Transcript Rapport - Proportion

Protecting human subjects
in research
Pawel Stefanoff
Key issues
• Historical perspective
• Guiding principles
• Guidance for protocol preparation
• Informed consent
• Ethical committee review
• Conducting the study
• Reporting the study
Ethical guidance for research:
Milestones
• Nuremberg code
– War crimes tribunal at Nuremberg (1947)
• Universal declaration of human rights
– United Nations General Assembly (1948)
• Declaration of Helsinki (1964)
– World Medical Association
• International technical guidelines
– Council for International Organisations of Medical Sciences
(CIOMS)
• World health Organization WHO
The Tuskegee syphilis study (1/2)
• Cohort study conducted
in the first part of the
20th century
Tuskegee, Macon
County, AL, USA
• Patients recruited with
syphilis and followed
up for decades to study
the natural history
The Tuskegee syphilis study (2/2)
• Issues
– No treatment given
– No information
– No consent
Spinal taps
• Dramatic consequences
• Epilogue
– President Clinton’s
apology (1997) to
survivors
Burial stipends
Basic ethical principles
• Autonomy
– Respect for the person who is a study subject
• Justice
– Burdens and benefits should be equally distributed
• Beneficence
– “Do good”
• Non-maleficence
– “ Do no harm”
Research vs. non-research
• Research
– Produces results that are generalizable
• Non-research
– Programme evaluation
– Surveillance
– Emergency operations
(e.g., outbreak investigation)
Ensuring the protection of human
subjects in epidemiology
• All projects
– Minimize risks
• Ensure confidentiality
– Maximize benefits
– Obtain informed consent
• Research projects
– The same general principles apply
– Ethical committee clearance required in addition
Exercise 1: Is this research?
? A case-control study of tick-borne encephalitis
risk factors
? A telephone survey collecting information on
attitudes towards vaccination
? An evaluation of a surveillance system for
aseptic meningitis
Criteria that a research protocol
must meet
• Useful research question
• Scientifically sound approach
• Appropriate procedures
• Planned analysis
• Vulnerable populations protected
• Low risks, maximum benefits
• Good tools
• Informed consent
Only good studies are ethical!
Example of vulnerable populations
• Pregnant women
• Adolescents
• Children
• Elderly
• Refugees
• Prisoners
• Those who can't give consent (unconscious)
• Persons with mental or behavioural disorders
Research in vulnerable populations
• Must not be studied if unnecessary
– Do not study a new drug among prisoners
• May be studied if the research question is of
direct relevance to the population
– Harm reduction strategies might be relevant to
prisoners among which illicit drug use is common
– Provide evidence that the vulnerable population
will not be exploited
Low risks and maximum benefits (1):
Study participants
• Risks and benefits for the participants
• Weight them honestly
– Do not under-estimate risks
– Do not over-estimate benefits
Low risks and maximum benefits (2):
Study population and other populations
• Benefit / harm for communities from which
the participants are drawn
• Benefit / harm for communities beyond the
research population
Maximize the welfare of participants
• Counsel participants
• Protect privacy and psycho-social needs
• Deal with adverse reactions
Exercise 2: Minimizing risks,
maximizing benefits
• You would like to conduct a study on the factors
associated with anemia among adolescent girls
• You propose to conduct a survey, to collect blood
samples and to identify the factors that are
associated with being anemic
• List two critical steps you would take to:
– Minimize harm
– Maximize benefits
Informed consent
• Ban undue inducements to participate
• Ensure free participation
• Make provision for:
– Those who can’t read / sign
– Those who can’t give personal consent
How does a person give
an informed consent?
• Information received
• Information understood
• Decision made without:
– Coercion
– Undue influence / inducement,
– Intimidation
The consent form (1/5)
• Attached to protocol
• Lay language
• Complete /adequate
• Clear mention of research
• Rationale for the study
• Details of what is asked from participants
• Duration of the research
The consent form (2/5)
• Nature, sequence and frequency of procedures
• Nature and likelihood of anticipated discomfort or
adverse effects
– Physical risks
– Psychological and social risks
– Clarifications
• What has been done to minimize risks
• Action to be taken if they occur
• Outlines the possible benefits, if any
The consent form (3/5)
• Outline of the procedure to protect
confidentiality
• Mention if confidentiality is not possible
• Mention that:
– Participation is voluntary
– Refusal to participate (or discontinue participation)
involves no penalty / loss
• Description of alternatives to participation
The consent form (4/5)
• Nature of any compensation /reimbursement
– Time
– Travel
– Person-days lost from work
• Plans for feedback to participants if any
• Contact information
The consent form (5/5)
• Provision for subjects incapable of reading
and signing
• Provision for participants incapable of giving
personal consent
Referring to the biological specimens
in the consent form (1/2)
• Nature, number and volume
• Procedures to be used
– Routine or experimental
– Invasive or not
• Use to which specimens will be put
– For the study
– In the longer term (e.g., left over)
Referring to the biological specimens
in the consent form (2/2)
• Will results will be returned to subjects?
