Global opportunities and challenges for trial registration ... · Global opportunities and...
Transcript of Global opportunities and challenges for trial registration ... · Global opportunities and...
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Global opportunities and challenges Global opportunities and challenges for trial registration: for trial registration:
Update from the WHO Registry PlatformUpdate from the WHO Registry Platform
October 26, 2006October 26, 2006
AnAn--Wen Chan, MD Wen Chan, MD DPhilDPhil
ScientistScientist
World Health Organization, GenevaWorld Health Organization, Geneva
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““All great truths begin as blasphemies.”
George Bernard Shaw
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OutlineOutline
Background and overviewBackground and overview
Global challenges Global challenges
Global opportunitiesGlobal opportunities
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Ethical obligations to participantsEthical obligations to participants
RiskKnowledge
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Declaration of Helsinki (2004)Declaration of Helsinki (2004)
“The design of all studies should be publicly available.”
“Negative as well as positive results should be published or otherwise publicly available.”
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Selectivestudy
publication
Access to trial informationAccess to trial information
Trial 1 Trial 3
Systematic reviews
PublicationPublication
OutcomesSelective outcomereporting
Trial 2Trial 2
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Why is WHO involved?Why is WHO involved?
Global, neutral, independent bodyGlobal, neutral, independent body
Authoritative roleAuthoritative role
Capacity buildingCapacity building
Political legitimacyPolitical legitimacy
Commitment to global equityCommitment to global equity
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Ministerial Summit on Health ResearchMinisterial Summit on Health Research
Mexico City, November 2004Mexico City, November 2004
52 health ministers decided that WHO should:
establish a network of trial registers
ensure identification of all trials
ensure a single website for access
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Dr J.W. LeeLate Director-General
Opening speech to World Health Opening speech to World Health Assembly, May 2005Assembly, May 2005
"We are ready to move
forward with an
international Clinical Trials
Registry. This will do much
to strengthen the research
process and its ability to win
public trust"
"We are ready to move
forward with an
international Clinical Trials
Registry. This will do much
to strengthen the research
process and its ability to win
public trust"
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WHO International Clinical Trials WHO International Clinical Trials Registry PlatformRegistry Platform
Established in August 2005Established in August 2005
Will NOT create a WHO registerWill NOT create a WHO register
Define a coordinated global network for trial registration and results reportingand results reporting
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Goal and Goal and objectivesobjectives
Overall GoalOverall Goal
Strengthen public trust in clinical trials by Strengthen public trust in clinical trials by promoting transparency & accountabilitypromoting transparency & accountability
ObjectivesObjectives
Registration of all clinical trials worldwideRegistration of all clinical trials worldwide
Disclosure of minimum set of resultsDisclosure of minimum set of results
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WHO Registry PlatformWHO Registry Platform overviewoverview
RegistersCT.gov, ISRCTN,
ACTR
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WHO Registry PlatformWHO Registry Platform overviewoverview
Journals
RegistersCT.gov, ISRCTN,
ACTR
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WHO Registry PlatformWHO Registry Platform overviewoverview
Journals
Resultsdatabases
RegistersCT.gov, ISRCTN,
ACTR
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WHO Registry PlatformWHO Registry Platform overviewoverview
WH
O R
egis
try
Plat
form
Journals
Resultsdatabases
RegistersCT.gov, ISRCTN,
ACTR
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WHO Registry PlatformWHO Registry Platform overviewoverview
WH
O R
egis
try
Plat
form
Journals
Resultsdatabases
WHO Search Portal
Registers
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OutlineOutline
Background and overviewBackground and overview
Global challenges Global challenges
Global opportunitiesGlobal opportunities
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Trial registration
Industry/Funders
Trial participants
Registers
Researchers
Journals
Governments
Challenge 1:Challenge 1:Coordination of multiple stakeholdersCoordination of multiple stakeholders
Ethics boards
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Trial registration
Commercial success
Create new knowledge
Patient care
Academic success
Journal success
Political gain
Challenge 1:Challenge 1:……with multiple interestswith multiple interests
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Current standards are variableCurrent standards are variable
Challenge 2:Challenge 2:Establishing global standardsEstablishing global standards
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Challenge 2:Challenge 2:Establishing global standardsEstablishing global standards
Trial registrationTrial registration
Which trialsWhich trials
What dataWhat data
WhenWhen
Results disclosureResults disclosure
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Which trials to register?Which trials to register?
