Over the last few decades, multiple studies have examined the understanding of participants in clinical research. They show variable and often poor understanding of key elements of disclosure, such as expected risks and the experimental nature of treatments. Did the participants in these studies give valid consent? According to the standard view of informed consent they did not. The standard view holds that the recipient of consent has a duty to disclose certain information to the profferer of consent because valid (...) consent requires that information to be understood. The contents of the understanding and disclosure requirements are therefore conceptually linked. In this paper, we argue that the standard view is mistaken. The disclosure and understanding requirements have distinct grounds tied to two different ways in which a token of consent can be rendered invalid. Analysis of these grounds allows us to derive the contents of the two requirements. It also implies that it is sometimes permissible to enroll willing participants who have not understood everything that they ought to be told about their clinical trials. (shrink)

Misconceived Consent: Miguel has stage IV lung cancer. He has nearly exhausted his treatment options when his oncologist, Dr. Llewellyn, tells him about an experimental vaccine trial that may boost his immune response to kill cancer cells. Dr. Llewellyn provides Miguel with a consent form that explains why the study is being conducted, what procedures he will undergo, what the various risks and benefits are, alternative sources of treatment, and so forth. She even sits down with him, carefully talks through (...) the most important points, and gives him time to ask questions. Though it is a Phase 1 study and the chance that he will benefit is very low, Miguel happily agrees to take part. A week later, after the first experimental injection, she asks him if he is worried about the risks. “Risks?” he asks. “I’m sure this is safe—you’re a doctor, after all!”. (shrink)

In recent years, an old challenge to informed consent has been rediscovered: the challenge of ignorance. Several authors argue that due to the presence of irreducible ignorance in certain treatments, giving informed consent to these treatments is not possible. The present paper examines in what ways ignorance is believed to prevent informed consent and which treatments are affected by that. At this, it becomes clear that if the challenge of ignorance truly holds, it poses a major problem to informed consent. (...) The paper argues, however, that from both an empirical and a theoretical point of view, it is not convincing that ignorance prevents informed consent. Still, it seems important that the presence of irreducible ignorance is openly discussed during the informed consent process. (shrink)

BackgroundHIV cure research involving cell and gene therapy has intensified in recent years. There is a growing need to identify ethical standards and safeguards to ensure cell and gene therapy (CGT) HIV cure research remains valued and acceptable to as many stakeholders as possible as it advances on a global scale.MethodsTo elicit preliminary ethical and practical considerations to guide CGT HIV cure research, we implemented a qualitative, in-depth interview study with three key stakeholder groups in the United States: (1) biomedical (...) HIV cure researchers, (2) bioethicists, and (3) community stakeholders. Interviews permitted evaluation of informants’ perspectives on how CGT HIV cure research should ethically occur, and were transcribed verbatim. We applied conventional content analysis focused on inductive reasoning to analyze the rich qualitative data and derive key ethical and practical considerations related to CGT towards an HIV cure.ResultsWe interviewed 13 biomedical researchers, 5 community members, and 1 bioethicist. Informants generated considerations related to: perceived benefits of CGT towards an HIV cure, perceived risks, considerations necessary to ensure an acceptable benefit/risk balance, CGT strategies considered unacceptable, additional ethical considerations, and considerations for first-in-human CGT HIV cure trials. Informants also proposed important safeguards to developing CGT approaches towards an HIV cure, such as the importance of mitigating off-target effects, mitigating risks associated with long-term duration of CGT interventions, and mitigating risks of immune overreactions.ConclusionOur study identified preliminary considerations for CGT-based HIV cure across three key stakeholder groups. Respondents identified an ideal cure strategy as one which would durably control HIV infection, protect the individual from re-acquisition, and eliminate transmission to others. Known and unknown risks should be anticipated and perceived as learning opportunities to preserve and honor the altruism of participants. Preclinical studies should support these considerations and be transparently reviewed by regulatory experts and peers prior to first-in-human studies. To protect the public trust in CGT HIV cure research, ethical and practical considerations should be periodically revisited and updated as the science continues to evolve. Additional ethics studies are required to expand stakeholder participation to include traditionally marginalized groups and clinical care providers. (shrink)

