Let’s not jump to conclusions regarding any breakthrough in the field
There has been an amount of apparent progress in the pandemic situation in Bangladesh; the eye-catching one is the development of a vaccine by a Bangladeshi biotech firm, and the other is the continued saga of the antigen/antibody detection kit of Gonoshasthaya (GS).
Obviously, the said invention of a vaccine by a local company has raised high expectations and much excitement. It eclipsed the importance of the coronavirus detection tool that had generated similar high expectations in our country. It did so particularly in the mass community, who feel trapped and suffocated by the social confinement that inevitably curtails their ability to earn day-to-day life-sustaining minimum income, raising the prospect of starvation in the coming days.
I would not be surprised if many were already exposed to the reality of starvation. I think it was early April this year, I had noticed the intriguing news of the invention of a diagnostic kit for the novel coronavirus by GS, and inevitably, I encountered a seriously mixed feeling in my gut.
On one hand, I felt supremely excited that a Bangladeshi company had been the pioneer in successfully producing a diagnostic test that was capable of detecting the deadly virus infection in humans in a record time of 5-15 minutes. Most importantly, for us belonging to developing economies, where a large chunk of the population struggle every moment of their lives, the cost of the test was only Tk300, less than $4. Exciting indeed!
This was a real breakthrough when the rest of the world, including the US, the UK, and other developed European economies had been struggling in the absence of such an important tool essential for fighting against the pandemic. Western liberal democracies had felt shaken by the possibility of imminent, impending political doom in the absence of providing a reliable test that would allow them to test, trace, and isolate, and provide them in their desperate bid to save their nation, avoiding the deaths of millions and an economic meltdown.
My inquisitive mind started inquiring into the prospect. Was this the ground-breaking scientific revelation that governments the world over, as well as scientists and health professionals all over transcontinental planes, were searching the horizon for in their quest, like the pied crested cuckoo, for saving humanity? Or was it a subterfuge to corner state machinery -- a search for a ruse when all other modus operandi had failed to rattle the ruling government of the day?
The enormity, the sheer fortuity jumbled with the flakiness associated with acclaimed discovery, was beyond comprehension. It appears that the government did not wish to be drawn into any conflict that could be avoided, as the political position of the GS authority in the bigger political ambience of Bangladesh had been pretty transparent, and the government and the prime minister had categorically instructed the relevant authorities to provide any assistance feasible to avoid any such targeted embarrassment.
GS had announced their intention to produce the test kit in early March, simultaneous to the discovery of the first Covid-19 patient in Bangladesh. Within a day of GS applying for the permission to import raw materials for the test, the Drug Administration Authority (DAA) of Bangladesh approved the application in record time in mid-March.
The application was handed to the DAA on March 18 and the approval issued on March 19, to be precise. After the arrival of the raw materials on April 5, the real drama started. On April 7, GS received blood samples of five coronavirus-infected patients from the government. Two days after the receipt of the blood sample, an announcement came from the GS authority that they were planning to hand over some of the test kits to the government.
What international authorities had to say
The information given with this announcement was puzzling to the extreme. They claimed that the diagnostic test was an antibody detecting test, not the RT-PCR test that uses viral genetic material requiring substantial time gaps from collecting samples of nasal or throat swabs to delivering the result, nor an antigenic test for the virus.
This made me ill at ease as, till that day, and it is true till today, no antibody test had been approved as a diagnostic tool for novel coronavirus detection. Let’s see what the different world authorities in the health sector said about the antibody test, and particularly a rapid one at that. CDC, Centre for Disease Control, the major operational department of the Health and Human Services of the US government is responsible “to protect America from health, safety, and security threats, both foreign and in the US.
Whether diseases start at home or abroad, are chronic or acute, curable or preventable, due to human error or a deliberate attack, CDC fights disease and supports communities and citizens to do the same.” The US Centre for Disease Control states that the antibody test may not detect a current infection, as it takes one to three weeks after infection for the human body to make antibodies.
On June 25, the CDC issued a statement saying that the antibody test should not be used to diagnose a current Covid-19 infection, especially not on its own. The CDC also emphasizes if someone has taken an antibody test and tests positive or negative for Covid-19 on a viral or an antibody test, they should still take preventive measures to protect themselves and others, as the CDC does not know yet and scientists are working to understand if people who recover from Covid-19 can get infected again.
The NHS England and the UK government’s official website states that the antibody tests detect antibodies to the Covid-19 virus in the blood to see if someone previously had the virus, and how it differs from the virus swab (PCR) tests that detect current coronavirus infections. If someone receives a positive antibody result, it does not mean that they are immune, or that they cannot pass on the virus to others.
Therefore, the value of antibody tests is currently limited to answering the question of whether someone has had the virus or not, and providing data and a greater understanding on the spread of the virus. The Medicines and Healthcare products Regulatory Agency (MHRA) of the UK government issued a warning that people who have so far used a finger prick antibody test should not consider the results to be reliable and should not take any action on it.
