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The Challenges of Research Informed Consent in Socio-Economically Vulnerable Populations: A Viewpoint From the Democratic Republic of Congo
Abstract
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 D emocratic R epublic of C ongo, 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.
... 13 14 17 18 In one very thoughtful piece, Kalabuanga and colleagues note, however, that witnesses may often impose their views on the consenting caregiver and their child, rather than encouraging dialogue and acting as a safeguard, especially since they are often recruited in an ad hoc fashion (eg, other literate patients or ancillary hospital staff). 18 Kalabuanga et al go on to suggest that these challenges may be mitigated by careful vetting and training of independent witnesses or, alternatively, by allowing potential consenting caregivers to use a trusted relative or friend as their witness. 18 Another issue identified in the review is that of emerging mandates in some LMICs to document consent procedures. ...
... 18 Kalabuanga et al go on to suggest that these challenges may be mitigated by careful vetting and training of independent witnesses or, alternatively, by allowing potential consenting caregivers to use a trusted relative or friend as their witness. 18 Another issue identified in the review is that of emerging mandates in some LMICs to document consent procedures. For example, in India, audiovisual documentation of obtaining informed consent is now required for The consent process was adapted to include community leaders and groups of women. ...
... 11 13 18 These considerations highlight the importance of considering the socioeconomic and cultural background of study settings well before beginning research and making plans to incorporate appropriate early, equitable benefit-sharing measures when possible, such as using study resources to improve community-level care, not just care for eligible trial participants. 18 Adolescents Adolescents constitute a special population with vulnerabilities different from those of adults and younger children, and they should be included in research that addresses their specific needs (table 7). However, as legal minors they often cannot give informed consent for research. ...
Introduction
Conducting research with children in low/middle-income countries (LMIC) requires consideration of socioeconomic inequalities and cultural and linguistic differences. Our objective was to survey the literature on informed consent in paediatric LMIC research, assessing for practical guidance for culturally and linguistically appropriate procedures.
Methods
We conducted a scoping review on informed consent in paediatric LMIC research searching the PubMed, Web of Science and PsycINFO databases. Eligible articles were published in English, from any date range, of any study design or format.
Results
The search identified 2027 references, of which 50 were included in the analysis following full-text review. Reviewed guidelines emphasised individual, informed and voluntary consent from parents and caregivers. Reviewed articles provided detailed practical guidance on adapting these guiding principles to LMIC settings, including considerations for community engagement, verbal or other alternative consent procedures for low-literacy settings or less commonly spoken languages and guarding against therapeutic misconception by caregivers. There was uncertainty, however, on how to best protect individual autonomy, especially when influenced by gender dynamics, leadership hierarchies or the social status of researchers themselves. There was, furthermore, limited research discussing the special case of research involving adolescents or of procedures for documenting assent by participating children.
Conclusions
A scoping review of paediatric research in LMICs revealed substantial guidance on several features of culturally appropriate informed consent. However, additional research and guidance is needed, especially in the areas of gender imbalances, research with adolescents and children’s own assent to participate in research.
... pharmaceutical research and development (R&D) has historically neglected the diseases that mainly or exclusively hit LMICs. 1 On the other hand, trial participants in LMICs may be more exposed to poor research practices and exploitation, in particular because of social vulnerability: poverty and lack of access to healthcare may limit voluntariness, and trial participation may become a strategic choice to secure otherwise unavailable health and non-health resources. [2][3][4] Concerns about possible exploitation have been raised in sub-Saharan Africa, 5 6 India, 7 Latin America, 8 9 and South-East Asia. 10 11 The last two decades have also seen the 'globalisation of clinical trials', that is, trials are increasingly delocalised to non-US and non-Western European settings. [12][13][14][15] This is due to different reasons, including external validity, that is, the need to test new interventions in a variety of epidemiological settings and populations; convenience, that is, the opportunity of lower costs, easier ethical/regulatory review and easier availability of participants; 12 16 and global health, that is, the need to address the specific health needs of local populations. ...
... This may be perceived as a breach of privacy, or as an imposition of the views of the witness, rather than an opportunity to foster dialogue and improve understanding. 2 These observations are limited to Central Africa and should be confirmed in comparable settings. However, they strongly suggest that the mere presence of an independent witness is not per se sufficient to ensure participants protection. ...
The Good Clinical Practices (GCP) codes of the WHO and the International Conference of Harmonization set
international standards for clinical research. But critics argue that they were written without consideration for
the challenges faced in low and middle income countries (LMICs). Based on our field experience in LMICs, we
developed a non-exhaustive set of recommendations for the improvement of GCP. These cover 3 domains: ethical, legal and operational, and 8 specific issues: the double ethical review of ‘externally sponsored’ trials; the
informed consent procedure in minors and in illiterate people; post-trial access to newly-developed products
for the trial communities; the role of communities as key research actors; the definition of sponsor; and the
guidance for contractual agreements, laboratory quality management systems, and quality assurance of
investigational medicinal products. Issues not covered in our analysis include among others biobanking, standard of care, and study designs. The international GCP codes de facto guide national legislators and funding agencies, so the current shortcomings may weaken the regulatory oversight of international research. In addition, activities neglected by GCP are less likely to be implemented or funded. If GCP are meant to serve the interests of global society, a comprehensive revision is needed. The revised guidelines should be strongly rooted in ethics, sensitive to different sociocultural perspectives, and allow consideration for trial-specific and context-specific challenges. This can be only achieved if all stakeholders, including researchers, sponsors, regulators, ethical reviewers and patients’ representatives from LMICs, as well as non-commercial researchers and sponsors from affluent countries, are transparently involved in the revision process. We hope that our limited analysis would foster advocacy for a broad and inclusive revision of the international GCP codes, to make them at the same time ‘global’, ‘context centred’ and ‘patient centred’.
... IC difficulties are also mentioned repeatedly in the literature [20,24,31,32]. For example, Kalabuanga et al. suggest changing the guideline to permit trial inclusion of children without a legally acceptable representative [33]. The length and technical language of the consent form is a highly debated topic in both the north and south, as is the view that its content serves mainly to protect sponsors [32,34]. ...
... IC difficulties are also mentioned repeatedly in the literature [20,24,31,32]. For example, Kalabuanga et al. suggest changing the guideline to permit trial inclusion of children without a legally acceptable representative [33]. The length and technical language of the consent form is a highly debated topic in both the north and south, as is the view that its content serves mainly to protect sponsors [32,34]. ...
Objectives:
To explore the advantages and challenges of working with the Good Clinical Practice (GCP) ICH E6 guideline and its interpretation from the perspective of clinical trial teams based in sub-Saharan Africa.
Methods:
We conducted 60 key informant interviews with clinical trial staff at different levels in clinical research centres in Kenya, Ghana, Burkina Faso and Senegal, and thematically analysed the responses.
Results:
Clinical trial teams perceived working with ICH-GCP as highly advantageous and regarded ICH-GCP as applicable to their setting and efficiently applied. Only for informed consent did some clinical trial staff (one third) perceive the guideline as insufficiently applicable. Specific challenges included meeting the requirements for written and individual consent, conditions for impartial witnesses for illiterates or legally acceptable representatives for children, guaranteeing voluntary participation and ensuring full understanding of the consent given. It was deemed important to have ICH-GCP compliance monitored by relevant ethics committees and regulatory authorities, without having guidelines applied overcautiously.
