With the death toll of more than 239,000 people, the Covid-19 outbreak is one of the biggest health crises in the past 50 years. Unfortunately, until now there is no drug that has proven effective against Covid-19.
By
MUHAMMAD HANIFI
·8 minutes read
AFP/GERARD JULIEN
In this file photo taken on February 26, 2020 Medical staff shows at the IHU Mediterranee Infection Institute in Marseille, a packet of Plaqueril, tablets containing hydroxychloroquine, drug that has shown signs of effectiveness against coronavirus.
By the end of April 2020, more than 3 million people in 210 countries and territories worldwide had tested positive for the SARS-CoV-2 virus. With the death toll of more than 239,000 people in four months, the Covid-19 outbreak is one of the biggest health crises in the past 50 years. Public intervention in the form of limiting social interaction, closing schools and tracking contact history are only effective in temporarily suppressing the growth rate of cases. Epidemiological modeling and case data from China show that clusters of infections can reappear after social restrictions are removed.
In the long run, public intervention is intended only to give us space and enough time to deal with sick patients, to protect vulnerable populations, and most importantly to develop vaccines and drugs. Unfortunately, until now there is no drug that has proven effective against COVID-19.
So, how long will it take for a vaccine or drug to be found? Can we accelerate its development? To understand how drug development can be accelerated, we need to look at how drugs and therapeutic compounds are usually developed. Normally, research and testing of prospective drugs can take up to a dozen years, from exploration of therapeutic targets to going through three stages of clinical trials. Only with such a long process, the drug can be publicly accessible. The first phase of the clinical tests is carried out to determine the safety profile of the drug, involving a small group (10-20 people) of healthy volunteers. After the safety profile of the drug is known, the second and third phases of the clinical tests are carried out to measure the effectiveness of prospective drugs to manage certain medical conditions. This process usually involves thousands of patients and the results can clearly show whether the potential drug can work effectively as expected.
"Drug repurposing"
In the context of COVID-19, waiting for dozens of years is clearly not an option. Therefore, to accelerate drug development, doctors and scientists use a strategy known as drug repurposing or the use of drugs that already have a marketing license with certain indications in dealing with new diseases. Aspirin, for example, is a drug that was originally developed as a pain killer. Later, aspirin is known to have other effects to inhibit blood clotting. After a series of additional clinical tests, aspirin can now be used to reduce blood clots in cases of acute cardiovascular disease.
The use of such as strategy can cut drug development time for two reasons: first, the safety profile of old drugs has been usually known so the preclinical testing and clinical phase one are no longer needed. Second, the stock of these drugs is widely available in many hospitals, making logistics and coordination easier for the third phase of the clinical trials.
The availability of drugs is also an important factor which can make the drug repurposing approach more easily adopted in Indonesia, rather than waiting for vaccine development. The World Health Organization (WHO) predicts it will take at least 12-18 months to develop the COVID-19 vaccine, maybe even longer to produce a vaccine in sufficient quantities to be accessible to patients in Indonesia.
In the context of COVID-19, antiviral drugs (remdesivir, favipiravir, ribavirin), immunomodulators (corticosteroids, immunoglobulins) and chloroquine have been widely discussed among doctors and scientists as candidates for drug repurposing for COVID-19. These drugs are also intended to target biological processes that are also relevant to SARS-CoV-2 infection so that the selection of these drugs as initial candidates does make sense. Remdesivir, for example, is a nucleotide analogue that was originally developed to inhibit the replication of the Ebola virus genetic material. Because the SARS-CoV-2 genetic material replication process is similar to the ebola virus, remdesivir may also be effective in treating COVID-19.
Although it sounds promising, until now there has been no definitive data that can prove the effectiveness of these drugs to treat COVID-19 patients. In the midst of the competition of many parties to innovate to find effective therapies, we must not forget the importance of conducting clinical trials before these drugs can be used as standard guidelines for COVID-19 treatment, because, ignoring data and weakening the commitment to use evidence-based medicine will only worsen the situation in the midst of the ongoing crisis.
