Kusnandi Rusmil, Chief, Covid-19 Vaccine Research & Clinical Trial Team: We Got a Head Start to Develop the Vaccine Faster
The phase III clinical trial of Sinovac Biotech Ltd’s Covid-19 vaccine has generated a lot of interest from prospective volunteers. Four days after the open registration began, over 1,000 volunteers have signed up for the trial conducted by the research team from the faculty of medicine of the Padjadjaran University in Bandung, West Java.
THE research team needed 1,620 volunteers from among Bandung residents for the trial. Besides being required to be healthy and free of Covid-19, potential candidates must be 18 to 59 years old. “I’m looking for the age group with a relatively strong immune system,” Kusnandi Rusmil, 70, the team leader, said during a special interview with Tempo via video conference on Tuesday, July 28.
The trial offers new hope as the cases of Covid-19 continues to skyrocket in the country. On Monday, July 27, Indonesia records more than 100,000 positive cases and almost 5,000 fatalities from the disease. The numbers surpassed those of China, the coronavirus’s origin. “Our death toll is already high,” Kusnandi stressed.
After carrying out the phase I and II trials in China, Sinovac partnered with Bio Farma to conduct mass testing in Indonesia. Bio Farma entrusted Kusnandi and his team to carry out the clinical trial before the mass production can begin. Kusnandi, a pediatric health professor with the Padjadjaran University, has over 20 years’ experience in vaccine research and has conducted 32 clinical trials.
To Tempo reporters—Sapto Yunus, Dody Hidayat, Mahardika Satria Hadi, and Anwar Siswadi—Kusnandi, who chaired the Ethics Council of the Indonesian Medical Association during the period 2014-2017 explained about his team’s preparedness for the phase III trial, opportunities for Sinovac’s vaccine as well as the need for antidote to SARS-CoV-2 in Indonesia.
Please tell us about the team’s preparedness after the Padjadjaran University’s (Unpad) research ethics committee approved the phase III trial for the Covid-19 vaccine.
Following the ethics committee’s approval, we also received great suggestions regarding the protection of the research team which led to a change in the procedure. Potential volunteers who were previously required to take the rapid test only will now have to take the PCR (polymerase chain reaction) swab test. Because of the change, we had to inform the volunteers again that they will have to take the PCR test. They should also be explained that the process is safe.
Are they also required to take the rapid test?
The rapid antibody test is still needed to measure the level of their antibodies.
What happens if the PCR test come out positive?
Then the given candidates may not participate in the trial. If a participant’s PCR result is negative but the rapid antibody result is positive, he or she will also be disqualified. So, both results must be negative.
Why wasn’t the PCR test a prerequisite from the beginning?
Until recently, the rapid test was not needed much for diagnosis, but the health ministry did use it for diagnosis so we follow the ministry’s regulation.
The PCR test result takes longer than the rapid test. How much will the PCR test requirement affect the trial schedule?
The trial was originally planned to begin in early August, but now there’s a 10 day-delay. The daily maximum PCR testing capacity is 25 samples in one location. For instance, if there are six locations, 150 people at the most can be tested per day. The forms and leaflets also have to be reprinted. The committee which was trained to take the rapid test only must learn to swab. Previously, the candidates were supposed to be injected as soon as they came, but now they have to come three days before the injection for interview and swab. So, the schedule has changed.
Is public’s enthusiasm still high following the new requirement?
The Garuda community health center (puskesmas) in Bandung alone already have 350 people. I told them not to add more because other puskesmas also wanted to participate. So, whoever received the leaflet can first register themselves at the given WhatsApp number. Whoever registers first will get tested first.
Who can register to be volunteers?
Only those who have the Bandung resident registration card. Those without the card, even though they live in Bandung, are not eligible. Many of my doctor friends from Jakarta want to come for immunization. I told them that Jakartans must wait as the research is carried out in Bandung. Who wants to do surveillance in Cianjur, Sukabumi? They can participate when the research is expanded later. The candidates should be between 18 and 59 years old. There will be 1,620 volunteers in total.
Why is the number of volunteers set at 1,620?
Statistics experts from Unpad have calculated and come up with the number. The benchmark is based on the vaccine effectiveness. Certain number of volunteers for certain level of effectiveness.
Why do the volunteers have to be within that age bracket?