Conclusion:
Clinical trial teams in sub-Saharan Africa perceived GCP as a helpful guideline, despite having been developed by Northern organisations and despite the high administrative burden of implementing it. To mitigate consent challenges, we suggest adapting GCP and making use of the flexibility it offers. This article is protected by copyright. All rights reserved.
... Improvements in the quality of routine care should not depend upon the willingness of the members of a community to participate in clinical trials and to accept the risks related to trial participation. This is particularly true for trials conducted in LMIC, where there may be few or no options to get comparable care of high quality outside of trial participation (Kalabuanga et al. 2015;Homedes and Ugalde 2015). In addition, the potential benefits of any infrastructure effect are very uncertain, and therefore cannot clearly outweigh the risks and complexities involved. ...
Clinical pharmacology studies are critical for determining the efficacy and safety of drugs. Due to the resource‐intensive nature of these studies, most have been conducted in high‐income countries, leading to a significant gap in clinical pharmacology data for patients in low‐ and middle‐income countries. This paper provides an overview of the minimal requirements for performing a clinical pharmacology investigator‐initiated trial (IIT), including pharmacokinetic sampling. We identify common challenges in resource‐limited settings and propose strategies to overcome them. This guideline covers regulatory approval, participant recruitment, drug storage, sample collection and handling, transport, bioanalytical analysis, and data management tailored to the constraints of resource‐limited settings. Strategies are proposed to minimize resource demands, including simplified study designs, the use of technologies like whole blood microsampling, and opportunities for collaboration. The goal is to provide practical guidance for those seeking to perform a clinical pharmacology IIT in resource‐limited settings to improve safe and effective drug treatment for patients worldwide. Beyond the scope of this guideline is a detailed step‐by‐step guide on how to perform clinical pharmacology studies.
Research engaging children and adolescents living with HIV (CALWH) is critical for youth-friendly services and HIV care, and researchers need to ensure that such engagement is ethical. We conducted a systematic review to identify key ethical considerations for the engagement of CALWH in research. The review focused on primary research articles conducted in African countries that examined ethical issues in CALWH engaged in research. Ten studies met the inclusion criteria; the following seven key domains were extracted: 1) justifications for engaging CALWH in research; 2) community involvement; 3) informed consent/assent; 4) caregiver involvement; 5) perceptions of benefits; 6) perception of the risks of involvement; and 7) confidentiality. These domains can inform the ethical engagement of CALWH in research.
Recognition that structural factors influence participation decisions and have potential to coerce participation, emerged relatively recently in research ethics literature. Empirical evidence to elucidate the nature of “structural” coercion and influence is needed to optimise respect for autonomy through voluntary informed consent. We present findings from ethnographic data about community co-researchers’ experiences designing and implementing demographic and health survey consent procedures in participatory health research in Eswatini. Informed by Bourdieu's sociological theory of multiple types of capital/power, our findings detail structural influences on research participation decisions, highlight the inherently power-laden dynamics of consent interactions, and suggest that to be optimally ethical, research ethics principles and practices should consider and account for structural power dynamics.
Background
Ethics review preparedness is a major foundation for national effective response to public health emergencies, because it promotes pertinent research and enhances the protection of research participants and communities. In low‐income countries, it can also promote equitable research partnership. However, most relevant literature is in English and not easily accessible for the members of research ethics committees in French‐speaking African countries.
Methods
A training module in French, addressing the issue of research ethics review during outbreaks and other public health emergencies, was designed based on a non‐systematic literature review, and in order to be complementary to the Democratic Republic of Congo (DRC) national guidelines for ethics review. The module was administered to 42 members of the five ethics committees in DRC that expressed their interest for the training.
Result
This training, co‐designed with local stakeholders, in the local working language and taking into account local circumstances and regulation, provided participants with up‐to‐date insights of research ethics (and research ethics preparedness) in public health emergencies. It resulted in rich reflection and knowledge‐sharing on good practices across the ethics committees.
Conclusion
As most participating ethics committees do not have yet explicit standard operating procedures for expedited review of protocols submitted in emergency situations, this would be a next important step to facilitate emergency reviews in the most efficient way.
Concerns around comprehension and recall of consent information by research participants have typically been associated with low health and research literacy levels. In genomics research, this concern is heightened as the scientific and ethical complexities of genetics research, such as biobanking, genetic susceptibility, data sharing, and incidental findings may be more difficult for potential research participants to understand. However, challenges to research participants’ comprehension of consent information may be compounded by factors beyond health and research literacy levels. To identify factors that may impact research participants’ understanding and recall of consent information, we designed a qualitative study to explore whether participants enrolled in a tuberculosis genetics study (TBGEN-Africa) in Cameroon understood the objectives of the study, the risks and benefits and certain key aspects of the study such as biobanking and data sharing. The results showed that research participants had limited understanding and/or recall of the TBGEN-Africa study goals and methods. Some participants were of the opinion that TBGEN-Africa was not a genetics study because tuberculosis is not an inheritable condition. Factors that may have hindered understanding and/or recall of study information are diagnostic misconception (research participants consider research as part of medical diagnosis), and information overload and situational vulnerability (consent at a time of physical and emotional distress). There is a need for improved practices to support research participants’ understanding of consent information in genetics studies including designing the consent process in ways that minimize psychological distress and diagnostic/therapeutic misconception.
Implementing an Ebola vaccine trial in a remote area in the Democratic Republic of the Congo (DRC), and being confronted with a dysfunctional health care system and acute unmet health needs of participants, ethical considerations were made regarding the ancillary care obligations of the sponsor and researchers. Spurred by the occurrence of non-related (serious) adverse events (NR-SAEs), the Universities of Antwerp and Kinshasa jointly developed an algorithm, accompanied by an algorithm policy. The algorithm consists of a set of consecutive questions with binary response options, leading to structured, non-arbitrary and consistent support and management for each NR-SAE. It is the result of dialogue and collaboration between the sponsor (University of Antwerp) and the principal investigator (University of Kinshasa), consultation of literature, and input of research ethics and social sciences experts. The characteristics of the project and its budgetary framework were taken into account, as well as the local socioeconomic and healthcare situation. The algorithm and related policy have been approved by the relevant ethics committee (EC), so field implementation will begin when the study activities resume in November 2021. Lessons learnt will be shared with the relevant stakeholders within and outside DRC.
If NR-SAEs are not covered by a functioning social welfare system, sponsors and researchers should develop a feasible, standardised and transparent approach to the provision of ancillary care. National legislation and contextualised requirements are therefore needed, particularly in low/middle-income countries, to guide researchers and sponsors in this process. Protocols, particularly of clinical trials conducted in areas with ‘access to care’ constraints, should include adequate ancillary care arrangements. Furthermore, it is essential that local ECs systematically require ancillary care provisions to enhance the well-being and protection of the rights of research participants. This project was funded by the European Union’s Horizon 2020 research and innovation programme, European Federation of Pharmaceutical Industries and Associations, and the Coalition for Epidemic Preparedness Innovations.