The MHRA warning does not apply to antibody tests using blood obtained from the veins, which requires a health care professional to administer. No reliable home test kit has yet been found and no one yet knows if the presence of antibodies indicates immunity from reinfection or transmission.
Despite a bitter experience in March, when the UK government bought 3.5 million antibody home tests and scientists at Oxford University found they were unreliable, the UK government continued to study the effectiveness of the Covid-19 antibody rapid response kits to enhance understanding of the combat strategy against novel coronavirus and is in the process of a large research study recruiting 2,500 volunteers from staff working in the NHS.
The Public Health England plans to launch a separate study of 10,000 health care workers to learn more about immunity against the virus. Despite the claim from the Rapid Test Consortium headed by the University of Oxford that their own kit produces results in 10 minutes, is highly accurate, and really has set the gold standard expected from such tests, approval is yet to come. The possible approval, if it occurs, may happen only after a reliable, population-based, randomized, controlled research trial.
But even then, not as a diagnostic mechanism. Since the rolling out of the rapid test kit trial, the British Medical Journal published on June 24 an article expressing concerns for attempted research on the kits without the benefit of assessment of performance of these tests to the standard typically demanded of a novel test.
The article also questions the resource implications and the rationale for the research in the absence of any specific clinical indication in individuals. They categorically inform that the test kits are not diagnostic tests, that neither a positive nor a negative is likely to alter clinical management, and that a positive result does not indicate immunity.
A Bangladeshi vaccine
Let us now focus on the topic of the Bangladeshi company’s success in the initial stage of vaccine development. I would like to congratulate the young Scientists of Globe Biotech Company for their successful completion of the exploratory phase of the new vaccine/ drug invention/discovery process.
They have done some preliminary work required in the preclinical stage. It is undoubtedly an exciting prospect in these days of hopelessness. I personally believe that the company has not made any claim of completing the process of producing a vaccine against coronavirus and, I suggest very strongly that our people are informed that this success in the exploratory stage, if scientifically proven to be true, may just be the nascent beginning of a long-drawn, lengthy process that is likely to take years to achieve.
What I gather from their press conference, the company Biotech has completed a part of the pre-clinical testing, which was done on animals -- in their case, on three rabbits. A pre-clinical trial is typically done on animals before clinical trials can begin on humans; this is done to ensure that no harm comes to human volunteers/subjects.
The company has made it clear that they have just completed the preliminary experiment, a small part of its pre-clinical trial, and would progress on to the major component of remaining pre-clinical trial soon, where it would do another controlled experiment on “mice and rats,” in contrast to the Oxford vaccine using chimpanzees, whose immune mechanisms resemble our human systems closely.
The Bangladeshi company mentioned submitting their research findings to NCBI or the National Centre for Biotechnology Information, which is the US national resource for molecular biology information, and has no authority to approve any vaccine or drug. What is critical is that the company, after completion of their preclinical trials, get proper approval of their process prior to achieving permission for clinical trials.
Any attempt by anybody to claim that the company has developed the vaccine will be an “argumentum ad novitatem” -- a fallacy frankly misleading and raising false hope for millions as no one can claim to have discovered a vaccine simply based on the preclinical trial results. The entire process of a new vaccine or a new drug follows a standard cycle approved by all international authorities, including the FDA of the US.
Each vaccine typically goes through an exploratory stage, a preclinical stage, a clinical development stage comprising Phases I, II, and III prior to regulatory review and approval before availability of the drug in the public domain. (Exploratory stage, pre-clinical stage, clinical development, regulatory reviews and approvals, manufacturing, quality control through monitoring).
Clinical development is a three-phase process (Phase I, II, and III) followed by a fourth (Phase IV) that is essential for quality-control through monitoring. However, due to the urgency now, a phase or two might have to be superimposed, the methodological aspects and their quality must be ensured under all circumstances.
Phase I is where small groups of healthy human subjects (usually 20-100) will receive the trial vaccine. Phase II is slightly expanded as in this stage, the vaccine is given to subjects who usually have characteristics including age and physical health similar to those of the coronavirus patients (elderly, children, number usually in hundreds). In Phase III, the vaccine is given to thousands of subjects.
This is the most critical phase where the vaccine is tested for its efficacy, safety, and effectiveness. My message is not aimed at discouraging the attempt at finding a vaccine by a Bangladeshi company, absolutely not. The progress made by Biotech so far is still quite promising, a significant step in the right direction.
However, the next stages, particularly the clinical trials, must be carefully designed and conducted as per regulations dictated by national and international standards.
Dr Raqibul Mohammad Anwar is a Specialist Surgeon and Global Health Policy and Planning Expert, Retired Colonel, Royal Army Medical Corps, UK Armed Forces.