Using Formative Research to Develop a Context-Specific Approach to Informed Consent for Clinical Trials

Participant understanding is of particular concern when obtaining informed consent. Recommendations for improving understanding include disclosing information using culturally appropriate and innovative approaches. To increase the effectiveness of the consent process for a clinical trial in Malawi on interventions to prevent mother-to-child transmission of HIV during breastfeeding, formative research was conducted to explore the community’s understanding of medical research as well as how to explain research through local terms and meanings. Contextual analogies and other approaches were identified to explain consent information. Guided by theory, strategies for developing culturally appropriate interventions, and recommendations from the literature, we demonstrate how the formative data were used to develop culturally appropriate counseling cards specifically for the trial in Malawi. With appropriate contextual modifications, the steps outlined here could be applied in other clinical trials conducted elsewhere, as well as in other types of research

Applying Research Ethics Guidelines: The View from a Sub-Saharan Research Ethics Committee

Considerable variation has been demonstrated in applying regulations across research ethics committees (RECs) in the U.S., U.K., and European nations. With the rise of international research collaborations, RECs in developing countries apply a variety of international regulations. We conducted a qualitative descriptive pilot study with members of the national REC in Malawi to determine criteria they use to review research, and their views on international collaborations. Qualitative content analysis demonstrated that international guidelines are interpreted in light of local African conditions such that emphasis is placed on examining benefit to the community and ensuring the informed consent process translates concepts in locally-meaningful ways. Members suggest that RECs often must comply with regulations that do not fit local conditions. Recommendations are provided for improving such international collaborations

Differences between international recommendations on breastfeeding in the presence of HIV and the attitudes and counselling messages of health workers in Lilongwe, Malawi

BACKGROUND: To prevent postnatal transmission of HIV in settings where safe alternatives to breastfeeding are unavailable, the World Health Organization (WHO) recommends exclusive breastfeeding followed by early, rapid cessation of breastfeeding. Only limited data are available on the attitudes of health workers toward this recommendation and the impact of these attitudes on infant feeding counselling messages given to mothers. METHODS: As part of the Breastfeeding, Antiretroviral, and Nutrition (BAN) clinical trial, we carried out an in-depth qualitative study of the attitudes, beliefs, and counselling messages of 19 health workers in Lilongwe, Malawi. RESULTS: Although none of the workers had received formal training, several reported having counseled HIV-positive mothers about infant feeding. Health workers with counselling experience believed that HIV-infected mothers should breastfeed exclusively, rather than infant formula feed, citing poverty as the primary reason. Because of high levels of malnutrition, all the workers had concerns about early cessation of breastfeeding. CONCLUSION: Important differences were observed between the WHO recommendations and the attitudes and practices of the health workers. Understanding these differences is important for designing effective interventions

FEM-PrEP: Adherence Patterns and Factors Associated With Adherence to a Daily Oral Study Product for Pre-exposure Prophylaxis

Background:Several clinical trials have demonstrated the safety and effectiveness of oral tenofovir disoproxil fumarate (TDF), with or without emtricitabine (FTC), as pre-exposure prophylaxis (PrEP) for reducing the risk of HIV acquisition. Adherence to the study product was insufficient to demonstrate the effectiveness of FTC/TDF in 2 PrEP clinical trials conducted among women (FEM-PrEP and the Vaginal and Oral Interventions to Control the Epidemic study), but further analyses of adherence in these studies may inform PrEP demonstration projects and future HIV prevention clinical trials.Methods:We randomly selected a subcohort of 150 participants randomized to FTC/TDF in 3 FEM-PrEP sites (Bondo, Kenya; Bloemfontein, South Africa; and Pretoria, South Africa) to examine adherence levels over time and to assess factors associated with adherence, based on plasma tenofovir and intracellular tenofovir diphosphate drug concentrations in specimens collected at 4-week visit intervals.Results:We observed drug concentrations consistent with good adherence in 28.5% of all visit intervals when drug was available to use, but only 12% of participants achieved good adherence throughout their study participation. In multivariate analysis, the Bloemfontein site [odds ratio (OR): 2.43; 95% confidence interval (CI): 1.32 to 4.48] and liking the pill color (OR: 2.93; 95% CI: 1.18 to 7.27) were positively associated with good adherence, whereas using oral contraceptive pills at enrollment was negatively associated with good adherence (OR: 0.37; 95% CI: 0.18 to 0.74).Conclusions:Most participants did not regularly adhere to the study product throughout their trial participation, although a small minority did. Few factors associated with good adherence to the study product were identified in FEM-PrEP

Accuracy of Self-Report and Pill-Count Measures of Adherence in the FEM-PrEP Clinical Trial: Implications for Future HIV-Prevention Trials

Oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) has been evaluated as pre-exposure prophylaxis (PrEP). We describe the accuracy of self-reported adherence to FTC/TDF and pill counts when compared to drug concentrations in the FEM-PrEP trial. Using drug concentrations of plasma tenofovir (TFV) and intracellular tenofovir diphosphate (TFVdp) among a random sub-sample of 150 participants assigned to FTC/TDF, we estimated the positive predictive value (PPV) of four adherence measures. We also assessed factors associated with misreporting of adherence using multiple drug-concentration thresholds and explored pill use and misreporting using semi-structured interviews (SSIs). Reporting use of ≥1 pill in the previous 7days had the highest PPV, while pill-count data consistent with missing ≤1day had the lowest PPV. However, all four measures demonstrated poor PPV. Reported use of oral contraceptives (OR 2.26; p=0.014) and weeks of time in the study (OR 1.02; p<0.001) were significantly associated with misreporting adherence. Although most SSI participants said they did not misreport adherence, participant-dependent adherence measures were clearly unreliable in the FEM-PrEP trial. Pharmacokinetic monitoring remains the measure of choice until more reliable participant-dependent measures are developed

Involving communities in the design of clinical trial protocols: The BAN Study in Lilongwe, Malawi

To learn the attitudes and concerns of the local community on participating in research, infant feeding practices, and maternal nutrition in order to inform the design of a clinical trial in Lilongwe, Malawi on the safety and efficacy of antiretroviral and nutrition interventions to reduce postnatal transmission of HIV

Improving Participant Understanding of Informed Consent in an HIV-Prevention Clinical Trial: A Comparison of Methods

Empirical research on informed consent has shown that study participants often do not fully understand consent information. This study assessed participant understanding of three mock consent approaches describing an HIV-prevention clinical trial in Lilongwe, Malawi prior to trial implementation. Pregnant women (n = 297) were systematically selected from antenatal-care waiting lines and sequentially allocated to receive an enhanced standard consent form (group 1), a context-specific consent form (group 2), or context-specific counseling cards (group 3). Understanding of research concepts and study procedures was assessed immediately postintervention and at 1-week follow-up. At postintervention, participants in groups 2 and 3 understood more about research concepts and study procedures compared with group 1. Group 3 participants also understood more about study procedures compared with group 2. At follow-up, participants in groups 2 and 3 continued to understand more about research concepts and study procedures. Context-specific approaches improved understanding of consent information in this study

Plasma Micronutrient Concentrations Are Altered by Antiretroviral Therapy and Lipid-Based Nutrient Supplements in Lactating HIV-Infected Malawian Women

Background: Little is known about the influence of antiretroviral therapy with or without micronutrient supplementation on the micronutrient concentrations of HIV-infected lactating women in resource-constrained settings

Adherence to extended postpartum antiretrovirals is associated with decreased breast milk HIV-1 transmission

Estimate association between postpartum antiretroviral adherence and breastmilk HIV-1 transmissio