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International Research and Subjects Protections. Richard Carpentier, National Council on Ethics in Human Research and FOCUS Secretariat, CANADA. Agenda. 1.Increase in International Research. 2. Ethical Breaches. 3.Sustaining Trust. 4.Capacity-building. 5. About International Standards. - PowerPoint PPT Presentation
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International Research and Subjects ProtectionsInternational Research
and Subjects Protections
Richard Carpentier, National Council on Ethics in Human Research and FOCUS Secretariat, CANADA
AgendaAgenda
1.Increase in International Research1.Increase in International Research
2. Ethical Breaches 2. Ethical Breaches
3.Sustaining Trust 3.Sustaining Trust
5. About International Standards 5. About International Standards
4.Capacity-building4.Capacity-building
6. A Word about FOCUS6. A Word about FOCUS
Why is Research Subjects Protections in International Research So Important Now?
Why is Research Subjects Protections in International Research So Important Now?
Because research activities are increasing
Because research is moving in countries with less experience and infrastructures
Because research is less and less in control of academic/public institutions and more in control of for-profit corporations
Because we have multiple experiences of ethical breaches
BECAUSE WE NEED TO SUSTAIN TRUST
Increase in International Research Activities
Increase in International Research Activities
Analysis of National Institutes of Health Awards to Analysis of National Institutes of Health Awards to International OrganizationsInternational Organizations
Distribution of Funded Grants to International Organizations for Human Distribution of Funded Grants to International Organizations for Human Subjects Research in FY 2003 Includes Funding of R&D ContractsSubjects Research in FY 2003 Includes Funding of R&D Contracts
$0
$5
$10
$15
$20
$25
$30Dollars in B
illion
1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003
Fiscal Year
NIH Budget History
Growth of International Federal Wide AssuranceGrowth of International Federal Wide Assurance
0
200
400
600
800
1000
1200
1400
1600
FY 2001 FY 2002 FY 2003 FY 2004
New FWAs
Total FWAs
Number of Overseas Human Clinical Trials for New DrugsNumber of Overseas Human Clinical Trials for New Drugs
0
1000
2000
3000
4000
5000
6000
7000
8000
'91 '92 '93 '94 '95 '96 '97 '98 '99 '00
Developed CountriesLess Developed Countries
Sources: FDA Biomonitoring Research database; Parexel’s Pharmaceutical R&D Statistical Sources: FDA Biomonitoring Research database; Parexel’s Pharmaceutical R&D Statistical Sourcebook 1999; Aculaunch; Washington Post ResearchSourcebook 1999; Aculaunch; Washington Post Research
Human Subjects in Clinical TrialsHuman Subjects in Clinical Trials
0
20000
40000
60000
80000
100000
120000
2000 2001 2002 2003
US
International
US decrease 40%
International increase 82%
Foreign Clinical TrialsForeign Clinical Trials
• Percentage of NDA submissions using foreign data– 1995 --- 9%– 1999 --- 27%
• Numbers of foreign human subjects participating in NDA clinical trials– 1995 --- 4,000– 1999 --- 400,000
U.S. Department of Health and Human Services
The Globalization of Clinical Trials: A Growing Challenge in Protecting
Human Subjects
U.S. Department of Health and Human Services
The Globalization of Clinical Trials: A Growing Challenge in Protecting
Human Subjects
Janet Rehnquist Inspector General, September 2001
The Globalization of Clinical TrialsThe Globalization of Clinical Trials
Purpose of the Report
To document the growth of non-U.S. clinical
drug trials contributing data to New Drug
Applications for Food and Drug Administration
(FDA) approval, and to assess FDA’s
capacity to assure human subject
protections in these trials.
The Globalization of Clinical TrialsThe Globalization of Clinical Trials
Background
In our June 2000 report, Recruiting Human Subjects: Pressures in Industry-Sponsored Clinical Research (OEI-01-97-00195), we drew attention to the fact that clinical drug trials conducted outside the U.S. can be an important source of data in FDA’s determination of the safety and efficacy of new drugs.
