OPTIMIZING SCIENTIFIC VALUE: SMART AND SYSTEMATIC APPROACHES TO MEDICAL PUBLICATIONS

Transcription

1 11TH ANNUAL MEETING OF ISMPP OPTIMIZING SCIENTIFIC VALUE: SMART AND SYSTEMATIC APPROACHES TO MEDICAL PUBLICATIONS April 27 29, 2015 Hyatt Regency Crystal City Arlington, VA, USA 11TH ANNUAL MEETING OF ISMPP 1

2 RARE DISEASES AND ORPHAN DRUGS: PUBLICATIONS AND PERSPECTIVES 11TH ANNUAL MEETING OF ISMPP 2

3 Learning Objectives Better understand rare disease drug development and regulatory pathways to approval Explore rare disease publication-related challenges from large and small company perspectives Gain insight into needs and perspectives of patient advocacy groups in rare disease settings with respect to industry-sponsored research and publications 11TH ANNUAL MEETING OF ISMPP 3

4 Speakers Louise Wyhopen, BSN, RN (Novartis Oncology) Scott Newcomer, MS (Shire Pharmaceuticals) Jonathan Goldsmith, MD (FDA) Lisa Schill (RASopathies Network USA) 11TH ANNUAL MEETING OF ISMPP 4

5 PUBLICATION PLANNING: RARE DISEASES VS HIGHLY RECOGNIZED DISEASES Louise Wyhopen The opinions expressed in this presentation and on the following slides are solely those of the presenter and not necessarily those of Novartis Pharmaceuticals Corporation ( NPC ). NPC does not guarantee the accuracy or reliability of the information provided herein. 11TH ANNUAL MEETING OF ISMPP 5

6 Is pub planning necessary for Rare diseases Limited physician expertise High unmet need Need for disease awareness Need for education on diagnosis and treatment options/patient management Ethical considerations 11TH ANNUAL MEETING OF ISMPP 6

7 Are there differences in pub planning for rare diseases Gap analysis/needs assessment Audience identification Identifying appropriate journal/congress Identifying medical experts Budget Resources 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 TH ANNUAL MEETING OF ISMPP 7

8 Importance of gap analysis, audience identification, and needs assessment Well-known disease Well-identified therapeutic area Many citations available Many treating physicians of all levels of practice Large patient populations RCTs as primary sources of data Rare disease Limited number of medical experts/multiple disciplines/ Minimal citations available Specific audience, mostly experts Small or very limited patient populations Small single-arm studies, case reports, patient registries 11TH ANNUAL MEETING OF ISMPP 8

9 Importance of planning resources and budget Well-known disease Rare disease Large internal teams Small internal teams Many investigators/experts Limited number of experts Often many resources Limited resources/budget 11TH ANNUAL MEETING OF ISMPP 9

10 Content generation for rare disease publications Sources of data Small single arm clinical trials Patient case reports Patient registries Data analysis Internal vs external statisticians Considerations for sharing data 11TH ANNUAL MEETING OF ISMPP 10

11 Challenges in getting data/information published Small single-arm studies Journal interest limited by their audience and vast number of manuscripts received Very small numbers may lead to incorrect interpretation Patient registries Limitations of data Patient reported data viewed as unscientific Journal interest in real-world data Patient case reports Limited number of cases Potential bias to good or poor outcomes 11TH ANNUAL MEETING OF ISMPP 11

12 Conclusion Publication planning is important for rare diseases Inherent challenges include Identifying target audience, congress, journal Internal and external resource limitations Physicians, patients, and care givers rely on published scientific data to provide the latest information to optimize outcomes 11TH ANNUAL MEETING OF ISMPP 12

13 PATIENT REGISTRIES IN RARE DISEASE SCOTT NEWCOMER, MS, ISMPP CMPP TM 11TH ANNUAL MEETING OF ISMPP 13

14 Challenges in Studying Rare Disease 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 11TH ANNUAL MEETING OF ISMPP 14

15 Patient Registry Observational study or database of patients Real-world: treatment not dictated by protocol Open-ended Minimal patient eligibility requirements 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 11TH ANNUAL MEETING OF ISMPP 15

16 NIH/NCATS GLOBAL RARE DISEASES PATIENT REGISTRY Global registry of any patient with a rare disease 11TH ANNUAL MEETING OF ISMPP 16

