually mildreactions (NNH = 6), usually mild
Economics:Economics:
$120,000 $120,000 –– $900,000/yr (+ personnel)$900,000/yr (+ personnel)
Ethics:Ethics:
Inequitable: Why should Inequitable: Why should ‘‘rarerare’’ be be ‘‘specialspecial’’??
Is Is ‘‘nono’’ discriminatory?discriminatory?
AldurazymeAldurazyme: Additional Risks : Additional Risks
Social:Social:
Foregone health benefits elsewhereForegone health benefits elsewhere
Premature acceptance of evidence; stifled Premature acceptance of evidence; stifled researchresearch
Political:Political:
Would Would ‘‘nono’’ blackmarkblackmark our pediatric genetics our pediatric genetics program?program?
Legal precedent, politically sensitiveLegal precedent, politically sensitive
Darla: Hurler’s Syndrome (MPS I)
HurlerHurler’’s Syndromes Syndrome
Respiratory DysfunctionRespiratory Dysfunction
Musculoskeletal DeformityMusculoskeletal Deformity
Cardiovascular DiseaseCardiovascular Disease
NeurologicNeurologic DeclineDecline
Premature DeathPremature Death
Treatment = Supportive +/Treatment = Supportive +/-- BMTBMT
Dominic: Fabry’s Disease
FabryFabry’’ss DiseaseDisease
PainPain
Renal DysfunctionRenal Dysfunction
Cardiovascular DiseaseCardiovascular Disease
Premature DeathPremature Death
Treatment = SupportiveTreatment = Supportive
What did we decide?What did we decide?
AldurazymeAldurazyme::
YesYes
FabrazymeFabrazyme::
NoNo
Expensive Drugs for Rare Diseases
I. Patient PerspectiveII. Hospital PerspectiveIII. Ministry of Health Perspective
Common Drug Review
Common Drug Review
Is that fair?Is that fair?
AldurazymeAldurazyme & & FabrazymeFabrazyme::
CEDAC says CEDAC says ‘‘nono’’..
Individual jurisdictions say Individual jurisdictions say ‘‘nono’’
But, some hospitals say But, some hospitals say ‘‘yesyes’’
Internationally, Internationally, fundersfunders say say ‘‘yesyes’’
Is institutional charity allowable, Is institutional charity allowable,
given the Canada Health Act?given the Canada Health Act?
Is that fair?Is that fair?
Who is Right?Who is Right?
‘‘RarityRarity’’ = Special Status?= Special Status?
Aspect Pro-Argument Counter-Argument Rarity + Gravity
Special value s/b applied for health gains in rare diseases
Is society willing to pay more for gains in rare than common severe diseases?
No other options
Ensure access when no other treatment exists
Should biologic modification be preferred over health gain?
Small population
Change the rules of ‘burden of proof’
Don’t stop short of best possible evidence!
Different forms of evidence
Registries to determine post-market effectiveness
Registries to determine natural history prior to drug intervention
Budget impact
Small budget impact Consider the opportunity costs
Equity Rare diseases have same right to treatment as common
…true only when the opportunity cost is minimized
1. Hughes et al, QJM 2005 2. McCabe 2006, Discussion Paper 3. Hollis, Discussion Paper 2006
‘‘RarityRarity’’ = Special Status?= Special Status?
Aspect Argument Counter-Argument Rarity + Gravity
Special value s/b applied for health gains in rare diseases
Is society willing to pay more for gains in rare than common severe diseases?
No other options
Ensure access when no other treatment exists
Should biologic modification be preferred over health gain?
Small population
Change the rules of ‘burden of proof’
Don’t stop short of best possible evidence!
Different forms of evidence
Registries to determine post-market effectiveness
Registries to determine natural history prior to drug intervention
Budget impact
Small budget impact Consider the opportunity costs
Equity Rare diseases have same right to treatment as common
…true only when the opportunity cost is minimized
1. Hughes et al, QJM 2005 2. McCabe 2006, Discussion Paper 3. Hollis, Discussion Paper 2006
‘‘RarityRarity’’ = Special Status?= Special Status?
