The perspectives of researchers on obtaining informed consent in developing countries

Background: The doctrine of informed consent (IC) exists to protect individuals from exploitation or harm. This study into IC was carried out to investigate how different researchers perceived the process whereby researchers obtained consent. It also examined researchers’ perspectives on what constituted IC, and how different settings influenced the process. Methods: The study recorded in‐depth interviews with 12 lecturers and five doctoral students, who had carried out research in developing countries, at a leading school of public health in the United Kingdom. A purposive, snowballing approach was used to identify interviewees. Results: Although the concept and application of the doctrine of IC should have been the same, irrespective of where the research was carried out, the process of obtaining it had to be different. The setting had to be taken into consideration and the autonomy of the subject had to be respected at all times. In areas of high illiteracy, and where understanding of the subject was likely to be a problem, there was an added responsibility placed on the researcher to devise innovative ways of carrying out the study, taking into consideration the peculiarities of the environment. Conclusion: The ethical issues for IC were the same, irrespective of where the research was conducted. However, because the backgrounds, setting, and knowledge of populations differed, there was the need to be similarly sensitive in obtaining consent. The problems of obtaining genuine IC were not limited to developing countries.     

The ethics of research on deep brain stimulation for depression: decisional capacity and therapeutic misconception

Research on deep brain stimulation (DBS) for treatment-resistant depression appears promising, but concerns have been raised about the decisional capacity of severely depressed patients and their potential misconceptions about the research. We assessed 31 DBS research participants with the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR), a well-validated capacity measure, and with a scale to measure therapeutic misconception, which occurs when subjects do not recognize key differences between treatment and clinical research. Correlations with baseline depressive symptoms were explored. Subjects' performance on the MacCAT-CR was excellent, but therapeutic misconception was still apparent. A trend toward significance was found in the correlation between baseline depression ratings and total therapeutic misconception score. Responses to open-ended prompts revealed both reassuring and concerning statements related to expectations of risk, benefit, and individualization. Even severely depressed patients did not manifest impairments in their capacity to consent to DBS research. Therapeutic misconception, however, remained prevalent.     

Is Consent Based on Trust Morally Inferior to Consent Based on Information?

Informed consent is considered by many to be a moral imperative in medical research. However, it is increasingly acknowledged that in many actual instances of consent to participation in medical research, participants do not employ the provided information in their decision to consent, but rather consent based on the trust they hold in the researcher or research enterprise. In this article we explore whether trust‐based consent is morally inferior to information‐based consent. We analyse the moral values essential to valid consent – autonomy, voluntariness, non‐manipulation, and non‐exploitation – and assess whether these values are less protected and promoted by consent based on trust than they are by consent based on information. We find that this is not the case, and thus conclude that trust‐based consent if not morally inferior to information‐based consent.     

Response to Frederic Bretzner et al. "Target populations for first-in-human embryonic stem cell research in spinal cord injury"

We address concerns raised in this issue by Bretzner et al. (2011) by explaining the rationale for including subjects with subacute, neurologically complete spinal cord injuries in the Phase 1 trial of GRNOPC1. We also present elements of the informed consent process that minimize the likelihood of therapeutic misconception.     

The Challenges of Research Informed Consent in Socio‐Economically Vulnerable Populations: A Viewpoint From the Democratic Republic of Congo

In medical research, the ethical principle of respect for persons is operationalized into the process of informed consent. The consent tools should be contextualized and adapted to the different socio‐cultural environment, especially when research crosses the traditional boundaries and reaches poor communities. We look at the challenges experienced in the malaria Quinact trial, conducted in the Democratic Republic of Congo, and describe some lessons learned, related to the definition of acceptable representative, the role of independent witness and the impact of socio‐economic vulnerability. To ensure children's protection, consent is required by the parents or, in their absence, by a legally mandated representative. In our setting, children's responsibility is often entrusted permanently or temporarily to relatives or friends without a tribunal mandate. Hence, a notion of ‘culturally acceptable representative’ under supervision of the local Ethics Committee may be more suitable. To ensure protection of illiterate subjects, an independent witness is required to confirm that the consent was freely given. However, in low‐literacy contexts, potential witnesses often don't have any previous relationship with patient and there may be power‐unbalance in their relationship, rather than genuine dialogue. In poor communities, trial participation may be seen as an opportunity to secure access to healthcare. Poverty may also lead to ‘competition’ to access the research‐related benefits, with a risk of disturbance at societal or household level. Adjusting consent procedures to sociocultural and socioeconomic realities is essential for fulfilling the underlying ethical principles. This requires a collaborative dialogue between researchers, regulators and ethics committees.     

