Covid-19 Vaccines Mythbusting — Part 3: Why it is not fair to compare vaccines based on efficacy and why you should get the one that is available to you immediately?
Recently, I have watched so many people on news channels and on social media using vaccine efficacy alone as a metric to make a claim that a specific vaccine is better than the other. There is also an emerging hesitancy over vaccines because of recent news and research that point out that vaccinated people may also spread the virus even if they are protected from the virus. I’d like to address these two concerns in this blog post and explain the importance of getting vaccinated as quickly as possible.
A lot of people are still worried about which vaccine to take because they are worried about the efficacy values of the vaccines approved here. Their argument is that the mRNA vaccines will protect us better than the other vaccines that have a higher ‘on paper’ efficacy. Notice that I have mentioned the words ‘on paper’ in quotes and I’ll explain the importance of that later.
There is a slight problem with categorizing some vaccines as good and the rest as bad by using their on paper efficacy rates. This has to do with the lack of knowledge among the public about what the purpose of the vaccines are and why the efficacy rates are not supposed to be the single metric that should be used to decide whether to take a specific vaccine or not.
However, the half-baked news coverage about the results of the clinical trials of various vaccines, the lack of trust between the public and government public health officials, and the general public’s affinity towards WhatsApp forwards from some random people, has implanted a bias among the public against certain vaccines.
A lot of people in the west are reluctant about receiving the Johnson&Johnson vaccine or the Oxford-AstraZeneca vaccine. They want to wait for the Moderna or Pfizer-BioNTech or Novovax vaccines because they believe that the efficacy rate number obtained from the trials is an indicator that the mRNA vaccines are better than the vaccines from Johnson&Johnson, AstraZeneca or Novavax.
So, let us try debunking all that misinformation and try understanding vaccines and the statistics from the trials’ reports.
Before we begin, let us pose the right questions and then try answering them. What is the purpose of mass vaccinations for Covid-19? Is the vaccine efficacy the most important metric when deciding which vaccine we should get? Is it fair to compare vaccines based on their efficacy? Why have governments around the world approved various vaccines from various companies? And why is it important to not worry too much about which vaccine you should get?
Alright. Let us first understand what ‘vaccine efficacy’ means before getting into the details and the comparisons between vaccines.
We must look at how this efficacy value is obtained in the first place.
Once a vaccine is deemed ready for the Phase-3 trials, tens of thousands of people are asked to volunteer for the trials. These volunteers are split into to two groups. One half receives the vaccine, while the others receive a placebo. A placebo is a substance that when given to someone will have no therapeutic value (could be just a saline injection).
However, the volunteers will have no idea whether they received a placebo or a vaccine. The group of people who receive the vaccine form the ‘experimental group’, while the ones who receive the placebo form the ‘control group’.
Once the volunteers have been administered with the vaccine or a placebo, they are asked to go and live their normal lives. The volunteers are monitored regularly for Covid-19 and other side effects. Remember, only the scientists will have access to who has been vaccinated and who has been given a placebo.
So, let us assume that 50000 people volunteered for the trials; 25000 are assigned to the experimental group and the remaining 25000 are assigned to the control group. Basically, it is a 50/50 split. I already mentioned that once the volunteers have received the vaccine or placebo, they are asked to continue their normal routine life and scientists monitor all of them closely.
The scientists notice that, of the 25000 people who received the vaccine, 100 people tested positive for the virus. On the other hand, they also notice that, of the other 25000 who received a placebo, 100 people also tested positive for the virus.
This means that the vaccine has an efficacy of 0. This is because, despite one group receiving the vaccine and the other group not receiving the vaccine, 100 people tested positive for the virus in both the groups. This means that the vaccine was completely ineffective.
Now, let’s consider another scenario for the above mentioned group.
If 100 people from the placebo group tested positive for the virus and no one from the group that received the vaccine tested positive for the virus, then the vaccine has an efficacy of 100%. This is so because no person who received the vaccine tested positive for the virus, while a lot of people who received the placebo tested positive for the virus. In other words, no one who received the vaccine got infected with the virus.
Let us consider another scenario to get things a bit more clear.
If only 5 people who received the vaccine got infected with Covid-19, while 75 people who received the placebo got infected with the virus, then it means that the vaccine’s efficacy is 93.75% or roughly 94%.
The calculation is as follows:
- Total number of people infected = 80
- Number of people who got infected despite receiving a vaccine = 5
- Number of people from the placebo group who got infected = 75
- Percentage of people who got infected despite receiving a vaccine = (5/80)*100 = 6.25%
- Therefore, efficacy = 100% — 6.25% = 93.75% (94% approx)
If the efficacy is 94%, it does not imply that 6 out of every 100 people will be affected by the virus. Statistical metrics only point to a probability most of the time. An efficacy of 94% means that there is only a 6% likelihood for a person to test positive for the pathogen after receiving the vaccine. Now, there are slight nuances with this interpretation, and I will deal with that in a while.
