1. WHO International Clinical Trial Registry Platform A.Metin Gülmezoglu Project Coordinator Department of Reproductive Health and Research World Health Organization

2. Why Registration  Fulfill ethical obligation to participants, the public  Address problem of publication bias  Contribute to development of unbiased systematic reviews  Advance science more quickly Speed disclosure of results Speed disclosure of results Increase effectiveness of research funding Increase effectiveness of research funding Increase participation by patients, doctors, researchers Increase participation by patients, doctors, researchers  Increase transparency of information about trials Reduce over-reporting & ambiguity Reduce over-reporting & ambiguity

3. Trials Registration - History  Historical calls for registration of human research; early small registers  Multiple studies establishing publication bias  Recent proliferation of local and specialty registers  Support from journal editors  AMA statement of support  NY Attorney General suit & disclosure settlement  Plans for industry trials registration  Support from speakers at Mexico City Joint plenary

4. People have suffered and resources have been wasted because disappointing results of research have not been reported.

5. Biased under-reporting of research is ethically and scientifically unacceptable, and it should be outlawed. Information about ongoing research should be registered prospectively and publicly. Sir Iain Chalmers, November 2004, Mexico City

6. WHO involvement  October 2003 London Dr JW Lee discusses WHO's role in global health systems research – trial registration is highlighted Dr JW Lee discusses WHO's role in global health systems research – trial registration is highlighted  April 2004 London stakeholder/funder discussion Registration will benefit informed decisions Registration will benefit informed decisions  April 2004 WHO registers its trials via ISRCTN

7. WHO involvement

8. Why WHO?  Global, neutral body  Role in setting norms and standards  Contribute to capacity building  Accountable to member states

9. Stakeholders’ Meeting October 2004 at Rockefeller Foundation  WHO  Medical journal editors  Research sponsors (industry/government/foundations)  Research investigators  Cochrane Collaboration  Regulators/government US, Canada, UK, Germany US, Canada, UK, Germany Office of NY State Attorney General Office of NY State Attorney General  ISRCTN & MetaRegister; ClinicalTrials.gov

10. Statement of NY stakeholders: Need for global approach to trials registration  Unambiguous identification of trials  Consensus needed on which trials; data; timing and disclosure of results  One-stop search portal; publicly available  System that is simple, effective, efficient  Capacity built where appropriate (cont’d)

11. Statement of NY stakeholders (cont’d): WHO should establish formal process  Appropriate governance; broad collaborative process  Existing structures leveraged; need for any new structures identified  WHO mindful of ICMJE deadline

12. Ministerial Summit – Mexico City November 2004  The Ministerial Summit on Health Research urges the WHO to work with stakeholders in developing a global system for trials registration Ensuring unambiguous identification of trials Ensuring unambiguous identification of trials Achieving consensus on which trials; data; timing and disclosure of results Achieving consensus on which trials; data; timing and disclosure of results Creating a one-stop public search portal Creating a one-stop public search portal Building on existing efforts Building on existing efforts Building capacity where needed Building capacity where needed  The Summit urges international funders to support initiative to enable launch of portal by 2006

13. Three Tracks I. Substantive Standards / Principles Major issues (e.g., registration scope, disclosure standards) Major issues (e.g., registration scope, disclosure standards) High-level review of technical implementation against standards High-level review of technical implementation against standards II.Technical Implementation IT structure, adaptable operating procedures IT structure, adaptable operating procedures Ongoing financial / sourcing model Ongoing financial / sourcing model III.Start-Up Funding

14. I. Substantive Standards – Structure WHO: Receives advice International Advisory Board (10-15) Senior, broad-based Endorses policies; leadership in communication / advocacy Technical Advisory Group (15-25) Expert group Principles / substantive standards Recommends policy to WHO Uses Issue Workgroups Project Staff / Support: Implementation Issue Workgroups Project Staff / Support WHO Technical Advisory Group International Advisory Board Standards Implementation

15. I. Principles Discussion in NY: General Agreements & Issues ComponentGeneral AgreementRequires Discussion Portal Registration Scope Content Unique ID Descriptors Updates Timing Access to Data Compliance Results Scope Content Timing One-stop global search; free access to all; basic implementation in 2005 Include randomized controlled trials (RCT “tbd” = to be defined) Unambiguous ID (unique & exclusive) Minimum data set (tbd); searchable fields “Significant” changes / EC approval (tbd) Register before enrolling first participant General data available to all Ethics Committee is potential key Trials supporting approved interventions Final registration info; links to pubs & data Whether to include all trials (possibly different standards for early trials) Whether to include detailed info, protocol Whether to limit access to detailed data Need EC input; role of laws / regulations Whether to disclose all registered trials Whether to disclose protocol(s) After trial completion or after approval? (of specific indication or any indication?)

16. II. Technical Implementation – Structural Design Central Office (CO) Network standards Register qualification Unique ID (UID) Global search Default register Local Registers Must be qualified Site of registration Point of all data entry Local language Central Office Register 1Register 2Register 3 Register NRegister 4 Default Register Structure to accommodate full range -- and amendments -- to standards Decentralized operations; avoid duplication of effort Allow flexibility / variation among Local Registers

17. II. Technical Implementation – Key Process Concepts  Qualification: Central Office (CO) “qualifies” limited number of local registers, provides contractual procedures / technical specs  Local Registration: A qualified (or default) register collects all data in local language, uses CO search tool to verify no existing Unique ID (UID), and transmits Standard Registration Data in English  Unique ID: CO verifies / stores in Central File, and then generates / transmits UID to local register (ideally, fully automated in both directions)  Search: CO search engine works with Standard Registration Data in Central File (may have distributed solution)  Self-Financed: Ongoing costs of CO / standards covered by nominal fee, collected by local register at time of data transmission (can share)  Results: At trial completion, results link added to Central File  Outsourcing: May outsource technical components, but not control

18. III. Start-Up Funding  Start-Up Costs: to set up the project, Secretariat In-Kind Funding: travel, meetings In-Kind Funding: travel, meetings Hard Dollar Funding: Will need to secure modest contributions from variety of stakeholders, beneficiaries, foundations Hard Dollar Funding: Will need to secure modest contributions from variety of stakeholders, beneficiaries, foundations  Maintenance costs: work towards a self-funding. automated system

19. Proposed Timing – Set Dates  Standards Track: March/April – TAG Meeting March/April – TAG Meeting May/June? – IAB Meeting May/June? – IAB Meeting  Technical Implementation Track: Present architecture to TAG for review / feedback Present architecture to TAG for review / feedback  Funding Track: Begin now; look to finish by May Begin now; look to finish by May

20. Thank you!