Research, Informed Consent, and the Limits of Disclosure

According to this paper, respect for informed consent implies that subjects should often be told a good deal more than ethical guidelines explicitly or implicitly require. Unless subjects are informed of the researchers' personal characteristics, views, and sponsors whenever they would be likely to consider them significant, their autonomy is being overridden. However, overriding subjects' autonomy is sometimes required by the interests of researchers in not being discriminated against or suffering intrusions into their privacy. This paper resolves the conflict between informed consent and the interests of researchers by recommending that (i) subjects generally should be told of the personal characteristics of researchers when relevant as part of the researchers' job and (ii) that subjects should be told of researchers' views when conceptually connected to the research and (iii) that subjects should almost always be told about sponsorship. While the paper explicitly limits the role of informed consent, these recommendations go significantly beyond most guidelines in their requirements about what information should be disclosed.     

On the Alleged Right to Participate in High‐Risk Research

Reigning regulatory frameworks for biomedical research impose on researchers and research ethics committees an obligation to protect research participants from risks that are unnecessary, disproportionate to potential research benefits, and non‐minimized. Where the research has no potential to produce results of direct benefit to the subjects and the subjects are unable to give consent, these requirements are strengthened by an additional condition, that risks should not exceed a certain minimal threshold. In this article, I address the question of whether there should be limits of permissible risks in non‐therapeutic research involving competent and healthy subjects. Some commentators argue that competent and informed individuals should have a right to participate even in extremely risky research and that research ethics committees should never reject studies because they are too dangerous. To use David Shaw's expression, competent volunteers should have ‘a right to participate in high‐risk research’. I argue that this idea is ill‐founded, as it does not take into account the social mission and complex collaborative nature of research practice as well as the inequity of power between researchers and subjects. Imposition of limits on permissible risks for healthy volunteers is justified by the need to protect research enterprise and the need to protect the weaker party, namely the subjects. Also, I suggest that the best way to set boundaries on research risks is to leave the judgment of risk acceptability to research ethics committees.     

Erosion of informed consent in U.S. research

This paper evaluates four recent randomized clinical trials in which the informed consent of participants was either not sought at all, or else was conducted with critical information missing from the consent documents. As these studies have been taking place, various proposals to conduct randomized clinical trials without consent have been appearing in the medical literature. Some of the explanations offered for why it is appropriate to bypass consent or disclosure requirements appear to represent a fundamental misunderstanding of applicable government regulations and even the research enterprise. Others are the result of conceptual disagreements about the importance and application of traditional research ethics norms to ‘comparative effectiveness research’ and modern research environments. Common among these explanations, however, is a failure to appreciate when a research intervention, rather than merely an observation or review of data, is taking place. Review committees and investigators are failing to see, or choosing to ignore, interventions in the lives of research subjects. When these studies have come to light, government agencies with oversight authority have done little or backed down. Prestigious medical journals have published research results knowing that the required consent was not obtained, or they have stood by the published studies even after the inadequacy of consent is discovered. This article critically examines this erosion of consent in theory and practice and calls for restoring the requirement of informed consent to its proper place as a priority in human subjects research.     

ADDICTION AND AUTONOMY: CAN ADDICTED PEOPLE CONSENT TO THE PRESCRIPTION OF THEIR DRUG OF ADDICTION?

It is often claimed that the autonomy of heroin addicts is compromised when they are choosing between taking their drug of addiction and abstaining. This is the basis of claims that they are incompetent to give consent to be prescribed heroin. We reject these claims on a number of empirical and theoretical grounds. First we argue that addicts are likely to be sober, and thus capable of rational thought, when approaching researchers to participate in research. We reject behavioural evidence purported to establish that addicts lack autonomy. We present an argument that extrinsic forces must be irresistible in order to make a choice non-autonomous. We argue that heroin does not present such an irresistible force. We make a case that drug-oriented desires are strong regular appetitive desires, which do not compromise consent. Finally we argue that an addict's apparent desire to engage in a harmful act cannot be construed as evidence of irrational or compulsive thought. On these arguments, a sober heroin addict must be considered competent, autonomous and capable of giving consent. More generally, any argument against legalisation of drugs or supporting infringement of the liberty of those desiring to take drugs of addiction must be based on considerations of harm and paternalism, and not on false claims that addicts lack freedom of the will.     

The role and responsibilities of witnesses in the informed consent process

Various mechanisms to ensure the protection of subjects in human research have been suggested, including the presence of witnesses during the informed consent process. For our commentary on the use of witnesses and their potential role and responsibility during the consent process, we start by addressing current guidelines for human subjects research in four Latin American countries. By using examples from public health research, we highlight some of the practical difficulties of using witnessed consent, from becoming a meaningless ritual at one end of the spectrum to the research subject feeling intimidated or coerced to participate at the other. Apart from these practical difficulties, it is unclear what responsibility the witness could and should have. We argue that there are important ethical questions about the role of witnesses that have not been adequately addressed in national and international regulations. This work addresses these gaps and argues that more debate is required to define the role and responsibilities of witnesses in the consent process, their training requirements and whether a universal legal requirement for witnessed consent, regardless of the type of research, is desirable.     