• How will the leftovers be handled?
• Will there be genetic/genomic testing?
Confidentiality of data
• Do not collect identifiers on data collection
instruments
– Use study codes
• Do not enter identifiers in electronic data files
Identifiers logs
• Contain identifying information
• Collected on paper
• Separated from the data collection
instruments after field verifications
• Kept under lock and key
• Destroyed after data analysis
Line listing and identifier log
• Electronic data file
– Not confidential, can be analyzed
Uni. ID
1
2
3
4
OnsetDate Ward
Block
City
01.mar.05
18
2 HYD
03.mar.05
22
1 HYD
05.mar.05
23
3 HYD
06.mar.05 SEC
AgeYearsSex
12
25
36
23
1
2
1
2
Hospital Death
HEVIgM HAVIgM
1
2
1
9
1
2
2
1
2
9
9
9
1
1
1
2
• Separate identifier log
– Confidential, cannot be analyzed, kept on paper
Uni. ID
1
2
3
4
Name
Salif Keita
K Suresh
A.D. Singh
R.T. Balaj
Address
234 Defense colony
234 Nugambakam High Road
234 Ring road
678 Vadapalani
Phone
044 12 34 56 78
044 87 65 43 21
044 98 87 65 41
044 14 25 36 78
Confidentiality of specimens
• Clinical specimens for investigations
(e.g., outbreaks)
– Identifier may be on the specimen
– Results given back to patient/ provider
• Research specimen
– Study code on the specimen
– Results given back or not, as relevant
Ethical committees
• Basic responsibilities
• Composition
• Terms of reference
• Review procedures
• WHO guidelines available
– http://www.who.int/tdr/publications/publications/e
thics.htm
Responsibilities of the ethical committee
• Safeguarding the dignity, rights, safety, and
well-being of research participants
• Consider principles of justice
• Review ethics of proposed studies
Composition of ethics committees
• Multidisciplinary / multi-sectoral
• 5-7 to 12-15 members
• External chairperson
• Member secretary
– Operates routine business
• Members from diverse origins
• Adequate age, gender and community
representation
Initial approval and follow up
• Review of proposed research
– Before its initiation
• Regular evaluation of ongoing studies
– All that received a positive decision
Ethical committee review
• Presentation of protocol
• Discussions / questions (quorum)
• Clear decision
– Clearance
– Conditional clearance
– Deferral
– Refusal
• Documentation of all processes
– Checklist / standard operating procedures
Exemption from ethical review
• Teaching
• Educational tests
• Research on existing data
• Programme evaluation
• Consumer satisfaction survey for food
Conducting the research according
to the protocol
• Follow protocol
• Ensure protection of human subjects as part
of the field work quality assurance
– Train field workers
– Standardize field work procedures
– Supervise
– Check forms and reports
Actually collecting informed consent
• Present the study
• Offer participation
• Collect consent if the patient agrees
• Leave a copy of the signed document
Data analysis
• Do not analyze files containing identifiers
• Make sure that the analysis would not
disclose personal information
– E.g., surveillance reports identifying cases in a
small community
Exercise 3: Ethical review needed?
? A case-control study of tick-borne encephalitis
risk factors
? A telephone survey collecting information on
attitudes towards vaccination
? An evaluation of a surveillance system for
aseptic meningitis
Elements to mention in the final report
• Risks and benefits to participants
• Measures taken to protect human subjects
• Clearance obtained (or exemption)
Take home messages
• Follow principles of autonomy, justice,
beneficence and non-maleficence
• Use a checklist to prepare your protocol
• Conduct the study according to protocol
• Only well planned, valid studies are ethical!
• Apply country rules, but act according to
universal ethical principles
Useful resources
• www.wma.net
• www.who.int/rpc/research_ethics/en/
• http://www.cioms.ch/
• http://www.hhs.gov/