protecting human subjects in research pawel stefanoff
TRANSCRIPT
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
• Patients recruited with syphilis and followed up for decades to study the natural history
Tuskegee, Macon County, AL, USA
The Tuskegee syphilis study (2/2)
• Issues– No treatment given
– No information
– No consent
• Dramatic consequences
• Epilogue– President Clinton’s
apology (1997) to survivors
Spinal taps
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 OnsetDate Ward Block City AgeYearsSex Hospital Death HEVIgM HAVIgM1 01.mar.05 18 2 HYD 12 1 1 2 1 92 03.mar.05 22 1 HYD 25 2 1 2 2 13 05.mar.05 23 3 HYD 36 1 2 9 9 94 06.mar.05 - - SEC 23 2 1 1 1 2
Uni. ID Name Address Phone 1 Salif Keita 234 Defense colony 044 12 34 56 782 K Suresh 234 Nugambakam High Road 044 87 65 43 213 A.D. Singh 234 Ring road 044 98 87 65 41 4 R.T. Balaj 678 Vadapalani 044 14 25 36 78
• Separate identifier log– Confidential, cannot be analyzed, kept on paper
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/ethics.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/