Any pAny prospectiverospective research studyresearch study thatthat
Assigns humans to an interventionAssigns humans to an intervention
Measures effects of the intervention on Measures effects of the intervention on health outcomes health outcomes
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Why register early Why register early ‘‘Phase 1Phase 1’’ trials?trials?
Ethical responsibilities to participantsEthical responsibilities to participants
Informed enrollmentInformed enrollment
Dangers of hidden knowledgeDangers of hidden knowledge
Preliminary indication of adverse effectsPreliminary indication of adverse effects
Inform future or ongoing researchInform future or ongoing research
Intellectual property protected by patentsIntellectual property protected by patents
“The rights of trial participants hold primacy over commercial and career interests”
Nuremburg Code (1947)
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What data to register? What data to register? WHO Registration Data Set (1.0)WHO Registration Data Set (1.0)
Trial administrationTrial administration1.1. Primary register and Trial ID#Primary register and Trial ID#
2.2. Date of registration in Primary RegisterDate of registration in Primary Register
3.3. Secondary Secondary ID#sID#s
4.4. Source(sSource(s) of monetary or material support) of monetary or material support
5.5. Primary sponsorPrimary sponsor
6.6. Secondary Secondary sponsor(ssponsor(s))
7.7. Contact for public queriesContact for public queries
8.8. Contact for scientific queriesContact for scientific queries
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9.9. Key Inclusion/Exclusion CriteriaKey Inclusion/Exclusion Criteria10.10. Countries of RecruitmentCountries of Recruitment11.11. Date of First Date of First EnrollmentEnrollment12.12. Recruitment StatusRecruitment Status
13.13. Public titlePublic title14.14. Scientific titleScientific title15.15. Health Health condition(s)/problem(scondition(s)/problem(s))16.16. Intervention(sIntervention(s))
17.17. Study typeStudy type18.18. Target sample sizeTarget sample size19.19. Primary Primary outcome(soutcome(s))20.20. Key secondary Key secondary outcome(soutcome(s))
Trial recruitmentTrial recruitment
Trial topicTrial topic
Basic methodologyBasic methodology
What data to register? What data to register? WHO Registration Data Set (1.0)WHO Registration Data Set (1.0)
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When to register and publicly disclose?When to register and publicly disclose?
Before recruiting the first trial participantBefore recruiting the first trial participant
Full public disclosure upon registrationFull public disclosure upon registration
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‘‘Commercially sensitiveCommercially sensitive’’ itemsitems
InterventionIntervention
Scientific titleScientific title
Primary outcomesPrimary outcomes
Key secondary outcomesKey secondary outcomes
Planned sample sizePlanned sample size
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No delayed disclosureNo delayed disclosure
Patents protect intellectual propertyPatents protect intellectual property
No evidence that disclosure threatens No evidence that disclosure threatens competition and hence innovationcompetition and hence innovation
Large variation in disclosure practicesLarge variation in disclosure practices
‘‘SensitiveSensitive’’ information is availableinformation is available
Who decides what information is Who decides what information is ‘‘sensitivesensitive’’
Sim I et al, Lancet, May 2006Sim I et al, Lancet, May 2006
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Results reportingResults reporting
TimingTiming
VenueVenue
ContentContent
Relation to journal publication (if any)Relation to journal publication (if any)
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Increasing number of trials in lower income Increasing number of trials in lower income countries:countries:
NonNon--US trials submitted to FDAUS trials submitted to FDA
271 in 1990 271 in 1990 →→ 4,458 in 19994,458 in 1999
(US Dept of Health & Human Services)(US Dept of Health & Human Services)
% in Latin America% in Latin America
2.1% in 1993 2.1% in 1993 →→ 7.5% in 2000 7.5% in 2000
(IMS Health)(IMS Health)
Challenge 3:Challenge 3:Capacity buildingCapacity building
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““Clinical trials remain a major concern for us. Clinical trials remain a major concern for us. South Africa is overwhelmed and our people are South Africa is overwhelmed and our people are exposed to too many trials. Regulation, exposed to too many trials. Regulation, coordination and better access to information on coordination and better access to information on which trials are going on are essential to protect which trials are going on are essential to protect the people.the people.””