It is important that you understand the process by which the efficacy is calculated, so re-read the above few paragraphs. It is also important to note that after the people are given the placebo or vaccine, they are asked to live their normal lives and are monitored meanwhile. So, the monitoring process does not happen in a lab environment (at least in the Covid-19 vaccines case).
In the case of Moderna’s mRNA vaccine, there were 30,420 volunteers. They were evenly split for the control and experimental groups; 15,210 people received the vaccine, while the other half received a placebo. Of the 30,420 volunteers, a total of 196 people tested positive for Covid-19. 185 of those who tested positive had received a placebo, while 11 people tested positive for the virus despite receiving the vaccine. So, a similar calculation from our example scenario will tell us that Moderna’s vaccine has an efficacy of 94.1%.
Let us now look at the efficacy of the other vaccines that have been approved by many countries:
1. Moderna — 94%
2. Pfizer-BioNTech — 95%
3. Sputnik V — 92%
4. NovaVax — 89%
5. Oxford-AstraZeneca — 67%
6. Johnson&Johnson — 66%
Now, looking at the above numbers might raise the following question in our minds, “Why should we care about the vaccines that have a lower efficacy when there are vaccines with higher efficacies?”.
That seems like a genuine question. To answer that question, we should first ask the question, “Is it fair to compare the efficacies of different vaccines without any context?”.
This is where things get tricky.
Even though the way Phase-3 trials are run and how the efficacy is calculated is the same across all vaccines, the time during which and the place at which the trials are run matters a lot.
Let us take a simple example.
Assume that the population of a city is 1500. In that 1500 people, assume that 800 people are currently infected with Covid-19. So, a company goes to that city, collects 100 volunteers for the phase-3 trials.
The volunteers are split 50/50, meaning 50 people are given the vaccine and 50 people are given a placebo. These people go live their normal lives. Now since, 800 people in that city were already infected when the trials started, the likelihood of the volunteers getting infected with the virus is extremely high. Hence, more people in the control and experiment group will naturally test positive because the chance of contacting the virus is higher.
If the same trial was conducted in a city where only 200 people currently infected with the virus, the likelihood of people who took the vaccine reporting an infection is going to decrease. This is because the chance of a person contacting the virus is lower because the cases are lower.
We know that there are multiple strains of Covid-19 that are spreading now. Some of those strains are more virulent than the other. So, if one vaccine was tested in a place where the less virulent virus was predominant, and the other vaccine is tested in a place where a more virulent strain is predominant, then even if the vaccines are identical, the trials’ results will differ very much.
That is the case with the vaccines that are available now. The Moderna and Pfizer-BioNTech vaccines’ trials were run in the USA when the cases per day was oscillating between 20,000 and 15,000 cases per day. The Johnson&Johnson vaccine trials in the USA were conducted when the number of cases went as high as 75,000 cases per day. In the Johnson&Johnson vaccine trials, there was more opportunity for a volunteer to get infected with the virus than in the case of the Moderna or Pfizer-BioNTech trials.
Also, the Johnson&Johnson trials also included volunteers from other countries like South Africa and Brazil. In countries like South Africa, we know that the strains were much more virulent than the ones in the US. When the trials began for Johnson&Johnson vaccine, we had the B.1.351 variant in South Africa and P.2 variant in Brazil which spread much quickly and are more likely to make the patient sick than the original strand. Close to 67% of the cases reported in the Johnson&Johnson vaccine trials were from the B.1.351 variant.
The Oxford-AstraZeneca trials were also organized when cases were at an all time high in many countries and new variants were emerging.
When the trials for the mRNA vaccines from Moderna and BioNTech-Pfizer, such different variants were not predominant or was not even present in the US.
The vaccine efficacy numbers might vary if the Moderna vaccine’s trials happened at the same time as the Johnson&Johnson vaccine or Oxford-AstraZeneca vaccine trials were run.
This is the reason why I emphasized on ‘on paper’ efficacy numbers, because when comparing vaccines, it isn’t fair.
But the whole point is that, when it comes to the Covid-19 pandemic, the metric called efficacy is not the most important metric at all.
We are looking at the vaccine from just one perspective, whether the vaccine will prevent an infection or not. But that is not the goal of these vaccines.
We must look at the vaccine and its outcomes as a spectrum.
The best vaccine is one that prevents the infection completely, which is great. On the other end of the spectrum is a vaccine that is not effective; meaning, taking it or not will have no outcome. In the middle of the spectrum, we have other outcomes. Some vaccines might not be able to prevent the infection but will prevent you from getting hospitalized or prevent you from death.
That is the point of all the Covid-19 vaccines that I mentioned above. All the vaccines have proven to protect you from any severe illness or hospitalization due to Covid-19. If you take any of the above-mentioned vaccines, you might get infected with Covid-19, but even if you do, it is going to feel like a slight cold or other mild symptoms.
Getting away with a slight cold is much better than getting severely ill and hospitalized. We can say with 100% confidence that all the above-mentioned vaccines will prevent severe illnesses and death due to the virus. For the delta variant, the most virulent variant detected today, most vaccines that have been approved prevent severe illness or hospitalization in at least 95% of the cases.
