Towards Greater International Transparency of Clinical Trials

Transcription

1 Karmela Krleza-Jeric,MD, M.Sc., D.Sc. CIHR - IRSC Towards Greater International Transparency of Clinical Trials Short Term Efforts for Long Term Benefits: CIHR trial policy

2 Outline Prospective trial registration and public disclosure of trial results International aspects: dialogue, initiatives, actions, shift of paradigm adg CIHR Trials policy 2010 Health research information research material research data results: numerical data Summary level or aggregate data Individual participant or micro-level data or raw data findings: numerical data with interpretation 2

3 Knowledge sharing initiatives Open Access Journals available online free of charge Budapest Open Access Initiative, Feb 2002 Self-archiving Open access peer-reviewed journals Berlin Declaration on Open Access to Knowledge, Oct 2003 Individual patient data / raw data Original scientific results Metadata etc Salvador Declaration on Open Access: The Developing World Perspective, Salvador, Bahia, Brasil, Sept 2005 Scientific information is openly accessible and freely available to all, forever. Why Build new knowledge on all knowledge, not just partial Ethical and scientific imperative Current system of reporting is suboptimal and inefficient in the Internet era Technology enables it - we can do it Overcome publication and outcome reporting bias Enable independent review 3

4 Bias Outcome reporting bias: selective reporting of results Publication bias: selective publication of trials as Clinical trial A prospective controlled or uncontrolled research study evaluating the effects of one or more health-related interventions assigned to human participants. 4

5 Trial registration components Unique ID Prospective registration and public release of protocol details Registration and public disclosure of results Protocol A document written before participant enrolment to describe the objectives, methodology, statistical analyses, organization, and administrative details of a trial. 5

6 Trial Registration Disclosure of Trial Results 6

7 Trial Registration Disclosure of Trial Results 7

8 Trial Registration Disclosure of Trial Results 8

9 Trial Registration Disclosure of Trial Results 9

10 Trial Registration Disclosure of Trial Results 10

11 Trial Registration Disclosure of Trial Results 11

12 Trial Registration Disclosure of Trial Results 12

13 Trial Registration Disclosure of Trial Results 13

14 Trial Registration Disclosure of Trial Results 14

15 Trial Registration Disclosure of Trial Results 15

16 Trial Registration Disclosure of Trial Results 16

17 WHO International standards for trial registration 2006 All trials ID Prospectively Minimum dataset Registry criteria WHO minimum dataset, May Unique trial number 2. Trial registration date 3. Secondary ID 4. Funding source(s) 5. Primary sponsors 6. Secondary sponsors 7. Responsible contact person 8. Research contact person 9. Brief trial title 10. Official scientific title 11.Countries of recruitment 12.Condition 13.Interventions 14.Inclusion /excl criteria 15.Study type 16.Anticipated start date 17.Target sample size 18.Recruitment status 19.Primary outcome 20.Key secondary outcomes 17

18 WHO search portal Network of registries 18

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20 cihr kkj-cihr Sept 2007 kkj-cihr Sept

21 kkj-cihr Sept 2007 Why are we not happy just with trial registration and publication of results in peer review journals? 21

22 Why. because Regain public trust Build on all knowledge, not just partial Access to raw data Current system is suboptimal and inefficient in the internet era Sponsor still controls clinical trials Without results reporting trial registration is an unfulfilled promise Trials results reporting initiatives Ottawa Statement part 3,

23 Ottawa Statement OTTAWA STATEMENT 1 ID Protocol DATA DATA DATA DATA OTTAWA STATEMENT 3 Results Disclosure 2 Individual participant p level dataset Systematic review after the trial TRIAL OTTAWA STATEMENT 2 ID# DATA DATA DATA DATA OTTAWA STATEMENT 3 Register 20 WHO items plus Results Disclosure 1 DATA consent form DATA Content: CONSORT + OS2 details of design items ethics approval OTTAWA STATEMENT 1&2 Sites / Countries countries & sites Any independent validation key dates Amendments of results full protocol Recruitment status List of any publications contract/ financial agreements Adverse events systematic review Interim analyses Early stopping kkj-cihr (if applicable) Sept 2007 Trials results reporting initiatives Ottawa Statement part 3, 2006 First Latin-American Conference on Health Research Rio de Janeiro, 2008 Declaration of Helsinki, 7 th revision, 2008 Regulations: FDAAA, 2007; Euro, 2009, etc Journal editors: ICMJE, PLoS, BMJ, Annals, BMC Funding Agencies (e.g. NIH, CIHR, Wellcome Trust) PROCTOR (Public Reporting Of Clinical Trials Outcomes and Results),