HIV remission clinical researchers are increasingly seeking study participants who are diagnosed and treated during acute HIV infection—the brief period between infection and the point when the body creates detectable HIV antibodies. This earliest stage of infection is often marked by flu-like illness and may be an especially tumultuous period of confusion, guilt, anger, and uncertainty. Such experiences may present added ethical challenges for HIV research recruitment, participation, and retention. The purpose of this paper is to identify potential ethical challenges (...) associated with involving acutely diagnosed people living with HIV in remission research and considerations for how to mitigate them. We identify three domains of potential ethical concern for clinicians, researchers, and ethics committee members to consider: 1) Recruitment and informed consent; (2) Transmission risks and partner protection; and (3) Ancillary and continuing care. We discuss each of these domains with the aim of inspiring further work to advance the ethical conduct of HIV remission research. For example, experiences of confusion and uncertainty regarding illness and diagnosis during acute HIV infection may complicate informed consent procedures in studies that seek to recruit directly after diagnosis. To address this, it may be appropriate to use staged re-consent procedures or comprehension assessment. Responsible conduct of research requires a broad understanding of acute HIV infection that encompasses its biomedical, psychological, social, and behavioral dimensions. We argue that the lived experience of acute HIV infection may introduce ethical concerns that researchers and reviewers should address during study design and ethical approval. (shrink)

Modern antiretroviral therapies are capable of suppressing HIV in the bloodstream to undetectable levels. Nonetheless, people living with HIV must maintain lifelong adherence to ART to avoid the re-emergence of the infection. So despite the existence and efficacy of ART, there is still substantial interest in development of a cure. But HIV cure trials can be risky, their success is as of yet unlikely, and the medical gain of being cured is limited against a baseline of ART access. The medical (...) prospect associated with participation in cure research thus look poor. Are the risks and burdens that HIV cure research places on participants so high that it is unethical, at present, to conduct it? In this paper, I answer ‘no’. I start my argument by describing a foundational way of thinking about the ethical justification for regulatory limits on research risk; I then apply this way of thinking to HIV cure trials. In offering this analysis, I confine my attention to studies enrolling competent adults and I also do not consider risks research may pose to third parties or society. Rather, my concern is to engage with the thought that some trials are so risky that performing them is an ethically unacceptable way to treat the participants themselves. I reject this thought and instead argue that there is no level of risk, no matter how high, that inherently mistreats a participant. (shrink)

Consent processes for clinical trials involving HIV prevention research have generated considerable debate globally over the past three decades. HIV cure/eradication research is scientifically more complex and consequently, consent processes for clinical trials in this field are likely to pose a significant challenge. Given that research efforts are now moving toward HIV eradication, stakeholder engagement to inform appropriate ethics oversight of such research is timely. This study sought to establish the perspectives of a wide range of stakeholders in HIV treatment (...) and research to inform consent processes for cure research. In total, 68 South African stakeholders participated in two qualitative research modalities. In-depth interviews were conducted with a purposive sample of 42 individuals - audiotaped with consent. Twenty-six stakeholders participated in three focus group discussions. Thematic analysis of transcribed IDIs and FGDs was conducted. The majority of respondents indicated that there could be unique challenges in HIV cure research requiring special attention. In particular, given the complexity of cure science, translation of concepts into lay language would be critical for potential participants to adequately appreciate risks and benefits in early phase research with experimental interventions. Furthermore, to aid understanding of risks and benefits against a background of desperation for a cure, specially trained facilitators would be required to assist with a psychological assessment prior to consent to avoid curative misconceptions. Long-term participant engagement to assess durability of a cure would mean that the consent process would be prolonged, necessitating annual re-consent. Building trust to maintain such long-term relationships would be critical to retain study participants. Unique consent requirements for cure research in South Africa would include significant efforts to maximise understanding of trial procedures, risks and the need for long-term follow-up. However, the psychological dimension of cure must not be underestimated. Beyond an understanding of cure science, the emotional impact of HIV cure advances the discourse from cure to healing. Consequently, the consent process for cure research would need to be enhanced to include psychological support and counselling. This has several important implications for research ethics review requirements for consent in HIV cure research. (shrink)

