THANK YOU FOR JOINING ISMPP U TODAY!

Transcription

1 THANK YOU FOR JOINING ISMPP U TODAY! The program will begin promptly at 10:00 am EDT August 20, 2013

2 ISMPP WOULD LIKE TO THANK.. the following Corporate Platinum Sponsors for their ongoing support of the society 2

3 ISMPP ANNOUNCEMENTS Mark your calendars! The 2013 European Meeting of ISMPP is on January 2013, ETC Venues, 200 Aldersgate, St Paul's, London, UK. Registration is now open Call for Abstracts is now open for the 2013 European Meeting. Submission deadline is October 12th at 5:00pm EST A Suggestions Document developed by ISMPP s Sunshine Act Task Force for interpretation and implementation of the legislation is available on the ISMPP website 3

4 IGNORE AT YOUR PERIL! WHY PUBLICATION PROFESSIONALS DO NEED TO KNOW ABOUT SPIRIT GUIDELINES FOR PROTOCOLS Speaker: An-Wen Chan, MD, DPhil, FRCPC Speaker: Julie A. Ely, MA, PhD, CMPP Moderator: Serina Stretton, BSc Hons, PhD, CMPP TM

5 IGNORE AT YOUR PERIL! (no matter where you live ) Image source: Paul Downey Flickr` Image source: / Freefoto.com 5

6 OBJECTIVES At the end of this session, attendees should be able to: Discuss the SPIRIT 2013 Statement and why it is needed Understand the appropriate use of the 33-item checklist Understand how the SPIRIT 2013 Statement benefits professional medical publication planning 6

7 INTRODUCTIONS Speaker: An-Wen Chan, MD, DPhil, FRCPC Phelan Scientist and Mohs Surgeon, Women's College Research Institute; Assistant Prof. of Medicine at the University of Toronto, in Canada Special Advisor to the Clinical Trials Unit of the Canadian Institutes of Health Research, helped coordinate the WHO International Clinical Trials Registry Platform in Geneva Chair, SPIRIT Initiative to improve the quality of clinical trial protocols 7

8 INTRODUCTIONS Speaker: Julie A. Ely, MA, PhD, CMPP Senior Medical Writer, ProScribe Medical Communications, Sydney, Australia PhD, University of California Many years of experience working in international pharma and biotechnology companies in all areas of drug development, from discovery research to phase IV clinical trials ; 9 years as a medical writer Has conducted multiple training sessions on SPIRIT in the USA and the Asia-Pacific region 8

9 INTRODUCTIONS Moderator: Serina Stretton, BSc Hons PhD, CMPP TM Head of Medical Writing, ProScribe Medical Communications, Sydney, Australia PhD, Flinders University of South Australia Many years of experience across the spectrum of medical communications in the Asia-Pacific region, from protocols to publication planning to patient information; > 15 years as a medical writer 9

10 DISCLOSURES The information presented reflects the personal knowledge and opinion of the presenters and does not represent those of their current or past employers or those of ISMPP 10

11 THE SPIRIT INITIATIVE: DEFINING STANDARD PROTOCOL ITEMS AUGUST 20, 2013 An-Wen Chan, MD DPhil Women s College Hospital & Research Institute University of Toronto

12 IMPORTANCE OF TRIAL PROTOCOLS Trial registries Trialists Patients & Trial participants Trial roadmap Journals Regulators/ Policymakers Scientific & ethics review Origin of subsequent reporting Transparency Healthcare providers Funders Ethics boards 12

13 CURRENT LANDSCAPE >15,000 trials completed annually Protocols are often suboptimal Incomplete information Variable format Variable standards 13

14 PROTOCOLS LACK IMPORTANT INFORMATION Allocation Allocation concealment concealment 59% Blinding Blinding 34% Primary Primary outcomes outcome 25% Power Power calculation calculation Harms reporting Harms reporting system system 40% 41% 0% 20% 40% 60% 80% 100% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% % of protocols with inadequate information Mhaskar R et al, J Clin Epid 2012; Chan AW et al, BMJ 2008, JAMA 2004; Scharf O, J Clin Oncol 2006; Pildal J, BMJ 2005; Hróbjartsson A et al, J Clin Epid