Background:
Informed consent (IC) is linked to the ethical principle of respecting patient autonomy, respect for human rights and ethical practice, while in many countries it is a standard procedure. Anecdotally, it should be noted that in the Democratic Republic of Congo (DRC) in many instances ICs are not obtained systematically. To date, no research appears to have been conducted on this matter. This study aimed to assess the knowledge and practice of obtaining IC from patients among health care providers (HCP) in the DRC.
Methods:
This was a cross-sectional study, with a convenient sampling of 422 participants. Data from the questions were collected on an imported Microsoft Excel spreadsheet for review at INSTAT.TM The authors set IC's accurate knowledge and practice at 80% or higher. The Fisher Exact test was used to compare categorical association results, and a p-value < 0.05 was considered statistically significant.
Results:
Results showed that giving information in detail to patients on their medical condition was associated with formal training on medical ethics and IC (p: 0.0028; OR: 1.894; CI: 1.246 to 2.881), which was also associated with answering the patient's questions in detail (p: 0.0035; OR: 1.852; CI: 1.236 to 2.774). About 127(30.09 %) of participants scored 80% or higher. Extracurricular training was associated with withholding information from patients, up to 27 times more than other factors (p< 0.0001; OR: 27.042; CI: 13.628 to 53.657). when it comes to get IC, HCP with many years of practice scored better than others, in one of the question the odd ratio was closer to 7 (p< 0.0001; OR: 6.713; CI: 4.352 to 10.356). Only 47(11.14%) of the participants scored 80% or more of the questions about practice of IC.
Conclusion:
For a variety of reasons, knowledge and practice of IC among HCPs was very low. A common programme for the country as part of formal training might lead to an improvement. In addition, patients' education on IC should be displayed in waiting areas at all medical centres.
Theoretically, community participation decolonises research ethics in settings where a ‘coloniality of power’ persists. We used ethnographic methods to document our experiences of ‘ethics in practice’, and interrogate the (de)colonising outcomes, of community participation in voluntary informed assent and consent (VIAC) procedures with 16–17-year-old Black South African youth and parents. Community participation decolonised by: (1) disrupting and problematising the power dynamics of written VIAC procedures and (2) minimally shifting power to youth and parents. However, community participation sometimes reinforced existing power hierarchies. In postcolonial qualitative research settings, community participation has potential to, but will not necessarily, decolonise ethics in practice.
Resumo Este artigo aborda a vulnerabilidade humana, apontando que as discussões sobre vulnerabilidade social e existencial não são suficientes para compreender determinadas situações de discriminação e exclusão a que algumas pessoas são submetidas. Trata-se de revisão teórica da temática estudada, a partir de abordagem interdisciplinar, como é próprio da bioética. A literatura deste campo já apresenta a distinção entre ser vulnerável, elemento próprio da condição humana, e estar vulnerável, indicando circunstâncias específicas. As situações de estar vulnerável revelam a chamada “vulnerabilidade social”; no entanto, há cenários em que a condição de vulnerabilidade de algumas pessoas é construída a partir de elementos abertamente morais, culturais, teóricos e, por isso, é defendida explicitamente. O artigo trata do conceito de vulnerabilidade moral, no âmbito da bioética, como uma chave de leitura para compreender a exclusão e discriminação a que alguns grupos são submetidos na atualidade, principalmente negros, mulheres e homossexuais.
Researchers of the Northeast Ethics Education Partnership (NEEP) at Brown University sought to improve an understanding of the ethical challenges of field researchers with place-based communities in environmental studies/sciences and environmental health by disseminating a questionnaire which requested information about their ethical approaches to these researched communities. NEEP faculty sought to gain actual field guidance to improve research ethics and cultural competence training for graduate students and faculty in environmental sciences/studies. Some aspects of the ethical challenges in field studies are not well-covered in the literature. More training and information resources are needed on the bioethical challenges in environmental field research relating to maximizing benefits/reducing risks to local inhabitants and ecosystems from research; appropriate and effective group consent and individual consent processes for many diverse communities in the United States and abroad; and justice considerations of ensuring fair benefits and protections against exploitation through community-based approaches, and cultural appropriateness and competence in researcher relationships.
We identify the ways the policies of leading international bioethics journals limit the participation of researchers working in the resource-constrained settings of low- and middle-income countries (LMICs) in the development of the field of bioethics. Lack of access to essential scholarly resources makes it extremely difficult, if not impossible, for many LMIC bioethicists to learn from, meaningfully engage in, and further contribute to the global bioethics discourse. Underrepresentation of LMIC perspectives in leading journals sustains the hegemony of Western bioethics, limits the presentation of diverse moral visions of life, health, and medicine, and undermines aspirations to create a truly “global” bioethics. Limited attention to this problem indicates a lack of empathy and moral imagination on the part of bioethicists in high-income countries, raises questions about the ethics of bioethics, and highlights the urgent need to find ways to remedy this social injustice.
Background
Qualitative study of motivations to participate in research into violence and other sensitive issues can help interpretation of findings from community based quantitative surveys. It is equally important to conduct research that may enable a deeper understanding on what motivates people to participate in GBV studies. To date, not much research has been conducted to investigate the factors that influence non-enrolment and enrolment in GBV studies from the viewpoint of the real participants. The present study sought to explore people’s reasons for participating in a non-intervention GBV community-based survey in Gauteng province, South Africa.
Methods
Twenty-two qualitative in-depth interviews were conducted with adult black African men and women who had participated in a gender-based violence survey conducted in a low-income setting in South Africa.
Results
Some participants reported motives for survey participation which could be interpreted as altruistic. Their motives included a desire to contribute to advancement of knowledge and to share life experiences so that unknown others could learn from these experiences. Yet, some participants hoped their participation will result in personal benefit or that they may be helped with their socio-economic challenges. The analysis further revealed a complex relationship between altruism and self-interest motives for participating in the survey amongst some of the participants.
Conclusion
We conclude that it is difficult to discern which motive was primary or preceded the other. This is because such motives are not fixed, probably multiple and owing to their fluidity, may shift in people’s minds at different times and depending on the nature of the conversation. Moreover, there may be a shift in the weight given to different motives over time.
Objective: To assess the effectiveness of a multimedia informed consent tool for adults participating in a clinical trial in the Gambia.
Methods: Adults eligible for inclusion in a malaria treatment trial (n = 311) were randomized to receive information needed for informed consent using either a multimedia tool (intervention arm) or a standard procedure (control arm). A computerized, audio questionnaire was used to assess participants’ comprehension of informed consent. This was done immediately after consent had been obtained (at day 0) and at subsequent follow-up visits (days 7, 14, 21 and 28). The acceptability and ease of use of the multimedia tool were assessed in focus groups.
Findings: On day 0, the median comprehension score in the intervention arm was 64% compared with 40% in the control arm (P = 0.042). The difference remained significant at all follow-up visits. Poorer comprehension was independently associated with female sex (odds ratio, OR: 0.29; 95% confidence interval, CI: 0.12–0.70) and residing in Jahaly rather than Basse province (OR: 0.33; 95% CI: 0.13–0.82). There was no significant independent association with educational level. The risk that a participant’s comprehension score would drop to half of the initial value was lower in the intervention arm (hazard ratio 0.22, 95% CI: 0.16–0.31). Overall, 70% (42/60) of focus group participants from the intervention arm found the multimedia tool clear and easy to understand.
