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AMCP Foundation Symposium Transplanting European Health Technology

Assessment (HTA) to America? What’s Wrong with Our Version?

October 15, 2013 San Antonio, TX

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AMCP Foundation Symposium Transplanting European Health Technology

Assessment (HTA) to America? What’s Wrong with Our Version?

October 15, 2013 San Antonio, TX

Welcome

Edith A. Rosato, RPh, IOM Chairman, Board of Trustees

Academy of Managed Care Pharmacy Foundation

Diana Brixner, RPh, PhD − Symposium Moderator Professor and Chair Department of Pharmacotherapy, Executive Director, Outcomes Research Center, University of

Utah College of Pharmacy

Transplanting European Health Technology Assessment (HTA) to America: What’s Wrong with Our Version?

PROGRAM OBJECTIVES

This program will help managed care pharmacists evaluate the factors that are important to their strategic resource development and decision structures. The purpose of this Program is to: • Review current drug evaluation policies and processes in the U.S. and compare to

those in Europe • Define key changes in Cost Effectiveness Research (CER), Health Technology

Assessment (HTA) and risk-adjusted contracting and the challenges they create for more robust specialty decision-making

• Identify barriers to widespread adoption of CER, HTA and Risk-adjusted pricing • Present case studies for audience to consider roles of CER, HTA, risk and outcomes in

formulary decision-making • Solicit stakeholder recommendations on the quick hits needed to improve CER, HTA,

research priorities, risk arrangements and formulary decision processes

Symposium Sponsors

GOLD SPONSOR

SILVER SPONSOR

BRONZE SPONSOR

This Grant will be used for the educational part of the program only.

AMCP Foundation would like to thank the following companies for their support of the symposium:

Challenges In Making Informed Health Care Decisions: Promoting High Integrity, Evidence-Based Decisions that Improve Patient Outcome Bryan Luce, PhD, MBA Chief Science Officer, PCORI

Need To Address Quality and Efficiency Gaps In US Healthcare

US Healthcare: • Innovative, but is this enough? • Lags behind many developed nations in treatable outcomes

including mortality rates • Far higher health care costs, consuming 18% of GDP in 2011 and

predicted to exceed 25% of GDP by 2025. • Variations in care that suggest 30% of spending is for medical care

of uncertain or questionable value. • Many medical treatments in common use are not backed by strong

empirical evidence. • Congressional Budget Office has determined that health care costs

represent the single greatest challenge to balancing the federal budget.

McClellan M, Benner J. 2009. Comparative Effectiveness Research: Will it Bend the Health Care Cost Curve and Improve Quality? Washington, DC: Engelberg Center for Healthcare Reform at Brookings

LIMITATIONS IN THE STATUS QUO

There is ample evidence that, under the status quo, there are critical limitations in how the US identifies and uses evidence on clinical effectiveness, including: (1) setting priorities for evidence assessment (2) assessing evidence through systematic reviews (3) developing trusted clinical practice guidelines

Institute of Medicine (IOM). 2008. Knowing what works in health care: A roadmap for the nation. Washington, DC: The National Academies Press

IOM: Value & Science-Driven Health Care

Vision: Our vision is for a healthcare system that draws on the best evidence… Goal: By the year 2020, 90% of clinical decisions will be supported by accurate, timely, and up-to-date clinical information, and will reflect the best available evidence. Context: …we are faced with similarly unprecedented challenges to identify and deliver the care most appropriate for individual needs and conditions. Care that is important is often not delivered. Care that is delivered is often not important. In part, this is due to our failure to apply the evidence … Core concepts and principles: …to the greatest extent possible, the decisions that shape the health of Americans…will be grounded on a reliable evidence base

• Evidence that has met some established test of validity • Evidence processes that are accessible and transparent to all stakeholders

IOM (Institute of Medicine). 2011. Learning What Works: Infrastructure Required for Comparative Effectiveness Research: Workshop Summary. Washington, DC: The National Academies Press

IOM: Our Common Commitment

We Have a Common Commitment To

• The right health care for each person • Putting the best evidence into practice • Establishing the effectiveness, efficiency, and safety of medical care

delivered • Building constant measurement into our healthcare investments • Establishment of healthcare data as a public good • Shared responsibility distributed equitably across stakeholders, both public

and private • Collaborative stakeholder involvement in priority setting • Transparency in the execution of activities and reporting of results • Subjugating the individual political or stakeholder perspectives in favor of

the common good

Strong Evidence Requires Being Clear About What EBM, CER & HTA Mean

Lack of clarity leads to unnecessary disagreements among key stakeholders concerning their appropriate role in health care decision making. Who Are the Key Stakeholders? • Medical professionals and other health care providers • Health care payers • Patients and patient advocacy groups • Legislators and regulators • Private and public health agencies • Manufacturers Taxpayers

The EBM-CER-HTA Framework

12

“Can it Work?” (Efficacy)

13

“Does it Work?” (Effectiveness)

14

“Is it Worth it?” (Value)

15

Putting it All Together

16

So, CER….

Is not a method per se It’s an analytical learning process to assist real world decision making Lives on the boundary of evidence development and evidence synthesis Is neither experimental nor observational; rather either or both, and Feeds into HTA and EBM processes

17

So….

Where does patient-centered outcomes research (as PCORI thinks of it)

fit into the EBM-CER-HTA

paradigm?

Patient-Centered Outcomes Research is….

Comparative effectiveness research (CER) that is “patient-centered”.

It’s not:

Payer-centered, nor… Society-centered, nor…

Regulatory-centered.

It’s explicitly patient-centered

What is PCORI?

Non profit research institute Created by Congress (ACA) (but arms-length) Funded via a new trust fund Some general federal revenues, Medicare trust fund Mainly (60%) fees from insurers and self-insured business

(covered lives) Does not feed directly into decision-making Does not fund CEA

Our National Priorities for Research

Assessment of Prevention, Diagnosis, and Treatment

Options Improving Healthcare

Systems Communication &

Dissemination Research

Addressing Disparities Accelerating PCOR and Methodological Research

21

Our Work Answers Patients’ Questions

Given my personal characteristics, conditions and preferences…

“What should I expect will

happen to me?”

“What are my options and what are the

potential benefits and

harms of those options?”

“What can I do to improve the outcomes that

are most important to

me?”

“How can clinicians and the

care delivery systems they work

in help me make the best decisions about my health and healthcare?”

22

How We Promote Participation in Research

Engagement Awards

Matching Challenge

Pilot Projects

Pilot Projects: methods for engaging patients in research and dissemination process. Challenge Grants: to connect patients and researchers as partners in research.

