Female Trial Participants Research Articles

Self-reported removal and expulsion of the dapivirine vaginal ring: qualitative reports from female ring users and their male partners in the Ring Study (IPM 027)

Background/aimsThe dapivirine vaginal ring is a self-administered, women-initiated, discreet, long-acting HIV-1 prevention option for women. It was found to be safe and effective in healthy HIV-negative women who adhered to product use instructions, and has been approved for use in women aged 18 and older in some African countries. A qualitative study was conducted to explore participants’ and their male partners’ discussions on accidental/purposeful vaginal ring removals during The Ring Study (IPM 027 clinical trial).MethodsData were collected via in-depth interviews and focus group discussions with female trial participants and their male partners, from seven research centres in South Africa and Uganda. Data were thematically analysed using NVivo.ResultsMore participants reported purposeful ring removals than accidental expulsions. Various factors influenced purposeful ring removal – including individual (discomfort during use/sex and to clean it), partner (to show them, because of discomfort during sex, to test if partners could feel it, and concerns of harm), organisational (doctor’s request), and socio-cultural (rumours about sickness and infertility). Some described their own ring use removal, others discussed why other participants removed their rings.ConclusionsVaginal ring adherence is critical to improve and support product efficacy. Counselling on vaginal anatomy, vaginal ring insertion and importance of adherence is important to minimise vaginal ring removal. Couples counselling is also important to facilitate support and long-term vaginal ring adherence behaviour. Understanding factors influencing vaginal ring adherence is important for tailoring and targeting messages to support correct and consistent vaginal ring use as it is made available to the public.

Sex Differences in the Generalizability of Randomized Clinical Trials in Heart Failure with Reduced Ejection Fraction.

To understand how sex differences impact the generalizability of randomized controlled trials (RCTs) in patients with heart failure and reduced ejection fraction (HFrEF, we sought to compare clinical characteristics and clinical outcomes between RCTs and HF observational registries stratified by sex. Data from 2 HF registries and 5 HFrEF RCTs were used to create three subpopulations: one RCT population (n=16,917; 21.7% females), registry patients eligible for RCT inclusion (n=26,104; 31.8% females), and registry patients ineligible for RCT inclusion (n=20,910; 30.2% females). Clinical endpoints included all-cause mortality, CV mortality, and first HF hospitalization at one-year. Males and females were equally eligible for trial enrollment (56.9% of females and 55.1% of males in the registries). One-year mortality rates were 5.6%, 14.0%, and 28.6% for females and 6.9%, 10.7%, and 24.6% for males in the RCT, RCT-eligible, and RCT-ineligible groups. After adjusting for 11 HF prognostic variables, RCT females showed higher survival compared to RCT-eligible females (Standardized mortality ratio (SMR) 0.72; 95% CI 0.62 - 0.83), while RCT males showed higher adjusted mortality rates compared to RCT-eligible males (SMR 1.16; 95% CI 1.09-1.24). Similar results were also found for cardiovascular mortality (SMR 0.89; 95%CI 0.76-1.03 for females, SMR 1.43; 95%CI 1.33-1.53 for males). Generalizability of HFrEF RCTs differed substantially between the sexes, with females having lower trial participation and females trial participants having lower mortality rates compared to similar females in the registries, while males had higher than expected cardiovascular mortality rates in RCTs compared to similar males in registries. This article is protected by copyright. All rights reserved.

Intrauterine contraceptive discontinuation reasons among female trial participants living with HIV in Cape Town, South Africa: A qualitative analysis.

While young women in South Africa may navigate both HIV infection and pregnancy risks, intrauterine contraceptive (IUC) use is low. Though IUCs have low failure rates, concerns exist about whether the IUC is an appropriate method choice for women living with HIV (WLHIV). In this qualitative study, we explore WLHIVs' experiences of using IUC and reasons for discontinuation. This qualitative study included in-depth interviews (IDIs) with 17 WLHIV who electively discontinued their allocated IUC while participating in a randomized controlled trial comparing the safety of the levonorgestrel intrauterine system (LNG-IUS) and the copper intrauterine device (C-IUD) in Cape Town, South Africa. The transcripts were coded and emergent themes were grouped to examine women's experiences with IUC use and reasons for discontinuation, highlighting experiential differences between the two methods. Women's experience with the allocated IUC related most commonly to bleeding and/or abdominal pain just after insertion. Most C-IUD discontinuers, but only one LNG-IUS discontinuer, complained of pain and/or increased bleeding as the main reason for removal. Three women (two LNG-IUS, one C-IUD) requested removal because they desired pregnancy, while two others discontinued due to fears the IUC was exacerbating non-gynecologic conditions (hypertension, diabetes). Generally, women acknowledged advantages of IUC use and many expressed their desire to continue use if not for the side effects. In the South African context, IUC use for WLHIV should be promoted with specific counseling considerations. Both providers and potential users should receive specific information about potential menstrual-related side effects and countering common misperceptions to enable informed contraceptive decision-making.

