| 7.
Research participants |
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Research
may be conducted on healthy volunteers or on patients. Within
each broad group a number of special groups require particular
ethics consideration.
7.1
Research on healthy volunteers
A
healthy volunteer has been defined as an individual who is not
known to suffer any illness relevant to the proposed study and
who is able to understand and give valid consent to the study.4
Although
it may be scientifically appropriate to use patients as controls
for a condition from which they do not suffer, they should still
be regarded as patients. Because of the subtle pressures to
which patients may be subjected, great care must be taken in
recruiting such volunteers.
Research
on healthy people is undoubtedly necessary, but concern for
the health, safety and rights of the healthy volunteer must
be paramount.
Research
on healthy volunteers, as on any research participants, must
be carried out with appropriate selection of volunteers, informed
consent and proper conduct of research. Where appropriate, compensation
for injury should be made in accordance with the principles
of the guidelines of the Association of the British Pharmaceutical
Industry as adapted for South Africa.10 (See Appendix
IV.)
Appendices
I and II are the MRC checklists provided to assist in compiling
healthy volunteer information sheets and consent forms.
7.1.1
Therapeutic and non-therapeutic research
By
definition, healthy volunteers will not be participants in therapeutic
research, but will participate in non-therapeutic research.
They will thus not benefit directly from the research in which
they participate. The risk to which healthy volunteers are subjected
must thus be no more than minimal (see also 9.12.4.3).
7.1.2
Recruitment and selection of healthy volunteers
Recruitment
of healthy volunteers for research projects may involve conscious
or unconscious pressures on both the investigator and the volunteer.
The motives that prompt people to volunteer are various. They
may be scientific or idealistic, but there must be no coercion,
overt or covert, to induce anyone to volunteer for research.
Initial
recruitment should be through circulars, notices and announcements
to groups, and not by individual approach. The method of recruitment
and source of healthy volunteers should be included in the study
protocol submitted to the Research Ethics Committee.
Excessive
use of any volunteer should be avoided and study organisers
should prevent this by maintaining lists of volunteers.
Conducting
research on oneself is not discouraged, but any persons planning
to experiment on themselves should seek the guidance of the
Research Ethics Committee before starting their research.
7.1.3
Special groups
Special
consideration must be given to protecting the welfare of certain
classes of research participants; for example, pregnant women,
children and adolescents, prisoners, people with mental disabilities
and the elderly, students and persons in dependent relationships.
7.1.3.1
Pregnant women
Special
attention must be given to non-therapeutic research that involves
women who are pregnant or may become pregnant, because of additional
health concerns during pregnancy and the risk of damage to the
fetus.
The exclusion
of pregnant women from research should be adequately justified,
both in terms of protecting the health of the fetus and from
the perspective that such exclusion is scientifically supportable.
7.1.3.2
Children
Non-therapeutic
research on healthy children (under the age of 18 years, according
to the Constitution) should be approved only if the research
places the child at no more than negligible risk (see also 9.12.4.3).
Research that would be equally informative if carried out on
adults, should never be done on children. Children should participate
only where their participation is indispensable to the research.
There must
be no financial or other inducement to participate for parent,
guardian or child, although reimbursement of expenses is allowed.
A small gift to the child after completion of the research is
acceptable.
In all cases
assent of the child and consent of the parent or legal guardian
must be obtained. A child's objection to participation in research
must always be respected (see also 5.3.1.2).
7.1.3.3
Prisoners
It
is not inherently unethical to carry out non-therapeutic research
on prisoners. However, particular care must be taken to ensure
that informed consent is given and that coercion in any form
is avoided. It must be made clear that participation in the
research will not lead to any favours, such as reduction of
sentence, or special privileges. Similarly, non-participation
will not have adverse consequences.
Research
Ethics Committees must pay attention to any proposal to undertake
research on prisoners, to avoid exploitation of these persons.
