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

Lead Research Organisation: Makerere University
Department Name: College of Health Sciences


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.

Technical Summary

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.
Description Increased awareness of pharmacovigilance methods by health workers in HIV care in Uganda
Geographic Reach National 
Policy Influence Type Contribution to new or improved professional practice
Impact The number of medication safety reports submitted to the National Pharmacovigilance Centre has increased tremendously from just about 4000 in 2021 to more than 12000 currently.
Description Understanding adverse drug reactions to dolutegravir and isoniazid in HIV-positive Ugandans: incidence, risk factors, management and patient-reporting
Amount £738,193 (GBP)
Funding ID MR/V030434/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 01/2023 
End 12/2027
Description AIDS Control Programme, Ministry of Health, Uganda 
Organisation Ministry of Health, Uganda
Country Uganda 
Sector Public 
PI Contribution The project provided well trained field teams who supported the Ministry of Health to sensitize health workers countrywide (368 health facilities) on the new HIV and TB treatment and prevention guidelines.
Collaborator Contribution The Ministry of Health provided the new guidelines used by the research team to promote pharmacovigilance of the new HIV drug dolutegravir and repurposed tuberculosis drug isoniazid.
Impact More than 3000 health workers trained on pharmacovigilance generally and in particular the safety of dolutegravir and isoniazid in people living with HIV.
Start Year 2022
Description Medicines and Healthcare products Regulatory Agency 
Organisation Medicines and Healthcare Regulatory Agency
Country United Kingdom 
Sector Public 
PI Contribution Provide suggested updates to the Med Safety App from users
Collaborator Contribution Receives the mobile app reports and relays them to Uganda's National Drug Authority Software updates the Med Safety App Manuscript co-publication
Impact Software upgrades to the Med Safety App
Start Year 2022
Description School of Public Health, Makerere University, Uganda 
Organisation Makerere University
Department School of Public Health
Country Uganda 
Sector Academic/University 
PI Contribution We provide research training to their staff who participate in the project as research assistants and data analysis personnel.
Collaborator Contribution Their Finance and Administration Office manages the grant and one of the Co-Investigators on the project is from the School of Public Health.
Impact 1. Training of 10 research assistants from the School of Public Health 2. Efficient and Robust financial management of our research grant 3. Identification of a new collaborator to support the economic evaluation component of the project in the near future
Start Year 2022
Description University of Liverpool, United Kingdom 
Organisation University of Liverpool
Department Institute of Integrative Biology
Country United Kingdom 
Sector Academic/University 
PI Contribution Training of the research team Hold regular research meetings to measure progress of the project Participate in data management and analysis
Collaborator Contribution Technical support through technical steering committee meetings.
Impact Improved quality of data in the National Pharmacovigilance Database
Start Year 2022
Description Pharmacovigilance sensitization and training 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact More than 3000 health workers at 368 health facilities received training on the basic principles and purpose of pharmacovigilance, methods used to report suspected adverse drug reactions, structure and function of the National Pharmacovigilance Centre and the common side effects associated with the new HIV drug dolutegravir and TB drug isoniazid. This training focused a lot more on the pharmacovigilance of HIV and TB drugs at HIV clinics in Uganda because the two types of drugs have been massively rolled out since 2019.
Year(s) Of Engagement Activity 2022