Conclusion: A multimedia informed consent tool significantly improved comprehension and retention of consent information by research participants with low levels of literacy.
Previous reviews on participants' comprehension of informed consent information have focused on developed countries. Experience has shown that ethical standards developed on Western values may not be appropriate for African settings where research concepts are unfamiliar. We undertook this review to describe how informed consent comprehension is defined and measured in African research settings.
We conducted a comprehensive search involving five electronic databases: Medline, Embase, Global Health, EthxWeb and Bioethics Literature Database (BELIT). We also examined African Index Medicus and Google Scholar for relevant publications on informed consent comprehension in clinical studies conducted in sub-Saharan Africa. 29 studies satisfied the inclusion criteria; meta-analysis was possible in 21 studies. We further conducted a direct comparison of participants' comprehension on domains of informed consent in all eligible studies.
Comprehension of key concepts of informed consent varies considerably from country to country and depends on the nature and complexity of the study. Meta-analysis showed that 47% of a total of 1633 participants across four studies demonstrated comprehension about randomisation (95% CI 13.9-80.9%). Similarly, 48% of 3946 participants in six studies had understanding about placebo (95% CI 19.0-77.5%), while only 30% of 753 participants in five studies understood the concept of therapeutic misconception (95% CI 4.6-66.7%). Measurement tools for informed consent comprehension were developed with little or no validation. Assessment of comprehension was carried out at variable times after disclosure of study information. No uniform definition of informed consent comprehension exists to form the basis for development of an appropriate tool to measure comprehension in African participants.
Comprehension of key concepts of informed consent is poor among study participants across Africa. There is a vital need to develop a uniform definition for informed consent comprehension in low literacy research settings in Africa. This will be an essential step towards developing appropriate tools that can adequately measure informed consent comprehension. This may consequently suggest adequate measures to improve the informed consent procedure.
In Democratic Republic of Congo access to health care is limited because of many geographical and financial barriers, while quality of care is often low. Global health donors assist the country with a number of community-oriented interventions such as free distribution of bednets, antihelminthic drugs, vitamin A supplementation and vaccination campaigns, but uptake of these interventions is not always optimal. The aim of this study was to explore the perceptions of poor urban communities of the capital Kinshasa with regard to health issues in general as well as their experiences and expectations concerning facility-based health services and community-oriented health interventions. Applying an approach rooted in the grounded theory framework, focus group discussions were conducted in eight neighborhoods of poor urban areas in the city of Kinshasa in July 2011. Study participants were easily able to evoke the city's major health problems, with the notable exceptions of malnutrition and HIV/AIDS. They perceive the high out-of-pocket cost of health services as the major obstacle when seeking access to quality care. Knowledge of ongoing community-oriented health interventions seems good. Still, while the study participants agree that those interventions are beneficial; their acceptability seems to be problematic. This is chiefly put down to a lack of information and government communication about the programs and their interventions. Furthermore, the study participants referred to rumors and the deterring effect of stories about alleged harmful consequences of those interventions. Along with improving the provision and quality of general health care, the government and international actors must improve their efforts in informing the communities about disease control programs, their rationale and benefit/risk ratio. Directly engaging community members in a dialogue might be beneficial in terms of improving acceptability and overall access to health services and interventions. Novel ways of reducing the high out-of-pocket expenditure should also be explored.
Over the last years, the number of clinical trials carried out in low-income countries with poor medical infrastructure and limited access to health care has increased. In these settings, the decision of participating in a clinical study may be influenced by factors related to participants' vulnerability that limit the efficacy of the informed consent.
A mixed methods social science study, based on the triangulation of qualitative and quantitative data, was carried out in a socio-economically disadvantaged and semi-urban area of Bobo Dioulasso, Burkina Faso. The study aimed at assessing the relevance of the informed consent procedure on the decision-making process of the parents and/or guardians of potential participants in a pediatric malaria trial.
For most parents (70.4%), the decision of participating had already been taken before undergoing the informed consent process and was based on the information conveyed through the community. Access to free and good quality health care often inspired this decision. In addition, the parents' willingness to have their child included in the trial made them develop active strategies to achieve this purpose.
In a context of socio-economic vulnerability and poor access to free health care, the process of informed consent does not always accomplish its goal of informing people and enabling them to make a free and informed decision. This information role is somehow anticipated by the community and trial participation becomes a strategic action to secure otherwise unavailable health resources leading community members to decide on participation even prior to the informed consent process.
Background:
Artemisinin-based combination therapy is currently recommended by the World Health Organization as first-line treatment of uncomplicated malaria. Recommendations were adapted in 2010 regarding rescue treatment in case of treatment failure. Instead of quinine monotherapy, it should be combined with an antibiotic with antimalarial properties; alternatively, another artemisinin-based combination therapy may be used. However, for informing these policy changes, no clear evidence is yet available. The need to provide the policy makers with hard data on the appropriate rescue therapy is obvious. We hypothesize that the efficacy of the same artemisinin-based combination therapy used as rescue treatment is as efficacious as quinine + clindamycin or an alternative artemisinin-based combination therapy, without the risk of selecting drug resistant strains.
Design:
We embed a randomized, open label, three-arm clinical trial in a longitudinal cohort design following up children with uncomplicated malaria until they are malaria parasite free for 4 weeks. The study is conducted in both the Democratic Republic of Congo and Uganda and performed in three steps. In the first step, the pre-randomized controlled trial (RCT) phase, children aged 12 to 59 months with uncomplicated malaria are treated with the recommended first-line drug and constitute a cohort that is passively followed up for 42 days. If the patients experience an uncomplicated malaria episode between days 14 and 42 of follow-up, they are randomized either to quinine + clindamycin, or an alternative artemisinin-based combination therapy, or the same first-line artemisinin-based combination therapy to be followed up for 28 additional days. If between days 14 and 28 the patients experience a recurrent parasitemia, they are retreated with the recommended first-line regimen and actively followed up for another 28 additional days (step three; post-RCT phase). The same methodology is followed for each subsequent failure. In any case, all patients without an infection at day 28 are classified as treatment successes and reach a study endpoint. The RCT phase allows the comparison of the safety and efficacy of three rescue treatments. The prolonged follow-up of all children until they are 28 days parasite-free allows us to assess epidemiological-, host- and parasite-related predictors for repeated malaria infection.
Trial registration:
NCT01374581 and PACTR201203000351114.
http://www.bmj.com/content/346/bmj.f2837/rr/650200
(Revising the Declaration of Helsinki)
Medical research in socio-economically disadvantaged communities: a delicate balance
Authors: Raffaella M Ravinetto, Koen Peeters Grietens, Halidou Tinto, Ermias Diro, Pascal Lutumba, Rezika Mohammed, Jean-Bertin Kabuja, Minne Casteels, Marleen Boelaert
17 June 2013
As pointed in the BMJ Editorial, the public consultation of the World Medical Association provided researchers with a unique opportunity to influence research governance, based on real-life experience. As a group of clinical ad social sciences researchers active in North-South collaborative research, we would like to draw the attention to the concept of “vulnerability” in medical research, on how it is currently defined in the Declaration, and on how it could be refined.
