Two-way risk communication mobile application versus traditional methods of adverse drug reaction reporting in Uganda: a randomized controlled trial

Thanks to the development of drugs known as antiretrovirals, people living with HIV (PLHIV) can live long, healthy lives. Unfortunately, PLHIV need to take antiretrovirals for the rest of their lives. Antiretrovirals are generally safe but can cause serious side effects in some people, particularly with long-term use. Common side effects are discovered in clinical trials. If a drug causes side effects that are too severe or too common it will fail the trial. It isn't possible to test enough people in a clinical trial to discover less common side effects. These are found by monitoring people taking the drug in the real world. It is also essential that the safety of a drug is monitored in people of all ethnicities because some side effects are more common in people belonging to a particular ethnic group.

Our work focuses on the 3.5% of the Ugandan population - 1.5 million people - who live with HIV. At the moment we have very little information about how many PLHIV suffer side effects due to antiretrovirals. The importance of encouraging and enabling healthcare professionals to report drug-related side effects is recognised by the Ugandan government. However, systems for monitoring drug-related side effects have only recently been developed in Uganda and the number of reports is very low. Only 400 reports on side effects due to antiretrovirals were made during the 12-months from October 2018 to September 2019.

We urgently need to improve reporting of drug-related side effects due to recent changes in the treatment offered to PLHIV in Uganda. In 2018, Uganda began a programme to rapidly roll-out antiretroviral combinations including dolutegravir (DTG), the new drug recommended by the World Health Organisation (WHO), to PLHIV. Uganda is also rolling-out Isoniazid Preventive Therapy (IPT) to prevent active tuberculosis - the main cause of death in PLHIV. Although DTG has some important advantages over other antiretrovirals, we know that in some people it can cause liver damage, high blood sugar, anxiety, insomnia or depression. In addition, the risk of side effects is likely to be higher when DTG and IPT are taken together.

We aim to test whether reporting via a mobile application is effective at increasing reporting of antiretroviral-related side effects by healthcare professionals. If successful, our project will also improve our understanding of which side effects are most common in Ugandan PLHIV and how many people they affect. These are essential first steps in our work to make sure that every PLHIV is treated with the right antiretrovirals at the right dose in the future.

The mobile application that we will test is called Med Safety(R). Med Safety(R) was developed by a European drug safety project and adapted for Uganda's National Drug Authority (NDA) by the UK's Medicines and Healthcare products Regulatory Agency (MHRA) but isn't yet widely used. We will recruit 3820 healthcare professionals from 382 HIV treatment centres to: 1) investigate factors that affect the success of rolling out Med Safety(R) among healthcare professionals and how healthcare providers feel about using the application; 2) discover whether using Med Safety(R) leads to more reports of drug-related side effects than the traditional web- and paper-based forms; and 3) whether using Med Safety(R) saves money for healthcare providers. We will also train researchers in drug safety.

This project will show whether Med Safety is effective at improving the reporting of drug-related side effects by healthcare professionals. Our learning from deploying the Med Safety(R) application across a population that encompasses large, developed cities and isolated rural areas will be invaluable for wider global efforts in drug safety monitoring. Our strong links with National and International agencies including the NDA, MHRA and WHO will help to ensure that our work improves the safety of PLHIV.

There is an urgent need to improve pharmacovigilance in Uganda. Despite efforts to improve reporting using web- and paper-methods, adverse drug reaction (ADR) reporting by healthcare professionals (HCPs) remains critically low. We aim to complete a cluster-randomised controlled trial to evaluate the effectiveness of a mobile application in addition to traditional web- and paper-based methods for ADR-reporting by HCPs.

Our goal is to recruit 3820 HCPs from 382 ART-sites in Uganda to evaluate the Med Safety(R) mobile application, developed by the European Union WEB-RADR programme to embed digital PV in healthcare. Med Safety(R) is available in English and Luganda and has been implemented in limited settings in Uganda since February 2020. We aim to discover the barriers and facilitators to Med Safety(R) uptake, its effectiveness in improving PV, and the cost-effectiveness of rolling it out to HCPs at ART-sites. Our study will have two arms: HCPs enrolled at ART-sites in the intervention arm will be trained in the use of Med Safety(R), paper- and web-based ADR-reporting methods and those in the control arm will be trained in the use of paper- and web-based ADR-reporting only. HCPs will be encouraged to report ADRs through onsite awareness campaigns, reminder WhatsApp and mobile phone short messages.

To-date we have enrolled 243 HCPs from 45 intervention sites and 386 HCPs from 41 control sites, using funding from Makerere University. We are requesting funds from the MRC to deliver the rest of this project. The work will deliver important insights into the practicality, acceptability and effectiveness of mobile application-driven ADR-reporting in a resource-limited setting and increase our knowledge of the safety of dolutegravir-regimens and isoniazid preventive therapy among people living with HIV in Uganda. This work underpins potential national roll-out of Med Safety(R) among HCPs in collaboration with Uganda's National Pharmacovigilance Centre.