15 PROTOCOLS LACK IMPORTANT INFORMATION Primary 1º outcome outcome analysis analysis 20% Handling Handling of missing of missing data data 77% Handling Handling of protocol of deviations deviations 47% Adjusted Adjusted analyses analyses 67% Subgroup analyses 95% 0% 20% 40% 60% 80% 100% % of protocols with inadequate information Chan AW et al, BMJ 2008; Al-Marzouki S et al, Lancet

16 SYSTEMATIC REVIEW OF PROTOCOL GUIDELINES 40 guidelines >380 protocol elements Most elements found in only 1 guideline No systematic methods or use of evidence Tetzlaff J et al, Systematic Reviews

17 BURDEN OF REVISIONS Among 288 industry trials submitted for ethics approval: REB requested revisions to 92% Protocol content (45%) Other related information (20%) Russ H, German Med Sci

18 BURDEN OF AMENDMENTS Among >3,400 industry protocols: 50% were amended 16 changes per trial One third classified as avoidable 1 amendment = 9 weeks of trial delay = 3.5 hrs of REB time Getz KA, Drug Info J 2011; Decullier E, BMC Med Ethics

19 OBJECTIVE To improve content and quality of clinical trial protocols through evidence-based guidance 19

20 DEFINITION OF PROTOCOL Pre-trial document submitted for ethics approval Background & objectives Population & interventions Methods & statistical analyses Ethical and administrative aspects Evolving document Transparent audit trail Related documents (SAP, contracts) 20

21 METHODS Systematic reviews: Existing protocol guidelines Evidence for key protocol items Delphi consensus survey Consensus meetings SPIRIT 2013 Checklist Explanatory document 21

22 DELPHI CONSENSUS SURVEY Preliminary checklist based on systematic review 3 survey rounds from Aug Nov participants from 17 countries Items rated from 1-10 Ratings and comments circulated in each round Median 8 Included Median 5 Excluded Tetzlaff J et al, Trials

23 CONSENSUS MEETINGS (DECEMBER 2007 AND SEPTEMBER 2009) 20 participants Trialists, methodologists, industry, ethicists, funders, journal editors Review of protocol items from Delphi survey 23

24 SYSTEMATIC REVIEW OF EVIDENCE citations screened (MEDLINE, EMBASE, Cochrane Methodology Register) 2433 articles reviewed 376 methodologic articles included 24

25 EVOLUTION OF SPIRIT CHECKLIST Systematic review of protocol guidelines 59 items Delphi consensus survey 71 items Consensus meetings 33 items Systematic review of evidence 25

26 SPIRIT 2013 CHECKLIST 33 items in five categories Administrative information Introduction Study methods Ethical considerations & dissemination Appendices Chan AW et al, Annals Intern Med 2013

27 SCHEMATIC PARTICIPANT TIMELINE Study period Randomizati on Preallocation Postallocation follow-up Clos e-out TIMEPOINT ENROLLMENT INTERVENTIONS ASSESSMENTS 27

28 SCOPE All clinical trials Minimum content Relevant information from contracts & operations manuals 28

29 RELATION TO OTHER GUIDANCE Declaration of Helsinki Good Clinical Practice CDISC Protocol Representation Group PRACTIHC (Pragmatic RCTs In Health Care) 29

30 SPIRIT EXPLANATION & ELABORATION Model example Rationale and explanation References to empirical evidence and further reading Chan AW et al, BMJ

31 Standard guidance (SPIRIT Statement) Educational resource (SPIRIT Explanatory paper) Improved protocol completeness TRIAL TEAM Better trial implementation Faster REB approval Fewer amendments EXTERNAL REVIEWERS Increased protocol consistency More efficient review Fewer amendments Saved time & resources High quality trials Chan AW et al, Lancet

32 ENDORSEMENTS WAME, Lancet, BMJ, Annals Clinical trial groups (NCIC, MRC, UCL) Academic institutions GSK, J&J 32

33 33

34 SEPTRE SPIRIT Electronic Protocol Tool & Resource Key features Evidence-based SPIRIT content Consistency across protocols Compatibility with trial registries and IRB platforms Cost savings (fewer amendments; faster ethics review) 34