They have to be healthy. Those aged between 18 to 59 years are generally healthy; therefore, their risks to fall sick is relatively small. Some countries set three age groups; under 18, 18-59 and above 59-65. However, for me, I look for an age group with a relatively stronger immune system as well as very few comorbidities compared to other age groups.
Why was Bandung picked as the location?
I also asked the same question to Bio Farma. They said, ‘You’ve done 32 trials over 20 years. Therefore, we trust you.’ It’s okay for them to trust me, right? They approached me. I also carry the good name of my faculty and university. The faculty is situated right next to Bio Farma. It’s close and easy to meet up.
Was ethnicity also considered in choosing prospective volunteers?
This is a universal vaccine. Vaccines manufactured by Bio Farma such as polio, toxoid tetanus and diphtheria vaccines are sold and used in more than 132 countries, Africa and Latin American countries among others, with good results. There has never been any complaint to this date. We made these vaccines using the polio and diphtheria viruses in Indonesia. There’s no difference between Indonesian and Chinese pathogens. I don’t think there’s any problem.
Aren’t the SARS-CoV-2 virus strains in Indonesia and China different?
There are new strains because of mutation, right? However, to explain the virus mutation figuratively, a sedan can’t morph into a bus. It is still a sedan. Now all the countries are vying to produce vaccines. For this vaccine, China has already run the phase I and II trials and handed over the phase III trial to Indonesia, Brazil, and three other countries. Brazil is already going ahead with 8,000 volunteers.
What is the purpose of the phase III trial?
Phase I and II trials test the vaccine’s safety and immunogenicity to see if the vaccine can create immune response. Only in the phase III, the vaccine’s efficacy will be examined. We compare (the responses) from people who receive the vaccine and who only receive the placebo. The committee will monitor the volunteers’ movements for six to seven months and see how many of those who were not injected with the vaccine will get Covid. At the end of the research, we will know how effective the vaccine is. Later we will reveal the data. We need to see the efficacy, that’s why we need many volunteers.
What is the trial procedure like?
First, we take the blood samples from the volunteers. Then we inject them with the vaccine twice with a two weeks-interval between the injections. Their blood samples are taken again one month after the second injection, and again after six months. We will keep monitoring to see the level of their antibodies as well as how many of them, with or without the antibodies, will get sick. That’s how we measure the efficacy.
What proportion of the volunteers are given the vaccine or the placebo?
Fifty percent each.
What are the rules about injection?
If a volunteer receives placebo for the first injection, he or she will have the placebo also for the second injection. They will all be vaccinated at the end of the trial.
Kusnandi Rusmil (center) at the press conference on the Covid-19 vaccine clinical test, at the Padjadjaran University hospital, Bandung, West Java, July 22./TEMPO/Prima Mulia
How will the volunteers carry on with their routines after injection?
As usual. They continue with their activities, be it going to office or doing business or going to school, but everyone must follow the health protocols. Otherwise, those on the placebo will be in trouble. We won’t know whoever gets the placebo or the vaccine.
What kind of risks volunteers have to bear?
Like any other people. They may have symptoms such as cough, nasal congestion, etc. At most, the risk of allergy just like taking any other medication but only by a few.
What happens when a volunteer is infected with Covid-19 during the trial?
Every participant will receive an insurance coverage that lasts until the trial is over. One can go to any hospital for treatment if he or she gets sick. We will then check with the attending physician whether they are sickened by Covid-19 or not. If it’s Covid, they will be treated and monitored until they recover. If they suffer a serious adverse event, one way is to have them hospitalized and remove the blinding (disclose the information) without waiting for six months to find out if they were injected with the vaccine or not.
Can they still continue as a volunteer?
Of course not, but they will be covered by insurance until they recover.
You said that the Covid-19 vaccine has 90 percent efficacy. What made you so sure?
The volunteers will be given three types of injections, high and medium doses of the vaccine and the placebo. Those who receive high dose have over 98 percent protection whereas those who receive medium dose have 90 percent protection. Half of the volunteers who get the vaccine will be divided into three batches. We will see the consistency as to whether each batch has the same level of protection or not. Then these three batches will be compared against those who get the placebo. The result from these three batches are consistent if their protection is 95-97 percent.
Indonesia is not the only country where the phase III trial of Sinovac’s vaccine is run. What if one of them fails?
There will be an evaluation by a team from the World Health Organization (WHO) which will decide whether the vaccine should be released or not.
How does the distribution mechanism work after the vaccine is approved for mass production?
