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