35 USERS 35

36 CONCLUSIONS SPIRIT checklist aims to improve protocol quality Potential impact on efficiency of protocol drafting, registration, submission, and review Opportunities for broad adoption 36

37 Trialists/Methodologists/Statisticians An-Wen Chan (Chair), Univ of Toronto Jennifer Tetzlaff, University of Ottawa David Moher, University of Ottawa Doug Altman, University of Oxford Kay Dickersin, Johns Hopkins University Caroline Doré, UK MRC Peter Gøtzsche, Nordic Cochrane Centre Asbjørn Hŕobjartsson, Nordic Cochrane Wendy Parulekar, NCIC CTG Ken Schulz, Family Health International Andreas Laupacis, University of Toronto Industry Jesse Berlin, Johnson & Johnson Frank Rockhold, GSK Journal editors Trish Groves, BMJ Bill Summerskill, Lancet Drummond Rennie, JAMA Hal Sox, Annals of Internal Medicine Government funders Karmela Krleža-Jerić, Canadian Institutes of Health Research Ethicists Howard Mann, University of Utah Genevieve Dubois-Flynn, Canadian Institutes of Health Research 37

38 A SPIRITed approach How publication professionals can use SPIRIT Dr Julie A. Ely, PhD, CMPP ProScribe Medical Communications, Sydney, Australia

39 OVERVIEW Why do we need SPIRIT? Protocol checklist items for publication professionals How publication professionals / medical writers can use SPIRIT Summary 39

40 WHY DO WE NEED SPIRIT? 40

41 INCONSISTENCY ACROSS CLINICAL TRIAL DOCUMENTS Incomplete / inconsistent information in clinical study reports vs registry data vs peer-reviewed publications Incomplete / biased reporting of results Information Clinical Study Report Completeness Registry Report Completeness Journal Publication Completeness Study methods 88% (533/606) 31% (147/468) 40% (458/1152) Primary endpoint 76% (77/101) 56% (44/78) 31% (60/192) Wieseler et al. BMJ 2012;344:d

42 IN THE BEGINNING ICH E6 GOOD CLINICAL PRACTICE GUIDELINES Published in 1996 Widely used international guideline on protocol content Provides minimal guidance about results dissemination (Section 6.15) 42

43 LANDSCAPE HAS CHANGED. Focus is now on transparency disclose results! 1997: FDA Modernization Act required trial registration for therapies used to treat serious or life-threatening diseases 2005: ICMJE (International Committee of Medical Journal Editors) requirement for trial registration to publish in ICMJE member journals 2007: FDA Amendments Act (FDAAA) requirement for trial registration & results posting 2011: EMA requirement for trial registration & results posting 2012 (draft): FDA TEST Act (Trial and Experimental Studies Transparency) expands the scope of trials requiring registration & results posting Corporate Integrity Agreements 1 1 Rodino F. Therapeutic Innovation & Regulatory Science 2013;47:

44 FIXING THE LINCHPIN WRITE BETTER PROTOCOLS! SPIRIT 2013 is an opportunity to: Enhance protocol quality, improve standardization of clinical research Document EARLY and STRONG commitment to trial registration and results dissemination Increase consistency Protocol, registry, results database, publications Build trust and transparency Right thing to do for participants! Educate the public 44

45 WHAT EVERY PUBLICATION PROFESSIONAL NEEDS TO KNOW.ABOUT SPIRIT What s new and unique in SPIRIT 2013 checklist 1? Protocol checklist items of particular relevance to: Publication professionals Regulatory medical writers 1 Word version of checklist available at: 45

46 TRIAL REGISTRATION DATA SET Item 2b: include a table with the minimum trial registration dataset (World Health Organization-compliant) Promotes complete and transparent trial registration Provides a structured synopsis of the trial If protocol amendments include registry items, registration data set table will serve as handy reminder to update registry information Chan et al. Ann Int Med 2013;158:200 46