The Committee must be convinced that the research cannot be
conducted on another population. If research on prisoners is
undertaken, the Research Ethics Committee must be satisfied
that it will be done under conditions of safety for all concerned.
7.1.3.4
People with mental impairment
Non-therapeutic
studies should not be done on the mentally handicapped if the
same information can be obtained from studies on any other group.
Research that is likely to benefit or prevent mental handicap,
and is possible only in mentally handicapped people, is acceptable
if precautions are taken, similar to those that apply to children
(see also 5.3.1.2).
7.1.3.5
The elderly
Particular
care should be paid to the elderly participant's ability to
comprehend what is entailed in volunteering as a research participant.
Because elderly people are often in a position of dependence
on caregivers, they must be reassured that failure to volunteer
carries no negative consequences.
No research
should be conducted on the elderly if the same information can
be obtained from research on other adults.
7.1.3.6
Students
Students
are particularly vulnerable to academic, personal and financial
pressures.
It should
be made clear that refusal to participate in, or a decision
to withdraw from a non-therapeutic study carries no negative
consequences. Equally, it must be made clear that participation
carries no hidden benefits. An investigator who is involved
in any way in the tuition or assessment of the student, should
not participate in the recruitment of that student. Investigators
should be aware of, and try to minimise factors such as the
desire to please or not displease, to gain favourable notice
or promotion.
Reimbursement
of expenses and a possible honorarium should be reasonable for
the amount of inconvenience, but should not be excessive or
unduly influence risk-taking.
7.1.3.7
Persons in dependent relationships (see also 5.3)
Persons
whose proposed involvement in non-therapeutic research arises
from dependent relationships, need additional attention to ensure
that their involvement is voluntary and that their consent is
adequately informed. They include those in junior or subordinate
positions in hierarchically structured groups such as:
- employees
and employers;
- wards
of State and guardians;
- patients
and health care professionals.
Patients
should be invited to participate in research as volunteers,
in the same way that healthy individuals are invited to participate.
Patients,
unlike healthy volunteers, are dependent on clinical advice
or treatment, and may feel under an obligation to clinicians.
This, and the fact that some patients may have an impaired capacity
to understand what is intended, necessitates safeguards to ensure
that volunteering is valid and is based on adequate information.
7.1.3.8
Vulnerable communities
The
characteristics of a vulnerable community include one or more
of the following:
- limited
economic development;
- inadequate
protection of human rights;
- discrimination
on the basis of health status;
- inadequate
understanding of scientific research;
- limited
availability of health care and treatment options;
- limited
ability of individuals in the community to provide informed
consent.
The ethics
of research in vulnerable communities and developing countries
is of growing concern11 (see also 11).
South Africa
is home to a number of vulnerable communities. Particular caution
must be exercised before permission is given to undertake research
involving such communities. The Research Ethics Committee must
be satisfied that the research cannot be carried out in a less
vulnerable community, and that the research is responsive to
the health needs and priorities of the community in which it
is to be carried out. The research protocol should demonstrate
some benefit to the community involved, and how feedback on
the outcome of the research will be transmitted to the community.
Particular
attention must be paid to the content, languages and procedures
used to obtain informed consent in vulnerable communities.
7.2
Research on patients
A
patient is defined in the research context as someone whose
participation in research derives from either:
- having
sought or accepted clinical care;
- having
been selected from the general population because of known
or suspected abnormality;
- a control
participant suffering from a disease which is not the subject
of study.
Although
it may be scientifically appropriate to use patients as controls
for a condition from which they do not suffer, they should still
be regarded as patients. Because of the subtle pressures to
which patients may be subjected, great care must be taken in
recruiting such volunteers.
The study
of disease as it occurs in patients, and of the effects of treatment,
are indispensable parts of the continuing process of improving
efficiency of diagnoses and effectiveness of treatment. Patients
may willingly participate in research: however, a patient is
in a position of at least partial dependence which may affect
the capacity to volunteer completely freely. In addition, the
ability of the patient to give informed consent may be impaired
by illness.