Engagement Awards: for patients and stakeholders to participate in PCORI research

23

How We Pick Research Questions to Study

Our Advisory Panels

25

Leverage knowledge and experience of clinicians, researchers, patients, and other experts to help PCORI achieve its goals Assure meaningful patient engagement in: Identifying research priorities and topics Monitoring research activities Conducting randomized clinical trials

Addressing Disparities

Assessment of Prevention,

Diagnosis, and

Treatment Options

Improving Healthcare Systems

Patient Engagement

Research Budget

2013: $427M 2014: $500M 2015: $500M

National Patient-Centered Clinical Research Network

8 Clinical Data Research Networks (CDRNs) Observational and RCT studies; PROs, collaborating

networks 18 Patient-Powered Research Networks (PPRNs) Data Coordinating Center Developmental Phase: ~ $68M over 18 months

27

28

National Patient-Centered Clinical Research Network: Our Vision

Steering Committee

• Awardees • PCORI • AHRQ, NIH, FDA,

ONC, CMS, VA

Scientific Advisory Board

Special Expert Group

In Sum PCOR…

Is simply a special case of CER

29

THANK YOU

Learning Assessment Question In describing Comparative Effectiveness Research (CER), which of the following is NOT true: 1.CER is an analytical learning process to assist real world decision making. 2.CER lives on the boundary of evidence development and evidence synthesis. 3.CER is derived from real world observational studies not randomized controlled trials. 4.CER feeds into Health Technology Assessment (HTA) and Evidence Based Medicine (EBM) processes.

HTA Outside the US: what, why and how?

Chris Henshall Associate Professor, Brunel University

Chair, HTAi Policy Forum Consultant in Health, Research and Innovation

Policy

Overview • Nature, origin and development of HTA • HTA in Europe

– Health systems and health spending in Europe – HTA systems in Europe – HTA methods

• "QALYs" versus "clinical added benefit” • considering costs and opportunity costs - assessing cost-

effectiveness/cost-utility/value for money

– Snapshots of Germany, France and England

• NICE - origins, development, science and politics

HTA • Health Technology Assessment is:

– Assessment of the effectiveness, costs and wider impact of health interventions

– Multi-disciplinary scientific research to inform decisions on policy and practice

– Draws on the science of clinical evaluation, systematic reviews and meta-analysis, epidemiology, economic analysis, modelling and decision analysis, ethics and other social sciences

• “Health Technology” broadly defined to include all health (care) interventions – at least in principle

• By considering effectiveness, costs and impact in the real world, HTA seeks to assess the actual value of interventions to patients and systems

Growth of HTA • Started in US Congressional Office of Technology Assessment • Initially applied to “big ticket” technologies • Focus on drugs in last 25 years; increasing application recently to

devices and diagnostics (e.g., Australia) • Well established in many countries in Europe, Canada, and Australia

at national and sometimes also regional and hospital levels • Growing rapidly in Asia and Latin America • Widely varying systems and approaches • Increasing patient and public scrutiny and involvement

HTA and Decisions • Three inter-related processes

– Assessment – collection and scientific analysis of the relevant data

– Appraisal – review of the conclusions of one or more assessments, along with other relevant factors not formally included in assessment – e.g., priorities, values, budget impact – to provide support/advice/guidance/recommendations for

– Decisions – on use of technology • In theory, HTA can be undertaken to support any decision

maker, including individual patients and doctors. In practice, it is most commonly used to support decision making at national, sub-national or institution level

HTA and Regulation • Why do we need HTA if we have regulation? • Regulators give market approval for products to be sold – they judge whether

benefits outweigh any risks • HTA supports consumer decisions on which products on the market are most

appropriate and affordable. The consumer in most HTA systems is a health system budget holder

• Regulators consider: – Safety and efficacy – typically vs placebo in RCTs

• HTA considers: – Comparative effectiveness – typically vs current care – Looking for patient relevant health benefits and value – And considering costs and wider impacts and system value – Wide range of research methods, e.g., RCTs, observational designs,

modeling etc. • HTA starts from regulators’ reports, but not all data can be shared and HTA

typically requires further information

HTA, value and PCOR • HTAi Policy Forum discussed “HTA and Value” in February – see paper in press

in IJTAHC and available free now at: www.htai.org/index.php?id=643 • The core of HTA is patient-centered health outcomes for a technology, in

comparison with current standard of care • HTA considers other factors relevant to understanding the wider value of a

technology in the real world: – Wider benefits for patients (eg choice, convenience) – Benefits for care givers (eg reduced care burden) – Benefits/costs for society (eg welfare costs, support for needy) – Benefits/costs for health system

• In systems with limited budgets, introducing technologies that increase costs has opportunity costs – for other patients and/or other parts of society. HTA can help decision makers to judge whether the benefits of new technology outweigh those opportunity costs

• In some systems, this information is used to support negotiations/decisions on price as well as uptake

http://www.htai.org/index.php?id=643




effectiveness/cost-utility/value for money

– Snapshots of England, France and Germany


Health systems in Europe • Systems and funding vary between countries • Total health spending in 2011 across EU was 9% of GDP, ranging

from 12.0% (Netherlands) to 6.0% (Romania): – UK 9.6%; France 11.6%; Germany 11.6%; (USA 17.7%)

• All countries have mix of “public” and “private” funding, with public generally dominating private

• Various models for public funding, primarily – Social insurance – government run/regulated/subsidized

insurance, eg France and Germany – Tax funded, e.g., UK

Pharmaceutical spend and HTA • Pharmaceutical spending as % of total health spending varies

widely, even across richer countries. – e.g., in 2011: UK 11.4%; Germany 14.1%; France 15.6%; Spain

17.4%; (US 11.7%) • Source of concern in many countries for some years • Various policy initiatives in response, including (but not limited to)

HTA • Various recent initiatives in response to 2008 financial crisis, e.g.,

price cuts, system changes • This, together with blockbusters going off patent, has slowed or

reversed growth in drug spend in some countries

HTA systems in Europe • Most national and some regional governments in Europe have

established “public” HTA bodies/systems to advise MoH and/or health service and/or Social Insurance System and/or other public “payers”

• All cover pharmaceuticals; some also cover devices • Some look at everything in their remit; others focus efforts on

“problems” they or the system identify • Advise on:

– Coverage: “yes”; “yes for defined indications”; “no” – And often also on cost-effectiveness, value for money or price

where this is set or negotiated • Options may include:

– Managed Entry/Risk Sharing schemes – Coverage with Evidence Development

HTA methods (1) • Measuring health benefits

– Disease specific measures – Clinical added benefit (e.g., Germany, France); IQWIG in Germany uses

categories: • major; considerable; minor; unquantifiable; no; less • Each defined in more detail, e.g., “major added benefit” means

“recovery from disease, significant extension of life, long-term freedom from severe symptoms”

• That definition is then operationalized as part of the development of the HTA for a specific technology

– Quality of life (QoL) measures applicable over different conditions, e.g., EQ5D (England, Netherlands)

– Utility measures such as Quality Adjusted Life Years (QALYs), derived from QoL measures

• Integral of changes in length and quality of life, weighted to reflect empirically derived utilities for different states of health

HTA methods (2) • Assessing value for money

– Utility based systems can calculate incremental cost per utility gained, e.g., cost per QALY

– This can be compared to cost-utility of other known options for spending, either specific alternative treatments, or known or assumed cost-utility of overall use of budget – a cost utility threshold – to ensure opportunity costs are likely to be less than benefits being gained

– Clinical added benefit systems can compare the added cost with the degree of added benefit. France uses cost-utility analysis or cost-effectiveness analysis. Germany uses an “efficiency frontier” method (specific to condition).

