CHAPTER FOUR RESULTS
4.4 LINE-DRAWING
are advantaged in relation to citizens, but unresolved questions about the correct ‘dosing’ of responses or consequences for decision-making, such as ‘bribery’, or even ‘coercion’, prevented them from committing these to paper. To offset some discomfort about privileging, site-staff implemented helping steps for volunteers as well as general citizens.
They took steps that demonstrably advantaged participants at some sites over participants at others but this was not necessarily experienced as a conflict.
REC representatives used the idea that some needs are ‘in focus’ to help them decide on appropriate responses that they themselves should implement. Members of all four RECs (with jurisdiction over all five trial sites) viewed the needs at the heart of the research as deserving more vigilant review, they linked their notions of what to ‘look for’ to what the research ‘looks for’, and they reported more scrutiny of plans for HIV needs than for non-HIV needs. They seemed to use the idea of needs ‘in-focus’ to help them to focus their own activities. This suggests that when needs were seen as strongly connected to the research investigation, they were viewed as somewhat privileged for more demanding review steps (‘understanding needs in focus as deserving more demanding review steps’).
So with regards to the first stage, the point of review, I have a feeling that it’s not very high on the committee’s radar, that the committee is not particularly vigilant about whether or not care and treatment will be provided for concurrent conditions or conditions that emerge in the course of the person’s enrolment, that’s an impression that I have, is that we would be much more concerned about provision of care and treatment for the condition that’s the focus of the study rather than related or concurrent or coincidental conditions [p/ HIV/ other] [c19, REC, jurisdiction over site A].
REC members also perceived that resource constraints (time and attention) must be considered when implementing protocol reviews. They described adjudicating how much time and energy was apportioned to firstly, HIV vaccine protocols versus other protocols, and secondly to ancillary-care concerns versus other ethical complexities (‘invoking costs/ time in review’). They used the notion of undertaking sound review for all submitted protocols to limit the resources they expended on reviewing ancillary care in HIV vaccine trials. REC representatives did appear to wonder, sometimes, if their responses were totally adequate:
…there is the human again, tension of watching the time and getting too waylaid by certain discussions and at the moment one tends to spend too much time worrying about one’s informed consent forms and you’re scared to raise the substantive issues because of the time around the debate so that is a tension [c6, REC, jurisdiction over site E].
In terms of addressing needs, site-staff and network representatives saw that they were oriented by a central ‘mandate’, ‘job; ‘business’, ‘goal’ or ‘mission’, characterized as
answering the scientific question, answering the research question, discovering important knowledge about HIV vaccines, or finding a biomedical HIV prevention intervention. This mission was viewed as significant, valued or non-trivial. They characterized the primary activity organizing their contact or interaction with participants as research (‘invoking the primary mission’):
…we only have so much capacity to take care of people as part of this answering this research question and you know once we start layering on different levels of care then or ensuring care then you know our job becomes more complex and more burdensome in order to answer the scientific question and the urgent need here is to answer the scientific question and it’s sort of a question of/ sort of/ it’s a matter of keeping your eye on the ball, for us, and making sure that we are working towards that goal…[p/other]
[c10, network representative].
Site staff and network representatives also characterized some needs of participants as
‘inside focus’ or ‘inside scope’ whereas others were not (‘understanding some needs as in focus’). The status of a need (as ‘in’ or ‘out’ of the focus) was used to help decide what responses were reasonable to implement. For example, several interviewees used this concept to help them justify that direct treatment onsite for general health problems was not reasonable. General medical conditions, they seemed to say, fall outside of the research focus so why should we address those needs in that way? (‘understanding needs in focus as requiring more demanding steps’). As another example, referral was frequently endorsed as an adequate response for non-HIV needs but far more active, assisted referral was frequently endorsed for HIV needs, along with special mechanisms such as the HIV treatment fund.