Association Between Selective Decontamination of the Digestive Tract and In-Hospital Mortality in Intensive Care Unit Patients Receiving Mechanical Ventilation

The effectiveness of selective decontamination of the digestive tract (SDD) in critically ill adults receiving mechanical ventilation is uncertain. To determine whether SDD is associated with reduced risk of death in adults receiving mechanical ventilation in intensive care units (ICUs) compared with standard care. The primary search was conducted using MEDLINE, EMBASE, and CENTRAL databases until September 2022. Randomized clinical trials including adults receiving mechanical ventilation in the ICU comparing SDD vs standard care or placebo. Data extraction and risk of bias assessments were performed in duplicate. The primary analysis was conducted using a bayesian framework. The primary outcome was hospital mortality. Subgroups included SDD with an intravenous agent compared with SDD without an intravenous agent. There were 8 secondary outcomes including the incidence of ventilator-associated pneumonia, ICU-acquired bacteremia, and the incidence of positive cultures of antimicrobial-resistant organisms. There were 32 randomized clinical trials including 24 389 participants in the analysis. The median age of participants in the included studies was 54 years (IQR, 44-60), and the median proportion of female trial participants was 33% (IQR, 25%-38%). Data from 30 trials including 24 034 participants contributed to the primary outcome. The pooled estimated risk ratio (RR) for mortality for SDD compared with standard care was 0.91 (95% credible interval [CrI], 0.82-0.99; I2 = 33.9%; moderate certainty) with a 99.3% posterior probability that SDD reduced hospital mortality. The beneficial association of SDD was evident in trials with an intravenous agent (RR, 0.84 [95% CrI, 0.74-0.94]), but not in trials without an intravenous agent (RR, 1.01 [95% CrI, 0.91-1.11]) (P value for the interaction between subgroups = .02). SDD was associated with reduced risk of ventilator-associated pneumonia (RR, 0.44 [95% CrI, 0.36-0.54]) and ICU-acquired bacteremia (RR, 0.68 [95% CrI, 0.57-0.81]). Available data regarding the incidence of positive cultures of antimicrobial-resistant organisms were not amenable to pooling and were of very low certainty. Among adults in the ICU treated with mechanical ventilation, the use of SDD compared with standard care or placebo was associated with lower hospital mortality. Evidence regarding the effect of SDD on antimicrobial resistance was of very low certainty.

Evaluation of the causes of sex disparity in heart failure trials

ObjectivesCardiovascular disease is one of the leading causes of mortality and morbidity in women. Despite this, even in contemporary research, female patients are poorly represented in trials. This study aimed...

Baseline findings and safety of infrequent vs. frequent screening of human papillomavirus vaccinated women.

Less frequent cervical cancer screening in human papillomavirus (HPV) vaccinated birth cohorts could produce considerable savings without increasing cervical cancer incidence and loss of life-years. We report here the baseline findings and interim results of safety and accuracy of infrequent screening among HPV16/18 vaccinated females. The entire 1992-1994 birth-cohorts (30,139 females) were invited to a community-randomized HPV16/18-vaccination trial. A total of 9,482 female trial participants received HPV16/18-vaccination in 2007-2009 at age of 13-15. At age 22, 4,273 (45%) of these females consented to attend a randomized trial on frequent (ages 22/25/28; Arm 1: 2,073 females) vs. infrequent screening (age 28; Arm 2: 2,200 females) in 2014-2017. Females (1,329), who had got HPV16/18 vaccination at age 18 comprised the safety Arm 3. Baseline prevalence and incidence of HPV16/18 and other high-risk HPV types were: 0.5% (53/1,000 follow-up years, 104 ) and 25% (2,530/104 ) in the frequently screened Arm 1; 0.2% (23/104 ) and 24% (2,413/104 ) in the infrequently screened Arm 2; and 3.1% (304/104 ) and 23% (2,284/104 ) in the safety Arm 3. Corresponding prevalence of HSIL/ASC-H and of any abnormal cytological findings were: 0.3 and 4.2% (Arm 1), 0.4 and 5.3% (Arm 2) and 0.3 and 4.7% (Arm 3). Equally rare HSIL/CIN3 findings in the infrequently screened safety Arm A3 (0.4%) and in the frequently screened Arm 1 (0.4%) indicate no safety concerns on infrequent screening despite the up to 10 times higher HPV16/18 baseline prevalence and incidence in the former.

