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

由于抗逆转录病毒药物的开发，艾滋病毒携带者(PLHIV)可以健康长寿。不幸的是，PLHIV需要在他们的余生中服用抗逆转录病毒药物。抗逆转录病毒药物通常是安全的，但可能会对某些人造成严重的副作用，特别是长期使用的话。临床试验中发现了常见的副作用。如果一种药物引起的副作用太严重或太常见，它将无法通过试验。在临床试验中测试足够多的人来发现不太常见的副作用是不可能的。这些都是通过在现实世界中监测吸毒者而发现的。同样重要的是，对所有种族的人监测药物的安全性，因为某些副作用在特定种族的人中更为常见。我们的工作重点是占乌干达人口3.5%的艾滋病毒携带者--150万人。目前，我们几乎没有关于有多少PLHIV因抗逆转录病毒药物而出现副作用的信息。乌干达政府认识到鼓励和使医疗保健专业人员报告与药物有关的副作用的重要性。然而，乌干达最近才开发了监测与毒品有关的副作用的系统，报告的数量很少。从2018年10月到2019年9月的12个月里，只有400份关于抗逆转录病毒药物副作用的报告。我们迫切需要改进对毒品相关副作用的报告，这是由于乌干达对艾滋病毒的治疗最近发生了变化。2018年，乌干达开始了一项方案，以迅速推出抗逆转录病毒组合，包括世界卫生组织(世卫组织)推荐的新药多洛替格雷(DTG)。乌干达还推出了异烟肼预防疗法(IPT)，以预防活动性结核病--PLHIV的主要死亡原因。虽然DTG与其他抗逆转录病毒药物相比有一些重要的优势，但我们知道，在一些人中，它会导致肝脏损伤、高血糖、焦虑、失眠或抑郁。此外，当DTG和IPT一起服用时，副作用的风险可能会更高。我们的目标是测试通过移动应用程序报告在增加医疗保健专业人员抗逆转录病毒相关副作用报告方面是否有效。如果成功，我们的项目还将提高我们对乌干达PLHIV最常见的副作用以及它们影响多少人的理解。这些是我们确保每个PLHIV在未来以正确的剂量使用正确的抗逆转录病毒药物治疗的重要第一步。我们将测试的移动应用程序称为Med Safe(R)。Med Safe(R)是由一个欧洲药物安全项目开发的，并由英国药品和保健产品管理局(MHRA)为乌干达国家药品管理局(NDA)进行了调整，但尚未广泛使用。我们将从382个艾滋病毒治疗中心招募3820名医疗保健专业人员：1)调查在医疗保健专业人员中推广Med Safe(R)的成功因素以及医疗保健提供者对使用该应用程序的感受；2)发现使用Med Safe(R)是否会导致比传统的网络和纸质表格更多地报告与药物有关的副作用；以及3)使用Med Safe(R)是否为医疗保健提供者节省了资金。我们还将对研究人员进行药物安全方面的培训。这个项目将展示医疗安全在改善保健专业人员报告与药物有关的副作用方面是否有效。我们从在包括大型发达城市和偏远农村地区的人群中部署Med Safe(R)应用程序中学到的经验，将对全球药品安全监测的更广泛努力具有宝贵价值。我们与包括NDA、MHRA和WHO在内的国家和国际机构的密切联系将有助于确保我们的工作改善PLHIV的安全性。

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.