IO – The massive impact of the Covid-19 pandemic on people’s life demands an urgent solution if socio-economic recovery is to take place, even in Indonesia. There isn’t a single country that has been able to escape the current pandemic. Almost all sectors are affected: not only health, but the economy has also suffered a serious downturn. Indonesia is no exception.
There are three main pillars that make up the Indonesian government’s policy in handling Covid-19: a focus on the health sector, community assistance in the form of a social safety net, and the country’s economic survival.
The world is now racing against time to find the most effective vaccine and cure to overcome the Covid-19 pandemic, one of the gravest challenges that modern healthcare sector has ever faced. Doctors and scientists are working around the clock to find life-saving treatment – methods, drugs and vaccine capable of preventing infection or to avoid deterioration of a patient’s condition.
The global race for a vaccine and cure
Current vaccine candidates have entered the final stage of clinical testing, but to date no country or institution in the world can claim to have found a specific cure or vaccine that can successfully deal with Covid-19.
Data from a vaccine tracker site:
(FIGURE-1)
The figure shows that there are more than 165 vaccines in development around the world; 32 of them are currently being trialed in human volunteers. Vaccines typically take years of research and rigorous testing before they are proclaimed safe for mass application, but in this case scientists are working on making them available by next year. We can see that two vaccines have been approved, although they are only used on specific populations (as opposed to the wider community).
WHO records that as of August 20, 2020, 30 vaccine candidates have entered a clinical trial phase. Those that are currently in phase three of the clinical trial are being developed by the University of Oxford/AstraZeneca, Sinovac Biotech, Wuhan Institute/ Sinopharm, Beijing Institute/ Sinopharm, BioNTech/Fosun Pharma, Moderna/NIAID America, CanSino Biological Inc/Beijing Institute of Biotechnology.
There is also an updated list of the 21 most talked about treatments for coronavirus. While evidence suggests that they are quite effective, most are still in an early stage. But there are also warnings about certain clinical trial results bordering on pseudoscience or are even fraudulent. (FIGURE-2)
FDA itself has not approved any specific treatment for Covid-19. While it has authorized several types of drugs to be used for emergency treatment, their effectiveness is yet to be proven in large-scale randomized clinical trials.
As many vaccine or drug candidates are currently in a clinical trial phase, we as lay people are left to ask whether this is good news, whether we can now breathe a sigh of relief or should we be more vigilant? Since the news about vaccine clinical trials broke, the Indonesian public has been asking a lot of questions: Is the vaccine effective and safe? Is it a scheme to use people as guinea pigs? Should I volunteer for a mass trial?
In fact, the progress of clinical trials in Indonesia has lagged behind other countries, even among ASEAN countries. But since the country is included in the Phase 3 clinical trial, Indonesia is now ranked above Vietnam, Myanmar, Cambodia, Laos and Brunei.
Of the 350,000 clinical trials for various diseases conducted globally, ASEAN accounts fo 7,000. Singapore is conducting 2,500 clinical trials, Thailand 2,700, and Malaysia 1,400, the Philippines about 1,000, while Indonesia less than 600. Thus, it is not surprising that the public does not know much about what a clinical trial is or how they can take part. Evidently, Indonesia as the country with the 4th-largest population in the world, has not made good use of the opportunity to clinically trial the latest medicines for the benefit of its own people.
In countries that have done many clinical trials, people looking for the opportunity to volunteer in experimental drug testing usually already know where and what to do. Covid-19 pandemic opens the window for such clinical trials in Indonesia. Indonesia is participating as one of a so-called “multi-center solidarity trial” conducted by the World Health Organization (WHO). Currently, the public is talking about a clinical trial for a vaccine in Bandung, namely, a collaboration between Bio Farma and Padjajaran University’s Faculty of Medicine, using a vaccine from China on which the country is pinning its hopes that it can offer a way out of this pandemic.
Clinical trials are experiments carried out on humans to study the efficacy and safety of a product such as drugs, vaccines and medical devices. This is typically the final phase of the multi-stage process of a medical product development before it is approved for extensive use.
Below is an illustration of clinical trial phases: (FIGURE-3)
Preclinical testing is research carried out in a laboratory to find out which chemicals are the most active. Afterward, animal trials are conducted. If a medication is deemed safe and effective in animals, then it will proceed to clinical trials in humans.
The stages of clinical testing in humans
Phase One. To determine the appropriate dose to be administered and how many times it should be taken in a day. Usually the number of participants or volunteers for clinical trials at this stage is around 20-100 people. After finding the right dosage, the second phase begins.
Phase Two. To determine the efficacy of the drug. This stage is usually carried out on a larger and more specific group of participants or volunteers, namely, people who already contracted the disease. It is enacted following very strict selection (inclusion) criteria. If the results are promising in terms of its efficacy, it will go on to phase three.
Phase Three. The recruitment of participants or volunteers in large numbers (around one thousand or more). This can be done in different populations, by including more than one country. And it is likely that the results may show different efficacy results which may not be as strong as phase two. The third phase usually takes longer, which can be up to a year or more. Data is then collected so the regulatory body can conclude whether the drug or vaccine is permitted for distribution.
Here, the clinical trial is over but product development is not yet complete, because even though it has been in circulation in the community, it must still be monitored for several years for fear there are unexpected or unwanted side effects.
Clinical trials generally take between 6-7 years, followed by 3 years of evaluation. But Covid-19 is no ordinary pandemic because the death rate is quite high. This means that exception can be made on the vaccine development process and clinical trials can be accelerated. We can learn from clinical trials in other countries or literature references to clinical trials of vaccines for previous outbreaks and apply these to SARS-Cov-2, so we don’t have to start from scratch.
