The ethical-legal framework for child research in South Africa
Currently South Africa does not have a comprehensive ethical-legal
framework regulating research with children. The Constitution (s12(2)
(c)) prohibits research without informed consent .
However, there is currently no health or child care legislation dealing
directly with child or adolescent research. Health rights are found
scattered through the Constitution, common law and various statutes and
they do not set out when and how children may participate in research.
The primary piece of legislation dealing with the protection of
children is the Child Care Act  which provides for some of a child's health rights but does not deal with research. In May 2005 the National Health Act 
became effective. It creates a national framework for health care
delivery. Section 71 of the Act covers health research with human
subjects including minors. This section has not been implemented as yet
and it is unlikely that it will come into effect before the middle of
2007. In June 2006 a new Children's Act 
was promulgated that will repeal the existing Child Care Act, however,
it is not yet in operation. In addition, there are 4 major sets of
ethical guidelines in South Africa bearing on child research [18-21]. Recently, draft regulations for research with human subjects were published for public comment .
It is envisaged that once the regulations are finalized, s71 will be
implemented. Given this state of flux, this article refers to both
current and future ethical-legal obligations.
Key considerations for lawful adolescent HIV vaccine trials
For research to be lawful within any legal system it must comply
with substantive and procedural requirements established in law and
ethical guidelines. The nature of these obligations varies from system
to system, however most establish requirements relating to consent,
ethical review and scientific validity. In South Africa, there are
three key issues that must be taken into account when ensuring that
adolescent research is lawful. These are elaborated on below:
(i) Consent requirements must be met
(ii) Legal obligations in child protection laws must be complied with; and
(iii) There must be compliance with requirements for ethical and regulatory review.
(i) Informed consent
Who must consent?
In South Africa, for adolescent trials to
be lawful, consent must given by a participant with legal capacity to
consent, or if not competent, by a person with the authority to consent
on the participant's behalf.
Independent consent by adolescents
In terms of
current South African law, there is no provision setting out when
children may provide their own independent consent to research. However
children may consent independently to medical treatment from the age of
Accordingly some legal scholars have argued that children of 14 and
older can consent independently to "therapeutic" research  while others have argued that such an equation cannot be easily made.25 With regard to "non-therapeutic" research some have argued for independent child consent if there is no risk at all  while others have asserted that proxy consent is always required, and can indeed only be given in restricted circumstances .
In terms of current South African law, there is also no guidance on who
may provide consent for child participation in research if children
lack this capacity themselves. It appears that most South African
research ethics committees (RECs) have relied on the recommendations
made in ethical guidelines which broadly require parental or
guardianship consent for research plus the assent of the child [20,21].
Consent by a parent or legal guardian and the child if capable of understanding
However under future law, in terms of s 71 of the National Health Act (NHA) 
consent will have to be obtained from a parent or legal guardian until
the age of majority is reached. Other care-givers or custodians will
not have the authority to provide consent for child research . Presently, minority ends at 21  however it will soon drop to 18 .
While future law will require consent from a sole parent or guardian,
some ethical guidelines require consent from both parents (if
reasonably available) depending on research risks in relation to direct
benefit for the child participant [18,20].
The NHA also specifies that consent must also be obtained from minors if they are "capable of understanding" .
There is an implied legal obligation to obtain assent, as assent is the
means to get the child's perspective to establish their "best
interests" required by s 28(2) of the Constitution for every matter
concerning the child .
The NHA means that the standard for persons under the age of majority
is not necessarily assent but rather that when children have sufficient
comprehension it is their consent that shall be required .
That is, the Act requires persons who are legal minors to consent
rather than assent if they have sufficient comprehension. However,
assessment of understanding is potentially complicated [29,30].
While trial sites tend to favour forced-choice checklists to assess
understanding because they are objective and easy to administer [31,32], there is some evidence that they may yield higher scores of understanding than open-ended measures like narratives  and may be vulnerable to rote memorisation [30,34].
