A multimedia consent tool for research participants in the Gambia: a randomized controlled trial.

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.

Participation in medical research as a resource-seeking strategy in socio-economically vulnerable communities: call for research and action.

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.

Multimedia Informed Consent Tool for a Low Literacy African Research Population: Development and Pilot-Testing.

BACKGROUND: International guidelines recommend the use of appropriate informed consent procedures in low literacy research settings because written information is not known to guarantee comprehension of study information. OBJECTIVES: This study developed and evaluated a multimedia informed consent tool for people with low literacy in an area where a malaria treatment trial was being planned in The Gambia. METHODS: We developed the informed consent document of the malaria treatment trial into a multimedia tool integrating video, animations and audio narrations in three major Gambian languages. Acceptability and ease of use of the multimedia tool were assessed using quantitative and qualitative methods. In two separate visits, the participants' comprehension of the study information was measured by using a validated digitised audio questionnaire. RESULTS: The majority of participants (70%) reported that the multimedia tool was clear and easy to understand. Participants had high scores on the domains of adverse events/risk, voluntary participation, study procedures while lowest scores were recorded on the question items on randomisation. The differences in mean scores for participants' 'recall' and 'understanding' between first and second visits were statistically significant (F (1,41)=25.38, p<0.00001 and (F (1, 41) = 31.61, p<0.00001 respectively. CONCLUSIONS: Our locally developed multimedia tool was acceptable and easy to administer among low literacy participants in The Gambia. It also proved to be effective in delivering and sustaining comprehension of study information across a diverse group of participants. Additional research is needed to compare the tool to the traditional consent interview, both in The Gambia and in other sub-Saharan settings.

Safety of daily co-trimoxazole in pregnancy in an area of changing malaria epidemiology: a phase 3b randomized controlled clinical trial.

INTRODUCTION: Antibiotic therapy during pregnancy may be beneficial and impacts positively on the reduction of adverse pregnancy outcomes. No studies have been done so far on the effects of daily Co-trimoxazole (CTX) prophylaxis on birth outcomes. A phase 3b randomized trial was conducted to establish that daily CTX in pregnancy is not inferior to SP intermittent preventive treatment (IPT) in reducing placental malaria; preventing peripheral parasitaemia; preventing perinatal mortality and also improving birth weight. To establish its safety on the offspring by measuring the gestational age and birth weight at delivery, and compare the safety and efficacy profile of CTX to that of SP. METHODS: Pregnant women (HIV infected and uninfected) attending antenatal clinic were randomized to receive either daily CTX or sulfadoxine-pyrimethamine as per routine IPT. Safety was assessed using standard and pregnancy specific measurements. Women were followed up monthly until delivery and then with their offspring up to six weeks after delivery. RESULTS: Data from 346 pregnant women (CTX = 190; SP = 156) and 311 newborns (CTX = 166 and SP = 145) showed that preterm deliveries (CTX 3.6%; SP 3.0%); still births (CTX 3.0%; SP 2.1%), neonatal deaths (CTX 0%; SP 1.4%), and spontaneous abortions (CTX 0.6%; SP 0%) were similar between study arms. The low birth weight rates were 9% for CTX and 13% for SP. There were no birth defects reported. Both drug exposure groups had full term deliveries with similar birth weights (mean of 3.1 Kg). The incidence and severity of AEs in the two groups were comparable. CONCLUSION: Exposure to daily CTX in pregnancy may not be associated with particular safety risks in terms of birth outcomes such as preterm deliveries, still births, neonatal deaths and spontaneous abortions compared to SP. However, more data are required on CTX use in pregnant women both among HIV infected and un-infected individuals. TRIAL REGISTRATION: Clinicaltrials.gov NCT00711906.

Doctors and vampires in sub-Saharan Africa: ethical challenges in clinical trial research.

Collecting blood samples from individuals recruited into clinical research projects in sub-Saharan Africa can be challenging. Strikingly, one of the reasons for participant reticence is the occurrence of local rumors surrounding "blood stealing" or "blood selling." Such fears can potentially have dire effects on the success of research projects--for example, high dropout rates that would invalidate the trial's results--and have ethical implications related to cultural sensitivity and informed consent. Though commonly considered as a manifestation of the local population's ignorance, these rumors represent a social diagnosis and a logical attempt to make sense of sickness and health. Born from historical antecedents, they reflect implicit contemporary structural inequalities and the social distance between communities and public health institutions. We aim at illustrating the underlying logic governing patients' fear and argue that the management of these beliefs should become an intrinsic component of clinical research.

Could the decision of trial participation precede the informed consent process? Evidence from Burkina Faso.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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.

Good clinical practice in resource-limited settings: translating theory into practice.

A Good Clinical Practices (GCPs) course, based on the combination of theoretical modules with a practical training in real-life conditions, was held in 2010 in Burkina Faso. It was attended by 15 trainees from nine African, Asian, and Latin American countries. There were some discrepancies between the average good results at the end of the theoretical phase and the GCP application during the first days of the practical phase, underlying the difficulties of translating theoretical knowledge into good practices. Most of the findings were not unexpected and reflected the challenges commonly faced by clinical investigators in resource-poor contexts (i.e., the high workload at peripheral health facilities, the need to conciliate routine clinical activities with clinical research, and the risk of creating a double standard among patients attending the same health facility [free care for recruited patients versus user fees for non-recruited patients with the same medical condition]). Even if limited in number and time, these observations suggest that a theoretical training alone may not be sufficient to prepare trainees for the challenges of medical research in real-life settings. Conversely, when a practical phase immediately follows a theoretical one, trainees can immediately experience what the research methodology implicates in terms of work organization and relationship with recruited and non-recruited patients. This initial experience shows the complexity of translating GCP into practice and suggests the need to rethink the current conception of GCP training.

Challenges of non-commercial multicentre North-South collaborative clinical trials.

The last decade has witnessed a substantial increase of multi-centre, public health-oriented clinical trials in poor countries. However, non-commercial research groups have less staff and financial resources than traditional commercial sponsors, so the trial teams have to be creative to comply with Good Clinical Practices (GCP) requirements. According to the recent experience of a large multicentre trial on antimalarials, major challenges result from the complexity of multiple ethical review, the costs of in-depth monitoring at several sites, setting up an adequate Good Clinical Laboratory Practices (GCLP) framework, lack of insurers in host countries, and lack of adequate non-commercial data management software. Public research funding agencies need to consider these challenges in their funding policies. They also could support common spaces where North-South collaborative research groups may share critical information, such as on research insurance and open-source, GCP-compliant software. WHO should update its GCP guidelines, which date back to 1995, to incorporate the perspectives and needs of non-commercial clinical research.