GPC-USA

FIRST ANNUAL MEETING

November 12th, 2013

Sean R. Tunis, MD, MSc. President and CEO

MEETING GOALS

Report and discuss progress since May 1 launch of

GPC-USA

Panel discussions on several interesting topics and

initiatives relevant to the work of GPC-USA

Discuss uptake and impact of EGDs: what does

success look like; how do we promote and measure

Explore potential future areas of work

GPC-USA UPDATE

GREEN PARK COLLABORATIVE - USA

• A multi-stakeholder forum to support dialogue and

consensus on methodological standards for clinical

research

‒ Focus on comparative effectiveness and value

‒ Informed by evidence expectations of patients,

clinicians and payers

• Primary outputs are “effectiveness guidance documents”

‒ Condition and technology-specific study design

recommendations for researchers

WHAT IS THE PROBLEM?

• “Because of the paucity of high quality

evidence, the data available – though

voluminous – may have little meaning or

value for informing clinical practice”

• Abernethy AP, Coeytaux RR, Carson K, et al. Technology assessment

report: report on the evidence regarding off-label indications for targeted

therapies used in cancer treatment. Agency for Healthcare Research and

Quality 2010

GPC – USA ORGANIZATIONAL STRUCTURE

GREEN PARK COLLABORATIVE – USA

GPC Advisory Committee

Chair: Sean Tunis, MD, MSc

Technical Working Group Place in Therapy

Chair: Anne Schott, MD

Technical Working Group Patient-Centered Outcomes

in Diabetes

Chair: Nisa Maruthur, MD, MHS

Oncology Consortium

Lead: Donna Messner, PhD

Endocrine – Metabolic Diseases Consortium

Lead: C. Daniel Mullins, PhD

GPC – USA ADVISORY COMMITTEE

Advisory Committee Structure

Gary Palmer Alexandra

Clyde Alan

Rosenberg James Murray

Sean Tunis

Chair

Mark

Skinner Amy

Abernethy Ethan Basch

Janet Corrigan

Ellen Sigal

Other

Payers

Life Sciences

Board Composition Key

Murray Ross

Lisa

Simpson/

Erin Holve

Lew Sandy

Ex Officio

FDA CMS PCORI NIH AHRQ VA Avalere

Bob

Temple

Patrick

Conway

Rachael

Fleurence

Michael

Lauer

Jean

Slutsky

David

Atkins

Tanisha

Carino

Murray

Sheldon

Louis

Jacques

Jason Gerson

Peter

Marks

Donna Cryer

ADVISORY COMMITTEE PRIMARY ROLES

Provides input on technical work of GPC-USA, including:

o Feedback on EGD topics and scope of EGDs

o Process for developing methodological standards

Advice on dissemination and mechanisms to promote uptake of

EGD recommendations

Communications

o Between AC members and broader GPC membership

o Inform/advise CMTP about related work

Helps identify new consortia, EGD topics, other GPC work

PANEL DISCUSSION

What are the Evidence Gaps Affecting Clinical Use of

Next Generation Sequencing Tests in Oncology?

Moderator: Patricia Deverka, MD, MS, MBE

Center for Medical Technology Policy

ANNUAL MEETING PANEL DISCUSSION

What are the Evidence Gaps Affecting Clinical Use

of Next Generation Sequencing Tests in Oncology?

Panelists: Robert Lechleider, Chief Scientific Officer

United States Diagnostics Standards, Inc.

Alberto Gutierrez, Director, Office of In Vitro Diagnostics

Center for Devices and Radiological Health, FDA

Sarah Zimmerman, Medical Science Liaison

Illumina

Gary Lyman, Professor of Medicine

Duke University School of Medicine and the Duke Cancer Institute

Elaine Jeter, Medical Director

Palmetto, GBA

11

DNA SEQUENCING COSTS

Wetterstrand KA. DNA Sequencing Costs: Data from the NHGRI Genome Sequencing Program (GSP) Available at: www.genome.gov/sequencingcosts. Accessed 9/16/13.

12

WHAT ARE THE DIFFERENCES?