Another complexity is that given that adolescents will not be able
to consent to research independently complex privacy issues arise.
Although the NHA does not specifically refer to a child/minor's right
to privacy in research, a child does have a constitutional and common
law right to privacy. In terms of this right a person with an
expectation of privacy is entitled to keep aspects of their life
private provided this expectation is regarded as reasonable by society . This is also referred to as the "legitimate expectation" of privacy test .
In circumstances where a child does not have a right to privacy,
researchers may disclose information to the parent or legal guardian as
a legitimate party in the research relationship who has provided
consent for participation. Applying this test to adolescent research is
complex because it is uncertain when society would regard an
adolescent's expectation of privacy to be reasonable. One example:
if an adolescent tests HIV infected during a trial, the adolescent may
expect the researchers to keep such information confidential, and
society may regard this as reasonable given that adolescent's have the
right to HIV testing and confidentiality from the age of 14 outside of
a trial context .
However, given that parents have provided consent to participation in a
trial involving regular HIV testing and given that HIV infected
adolescents would require care and support, it may be reasonable to ask
adolescent trial participants to waive their privacy rights by agreeing
to disclose their HIV status to a trusted adult within a certain time
A second example: adolescents may have expectations of
privacy regarding their sexual risk information. In this instance
society may not regard this as reasonable as parents are legally
responsible for their children and are required to protect them from
harm. Withholding information from parents regarding risks facing their
children such as experimentation with drugs or alcohol may mean that a
parent is unable to meet their legal obligations to protect the child.
Therefore a parent may be entitled to risk information. However parents
could be asked to waive their right to access such information, if
other safeguards are in place like referral to counselling, and if the
information does not involve significant risks and criminal activity
like sexual abuse.
A further complexity is that there is evidence that adolescents when
compared to adults are less likely to spontaneously consider risks and
benefits,  are less likely to evaluate long-term consequences of decisions, [38-40] are more likely to place weight on benefit than risk,  are more likely to be short-term focused,  and are less likely to recognize the vested interests of others . More risky decisions may be made in groups than individually .
Obviously parental consent provides some degree of protection against
immature decision-making, however, researchers should try to enhance
adolescent understanding to the fullest extent possible.
For South African trials, we
recommend that HIV vaccine trial researchers anticipate a future change
in the age of majority. Researchers could currently consider obtaining
parental consent for all under-21's, and be prepared to submit protocol
amendments to obtain expedited approval to obtain parental consent for
under-18's when the change in the law becomes effective. For trials
requiring large numbers of adolescents to be enrolled, researchers must
consider how they will assist primary care-givers looking after orphans
with the complex legal process of transferring guardianship to enable
them to provide lawful consent to adolescent participation. For other
jurisdictions, we recommend that clarity be obtained on whether adolescents can consent independently to research or if they cannot, which adults have the capacity to provide proxy consent byexamining
research specific legislation, legislation that establishes the age of
majority or that provides adolescents with capacity to consent to
specific acts such as medical treatment. Child Care legislation may
also describe the persons with legal authority to act on behalf of
children. Ethical guidelines should also be consulted for advice.
We recommend that South African researchers consider how they will
establish when an adolescent has the necessary depth of understanding
for the higher standard of competence required for consent 
or whether adolescents meet the less strenuous requirements of assent,
including basic comprehension of purpose and procedures, and right to
withdraw  and the ability to indicate a preference . No-one has yet developed an "assent assessment tool" or described what such a tool would assess .
As true-false checklists may be inappropriately constituted for the
necessary probing required to establish depth of understanding of
complex trial concepts ,
sites must consider open-ended measures that probe understanding.
Stakeholders outside of South Africa are also likely to be concerned
with appropriate "tests" of understanding.
