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Scientific Drug Testing
The Coronavirus (COVID-19) has everyone concerned, sheltering in place and wondering what will happen next. There are many processes that are helping to keep our resources available to us, new ways of keeping in touch with others and improvements in testing for the virus. A solution is being sought. One is the possibility of using already developed medications repurposed for treating the virus. At the same time, new treatments and vaccinations are being created. This can get quite muddled but let’s break it down.
Before testing drugs, there is a process that is followed to protect people from releasing medications without full knowledge of how they work or about long-term side effects. The United States has a very rigorous process. This ensures the safety of our population. Many other countries follow the same process to keep their populations safe as well. This is a brief summary of how the scientific process works. The normal print represents the usual process. Italicized print explains how the process has been adapted for the urgency of the COVID-19 pandemic.
Thinking about a new drug
When a scientist or researcher has a thought about a problem, they carefully study the physiology of the issue or how our bodies react to illness. Then they intently study what has been previously achieved. This is to avoid repeating work as well as to see what has been accomplished to date. Sometimes, a new product does not work but the delivery method might not be up to date or perhaps new science has been discovered to enhance previously accomplished work. Even failed studies are important to understand why something did not work so as not to repeat it.
For coronavirus (COVID-19), some scientist will begin with the above step. Since this is a brand-new virus, they will need to see if there is anything similar and gather information about how this specific virus affects the body. This work is underway. There are several drugs that have been developed for other viruses that are being re-examined or re-formulated for treatment of COVID-19, around the world.
When there is an understanding of the problem, scientific researchers begin to seek solutions. They will develop ideas from their education, internships in laboratories and their own study. Usually, scientist choose a specialty and stick with it building on their past work and the work of others. The building concept enables more discoveries to be built on previous work.
As a result of dedicated scientists, the treatment for COVID-19 is not starting from nothing. Many individuals have been studying infectious diseases. There is an excellent foundation for starting to find treatments for COVID-19.
Once a plan is formulated on paper, the scientific researcher will transition their idea into testing in the laboratory. This could include chemical development, studies on tissues or even animals. Animals used in laboratory studies are cared for by veterinarians, with super strict rules about ethical treatment and health concerns for the animals.
As soon as there appears to be safety and efficacy in animal or other laboratory studies, the process might be ready for human trials. An application must be made before this can be done. The protocol or outline of the process to be attempted in humans must relate the results of laboratory studies and step by step process of the projected human research. This protocol is reviewed by an Internal Review Board (IRB) which consists of healthcare professionals, researchers and at least one community member if not more. The IRB members will review the protocol to determine if the idea is reasonable and within the rights of people.
For COVID-19, the above process will be followed. Due to the urgent nature of this pandemic, modifications of current medications developed for other health issues are being considered. Even after this pandemic is resolving, more studies using traditional methods will be performed. Laboratory studies will continue to develop more ideas for treatment.
If the protocol for human study or clinical trial is approved, the process moves to study in living people. The research design is highly developed. The clinical trials process is set up in phases.
Phase I clinical trials are the first research efforts outside the laboratory. These are conducted with a very small number of people. This can be one person to perhaps as high as ten people with the average in the single digits. These studies are conducted to test safety. The questions for this level of research is, will this cause harm to a human? Is this study safe in humans?
This is the step currently underway testing existing medications developed for other diseases to see if they will work to treat COVID-19. There are many medications being studied both separately and in combinations in the U.S. and around the world. Because safety of the existing drugs has been studied, this part of the process can be expedited. The sample size of individuals for one clinical study in Seattle, Washington is 40 but I think that has been expanded by now. There is some conversation that this study will take place in several ‘hot spots’ of COVID-19 around the country. This aim of the study is to see if the medication is safe in humans particularly for those who have COVID-19.
Phase I studies will not necessarily be designed to alter human function, but they are designed to act as a trial to see what happens when the study is done. In spinal cord injury, there are not many treatments available so sometimes people in phase I studies will think they are secretly getting a cure. This is just not the case. The Principle Investigator (P.I.) is the leader of the clinical trial. The P.I. and the people working on the clinical trial will make an extra effort to ensure you understand the purpose of this level of study. Still, I see people hopeful for more because their options are so limited.
The current study underway using existing medication is not yet being tested in individuals specifically with spinal cord injury that I am aware. This is because the reactions by individuals with other medical conditions can be different. Typically, studies will be attempted with the general population followed by individuals with specific diseases or diagnoses. This includes all other diseases such as heart disease, respiratory disease, etc., not just SCI. On the other hand, individuals with SCI might move to the top of the list due to respiratory compromise that accompanies the diagnosis. Trials specifically for children typically begin later. All these exclusions may be eliminated due to the urgency of the issue.