I informed President Joko Widodo and Pak Erick Thohir (State-Owned Enterprises Minister) during a meeting that we could not produce sufficient vaccine for the entire Indonesian population. As a result, it will be difficult for us to decide whom we should give the vaccine first. Finally, Pak Erick gave an idea, “Just give it to the seven provinces with the highest cases first to stem Indonesia’s fatality rate.”
Which are the priority regions?
The seven regions with the highest Covid cases, among others Jakarta, East Java, Central Java, South Sulawesi and Kalimantan. We cannot immediately produce the vaccine in large quantities.
How many doses will Bio Farma produce?
Pak Honesti Basyir (Bio Farma’s CEO) said the initial number will be around 40 million doses. Later it will be increased to 100 million. The production capacity will be increased gradually.
How many doses exactly are needed for Indonesia?
Around 200 million doses just for one shot while in fact we need two shots (for each person).
What does the vaccine distribution scheme in the seven provinces look like?
Usually the central government will send it to the provinces which will determine how it is distributed as they are the ones who know which areas need it the most. That’s the government’s policy. I don’t have the authority.
How were previous vaccines distributed?
The health ministry received the vaccines from Bio Farma. After the ministry made payments, Bio Farma distributed the vaccines to all the provinces for further distribution by the provincial governments.
Whoever is entitled to receive the vaccine?
Healthy people since it is to prevent them from getting sick, you see. Those who are already sick with Covid will receive treatment.
The government is also preparing to manufacture the Merah Putih vaccine. Are you involved in there as well?
Prof. Amin Soebandrio (Director of Eijkman Institute for Molecular Biology) chatted with me about it. We are in the same group at ITAGI (Indonesian Technical Advisory Group on Immunization), which advises the health ministry on immunization.
How is it progressing?
Prof. Soebandrio is looking for vaccine antigens to be injected into animals. Only if they are found to be effective, their stability will be examined. Then the research will enter phases I, II and III, but I don’t follow the details of his research. The aim of the research is also different. We aim to determine the vaccine’s efficacy whereas he aims to identify the pathogens.
Besides the ongoing vaccine research, are there any other candidate vaccines?
That’s the only one Indonesia has, but the United States also has and so does Brazil. The WHO is also developing (a vaccine) but the closest is this one by Sinovac.
Do all the vaccine raw materials come from Sinovac?
We use the same materials used in the phase I and II in China. It gave us a head start so we could produce the vaccine faster. That’s the objective conveyed by Pak Jokowi and Pak Erick Thohir. There are already too many deaths in Indonesia.
Is it true that you rejected the President’s request to produce the vaccine in three months?
I did not reject it, but informed him that it was not possible. I said it would at least take six months so that we can find out the pros and cons of the vaccine. We have to be fair.
How did the President respond when you didn’t say yes to his request regarding the duration of the trial?
He laughed. I was also answering while laughing, (chuckles)...
• Place and date of birth: Payakumbuh, West Sumatra, May 14, 1950 • Education: Bachelor of Medicine, Padjadjaran University, Bandung (1977); Master in Pediatrics, Padjadjaran University (1989); Masters’ Degree, Padjadjaran University (2000); PhD, Padjadjaran University (2008); Professor of Pediatrics, Padjadjaran University (2014) • Career: Member, National Immunization Week for West Java Province, (1995-1997); Chairman, Indonesian Pediatrician Association (IDAI), West Java, (1999-2002); Chairman for Growth and Development of Social Pediatrics, IDAI (2002-2011); Chairman, Honorary Ethics Council, Indonesian Medical Association (2014-2017), Head, Growth and Development Division, Social Pediatrics and Child Health Department, Hasan Sadikin Hospital/Faculty of Medicine, Padjadjaran University (2004-2018); Leader, Covid-19 Vaccine Research and Clinical Trial Team (2020)
What was the President’s consideration behind his wish for the expedited trial?
He wants to see the economy up and running again. The longer the pandemic stays, the more problems we will face. The government has spent a lot of money to give compensation to the people, factories and so on and has ended up in huge deficit, you see. The President asked, ‘Can we do it in three months?’ It’s quite a normal question from someone who is not familiar with vaccinology. But he wasn’t adamant. He said the government would provide anything I needed (for the trial).
Is there a special request from the President?
‘If you need anything, just let me know.’ He wants to throw his maximum support behind the research. Pak Erick also said the same thing.
Do you have a special request for the President?
I don’t need anything because I already have the sponsor Bio Farma.