7.2.1
Therapeutic and non-therapeutic research (see also 2.1.2)
In
most cases, research on patients will be therapeutic research;
that is, investigating an intervention that might be of therapeutic
benefit to the patient.
In therapeutic
research, the benefits likely to accrue to the individual patient
participating should outweigh the risk of harm. As a general
rule, research involving patients should incur no more than
minimal risk unless there is great potential benefit to the
individual.
7.2.2
Special groups
Investigators
must ensure that research protocols exclude groups that might
be markedly more at risk than others, unless their inclusion
is absolutely necessary.
Inclusion
of an individual or group that may be especially vulnerable
- children, for instance - should be approved only if the Research
Ethics Committee considers such inclusion to be essential, and
that the participation of less-vulnerable subjects would not
answer the purpose of the research.
Patients
must be made aware that they may decline to participate in a
research study, and that they may withdraw from the study at
any time without suffering any discrimination or adverse consequences.
The patients' decision will be respected and accepted without
question, and they will be treated as though the matter had
not arisen, without compromising future care.
Those special
groups addressed in 5 require the same sort of special consideration
whether they are participating in research as healthy volunteers
or as patients. One other group requires particular consideration
as patients.
7.2.2.1
Persons with cognitive or mental impairment
This
group includes people with psychiatric or developmental disorders,
or people who are substance abusers. They may have reduced capacity
to comprehend the research and to agree to participate in it.
Institutionali-sation may also compromise an individual's capacity
to make a truly voluntary decision to participate in a research
study.
Persons
with a cognitive or mental impairment should not participate
in research that could equally well be conducted on persons
without this impairment.
The research
must be relevant to cognitive impairment, possible to evaluate
only in people with such impairment and likely to benefit or
prevent cognitive impairment.
7.2.3
Confidentiality
Any
list of patients' names must be confidential to the person responsible
for its compilation. Use of a coding system should ensure this.
In most circumstances, the person who recruits the patient should
be the clinician responsible for the routine clinical care of
that patient.
7.2.4
Use of clinical records in research (See also 6.6)
Personal
clinical records are a vital tool for much clinical and epidemiological
research. Great care must be exercised to protect privacy and
maintain confidentiality, to avoid causing harm or distress
to patients or their relatives. Research that will involve access
to personal health records must receive approval from a Research
Ethics Committee.
In general,
the researcher should seek the consent of the clinician currently
or most recently responsible for the care of the patient, before
using the record for research purposes.
In principle
it is also necessary to obtain the consent of the patient before
the clinical record is used as a source of information for research
purposes, especially if the patient's right to privacy might
be infringed - by linking the research with the patient, for
example. The point at which a record review is decided on has
been seen in the past as decisive. Retrospective record analyses
may be done without patient consent, provided they are done
anonymously, but prospective record analyses require patient
consent. However, the better ethical and legal view is that
consent should also be obtained, if possible, for retrospective
analyses.
Information
derived from personal clinical records stored in computers requires
the same safeguards as conventional paper-based records. Particular
care is required where information from clinical records is
transferred to computers that can be accessed by many users.
Since this
is a confusing issue, here is some clarification:
The right
to privacy - which includes autonomy over personal information
- is a common-law and constitutional right. This means inter
alia that clinicians must keep confidential all private information
pertaining to their patients. Privacy is at stake only when
the bearer of the right can be identified through the private
information divulged. Clinicians who pass on personalised data
to third parties, including research investigators, without
the patient's informed consent, may be liable for breach of
confidentiality.
In principle
the patient's consent to disclosure of named data must be sought,
whether the envisaged research is retrospective or prospective
in nature. In such instances privacy must be adequately safeguarded,
by not allowing unauthorised persons access to the information,
for example, and by requiring all investigators involved to
sign a confidentiality agreement. Consent may be dispensed with
only in exceptional circumstances, such as where the public
interest in the information being passed on clearly outweighs
the individual interest in privacy.