• Making coverage and pricing decisions – This involves judgment and discussion/negotiation in all systems – Elements not formally considered in assessments are factored in – In QALY based systems, the cost per QALY and threshold are used as a

guide, not a rigid algorithm

Decision on directives

Commissioning

Recommendation

(Federal Joint Committee)

Legal Supervision

(Federal Ministry of Health)

Social Code Book (SGB) provides legal framework

Health services funded by statutory health insurances (coverage ~90% of German population)

§139 SGB V

Appraisal Assessment

Actors in the German system

Adapted from: B. Wieseler, IQWiG

HTA process in Germany

HAS Sept 2011

HAS: HTA guidance

CEPS Economic Committee for

Healthcare Products

NHI Union (mandatory and

voluntary )

Ministry of Health, M. of Social Security

L I S T I N G

Decision

Price

Copayment Level

Actors in the French system

http://www.has-sante.fr/portail/index.jsp

Clinical aspects

• clinical efficacy

• clinical effectiveness

• relative effectiveness

Other aspects • disease characteristics

• target population

• impact on public health

• impact on healthcare organisation (qualitative)

Actual Benefit

Sufficient

Insufficient

Clinical added value

No CAV(V)

Minor CAV (IV)

No reimbursement

Reimbursement only if price inferior to comparators

European Price

Dimensions Criteria Results

P R I C I N G

HTA: HAS Guidance Decision: Ministry Pricing:

Economic Committee

Initial listing: From HAS guidance to CEPS pricing (slide from HAS)

Price may be higher than comparators High to

moderate CAV(I,II,III)

HAS Sept 2011

Link between guidance and decision (slide from HAS)

HAS Guidance

Added clinical benefit (ASMR)

Target population

Request for additional study

Price

Price – Volume agreements

Risk sharing agreements

IQWiG HAS Major added benefit Essential therapeutical progress Considerable added benefit Significant improvement Minor added benefit Moderate improvement Non-quantifiable added benefit Minor improvement No added benefit No improvement Less benefit Benefit: not sufficient

Results IQWiG Results HAS Results Pharm. Company

Decision G-.BA

Vemurafenib Ipilimumab Rilpivirin Belatacept Emtricitabin/Rilpivirin/Tenofovir Apixaban Eribulin (no data for harm) Telaprevir Cabazitaxel Fingolimod Abirateron

Boceprevir Ticagrelor

HTA and decisions in Germany and France (taken from joint presentation by IQWIG and GBA)

NICE process in England • Technology(ies) for assessment selected and issues/questions scoped • Information sought from manufacturer(s)/sponsor(s) • Evidence Review Group (ERG) report commissioned from independent

academic centre • Appraisal Committee considers:

– ERG report and comments on it; written submissions; patient expert personal statements; clinical specialist personal statements

• Appraisal Committee produces – Appraisal Consultation Document (if restricting access) – Final Appraisal Determination (FAD)

• FAD issued as NICE Guidance (unless appeal lodged and upheld) • Decisions are based on cost/QALY with threshold c£20-30k




effectiveness/cost-utility/value for money – Snapshots of England, France and Germany


Origins and role of NICE • 1991 reforms created local “purchasers” of health care.

Responsibilities included setting priorities. • NHS HTA Programme launched in 1993 to review evidence to

inform decisions by purchasers, providers, clinicians and patients • Public and political concern at differing decisions and “post-code

prescribing” in a “national” health service • National Institute of Health and Clinical Excellence (NICE)

established in 1999: – National guidance on key technologies referred by Ministers – Guidance based on clinical and cost-effectiveness – Stated aims did NOT include cost reduction and NICE does not

look at budget impact – Stated aims DID include promoting innovation – Expectations of consultation, transparency and rights for input,

challenge and appeal

Perceptions and impact of NICE • Industry initially hostile but now see NICE as better model for HTA

than most others. Negative guidance can still be hotly contested, and industry would like to see more rapid and consistent implementation of NICE guidance

• Patient groups and press frequently hostile. Negative guidance often hotly contested. Understanding and support in general public may be more positive

• NHS managers ambivalent – some like having difficult decisions made centrally, but many resent impact on their ability to set priorities and manage budgets.

• Various reports suggest slow uptake of guidance across NHS

Related policy developments • Various responses to media/public/industry concern about access

to expensive drugs: – 2009 “End of Life” criteria for cancer drugs; higher ICER if

• small patient population, short life expectancy (<2 years), extension of life expectancy (>3 months), no alternative treatment

• 12 positive recommendations for 44 drugs considered – Patient Access Schemes (PAS)

• Introduced in PPRS review in 2009 • 2011 review of PAS reported 17 to date

– Cancer Drugs Fund • Introduced in 2011 and recently extended to 2015 • £200m pa to fund cancer drugs “not yet approved by NICE”

– Transfer of review of ultra-orphans to NICE in 2013 – Value-Based Pricing of pharmaceuticals – from 2014

Conclusions • European health systems operate within tightly limited budgets • HTA is used by many to help manage spending on drugs and some

other technologies and ensure it delivers value for money • Health and political systems vary between countries, and so do HTA

policies, systems and methods • NICE is widely regarded internationally as a model for QALY-based

systems, but it is not typical of some other major economies in Europe

• NICE methods, transparency and conclusions can lead to intense public criticism of NICE and politicians

Advertisement • Health Technology Assessment International is the international

professional society for those doing and using HTA in the public, private, not-for-profit and academic sectors

• Next Annual Scientific Meeting is in: Washington DC, June 15– 18, 2014 • See www.htai.org

Thank you This presentation will be made available by the meeting

organisers

I am happy to respond to questions during and after the meeting

Chris Henshall

[email protected]

Are the Europeans Doing a Better Job Evaluating Drugs than US P&T Committees?

The Gap Between CER and HTA

Lou Garrison, Ph.D. University of Washington

Premera Value Assessment Committee

Acknowledgments/Disclaimers • Disclaimer: One personal view of one US plan • Acknowledgments:

– John Watkins, Premera – Dan Danielson, Premera – Premera Value Assessment Committee – Cate Lockhart—Apixaban Premera Analysis

Health Technology Assessment and Value Health technology assessment (HTA) is the structured analysis of health care technologies—medicines, vaccines, medical devices, diagnostics, healthcare procedures, and health systems—performed for the purpose of providing input into regulatory, coverage/formulary (including essential medicines lists), and/or reimbursement policy decisions. (OHE/UW, 2012) What is “value”? •Problem—public perception of “cheapness” •Economic view: “what fully informed consumers would be willing to pay.” •One interpretation: cost-effective

82 An independent licensee of the Blue Cross Blue Shield Association

Health Technology Assessment at Premera: A “Value-Based” Formulary (VBRx)

• Premera has embraced the concept and term “value-based formulary”

– This is despite some of the controversy around “value-based insurance design”

– Note that: ACA mentions VBID • Premera Value Assessment Process • VBRx Experience to date

Purpose: To describe Premera’s technology assessment process and experience to date with its value-based formulary.