First Generation

Sequencing (Sanger)

• Widely available

• Accurate, well-defined method

• Identifies linear sequences of

nucleotides (DNA fragments)

• Throughput is main limitation

• Would cost ~$5-30 million to

sequence human genome and

take 60 years (if using one machine)

Next Generation

Sequencing (Massively parallel)

• High throughput sequencing of large

numbers of different DNA sequences

in a single reaction

• Advantages are speed, breadth and

depth of coverage • Unclear whether claims of lower (total)

costs of testing are realistic

• Large volume of information

produced has shifted emphasis to

bioinformatics and data analysis

components, as opposed to

technical assay component to

generate data

13

GENOMIC SEQUENCING* AS A CONTINUUM

Whole genome sequencing

Whole exome sequencing

Gene panels

Single gene testing

*Inherited/germline vs. acquired/somatic

Clin

ical Utility

Dat

a vo

lum

e

14

NGS: WHAT ARE THE ISSUES?

• Need to distinguish discussions of

technology itself from discussions of

various clinical applications • NIPT

• Oncology

• Rare childhood disorders

• DTC

• Need standards for AV and CV in

addition to CU

• For many applications the results are

dynamic, not static • Reimbursement as well as ethical implications

• Complexity of issues argues for focusing

on near-term priorities • e.g., NGS testing in oncology

15

NGS TESTING IN ONCOLOGY

Redefining cancer

• Use NGS test to measure large number of molecular markers at

a single time

• Goal is to identify a treatment which targets the biological

pathway involving the marker

• Results in a different treatment that usually selected for patient

based on the type of cancer and its stage

• Choosing a treatment based on biological pathways rather than

tumor site or histology is hypothesized to be a better method of

selecting treatment

• Is this test a ‘bundle of markers’ or a new capability facilitating

comprehensive classification & management of tumors?

16

PAYER ASSESSMENT OF NEW TESTS

Analytic validity

Clinical validity

Clinical utility

Does the test accurately/reliablydetect analyte(s) of interest?

Is there a significant association between the test results and clinical phenotype?

Does use of the test lead to improved patient outcomes compared with the alternative? (test must impact clinical decision-making)

17

PANEL DISCUSSION

• Does this current framework apply to

NGS testing in oncology?

• How will payers, clinicians and patients be

confident in the analytic and clinical validity of

oncology tests?

• How will test results differ across different

platforms?

• What is the clinical significance of these

differences? Of known issues re error rates?

• What role should FDA play?

• Will the current definition of clinical utility

need revisiting given small numbers of

patients with particular genomic profile?

• What role can group like GPC-USA play

to facilitate evidence for informed

decision-making?

GPC-USA ONCOLOGY

CONSORTIUM

UPDATE

Donna A. Messner, PhD | November 12, 2013

Consortium team: Ellen Tambor, Srijana Rajbhandary

POLICYMAKERS & REGULATORS

RESEARCH FUNDERS

LIFE SCIENCES INDUSTRY

PATIENTS AND CONSUMERS

PAYERS AND PURCHASERS

HEALTHCARE PROVIDERS

RESEARCHERS

Eli Lilly and Company Foundation Medicine, Inc. Genentech, Inc. GlaxoSmithKline Merck Millennium Novartis US Diagnostic Stds

National Coalition for Cancer Survivorship The Avon Foundation Breast Center (JHU) Research Advocacy Network Patient Advocates in Research

Aetna BCBSA CMS United Health Group WellPoint

Veterans Affairs Kaiser Permanente

Duke University U of Michigan/SWOG Angiogenesis Foundation

ASCO FDA NCCN

NCI PCORI

ONCOLOGY CONSORTIUM AT A GLANCE

CLINICIANS

Community oncologists (pending)

PROCESS TO NARROW TOPIC LIST FOR DISCUSSION

Literature review,

analysis of evidence gaps

Creation of prospective

topic list

Narrowing of topic list for

in-depth consideration

20 phone calls with 23

people plus 2 written

comments

In-depth discussion of two topics in

inaugural meeting and group voting

DEC

ISION

SELECTED TOPIC: “PLACE IN THERAPY”

• For situations where multiple therapeutic options exist

and the optimal priority order (individual or in

combination) of administration has not been established

• Methodologic recommendations and data collection

strategies for efficient evaluation of the most beneficial

ordering of therapies for cancer patient management

• The recommendations will include consideration of

patient-centered preferences in tradeoffs between

effectiveness or other benefits vs. toxicity, cost,

convenience of administration, life style alterations

IMPORTANCE OF TREATMENT SEQUENCING

EXAMPLE: RENAL CELL CARCINOMA (RCC)

• Treatment Options RCC:

– Mid-2000s - Cytokine therapy was the treatment of choice for

mRCC

– December 2005 – February 2012 – 7 new agents approved for

the treatment of mRCC (sorafenib, sunitinib, temsirolimus,

everolimus, interferon/bevacizumab, pazopanib, axitinib)

NCCN GUIDELINES – KIDNEY CANCER

WHAT IS THE ‘EVIDENCE GAP’ IN TREATMENT SEQUENCING IN RCC?