The Globalization of Clinical TrialsThe Globalization of Clinical Trials
We recommend that FDA:
•Obtain more information about the performance of foreign institutional review boards
•Help foreign review boards build capacity to conduct effective human subject reviews
The Globalization of Clinical TrialsThe Globalization of Clinical Trials
•Encourage sponsors to obtain attestations from foreign investigators that they will adhere to ethically sound principles of research
•Encourage greater sponsor monitoring
•Develop a database to track the growth and location of foreign research
The Globalization of Clinical TrialsThe Globalization of Clinical Trials
We recommend that the Office for Human Research Protections
•Exert leadership by developing strategies to ensure that adequate human subject protections are afforded for non-U.S. clinical trials that are funded by the Federal government and/or that contribute data in support of a New Drug Application
The Globalization of Clinical TrialsThe Globalization of Clinical Trials
Encourage accreditation of institutional review boards in a voluntary accreditation system as one way to improve the capacity to conduct appropriate reviews of human subject protections in proposed research.
The Office for Human Research Protections, working with FDA, NIH, and others, can help develop such a system internationally
Department of Health & Human Services Office of Inspector General
The Orange Book 2005
Department of Health & Human Services Office of Inspector General
The Orange Book 2005
Daniel R. Levinson, Inspector General
The Orange Book 2005: Obtain Data on IRBsThe Orange Book 2005: Obtain Data on IRBs
We recommended that FDA examine ways to obtain
more information about the performance of non-
US IRBs and help those inexperienced IRBs build
their capacities; encourage all non-US investigators
participating in research to sign attestations upholding
human subject protections; and develop a database to
track the growth and location of foreign research.
The Orange Book 2005The Orange Book 2005
We recommended that OHRP exert leadership in
developing strategies to ensure adequate human
subject protections for non-US clinical trials
funded by the Federal Government and those that
contribute data to new drug applications.
Ethical BreachesEthical Breaches
Illegal Trials in IndiaIllegal Trials in India
OVER 430 unsuspecting young women have been
used as guinea pigs by self-styled researchers in
India to test if an anti-cancer drug, Letrozole, can be
used to induce ovulation.
The clinical trials have been conducted illegally,
predominantly at private clinics not recognised as
research centres. At least one ‘‘investigator’’ with
just a diploma in gynaecology could hardly claim to
be qualified or competent enough to try untested
drugs.
Improper Research by Johns Hopkins Researcher in India Improper Research by Johns Hopkins Researcher in India
A Johns Hopkins University scientist, Dr
Ru Chih C. Huang, tested experimental
cancer drugs on patients in India without
required federal approval, nor university
research ethics approvals and without
adequate preliminary tests in animals.
Use of placebos in AIDS vaccine research in BankokUse of placebos in AIDS vaccine research in Bankok
A Thai nurse prepares a syringe with an experimental AIDS vaccine to inoculate a "volunteer" at the Bangsue Narcotics Clinic in Bangkok. Some participants in the drug study are given placebos, not real medicine.
VanTx Research, Basel, SwitzerlandVanTx Research, Basel, Switzerland
•In 1998-1999, VanTx, a CRO, was recruiting
Estonian and Polish students, proposing
‘vacations in Switzerland’, with high salary. It
was working for major pharmas.
•Reports say subjects were sequestrated with
passports confiscated
VanTx Research, Basel, SwitzerlandVanTx Research, Basel, Switzerland
•Use of non-recognized ethics committee
•Consent form signed after minimal
information, in a foreign language (German)
•Participants coerced to remain enrolled in
trials
•The firm falsified test results
•Absence of medical follow-up after study
Has Canada Let Her Down?Has Canada Let Her Down?
After more than 20 years of having her
remarkable resistance to HIV studied
by Canadian and Kenyan scientists,
she is grateful for the free medical
service she receives in return but pines
to escape her life of prostitution. ‘I feel
they take advantage of me,’ she says of
the researchers, ‘because I’ve made
such a big name all over the world [for
the project], but I’m still in this
business. I need something to lift me
out of Majengo.’
The Globe and Mail, January 7, 2006
Lack of Ethics ReviewLack of Ethics Review
A survey of more than 200 developing-country health researchers has found that a quarter of clinical trials carried out in developing countries do not undergo any kind of ethical review in the host nation.
