2.5 Ethical issues in international biomedical research
2.5.10 Post-trial access
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recommendations regarding ancillary care in HIV vaccine trials in existing ethical guidelines were being achieved, and whether stakeholders encountered challenges. She concluded that all five sites surveyed had mostly met the guideline recommendations for engaging host community in which research is conducted, and recommendations for “moral negotiation” were met to a lesser extent.
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A systematic review by Sofaer and Strech (2011) assessed the reasons why post-trial access to trial drugs should, or need not be provided to research participants. The authors identified a range of reasons broadly based on morality, legality, interests/incentives, or practicality of offering post-trial access. Proponents of post-trial access invoke the ethical principles of beneficence (an obligation to help others further their important and legitimate interests), nonmaleficence (an obligation not to inflict ham on others) (Grady, 2005b; NBAC, 2001) and justice (NBAC, 2001; Macklin, 2006; Shapiro & Benatar, 2005).
The NBAC (2001) supported post-trial access based on the principle of justice as reciprocity, implying that because participants enrolled in research assume some risk and burdens for altruistic reasons for the good of society and scientific advancement, certain things are owed to them in return for their participation. According to NBAC (2001), “justice as reciprocity is concerned with what people deserve as a function of what they have contributed to an enterprise or to society. In the context of clinical trials, justice as reciprocity could mean that something is owed to research participants even after their participation in a trial has ended, because it is only through their acceptance of risk and inconvenience that researchers are able to generate findings necessary to advance knowledge and develop new medical interventions” (p. 59).
However, Merritt and Grady (2006) question the reciprocity-based justification for offering priority access to ART trial participants when ART must be rationed. They argue that justifying the provision of ART on the principle of reciprocity depends on several variables, including the quantity of ART available, the number of people in the country who need ART, and whether the country’s concurrent allocation policy selects specific subpopulations (such as HIV-infected
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mothers of young children) for priority. They conclude that the reciprocity-based justification for giving ART trial participants priority over equally needy HIV-infected citizens is relevant only under some circumstances, at best. In other words, they are cautioning against the prioritizing the provision of post-trial access to trial participants based on reciprocal justice without giving due consideration to the possible burden on people who did not participate in the trial (Merritt &
Grady, 2006).
While the principle of providing post-trial access is recognized by various research ethics guidelines (CIOMS, 2002; Department of Health, 2015; UNAIDS/WHO 2012; WMA, 2013), there is little empirical research about how RECs, investigators and research participants deal with issues of post-trial access in practice. One study in the US surveyed 65 IRB/REC chairs, 117 investigators, and 500 research participants in a multinational HIV trial in 25 countries to assess their views about post-trial access to interventions proven effective in the study. The authors reported that 29% of IRB/REC chairs, 42% of researchers and 83% of research
participants believed the study product should be guaranteed for every HIV-infected person in the world if proven effective (Pace et al., 2006). They also found different views in terms of availability of the product, with most European and Latin American research participants saying it should be provided freely, while North American, Australian, and Thai participants felt it should be provided at a price affordable to the average person. Furthermore, REC chairs and researchers believed that the “reasonable availability” requirement (CIOMS, 2002, p. 51) is meant for people in the country where the study was conducted and meant a drug should be available at a price the average person could afford and that host country governments had primary responsibility for making it available (Pace et al., 2006).
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Another US study investigating how closely researchers followed NIH guidance on post-trial access found that all 18 research protocols included plans for post-trial access for trial
participants and more than 13 of the 18 (70%) had specific mechanisms for post-trial access, but none guaranteed long-term sponsor funding after the trials (Shah, Elmer & Grady, 2009). The views and attitudes of trial participants in the US about whether or not, and why, they should receive post-trial access were investigated and it was found that the majority of respondents believed that various stakeholders (investigators, sponsors, health insurers, and others) have a shared obligation to facilitate post-trial access to the trial drug (or to a therapeutic equivalent) if it benefited the participant. Furthermore, the same study found that while some believed post- trial access obligations include providing transition care (referrals to non-trial physicians or other trials, limited follow-up, short-term drug supply) or care for long-term adverse events, others said, that there should be no post-trial access obligations on drugs or care. Additionally, they found that participants frequently expressed reasons such as health needs, cost, reciprocity, free choice, and sponsor self-interest to justify their views on post-trial access (Sofaer et al., 2009).
A systematic review by Cohen, O'Neill, Joffres, Upshur and Mills (2009) investigating the extent to which registered international RCTs report the use of standard of care and post-trial
obligations found that out of 312 studies identified, only 4 (1.3%) mentioned provisions for post- trial access. Of those, one stated that the post-trial drug would be provided by the governments of the respective countries; another mentioned that participants who became infected with HIV during the trial would be provided with free HIV counselling and education and access to required healthcare, as well as free antiretroviral drugs, if clinically indicated. The same study noted, however, that there was no mentioning of who will offer these provisions and who will
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ensure that these are provided (Cohen et al., 2009). Another US study by Ciaranello et al. (2009) investigated how details about post-trial access were included in the trial’s protocols and
informed consent forms. They found that post-trial access was mentioned in 14 of 31 trials (45%), access to medications in 12 of 31 (39%) and access to medical care in 5 of 31 (16%) trials.
The views of HIV/AIDS clinical trial participants, researchers and research administrators were investigated in Kenya and it was found that most research participants expressed a desire for post-trial access to drug therapy, most often life long, after their participation in a clinical trial.
Furthermore, participants felt that subsidisation of drug therapies and education were essential forms of compensation for clinical trial participation. Similarly, clinician researchers and
administrators believed that there was a moral obligation from researchers to facilitate continued post-trial access of the drug to participants (Shaffer et al., 2006). The views of twenty-nine South African community members regarding the provision of treatment in HIV prevention trials were investigated and the study reported that most respondents believed that researchers should facilitate access of treatment and care to participants. The same study found that respondents felt that researchers can help through referrals until such time that participants are capable of
accessing care and treatment on their own (Barsdorf et al., 2010). In a study aimed at
investigating post-trial access in HIV prevention trials, it was reported that , found that while all nine biomedical prevention trials they analysed had offered post-trial access, there was
considerable variation in the mechanisms, duration and timeliness of post-trial access (Haire &
Jorderns, 2015).
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