Towards Greater International Transparency of Clinical Trials Short - - PDF document

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Towards Greater International Transparency of Clinical Trials Short - - PDF document

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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

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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

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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

  • pa ad g
  • CIHR Trials policy 2010

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Health research information

  • research material

research material

  • research data
  • results: numerical data
  • Summary level or aggregate data
  • Individual participant or micro-level data or

d t raw data

  • findings: numerical data with

interpretation

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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

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Bias

  • Outcome reporting bias: selective
  • Outcome reporting bias: selective

reporting of results

  • Publication bias: selective publication of

trials a s

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Clinical trial

A prospective controlled or uncontrolled research study evaluating the effects of

  • ne or more health-related interventions

assigned to human participants.

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Trial registration components

  • Unique ID
  • Prospective registration and public

release of protocol details

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  • Registration and public disclosure of

results

Protocol

A document written before participant A document written before participant enrolment to describe the objectives, methodology, statistical analyses,

  • rganization, and administrative details
  • f a trial.

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Trial Registration Disclosure of Trial Results

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Trial Registration Disclosure of Trial Results

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Trial Registration Disclosure of Trial Results

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Trial Registration Disclosure of Trial Results

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Trial Registration Disclosure of Trial Results

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Trial Registration Disclosure of Trial Results

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Trial Registration Disclosure of Trial Results

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Trial Registration Disclosure of Trial Results

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Trial Registration Disclosure of Trial Results

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Trial Registration Disclosure of Trial Results

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Trial Registration Disclosure of Trial Results

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WHO International standards for trial registration 2006

  • All trials
  • ID
  • Prospectively
  • Minimum dataset
  • Registry criteria

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WHO minimum dataset, May 2006

  • 1. Unique trial number
  • 2. Trial registration date

11.Countries of recruitment 12.Condition

  • 3. Secondary ID
  • 4. Funding source(s)
  • 5. Primary sponsors
  • 6. Secondary sponsors
  • 7. Responsible contact person

8 R h 13.Interventions 14.Inclusion /excl criteria 15.Study type 16.Anticipated start date 17.Target sample size 18 R i

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  • 8. Research contact person
  • 9. Brief trial title

10.Official scientific title 18.Recruitment status 19.Primary outcome 20.Key secondary outcomes

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  • WHO search portal

WHO search portal

  • Network of registries

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cihr

kkj-CIHR Sept 2007 kkj-CIHR Sept 2007

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Why are we not happy just with with trial registration and publication of results in peer publication of results in peer review journals?

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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

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Trials results reporting initiatives

  • Ottawa Statement part 3, 2006

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OTTAWA STATEMENT 1

  • ID

OTTAWA STATEMENT 3 Results Disclosure 2 Individual participant level dataset

Ottawa Statement

OTTAWA STATEMENT 2 Register 20 WHO items plus

  • consent form
  • details of design
  • Protocol

TRIAL ID#

DATA DATA DATA DATA

OTTAWA STATEMENT 3 Results Disclosure 1 Content: CONSORT + OS2

DATA DATA DATA DATA

p p Systematic review after the trial

DATA DATA

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OTTAWA STATEMENT 1&2 Amendments Recruitment status Adverse events Interim analyses Early stopping (if applicable)

  • details of design
  • ethics approval
  • countries & sites
  • key dates
  • full protocol
  • contract/ financial

agreements

  • systematic review

items Sites / Countries Any independent validation

  • f results

List of any publications

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, 7th revision, 2008
  • Regulations: FDAAA, 2007; Euro, 2009, etc
  • Journal editors: ICMJE, PLoS, BMJ, Annals, BMC
  • Funding Agencies (e.g. NIH, CIHR, Wellcome Trust)

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  • PROCTOR (Public Reporting Of Clinical Trials

Outcomes and Results), 2008

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PROCTOR discussion topics

  • why
  • monitoring quality

why

  • for whom
  • when
  • which trials
  • how much detail
  • monitoring quality
  • accountability
  • website features
  • who should/not fund
  • who should/not run
  • what format
  • responsibility

websites

  • barriers

KKJ-SCT-May 2009

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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

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Privacy and transparency

What we need to do to achieve the universal results reporting?

The Tradeoffs

Thanks to Khaled El Emam

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CIHR perspectives

Promotes open access of research it funds and trial registration culture International standards vs national registry

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Development of CIHR Trial Policy

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Innovation & New

CIHR 2003

RCT & New clinical practices New Knowledge Shared Knowledge Silent Knowledge Databa Registra Final Re RCT

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ase ation eport

Development of CIHR Trial Policy

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Development of CIHR Trial Policy

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CIHR Trial Database

A d RCT Final report CONSORT guidelines

Interim / renewal

Approved RCT Summary form s.1 CONSORT guidelines & Summary form s3

Interim / renewal Summary form s2

Stage 1 + Stage 2 + Stage 3

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Development of CIHR Trial Policy

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Development of CIHR Trial Policy

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Policy related international

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)

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Policy related international

engagement & leadership

  • Ottawa group dialogue

M i S it

  • Mexico Summit
  • 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).

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Policy related international

engagement & leadership

  • Ottawa group dialogue
  • Mexico Summit
  • Mexico Summit
  • WHO trial registration project and development
  • f International standards (ICRTP) 2004 - 2007
  • PROCTOR dialogue 2008-
  • Declarati0on of Helsinki (DoH)

( )

  • Public consultation on FDAAA (2009)
  • PAHO

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CIHR trial policy 2010 CIHR trial policy 2010

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Objective of the Policy

to increase transparency and accessibility

  • f 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.

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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

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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

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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
  • report to CIHR and the trial registry early

stopping or termination of a trial, within 30 days.

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c) Grantees are required to

  • submit CONSORT based report to CIHR

l ith th CIHR P li A t

  • 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 micro (individual participant) level data on an unbiased freely accessible website

  • report any severe adverse effect (event) or

harm

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d) Grantees are required to

  • Retain all trial information for 25 years
  • 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
  • WHO International standards
  • ICMJE requirements
  • Declaration of Helsinki

and thereby contributes to global initiatives to thereby contributes to global initiatives to increase accountability of publicly funded health research.

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Policy implementation

  • Internally
  • Procedures

Nationally

  • Nationally
  • Information, dialogue
  • Research
  • Learning modules
  • Internationally

Internationally

  • Communication (exchange, dialogue)
  • Research
  • Standards, results depositories

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acknowledgments

  • Various stakeholders
  • Various stakeholders
  • Apropomedia
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Thank you

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