The consent problem within DNA biobanks

Large prospective biobanks are being established containing DNA, lifestyle and health information in order to study the relationship between diseases, genes and environment. Informed consent is a central component of research ethics protection. Disclosure of information about the research is an essential element of seeking informed consent. Within biobanks, it is not possible at recruitment to describe in detail the information that will subsequently be collected because people will not know which disease they will develop. It will also be difficult to describe the specific research that will be performed using the biobank, other than to stipulate categories of research or diseases that are not included. Potential subjects can only be given information about the sorts of research that will be performed and by whom. Organisations responsible for biobanks usually argue that this disclosure of information is adequate when seeking informed consent, especially if coupled with a right to withdraw, as it would not be feasible or it would be too expensive to seek consent renewal on a regular basis. However, there are concerns about this 'blanket consent' approach'. Consent waivers have also been proposed in which research subjects entrust their consent with an independent third party to decide whether subsequent research using the biobank is consistent with the original consent provided by the subject.     

Respecting Autonomy Over Time: Policy and Empirical Evidence on Re‐Consent in Longitudinal Biomedical Research

Re‐consent in research, the asking for a new consent if there is a change in protocol or to confirm the expectations of participants in case of change, is an under‐explored issue. There is little clarity as to what changes should trigger re‐consent and what impact a re‐consent exercise has on participants and the research project. This article examines applicable policy statements and literature for the prevailing arguments for and against re‐consent in relation to longitudinal cohort studies, tissue banks and biobanks. Examples of re‐consent exercises are presented, triggers and non‐triggers for re‐consent discussed and the conflicting attitudes of commentators, participants and researchers highlighted. We acknowledge current practice and argue for a greater emphasis on ‘responsive autonomy,’ that goes beyond a one‐time consent and encourages greater communication between the parties involved. A balance is needed between respecting participants' wishes on how they want their data and samples used and enabling effective research to proceed.     

Genetic research and consent: On the crossroads of human and data research

This paper explores the legal and ethical concept of human subject research in order to determine whether genetic research with already available biosamples and data falls within this concept. Although the ethical concept seems to have evolved to recognize research based on data as human research, from a supranational legal perspective this form of research is not considered human subject research. Thus human subject research regulations do not apply and therefore do not invoke the requirement of obtaining consent prior to using an individual’s biosample or genetic data in research. Furthermore, it remains ambiguous in both the legal and ethical realm whether the use of biosamples or genetic data without additional links to the individual would invoke the same safeguards as research involving additional or specific identifiers. Seeing that research based on already available biosamples and genetic data is not governed by rules concerning human subject research, the second part of the paper analyses whether any consent requirements apply for the further use of already available bio‐samples or genetic data in research. Whereas further use of biosamples is subject to considerably lax consent requirements under Article 22 of the Oviedo Convention, under the General Data Protection Regulation further use of genetic data might not be subject to a prior consent requirement at all, unless it is stipulated in national laws. When it comes to clinical trials, however, sponsors will have the possibility under Article 28(2) of Regulation 536/2014 to obtain open consent for further use of data in any kind of future research.     

RESPECTING AUTONOMY WITHOUT DISCLOSING INFORMATION

There is widespread agreement that it would be both morally and legally wrong to treat a competent patient, or to carry out research with a competent participant, without the voluntary consent of that patient or research participant. Furthermore, in medical ethics it is generally taken that that consent must be informed. The most widely given reason for this has been that informed consent is needed to respect the patient's or research participant's autonomy. In this article I set out to challenge this claim by considering in detail each of the three most prominent ways in which ‘autonomy’ has been conceptualized in the medical ethics literature. I will argue that whilst these accounts support the claim that consent is needed if the treatment of competent patients, or research on competent individuals, is to respect their autonomy, they do not support the claim that informed consent is needed for this purpose.     

Addiction,Voluntary Choice,and Informed Consent: A Reply to Uusitalo and Broers

In an earlier article in this journal I argued that the question of whether heroin addicts can give voluntary consent to take part in research which involves giving them a choice of free heroin does not – in contrast with a common assumption in the bioethics literature – depend exclusively on whether or not they possess the capacity to resist their desire for heroin. In some cases, circumstances and beliefs might undermine the voluntariness of the choices a person makes even if they do possess a capacity for self‐control. Based on what I took to be a plausible definition of voluntariness, I argued that the circumstances and beliefs typical of many vulnerable heroin addicts are such that we have good reasons to suspect they cannot give voluntary consent to take part in such research, even assuming their desire for heroin is not irresistible. In a recent article in this journal, Uusitalo and Broers object to this on the grounds that I misdescribe heroin addicts' options set, that the definition of voluntariness on which I rely is unrealistic and too demanding, and, more generally, that my view of heroin addiction is flawed. I think their arguments derive from a misunderstanding of the view I expressed in my article. In what follows I hope therefore to clarify my position.     

