No country has been left unscathed by COVID-19, therefore a key aim for RECOVERY was to find effective treatments that can be accessed by all countries. Thanks to Oxford University’s established research partnerships across Asia, in February 2021 RECOVERY expanded internationally to Vietnam, Indonesia and Nepal Here, Professor Raph Hamers and Dr Erni Nelwan describe the challenges, highlights and lessons learnt from setting up the study in Indonesia.
Could you summarise your roles?
Raph: I am an Associate Professor for the Eijkman-Oxford Clinical Research Unit (EOCRU) in Jakarta, Indonesia, hosted by the Faculty of Medicine at the University of Indonesia. EOCRU is a sister site of the Oxford University Clinical Research Unit (OUCRU) in Ho Chi Minh City, Vietnam, which is supported by The Wellcome Trust’s Africa Asia Programme. OUCRU works with partner institutes across Indonesia, Nepal and Vietnam to develop clinical research capacity in these countries.
At EOCRU, we support a vibrant research programme involving multiple local hospitals and organisations across the country. There is a lot of potential to participate in global clinical research here, thanks to several excellent medical facilities and partners. However, these lack the direct experience of running large-scale studies. One of my roles is to connect local principal investigators (PIs) in Indonesia with the support they need from Oxford University’s world-leading trial management teams.
Erni: I am an Associate Professor of internal medicine and tropical infectious diseases at the Faculty of Medicine, Universitas Indonesia, Jakarta. I oversee a varied programme of research into how to prevent, diagnose, and treat a wide range of diseases, including HIV/AIDS, opportunistic infections, tuberculosis, hepatitis, malaria, dengue fever and typhoid. I am the country PI with Raph for RECOVERY International in Indonesia.
Why was it important to launch RECOVERY in Indonesia and other international sites, such as Vietnam and Nepal?
Raph: COVID-19 is a global pandemic, so the aim of RECOVERY International is to find treatments that are effective across all populations and settings. Therefore, the RECOVERY chief investigators rightly decided, after their initial successes in the UK, to expand internationally to include a diversity of settings where the pandemic was still rife, such as Indonesia and Nepal.
RECOVERY International evaluates therapeutics that, if shown to be effective, can be rapidly and widely implemented in low resource settings, and have a direct impact. We are very proud to have been included among the first countries to launch RECOVERY International.
Erni: I would add that from the perspective of clinical research in general, we were very keen to demonstrate that Indonesia can take part in important global health studies, and make valuable contributions to these.
What are your day-to-day duties?
Erni: I oversee all the research teams and hospital sites conducting RECOVERY International in Indonesia. Currently, this involves four hospital sites in Jakarta, Surabaya, Medan and Bandung. I work closely with the teams at these hospitals to make sure they have all the permissions, equipment and training needed to run the study. This includes implementing the research protocols correctly, obtaining patient consent to participate, and completing all the required documentation. I also liaise with Indonesia’s National Agency of Drug and Food Control to obtain their approval for the study treatments, and work out how these can be sent to Indonesia. Thankfully, the team at Oxford provides support to manage a lot of the paperwork and ethics submissions, so I can focus on practical issues.
Raph: At EOCRU, I lead the clinical trial support team, with regular meetings to discuss enrolment progress, potential safety concerns and any other issues that arise. We take care of financial agreements, contracts with the study sites and regulatory approvals. We also have frequent meetings with the PIs at the study sites, including Erni, to hear their experiences ‘from the front line’ and to share important updates. Because RECOVERY is a dynamic, very fast-moving trial, we are also in continuous communication with the Oxford-based team, so that we can implement forthcoming changes to the protocol as soon as possible.
What were the challenges of adapting RECOVERY to a different healthcare setting?
Raph: Compared with the UK, health research in Indonesia has to contend with more bureaucracy and regulatory hurdles, particularly as there is no unified health system like the NHS. For instance, the Indonesian Regulatory Authorities required that we provided all the study drugs for RECOVERY trial participants ourselves, instead of permitting use of hospital pharmacy stocks. Because RECOVERY is such a fast-moving trial running at multiple locations, we asked all sites to accept the decision of a single, umbrella ethical committee at Universitas Indonesia, rather than each site having a separate approval process. I believe this is unprecedented for Indonesia, and could be a model for clinical research here in the future.
Top (L to R): Dr Sandhi (anaesiologist), Dr Wanda (GP), Dr Affyarsyah (pulmonologist), Mrs Mannaria (pharmacist) Bottom: Mrs Ajeng (nurse), Ms Diah, (nurse), Dr Tesha (GP), Dr Erni, (tropmed internist/site PI) Credit: RS MMC Jakarta, private hospital.
Erni: Like countries everywhere, we faced many challenges in running a clinical trial during a pandemic of a highly contagious disease. This included the need to procure personal protective equipment, and ensure that each hospital site had proper procedures in place to minimise the risk of cross-infection to research staff. However, we also had cultural issues more specific to Indonesia. For example, the Indonesian public can be very hesitant about participating in clinical trials. Consequently, communication and two-way engagement are essential to reassure patients that the treatments are safe to use. There is also the issue of background endemic infectious diseases, such as tuberculosis and Hepatitis B, which require additional screening and management.
Having said that, RECOVERY’s simple protocol and user-friendly data collection methods were enormously helpful in minimising the burden on our clinicians.
What have been your highlights so far from RECOVERY International?
Raph: In launching a very dynamic, adaptive clinical trial in Indonesia, RECOVERY International has introduced a new model of research for this country. Many of the normal regulatory barriers were removed, because everyone felt the most important thing was to contribute towards finding better treatments. It has been very rewarding to help establish these collaborations and bring people together with this shared purpose.
Erni: It is very exciting to be part of a large trial that is delivering impacts in real time. Even before Indonesia joined the study, the results from RECOVERY UK had already improved the care of our COVID-19 patients. For instance, dexamethasone is now used widely here to treat COVID-19. But it is also important to prove which treatments don’t work. Particularly at the start of the pandemic, many different treatments were used to treat COVID-19 patients in Indonesia, even though there was no evidence that any of these were effective.
What are the future plans for RECOVERY in Indonesia?
I hope we can maintain the highly motivated networks we have established – between clinicians, institutions and committees -so that we can continue to build capacity in Indonesia to accommodate more of these types of trial in the future.
Erni: Our aim is to recruit 2,000 COVID-19 patients over two years, and we are about to launch a new arm of the study to investigate the diabetes drug empagliflozin, which also has immunomodulatory effects. We are also in negotiations to open at least three more hospital sites to the trial. Vaccination rates outside the capital are still low, so it is important that we expand to include more areas across the country.