The website ClinicalTrials.gov, which is maintained by the U.S. National Institutes of Health, is the most extensive database of clinical trials in existence. This immense repository currently shows more than 1,700 results from clinical trials being conducted around the world to treat COVID-19. The number has multiplied exponentially in recent weeks and continues to grow.
The numerous trials to find a vaccine and the most effective treatment as soon as possible are not surprising considering that the virus has paralyzed activity in many countries around the world for weeks now. However, WHO Director General Tedros Adhanom Ghebreyesusel warned in February that it would take at least 18 months for a vaccine to be ready. Why isn’t this possible sooner given the enormous efforts taking place globally? The answer lies in the long journey that any kind of medicine must undergo before it can be administered to people.
The life cycle of clinical trials
In the words of the Spanish Society for Medical Oncology, a clinical trial is “an experimental evaluation of a medication in human beings to assess its safety and effectiveness. When an experimental medicine is compared to a medicine that has already been approved and is used in common practice, it makes it possible to determine whether the drug being researched offers more benefits than the existing medication.”
In order to develop drugs both for treatment and prevention – which includes vaccines – prior to the start of a clinical trial, a research phase in the laboratory, and a pre-clinical phase are carried out, which tests the way the drug functions in cellular cultures and in animals. This is followed by a total of three clinical phases in which the medicine is given to a group of volunteers that increases in size. In phase I, the treatment is tested on a very small group of volunteers to ensure that the product is innocuous and does not produce any problems. In phase III, in the case of vaccines, it is tested on a large number of healthy people who have been exposed. In the words of José Antonio López, director of the Neurovirology group at UAM, in this phase III, “In the case of the vaccine for the COVID virus, it would be ideal to do so on healthcare workers and those working for state security forces who are in contact with more infected people and are more likely to get infected.”
The danger of curtailing the phases varies for treatment and preventative drugs. “For treatment drugs, in a health emergency like the current one, it is possible to reduce the amount of time and use what is called compassionate use drugs. In other words, even if they have not passed all of the clinical phases, if we see that a patient is very ill and there is no other therapeutic alternative, they are used as a last resort even if they haven’t passed the corresponding phase,” says José Antonio López. “In the case of a vaccine, reducing the time significantly would be dangerous because the vaccine is a medicine that is given to thousands and thousands of people when we are healthy. Any problem in the design of the clinical phase, any minor side effect that was not detected because we used a small number of people, or because we significantly reduced the evaluation times could be very severe when it is later introduced administered to society in general.”
“In the case of a vaccine, reducing the time significantly would be dangerous because the vaccine is a medicine that is given to thousands and thousands of people when we are healthy.“
In normal conditions, all of these phases and evaluation measures needed for safety clearly translate into time. It normally takes several years before a drug or vaccine can be given to the population: “There is a wide range of variation, but we are talking about years – from four or five to probably a decade in some cases, depending on whether there are any problems in any of the phases,” explains the researcher and microbiology professor, who admits that in extraordinary conditions like the present, this time can be reduced to a certain extent. “I doubt that a vaccine for a pathogen we knew nothing about four months ago would be on the market before a year and a half, or unfortunately, nearly two years. Less than that and I think the risk becomes unacceptable.”
The race for the COVID-19 vaccine
Nevertheless, some companies and institutions claim they could have a vaccine ready before the end of 2020, like the U.S. company Moderna or Oxford University’s Jenner Institute. In both cases, clinical trials with people have already started with positive results, but they must be viewed with caution, warns the expert. “Cutting the time to less than a year, like what is being said now about some vaccines, could be dangerous because we would most likely be merging clinical phases, with fewer people, less time… We could have side effects that were not identified in those trials until the drug reaches the market due to the emergency, the haste and the lack of time. For example, the case of thalidomide.”
Despite all of this, is there reason for hope? “It is a rare virus, a complex virus, a respiratory virus that tends to induce a poor immunological response, a type of virus for which vaccines tend to offer less protection because it has less contact with the immune system in general,” explains José Antonio López. “There are reasons to be moderately optimistic because it has been seen that people who have had the infection are protected, so they do develop neutralizing antibodies, but we will have to see when the time comes. In terms of therapeutic drugs, there are also trials for many combinations of drugs that are already currently being used for other pathologies, as well as specific trials to fight this particular virus.There are reasons to be optimistic that a drug could be identified after about a year.”