In clinical drug trials, researchers have an obligation to safeguard participants against harms which may be related to the interventional drug, and to ensure the benefit-to-harms ratio remains favourable for the participant throughout the trial. But what if the intervention isn’t a drug? Some research involves the implementation of novel interventions, which although not invasive or medically active, may still cause a participant harm, whether directly or indirectly; researchers have an obligation to anticipate potential harms and put measures in place to prevent them. But not all harms can be anticipated and participants need to be monitored so that any unexpected issues, which may possibly be related to the trial intervention, are detected and managed appropriately. Safeguarding of trial participants isn’t the only reason this is important – if the results of your trial show an intervention to be effective, wider implementation is more likely if you can also show that it causes minimal harm, or a justifiable benefit-to-harms ratio, and unless you have robust harms monitoring data, a lack of harm cannot be assumed.
Dr Penelope Phillips-Howard from the Liverpool School of Tropical Medicine and Dr Daniel Kwaro from the Kenya Medical Research Institute, are the Principal Investigators currently in the early stages of a trial who are researching, with a large multi-disciplinary team, whether menstrual cups or cash transfer, alone or in combination, in comparison to ‘usual practice’ controls, have any impact on a composite of deleterious outcomes, namely HIV, HSV-2 infection and school dropout, amongst schoolgirls in rural Western Kenya. The study is funded through the Joint Global Health Trials award scheme, and follows on from a successful pilot study in the same area examining feasibility, use and safety of menstrual cups among schoolgirls aged 14-16 years[2,3]. Ensuring girls receive an education is important - prior research has shown a positive association between girls’ education and their health and economic potential, and school attendance has also been shown to protect against early marriage, teen pregnancy and HIV infection[5-8].
Teachers attending the randomisation ceremony. Photo by Dr. Penelope Phillips-Howard.
The two interventions pose interesting questions around anticipating and monitoring of harms. The menstrual cup raises fear of Toxic Shock Syndrome (linked with highly absorbent tampons [9,10]), and so monitoring the girls for this rare but serious occurrence is obviously of importance. Documenting the cup as a medical device, with receipt of approval from the Kenyan Pharmacy and Poisons Board, as well as ethical committee approvals, was required to ensure safe and ethical management of the trial.
But then, what about the cash transfer? As cash is a commodity used throughout the community, surely this is a safe and straightforward intervention? Whilst it is hoped this is the case, given the baseline incidence of physical and sexual violence amongst women in this area is one of the highest in Kenya, it is paramount that any interventions designed to improve the long-term outcomes for these girls does not come with an increased risk of harassment or violence which could deleteriously affect their health, wellbeing, and outcomes for the trial. So, alongside implementing strategies to make the cash transfer as safe as possible, an effective safety monitoring plan needs to be put in place to ensure any incident episodes of violence-related harms, above the background prevalence, are detected and managed.
Cash transfers are becoming more popular as a way of donating aid money to places and populations in need. Previously, research has focused on effectiveness – does giving cash to school girls (or their caregivers) increase school attendance and reduce risky sexual behaviours that may result in infections such as HIV, or early pregnancy and possibly marriage? But few, if any, have examined or answered the question as to whether giving cash directly to girls as pocket-money increases their risk of physical violence, harassment, or theft.
One hypothesis of cash transfer is that it will reduce the incidence of violence in a population, but there is little in the way of published evidence to support this. Some research has shown that being in receipt of a cash transfer may make young girls less likely to engage in risky sexual behaviours, especially when given financial literacy training, but few studies make any mention of the impact the cash transfer had on the effect of violence towards the recipient - many of the studies make no mention of violence at all and an absence of a relationship between cash transfer and increased violence cannot be assumed if such harms were never monitored in the first place.
At intervention, girls will receive financial literacy training and cash cards with guidance on safe use. During the study, the girls will be questioned periodically regarding episodes of violence or harassment (both prior to receiving the intervention and after), and systems are in place at community, school, and facility level to refer girls who report violence or harassment to designated study nurses to ensure referral for treatment and care services. The nurses in parallel will document such incidences, including among controls, on standardised forms starting with a triage and culminating in a complete appraisal of a serious adverse event, should this be identified. These data will be assessed routinely through the trial’s Data Monitoring and Ethics Committee, which includes a senior clinician, adolescent sexual and reproductive health specialist, and biostatistician as well as key trial investigators, and a pharmacovigilance monitor. At the end of the three years, this data will contribute to the outcomes of the study by determining whether there is any increase in harms experienced by the girls after implementation of the interventions, or any difference between the girls who are and are not receiving cash or cups. With three years’ worth of data, this information on potential harms associated with cash transfers will add to the growing body of evidence of the effectiveness of cash transfers and their use to empower vulnerable populations and support their autonomy.