17 Registry Data Demographics Disease pathogenesis/natural history Treatment and diagnostic patterns Quality of life Safety Efficacy Effectiveness Ideal conditions Routine conditions Specific, narrow patient population Randomized, controlled trial Few specific entry criteria Observational study 11TH ANNUAL MEETING OF ISMPP 17

18 Registries in Rare Disease Contribute to understanding of natural history of disease Centralized list of patients Safety monitoring Effectiveness Large data output for rare disease 11TH ANNUAL MEETING OF ISMPP 18

19 Registries: Challenges Patient privacy Limited data collected Data completeness Understanding and communicating limitations of data Journal interest in real-world observational data from uncontrolled study Non-specialist journal interest in rare disease limited 11TH ANNUAL MEETING OF ISMPP 19

20 Open-Access Journals 11TH ANNUAL MEETING OF ISMPP 20

21 The Future?? 11TH ANNUAL MEETING OF ISMPP 21

22 Key Take-Aways Patient registries can contribute to he understanding of the natural history of rare diseases and the benefit-risk profile of treatments Limitations of data from registries must always be considered and communicated Publication professionals should understand the opportunities and challenges associated with registries 11TH ANNUAL MEETING OF ISMPP 22

23 Acknowledgements Andrew Desson Nick Combates Mary Whitman 11TH ANNUAL MEETING OF ISMPP 23

24 Rare Diseases and Orphan Drugs: Publications and Perspectives Jonathan C. Goldsmith, MD, FACP Acting Associate Director Rare Diseases Program/Office of New Drugs Center for Drug Evaluation and Research/FDA International Society for Medical Publication Professionals Crystal City, Virginia 29 April

25 Disclosures No Conflicts of Interest Nothing to Report

26 RARE DISEASES PROGRAM Mission Statement: Facilitate Support Accelerate the development of drug and biologic products for the treatment of patients with rare disorders 26

27 What Makes Drug Development For Rare Diseases More Difficult? These diseases are often poorly or incompletely understood Rarity is often inversely proportional to the understanding Small disease populations may restrict study design and ability to replicate trials Phenotypic diversity within specific disorders adds to complexity as do genetic subsets Lack of precedent for drug development More and more careful program planning is needed 27

28 Expediting Rare Diseases Drug Development Fast Track (FDAMA 1997/FDASIA 2012) Breakthrough Designation (FD&C Act/FDASIA 2012) Priority Review (PDUFA 1992) Accelerated Approval (21CFR314 subpart H, 601 subpart E/FDASIA 2012) Regulatory Flexibility Guidance for Industry Expedited Programs for Serious Conditions Drugs and Biologics, May

29 CDER Novel New Drug Approvals Flexible Clinical Development Programs - CY2014 Expedited Programs Number Rare N = 17 Number Non-Rare N = 24 Fast Track 10 (59%) 7 (29%) Breakthrough Designation 6 (35%) 3 (13%) Priority Review 16 (94%) 9 (38%) Accelerated Approval 8 (47%) 0 (0%) First in Class 11 (65%) 6 (25%) 29

30 The Importance of Rare Disease Natural History Studies to Inform Drug Development The natural course of a disease from the time immediately prior to its inception, progressing through its presymptomatic phase and different clinical stages to the point where the patient is either cured, chronically affected... or dead without external intervention. Modified from: Posada de la Paz M; Groft SC. Adv Exp Med Biol 2010;686:

31 Characteristics of a Natural History Study Natural History Studies Registries Natural History Studies: Have a Specific Purpose Improve understanding of an identified disease Are prospectively planned and designed to be comprehensive and detailed Describe the disease independently of specific observers, clinical sites and interventions 31

32 Characteristics of a Natural History Study Natural History Studies Registries Natural History Studies: Involve all stakeholders and should be widely available Intended to describe the disease under study Provide important information to shape drug development such as clinically meaningful endpoints 32

33 Types of Natural History Studies Retrospective May be incomplete, difficult to interpret, may lack agreed upon terms. Historical controls may lack important prognostic covariates and unknown or unrecorded historical data Prospective strongest design Cross-sectional static not dynamic assessment Prospective/longitudinal Most Useful 33

34 Natural History Studies: Informing Rare Diseases Drug Development Define the disease population: describe the full range of disease manifestations and subtypes Intra patient day to day severity Inter patient variability - Phenotypes Study duration issues: Time required for performance The standard of care can change while a study is in progress Development and selection of outcome measures more specific or sensitive to changes in the manifestation of the disease or more quickly demonstrate safety and efficacy concerns to economize development 34

