3. Methods
3.9. Ethical issues in studies
Throughout the history of the response to the HIV epidemic, numerous ethical dilemmas have arisen, which have challenged clinicians, researchers and policymakers to reflect on how their actions can impact upon some of the most vulnerable members of society, particular in developing countries432. Key areas of ethical contention have centred on the
struggle to obtain affordable access to ART in the poorest countries that have been worst affected by HIV epidemics and implementation of international travel restrictions for individuals infected with HIV. Other important debates continue around whether it is ethically acceptable to adopt more utilitarian approaches to HIV testing to control the epidemic. For example some ethicists have argued that efforts to achieve universal coverage of HTC during pregnancy could subvert women’s right to autonomy, with implementation of some testing PITC programmes potentially giving insufficient opportunity for women to make informed decision to opt in or out of testing433.
In designing and undertaking the studies in this thesis, a number of ethical issues arose that required careful consideration to minimise the risk of harm to participants and the wider study communities in Blantyre. Findings from studies also raised important ethical questions relating to how clinical research can best inform clinical practice, maximise the health of the population and ensure that the rights of individuals populations are
protected.
In the prospective cohort study described in Chapter 4, I set out to investigate rates uptake of HTC and linkage into HIV care under routine programme conditions in primary
health care centres in Blantyre. In designing this study, I decided to not offer additional research-‐supported services to improve uptake of HTC or access to HIV care in the study clinics. This decision was taken to allow collection of accurate and generalizable
epidemiological data and identification of risk factors for failure of linkage into care. Offering additional interventions (such as making study staff available for HIV counselling or testing, providing on-‐site measurement of CD4 counts or encouraging participants to complete care-‐seeking steps) would have undoubtedly influenced participant behaviour and study outcomes, making it more difficult to describe key health system failures and develop interventions to improve linkage into HIV care. Additionally, it was important in the cohort study to achieve low rates of loss to follow-‐ up among participant groups that other studies have found difficult to effectively retain in care. Recognising that many participants would likely not return to clinics,
undertaking home tracing visits would be important to minimise loss to follow-‐up. However, this could potentially compromise the privacy of participants who had been recently diagnosed with HIV.
These decisions raised a number of ethical questions. In particular, was it justifiable to not offer participants additional research-‐supported services above and beyond what was being provided through the routine health system, especially given the large individual and public health benefits gained through knowledge of HIV status and
accessing care? There is an additional clear gap between services that are recommended in WHO and Malawi National HIV care guidelines, and what was provided through the primary health care clinics during the study. Would it be justified to provide additional research-‐supported services for the duration of the study, then remove these services once the study was complete (with the understanding that study resources were not infinite and could not support services indefinitely)?
There are often competing ethical principles and frameworks to be considered in clinical and public health research434, with individuals, community and the wider population
frequently having different needs and requirements. Ultimately, in consultation with supervisors, other researchers and providers in the study clinics, I made a decision to conduct an observational cohort study, without offering any additional study-‐supported interventions. The ethical reasons for this were based upon a consequentialist public health ethical platform434: whilst the health of individual study participants would not be
adversely affected by their participation in the study (in comparison to what would have been expected through non-‐participation given the resources available in the routine health system), a substantially greater number of individuals in the study clinics, in Blantyre and in other regions in Malawi and in Africa could be expected to receive wider benefit from the study. Critically, this ethical approach is dependent on study findings being widely disseminated and resulting in improved patient care and policies.
Although a utilitarian approach was adopted participants right to be protected from harm and treated with respect was protected. Moreover, from a justice perceptive, individuals (and study clinics) participating in the study were not unduly favoured by receiving additional unsustainable resources compared to non-‐participants. The Declaration of Helsinki435 states that underrepresented groups (such as people infected
with HIV, women and pregnant women) should be provided with appropriate access to participation in research. In this study, such underrepresented groups were eligible to participate.
In considering the issue of undertaking home tracing to ascertain outcomes of study participants, considerable ethical dilemmas were raised. Liberal ethical theories hold that individuals have rights to privacy and to be protected from harm at the expense of
others (although in some cases, such as vaccination or quarantine, these rights are overridden)434. However, failing to achieve high rates of follow-‐up could compromise the
integrity of the study and invalidate the results, negating any potential benefits from the study to the wider population. A pragmatic decision was ultimately taken that would protect the rights of participants, whilst maximising the opportunities for public health benefit. Following recruitment, participants were offered a choice of options for home-‐ based follow-‐up in the event that they did not return to the study clinic: no home-‐ follow-‐up; telephone tracing only; or home visits after an appointment was made by telephone. During the study, all participants gave written informed consent to home visits after a telephone appointment, suggesting that this issue was possibly not as problematic as we first supposed.
The cluster-‐randomised trial described in Chapter 6 raised particular ethical issues. Concerns over privacy and confidentiality were not as prominent as in the cohort study as community members could make an informed decision to request HIV self-‐testing and home assessment and initiation of care through the community counsellors, and no incentives were offered to participants to take up home-‐based services. Additionally, study nurses were careful to maintain privacy during home visits: timings of visits were arranged beforehand by telephone and nurses did not wear any identifying uniforms or logos that might suggest they were providing HIV-‐related services.
The design of cluster-‐randomised trials are well-‐recognised to provide particular ethical challenges436. In this study, although individual-‐level consent for participation in the trial
was sought from individuals undergoing HIVST and ART initiation, consent for
this was ethically justified as they would not receive any study interventions (if they did not opt to request HIV self-‐testing) and so would not be exposed to any potential harm.
A key area of debate centred on how results of the cluster randomised trial should inform policy and practice, and how participants in the control arm wider population could access study interventions following completion of the study. The Declaration of Helsinki states that researchers and host country governments should make provisions for post-‐trial access for participants who need an intervention identified as beneficial in the trial435. Following the completion of the cluster-‐randomised trial, access to home
initiation of HIV care (the intervention being assessed) was expanded to all 14 clusters receiving access to HIV self-‐testing for the remaining duration of the parent trial. Thus participants in the intervention arm and control arm received 24 months and 18 months of access to home initiation of HIV care respectively. This duration of availability should be sufficient to allow all study participants to access home initiation of HIV care if they wish.
Determining how the trial intervention could be made available to the wider HIV-‐ positive community in Malawi and in other countries raises greater challenges.
Throughout the research process, we developed strong links with the HIV Department of the Ministry of Health of Malawi, who were very supportive of the study. Nevertheless, even if trial interventions are shown to be cost-‐effective, Malawi (and other countries) may not have capacity or economic resources to implement them immediately. Working with international organisations (such as WHO) to promote adoption of HIV self-‐testing and home initiation of care within guidelines and policy, and to better direct
may achieve wider implementation. It is encouraging to note that trial results were highlighted in the 2013 UNAIDS Report on the Global Epidemic437.