24 PROCTOR discussion topics why for whom when which trials how much detail what format responsibility monitoring quality accountability website features who should/not fund who should/not run websites barriers -SCT-May

25 PROCTOR discussion topics What we need to do to achieve the universal results reporting? PROCTOR: some challenges Intellectual property -TRIPS Privacy - de-identification Technical issues Levels of info for different users with various levels of access Prepublication 25

26 Privacy and transparency What we need to do to achieve the universal results reporting? The Tradeoffs Thanks to Khaled El Emam 26

27 CIHR perspectives Promotes open access of research it funds and trial registration culture International standards vs national registry Development of CIHR Trial Policy 27

28 CIHR 2003 RCT Shared New Knowledge Silent Knowledge Innovation &New clinical practices Final Re eport Registra ation Databa ase Development of CIHR Trial Policy 28

29 Development of CIHR Trial Policy 29

30 CIHR Trial Database Approved RCT Summary form s.1 Interim / renewal Summary form s2 Final report CONSORT guidelines & Summary form s3 Stage 1 + Stage 2 + Stage 3 Development of CIHR Trial Policy 30

31 Development of CIHR Trial Policy 31

32 Policy related international engagement & leadership Ottawa group dialogue Mexico Summit WHO trial registration project and development of International standards (ICRTP) PROCTOR dialogue Declaration of Helsinki (DoH) 32

33 Policy related international engagement & leadership Ottawa group dialogue Mexico Summit WHO trial registration project and development of International standards (ICRTP) PROCTOR dialogue Declaration of Helsinki (DoH) Public consultation on FDAAA (2009). 33

34 Policy related international engagement & leadership Ottawa group dialogue Mexico Summit WHO trial registration project and development of International standards (ICRTP) PROCTOR dialogue Declarati0on of Helsinki (DoH) Public consultation on FDAAA (2009) PAHO 34

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36 CIHR trial policy

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38 Objective of the Policy to increase transparency and accessibility of trials by prospective registration and disclosure of their results. expected to help reduce publication bias, and fulfill ethical responsibilities to share knowledge gained from trials. 38

39 CIHR Trial Policy 2010 a) Prospective registration of trials b) Public disclosure of trial information during trial c) Public reporting (disclosure) of trial results d) Data retention a) Grantees are required to register all CIHR funded trials following the 2006 (WHO) international standards plus ethics approval and the systematic review register the trial only once provide CIHR with the name of registry and the ID assigned 39

40 b) Grantees are required to update trial information in the registry report to CIHR and the registry all major changes to the protocol upon approval by the ethics board, within 30 days. report to CIHR and the trial registry early stopping or termination of a trial, within 30 days. c) Grantees are required to submit CONSORT based report to CIHR comply with the CIHR Policy on Access to Research Outputs submit trial results to a publicly accessible results databank post the aggregate (summary) data and micro (individual participant) level data on an unbiased freely accessible website report any severe adverse effect (event) or harm 40

41 d) Grantees are required to Retain all trial information for 25 years unless they are deposited in afreely accessible data repository CIHR trial policy 2010 complies with WHO International standards ICMJE requirements Declaration of Helsinki and thereby contributes to global initiatives to increase accountability of publicly funded health research. 41

42 Policy implementation Internally Procedures Nationally Information, dialogue Research Learning modules Internationally Communication (exchange, dialogue) Research Standards, results depositories acknowledgments Various stakeholders Apropomedia 42

43 Thank you 43