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March 25, 2015

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QUESTIONS…

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• To ask a question, please type your query into the Q&A box. – To ensure anonymity and that all panelists

receive your question, please choose the drop down box option "Hosts, Presenters and Panelists." Otherwise, all audience members will be able to see your submitted question.

• Every attempt will be made to respond to all questions.

NOTE: Make sure you send your question to “Host, Presenter, and Panelists”

REGISTRY DATA USE IN PUBLICATIONS & PUBLICATION PLANNING

INTRODUCTIONS

• Faculty: Nicholas J. Combates is an Associate Director in Global Scientific Communications at Celgene supporting Multiple Myeloma. Nick has over 10 years experience in strategic publication planning and execution and has worked on disease registries in Multiple Myeloma, Prostate Cancer and Benign Prostatic Hyperplasia . He earned his PhD in Cell and Developmental Biology from Rutgers University. While a post-doctoral scientist he conducted preclinical research in oncology and skin biology, and is an author on over a dozen peer-reviewed publications. Nick is a Certified Medical Publication Professional and has been an ISMPP member since its inception.

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INTRODUCTIONS

• Faculty: Scott Newcomer is an Associate Director of Scientific Publications at Shire supporting the angioedema products. Scott has worked in the pharmaceutical industry since 1999 and specifically in scientific publications since 2002. Scott came to Shire in 2014 as part of the acquisition of ViroPharma, where he had worked since 2012. Before that, Scott worked in scientific publications at Cephalon/Teva and Centocor. Scott received an MS degree in Biology from the University of Houston and a BS degree from Juniata College. Scott is a Certified Medical Publication Professional and a member of ISMPP.

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INTRODUCTIONS

• Moderator: Manon Boisclair is the Director of the Global Publication Operations at Celgene leading a team involved in the strategic optimization of departmental processes and publications activities. She has more than 17 years of experience in the pharmaceutical/biotech industry. During the past 8 years, Manon has held a number of leadership roles in global strategic publication planning, lifecycle management, pre & post-launch activities for several hematology & oncology blockbusters as well as pipeline compounds at Celgene and Novartis. Previously, she has held medical field positions in Canada at Novartis and Merck in oncology, cardiovascular disease and pneumology. Manon completed her graduate studies in nursing at McGill University/University de Montreal (U of M); she has been an adjunct professor at U of M with the faculty of nursing while working as a clinical and research nurse. Manon is a Certified Medical Publication Professional (CMPP) member, and has been an invited speaker at ISMPP, TIPPA, and CBI. She is an ISMPP member who is actively involved with the ISMPP University committee since the past 4 years, and has also been part of the GPP3 taskforce.

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TODAY’S OBJECTIVES

• At the conclusion of this educational session, attendees should be able to:– Understand the characteristics of patient registries and how they differ

from conventional studies– Understand the opportunities and challenges associated with

publishing data from patient registries

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DISCLAIMER

• Nicholas J. Combates– Please note that the views and opinions expressed in this presentation

are my own and do not necessarily reflect those of Celgene Corporation

• Scott D. Newcomer– Pease note that the views and opinions expressed in this presentation

are my own and do not necessarily reflect those of Shire, plc.

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INTRODUCTION

.

Nicolas J. Combates, PhD, ISMPP CMPPTM

Associate Director Global Scientific Communications PublicationsCelgene

Scott D. Newcomer, MS, ISMPP CMPPTM

Associate Director, PublicationsShire Pharmaceuticals

WHAT IS A PATIENT REGISTRY?

• Observational and non-interventional– Physicians treat patients according to their own practice

– Not comparing treatments in a controlled way

• Can be “open ended” in duration of follow-up• Minimal eligibility requirements• Can be disease based• Can be therapeutic based• Product safety (surveillance)• Data as reported

Gliklich RE, Dreyer NA, eds. Registries for Evaluating Patient Outcomes: A User’s Guide. 2nd ed.AHRQ Publication No.10-EHC049. Rockville, MD: ARHQ. September 2010.

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REGISTRY ORGANIZATION

• Clear Objective• Charter

– Role of the sponsor– Role of the Steering Committee

• Protocol– Data collection– Case report form

• Statistical Analysis Plan• Adverse event reporting• Ethical and legal considerations

– Patient privacy

Gliklich RE, Dreyer NA, eds. Registries for Evaluating Patient Outcomes: A User’s Guide. 2nd ed.AHRQ Publication No.10-EHC049. Rockville, MD: ARHQ. September 2010.