Privacy rights for sexual risk information and HIV status will have
to be delineated and both parents and adolescents will have to
understand what information parents will/will not have access to. In
South Africa this detailed work will hinge on the "legitimate
expectation" of privacy test. In other jurisdictions, however, this
analysis should also be done using relevant legal principles.
In all settings considering trials, consent processes should be
designed that are sensitive to characteristics of adolescent
decision-making. While group formats, like Vaccine Discussion Groups,
may be effective for disseminating information about trials, cognizance
should be taken of how peer influence may affect the evaluation of
risk. It is likely that extended interpersonal contact with a
knowledgeable trial site counsellor may effectively improve
and counsellors should be trained to enhance understanding of potential
long-term harms. Adolescent-friendly materials should also be developed
with advice from adolescent consultants .
What can be consented to?
In order for adolescent
participation in HIV vaccine trials to be lawful in South Africa,
current common law requirements must be met, that is consent to such
research must be in accordance with public policy . In other words consent to the harm or risk of harm must be legally permitted . To determine this, it has been proposed that, amongst other factors, the research must present acceptable standards of risk . Neither current South African law nor future law (s71 of the NHA)  provides a clear standard for acceptable research risk . Draft regulations 
assert that research with children is only permissible if it poses
minimal risk, or greater than minimal risk but holds out benefit for
the child. An important third category is not included in the draft
regulations – namely, research that poses more than minimal risk but
holds out no prospect of direct benefit. South African ethical
guidelines are not unanimous on risk standards however they are
approaching harmonisation . Three out of four South African ethical guidelines [18-20] assert that when the intervention or research does not hold
out the prospect of direct benefit, the allowable risk level is a minor
increase over the risks of daily life or routine medical and
psychological tests ("everyday risk"); if justified by the
risk-knowledge ratio. The one guideline in exception  permits no increase at all . Most South African ethical guidelines assert that when the intervention or the research does hold
out the prospect of benefit there is no explicit upper limit of risk
however the risks must be justified by the benefit. It is likely that
if HIV vaccine trials are reviewed by a number of RECs, they will
disagree on how to apply the risk standards for non-beneficial research
It is possible that different RECs may categorise the same
non-beneficial intervention like blood draws for lab testing as minimal
risk (permitted), a minor increase over minimal risk (permitted) or
more than that (not permitted).
Because the majority of recent
guidelines now require it, we recommend that RECs become familiar with
"component analysis" to demarcate interventions as beneficial or
and to assess if non-beneficial interventions meet national risk
standards. Investigators should begin now to prepare documentation on
risks so that RECs can make these complex assessments for both product
related risks and social harms. Data should be available, at least in
part, from prior trials with less vulnerable participants such as
adults. Inputs should be made to the draft regulations to bring them in
line with national ethical guidelines that set acceptable standards of
risk for non-beneficial research.
(ii) Complying with legal obligations in child protection laws
It is a principle of international law that special legal protections ought to exist to protect persons during childhood .
South Africa, like most other states therefore have developed a range
of special laws that protect children against maltreatment and abuse.
For example, in South Africa, the Sexual Offences Act 
contains specific offences relating to children, such as the
criminalization of sex under the age of 16 and child prostitution in s
14(1)(a), 14(3) and 9. Consent is not a defense to these crimes .
Furthermore while there is generally no legal obligation to report a
crime, South African law includes special protection for children who
may be facing abuse, ill-treatment or neglect. The Child Care Act11 in section 42 requires medical practitioners,
amongst others, to report suspected ill-treatment, abuse or neglect of
children to the Department of Social Development. Failure to report is
a criminal offence. Additionally, the Family Violence Act  states that any person who
examines, treats, attends to, advises, instructs or cares for any
child, who suspects that the child has been ill-treated, must report
this to a Commissioner of Child Welfare, a social worker or the police.