Furthermore, site-staff and network representatives used the idea of possible damage to the overall research mission to help them decide whether certain helping-based responses were reasonable. They saw that implementing certain responses could make the research ‘shut down’ or be ‘brought down’ or be damaged through the bleeding-off of resources or capacity, for example, by diverting of staff attention (‘invoking costliness of certain responses on the primary mission’). This idea (of not damaging the research) seemed to be used to select reasonable helping-based responses from a presumptive array of possible responses. They understood ‘costing’ the research initiative too much as an important way of setting limits on
their responsibilities. Here the notion that there are responses that are ‘reasonable’ seemed to be key (and by comparison there are ‘unreasonable’ ones). One way they tried to weed out unreasonable responses was by using the idea that reasonable responses do not cost the primary mission too much:
You know, it’s hard enough to conduct research in these settings, without now coming up with a whole plan about what to do for every ache and pain. I think people must be reasonable, you know. One, we’re looking for a biomedical intervention to prevent HIV and you know, one can do so much…[p/other] [c4, site-staff, site B].
Site staff and network representatives understood that there are various ways of ‘costing’ the research enterprise in terms of the impact on resources (most often staff time and energy, sometimes money, and infrequently shouldering legal responsibility for participants’ care) as well as the impact on the scientific integrity of the trial. For example, a site-staff representative questioned whether contraceptive IUDs should be provided to participants (instead of injectable hormonal contraception speculated to increase HIV-risk) given the lack of availability of IUDs in the public sector at the time, the substantial re-training of site-staff that would be required, and their overall cost. (These interviewees recognized that contraceptive mandates were required for safety, but still questioned whether such responses could be implemented more helpfully). Site-staff and network representatives questioned whether participants should be provided with diagnostic-based screening for STIs, given that this may exclude participating sites without closely located laboratory capacity. A network representative questioned whether providing participants acquiring HIV with early treatment would prevent researchers from establishing if the experimental HIV vaccine reduces viral load (a critical secondary endpoint of such trials). This latter observation represents an example of where implementing a response to help participants address their medical needs was perceived to clash with the critical scientific objectives of the trial, as evidenced in the quote below:
…If we are moving toward earlier and earlier treatment in the course of natural infection, and that treatment/ the recommendations are the treatment be given as early as possible, that would interfere with the potential of measuring any reduction in viral load or disease modification that a vaccine would provide/ any of those benefits. We were concerned about this in (named trial) especially in communities such as San
Francisco where the Department of Health in San Francisco have recommended to provide treatment as early possible. That said, most practitioners and most individuals who get infected are more comfortable waiting, you know, rather than going on ART during acute or early infection most of them do wait until their CD4s start dropping. If we haven’t seen that yet in San Francisco we’re not likely to see it in South/ Southern Africa but it nonetheless will be an issue as more and more evidence emerges that early infection [sic] does reduce longer term sequelae of infection and other peripheral effects of early immunodeficiency…[p/ HIV] [c 14, network].
In some instances, stakeholders appeared to do line-drawing by invoking the responsibilities of others. That is, they were not necessarily saying ‘we don’t take this step because it will cost the research too much’ but rather ‘we don’t take this step because it should be taken by someone else’. For example, network representatives described requiring researchers to do detailed written planning about how they will address HIV needs, but they assigned to researchers the responsibility to monitor these plans. Network representatives reported they can assist sites to provide treatment for STIs, but they largely assigned to researchers the responsibility to address participants’ contraceptive needs and STI needs. These are instances where the idea that responsibilities are apportioned seemed important. They were recognizing that other partners should also share responsibilities for care-related activities.
This issue, and related concerns, is discussed more fully under the next and final master theme (‘Partnering’).