Phase II studies involve more individuals, perhaps up to 100. This is the first study for dosing. The dose can be for medication, number of therapy sessions, amount of electrical input or whatever the dose is for the item under study. In phase II clinical trials, the researcher is attempting to understand if a little does good or if results will come with an increase of the experimental treatment. Sometimes, a smaller dose is better than a larger one. Finding the correct amount is the purpose. If you participate in a phase II study, you might see some change in your condition, but this is not certain.
Interestingly, an alteration in the typical pattern of drug testing has been made due to the urgency of the situation. For existing medication being tested for COVID-19, this segment of the plan is being conducted seemingly at the same time as the phase I study. Since the dose is known for other conditions, the researchers are using that dose for the initial trial. It may later be demonstrated that a lower or higher dose is needed to treat COVID-19 or it may be discovered that the existing medication is not effective.
Phase III studies use large numbers of people, in the hundreds or thousands. Typically, in SCI, we do not often see research in the thousands as the number of people with SCI is relatively low.. Thousands of people in a clinical trial are typically in drug studies especially in cancer or heart conditions because there are so many more of them. Phase III studies refine dosing. In phase III studies, you are likely to see a change in your condition. Some studies convert to market availability at the end of a phase III study others go on for further research.
In testing existing drugs, people may or may not see a change in their condition of COVID-19. Because the usual pattern of drug testing is being altered, there still is a chance that the outcome of testing could be that the existing drugs do not work with COVID-19. However, the thought process of drug study would indicate the chance of a positive outcome is highly possible.
Phase IV is the last clinical trial before putting the treatment on the market. This is a clinical trial that answers any lingering questions or any issues that came up due to the larger numbers of people in phase III. Phase IV is fine tuning the process under study. You would have a highly likely change in your condition if you participate in this level of study.
Again, because of the urgency of the pandemic, if the existing drugs appear to have an effect in reducing COVID-19, they will become available sooner while detailed studies continue. We will not know the long-term effect of the existing medications in a body with COVID-19. That might not be available for years to come.
There is another deviation from the typical scientific process. This is called compassionate use. It is really donating your living body to science. Compassionate use of medications is done when there is no other alternative treatment and death could occur. This is the method of testing being conducted with the medications that are suspected of treating COVID-19. It is how the four phases of clinical trials are modified as I have indicated above.
All these parts of a drug review, study, laboratory study and clinical trials can take years to be accomplished. On average, it can take 10-15 years to develop a new drug from concept to market. Since this pandemic is so dangerous, rushing medical testing has been deemed appropriate and necessary. The goal for treatment of COVID-19 is to modify the normal time of drug discovery to 5-7 months, or sooner if possible.
There are some alterations that can be made to the typical development plan. Changing the research process happens for a variety of reasons, not just for a pandemic. For example, Rogaine is a very popular drug for male baldness. But did you know, it was developed as a blood pressure medication. Some people still take a Rogaine pill for high blood pressure control. A side effect of the drug was excessive hair growth, all over the body. Once this was discovered, the product was reformulated as a lotion to be rubbed on the head to stimulate hair growth just where it is desired.
There are other drugs and treatments that have been repurposed. Two individuals that had bone marrow transplants for cancer also had elimination of the AIDS virus. More testing will be attempted to see if bone marrow transplant is a cure for AIDS. There are other medical treatments that have been found in the serendipitous manner. Not often but it does happen.
This is what is thought might be the case in treating coronavirus with currently existing medications. To properly assess this, the scientific process must occur. Even if the process works, the next question is what will happen to your body in 5, 10 or more years. The body can be changed by viruses and it can be changed by medication. If these drugs work for their intended purpose, we don’t know what will happen in a body with coronavirus. It could be nothing or it could be extremely dangerous in the long run or somewhere in between.
Risk vs. benefit must be considered by the scientists developing medications as well as the individual who will take the medication. Fortunately, the scientific community from around the world is eagerly working toward a treatment and vaccination for COVID-19 as we are eager to receive it. Nurse Linda
Pediatric Consideration: As mentioned above, pediatric drug testing typically occurs after adult testing is completed. Testing of drugs in women who are pregnant is even slower to the high and unknown risks of damage to the fetus. All research is based on risks vs. benefits, just as in accepted clinical care.
Initially, it was presumed that children were at less risk than adults, especially older adults. This has been demonstrated to be untrue. As the virus continues and more information becomes available, information changes. We all need to be alert and follow the guidelines provided by the Center for Disease Control, CDC.gov, for the latest and more accurate information. Nurse Linda
Linda Schultz, Ph.D., CRRN, a leader and provider of rehabilitation nursing for over 30 years, and a friend of the Christopher & Dana Reeve Foundation for close to two decades. Within our online community, she writes about and answers your SCI-related healthcare questions in our Heath & Wellness discussion.