Testing to treat or treating to test

Searching for effective therapies for Covid-19 infection is a complex process

We are ten weeks into the Covid-19 pandemic in Pakistan. Although our case fatality rate remains lower than other countries, the number of confirmed infections is rising despite the lockdowns, social distancing and test-track-and-quarantine operations (TTQs). The social, psychological and economic costs are taking a toll on everyone.

Reducing infectiousness of symptomatic patients through antiviral treatment and reducing the susceptibility of uninfected individuals through vaccines will allow greater control of the pandemic. However, to date no drugs or biologics have been proven to be effective for the prevention or treatment of Covid-19. Numerous antiviral agents, immunotherapies and vaccines are being investigated and developed as potential therapies. More than 600 studies worldwide have been registered to explore the efficacy of treatments such as antivirals, hydroxyl chloroquine, immune modulators, plasma therapy, and stem cells. Searching for effective therapies for Covid-19 infection is a complex process.

From design to delivery

New treatment options are being tested around the world. However, they are being tested within the framework of a clinical trial, which is a specially designed study conducted to gather data and evidence about the effects of a drug/procedure on a group of patients.

Our understanding of diseases and how to treat them comes from studying them, by doing research. The difference between new treatments and established clinical treatments, in other words the difference between medical research and clinical practice (established standards of care), is that for the latter we have evidence to demonstrate safety, efficacy and accuracy.

Testing new treatments and vaccines

Before a potential new treatment can reach patients, it goes through several clinical trial phases. Altogether, clinical trial phases take six to seven years on average. In the first phase, the drug is given to a small number of healthy people and people with a disease to look for side effects and to figure out the best dose. In phase II, the drug is given to several hundred people who have the disease, looking to see whether it works and if there are any side effects that were not caught during the initial testing. Phase III is a large-scale trial in which the drug is given to several hundred (up to 3,000) people. A similar group of people take a placebo, or inactive compound. The trial is usually randomised and can take between one and four years. This stage provides the best evidence of how the drug works and the most common side effects. During the final phase, drugs that are approved for use undergo continued monitoring to make sure there are no other side effects, especially serious or long-term ones.

Evaluating risk and benefit

As doctors and researcher from around the world come to grips with the virus, there are daily updates and new publications on experiences and results of various treatments. The studies being conducted need to be robust and designed and conducted properly to be scientifically valid and informative. There is conflicting data on almost all treatments being tested which makes it even harder to evaluate the risk and benefit as the status quo changes with the publication of newer studies.

Therefore, we need a regulatory system on a national, provincial and institutional level to ensure that any potential therapies or studies planned in Pakistan are carefully evaluated and reviewed for scientific validity and ethical content. We need to have a mechanism to safeguard our patients and population.

As doctors and researchers in Pakistan have started to explore therapies and collaborate on international trials, two important committees have sprung into action: the Drug Regulatory Authority of Pakistan (DRAP), and the National Bioethics Committee (NBC), with the former reviewing the technical aspects and the latter concerned with reviewing ethical aspects of trials. Both have developed processes to expedite the review of Covid-19 projects. However, information about registration of trials with the DRAP and the NBC needs to filter through to provinces and individual institutions to ensure that all projects pass through the review process.

It is very important that we keep in mind that science done badly is not only harmful to patients but also adds to uncertainty about a disease.

How soon will we have a vaccine?

On April 20, the WHO published a list of Covid-19 candidate vaccines of which five have been approved for clinical trials on people and are in Phase I of testing. Another 71 potential vaccine candidates are undergoing pre-clinical tests in animals.

The traditional vaccine trajectory is being accelerated and compressed; changes may include simultaneous rather than sequential clinical trials that are run in parallel. These trials may be optimised for multiple target populations at the same time and run in different countries.

However, it will still take a least a year before we have something. Also, having a vaccine that is known to work is not the same as having billions of doses of the vaccine that can instantly be given to everyone. Once a vaccine is licensed, there will still be political obstacles to getting it to where it’s needed, because each country or public health jurisdiction has to make its own decision to roll it out. There will also be issues of prioritisation – who should get it first, if supplies are limited, and how will countries like Pakistan have access.

What are our other options?

While we wait for an effective vaccine to become available, antiviral drugs are also critically important for use in treating persons who are sick and can mitigate the effects of a pandemic.

Currently, there is no specific antiviral treatment because it is novel, and we are still trying to understand how it is causing disease. Therefore, drugs previously developed to treat other viral infections, especially from the same family of coronaviruses (SARS and MERS) are being tested to see if they might also be effective against SARS-CoV-2 virus that causes Covid-19. Most of these have cleared the first two phases of clinical testing that evaluate safety and therefore, are likely to be available before a vaccine. Evidence related to effectiveness of different antivirals is filtering through but again it is conflicting.

Coming months

We need to strengthen our regulatory processes and research systems to enable Pakistan to participate in evaluating therapies for Covid-19. These are testing times – hours, days, and weeks matter but all we can do is wait for more evidence before we can move forward. While we wait for the elixir that will rid us of this virus, we need to take care and observe infection control precautions both on an individual and collective level.

The writer is a consultant molecular biologist at the Aga Khan University Hospital regional lab in Lahore. The institution may not necessarily subscribe to the views expressed by the author

Testing to treat or treating to test: Searching for effective therapies for Covid-19 infection is a complex process