“Vulnerability” is explicitly addressed in the Article 19 and Article 20 of the Draft Version for Public Consultation of the Declaration. In the Article 19, it is described as being unable to give or refuse consent, or as being at risk of coercion or undue influence, and is defined in terms of age, mental capacity or autonomy. For instance, young children and the mentally incapacitated are not in the position to consent for themselves; and prisoners and other persons living in highly hierarchized environments are potentially subject to some form of coercion or undue influence. Thus, these categories of people should always be considered as [potentially] vulnerable in the context of medical research: they have “an increased likelihood of incurring additional and greater harm”, and they need “specifically considered protection”. The concepts of coercion or undue influence, and of inability to consent, are retaken in the Articles 27 and 28, which require appropriate measures for consent if “the potential subject is in a dependent relationship with the physician or may consent under duress”, and if the potential research subject is incompetent.
But nowadays, we face situations where identifying vulnerable individuals or communities in medical research is less straightforward than Article 19 seems to portray. In fact, the substantial increase in the number of commercial and non-commercial clinical studies conducted in limited-resources settings has brought new opportunities as well as new challenges (1). In particular, research participants are more and more frequently recruited from [severely] socio-economically disadvantaged populations, whose status could be described in terms of poverty (i.e. the lack of physical necessities, assets and income) (2) and/or social exclusion. Social exclusion consists of dynamic, multi-dimensional processes driven by unequal power relationships interacting across an economic, political, social and cultural dimension and operating at different levels, including individual, household, group, community, country and global levels. It results in a continuum of inclusion/exclusion characterized by unequal access to resources, capabilities and rights, which leads to health inequalities (3). Patients recruited in these settings may have diminished autonomy and be vulnerable to exploitation (4) due to more subtle reasons than those traditionally considered (5), something which may directly impair their freedom to consent and expose them to exploitation. The lack of/limited access to quality health care, for example, may push these populations towards participation in research, simply because it is a way to get free access to quality health care. Noteworthy, the proposed Article 20 of the Declaration refers to “disadvantaged or vulnerable population or community”, but does not give defining criteria for them.
We acknowledge the WMA workgroup’s statement that specific vulnerable groups should not be mentioned explicitly in the Declaration and that a general regulation on vulnerability is more appropriate, to avoid misinterpretation. Nonetheless, in order to avoid such misinterpretation and ambiguity when defining vulnerable study populations, we propose that the general regulation should include at least a clear definition/defining criteria of the categories of people that constitute vulnerable groups (i.e. age, autonomy, poverty). In fact, the causes and features of vulnerability may vary, and the ways and tools to ensure protection of different vulnerable persons/communities will vary accordingly (i.e. assuring ethical research conduct for socially excluded/stigmatized persons will require different protective measures then for those who are poor but fully participating members of society). In light of the above, we suggest that both poverty and social exclusion are explicitly acknowledged in the Declaration of Helsinki as criteria to define vulnerable groups.
Noteworthy, vulnerability due to poverty and/or social exclusion should never in itself lead to exclusion from medical research, as research in socio-economically vulnerable populations is most often badly needed to address the specific health problems of these communities. Excluding them from pertinent medical research would result in a breach of the ethical principles of fairness and justice. And fortunately, in recent years there has been an increase in medical research on e.g. neglected tropical diseases addressing health needs of the most neglected patients (6,7). These additional criteria in the Declaration should be seen as a reason for taking special care to avoid both exploitation and neglect. We hope that this would contribute to achieve the best protection of research subjects and their communities, irrespectively of their socio-economic status, and in a timeless manner.
REFERENCES
1. Halidou Tinto, Ramadhani A. Noor, Charles L. Wanga, Innocent Valea, Maimouna Ndour Mbaye, Umberto D'Alessandro, and Raffaella M. Ravinetto. Good Clinical Practice in Resource-Limited Settings: Translating Theory into Practice. Am J Trop Med Hyg 2013;88 608-613
2. Chambers R. Poverty and livelihoods: whose reality counts? Environ Urban 1995; 7:173-204. SAGE Publications. Available online at http://eau.sagepub.com/content/7/1/173
3. Popay J, Escorel S, Hernández M, Johnston H, Mathieson J, Rispel L. Understanding and tackling social exclusion. Final report to the WHO Commission on Social Determinants of Health. From the Social Exclusion Knowledge Network WHO, 2008. Available at: www.who.int/social_determinants/knowledge_networks/final_reports/sekn_fi...
4. Editorial: Strengthening clinical research in India. The Lancet 2007; 369 (9569): 1233
5. Kipnis K. Vulnerability in research subjects: a bioethical taxonomy. In: National Bioethics Advisory Commission. Ethical and policy issues in research involving human participants. Vol. II. Washington, DC: US Government Printing Office, 2001.
6. Boelaert M, Meheus F, Robays J, Lutumba P. Socio-economic aspects of neglected diseases: sleeping sickness and visceral leishmaniasis. Ann Trop Med Parasitol. 2010 Oct;104(7):535-42. doi: 10.1179/136485910X12786389891641. Review. PubMed PMID: 21092391.
7. Picado A, Rijal S, Sundar S, Boelaert M. Visceral leishmaniasis treatment in the Indian subcontinent: how to reach the most vulnerable. Expert Rev Anti Infect Ther. 2012 Aug;10(8):839-41. doi: 10.1586/eri.12.71. PubMed PMID: 23030320.
Competing interests:None declared
Background
The intervention reported in this paper was a follow up to an empirical study conducted in Malawi with the aim of assessing trial participants’ understanding of randomisation, double-blinding and placebo use. In the empirical study, the majority of respondents (61.1%; n=124) obtained low scores (lower than 75%) on understanding of all three concepts under study. Based on these findings, an intervention based on a narrative which included all three concepts and their personal implications was designed. The narrative used daily examples from the field of Agriculture because Malawi has an agro-based economy.
Methods
The intervention was tested using a sample of 36 women who had been identified as low scorers during the empirical study. The 36 low scorers were randomly assigned to control (n=18) and intervention arms (n=18). The control arm went through a session in which they were provided with standard informed consent information for the microbicide trial. The intervention arm went through a session in which they were provided with a narrative in ChiChewa, the local language, with the assistance of a power point presentation which included pictures as well as discussions on justification and personal implications of the concepts under study.
Results
The findings on the efficacy of the intervention suggest that the 3 scientific concepts and their personal implications can be understood by low literacy populations using simple language and everyday local examples. The findings also suggest that the intervention positively impacted on understanding of trial procedures under study, as 13 of the 18 women in the intervention arm, obtained high scores (above 75%) during the post intervention assessment and none of the 18 in the control arm obtained a high score. Using Fischer’s exact test, it was confirmed that the effect of the intervention on understanding of the three procedures was statistically significant (p=0.0001).
Conclusions
Potential trial participants can be assisted to understand key clinical trial procedures, their justification and personal implications by using innovative tailored local narratives.