• Recently approved products (except temsirolimus) were approved based on improvements in PFS.

• Oncologists can now sequence therapies from the available treatment options, however, there is a lack of H2H comparative evidence to enable their decision about which treatment option to select and the sequencing of different therapies.

• Limited comparative effectiveness evidence from clinical trials across multiple therapies has resulted in Oncologists relying on what is observed in clinical practice (“real world”) or retrospective studies.

PROCESS FOLLOWING TOPIC SELECTION

Assemble appropriate TWG

and designate chair

TWG helps to develop scope,

frames recommendations

in collaboration with consortium

Consortium provides input,

reviews recommendations

Recommendations finalized by CMTP

with TWG and consortium

DEC

ISION

DISSEM

INA

TION

September 2013

April 2014

TECHNICAL WORKING GROUP TARGET COMPOSITION

TWG Chair: Dr. Anne Schott,

U of Michigan, SWOG

Methodologist (PROs)

Methodologist (decision

modeling)

Methodologist (Registries ,

EHR, and data mining)

Patient (2)

Med center P&T (clinician,

pharmacologist)

Community practice

buying group member

Oncologists (2)

(community)

Oncology clinical trialist

GPC-USA ENDOCRINE-

METABOLIC CONSORTIUM

PROGRESS REPORT

Nisa M. Maruthur, MD, MHS | November 12, 2013

Consortium team: C. Daniel Mullins, PhD, Srijana Rajbhandary

POLICYMAKERS & REGULATORS

RESEARCH FUNDERS

LIFE SCIENCES INDUSTRY

PATIENTS AND CONSUMERS

PAYERS AND PURCHASERS

HEALTHCARE PROVIDERS

RESEARCHERS

Covidien Eli Lilly and Company GlaxoSmithKline Medtronic, Inc. Merck Novartis Sanofi

ADA National Alliance for Caregiving Individual patients

Aetna BCBSA Highmark Johns Hopkins Healthcare New Hampshire Medicaid United Health Group Wellpoint

The Johns Hopkins Hospital and Johns Hopkins Health System

Duke University HealthPartners Institute Johns Hopkins University MedStar Health Research Institute Universities of : Illinois, Maryland, Michigan

CDC Maryland Department of Health and Mental Hygiene

NIA PCORI

ENDOCRINE-METABOLIC CONSORTIUM AT A GLANCE

CLINICIANS

The Frist Clinic VA Maryland Health Care System

ENDOCRINE-METABOLIC CONSORTIUM

TECHNICAL WORKING GROUP MEMBERS (TO DATE)

Member Affiliation

Carolyn Alexander The Community College of Baltimore County

John E. Anderson, MD American Diabetes Association, The First Clinic

Vanita R. Aroda, MD MedStar Health Research Institute

Ranee Chatterjee, MD,MPH Duke University

Jon Eaton, MCP, MCSA Leach Wallace Associates, Inc.

Hugh Fatodu, RPh, MBA Johns Hopkins HealthCare

Felicia Hill-Briggs, PhD, ABPP Johns Hopkins Medical Institutions

Mary Muth Kats and Associates/Keller Williams

Robert E. Ratner, MD, FACP American Diabetes Association

Deneen Vojta, MD UnitedHealth Group

Consortium Lead C. Daniel Mullins, PhD University of Maryland School of Pharmacy

TWG Chair Nisa M. Maruthur, MD, MHS The Johns Hopkins University

EGD PROCESS: EMC-YEAR 1

Literature review,

analysis of evidence

gaps

CER Workshop

on Diabetes - October

2012

Preliminary draft recommendations;