Scope of the Problem

• Typical plan sponsor responses – change benefit designs

• Increase member cost shares • Adopt consumer-directed benefits and Health Savings Accounts

– Increase emphasis on • Member accountability for their own health • Health coaching, enhanced disease management and wellness programs with

positive and negative incentives • Primary and secondary prevention to reduce costs and improve members’health

Rapidly rising Rx benefit costs; specialty drugs a major driver

Without proper member support; can have negative effects on adherence, driving up total health care costs


Traditional Pharmacy Benefits

• Traditional Formularies based on what a drug is: – Brand or Generic? – Preferred or Non-Preferred

• Only value judgment applied to certain brand drugs – If designated equivalent Lowest net unit cost

20th century solutions to 21st Century crisis


A More Comprehensive Technology Assessment Strategy

• Earlier value-based pharmacy benefits focused on eliminating copays for high-value diseases, not specific drugs

• Premera’s VBRx separates high value drugs from low value ones.

Incent use of high value therapies; discourage use of low value ones

Strategies to

discourage Most cost-effective care

Least cost-effective care Strategies

to encourage

- Fendrick AM, Smith DG, Chernew ME. Health Affairs 2010;29(11):2017-2021.


What is Value?

“… value in health care relates to whether a medical intervention (drug, device, program, surgery)… improves health outcomes enough to justify additional dollars spent compared to another intervention.”

– Academy of Managed Care Pharmacy Format Executive Committee (2004)


Value-Based Formulary Principles—Considering Comparative Effectiveness and Cost • Objective

– Develop a new type of formulary based on incremental comparative effectiveness

– Clinical value/cost focus

• Strategy – Achieve higher quality health care from the health care dollar

• Guiding Principles – Evidence-based – Internal and external decision-making committee – Leverage input from practicing physicians and other providers – Transparent processes – Use healthcare economic data


Pharmacy & Therapeutics Committee

Value Assessment Committee

How is value determined? Value Assessments occur after P&T’s detailed clinical review

• Effectiveness • Safety • Drug cost (last consideration)

Clinical Benefit

• Comparative Effectiveness • medical cost • quality of life/productivity • life years gained

Cost/Benefit

• Preferences • Equity • Endo of Life

Societal Values


Technology Assessment Process


VBRx Implementation

•Drugs Tiered based on Incremental Cost Effectiveness Ratio (ICER)

•Exceptions may be made in certain cases

Detailed Economic

Review

•Research scoping •Evidence synthesis •VAC Committee

Review

Preliminary Economic

Assessment

•Assess Economic Evidence

•Monitor •Do not review

Detailed Clinical Review

•Research scoping •Evidence synthesis •Peer Review •P&T Committee

Review

Preliminary Assessments

•Queue for full clinical reviews

•Monitor •Do Not Review

Pipeline Surveillance

•Premera’s Market Watch

•Industry pipelines •PBM reports •Industry press

Value-Based Formulary is integrated

• From pipeline surveillance through implementation of formulary decisions, we use one holistic process

Into Premera’s Health Technology Assessment process

Tiering is not just the end product of a calculation


HTA-Based Formulary

Focus in on Economic Review Process

VBRx Implementation

• Extenuating clinical or societal circumstances

Detailed Economic

Review

• Detailed evidence review • Model specification (reverse

engineering) • Model build, run and sensitivity

testing • Evidence synthesis and

monograph creation • Peer review • VAC presentation

Preliminary Economic

Assessment

• Are there CEA’s in the peered reviewed literature?

• Is there a credible US-focused manufacturer model available?

• Is there sufficient evidence to reverse engineer an existing model and modify to US-focus?

• Is it worth the effort?


Finding economic information

• Center for the Evaluation of Value and Risk in Health (CEVR, Tufts University) CEA Registry

• National Institute for Health and Care Excellence (NICE) • PubMed.gov • Manufacturers Models • Value Assessment Committee Members

Credible sources


Who will determine value?

Independent committees make clinical and value assessments:

• Pharmacy & Therapeutics Committee – 7 MDs, 3 pharmacists, 1 lay member – no Premera associates

• Value Assessment Committee – Sean Sullivan, PhD, RPh Pharmaceutical Outcomes Program Director,

UW School of Medicine – Scott Ramsey, MD, PhD, Practicing Internist and Health Economist,

Fred Hutchinson Cancer Research Center – 1 PhD, Bioethics, UW – 2 PhD, Pharmacoeconomists, UW – 1 Community-based oncologist – 1 Lay member, Benefits Manager, large WA-based company


How Are Value-Based Formulary Tiers Assigned?

Standard Thresholds*

Tier 1: Highly Cost-effective: <$10,000/QALY

Tier 2: Cost-effective: <$50,000/QALY

Tier 3: Somewhat cost-effective: <$150,000/QALY

Tier 4: Minimally cost-effective: >$150,000/QALY, or insufficient evidence to determine cost-effectiveness *Tier thresholds are explicit but flexible. A “preventive list” similar to those used by

other plans is included with VBRx. More liberal thresholds are applied to ultra-orphan drugs.


Formulary Tiers and Copays


Interaction with Drug Manufacturers

• Modeling requirements for submission of new drugs:*

– Transparent – Evidence-based – Disease-based, including medical cost-offsets – Clinically appropriate – Identifying cost-effective patient subgroups

• We thank the following manufacturers for working with us: – Novartis – first to adapt a European model for us – BMS, Amgen, Lilly, Sanofi-Aventis – Others showing interest

*AMCP Format for Formulary Submissions, v.3.1, sect. 4. (http://www.amcp.org/format/pub.pdf)


Premera New Formulary Experience


Member Experience

• Impact of cost shift: – High utilizers: some copays decreased; a few increased – Low utilizers generally experienced higher out of pocket costs

• Members’ reported response to higher copays: – Ask MDs to prescribe lower cost drugs – Pay the higher cost, continue same medications – Skip medications cut tablets, etc. (only one individual mentioned this)

• Generally positive reaction to value-based formulary concept: – An evidence-based approach – An effort to hold down rising costs – Having consumers take more responsibility for their health – Perception that the employer cares and is trying to help with Rx costs – Want to know who determines the value of drugs


Plan PMPM Savings 7/2010 – 6/2011

• Interrupted Time Series Analysis: – 36 months prior to

implementation were used to forecast PMPM for 7/2010–6/2011

– adjusted downward to account for observed decrease in the trend using actuarial data

– Savings were measured as the difference between the forecast and actual PMPM

• Results (Rx $ PMPM): – 10-11% projected savings – 3.25% actual reduction

from 2009-10 benefit year – 8% Rx Trend (Premera

BOB) – 6% increased utilization of

high value drugs


Cost-Shifting and Adherence in Selected Subgroups

No significant decrease in utilization or adherence was observed in any of the target drug classes.