35 Natural History Studies: Informing Rare Diseases Drug Development Facilitate design and conduct of adequate and wellcontrolled studies and provide needed scientific foundation Inform the risk benefit analysis critical to regulatory decision making Help identify and evaluate biomarkers Develop new/optimized biomarkers that may provide proof of concept, guide dose selection, early recognition of safety issues Validate predictive value of a proposed biomarker including measurement technologies 35

36 Use of Natural History Studies to Support Drug Development alglucosidase alfa has been shown to improve ventilator independent survival in infantile onset Pompe disease. glucarpidase, a carboxypeptidase enzyme for the treatment of toxic plasma methotrexate concentrations in patients with delayed clearance due to impaired renal function ERTs for treatment of Gaucher s Disease hydrolytic lysosomal glycosaminoglycan (GAG)- specific enzyme for the treatment of Morquio A(MPS IV A) 36

37 Key Aspects of Drug Development for Rare Diseases Expedited Programs Regulatory Flexibility Natural History Studies Planning, Planning and Planning 37

38 Lisa Schill Vice President, RASopathies Network USA Patient Advocacy Outreach Consultant 11TH ANNUAL MEETING OF ISMPP 38

39 My Journey into the Rare Disease World 11TH ANNUAL MEETING OF ISMPP 39

40 11TH ANNUAL MEETING OF ISMPP 40

41 11TH ANNUAL MEETING OF ISMPP 41

42 11TH ANNUAL MEETING OF ISMPP 42

43 INTERNET SEARCH There is no one place to get the most accurate information about your rare disease Outdated information Patient advocacy/support groups may not exist 11TH ANNUAL MEETING OF ISMPP 43

44 WE RELY ON JOURNAL ARTICLES TO Find a diagnosis Locate the best specialists Find active research studies Get the most recent information Inform our doctors of important new advances Extrapolate information 11TH ANNUAL MEETING OF ISMPP 44

45 How Do Families Interpret Data? 11TH ANNUAL MEETING OF ISMPP 45

46 Extrapolate Information 11TH ANNUAL MEETING OF ISMPP 46

47 DATE OF PUBLICATION Interpretation: Lymphedema leads to elephantiasis in Noonan Syndrome 11TH ANNUAL MEETING OF ISMPP 47

48 HOW MANY PARTICIPANTS? Hemostatic abnormalities in Noonan syndrome. Artoni A 1, Selicorni A 2, Passamonti SM 1, Lecchi A 1, Bucciarelli P 1, Cerutti M 3, Cianci P 2, Gianniello F 1, Martinelli I 4. CONCLUSIONS: Nearly 40% of patients with the Noonan syndrome had a bleeding diathesis and >90% of them had platelet function and/or coagulation abnormalities. Results of these tests should be taken into account in the management of bleeding or invasive procedures in these patients Interpretation: 90% of those with Noonan Syndrome have bleeding disorders 11TH ANNUAL MEETING OF ISMPP 48

49 History of the RASopathies 2006: First CFC conference with leaders of Noonan and Costello support groups - Research included DNA extraction Families partnered with scientists and managed the CFC Bio Bank - Genes for CFC Identified Research that took Dr. Rauen 5 years to collect in her lab took days partnering with an advocacy group 11TH ANNUAL MEETING OF ISMPP 49

50 11TH ANNUAL MEETING OF ISMPP 50

51 Created in 2010 after American Society of Genetics Meeting Mission: To advance research of the RASopathies by bringing together families, clinicians, and scientists Scientific Meetings Berkley California Chicago, IL 2013 Orlando, Florida 2015 Seattle, Washington 43 publications have been produced directly from the past three meetings 11TH ANNUAL MEETING OF ISMPP 51

52 Recommendations Work WITH patient groups to save time and resources Abstracts should be written on an 8 th grade reading level Make date of publications and number of participants easier to identify 11TH ANNUAL MEETING OF ISMPP 52

53 QUESTIONS? 11TH ANNUAL MEETING OF ISMPP 53

54 11TH ANNUAL MEETING OF ISMPP OPTIMIZING SCIENTIFIC VALUE: SMART AND SYSTEMATIC APPROACHES TO MEDICAL PUBLICATIONS April 27 29, 2015 Hyatt Regency Crystal City Arlington, VA, USA 11TH ANNUAL MEETING OF ISMPP 54