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发展，艾滋病毒感染者可以过上健康长寿的生活。不幸的是，艾滋病毒感染者需要终生服用抗逆转录病毒药物。抗逆转录病毒药物通常是安全的，但对某些人可能会产生严重的副作用，特别是长期使用。常见的副作用是在临床试验中发现的。如果一种药物引起的副作用太严重或太普遍，它就会失败。在临床试验中不可能测试足够多的人来发现不太常见的副作用。这些都是通过监测现实世界中服用药物的人而发现的。同样重要的是，在所有种族的人群中监测药物的安全性，因为某些副作用在属于某一特定种族的人群中更为常见。我们的工作重点是乌干达3.5%的人口，即150万人，他们携带艾滋病毒。目前，关于有多少艾滋病毒感染者因抗逆转录病毒药物而产生副作用，我们知之甚少。乌干达政府认识到鼓励和使卫生保健专业人员报告药物相关副作用的重要性。然而，监测与药物有关的副作用的系统最近才在乌干达建立起来，报告的数量非常少。在2018年10月至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。由于乌干达提供给艾滋病毒感染者的治疗方法最近发生了变化，我们迫切需要改进药物相关副作用的报告。2018年，乌干达启动了一项计划，迅速推广抗逆转录病毒药物组合，包括世界卫生组织（世卫组织）推荐的治疗艾滋病毒的新药多替格拉韦（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——艾滋病病毒感染者死亡的主要原因。尽管DTG比其他抗逆转录病毒药物有一些重要的优势，但我们知道，在一些人身上，它会导致肝损伤、高血糖、焦虑、失眠或抑郁。此外，当DTG和IPT同时使用时，副作用的风险可能更高。我们的目的是测试通过移动应用程序报告是否有效地增加了医疗保健专业人员对抗逆转录病毒相关副作用的报告。如果成功，我们的项目也将提高我们对哪些副作用在乌干达艾滋病毒感染者中最常见以及受其影响的人数的理解。这些是我们工作中必不可少的第一步，以确保今后每一名艾滋病毒感染者都能得到正确剂量的抗逆转录病毒药物治疗。我们将测试的移动应用程序称为Med Safety(R)。Med Safety(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监管机构（MHRA）为乌干达的国家药品管理局（NDA）进行了改编，但尚未被广泛使用。我们将从382个艾滋病毒治疗中心招募3820名医疗专业人员，以：1)调查影响医疗专业人员成功推出Med Safety(R)的因素，以及医疗服务提供者对使用该应用程序的感受；2)发现使用Med Safety(R)是否比传统的网络和纸质表格导致更多的药物相关副作用报告；3)使用Med Safety(R)是否为医疗保健提供者节省了资金。我们还将培训药品安全研究人员。该项目将显示Med Safety在改善医疗保健专业人员对药物相关副作用的报告方面是否有效。我们在包括大型发达城市和偏远农村地区在内的人口中部署Med Safety(R)应用程序的经验教训，将对更广泛的全球药物安全监测工作具有宝贵价值。我们与国家药监局、MHRA和世卫组织等国家和国际机构的紧密联系将有助于确保我们的工作提高艾滋病毒感染者的安全性。

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.