Premera Associates relative to an external comparison group: • Utilization and adherence increased significantly in the hypertension patient

group • Other patient group differences were not statistically significant • VBRx permitted a 12% overall cost shift to members with no reduction in

adherence in these high value drug classes

Population Average Cost Shift %*

Overall Group Members 12%

Diabetes Patients 5%

Hypertension Patients 8%

Dyslipidemia Patients 2% * Includes all medications prescribed for each patient in the group.

Case Study— Eliquis (apixaban) for

Nonvalvular Atrial Fibrillation

Background—Disease/Product Background • FDA approved apixaban (Xa inhibitor) in December 2012 • Indication: “anticoagulant indicated to reduce the risk

of stroke and systemic embolism in patients with nonvalvular atrial fibrillation.”

• Competitors: warfarin, dabigatran, rivaroxaban • Epidemiology—prevalence of about 5 million in US • Epidemiology—clinical—increases risk of stroke 5-fold

Background—Clinical Results

Background—Economic Evaluations

Cost-Effectiveness Model—Premera Constructed

Comparative Efficacy

Premera CEA Results

VBRx Formulary Placement—Novel Oral Anticoagulants

• Apixaban: Tier 2 • Dabigatran: Tier 2 • Rivaroxaban: Tier 2 • Warfarin: Tier 1

Thanks! Questions?

Assessing the Value of new Drugs

Professor Peter Littlejohns

King’s College London 1999-2012 Founding Clinical and Public Health

Director NICE

Summary of Presentation

• Set context - common challenge

• Defining “value(s)” and role of NICE

• Specific appraisal examples

A common challenge

All health care systems are facing the challenge of ensuring that high quality care is provided to all those who need it, at a cost that the country can afford.

This comes at a time when people are living

longer, have increasing expectations of what care should be provided, and when the speed of health care innovation continues to offer ever greater options for intervention.

Because no country can afford to provide all its

residents with every possible medical or public health intervention, all health systems are facing the problem of how to set priorities in the allocation of health care resources.

Money is not everything

A new approach?

One way to deal with the priority-setting challenge is to pursue ever more rigorous assessments of comparative clinical effectiveness ( what works) and cost effectiveness (value for money). The NHS has well developed systems for carrying out such assessment. However There is no reason to think that all hard trade-offs can be avoided by greater efficiency in the use of resources, these apparently technical analyses are not only technical. They also contain social value judgments about, for example, how much quality of life is sufficient to make an intervention value for money, how that quality of life should be measured and even if some lives are worth more than others.

The value of evidence or evidence of value?

Procedural Justice

Provides for ‘accountability for reasonableness’. For decision-makers to be ‘accountable for their reasonableness,’ the processes they use to make their decisions must have four characteristics

The National Institute for Health and Care Excellence (NICE)

NICE is the independent organisation responsible for providing national guidance on the promotion of good health and the prevention and treatment of ill health. The National Institute for Clinical Excellence was established in 1999 as a NHS Special Authority. In 2005 it was expanded to include the public health functions of the Health Development Agency to become the National Institute for Health and Clinical Excellence In 2013 it became the National Institute for Health and Care Excellence and its remit was expanded to cover social care. It left the NHS to become a non departmental public body.

The Institute encourages cost effective practice by issuing guidance

NICE Principles underpinning all its programmes

http://www.nice.org.uk/

http://www.nice.org.uk/

NICE's approach to economic evaluation

On its own (comparative) clinical effectiveness is insufficient for maintaining or introducing any clinical procedure or process.

Cost must also be taken into account. When good evidence exists of the therapeutic

equivalence between two or more clinical management strategies, the cheaper option is preferred.

However, in most instances NICE is confronted

with a clinical management strategy that is better than current standard practice but which costs more. NICE must then decide what increase in health (compared with standard practice) is likely to accrue from the increase in expenditure. This is the incremental cost effectiveness ratio

Justification for using a Quality Adjusted Life Year (QALY)

• Allows all treatments to be judged the same • It is a unit of health gain • QALY calculated by how much the treatment improves the

utility (health) and how long it works (years) • If a treatment really improves the health (utility) and has a

long lasting effect it produces lots of QALYs • How much does it cost to get one extra QALY for the

patient group? (cost per QALY)

Value of a QALY

What is meant by utility ? • Utility = how well you are (QOL) • 0 - 1 • 0 is dead • 1 is full health • Age 80 = 0.75 • Moderate Stroke = 0.39 • Flu = 0.07 on day 1, 0.61 on day 5 • Coma = 0.0162

The NHS Threshold

• How must does it cost to get one QALY more than with existing treatment? ie cost per QALY

• Under £20,000 per a QALY is cost effective • £20,000-30,000 may be cost effective • Over £30,000 - needs to be justified on other

grounds (exclusivity and/or severity of disease) • End of life criteria: If patient is likely to die

within 2 years and treatment gives 3 months extra life – threshold increased up to £50,000)

NICE’s underlying social values

Principle 1 – evidence NICE should not recommend an intervention (that is, a treatment, procedure, action or programme) if

there is no evidence, or not enough evidence, on which to make a clear decision. Principle 2 – value for money Those developing clinical guidelines, technology appraisals, or public-health guidance must take into

account the relative costs and benefits of interventions (their cost-effectiveness) when deciding whether or not to recommend them.

Principle 3 - fairness Decisions about whether to recommend interventions should not be based on evidence of their relative

costs and benefits alone. NICE must consider other factors when developing its guidance, including the need to distribute health resources in the fairest way within society as a whole.

Principle 4 – provide explanation NICE should explain its reasons when it decides that an intervention with an ICER below £20,000 per QALY

gained is not cost effective; and when an intervention with an ICER of more than £20,000 to £30,000 per QALY gained is cost effective.


Principle 5 – limits of autonomy Although NICE accepts that individual NHS users will expect to receive treatments to which

their condition will respond, this should not impose a requirement on NICE’s advisory bodies to recommend interventions that are not effective, or are not cost effective enough to provide the best value to users of the NHS as a whole.

Principle 6 – consultation but not consensus NICE should consider and respond to comments it receives about its draft guidance, and

make changes where appropriate. But NICE and its advisory bodies must use their own judgement to ensure that what it recommends is cost effective and takes account of the need to distribute health resources in the fairest way within society as a whole.


Principle 7 – non discriminatory NICE can recommend that use of an intervention is restricted to a particular group

of people within the population (for example, people under or over a certain age, or for women only), but only in certain circumstances. There must be clear evidence about the increased effectiveness of the intervention in this subgroup, or other reasons relating to fairness for society as a whole, or a legal requirement to act in this way.

Principle 8 – reduce inequalities When choosing guidance topics, developing guidance and supporting those who

put its guidance into practice, [NICE] should actively consider reducing health inequalities, such as those associated with sex, age, race, disability, and socioeconomic status.