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STEERING COMMITTEE STRUCTURE

• Stakeholders– Steering committee– Medical– Statistician– Study manager

• Steering committee meetings and WebEx– Brings everyone together

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ANALYSIS APPROACH

Data generation

Interpretation

Abstract/Manuscript Development

Clinical Question

SC Discussion

Analysis

Publication Basis

Steering Committee generate hypotheses

Analysis specifications developed

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MEASURING OUTCOMES IN REGISTRIES

EfficacyIdeal conditions

Specific, narrow patient population

Randomized, controlled trial

EffectivenessRoutine conditions

Few specific entry criteria

Observational study

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STRATEGIC PUBLICATION PLAN: ROLE OF A REGISTRY

• Supplement clinical data• Longer follow-up/stronger the data• Data analysis needs to be planned

– Abstract submission dates– Congress dates– Steering Committee Meetings– Publication milestones

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STRATEGIC PUBLICATION PLAN:ROLE OF REGISTRY

• Longitudinal data can provide clinical insights

Grothey et al. JCO. 2008;26:5326-5334.

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THE FRAMINGHAM STUDY - LEGACY REGISTRY

Framingham Heart Study started in Massachusetts in 1948:• Goal: It is an epidemiological project from the National Heart,

Lung and Blood Institute to identify and correlate various risk factors such as genetics, lifestyle and environmental factors, on cardiovascular disease (CVD)

• Assessed numerous variables - cholesterol (levels, fractions), blood pressure, age, gender, obesity, smoking, BMI, psychological condition, effect of medication (ASA, statins, etc)

20www.framinghamheartstudy.org

• Longest (77 yrs in existence) and largest registry which enrolled > 15,000 individuals over 3 generations 1st cohort (n=5,209 healthy men & women)

2nd cohort (5,124 children of the 1st cohort)

3rd cohort ( grandchildren of the 1st cohort)

• Lead to the “Framingham Risk Score”

• Single study which produced the highest number of publications > 1,200 congress presentations & articles in leading medical journals

Providing valuable insights and generated several clinical hypothesis which were tested in order randomized phase 3 clinical trials

21www.framinghamheartstudy.org

THE FRAMINGHAM STUDY - LEGACY REGISTRY

CASE STUDY:CONNECT® MM MULTIPLE MYELOMA DISEASE REGISTRY

Nicolas J. Combates

CONNECT® MM:STUDY DETAILS

• Multiple Myeloma Disease Registry (NCT01081028)• Purpose

– Explore the natural history and real world management of patients with newly diagnosed symptomatic multiple myeloma (MM)

– Provide unique insights into the management of MM and the impact of this hematologic disorder on patients

• Initiated September 2009• Patients enrolled at 243 Community, Academic, and Veteran Administration

sites• 1493 patients enrolled in Cohort I

Connect MM is sponsored by Celgene Corporation.

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• Inclusion Criteria– ≥18 yrs of age– Newly diagnosed MM within

60 days of enrollment– Willing and able to provide signed

informed consent– Agree to complete patient

assessment questionnaires• Exclusion Criteria

– None

CONNECT® MM:STUDY DETAILS

Connect MM is sponsored by Celgene Corporation.24

CONNECT® MM:PUBLICATIONS

• 20 abstracts & 3 manuscripts submitted since 2010• Topics included

– Baseline demographics and disease characteristics– HRQoL

• Insurance status• Gender• Race• Disease characteristics

– Diagnostic patterns– Survival analysis

Connect MM is sponsored by Celgene Corporation.

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CONNECT® MM:BASELINE MANUSCRIPT

Challenge: Must be interesting and clinically relevant

Goal: Publish manuscript on baseline data

Connect MM is sponsored by Celgene Corporation.26

Rifkin et al. Clin Lymphoma Myeloma Leukemia. 2014 (ePub).