To tell or not to tell: male partner engagement in a Phase 3 microbicide efficacy trial in South Africa

Gender norms that privilege men's sexual power and pleasure, and distrust of condom use in intimate relationships, leave women vulnerable to HIV and other sexually transmitted infections. Vaginal microbicides allow women to exert a degree of control over their sexual health, through responsibility for product insertion as well as the possibility of covert use. In practice, however, the uptake of new HIV-prevention products is heavily influenced by partnership dynamics. This paper presents a secondary analysis of data from two qualitative sub-studies conducted during a Phase 3 microbicide efficacy trial in South Africa. Using transcripts from in-depth interviews and focus group discussions with 278 female trial participants and 27 male partners, we investigated the extent to which women disclosed microbicide use to their partners, and the level and types of male engagement with microbicide use. Most women chose to communicate with their partners about the trial, but the timing and content of associated discussions differed according to their motivation for disclosure. Men provided their partners with both moral and practical support, but reported a desire for greater involvement in decision-making surrounding microbicide uptake and use. The findings inform recommendations for constructive male participation in future trials and, ultimately, introduction of a marketed product.

Influences on visit retention in clinical trials: insights from qualitative research during the VOICE trial in Johannesburg, South Africa.

BackgroundAlthough significant progress has been made in clinical trials of women-controlled methods of HIV prevention such as microbicides and Pre-exposure Prophylaxis (PrEP), low adherence to experimental study products remains a major obstacle to being able to establish their efficacy in preventing HIV infection. One factor that influences adherence is the ability of trial participants to attend regular clinic visits at which trial products are dispensed, adherence counseling is administered, and participant safety is monitored. We conducted a qualitative study of the social contextual factors that influenced adherence in the VOICE (MTN-003) trial in Johannesburg, South Africa, focusing on study participation in general, and study visits in particular.MethodsThe research used qualitative methodologies, including in-depth interviews (IDI), serial ethnographic interviews (EI), and focus group discussions (FGD) among a random sub-sample of 102 female trial participants, 18 to 40 years of age. A socio-ecological framework that explored those factors that shaped trial participation and adherence to study products, guided the analysis. Key codes were developed to standardize subsequent coding and a node search was used to identify texts relating to obstacles to visit adherence. Our analysis includes coded transcripts from seven FGD (N = 40), 41 IDI, and 64 serial EI (N = 21 women).ResultsWomen’s kinship, social, and economic roles shaped their ability to participate in the clinical trial. Although participants expressed strong commitments to attend study visits, clinic visit schedules and lengthy waiting times interfered with their multiple obligations as care givers, wage earners, housekeepers, and students.ConclusionsThe research findings highlight the importance of the social context in shaping participation in HIV prevention trials, beyond focusing solely on individual characteristics. This points to the need to focus interventions to improve visit attendance by promoting a culture of active and engaged participation.

Sharing the trousers: gender roles and relationships in an HIV-prevention trial in Zimbabwe

Male and female gender roles and inequalities are important in contributing to the disproportionate burden of HIV experienced by women in sub-Saharan Africa. Within the context of an HIV prevention trial, we aimed to describe and understand male partner influence on women's use of HIV-prevention methods. Our presumption was not that regressive gender norms prevailed – rather, that a wide range of gendered attitudes and dynamics would be expressed among couples. Data from 16 focus groups with Zimbabwean female trial participants and their male partners and 4 in-depth couples interviews were collected, and form the basis of the analysis. Findings offer descriptions of how couples have adapted techniques for negotiating modern household economies and sexual decision-making in a manner that both preserves traditional gender roles, while accommodating women's entrance into new domains such as the workforce or an HIV-prevention trial. Women's agency to introduce novel female-initiated-method use into her intimate relationships is described. Men and women's accounts of method introduction and use suggest different perceptions about the locus of sexual decision making. The study provides unique insight into a gendered context that is dynamic yet sensitive to change, which in turn can provide useful information to more appropriately guide HIV-prevention activities in this setting.