• Set context - common challenge

• Defining “value(s)” and role of NICE • Specific appraisal examples

Apixaban for preventing Stroke

Summary of Appraisal Committee's key conclusions (i)

Implementation issues

Local implementation (i)

Local Implementation (ii)

Thank you for listening

“Those are my principles, and if you don't like them.......... well, I have others. Groucho Marx US comedian with Marx Brothers (1890 - 1977)

Panel Discussion

How is Value Determined?

ACO Staying Power—Will ACO and MCO Success Depend on New Risk Paradigms for

Specialty Drugs?

Robert W. Dubois, MD, PhD Chief Science Officer

Topics For Today • Ex-US HTAs determine when interventions are

worth paying for • US payers perform somewhat similar

assessments

My Topics • Providers are assuming more risk • The ESRD bundling program provides lessons • A framework for medications in bundled

payment • ACOs are not ready to manage medications • Industry may share the risk

Risk Shifts Towards The Provider

Payer

Provider

Compared to today’s payers, how well will ACOs manage medications?

A – Significantly better than payers B – Somewhat better than payers C - About the same D– Somewhat worse than payers E – Significantly worse than payers

144

My Topics • Providers are assuming more risk

• The ESRD bundling program provides lessons

Implementation of the new bundled payment system was consistent with our 2006 recommendation that the bundled payment be expanded to include payment for all ESRD services to improve efficiency and remove financial incentives to provide more injectable drugs than necessary.

” GAO Tracks Decline in ESA Use Following Regulatory Changes” Scott Steinke, The Pink Sheet DAILY, December 12, 2012

151

ESRD Payment policy changes: the new “bundled” dialysis prospective payment system in the US; Allan Collins, MD Director, United States Renal Data System Coordinating Center;

www.usrds.org/2012/pres/USDialysisBundle_impact_NKFCM2012.pdf

152

Analyses of data from the U.S. Renal Data System, show that the proportion with a transfusion increased from 2.4% in September 2010 to 3.0% in September 2011 (a 24% increase)

My Topics • Providers are assuming more risk • The ESRD bundling program provides lessons • A framework for medications in bundled payment

Siloed Resources Must Merge

Silos and FFS ACO OPPORTUNITY

Premier-AMGA-Dartmouth-NPC ACO Collaboration

Develop Framework

Assess Readiness

Identify Gaps

Develop Toolkit

New Payment Approaches Can Incorporate the True Value of Pharmaceuticals

Condition

Cost for Episode of Care Quality Benchmarks

Pharmaceutical Share of Costs

Cost Offsets from

Pharmaceuticals

Direct Measure of

Pharmaceutical Use

Indirect Impact of

Pharmaceuticals

Heart Failure Modest Impact on

re-hospitalization

Compliance with therapy

% of patients requiring re-hospitalization

Rheumatoid Arthritis High Minimal None

157

My Topics • Providers are assuming more risk • The ESRD bundling program provides lessons • A framework for medications in bundled payment • ACOs are not ready to manage medications

ACO Readiness Assessment

ACO Type % Integrated delivery system

37%

Hospital system- 20%

Physician practice 30%

Other 13%

Size (# MDs) % <50 9% 50-100 6% 100-300 28% 300-1000 33% >1000 24%

N=46 50% Medical Directors; 50% Pharmacy Directors

Respondent Profile

What ACOs Are Doing Well

% of Respondents Indicating Practice is Currently in Use N=46

What ACOs Are Sort Of Doing Well

N=46 % of Respondents Indicating Practice is Currently in Use

What ACOs Are Not Doing Well Quality/Financial Metrics


Care Protocols


What ACOs Are Not Doing Well

Provider Engagement


What ACOs Are Not Doing Well

My Topics • Providers are assuming more risk • The ESRD bundling program provides lessons • A framework for medications in bundled payment • ACOs are not ready to manage medications • Industry may share the risk

Payers

Providers

Industry

Sharing Risk More Broadly

Growth in Risk-Sharing Agreements is Slowing

0

20

40

60

80

100

120

140

160

180

200

1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013

Num

ber o

f Sch

emes

Cumulative RSAs by Year

CED PLR CTC FU

CED: Coverage with evidence development; CTC: Conditional treatment continuation; PLR: Performance linked reimbursement; FU: Financial or utilization based agreements

Provided by L Garrison, Univ Washington

Januvia and Janumet (Merck) for Diabetes and CIGNA

1. CIGNA assessed the blood sugar levels (A1c lab values) for pts on any oral antidiabetic medications.

• If the A1c values, in aggregate, improve by the end of the agreement period, the discounts will increase by a pre-agreed amount.

2. CIGNA used claims data to determine if patients were taking Januvia and Janumet as prescribed

• Merck will further increase the discounts

3. Better placement on CIGNA’s formulary + lower copayment versus that for other branded drugs.

Risedronate (Proctor & Gamble, Sanofi-Aventis) for Osteoporosis and Health Alliance

• Reimburse the insurer for the costs of treating non-spinal fractures

• Hip and wrist fractures cost approximately $30,000 and $6,000, respectively.

How likely is it that industry will share episode cost risk?

A – Very likely B – Somewhat likely C - Somewhat unlikely D– Very unlikely

Will ACO and MCO Success Depend on New Risk Paradigms?

COST

QUALITY

ACO and MCO Success WILL Depend on New Risk Paradigms

COST QUALITY

Website: www.npcnow.org Twitter: @npcnow

Facebook: facebook.com/npcnow

HTA’s “Is It Worth It” and the Ethics of Oncology Decision Making.

European vs. US and Which Will Prevail?

Mirta Millares, PharmD, FCSHP, FASHP Manager, Drug Information Services &

Pharmacy Outcomes Research Kaiser Permanente

Acknowledgments • Jennifer T Chang, PharmD, MPH, BCPS

– Pharmacist Evidence Analyst & Strategist, KP Drug Information Services, CA Regions

• TPMG Regional Pharmacy & Therapeutics Committee • SCPMG Regional Pharmacy & Therapeutics Committee • TPMG Chiefs of Oncology • SCPMG Heme/Onc Committee; Regional Cancer Comm • Pharmacy Outcomes Research Group (PORG)

– Jim Chan, PharmD, PhD – Rita Hui, PharmD, MS – Michele Spence, PhD

Objectives • Detail a formulary decision-making process that

incorporates CER. • List common features of a new drug that are

included in a drug monograph and are evaluated by a P&T Committee.

Pre-Test Question 1

Starting January 2014, pharmaceutical manufacturers will be required to submit comparative effectiveness research (CER) data to the FDA for all New Drug Applications (NDAs)? 1.True 2.False

Pre-Test Question 2

In order to be useful for formulary decision-making, CER data must be available at the time of drug approval? 1.True 2.False

Kaiser Permanente • Integrated health care system

– Kaiser Foundation Health Plan Inc., – Kaiser Foundation Hospitals – The Permanente Medical Groups

• 9.1 million members • Staff model • 35 hospitals • 611 outpatient facilities • >17,000 physicians

182

Kaiser Permanente Formulary Process • Permanente Medical Group

P&T decisions • Collaboration between

medical group and pharmacy • >95% F prescribing • Open NF exception process

based on medical necessity • Electronic medical record

– Outpatient – Inpatient – Clinic (in progress) – Beacon (oncology)

183

Formularies Commercial Medicare Part D ACA Exchange

Medications provided or administered to commercial plan members in KP patient care settings (clinic, inpatient, outpatient)

Maintained under authority of Regional P&T Committee

National - Outpatient Medicare Prescription Drug Benefit.