TWG recruiting; early TWG

response to recommendations

Key Informant

Interviews -

Preliminary diabetes

topic

Discussion of draft recommendations

EMC Meeting

10/23/13

Refin

em

en

t

EGD PROCESS: EMC-YEAR 1

In-person TWG

meeting –

12/16/13

TWG refines EGD scope and

recommendations based on EMC input

EMC input/review of

recommendations

Recommendations finalized by CMTP

with TWG and Consortium; EGD

released

Refin

em

ent

DISSEM

INA

TION

December 2013

April 2014

EMC MEETING 10/23/13

SCOPE OF DIABETES EGD

• Focus on type 2 diabetes

• Focus on medication interventions

• Use PICOT framework rather than

focusing on PROs alone

• Devices deserve separate guidance

EMC MEETING 10/23/13

DRAFT RECOMMENDATIONS

Population

• Selection criteria should purposefully oversample targeted

populations

– including patients with advanced age, diverse race/ethnicity,

level of diabetes control, and co-morbid conditions

• Subgroup analyses for age, race/ethnicity, and HbA1c subgroups

should be conducted uniformly across studies using pre-defined

categories

– Age: <65 and ≥65 years

– Race: white, African American, Asian, Native American

– Ethnicity: Hispanic and non-Hispanic

– Baseline HbA1c: <8.0% and ≥8.0%

EMC MEETING 10/23/13

DRAFT RECOMMENDATIONS

Outcomes

• Evaluate patient-reported outcomes (PROs) in a

standardized fashion across studies using validated

instruments

– Domains: global health; physical health; mental health; and

social health

• Establish definitions for and measure clinically-relevant,

treatment- related weight change

• Provide credible evidence of the link between

intermediate or surrogate outcomes and long-term

cardiovascular and cerebrovascular outcomes

EMC MEETING 10/23/13

DRAFT RECOMMENDATIONS

Methods

• Distinguishing subpopulation characteristics (e.g., cultural beliefs

about treatment) should be incorporated in study design and

analysis

– Consideration of appropriate covariates.

• System level studies should collect and analyze relevant patient-

level, provider level, and system-level variables

• Define measures of adherence and barriers to adherence and

assess these uniformly.

• Studies should use rational comparators based on the established

highest standard of care

– including optimal dosing, intensity, and follow up.

EMC MEETING 10/23/13

DRAFT RECOMMENDATIONS

Additional Patient-centered Considerations

• Measure factors related to cost and patient burden which are likely

to impact outcomes of the diabetes intervention once applied in a

real-world setting.

• Evaluate decision support tools (incorporating benefits, harms, and

burden) which allow patients to participate in diabetes treatment

decision-making.

LUNCHEON PRESENTATION

THE COMET (CORE OUTCOME MEASURES IN

EFFECTIVENESS TRIALS) INITIATIVE

PAULA WILLIAMSON

MRC NORTH WEST HUB FOR TRIALS METHODOLOGY

RESEARCH

Core Outcome Measures in Effectiveness Trials

www.comet-initiative.org

Acknowledgements

• COMET Management Group:

Doug Altman, Jane Blazeby, Mike Clarke, Paula Williamson

• COMET project coordinator: Elizabeth Gargon

• Collaborators: Peter Tugwell, Maarten Boers, Caroline Terwee, Holger Schunemann, Michael Rose, Sunita Vohra, Roberto D’Amico, Lorenzo Moja

International Advisory Group

• Professor Jacques Demotes-Mainard (ECRIN)

• Dr Irmgard Eichler (EMA)

• Professor David Flum (PCORI)

• Dr Piero Olliaro (WHO)

• Dr Sean Tunis (CMTP)

• Ms Liz Whamond (Cochrane)

DMARD trials for rheumatoid arthritis

Health care research is untidy

• It needs to be tidied up if it is to achieve its aim of helping practitioners and patients to improve health care and health

• This needs initiatives such as the Cochrane Collaboration and Green Park Collaborative

• And COMET …..

Core outcome set

• An agreed standardised set of outcomes that should be measured and reported, as a minimum, in all clinical trials in specific areas of health or health care

Scope of a COS

• “The specific area of health or healthcare that the COS is to apply to, in terms of health condition, population and types of interventions needs to be determined.”