Background
International collaborators face challenges in the design and implementation of ethical biomedical research. Evaluating community understanding of research and processes like informed consent may enable researchers to better protect research participants in a particular setting; however, there exist few studies examining community perspectives in health research, particularly in resource-limited settings, or strategies for engaging the community in research processes. Our goal was to inform ethical research practice in a biomedical research setting in western Kenya and similar resource-limited settings.
Methods
We sought to use mabaraza, traditional East African community assemblies, in a qualitative study to understand community perspectives on biomedical research and informed consent within a collaborative, multinational research network in western Kenya. Analyses included manual, progressive coding of transcripts from mabaraza to identify emerging central concepts.
Results
Our findings from two mabaraza with 108 community members revealed that, while participants understood some principles of biomedical research, they emphasized perceived benefits from participation in research over potential risks. Many community members equated health research with HIV testing or care, which may be explained in part by the setting of this particular study. In addition to valuing informed consent as understanding and accepting a role in research activities, participants endorsed an increased role for the community in making decisions about research participation, especially in the case of children, through a process of community consent.
Conclusions
Our study suggests that international biomedical research must account for community understanding of research and informed consent, particularly when involving children. Moreover, traditional community forums, such as mabaraza in East Africa, can be used effectively to gather these data and may serve as a forum to further engage communities in community consent and other aspects of research.
Background
Clinical trials involving children previously considered unethical are now considered essential because of the inherent physiological differences between children and adults. An integral part of research ethics is the informed consent, which for children is obtained by proxy from a consenting parent or guardian. The informed consent process is governed by international ethical codes that are interpreted in accordance with local laws and procedures raising the importance of contextualizing their implementation.
Findings
In Zimbabwe the parental informed consent document for children participating in clinical research is modeled along western laws of ethics and requires that the parent or legally authorized representative provide consent on behalf of a minor. This article highlights the experiences and lessons learnt by Zimbabwean researchers in obtaining informed consent from guardians of orphaned children participating in a collaborative HIV clinical trial involving the Medical Research Council, United Kingdom and four centers, three of which are in Uganda. Researchers were faced with a situation where caregivers of orphaned children were not permitted to provide informed consent for trial participation. The situation contrasted with general clinical practice where consent for procedures on orphans is obtained from their caregivers who are not legal guardians.
Conclusion
The challenges faced in obtaining informed consent for orphans in this clinical trial underscores the need for the Zimbabwe ethics committee to develop an ethical and legal framework for pediatric research that is based on international guidelines while taking into account the cultural context. The Medical Research Council of Zimbabwe has since started the process that is expected to involve critical stakeholders namely the community including children, ethicists, the legal fraternity and researchers.
As part of a cluster of articles leading up to the 2012 World Health Report and critically reflecting on the theme of "no health without research," Suerie Moon and colleagues argue for a global health R&D treaty to improve innovation in new medicines and strengthening affordability, sustainable financing, efficiency in innovation, and equitable health-centered governance.
Informed consent (IC) has been an international standard for decades for the ethical conduct of clinical trials. Yet frequently study participants have incomplete understanding of key issues, a problem exacerbated by language barriers or lack of familiarity with research concepts. Few investigators measure participant comprehension of IC, while even fewer conduct interim assessments once a trial is underway.
We assessed comprehension of IC using a 20-question true/false quiz administered in 6-month intervals in the context of a placebo-controlled, randomized trial for the prevention of tuberculosis among HIV-infected adults in Botswana (2004-2009). Quizzes were offered in both Setswana and English. To enroll in the TB trial, participants were required to have ≥ 16/20 correct responses. We examined concepts understood and the degree to which understanding changed over three-years. We analyzed 5,555 quizzes from 1,835 participants. The participants' highest education levels were: 28% primary, 59% secondary, 9% tertiary and 7% no formal education. Eighty percent of participants passed the enrollment quiz (Quiz1) on their first attempt and the remainder passed on their second attempt. Those having higher than primary education and those who took the quiz in English were more likely to receive a passing score on their first attempt (adjusted odds ratios and 95% confidence intervals, 3.1 (2.4-4.0) and 1.5 (1.2, 1.9), respectively). The trial's purpose or procedures were understood by 90-100% of participants, while 44-77% understood randomization, placebos, or risks. Participants who failed Quiz1 on their initial attempt were more likely to fail quizzes later in the trial. Pass rates improved with quiz re-administration in subsequent years.
Administration of a comprehension quiz at enrollment and during follow-up was feasible in a large, international collaboration and efficiently determined IC comprehension by trial participants. Strategies to improve understanding of concepts like placebos and randomization are needed. Comprehension assessments throughout a study may reinforce key concepts.
Initial responses to questionnaires used to assess participants' understanding of informed consent for malaria vaccine trials conducted in the United States and Mali were tallied. Total scores were analyzed by age, sex, literacy (if known), and location. Ninety-two percent (92%) of answers by United States participants and 85% of answers by Malian participants were correct. Questions more likely to be answered incorrectly in Mali related to risk, and to the type of vaccine. For adult participants, independent predictors of higher scores were younger age and female sex in the United States, and male sex in Mali. Scores in the United States were higher than in Mali (P = 0.005). Despite this difference participants at both sites were well informed overall. Although interpretation must be qualified because questionnaires were not intended as research tools and were not standardized among sites, these results do not support concerns about systematic low understanding among research participants in developing versus developed countries.
Our aim is to raise awareness of the issues faced by researchers in developing countries and to introduce an initiative we are developing.
We propose that the gaps and issues we have outlined could be largely addressed by building a community of researchers from all the various roles who will be able to access the information, guidance and resources they need, whilst also be able to share methods and pragmatic operational practices that have been locally derived and known to work. Some examples include template consent forms, data management systems, and example protocols and laboratory sample collection and handling methods.
We emphasize that this initiative is entirely based on an ethos of collaboration, open access, and sharing practice; indeed it will only be successful if research groups both use the resource and contribute to its development. The development of a prototype of web site for this initiative is underway and can be found at http://pilot.globalhealthtrials.org/. We are making this public at this early juncture as we are seeking involvement from our colleagues right from the outset in line with the open and collaborative ethos that is envisaged. Therefore, we encourage colleagues to become part of this initiative by providing content, commenting on the Web site, and sharing their operational tools. We also welcome all those engaged in trials to register and build their own personal professional development record to track their career and training record, and to provide a review structure.
HIV prevention trials conducted among disadvantaged vulnerable at-risk populations in developing countries present unique ethical dilemmas. A key concern in bioethics is the validity of informed consent for trial participation obtained from research subjects in such settings. The purpose of this study was to investigate the effectiveness of a continuous informed consent process adopted during the MDP301 phase III vaginal microbicide trial in Mwanza, Tanzania.
A total of 1146 women at increased risk of HIV acquisition working as alcohol and food vendors or in bars, restaurants, hotels and guesthouses have been recruited into the MDP301 phase III efficacy and safety trial in Mwanza. During preparations for the trial, participatory community research methods were used to develop a locally-appropriate pictorial flipchart in order to convey key messages about the trial to potential participants. Pre-recorded audio tapes were also developed to facilitate understanding and compliance with gel-use instructions. A comprehension checklist is administered by clinical staff to all participants at screening, enrolment, 12, 24, 40 and 50 week follow-up visits during the trial. To investigate women's perceptions and experiences of the trial, including how well participants internalize and retain key messages provided through a continuous informed consent process, a random sub-sample of 102 women were invited to participate in in-depth interviews (IDIs) conducted immediately after their 4, 24 and 52 week follow-up visits.
