Data Analysis of All Clinical Trials
COVID-19: The Closest Treatment Ranking
How a simple data analysis can organize everything related to COVID-19 treatment development.
Every single day I come across some piece of news showing a new super-effective potential treatment. Sometimes it is an antiviral, sometimes it is a brand new vaccine, sometimes it comes from China, or Germany, or the US…
How can we tell which of these potential medicines are closest to becoming effective treatments for COVID-19?
The question above appeared in my mind last week when my grandpa emailed me information about another promising vaccine that had just emerged.
I believe we should develop some criteria to distinguish between drugs that are close to becoming effective treatments and those that still have a long journey ahead.
Even though there is a lot of research going on all over the world and there are many promising treatments coming out every day, most of them are still in a preclinical stage. All of them will have to go through several clinical trials to become a reality.
We will not miss any of those trials if we monitor them closely. Therefore, we may be able to always be aware of which are the most promising treatments.
However, we should always keep in mind that the fact that a drug hasn’t been tested in humans does not discard it from being a possible treatment. So what we can infer is that we may have to wait a long time for that to happen.
So, which treatments are closest to the finish line?
Until last Tuesday, the US clinical trials database registers 366 clinical trials proposed of which 189 are seeking for treatment by using 75 different drugs distributed among them.
The information their proposals carry gives us a unique opportunity to do some simple data analysis and answer this last question.
The Starting Point
Since the number of trials in the database is huge, we should start our analysis looking at the big picture before we narrow down into the data. An excellent way to accomplish that is by classifying all these treatments according to their nature.
As we can see in this pie chart, all kinds of treatments are going through clinical trials.
43 small molecules, 8 antibodies, 8 vaccines, 4 dietary supplements, 4 cell lines, convalescent plasma, and another 3 in the “other” group are between those treatments.
What if we add the number of trials per drug?
We can see that the chart changes a little. Despite the obvious fact that most trials include small molecules, we can also see some other interesting facts. Let’s pay attention to the variation of each piece.
The first thing we can notice is that vaccines and dietary supplements remained with almost the same number as before. This means that each treatment included in those types is going through, on average, a single clinical trial.
On the other hand, if we look at all the rest, we can see that the number increases. Many treatments in those groups are going through more than one trial, they are not all the same.
Which Treatments are Getting More Attention?
For a treatment to be considered capable of a clinical trial, many scientists need to support it. This is emphasized when multiple clinical trials are conducted in different parts of the planet.
So, now we understand that not all of these treatments are going through the same number of trials, it would be interesting to see if any of them stands out from the others:
We can easily see which treatments have gained more attention than the others during the pandemic. Again, this doesn’t mean that the others are not promising, but it’s a starting point and now we can simply analyze them.
Let’s do it quickly.
The one clearly standing out is hydroxychloroquine which is undoubtedly the drug of the moment. This old malaria drug was one of the first treatments that proved to be effective against the virus in vitro and is the most used as a treatment by far right now. It is being tested alone or in combination with azithromycin (11 trials), with some questionable outcomes already published.
Between the other drugs in the purple group, we can find the ones that, together with hydroxychloroquine, are part of WHO’s Solidarity mega-trial. These are chloroquine (7), remdesivir (8), ritonavir (12) and lopinavir (11).
On this list, we can also find that the use of stem cells (10) and convalescent plasma (9) is getting some attention, as we have deduced before.
Finally, the other two treatments that stand out are tocilizumab (11) and nitric oxide (NO) (6). While the first one is the only antibody on this list, the second one is being tested because of its previously known antiviral activity.
Where Are They in the Process?
Up to now, we have already selected a primary promising treatment list.
Our next step is to analyze how far they are from becoming effective treatments. We can do that by taking a look at each trials phase:
This last graphic needs more effort to be analyzed than the previous ones. To understand it we should do a small review of the main goals of each phase:
Once we have this in our minds, we can begin.
At first sight, we can see only one dark blue box saying that hydroxychloroquine is the one having most phase III trials going on and the only one with two already in phase IV trials.
As we could see in the table above, this means that hydroxychloroquine is being administered to a large group of patients and is presumed to have some effect on the virus. Some results of these trials have already been published, and in them 78 out of 80 patients recovered successfully using this drug in conjunction with azithromycin. However, the validity of the methods used in this study was quite debatable, as we can see in my previous article.
Another thing coming out of the graphic is that the second most promising treatment seems to be remdesivir, with 5 phase III trials going on.
As we just mentioned azithromycin is mostly used together with hydroxychloroquine, and this puts it out of competition for the third place.
Therefore, this last place on the podium goes to lopinavir and ritonavir (also applied simultaneously). Of course, it is no coincidence that these drugs are the ones that are part of WHO’s mega-trial.
From the entire list we previously created, we can see that only two treatments haven’t gone further than Phase II: nitric oxide and Stem Cells, and maybe we should still add convalescent plasma too. This means that, at least up to this moment, all of them are being tested in small groups of people and none of these trials have shown accurately if they are effective enough to move on to the next phase.
We can also see that chloroquine has only one phase III clinical trial going on, mainly because its place was taken by hydroxychloroquine, which has a better safety profile.
Last but not least, we can observe that tocilizumab also seems to be a promising option. It has 2 phase III clinical trials and also several phase II registered in the database. More than enough to be taken seriously.
These are the Treatments that are Closest to Help Us
This is it! We made it! Now we can build our own “ranking” of treatments that are most capable of saving us in the short term.
Hydroxychloroquine
Hydroxychloroquine+ azithromycin
Remdesivir
Ritonavir + lopinavir
Tocilizumab
Chloroquine
Maybe soon stem cells, convalescent plasma and nitric oxide will prove to be effective and we can add them to the list.
Summary & Final Thoughts
As we could see during our data analysis, once we get the accurate dataset we can explore it until we reach lots of interesting facts. Here are some of them:
- There are 187 proposed clinical trials for treating COVID-19.
- These treatments are of all types.
- 57% are old small molecules and they are included in 61% of the trials.
- Ten of these treatments concentrate 64% of the experiments.
- From that list, hydroxychloroquine is by far the one being more tested and therefore the one with most chances to become a solution in the short term.
- 50% of this same list is part of WHO’s “Solidarity” mega trial.
- We should watch closely treatments with convalescent plasma and tocilizumab, which seem to be taking their first steps towards phase III.
In conclusion, I believe that looking for treatments that have been tested in patients is a good starting criterion to distinguish between the ones that are closer to completion and the ones that need more time to develop.
Starting with that, we now can add some other aspects to the equation, such as the number of trials per drug or the phases in which those trials are. All these combined make us able to get a complete picture of the matter and understand how far we are from an effective treatment.
Source
- National Library of Medicine: Clinical trials on COVID-19. https://clinicaltrials.gov/ct2/results?cond=COVID-19
(Article written by Lic. Julián Fernández and edited by Ed. Candela Capra Coarasa)