Re Journal of Medical Ethics, February 2004
Sustaining TrustSustaining Trust
Erosion of Public TrustErosion of Public Trust
• There is a public perception that subjects of clinical trials are equivalent to guinea pigs•Trust is an essential ingredient in the success of clinical trials – as necessary to recruit subjects•Need to be very honest with subjects about the nature of research (this is not treatment) the risks and benefits, and avoid conflicts of interest
2004 International Will & Why Survey2004 International Will & Why Survey
"Of the Polish respondents who would
not participate in a clinical trial, 45
percent responded because of the
health risks in clinical trials and 28
percent responded because of the
"guinea pig" perception associated with
clinical trials. "
Erosion of Public TrustErosion of Public Trust
• People are not aware that over and above the confidence they have in their doctors, there are protections in place
• International research should not create double standards in terms of experimental treatment
• Need to publicize ethical protections, make policies available
Erosion of Public TrustErosion of Public Trust
There is a fear that only lip service paid to ethics
Ethics Committees are instruments which should help maintaining trust
Ethics Committees are instruments which should help maintaining trust
Need for capacity-building
Capacity-building for Ethics CommitteesCapacity-building for Ethics Committees
• Local research ethics committees are essential as they provide the knowledge of the local research context
– Vulnerability of research participants– Specific conditions of research and of
health system– Cultural variability in the application of
norms and policies– Assessing risks and benefits,
appropriate language
Capacity-building for Ethics CommitteesCapacity-building for Ethics Committees
• National education strategy aimed at researchers, institutions and Research Ethics Committees
– Applicable law, regulations and policies– How to review a protocol– Rules for informed consent
•Inventory of RECs
Capacity-building for Ethics CommitteesCapacity-building for Ethics Committees
• Development of national criteria and standards based on cultural background and needs
• Friendly educational visits to help at the application of criteria and standards … to develop eventually into accreditation
About International StandardsAbout International Standards
International StandardsInternational Standards
• Most standards are principle-based
• Most standards are voluntary, for example Helsinki and CIOMS;
• International declarations agreed upon by states need to be embedded in enforceable instruments
• However there is little verification in terms of quality of implementation
International StandardsInternational Standards
• The implementation of other standards subject to better monitoring:– Good clinical practice– US Regulations (FDA, OHRP)
US FWAUS FWA
• One of the most powerful instrument is perhaps the FWA required from all institutions receiving funds from HHS
• Many institutions seem to adopt a naïve attitude and not to read the fine prints: but signatory institutions commit themselves to doing many things
US FWAUS FWA
• All research in the institution must be guided by a statement of ethical principle
• Need written procedures for:– Reporting to the EC and appropriate officials
• Unanticipated problems creating risks to subjects• Serious or continuous non-compliance• Suspension or termination of research
– Conducting initial and continuing review– Determining which projects need more than
annual review
US FWAUS FWA
• Ensuring prompt reporting to EC of proposed changes to research activities and ensuring they are not implemented without EC approval, unless I would eliminate risks to subjects
• AND THERE IS MORE TO READ …
• Inspections may be conducted on the basis of FWA and use of research funds suspended if not satisfactory
FOCUS : the Canada-US Forum
FOCUS : the Canada-US Forum
About FOCUSAbout FOCUS
FOCUS strives to achieve its objective through the following activities:
– Providing a forum for regular meeting and discussion of
research ethics issues common to Canada and the United
States and to facilitate dialogue, co-operation and exchange of
experience between individuals and organization in order to
enhance the protection of human participants in research;
– Fostering communication and partnerships between Canada
and the United States, between governments and other
organizations that share common values and goals;
About FOCUSAbout FOCUS
• Improving communication among IRBs/REBs;
• Promoting the development and implementation of
actions designed to improve the quality of ethics
review (e.g., accreditation);
• Promoting education about the ethics of research
in humans across all disciplines.
Annual Conferences and PublicationsAnnual Conferences and Publications
• 2003 Canadian and American Perspectives on Quality Improvement and Performance Evaluation in Systems of Human Research Protection
•2004 International Conference on Conflicts of Interest
•2005 Ethical Issues in Behavioral and Social Sciences Research
•2006 Research Ethics Education for Investigators •2007 Maintaining Public Trust in Clinical Research
Thank you!
www.ncehr-cnerh.org