Lab technicians load filled vials of investigational coronavirus disease (COVID-19) treatment drug remdesivir at a Gilead Sciences facility in La Verne, California, U.S. March 18, 2020. Picture taken March 18, 2020. Gilead Sciences Inc.
Global solidarity for clinical trials
In the midst of the increasingly urgent need for COVID-19 drugs, we need to take a pragmatic approach to obtain sufficient clinical data in a short time. To bridge this need, the WHO has launched a global clinical trial platform which is expected to cut testing time by up to 80 percent. In contrast to clinical trials in general, the global clinical trials which, not by chance named "SOLIDARITY", rely on the participation of hospitals and clinicians from around the world to collect and analyze patient data simultaneously.
The WHO proposed clinical trial aims to measure the effectiveness of four of the most promising candidates for drug repurposing: remdesivir, chloroquine, combination of lopinavir and ritonavir and the lopinavir /ritonavir / interferon beta-1a combination. The combination of these two strategies, namely the use of drug repurposing and global collaboration in clinical trials, is expected to be able to accelerate the collection and analysis of data so that certainty of the benefits of these drugs can be immediately known.
Furthermore, investigating the effects of drugs in the SOLIDARITY clinical trial is designed as simply as possible to minimize the workload for health workers and hospitals who are now beginning to be overwhelmed in handling the surge in COVID-19 cases.
To reduce the logistical burden, hospitals can contribute by using drugs that are readily available. Medical personnel also only need to record basic medical outcomes without the need to report the results of examinations that relatively consume resources, such as radiology or blood gas analysis results. Although simple, this clinical trial strategy can still answer the most important questions, such as whether the drug being tested can reduce mortality and can it reduce the need for ventilators or hospitalization?
Kompas
Dr. Sonia Macieiewski (R) and Dr. Nita Patel, Director of Antibody discovery and Vaccine development, look at a sample of a respiratory virus at Novavax labs in Rockville, Maryland on March 20, 2020, one of the labs developing a vaccine for the corona virus, COVID-19.
In the context of COVID-19 medical treatment, Indonesia\'s participation in clinical trials initiated by the WHO is important for two reasons. First, we need sufficient data representation from the population of Indonesia and Southeast Asia. Most of the medical data related to COVID-19 today are obtained from clinical trials conducted for ethnic East Asian populations (mainly China and South Korea) and Caucasians (Europe and North America), which may not be fully extrapolated to the Indonesian population. This is increasingly important given the indications that the course of the disease and the severity of COVID-19 complications can be influenced by one\'s ethnic background. Without sufficient data representation, we will not be able to know in depth the extent of the safety and effectiveness of the drugs being tested for the Indonesian population.
Second, we have the same moral responsibility as other countries to accelerate the development of effective medicines to cope with COVID-19. As the name suggests, SOLIDARITY clinical trials cannot run effectively without the presence of global solidarity that encourages hospitals, medical personnel, and patients to take an active role in the development of therapies, including from Indonesia. The more parties contribute to this clinical trial, the sooner we can find a useful drug for COVID-19.
Focus on science and data
In carrying out their work, doctors and other medical personnel always make decisions based on scientific data and adhere to the principles of evidence-based medicine. In fact, the lack of data makes this difficult to do in the context of COVID-19 diagnosis and therapy. Of course doctors can still prescribe the above drug candidates "off-label" to patients, but claiming the effects of drugs prematurely can be dangerous. Some hospitals, for example, have stopped using chloroquine in the COVID-19 case due to reports of severe side effects in patients.
In the midst of the increasing number of cases around the world, it is no exaggeration to consider that the acceleration of drug development should be a global priority. Without adequate data and clinical trials, health workers are forced to guess the effectiveness and side effects of existing drug candidates. Therefore, the acceleration of the development of therapy with a drug transfer strategy and the cooperation of global clinical trials should be supported by all parties so that the management procedures for COVID-19 can be immediately formulated.
MUHAMMAD HANIFI, Doctoral student at the Weatherall Institute of Molecular Medicine at the University of Oxford; member of Indonesia\'s Innovator 4.0.