The government strives to procure Covid-19 vaccine as quickly as possible, either by developing it independently or in collaboration with other countries or companies overseas.
If the nation’s best brains can develop a superior locally-produced vaccine, this will be pride of the nation and we can achieve independence in the medical field. Certainly, the vaccine candidate must go through a proper clinical trial process in accordance with prevalent rules and regulations. Indonesia is currently developing a locally-innovated Covid-19 vaccine, dubbed Merah Putih (Red and White) vaccine, a collaborative effort between the Eijkman Biomolecular Institute and several government agencies comprising the Agency for the Assessment and Application of Technology (BPPT), the Indonesian Institute of Sciences (LIPI), the Food and Drug Monitoring Agency (BPOM), the Ministry of Research and Technology, and a handful of universities.
Head of the Eijkman Institute for Molecular Biology Amin Soebandrio said that the development of a made-in-Indonesia Covid-19 vaccine will take some time. The vaccine itself is expected to complete the animal trials stage by the end of 2020. If it is proven effective, the vaccine candidate will be passed on to Bio Farma for preclinical and clinical trials. Nevertheless, Eijkman is still trying to accelerate the development of Merah Putih vaccine to compete with the Chinese-made Sinovac vaccine which is currently being trialed by Bio Farma.
Apart from the Merah Putih vaccine and Bio Farma-Sinovac vaccine currently in phase three clinical trials at Padjadjaran University in Bandung, there are also other vaccine candidates being developed by Kalbe Farma in collaboration with Genexine, a biotechnology company from South Korea, to produce a vaccine named GX19 (Genexine-19) scheduled for phase two clinical trials by the end of 2020. Kimia Farma is also in talk with G42, a technology company based in United Arab Emirates, and Sinopharm to procure vaccine which have gone through phase one and two. The vaccine will be further developed before being mass produced. There is also a plan to procure vaccines developed by a British company AstraZeneca. The company is currently testing its vaccine, named AZD1222, on humans, and is expected to be mass produced later this year.
The government has made its goal very clear. It wants to quickly and thoroughly provide protection for all Indonesian people so as to create a healthy and safe Indonesia immune from Covid-19.
Sinovac vaccine clinical testing in Indonesia
Neni Nurainy, Senior Manager of Research and Development Integration of PT Bio Farma, revealed two strategies Bio Farma has taken to develop the Covid-19 vaccine. First, a short-term strategy, through collaboration with Sinovac, to make the vaccine available soon. Second, a long-term strategy to independently create a locally-made vaccine in collaboration with the Eijkman Institute.
Efforts to make Covid-19 vaccine available in Indonesia have entered a new phase, following the start of phase three trial for Sinovac vaccine being carried out in Bandung, West Java. The same vaccine is also being trialed in Brazil, Chile, Bangladesh and Turkey.
It is hoped that the clinical trial will run well so that valid data can be obtained ethically and scientifically to prove that the product is of good quality, safe and efficient.
The role of BPOM is to ensure the efficacy and safety of the Covid-19 vaccine before and after it is circulated. The State-owned Enterprises Ministry appointed PT Bio Farma Indonesia to collaborate with Sinovac Biotech Ltd in producing the vaccine. Sinovac Biotech Ltd is a Chinese pharmaceutical company specialized on research, development, manufacturing and commercialization of vaccines to provide human with protection against infectious diseases.
Indonesia has made a breakthrough in being involved in global vaccine development with the phase three clinical trial. Although the success rate of a vaccine candidate trial is only around 30-50%, it is highly beneficial to the country and will inject a new optimism in overcoming the still raging Covid-19 pandemic. It is feared that this will be a long fight, lasting more than two years with numerous waves of infections.
Additionally, Indonesia has also entered into an initial agreement to obtain 10 million doses of vaccine from the Abu Dhabi-based G42 Group which collaborates with Sinopharm. Indonesia, through its pharmaceutical SOEs Kimia Farma and Indo Farma has secured a commitment for 10 million doses by 2020, and extends the agreement to include research and development, clinical trials, production, marketing and distribution.
Efforts to immediately obtain a reliable vaccine by conducting initial negotiations when a vaccine candidate is available are considered a breakthrough in international business, even though there is a risk of failure to produce a vaccine that is accepted by the international scientific community.
Is vaccination the solution to a pandemic? Now people are beginning to understand that a vaccine is not a silver bullet solution. Who should be vaccinated first? How many people should be vaccinated and how can we quickly and efficiently administer it to 80 percent of the population? Those are the lingering questions. In addition, there is still a debate about the issue of accessibility, because not every country can have a fair access to vaccines. If there are still countries battered by a pandemic, then the planet is not entirely safe. This notwithstanding, there are several initiatives to fight for equitable access to vaccine globally, such as the COVAX movement by GAVI, the Coalition for Epidemic Preparedness Innovations (CEPI) and WHO. The aim is to ensure there is a mechanism for rapid, fair and equitable access to COVID-19 vaccines worldwide. (Dr. Pandu Riono, MPH, PhD)
Dr. Pandu Riono, MPH, PhD is a Senior Staff with the Department of Biostatistics and Population of the Faculty of Public Health, Universitas Indonesia. He graduated from the Faculty of Medicine at Universitas Indonesia and acquired a Master’s Degree in Biostatistics from the University of Pittsburgh, US.