World Health Assembly, May 2005World Health Assembly, May 2005
Manto Tshabalala Msimang
Minister of Health, South Africa
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>400 listed on >400 listed on TrialsCentralTrialsCentralTMTM
Highly variable:Highly variable:
PurposePurposeScopeScopeContentContentQualityQualityAccessibility Accessibility
Challenge 4:Challenge 4:Global coordination of registersGlobal coordination of registers
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Researcher/Sponsor
Associate Registers
Primary Registers
WHO Registers NetworkWHO Registers Network
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Only 2/3 of US prostate/colon cancer Only 2/3 of US prostate/colon cancer
trials of new drugs were publicly trials of new drugs were publicly
registered despite legislationregistered despite legislation
ManheimerManheimer E & Anderson D, E & Anderson D, BMJBMJ 20022002
Challenge 5:Challenge 5:Compliance with registering trialsCompliance with registering trials
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ClinicalTrials.govClinicalTrials.gov fields:fields:
Industry trialsIndustry trials Blank Blank UselessUseless
Primary outcomePrimary outcome 24%24% 36%36%
Intervention nameIntervention name 0%0% 2%2%
All nonAll non--industry trials had full information industry trials had full information
Zarin D et al, Zarin D et al, NEJMNEJM 20062006
Challenge 5:Challenge 5:Compliance with Data Set itemsCompliance with Data Set items
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Review of information recorded in 21 Review of information recorded in 21 registers in 2005registers in 2005
12 of 20 WHO Data Set items 12 of 20 WHO Data Set items
Moja L et al, Moja L et al, submittedsubmitted
Challenge 5:Challenge 5:Compliance with Data Set itemsCompliance with Data Set items
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Compliance mechanismsCompliance mechanisms
World Health Assembly resolutionWorld Health Assembly resolution
LegislationLegislation
Journal editorsJournal editors
Funding agenciesFunding agencies
Research ethics committeesResearch ethics committees
Register policiesRegister policies
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OutlineOutline
Background and overviewBackground and overview
Global challengesGlobal challenges
Global opportunitiesGlobal opportunities
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Global opportunitiesGlobal opportunities
EthicsEthicsTransparency Transparency AccountabilityAccountabilityInformed enrollmentInformed enrollment
PracticePracticeInformed policy Informed policy Research efficiencyResearch efficiency
Ethics reviewEthics reviewGrant reviewGrant reviewTrial recruitment Trial recruitment CollaborationCollaboration
Systematic reviewsSystematic reviewsMethodological Methodological researchresearch
Improved public trust
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How can Cochrane contribute?How can Cochrane contribute?
Advocacy and promotionAdvocacy and promotion
Methodological research Methodological research
Participation in ongoing discussionsParticipation in ongoing discussions
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ConclusionsConclusions
Strong rationale for public disclosureStrong rationale for public disclosure
WHO is leading a coordinated, global WHO is leading a coordinated, global network for trial registration & reportingnetwork for trial registration & reporting
Policies will be monitored and rePolicies will be monitored and re--visitedvisited
Overriding principle:To promote ethical & scientific integrity
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WHO Registry Platform TeamWHO Registry Platform Team
StaffStaffDavina Ghersi (coordinator)Davina Ghersi (coordinator)Esther AwitEsther AwitAnAn--Wen ChanWen ChanGhassan KaramGhassan KaramIda SimIda SimPatrick UnterlerchnerPatrick Unterlerchner
Other WHO Other WHO Metin Metin GGüülmezoglulmezogluLuis Gabriel Cuervo (PAHO)Luis Gabriel Cuervo (PAHO)Tikki PangTikki Pang
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““The difference between what we do and The difference between what we do and
what we are capable of doing would suffice what we are capable of doing would suffice
to solve most of the world's problems.to solve most of the world's problems.
Mahatma Gandhi Mahatma Gandhi