99 women completed interviews at 4-weeks, 83 at 24-weeks, and 74 at 52 weeks (a total of 256 interviews). In all interviews there was evidence of good comprehension and retention of key trial messages including that the gel is not currently know to be effective against HIV; that this is the key reason for conducting the trial; and that women should stop using gel in the event of pregnancy.
Providing information to trial participants in a focussed, locally-appropriate manner, using methods developed in consultation with the community, and within a continuous informed-consent framework resulted in high levels of comprehension and message retention in this setting. This approach may represent a model for researchers conducting HIV prevention trials among other vulnerable populations in resource-poor settings.
Current Controlled Trials ISRCTN64716212.
Research participants may not adequately understand the research in which they agree to enroll. This could be due to a myriad of factors. Such a missing link in the informed consent process contravenes the requirement for an "informed" consent prior to the commencement of research. This study assessed the post consent understanding of Nigerian study participants of the oral health research they were invited to join.
A descriptive cross sectional study with research participants who had just consented to one of three ongoing research studies on oral health. Study sites included two centers, one in the northern and one in the southern part of Nigeria. Data were collected using a combination of quantitative and qualitative methods.
A total of 113 research participants were interviewed. The southern part of the country had 58 respondents with the north having 55. The age range was 21 - 80 years. Mean age was 46.1 (SD16.3). The sample was predominantly male (69.9%) and married (64.6%). There was poor understanding of some key elements of the informed consent process such as involvement in research, benefits, contacts, confidentiality and voluntariness. Some identified factors potentially compromising understanding were poverty, illiteracy, therapeutic misconception and confusion about the dual roles of the Dentist and the researcher.
The participants recruited into the oral health research in Nigeria did not adequately understand the studies they were invited to join nor do they understand their rights as research participants. Measures should be taken to include research bioethics into the curricula of Dental schools and to train oral health researchers in the country on research ethics.
Available data suggest that prospective research participants may frequently not understand information disclosed to them in the informed consent process. Little is known about how understanding can be improved.
To review research on interventions to improve research participants' understanding of information disclosed in the informed consent process.
A search of MEDLINE was performed using the terms informed consent and clinical research and informed consent and (comprehension or understanding) from 1966 to March 2004 , which included randomized controlled trials, longitudinal trials, and controlled trials with nonrandom allocation that compared the understanding of research participants who had undergone only a standard informed consent process to that of participants who had received an intervention to improve their understanding. A comprehensive bibliography of empirical research on informed consent published in January 1999 was also reviewed, as were personal files and all issues of the journals IRB and Controlled Clinical Trials.
Study design, quality criteria, population characteristics, interventions, and outcomes for each trial were extracted. The statistical significance of the interventions' effects on understanding were noted, as were mean scores for understanding for each group of each trial. For those trials that measured the secondary outcomes of satisfaction and willingness to enroll, results were also summarized.
Thirty studies described 42 trials that met inclusion criteria. Of 12 trials of multimedia interventions, 3 showed significant improvement in understanding. Of 15 trials of enhanced consent forms, 6 showed significant improvement in understanding (all P<.05), but 5 of 6 trials were of limited quality, casting doubt on their practical relevance. Of 5 trials of extended discussion, 3 showed significant improvement in understanding (all P<.001) and 2 showed trends toward improvement (P=.054 and P=.08). Of 5 trials of test/feedback, all showed significant improvement in understanding (all P<.05) but were flawed in that they may have mistaken rote memorization for improvement in understanding. Another 5 trials were put into a miscellaneous category and had varying impact on understanding. Some demographic factors, particularly lower education, were associated with less understanding. Satisfaction and willingness to enroll were never significantly diminished by an intervention .
Efforts to improve understanding through the use of multimedia and enhanced consent forms have had only limited success. Having a study team member or a neutral educator spend more time talking one-on-one to study participants appears to be the most effective available way of improving research participants' understanding; however, further research is needed.
In our research unit on the Kenyan Coast, parents sign consent for over 4000 children to be involved in research activities every year. Children are recruited into studies ranging from purely observational research to the testing of new procedures and drugs. Thousands more community members consent verbally or in writing to the interviews and sometimes invasive procedures required in community-based research. Although every study and consent form is reviewed in advance by independent national and international committees, the views and understanding of the 'subjects' of these activities had not been documented before this study. In this paper, we focus on participant understanding of one field-based and two hospital-based studies, all of which involve blood sampling. The findings highlight a range of inter-related issues for consideration in the study setting and beyond, including conceptual and linguistic barriers to communicating effectively about research, the critical and complex role of communicators (fieldworkers and nurses) in consent procedures, features of research unit-community relations which impact on these processes, and the special sensitivity of certain issues such as blood sampling. These themes and emerging recommendations are expected to be relevant to, and would benefit from, experiences and insights of researchers working elsewhere.
We surveyed Ugandan parents who enrolled their children in a randomized pediatric malaria treatment trial to evaluate the parents' levels of understanding about the treatment trial and the quality of the parents' consents to allow their children to participate in the study.
We conducted 347 interviews immediately following enrollment at 4 Ugandan sites.
A majority (78%) of the parents, most of whom where mothers (86%) had at most a primary school education. Of the participating mothers, a substantial percentage reported that they remembered being told about the study's purpose (77%), the required number of visits (88%), the risks involved (61%), treatment allocation (84%), and their ability to discontinue their children's participation (64%). In addition, most reported knowing the trial's purpose (80%) and the required number of visits (78%); however, only 18% could name possible side effects from the drugs being administered, and only 19% knew that children would not all be administered identical treatments. Ninety-four percent reported that they made the enrollment decision themselves, but 58% said they felt pressure to participate because of their child's illness, and 15% said they felt some type of pressure to participate from others; 41% reported knowing that they did not have to participate.
The consent Ugandan parents provided to allow their children to participate in the malaria study was of mixed quality. Parents understood many of the study details, but they were not very aware of the risks involved or of randomization. Many parents felt that they could not have refused to participate because their child was sick and they either did not know or did not believe that their child would receive treatment outside of the study. Our results indicate that further debate is needed about informed consent in treatment studies of emergent illnesses in children.
To explore how subjects in a placebo-controlled vitamin A supplementation trial among Ghanaian women aged 15-45 years perceive the trial and whether they know that not all trial capsules are the same, and to identify factors associated with this knowledge.
60 semistructured interviews and 12 focus groups were conducted to explore subjects' perceptions of the trial. Steps were taken to address areas of low comprehension, including retraining fieldworkers. 1971 trial subjects were randomly selected for a survey measuring their knowledge that not all trial capsules are the same. The subjects' fieldworkers were also interviewed about their characteristics and trial knowledge. Factors associated with knowledge were explored using multi-level modeling.
Although subjects knew they were taking part in research, most thought they were receiving an active and beneficial medication. Variables associated with knowledge were education and district of residence. Radio broadcasts benefited those with some schooling. Fieldworkers' characteristics were not associated with subjects' knowledge.
Research and debate on new or improved consent procedures are urgently required, particularly for subjects with little education.