• All stages or severity of a specific health condition or focussed on a particular disease category

- e.g. in colorectal cancer, a COS might be developed for all patients or it may focus on patients with metastatic disease

• All treatment types or for a particular intervention

- e.g. in morbid obesity, a COS may be created to use in trials of all interventions or just bariatric surgery alone

• www.omeract.org • Trials 2007 8:38

Improvements over time (Kirkham et al, Trials 2013)

Studies reporting

full RA COS (%)

WHO/ILAR

RA COS

EMA

guideline

FDA

guideline

100

80

60

40

20

1985 1990 1995 2000 2005 2010

0

Mean number of

clinical outcomes

6.0

6.5

7.0

0.0

drug studies

non-drug studies

The COMET Initiative • To raise awareness of current problems with

outcomes in clinical trials

• To encourage COS development and uptake

• To provide resources to allow practitioners to develop COS, e.g. COMET database, guidance

• An international network of trialists, systematic reviewers, health service users, practitioners, editors, funders, policy makers, regulators

COMET Initiative

• ‘What’ to measure

• ‘How’ to measure (validity, reliability, feasibility)

- COSMIN

- PROMIS

- PROQOLID

- TREAT-NMD ROM

Website

Background

COMET Database

• Systematic review - 28,000+ abstracts

• 198 published COS

- 62 explicitly for a particular intervention type (e.g. drugs, surgery, etc)

- 35 explicitly involved patients or carers

- 147 involved US/Canada

• Plus a further 50+ ongoing COS projects

• Other relevant articles

Scope

Identifying existing knowledge

Stakeholder involvement

Consensus methods

Achieving global consensus

Regular review, feedback, updating

Implementation

Clear presentation

Stakeholder involvement

• Health care practitioners

• Patients, carers, representatives

• Regulators

• Industry representatives

• Researchers

• Stage of involvement may vary by group

Patient and public involvement

• Impact of involvement

– Rheumatology (OMERACT): fatigue

– Chronic pain (IMMPACT): expansion of previously proposed core outcome domains

– Multiple sclerosis: fatigue, continence

Professor Hywel Williams, Chair of the NIHR HTA

Commissioning Board: ‘Patients and professionals

making decisions about health care need access to

reliable evidence. The new COMET database will help

researchers across the NIHR family and beyond when

choosing the outcomes to include in the studies that will

establish this evidence base'.

Response to EMA consultation SINHA ET AL

REDDELL ET AL BUSSE ET AL

5-11 years 12+ years

TOP 6 PARENTS +/- CLINICIANS ESSENTIAL OPTIONAL ESSENTIAL OPTIONAL ESSENTIAL OPTIONAL

Symptoms

√ √ √

Exacerbations

√ √ √ √

QoL

√ √ √ √

Death

√ √

Normal activities

√ √

Exercise ability

√

Reliever use

√ √

Lung function

√ √ √

Tx side effects

√

Healthcare utilisation

√ √ √

Biomarkers

√

Hyper-responsiveness

√

NICE clinical guidelines

• Selection of outcomes always been important

• GRADE since 2009 - assesses the quality of the evidence by outcome rather than study

• PICO framework for each clinical question

• Addition to methods within NICE to check the COMET database

• Project underway comparing published COS with outcomes in related NICE clinical guidelines

Journal endorsement

• Core Outcomes in Women’s Health (CROWN)

- a consortium of 29 O&G journals to implement core outcome sets across the board, including AJOG, BJOG, Cochrane, etc

• Co-ordinating rapid peer-review of manuscripts describing core outcome sets and publishing these simultaneously across participating journals

Future work

• Maintain and keep the database up to date

• Quality assessment tool

• Methods for COS development

• Methods for engaging consumers - initial meeting of UK PPI organisations

• Methods to promote implementation

• Monitoring uptake

COMET and GPC

• GPC identifies priority clinical areas

• COMET searches database and non-database list (50+ ongoing projects)

• Existing COS: GPC appraisal

• Gap identified: GPC and COMET facilitate COS development

www.comet-initiative.org

e.gargon@liv.ac.uk

Twitter: @COMETinitiative

ANNUAL MEETING PANEL DISCUSSION

Improving the Science & Methods of Patient-Centered Outcomes Research:

The PCORI Methodology Report

Moderator: Sean Tunis, CMTP

Panelists: Naomi Aronson

Blue Cross and Blue Shield Association

Ethan Basch

University of North Carolina at Chapel Hill

Deborah Collyar

Patient Advocates in Research

ANNUAL MEETING PANEL DISCUSSION

Medical Devices: Prospects & Priorities for Developing Methodological

Standards

Moderator: Tanisha Carino, PhD, Avalere

Panelists: Robert Giffin, PhD

Vice President, Health Economics & Outcomes Research, Covidien

Louis Jacques, MD

Director, Coverage & Analysis Group, CMS

Danica Marinac-Dabic, MD PhD

Director of the Division of Epidemiology, FDA

Murray Sheldon, MD

Associate Director for Technology and Innovation, FDA