The future Children's Act  in section 150 will oblige any person to
identify children in need of care and protection (e.g. living in a
child headed household, required to perform child labour, being
maltreated, abused, or exploited) and to refer these to a social
worker. In terms of these laws, it is argued that HIV vaccine trial
staff would have a legal duty to report abuse or ill-treatment
disclosed by adolescent in a trial. Due to the broad meaning of terms
such as "ill-treatment" disclosures of rape and or some cases of
under-age sex would need to be reported to the appropriate authorities.
We recommend that study staff be trained to
recognise those disclosures that trigger a mandatory reporting
response. Consent procedures should inform parents and adolescents
about this limit to confidentiality. The protocol should not only spell
out how formalistic legal requirements will be met but broader ethical
requirements to promote children's' welfare, such as whether such
information will be disclosed to parents. Furthermore, stakeholders in
other jurisdictions will need to establish whether any special
protections exist for children, such as the mandatory disclosure of HIV
status, and if any special obligations are placed on researchers
regarding children in need of care or protection. Such laws may either
be found in criminal codes or in child specific laws.
(III) There is compliance with procedural requirements for ethical and scientific review of the research
To be lawful, research must be approved by the relevant authorities.
Ethical approval by an REC
The NHA (s73) 
sets out the current legal obligations of RECs. It provides that RECs
must approve research where it meets the "ethical standards of the
committee". It is likely that the MRC (2003) 
guidelines drafted for HIV vaccine trials will need to be consulted
which allow child participation provided risk standards, consent and
scientific necessity requirements are met.
Authorisation for the use of a genetically modified organism
terms of current law, for all HIV vaccine trials, a permit must be
obtained from the Executive Council of Genetically Modified Organisms
for any research into a genetically modified organism such as an HIV
vaccine. This is a body established within the Department of
Approval by the Medicines Control Council (MCC)
In terms of current law ,
the Minister of Health in consultation with the MCC has the power to
issue regulations on the control and conduct of clinical trials. These
have been issued and provide (amongst other things) that clinical
trials must be conducted in accordance with Good Clinical Practice
guidelines issued by the MCC or the Department of Health from time to
time . While the MCC 
has also prepared a set of guidelines for phase I trial applications
they do not appear to have issued any guidance on adolescents.
Ministerial consent for "non-therapeutic" research
Phase I adolescent HIV vaccine trials may be classed as "non-therapeutic". When Section 71(3)(b)(iv) of the NHA 
becomes effective, "non-therapeutic" research on children may not be
done without first obtaining consent from the Minister of Health. S/he
may not consent to such research if amongst others it poses a
"significant risk" to the health of a child, or "some" risk that is not
outweighed by benefit. No definition is provided of "significant risk",
and this is not provided for in the draft regulations . This condition adds an additional layer of administrative scrutiny [23,27].
However, much remains to be clarified, including which research falls
into its scope, its place in the sequence of approvals investigators
must obtain, and the entity that will carry out this function. This
detail is also not provided in the draft regulations .
We recommend that RECs begin to network with
each other to build consensus about adolescent trials, including the
acceptability of trial interventions in terms of national risk
standards. Like regulatory authorities in all the jurisdictions
planning adolescent HIV vaccine trials, the Medicines Control Council
should be requested to articulate the data it will require to firstly, allow adolescents into trials and secondly,
to license an adolescent vaccine. Very specifically, in the South
African setting, we recommend that researchers anticipate the public
policy assessment that the Minister will have to undertake by framing
their protocols in a way that assists the Minister, or delegated
authority, to make a speedy determination. RECs in all jurisdictions
planning such trials should be aware that public policy considerations
are becoming increasingly important in the regulation of research and
are being reflected in law. Therefore research-specific and health
specific laws should be consulted to establish whether there are
specific limits on certain forms of research. Researchers who craft
their protocols with thoughtful attention to ethical guidelines may
meet most, if not all, of the legal requirements. Where the law is
unclear, researchers should consult with their REC or get legal advice
from a lawyer trained in research ethics and law.