‘The study has taught me to be supportive of her’: empowering women and involving men in microbicide research

Recognising that women often have little control over most HIV-prevention methods, including condoms, researchers have made efforts to develop new bio-technological interventions, such as microbicides, that could allow women greater autonomy in HIV-prevention decision making. In many situations, women are unable to negotiate condom use with their partners, meaning that they could be better protected through the use of an effective microbicide. This paper uses qualitative data from the Microbicide Development Programme 301 (MDP301) microbicide trial in Johannesburg, South Africa. Data is taken from in-depth interviews with male partners of female trial participants (n = 28), six focus-group discussions involving male partners of trial participants (n = 4) and female participants (n = 2). Data show that men's involvement in microbicide research ranges from a disinterest in trials to the desire to actively take part in and promote research that affects the health of themselves and their partners. Results showed that some participants were reluctant to disclose trial involvement and product use to their partners, making identifying men as potential research participants problematic. This paper considers how to involve men in microbicide research without undermining women's sense of empowerment and ownership of the trial and the product that is being tested.

Rumours about blood and reimbursements in a microbicide gel trial

A rumour that emerged during a microbicide gel trial tells the tale of clinic staff purchasing trial participants’ blood. This paper documents the rumour and explores its divergent interpretations and meanings in relation to the context of the trial and the social and economic setting at two of the trial sites (Soweto and Orange Farm) in South Africa. The article is based on qualitative research conducted during the Microbicides Development Programme (MDP) 301 trial to evaluate a microbicide vaginal gel for HIV prevention in women. The research incorporated in-depth interviews with female trial participants and their male partners, focus group discussions with male and female community members, and participant observation in the trial clinic and community setting at the two sites. The article analyses the different perspectives among the clinic staff, community and trial participants in terms of which the rumour about the exchange of blood for cash is seen as: 1) the result of ignorance of the clinical trial procedures; 2) the exploitation of poor and vulnerable women; 3) an example of young women's desire for material gain; and 4) a reciprocal exchange of ‘clean blood’ for cash between women trial participants and the health services. We suggest that the rumours about selling blood verbalise notions of gender and morality while also providing an appraisal of the behaviour of young women and a critique of social relationships between foreign researchers and local participants. Through stories about the clinical trial procedures and its potential reimbursements, the participants were creating and reconfiguring social relationships. Ultimately, rumours are one way in which foreign enterprises such as a clinical trial are rendered local.

Re-framing microbicide acceptability: findings from the MDP301 trial

Microbicides are most usually conceptualised within a disease prevention framework and studies usually define acceptability in terms of product characteristics, willingness to use and risk reduction. This starting point has led to assumptions about microbicides which, rather than being challenged by empirical studies, have tended to foreclose the data and subsequent conceptual models. Few studies take an emic (‘insider’) perspective or attempt to understand how microbicides fit into the broader context of women's and men's everyday lives. As part of the integrated social science component of the MDP301 Phase III microbicide trial, in-depth interviews were conducted with female trial participants in South Africa, Zambia, Tanzania and Uganda. Women's experiences of the gel challenge several assumptions that have commonly been reiterated about microbicides. Our analysis suggests that current definitions and conceptual frameworks do not adequately account for the range of meanings that women attribute to gel. Even within the context of a clinical trial, it is possible to obtain a richer, ethnographic and cross-cultural concept of acceptability based on women's practice and emic interpretations. We now need to move beyond limited notions of acceptability and consider how microbicides fit into a more holistic picture of women's and men's sexuality and sexual health.

Sexual Pleasure, Gender Power and Microbicide Acceptability in Zimbabwe and Malawi

Topical vaginal microbicides are being developed to reduce HIV infection in women for whom correct and consistent condom use is impossible or undesirable. Although microbicides have been heralded as a "women-initiated" method that requires no action of the male partner, gender norms for sexual relationships and sexual practices could impede acceptability and use. To facilitate development of microbicides and look ahead to their eventual introduction, it is necessary to understand couples' sexual dynamics, including power and pleasure. This article presents data from a study of microbicide acceptability ancillary to a microbicide clinical trial in Malawi and Zimbabwe. Female trial participants, male partners, health care professionals and community stakeholders were interviewed about norms for sexual decision-making, sexual pleasure, and associated intravaginal practices that ensure this pleasure. Even though acceptability of microbicides was found to be high, sexual intercourse is accompanied by issues of power and gender norms that place women, particularly those in stable union, at a disadvantage for enactment of risk reduction strategies. Although woman-initiated use is an important goal in development of microbicides, the need for men's cooperation or agreement must be addressed in strategies for future product introduction.