Maintained by the KP Interregional Medicare Part D P&T Committee

Subject to CMS regulations

New, Jan. 1, 2014

Affordable Care Act (ACA) Exchange Formulary

KP CA maintained under authority of TMPG and SCPMG Regional P&T Committees

Subject to federal & state regulations

Regional National Statewide

KP Formularies

KP Formulary Process Identify Drug for Review FDA Drug Approval Permanente Chiefs Group,

Task Force Significant new data

Cost, Contracting Efficacy or Safety




DIS Evidence Analysis Manufacturer, AMCP Dossier PubMed Systematic Reviews Clinicaltrials.gov Meeting abstracts FDA Medical Review document




Additional data Cost, contracting Population data Utilization data Decision model





Drug Monograph



KP Formulary Process Drug Monograph (selected) Drug Monograph Appendices (selected) FDA Approval Information Clinical Trial Analysis Issues to be Determined Current Therapeutic Modalities Efficacy Summary Disease State Review Safety FDA Review History Other Considerations REMS Summary Special Populations Potential Off-Label Uses Pharmacology, MOA, dosing, storage Comparative Cost of Therapy Projected Role in Therapy


Task Forces Significant new data



Drug Monograph


Permanente Med Group Chiefs of Service Specialty consultants

Multidisciplinary groups Task Forces Advisory Committees Guideline Groups

Service Area P&T Committees Individual physicians,

other providers




DIS Evidence Analysis Manufacturer, AMCP Dossier PubMed Systematic Reviews (e.g.

Cochrane Collab, AHRQ, etc.) Clinicaltrials.gov

Drug Monograph


Permanente Med Group Chiefs of Service Specialty consultants

Multidisciplinary groups Task Forces Advisory Committees Guideline Groups

Service Area P&T Individual physicians,

other providers

KP Formulary Process

Drug Monograph With recommendations

from DIS, Permanente Med Group, Service Area P&Ts

•Formulary •Non-Form •Tiers (MPD)

Formulary Status

•Restrictions •Guidelines •Limited quantities •Re-review date

Additional Status

•Decision Support

EHR

•MUE •Utilization data •CER

Other recommendations

KP Regional P&T Committee

KP Formulary Process: Post P&T Review – CER, Utilization

• Integrated health care system and EHR provide opportunity to gather real world outcomes data in our population.

• In addition to comparative efficacy, CER can provide institution-specific data on – Medication adherence and persistence – Adverse events – Subpopulations – Resource utilization – Total health care cost

KP Formulary Process: Post P&T Review – CER, Utilization

• CER data can be used to – Support, repeal, or modify formulary status – Inform contracting – Identify subpopulations – Identify safety issues – Inform prescribing

KP CER Example: Boceprevir and Telaprevir • Approved late 2011 • RCTs vs best available therapy; no boceprevir vs

telaprevir CER • Contracting potential • KP IR Hepatitis Workgroup

– guideline development – PORG CER Study

• Formulary status with implementation date pending future recommendations

• Drug Use Management

BOCEPREVIR VS. TELAPREVIR IN HEPATITIS C INFECTIONS

Jim Chan, PharmD, PhD Rita Hui, PharmD, MS Michele Spence, PhD Mirta Millares, PharmD

Pharmacy Outcomes Research Group Drug Information Services

KP CER Example: Boceprevir and Telaprevir

KP CER Example: Study Purpose

To evaluate the relative effectiveness of boceprevir and telaprevir in genotype 1 hepatitis C infection in KP California

– Phase 1 : early indicators of comparative effectiveness and safety

– Phase 2: SVR and development of a predictive model based on patient characteristics and treatment selection

KP CER Example: Study Design and Setting

•Concurrent data collection •Retrospective cohort analysis •Population

–all patients initiated on boceprevir or telaprevir

•Data sources –KPNC and KPSC –Legacy data and HealthConnect

KP CER Example: Measurable Outcomes • Patient groups:

– Treatment naïve vs. previously treated

• Proportion of patients with early virologic response (EVR) and sustained virologic response (SVR)

• Proportion of patients who had early discontinuation due to futility rule • Proportion of patients who had early discontinuation due to apparent

intolerance • Proportion of patients with anemia and proportion prescribed EPO • Cost effectiveness analysis • Compliance to recommended algorithm for dosing and monitoring • Estimate preventable and non-preventable wastage

KP CER Example: Outcome Measures for Early Interim Analysis

• Primary – Proportion of patients who reached early undetectable viral

load (<615 IU/mL for KPNC and <43 IU/mL for KPSC)

• Secondary – Proportion of patients with an initial 2 log drop in viral load – Proportion who discontinued treatment – Proportion who initiated treatment with erythropoietin

KP CER Example: Early Interim Analysis • Proportion of patients reaching early undetectable viral load not

significantly different – TEL earlier with BOC catch-up with treatment completion – Greater difference was between regions, not drug

• Proportion of patients with an initial 2 log drop in viral load – Trend for TEL, NS

• Proportion who discontinued treatment – NS

• Proportion who initiated treatment with erythropoietin – Significantly higher for BOC

• Consequences: – Evaluation of care management differences – Guideline endorsement – Coordinated care management

Case Study: Ruxolitinib

http://www.incyte.com/pressroom/jakafipresskit Jakafi (ruxolitinib) Press Kit

http://www.incyte.com/pressroom/jakafipresskit

Case Study: Ruxolitinib • US FDA approval Nov 2011 • FDA rating: 1 = New molecular identity; P = Priority

review • First-in-class JAK (Janus associated kinase) inhibitor • FDA approved indication:

– for treatment of patients with intermediate- or high-risk myelofibrosis (MF), including primary MF, post-polycythemia vera myelofibrosis (PPV-MF) and post-essential thrombocythemia myelofibrosis (PET-MF).

• Oral: 5 mg, 10 mg, 15 mg, 20 mg and 25 mg tablets • Approximately $7,000 per month

Case Study: Ruxolitinib Available data: 2 PIII trials: 1 PC RCT, 1 OL RCT compared to BAT

– Verstovsek S, Mesa RA, Gotlib JR, et al. Results of COMFORT-I, a randomized double-blind phase trial of JAK 1/2 inhibitor INCB18424 (424) versus placebo (PB) for patients with myelofibrosis (MF). J Clin Oncol. 2011;29. Abstract #6500 and Oral Presentation at American Society of Clinical Oncology Meeting in Chicago, IL 2011.