The vaccines may not completely prevent infection, but it will save all deaths that might be due to Covid-19. This is the number that matters. A 100% protection from severe illness and death matters more than what the efficacy is, and that is key to ending the pandemic.
There is another recent concern among people. In recent times, we’ve been hearing that fully vaccinated people, can still be vectors of transmission.
Yes, that is true.
But, to understand this, we must understand what the term ‘viral load’ means. In simple terms, a viral load is the amount of viral particles present in the infected persons body. It is the using the viral load can we determine the likelihood of transmissibility of the virus by the infected person to another person.
Too many studies show that all the approved vaccines help reduce the viral load in the infected person. Due to this, the vaccinated person is very much protected and may not feel the symptoms, the person still has virus particles in them and can spread the virus when they sneeze or cough. But in comparison to the other unvaccinated people, the fully vaccinated ones are less likely to spread to the virus and be transmission vectors.
So, even if your vaccine has less efficacy, it can not only prevent severe illness, but also heavily reduces the likelihood of the person transmitting the virus to another person. To reduce the transmission even more, it is still recommended to wear a mask, because masks and social distancing are still the best options we have to prevent transmission of the virus. And I don’t see why is it that big a problem for people to wear a mask.
But, another question a person asked me is, “If majority of the people get vaccinated, why is it required to wear a mask if majority of them are protected?“.
This is where we must understand how variants come into existence. I’ll write a detailed post detailing the science behind it, but let me give an abstract view.
Variants come into existence when the virus keep replicating. There are over 300 variants that we know and a lot of these variants are actually less virulent than the original Covid-19 whose genome we sequenced back in January 2020 itself. Some variants have even lost the ability to replicate, so they don’t exist anymore. But a few variants, by chance, have gained the ability to be even more virulent, like the delta variant.
Now we know that the delta variant can replicate more quickly, and higher rate of replication means higher likelihood of us getting a more virulent variant than the delta variant. It is likely that one is already present, I’m not sure.
But how can the vaccines help here? Well, it is known that, irrespective of the variant, all the vaccines help reduce viral load, meaning lesser viral load in people, which leads low amount of replications and lower likelihood of transmission to another person. If the infected person is unvaccinated, then a heavier viral load will be present in that person and that means more virus are replicating. All this means that, by vaccinating ourselves, we reduce the likelihood of a new more virulent variant coming into existence. If we continue wearing masks, then we reduce the transmission even more, hence reduce the likelihood of a new more virulent variant coming into existence.
And this is why it is important to ensure that both low income and high income countries should be vaccinated as quickly as possible.
We are seeing a huge disparity in vaccination rates and availability between high income countries and low income countries. If your country has a high vaccination rate, but African countries don’t, then we leave the possibility of new variants being formed in African countries which will reduce the effectiveness of existing vaccines. So we must quickly vaccinate the entire world as soon as possible or else we leave the door open for new more virulent variants of the virus.
We have a really good understanding of why we are seeing new variants, but for me to explain that, I’ll have to explain a few concepts from molecular biology, so I’ll reserve that for a new post. But, it is very very interesting science, because when we understand it from a molecular level, we also understand the basis for evolution.
Moving on. If the question is, ”Which vaccine will prevent you from getting severe illness due to Covid-19?” or “Which vaccine will prevent a death due to Covid-19?” or “Which vaccine should we take to reduce transmission?”, then it does not matter which vaccine you are taking because in the case of preventing deaths, all the vaccines give the 100% resistance from severe illness and death irrespective of their efficacy is. And the quicker we vaccinate more people, we reduce the likelihood of new variants coming into existence.
We cannot rely totally upon the mRNA vaccines from Moderna and BioNTech-Pfizer because they are costly to manufacture which is a trouble for low-income countries and mRNA vaccines have too many requirements when transporting them. mRNA vaccine technology is fairly new and need to be stored and transported at -20 degree Celsius. These logistical capabilities aren’t currently present in most parts of India and manufacturing requirements for mRNA vaccines aren’t available in most large scale vaccine manufacturers in most low income countries.
The Oxford-AstraZeneca vaccine is extremely cheap and is easy for low-income countries to receive them because their vaccine is easy to transport with normal fridge temperature. In fact AstraZeneca is giving away all these vaccines with net zero profit, which is a great initiative from a large pharmaceutical company when it could have easily capitalized on it.
The Johnson&Johnson vaccine is a game changer because it only requires a single dose unlike the other vaccines and hence it is easier to administer the vaccine a wide range of population quickly.
The goal of the vaccines is to reduce transmission and prevent deaths, not to prevent you from getting the infection. So please, do not worry too much about the efficacy because it is not fair to compare vaccines based on the efficacy values because the data is obtained at different circumstances.
So, the best vaccine is the vaccine that is available to you now immediately, because the quicker you get the vaccine, the easier it is for the entire world to move forward from the pandemic.
P.S: It is likely that you might receive a lot of information on social media that is misleading. It is hard to tackle fake news, but it is possible if we spend a little amount of time to understand the basic science behind any information.