The law
may also oblige clinicians to disclose private information,
such as that concerning notifiable medical conditions, to public
health authorities. The Promotion of Access to Information Act,
No 2 of 2000, gives effect to the constitutional right of access
to information held by the State or its departments. An official
of a State department in the national or provincial sphere,
or a contractor engaged by such department as an independent
contractor, may give access to information held by that body.
This means, for example, that if the Department of Health has
contracted with someone to act as an independent contractor,
this contractor may give access to data (concerning notifiable
medical conditions, for instance) held by the Department, if
all the requirements of the Act are met. Access to records will
be refused if it might involve the unreasonable disclosure of
personal information about a third party, including a deceased
individual. However, even such unreasonable disclosure of information
may be warranted if the individual consented to the disclosure,
or had been informed by the public body before the information
was given, that the information belonged to a class of information
that would or might be made available to the public. Unreasonable
disclosure may also be warranted if the public interest clearly
outweighs the potential harm resulting from disclosure of the
information.
When patients
are asked to consent to the use of their records or personal
information in research, they should be informed whether (i)
their coded information will be used for research purposes (which
will be the first option), or (ii) their named information will
be used for research purposes, and, if so, which safeguards
will protect their privacy. In general, all patients or participants
should be informed of confidentiality procedures as part of
the consent process. This would apply to both category (i) and
(ii) research. Coded information should preferably be used.
Codes should be used to distinguish between patients and participants.
Where identifiers are needed to link data with a patient or
research participant, they should be kept separately from the
individuals' records. Upon completion of the research, these
identifiers should be destroyed.
Occasionally
it may be permissible to dispense with patients' consent to
use their hospital or clinic records in prospective record reviews
provided that:
- A risk
benefit analysis shows that the public interest in the information
being passed on clearly outweighs the individual interest
in privacy.
- All
information is normally de-identified, which means that it
is not possible to identify a specific individual. Examples
of identifiers include the individual's name, hospital number,
ID number, date of birth and address.
- The
methods for de-identifying record information are stated and
acceptable to a Research Ethics Committee.
- Individuals
de-identifying the records have acceptable training in the
de-identifying method acceptable to a Research Ethics Committee.
- The
individuals de-identifying the records have signed a confidentiality
declaration acceptable to a Research Ethics Committee.
- Security
standards for the storage and use of the records are acceptable
to a Research Ethics Committee.
- Use
of the records is limited to individuals who have signed an
acceptable confidentiality declaration and who are approved
by a Research Ethics Committee.
- No one
may have access to the de-identified records without approval
by the Research Ethics Committee that approved the original
record review.
- Each
new use of the information is acceptable to the Research Ethics
Committee that approved the original record review.
- Any
financial benefits from the reproduction or use of the information
must be openly declared and be acceptable to the Research
Ethics Committee that approved the original record review.
- A complaint
procedure regarding use of the records is available.
- The
collection, storage and use of the records fulfil South African
legal requirements.
It is the
responsibility of the current investigator to ensure that the
above criteria are met.
7.2.5
Protection against excessive requests
Some
groups of patients, such as those with rare diseases, may be
at risk of exploitation through frequent requests to take part
in research that may not directly benefit them. Investigators
must be sure that such patients, or patients who are readily
available and compliant, are not exploited for the sake of convenience
and that they do not feel obliged to participate in research
as a condition of receiving care.
7.2.6
Consultation with other clinical advisers
Where
a research project originates in a hospital or other health
institution, the patient's personal clinician, under normal
circumstances, should be informed of and should agree to the
intended research. Only in the case of research of a minor and
non-invasive nature need the personal clinician not be informed.
Proper communication
is essential between all health care workers who share responsibility
for the care of the patient.
7.2.7
The patient as a volunteer
Patients
should be invited to participate in research as volunteers,
in the same way that healthy individuals are invited to volunteer.
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