– Harrison CN, Kiladjian, Al-Ali K, et al. COMFORT-II. Results of a randomized study of the JAK inhibitor ruxolitinib (INC424) versus best available therapy (BAT) in primary myelofibrosis (PMF), post-polycythemia vera-myelofibrosis (PPV-MF) or post-essential thrombocytopenia-myelofibrosis (PET-MF). J Clin Oncol. 2011;29. Abstract #LBA6501 and Oral Presentation at American Society of Clinical Oncology Meeting in Chicago, IL 2011.

– Tefferi A, Litzow M, Pardanani A. Long-term outcome of treatment with ruxolitinib in myelofibrosis. N Engl J Med. 2011;365(15): 1455-57.

– FDA Drug Approval Package

Case Study Ruxolitinib: Myelofibrosis • Epidemiological data on MPDs are limited in general and not adequately

reported. – The incidence of primary MF is approximately 1/100,000 per year. – Incidence of secondary post-ET or post-PV MF are not well reported. – Life expectancy with MF varies from approximately two years to 11 years (median

survival 69 months in one report) • Currently no cure for MF except allogeneic stem cell transplantation. The goal

of treatment for MF remains palliative. • A number of agents have been used to control cytopenias in MF, including

erythropoietin, danazol, thalidomide, thalidomide with steroids, and lenalidomide.

• Some agents have been used to target myeloproliferation in MF, such as the immunomodulatory drugs, hyroxyurea and alkylating agents.

• Splenectomy does not change the course of disease but may help control the symptoms of hypersplenism.

Case Study Ruxolitinib: Positives • Ruxolitinib (RUX) significantly reduced spleen size in two pivotal

Phase 3 trials (COMFORT 1 and COMFORT 2), achieving the primary endpoint of ≥ 35% reduction from baseline in spleen volume at 24 and 48 weeks compared to placebo and the best available therapy (BAT).

• COMFORT 2: – BAT included antineoplastics (51%) , hydroxyurea (47%) , glucocorticoids

(16%), epoetin alfa (7%), immunomodulators (7%), others. – Significantly more RUX received RBC transfusions; more became

transfusion dependent – RUX offers symptomatic relief based on the total symptom score

(abdominal discomfort, pain under the left ribs, a feeling of fullness in the abdomen, night sweats, bone and muscle pain and itching) and improved quality-of-life (improvement in appetite, insomnia, dyspnea).

Case Study Ruxolitinib: Positives • Oral treatment option for patients with MF and splenomegaly in

need of symptomatic relief. • This is a non-surgical option for patients; avoidance of surgical

intervention. • The manufacturer has committed to fulfill six post-marketing

studies including a long-term, 3-year follow-up on efficacy and safety outcomes of the COMFORT-1 and COMFORT-2 trials.

Case Study Ruxolitinib: Negatives • Ruxolitinib was approved by the FDA based on a surrogate

marker end point, reduction in spleen volume. • Ruxolitinib is not a cure for MF. Currently available data have not

shown an improvement in progression-free survival or overall survival in patients with MF.

• Long-term data not yet available. • Unclear whether ruxolitinib will improve anemia in transfusion-

dependent patients; moreover, some patients had worsening of anemia.

• Significant adverse effects include thrombocytopenia, anemia, neutropenia, active infection, and serious withdrawal effects (rebound thrombocytopenia and anemia).

• Significantly greater cost than off-label use of hydroxyurea.

Case Study Ruxolitinib: Expert Input • First in class JAK-inhibitor; first FDA-approved therapy to reduce

spleen size and improve symptoms. • A palliative option for patients in need of spleen reduction and

relief of constitutional symptoms. • Should be at least a second line option for patients with MF

especially in patients who have been on hydroxyurea with minimal change or worsening of painful spleen.

• There is a role for ruxolitinib in MF patients who are not transplant candidates.

Case Study Ruxolitinib: P&T Committee • Accepted, Restricted to Hematology/Oncology • Guidelines • BEACON protocol

– Provider reminders regarding safety and monitoring

• Utilization reporting – Safety – Guideline concurrence – Discontinuation

Case Study Ruxolitinib: Guideline • Ruxolitinib is reserved for patients with intermediate-or high-risk

myelofibrosis (MF), including primary MF, post-polycythemia vera myelofibrosis (PPV-MF) and post-essential thrombocythemia myelofibrosis (PET-MF). – Risk is defined by the presence of the following (Intermediate risk = 2

factors; High-risk = 3 or more factors): • Age 65 years • Hemoglobin level of <10 g/dL • White blood cell count >25 x 109/L • 1% circulating myeloblasts • Presence of constitutional symptoms

• Ruxolitinib is effective in patients with MF regardless of the JAK2V617 mutation status.

Case Study Ruxolitinib: Guideline • Dosing

– Recommended starting dose – Maximum restarting doses after dose interruption for thrombocytopenia – Dosing recommendations for thrombocytopenia – Dosage adjustments if response is considered insufficient – Discontinuation – Dose adjustments for use with strong CYP3A4 inhibitors – Dose adjustments for renal impairment – Dose adjustments for hepatic impairment – Laboratory monitoring

• Guideline Implementation strategy: – Incorporated protocol into oncology electronic order entry (BEACON) – Linked in to KP on-line formulary monograph

Question Review

1. An integrated electronic medical record (EMR) is a valuable resource for gathering data for formulary decision-making.

2. Starting January 2014, pharmaceutical manufacturers will be required to submit comparative effectiveness research (CER) data to the FDA for all New Drug Applications (NDAs).

3. In order to be useful for formulary decision-making, CER data must be available at the time of drug approval.

Assessing the Value of new Drugs (ii)

Professor Peter Littlejohns

King’s College London 1999-2012 Founding Clinical and Public Health

Director NICE


• Specific appraisal example

• Quantifying social value

Appraisal

Committee’s conclusions

Committee’s conclusions (ii)

Explicit Assessment of Social Values

The Committee considered ruxolitinib to be an innovative treatment for patients with splenomegaly and myelofibrosis The technology is a targeted treatment and offers a step change in treating splenomegaly because it manages symptoms for which there is currently no available treatment. The Committee considered whether high-risk patients could be considered to meet end-of-life criteria. The Committee acknowledged that there was uncertainty in the prognosis of high risk patients, because survival estimates ranged from a median of 1.3 to 2.3 years depending on the scoring system used. The Committee noted that the manufacturer had not demonstrated survival benefit in terms of additional months gained. The Committee concluded that it had not been provided with evidence that high-risk patients met the end-of-life criteria. The Committee discussed whether NICE's duties under the equalities legislation required it to alter or add to

its recommendations in any way. No equality issues within the scope of this appraisal were raised during the appraisal process or At the Committee meetings, and therefore the Committee concluded that no alterations or additions to its recommendations were needed.

End of Life Criteria

End of Life Criteria (ii)

Thank you for listening

Panel Discussion

Making Decisions Based on QALYs: Can It Work on

Both Sides of the Atlantic?

Panel Discussion

What Role Should AMCP Play in Spearheading Advances in CER, HTA,

Research Methodologies, Transparent Risk Arrangements, and

Formulary Decision Processes?

THANK YOU!

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