KKJ Karmela Krleza-Jeric,MD, M.Sc., D.Sc. CIHR - IRSC Towards Greater International Transparency of Clinical Trials Short Term Efforts for Long Term Benefits: Short Term Efforts for Long Term Benefits: CIHR trial policy 2010 KKJ 1
Outline • Prospective trial registration and • Prospective trial registration and public disclosure of trial results • International aspects: dialogue, initiatives, actions, shift of paradigm a es, ac o s, s o pa ad g • CIHR Trials policy 2010 KKJ Health research information • research material research material • research data • results: numerical data Summary level or aggregate data Individual participant or micro-level data or raw data d t • findings: numerical data with interpretation KKJ 2
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, 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 KKJ 3
Bias • Outcome reporting bias: selective • Outcome reporting bias: selective reporting of results • Publication bias: selective publication of trials a s KKJ Clinical trial A prospective controlled or uncontrolled research study evaluating the effects of one or more health-related interventions assigned to human participants. KKJ 4
Trial registration components • Unique ID • Prospective registration and public release of protocol details • Registration and public disclosure of results KKJ Protocol A document written before participant A document written before participant enrolment to describe the objectives, methodology, statistical analyses, organization, and administrative details of a trial. KKJ 5
Trial Registration Disclosure of Trial Results KKJ 6
Trial Registration Disclosure of Trial Results KKJ 7
Trial Registration Disclosure of Trial Results KKJ 8
Trial Registration Disclosure of Trial Results KKJ 9
Trial Registration Disclosure of Trial Results KKJ 10
Trial Registration Disclosure of Trial Results KKJ 11
Trial Registration Disclosure of Trial Results KKJ 12
Trial Registration Disclosure of Trial Results KKJ 13
Trial Registration Disclosure of Trial Results KKJ 14
Trial Registration Disclosure of Trial Results KKJ 15
Trial Registration Disclosure of Trial Results 16
WHO International standards for trial registration 2006 • All trials • ID • Prospectively • Minimum dataset • Registry criteria KKJ WHO minimum dataset, May 2006 1. Unique trial number 11.Countries of recruitment 2. Trial registration date 12.Condition 3. Secondary ID 13.Interventions 4. Funding source(s) 14.Inclusion /excl criteria 5. Primary sponsors 15.Study type 6. Secondary sponsors 16.Anticipated start date 7. Responsible contact person 17.Target sample size 8 8. Research contact person R h 18.Recruitment status 18 R i 9. Brief trial title 19.Primary outcome 10.Official scientific title 20.Key secondary outcomes KKJ 17
• WHO search portal WHO search portal • Network of registries KKJ KKJ 18
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cihr kkj-CIHR Sept 2007 kkj-CIHR Sept 2007 20
kkj-CIHR Sept 2007 Why are we not happy just with with trial registration and publication of results in peer publication of results in peer review journals? 21
Why…. because • Regain public trust • Build on all knowledge not just partial 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 Sponsor still controls clinical trials • Without results reporting trial registration is an unfulfilled promise KKJ Trials results reporting initiatives • Ottawa Statement part 3, 2006 KKJ 22
Ottawa Statement OTTAWA STATEMENT 1 OTTAWA STATEMENT 3 Results Disclosure 2 Individual participant level dataset p p • ID Systematic review after the trial • Protocol DATA DATA DATA DATA TRIAL OTTAWA STATEMENT 2 ID# DATA DATA OTTAWA STATEMENT 3 DATA DATA Register 20 WHO items plus Results Disclosure 1 DATA • consent form Content: CONSORT + OS2 DATA • details of design • details of design items • ethics approval Sites / Countries OTTAWA STATEMENT 1&2 • countries & sites Any independent validation • key dates of results Amendments • full protocol List of any publications Recruitment status • contract/ financial Adverse events agreements Interim analyses • systematic review kkj-CIHR Sept 2007 Early stopping (if applicable) Trials results reporting initiatives • Ottawa Statement part 3, 2006 • First Latin-American Conference on Health Research 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), 2008 KKJ 23
KKJ PROCTOR discussion topics • why why • monitoring quality • monitoring quality • for whom • accountability • when • website features • which trials • who should/not fund • how much detail • who should/not run websites • what format • barriers • responsibility KKJ-SCT-May 2009 24
PROCTOR discussion topics What we need to do to achieve the What we need to do to achieve the universal results reporting? PROCTOR: some challenges • Intellectual property TRIPS • Intellectual property -TRIPS • Privacy - de-identification • Technical issues • Levels of info for different users with various levels of access various levels of access • Prepublication KKJ 25
Privacy and transparency What we need to do to achieve the universal results reporting? The Tradeoffs Thanks to Khaled El Emam 26
CIHR perspectives Promotes open access of research it funds and trial registration culture International standards vs national registry KKJ Development of CIHR Trial Policy 27
CIHR 2003 Innovation & New & New RCT RCT Shared Knowledge New Knowledge clinical practices Silent Knowledge Registra Final Re Databa ation eport ase KKJ Development of CIHR Trial Policy 28
KKJ Development of CIHR Trial Policy 29
CIHR Trial Database Final report CONSORT guidelines CONSORT guidelines Interim / renewal Interim / renewal A Approved RCT d RCT & Summary form s2 Summary form Summary form s3 s.1 + Stage 2 + Stage 3 Stage 1 KKJ Development of CIHR Trial Policy 30
Development of CIHR Trial Policy 31
Policy related i nternational engagement & leadership • Ottawa group dialogue • Mexico Summit • Mexico Summit • WHO trial registration project and development of International standards (ICRTP) 2004 - 2007 • PROCTOR dialogue 2008- g • Declaration of Helsinki (DoH) KKJ 32
Policy related i nternational engagement & leadership • Ottawa group dialogue • Mexico Summit M i S it • WHO trial registration project and development of International standards (ICRTP) 2004 - 2007 • PROCTOR dialogue 2008- g • Declaration of Helsinki (DoH) • Public consultation on FDAAA (2009). KKJ 33
KKJ Policy related i nternational engagement & leadership • Ottawa group dialogue • Mexico Summit • Mexico Summit • WHO trial registration project and development of International standards (ICRTP) 2004 - 2007 • PROCTOR dialogue 2008- • Declarati0on of Helsinki (DoH) ( ) • Public consultation on FDAAA (2009) • PAHO KKJ 34
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CIHR trial policy 2010 CIHR trial policy 2010 KKJ KKJ 36
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KKJ Objective of the Policy to increase transparency and accessibility of trials by prospective registration and disclosure of their results. …expected to help reduce publication expected to help reduce publication bias, and fulfill ethical responsibilities to share knowledge gained from trials. KKJ 38
CIHR Trial Policy 2010 a) Prospective registration of trials b) Public disclosure of trial information during trial c) Public reporting (disclosure) of trial c) Public reporting (disclosure) of trial results d) Data retention KKJ a) Grantees are required to • • register all CIHR funded trials 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 KKJ 39
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