Aspect Argument Counter-Argument Rarity + Gravity
Special value s/b applied for health gains in rare diseases
Is society willing to pay more for gains in rare than common severe diseases?
No other options
Ensure access when no other treatment exists
Should biologic modification be preferred over health gain?
Small population
Change the rules of ‘burden of proof’
Don’t stop short of best possible evidence!
Different forms of evidence
Registries to determine post-market effectiveness
Registries to determine natural history prior to drug intervention
Budget impact
Small budget impact Consider the opportunity costs
Equity Rare diseases have same right to treatment as common
…true only when the opportunity cost is minimized
1. Hughes et al, QJM 2005 2. McCabe 2006, Discussion Paper 3. Hollis, Discussion Paper 2006
‘‘RarityRarity’’ = Special Status?= Special Status?Aspect Argument Counter-Argument Rarity + Gravity
Special value s/b applied for health gains in rare diseases
Is society willing to pay more for gains in rare than common severe diseases?
No other options
Ensure access when no other treatment exists
Should biologic modification be preferred over health gain?
Small population
Change the rules of ‘burden of proof’
Don’t stop short of best possible evidence!
Different forms of evidence
Registries to determine post-market effectiveness
Registries to determine natural history prior to drug intervention
Budget impact
Small budget impact Consider the opportunity costs
Equity Rare diseases have same right to treatment as common
…true only when the opportunity cost is minimized
Carte Blanche Stifled
Innovation
‘‘RarityRarity’’ = Special Status?= Special Status?Aspect Argument Counter-Argument Rarity + Gravity
Special value s/b applied for health gains in rare diseases
Is society willing to pay more for gains in rare than common severe diseases?
No other options
Ensure access when no other treatment exists
Should biologic modification be preferred over health gain?
Small population
Change the rules of ‘burden of proof’
Don’t stop short of best possible evidence!
Different forms of evidence
Registries to determine post-market effectiveness
Registries to determine natural history prior to drug intervention
Budget impact
Small budget impact Consider the opportunity costs
Equity Rare diseases have same right to treatment as common
…true only when the opportunity cost is minimized
Carte Blanche Stifled
Innovation
‘Credits’
Equity? It depends. . .
““Reimbursement of Reimbursement of laronidaselaronidase would raise would raise questions about equity, since drugs that have questions about equity, since drugs that have not been shown to be costnot been shown to be cost--effective for other effective for other diseases are not generally reimburseddiseases are not generally reimbursed””
CEDAC, CEDAC, AldurazymeAldurazyme Final Recommendation, 2005Final Recommendation, 2005
Orphan Drugs in UKOrphan Drugs in UK
Given resources that do not meet all needs, money spent Given resources that do not meet all needs, money spent on one service means another service cannot be provided on one service means another service cannot be provided
Funding decisions should not be posed as isolated Funding decisions should not be posed as isolated questionsquestions
Cost effectiveness thresholds are a shorthand way of Cost effectiveness thresholds are a shorthand way of accounting for opportunity cost; if decisions breach these accounting for opportunity cost; if decisions breach these norms they should be justified by principled argument norms they should be justified by principled argument
The current system, which obscures the opportunity cost, The current system, which obscures the opportunity cost, is inefficient, unfair, and unsustainable given the growth in is inefficient, unfair, and unsustainable given the growth in orphan drugsorphan drugs
Burls et al. BMJ 2005;331:1019Burls et al. BMJ 2005;331:1019--2121
What do Citizen’s Say?
Difficult decisions do have to be made within the NHS. Difficult decisions do have to be made within the NHS. Too often these decisions are made in secret. But they Too often these decisions are made in secret. But they should know that we do support them and we know they should know that we do support them and we know they have to keep within a budget. The NHS shouldn't be have to keep within a budget. The NHS shouldn't be frightened of the public finding out about all thisfrightened of the public finding out about all this——they they should discuss it more with the public. They'll only keep should discuss it more with the public. They'll only keep our confidence if they level with us about the difficult our confidence if they level with us about the difficult choices that have to be made.choices that have to be made.