In some instances, stakeholders questioned whether the approach they had adopted (for participants largely) was the correct approach, or whether they could be doing more. That is, even after they had engaged in various forms of line-drawing such as considering ‘needs-in- focus’ or considering costs to the research initiative, they seemed to be left with some doubts about where they had drawn the line. They were questioning whether they should in fact be doing more (‘questioning approach/ wondering if more should be done’). These instances of questioning whether an approach was correct, or whether more should be done, cut across various needs (HIV, contraception, STIs).
For example, certain site-staff reported unease at initiating participants with HIV on ART using national treatment guidelines when international treatment guidelines recommended earlier initiation. Site-staff were concerned that participants with HIV would not have access to a third-line regimen in the South African public sector, should they fail to respond to first or second line ART regimen. Site staff described providing counselling and HIV test results to HIV-infected volunteers screened-out of trials yet questioned whether they should be providing better monitoring to such persons, in the form of CD4 counts and viral load results.
Site-staff questioned whether they should move away from syndromic management of STIs in participants as recommended by national treatment guidelines to diagnostic-screening of STIs. Site-staff questioned whether they should be moving towards different forms of contraception (for example, IUDs) for participants and away from hormonal contraception (especially progestogen-only injectables) routinely offered in the public health-care system but speculated to possibly increase HIV risk. Network representatives described sourcing money for an HIV treatment fund for participants from low-income countries but questioned whether access should be allowed to domestic (US-based) participants, as evidenced in the following quote:
…we’ve actually been concerned that because of constrained resources in some of the communities within the US we’re now wondering whether or not you know this would be an issue domestically as well, you know - hopefully not - and we’re advocating of course within our own communities to ensure that provisions for treatment are not lost you know because of some of the economic constraints within the US (…) You know I’m not sure if it were raised to a level of real worry but it’s been raised in our discussions and in hearing from our sites that on the site-level they are concerned that some of the infrastructure and resources to provide care and treatment domestically are threatened [p/HIV] [c14, network].
These perceptions were sometimes but not exclusively reported in response to questions about current ethical guideline requirements. This experience (of having lingering questions about their approach or whether the approach should be revised) was linked to yet distinct from the experience described under ‘Privileging’ of having uncertainty (both within and between-person) about the special treatment for participants versus citizens because that experience was about worrying about participant advantaging in relation to non-participants
and this experience was about questioning whether the steps being taken were sufficient - quite simply whether more should be done by them (‘questioning approach’).
Network and site-staff also engaged in line-drawing practices when it came to engaging the participating community or stakeholders more broadly in decisions about care, or consulting them about such decisions. Therefore, they did not only do line-drawing when addressing needs. They perceived some stakeholders as more critical than others for consultation. They used the idea of their primary mission, and not scuppering this mission, to weed out the steps considered reasonable (consulting during protocol writing) from those considered unreasonable (consulting via large-scale meetings before every trial). They did appear to have some nagging concerns about whether their engagement steps were enough.
In summary, the findings captured under this master theme suggest that site-staff, network and REC representatives tried to draw the line or set limits around their responsibilities in non-arbitrary and thoughtful ways (for addressing needs, engaging the community, and reviewing protocols). For addressing needs, stakeholders used important ideas to help them to work out what is reasonable or acceptable in terms of ancillary-care responsibilities. They did not see all needs as equal – that is they characterized some needs as standing out from the array of needs, and this ‘standing out’ was accomplished by viewing some needs as strongly linked to the research investigation (the business that brought participants and researchers together). They appeared to view these needs as deserving more attention in the form of more demanding responses, both ethical-review responses and addressing-needs responses. Stakeholders viewed certain responses as undermining the research enterprise (which they deemed to be very valuable) and these notions of not-hurting the research were seen as non-trivial ways to set limits on responses. They also assigned responsibilities to partners as a way of setting limits on their responsibilities. Despite using important ideas used to set limits on responsibilities, stakeholders still experienced nagging concerns about whether their responses were reasonable or whether a case could be made they could be doing more. These findings do not support the view that they felt acutely conflicted but that they experience subtle on-going questioning about their approaches.