CONNECT® MM:BASELINE MANUSCRIPT

• Baseline demographic and diagnostic testing data were collected– Diagnostic testing compared to

National guidelines– Certain diagnostic tests were

routinely performed while others were less so

– Suggests there is an educational need

• Medical History 100%

• Bone Marrow Biopsy 92%

• Skeletal Survey 85%

• Cytogenetics 63%

• Lactate Dehydrogenase 38%

Connect MM is sponsored by Celgene Corporation.

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CONNECT® MM:MANUSCRIPT CHALLENGES

• During development– Additional questions arise– Objectives can change– Follow-up– Missing data– Last minute comments

? ??

Connect MM is sponsored by Celgene Corporation.

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CONNECT® MM:MANUSCRIPT STEPS TO SUCCESS

• Regular communication– Internal: Statistician, Medical, Study Team– Steering Committee: Frequent updates– Authors: Frequent teleconferences and touchpoints– Strong Steering Committee Chair

• “Velvet hammer”

• Will help lead the way

Connect MM is sponsored by Celgene Corporation.

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Rifkin et al. Clin Lymphoma Myeloma Leukemia. 2014 (ePub).

CONNECT® MM:MANUSCRIPT

Connect MM is sponsored by Celgene Corporation.

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PATIENT REGISTRIES AND RARE DISEASE

Scott D. Newcomer

RARE DISEASE

Regulatory Definition•US: <200,000 patients•Europe: 5 in 10,000, life-threatening or debilitating•Not well defined for rest of world•Types

– Genetic diseases– Pediatric cancers– Some autoimmune diseases– Other rare conditions

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ORPHAN DRUGS

• Regulatory designation designed to provide incentives for industry to develop drugs for rare diseases

• Extended market exclusivity• Reduced requirements for evidence of efficacy and safety

– Agency may require a single randomized, controlled trial instead of two; placebo arm may be unethical

– Registry required after approval

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RARE DISEASES: CHALLENGES

• Few patients; small studies • Difficulty in diagnosis

– Diseases not well known outside specialists – Rare diseases with nonspecific symptoms may be undiagnosed

• Ambiguous therapeutic area– Experts from multiple specialties– Appropriate journal target not always clear

• Require physician specialization• High unmet need

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REGISTRIES FOR PATIENTS WITH RARE DISEASE

• Natural history of disease• Drug Registry: includes only patients on a certain drug• Disease Registry: includes all patients with disease regardless of therapy

– May provide more information about natural history of disease and untreated patients

– Challenges in avoiding temptation to compare effectiveness• Primarily for safety monitoring

– Effectiveness is evaluated, but interpretation of data from studies without controls is limited

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REGISTRIES FOR PATIENTS WITH RARE DISEASE: CHALLENGES

• Limited data collected• Understanding and communicating limitations of data

– Data completeness• Journal interest in real-world observational data from uncontrolled study• Non-specialist journal interest in rare disease limited• Large data output for rare disease• Inclusion of data from outside registry in publication• Off-label use

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OPEN-ACCESS JOURNALS

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REGISTRY CASE STUDY: RARE DISEASE X

• Patients with Rare Disease X have unpredictable swelling attacks that are potentially life threatening

• Diagnosis is complicated by nonspecific symptoms• Treatment Y has been shown in randomized, controlled, clinical trials to

reduce the duration of swelling events• A registry was established for patients receiving Treatment Y as a post-

marketing committment• Patients who receive at least one dose of Treatment Y are eligible for the

registry

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PUBLICATION #1: EARLY TREATMENT OF SWELLING ATTACKS

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PUBLICATION #2: REGISTRY OUTCOMES VERSUS CLINICAL TRIAL OUTCOMES

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CONCLUSION

• Registries are vital for the understanding of the natural history of rare diseases and the evaluation of the safety and effectiveness of treatments

• Limitations of data from registries must always be considered and communicated

• Publication professionals should understand the opportunities and challenges associated with registries

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ACKNOWLEDGEMENTS

• Scott would like to thank Andrew Desson, Shire’s Head of Scientific Publications, International Regions, for discussions that helped him formulate his thoughts for this presentation

• Nick and Scott would like to thank the ISMPP-U Committee for guidance

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QUESTIONS......

To ask a question, please type your query into the Q&A box.

To ensure anonymity, please choose the drop down box option "Hosts, Presenters and Panelists." Otherwise, ALL audience members will be able to see your submitted question.

Every attempt will be made to respond to all questions.

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