Lay member, NICE CitizenLay member, NICE Citizen’’s Councils Council
Making Tradeoffs Explicit
We need to learn how to make tradeWe need to learn how to make trade--offs between equity offs between equity and efficiency that are explicit, principled, and and efficiency that are explicit, principled, and generalisablegeneralisable and how to admit openly when there are and how to admit openly when there are treatments and services that are not being fundedtreatments and services that are not being funded
Burls et al. BMJ 2005;331:1019-21
Impact on Decision-making
What you get What you get …… What you 4Go What you 4Go ……PCI = 2 lives PCI = 2 lives
APC = 0.75 livesAPC = 0.75 lives
LL--AmphoAmpho = 4 lives= 4 lives
Unknown clinical Unknown clinical benefitbenefit
Political Political ‘‘CorrectnessCorrectness’’
Media FriendlinessMedia Friendliness
If we fund Aldurazyme…
What you 4Go What you 4Go ……
Unknown clinical benefitUnknown clinical benefit
Political Political ‘‘CorrectnessCorrectness’’
MediaMedia--FriendlinessFriendliness
What you Get What you Get ……
PCI = 2 lives PCI = 2 lives
APC = 0.75 livesAPC = 0.75 lives
LL--AmphoAmpho = 4 lives= 4 lives
If we do not fund Aldurazyme…
Provincial Disparity
Working Toward SolutionsWorking Toward Solutions
Develop a National FrameworkDevelop a National Framework
NPS has named orphan drugs as a priorityNPS has named orphan drugs as a priority
Achieve universality and consistency (HCA)Achieve universality and consistency (HCA)
NPS recommendations + national fundingNPS recommendations + national funding
Without a National FrameworkWithout a National Framework
Inequities in access will prevail Inequities in access will prevail
Pressure on hospitals will continuePressure on hospitals will continue
(Reverse) rationing at the bedside will occur(Reverse) rationing at the bedside will occur
At the very least . . . At the very least . . .
Criteria for public funding should be defined along Criteria for public funding should be defined along with the citizens of Canadawith the citizens of Canada
When is deviation from conventional criteria When is deviation from conventional criteria allowed?allowed?
Best possible evidence should be requiredBest possible evidence should be required
Require registries at the outsetRequire registries at the outset
Define stopping rulesDefine stopping rules
New methodologies should be exploredNew methodologies should be explored
And, ideally . . . And, ideally . . .
Thresholds should be defined Thresholds should be defined ‘‘a prioria priori’’Define Define ‘‘clinicallyclinically--important differenceimportant difference’’ (CID)(CID)Define willingness to pay for CIDDefine willingness to pay for CID
Policies should prevent Policies should prevent ‘‘loopholesloopholes’’Special Access Program (SAP) circumvents marketingSpecial Access Program (SAP) circumvents marketing
Policies should consider pricing transparencyPolicies should consider pricing transparencyHow much is too much? Blockbuster? How much is too much? Blockbuster?
Policies need to incorporate riskPolicies need to incorporate risk--sharingsharingNo cure, no pay!No cure, no pay!For example, payer pays based on For example, payer pays based on ‘‘degree of certaintydegree of certainty’’ of of
outcomes, or outcomes, or ‘‘achievementachievement’’ of outcomesof outcomes
Does rarity require special status?
What is the real cost?
Relevance:Based on “fair-minded” relevant criteria
Publicity:Rationale publicly accessible
Dispute Resolution:Opportunity to appeal
Enforcement:A4R framework accountability
EmpowermentSupported by change-facilitating strategies
Accountability for Reasonableness (A4R)
No comprehensive framework in place
New orphan drugs are on the horizon
The time for setting policy framework is now
Past decisions should not lock future decisions (Gaucher’s)
A new framework is required for this new era
Timing is Crucial
Many thanks . . .
LHSC
CIHR
UWO
LHRI
CCOHTA
…our team!
gohitec.com
know4go.org