Consent and confidentiality in the light of recent demands for data sharing

Many attempts have been made to formalize ethical requirements for research. Among the most prominent mechanisms are informed consent requirements and data protection regimes. These mechanisms, however, sometimes appear as obstacles to research. In this opinion paper, we critically discuss conventional approaches to research ethics that emphasize consent and data protection. Several recent debates have highlighted other important ethical issues and underlined the need for greater openness in order to uphold the integrity of health‐related research. Some of these measures, such as the sharing of individual‐level data, pose problems for standard understandings of consent and privacy. Here, we argue that these interpretations tend to be overdemanding: They do not really protect research subjects and they hinder the research process. Accordingly, we suggest another way of framing these requirements. Individual consent must be situated alongside the wider distribution of knowledge created when the actions, commitments, and procedures of researchers and their institutions are opened to scrutiny. And instead of simply emphasizing privacy or data protection, we should understand confidentiality as a principle that facilitates the sharing of information while upholding important safeguards. Consent and confidentiality belong to a broader set of safeguards and procedures to uphold the integrity of the research process.     

Autonomy is a Right,Not a Feat: How Theoretical Misconceptions have Muddled the Debate on Dynamic Consent to Biobank Research

Should people be involved as active participants in longitudinal medical research, as opposed to remaining passive providers of data and material? We argue in this article that misconceptions of ‘autonomy’ as a kind of feat rather than a right are to blame for much of the confusion surrounding the debate of dynamic versus broad consent. Keeping in mind two foundational facts of human life, freedom and dignity, we elaborate three moral principles – those of autonomy, integrity and authority – to better see what is at stake. Respect for autonomy is to recognize the other's right to decide in matters that are important to them. Respect for integrity is to meet, in one's relationship with the other, their need to navigate the intersection between private and social life. Respect for authority is to empower the other – to help them to cultivate their responsibility as citizens. On our account, to force information onto someone who does not want it is not to respect that person's autonomy, but to violate integrity in the name of empowerment. Empowerment, not respect for autonomy, is the aim that sets patient‐centred initiatives employing a dynamic consent model apart from other consent models. Whether this is ultimately morally justified depends on whether empowerment ought to be a goal of medical research, which is questionable.     

Solidarity and justice as guiding principles in genomic research

In genomic research the ideal standard of free, informed, prior and explicit consent is sometimes difficult to apply. This has raised concern that important genomic research will be restricted. Different consent procedures have therefore been proposed. This paper explicitly examines the question how, in genomic research, the principles of solidarity and justice can be used to justify forms of diminished individual control over personal data and bio-samples. After a discussion of the notions of solidarity and justice and how they can be related to health care and genomic research, we examine how and in which situations these notions can form a strong moral basis for demanding certain financial sacrifices. Then we examine when these principles can justify consent procedures which diverge from the ideal standard. Because much genomic research is not expected to lead to immediate (clinical) benefits we also discuss the question of whether we can be obliged to make any sacrifices for future (not yet existing) patients. We conclude with the formulation of a number of conditions that have to be met before autonomy sacrifices can be reasonably demanded in genomic research.     

Informed consent and collaborative research: perspectives from the developing world

Introduction: Informed consent has been recognized as an important component of research protocols and procedures of disclosure and consent in collaborative research have been criticized, as they may not be in keeping with cultural norms of developing countries. This study, which is part of a larger project funded by the United States National Bioethics Advisory Commission, explores the opinions of developing country researchers regarding informed consent in collaborative research. Methods: A survey of developing country researchers, involved in human subject research, was conducted by distributing a questionnaire with 169 questions, which included questions relating to informed consent. In addition, six focus group discussions, eight in-depth interviews and 78 responses to open-ended questions in the questionnaire provided qualitative data. Results: 203 surveys were considered complete and were included in the analysis. Written consent was not used by nearly 40% of the researchers in their most recent studies. A large proportion of respondents recommended that human subject regulations should allow more flexibility in ways of documenting informed consent. 84% of researchers agreed that a mechanism to measure understanding should be incorporated in research studies as part of the process of informed consent. Discussion: This paper is an empirical step in highlighting the ethical issues concerning disclosure. Health researchers in developing countries are well aware of the importance of consent in health research, and equally value the significance of educating human subjects regarding study protocols and associated risks and benefits. However, respondents emphasize the need for modifying ethical regulations in collaborative research.