The informed consent is an ethical and legal requirement for potential participants to enroll in a study. There is ample of evidence that understanding consent information and enrollment is challenging for participants in clinical trials. On the other hand, the reasoning process behind decision-making in HIV clinical trials remains mostly unexplored. This study aims to examine the decision-making process of people living with HIV currently participating in antiretroviral clinical trials and their understanding of informed consent. We conducted a qualitative socio-constructivist (...) study using semi-structured interviews. Eleven participants were selected by purposive sampling in Argentina until data saturation was reached. A content analysis was performed. The findings highlight the fact that some participants decided to enroll on the spot, while others made the decision a few days later. In all cases, the decision was based on different aspects of trust (in doctors, in the clinical research site, in the clinical trials system) but also on emotions associated with HIV and/or treatment. Moreover, while people living with HIV felt truly informed after the consent dialogue with a researcher, consent forms were unintelligible and unfriendly. The immediacy of patient decision-making has rarely been described before. Enrollment in an HIV clinical trial is mainly a trust-based decision but this does not contradict the ethical values of autonomy, voluntariness, non-manipulation, and non‐exploitation. Thus, trust is a key issue to be included in reshaping professional practices to ensure the integrity of the informed consent process. (shrink)

Despite existing international, regional and national guidance on how to obtain valid consent to health-related research, valid consent remains both a practical and normative challenge. This challenge persists despite additional evidence-based guidance obtained through conceptual and empirical research in specific localities on the same subject. The purpose of this paper is to provide an account for why, despite this guidance, this challenge still persist and suggest conceptual resources that can help make sense of this problem and eventually mitigate it’. This (...) paper argues that despite the existence of detailed official guidance and prior conceptual and empirical research on how to obtain valid consent, the question of ‘how to obtain and ascertain valid consent to participation in health-related research’ cannot always be fully answered by exclusive reference to pre-determined criteria/guidance provided by the guidelines and prior research’. To make intelligible why this is so and how this challenge could be allayed, the paper proposes six concepts. The first five of these are intended to account for the persistent seeming inadequacies of existing guidelines. These are fact-skepticism; guideline insufficiency; generality; context-neutrality and presumptiveness. As an outcome of these five, the paper analyzes and recommends a sixth, called bioethical reflexivity. Bioethical reflexivity is reckoned as a handy tool, skill, and attitude by which, in addition to guidance from context-specific research, the persisting challenges can be further eased. Existing ethical guidelines on how to obtain valid consent to health-related research are what they ought to be – general, presumptive and context-neutral. This explains their seeming inadequacies whenever they are being applied in concrete situations. Hence, the challenges being encountered while obtaining valid consent can be significantly eased if we appreciate the guidelines’ nature and what this means for their implementation. There is also a need to cultivate reflexive mindsets plus the relevant skills needed to judiciously close the unavoidable gaps between guidelines and their application in concrete cases. This equally applies to the gaps which cannot be filled by reference to additional guidance from prior conceptual and empirical research in specific contexts. (shrink)

The controversy surrounding the use of hydroxychloroquine, an antimalarial drug, for COVID-19 has raised numerous ethical and policy problems. Since the suggestion that HCQ has potential for COVID-19, there have been varying responses from clinicians and healthcare institutions, ranging from adoption of protocols using HCQ for routine care to the conduct of randomised controlled trials to an effective system-wide prohibition on its use for COVID-19. In this article, we argue that the concept of ‘disease public profile’ has become a prominent, (...) if not the sole, determinant in decision-making across various healthcare responses to the pandemic. In the case of COVID-19, the disease’s public profile is based on clinical and non-clinical factors that include contagiousness, clinical presentation and media coverage. In particular, we briefly examine the dangers of a heightened public profile in magnifying the inequality of diseases and undermining three key ethical concepts, namely evidence-based practice, sustainable allocation and meaningful consent. (shrink)