The individual informed consent model remains critical to the ethical conduct and regulation of research involving human beings. Parental informed consent process in a rural setting of northern Ghana was studied to describe comprehension and retention among parents as part of the evaluation of the existing informed consent process.
The study involved 270 female parents who gave consent for their children to participate in a prospective cohort study that evaluated immune correlates of protection against childhood malaria in northern Ghana. A semi-structured interview with questions based on the informed consent themes was administered. Parents were interviewed on their comprehension and retention of the process and also on ways to improve upon the existing process.
The average parental age was 33.3 years (range 18-62), married women constituted a majority (91.9%), Christians (71.9%), farmers (62.2%) and those with no formal education (53.7%). Only 3% had ever taken part in a research and 54% had at least one relation ever participate in a research. About 90% of parents knew their children were involved in a research study that was not related to medical care, and 66% said the study procedures were thoroughly explained to them. Approximately, 70% recalled the study involved direct benefits compared with 20% for direct risks. The majority (95%) understood study participation was completely voluntary but only 21% recalled they could withdraw from the study without giving reasons. Younger parents had more consistent comprehension than older ones. Maternal reasons for allowing their children to take part in the research were free medical care (36.5%), better medical care (18.8%), general benefits (29.4%), contribution to research in the area (8.8%) and benefit to the community (1.8%). Parental suggestions for improving the consent process included devoting more time for explanations (46.9%), use of the local languages (15.9%) and obtaining consent at home (10.3%).
Significant but varied comprehension of the informed consent process exists among parents who participate in research activities in northern Ghana and it appears the existing practices are fairly effective in informing research participants in the study area.
The freedom to consent to participate in medical research is a complex subject, particularly in socio-economically vulnerable communities, where numerous factors may limit the efficacy of the informed consent process. Informal consultation among members of the Switching the Poles Clinical Research Network coming from various sub-Saharan African countries, that is Burkina Faso, The Gambia, Rwanda, Ethiopia, the Democratic Republic of Congo (DRC) and Benin, seems to support the hypothesis that in socio-economical vulnerable communities with inadequate access to health care, the decision to participate in research is often taken irrespectively of the contents of the informed consent interview, and it is largely driven by the opportunity to access free or better quality care and other indirect benefits. Populations' vulnerability due to poverty and/or social exclusion should obviously not lead to exclusion from medical research, which is most often crucially needed to address their health problems. Nonetheless, to reduce the possibility of exploitation, there is the need to further investigate the complex links between socio-economical vulnerability, access to health care and individual freedom to decide on participation in medical research. This needs bringing together clinical researchers, social scientists and bioethicists in transdisciplinary collaborative research efforts that require the collective input from researchers, research sponsors and funders.
ANRS 1201/1202 Ditrame Plus Study Group: Principal Investigators: François Dabis, Valériane Leroy, Marguerite Timite-Konan, Christiane Welffens-Ekra. Coordination in Abidjan: Laurence Bequet, Didier K. Ekouévi, Besigin Tonwe-Gold, Ida Viho. Clinical team: Clarisse Amani-Bosse, Ignace Ayekoe, Gédéon Bédikou, Nacoumba Coulibaly, Christine Danel, Patricia Fassinou, Appolinaire Horo, Ruffin Likikouet, Hassan Toure. Laboratory team: Dominique Bonard, André Inwoley, Crépin Montcho, François Rouet. Biostatistics and data management: Renaud Becquet, Laurence Dequae-Merchadou, Gérard Allou, Charlotte Sakarovitch, Dominique Touchard. Psycho-social team: Hortense Aka-Dago, Annabel Desgrées du Loû, Alphonse Sihé, Benjamin Zanou. Scientific Committee: Stéphane Blanche, Jean-François Delfraissy, Philippe Lepage, Laurent Mandelbrot, Christine Rouzioux, Roger Salamon.
These guidelines, from the Council of International Organizations of Medical Sciences, describe the proper application of the principles of the Declaration of Helsinki and focus particularly on research sponsored by or initiated in developed countries and carried out in developing countries.
This article has no abstract; the first 100 words appear below.
The Helsinki Declaration outlines clear ethical principles, including the basic concepts of informed consent, for physicians conducting biomedical research. There are guidelines for applying those principles specifically in research conducted in developing countries.¹–⁴ One guideline allows a community-based approach to enrollment, according to which the decision whether or not to participate can be elicited through an intermediary, such as a trusted community leader, who helps convey information about the research to the people in the community.¹ There is considerable debate about the appropriateness of obtaining individual informed consent in non-Western cultures.⁵–⁸ In the process of conducting a study . . .
Marie-Pierre Préziosi, M.D.
Ablaye Yam, M.D.
Malick Ndiaye, M.D.
Aminata Simaga, M.D.
François Simondon, M.D.
Institut Français de Recherche Scientifique pour le Développement en Coopération, Dakar, Senegal
Steven G.F. Wassilak, M.D.
Centers for Disease Control and Prevention, Atlanta, GA 30333
This trial was cofinanced by the Institut Français de Recherche Scientifique pour le Développement en Coopération (ORSTOM), Paris, and by Pasteur Mérieux Sérums et Vaccins, Marnes la Coquette, France. The institutions of co-investigators — Cheikh Anta Diop University, Dakar, Senegal; the Centers for Disease Control and Prevention, Atlanta; and the Pasteur Institute, Paris — contributed personnel and supplies.
We are indebted to the members of the team of the Niakhar Project for their determined participation in this work, and to Dr. Michel Cadoz (Pasteur Mérieux Sérums et Vaccins, Marnes la Coquette, France) and Dr. Carlton Meschievitz (Connaught Laboratories Inc., Swiftwater, Pa.) for their advice.
Source Information
Address reprint requests to Dr. Préziosi at Projet Niakhar, ORSTOM, B.P. 1386, Dakar, Senegal.
It has recently been debated whether it is possible or desirable to have one internationally recognised standard of "informed consent" or whether research ethics should be adapted to the culture and educational level of the study population. This study examined the attitudes of the Gambian people to consent to medical research, and evaluated the informed consent process used in a major efficacy trial of a Haemophilus influenzae vaccine. Consent was requested after parents had received a verbal explanation and an information sheet which described the vaccine trial in a local language. A semi-structured interview was conducted with 137 acceptors and 52 refusers. Certain points of knowledge were recalled well by the acceptors; 90% knew the purpose of the vaccine was to prevent disease, but the placebo control design was understood by only 10%. The prime motive for consenting was to receive the HIB vaccine (93%) and that for refusing was that the vaccine was experimental (35%) and might have unknown side effects (29%). Although parents took advice from researchers (50%), health workers (24%), friends (16%) and family (12%), in all cases the decision was made by one of the child's parents. Only 1% of parents sought the opinion of traditional or religious leaders. The principles of informed consent, that it should be free, autonomous and informed were affirmed by this community. Therefore, in The Gambia, the international code of informed consent is appropriate.
Lignes directrices pour l'évaluation éthique de la recherche impliquant des sujets humains en RDC
- République Démocratique Du Congo Rdc Ministère De La Sante
Special Programme for Research and Training in Tropical Diseases/World Health Organization
- Who - Tdr