47 ROLE & RESPONSIBILITIES OF SPONSOR / FUNDER Item 5c: Role of study sponsor and funders Study design Collection, management, analysis, and interpretation of data Writing of clinical study report Decision to submit the report for publication* State if sponsor/funder has ultimate authority over any of these activities *International Federation of Pharmaceutical Manufacturers & Associations (IFPMA): A Joint Position on Publications requirement 47

48 INVESTIGATOR ACCESS TO TRIAL DATA Item 29: Access to the final trial dataset & disclosure of any agreements that limit investigator access to the data Who will have access to raw/cleaned data sets? Description of any restrictions to data access Storage location for data blog.clinicaldata.us 48

49 RESULTS DISSEMINATION POLICY Item 31a: Communicating trial results to participants, healthcare professionals, and the public Emphasis on early planning for: Publications (ie, publication planning, publication steering committee) Any conditions relating to the Investigator s right to publish (ie, should be Good Publication Practices 2 [GPP2]-compliant) Warning: 1 in 4 trials on had non-compliant information, and 40% of these trials involved the Asia-Pacific region! 1 Results disclosure databases Other data-sharing arrangements 1 Stretton et al. Seventh International Congress on Peer Review & Biomedical Publication; September 8-10, 2013, Chicago, IL 49

50 AUTHORSHIP POLICY Item 31b: Authorship/contributorship Based on ICMJE Uniform Requirements for Manuscripts Plans for the use of professional medical writers and funding source No ghost authorship, guest/gift authorship, or ghostwriters! 50

51 PUBLIC ACCESS Item 31c: any plans for granting public access to: Full study protocol Clinical study report (CSR) Participant-level datasets (de-identified) Statistical code (to allow verification and replication of analyses) Precedence for public access to participant-level data sets and CSRs New & draft EMA regulatory policies 1 GlaxoSmithKline; NIH NIAID Immune Tolerance Network 2 1 EMA Policy 0043 (2010); EMA Draft Policy 70 (2013); 2 N Engl J Med. 2013;369: ,

52 SPIRIT AND PUBLICATION PROFESSIONALS: WHAT CAN WE DO? EARLY planning for trial registration, results dissemination, and publication strategy Publication planning committee; sufficient budget available GPP2-compliant publication agreements Provide input during the protocol writing phase Protocol review committee; protocol quality review May add time to protocol review cycle; benefits outweigh risks Review/update your organization s protocol template/protocol template instructions 52

53 WHAT CAN PUBLICATION PROFESSIONALS DO? Increase awareness of SPIRIT in your organization Provide SPIRIT checklist to your colleagues Implement global training on use of checklist (esp. Asia-Pacific region) SPIRIT 2013 Explanation & Elaboration publication 1 Real-life examples for each checklist item Translations of checklist currently underway Chinese, Italian, German Japanese (?), Hindi (?) 1 Chan et al. BMJ 2013;346:e7586; Available at: 53

54 WHAT CAN PUBLICATION PROFESSIONALS DO? Use SPIRIT checklist as a tool for education and audits Non-proprietary; checklist freely available to download Service providers (a must for protocol writers?) Investigator use (a must for funding support of investigator-initiated trials?) Ethics committees (evidence-based rationale for protocol content) cdn2.hubspot.net 54

55 SUMMARY Using the SPIRIT 2013 checklist should: Improve protocol quality Enhance timely trial registration & results dissemination Minimise publication bias Increase transparency Enhance public trust in clinical research 55

56 QUESTIONS... To ask a question, please type your query into the Q&A chat box at the bottom left of your screen. Every attempt will be made to answer all questions.

57 NEXT ISMPP U PRESENTATIONS Date: September 18 Topic: Report on 7 th International Congress on Peer Review and Biomedical Publication Presenters to be announced Date: to be announced Encore presentation of Sunshine Act ISMPP U with live Q&A session for members unable to attend on August 14 57

58 THANK YOU FOR ATTENDING! We hope you enjoyed today's presentation. Please take a moment to click on the link that will be provided to you and complete the survey. We depend on your valuable feedback as we develop future educational offerings. 58