What should you consider when getting a vaccine?

If you told people that there was a safe and effective vaccine for COVID-19 last year at the start of the pandemic, many would have rushed to get it and they would not have cared who made the vaccine or where it came from. Now that there are several safe and effective vaccines with emergency authorization, there is some confusion on which vaccine is the best, and which one to pick. Should you wait for the best vaccine, or take the first one that is available? The answers to these questions can get very technical and can go beyond just looking at the touted vaccine efficacy numbers in mainstream media.

Safety

The two most important traits of any COVID-19 vaccine are its safety and efficacy. Safety is established through an increasing number of patients from Phase 1 to Phase 3 clinical trials. If a vaccine is found to be unsafe in the early studies, it will never get to Phase 3 because no one will use a vaccine that carries substantial risk. The key term here is reasonably safe, as most vaccines will give you a sore arm and some may cause fever. Any deaths during the trials are thoroughly investigated to see if it may be somehow linked to the vaccine. If an experimental vaccine is linked to a significant number of deaths, clinical trials are unlikely to progress further.

Phase 3 trials typically involve thousands to tens of thousands of participants. The number of people recruited depends on the effect that is being looked at. The degree of safety for these kinds of trials makes it unlikely that any severe reaction that occurs more than once out of 1,000 vaccine doses will be missed.

The length of follow-up for safety vaccine recipients is usually set at one to two years before a vaccine is approved for market. With the current pandemic, however, too many people will die if we wait that long before we deploy a potentially effective vaccine. Two million people have already died of COVID-19 in just one year. To address the pandemic emergency, many of the country regulatory authorities have turned to the emergency use authorization designation (EUA).

An EUA allows vaccines for limited use as long as they have demonstrated a minimum clinical efficacy of at least 50 percent and a minimum length of safety follow-up over at least two months. The minimum level of efficacy is set at 50 percent because patient populations that are at higher risk for dying will already substantially benefit from such a vaccine. This benefit is greater than the potentially rare adverse events that may be found later on. For people outside the high-risk groups, the benefit over the risk may still be favorable, but it may also be reasonable to wait for longer safety follow-up or a better vaccine without as high a risk of a bad outcome.

Efficacy

When clinical trials are designed to see how well a vaccine works, the most important value that is measured is the primary outcome. This is the outcome that is measured to determine whether a vaccine works or not, and how well the vaccine works. There are many ways of looking at vaccine efficacy, depending on the primary outcome. The easiest way to measure vaccine efficacy is to see how often someone who gets the vaccine develops clinical disease compared with someone who got a placebo or an inactive ingredient.

Clinical disease means that someone is infected and manifests symptoms of disease. When all infections result in symptoms, vaccine clinical efficacy usually correlates well with the ability of the vaccine to prevent infection. When there are a significant number of asymptomatic infections like in COVID-19, it becomes more difficult to measure a vaccine’s ability to prevent all infection. Since even asymptomatic COVID-19 patients can infect others, the clinical efficacy of any COVID-19 vaccine will not translate into its ability to prevent infection.

Clinical trials for the current Phase 3 vaccines that have been approved for COVID-19 have focused on clinical efficacy to expedite the rollout of an effective vaccine. After someone gets the vaccine or a placebo, the clinical trials investigators instruct the patients to seek care if they develop any COVID-19 symptoms. Only then will they test them to see if they truly have COVID-19. A comparison is made between the number of patients who get COVID-19 in the vaccine group versus the number of patients who get COVID-19 in the placebo group. The vaccine clinical efficacy is derived from this. The vaccine clinical efficacy for preventing any symptomatic clinical disease for the Pfizer vaccine is 95 percent, while for Moderna it is 94 percent. It is 62 percent for the Astra vaccine and 50.4 percent for Sinovac. None of these values reflect the ability to prevent transmission, only the ability to prevent clinical disease.

Beyond prevention of clinical disease, it is also important to think about how well a vaccine prevents severe disease. While Pfizer was able to prevent 95 percent of clinical disease among its vaccinees, it was only able to prevent 89 percent of severe disease compared to placebo. Astra, Moderna, and Sinovac had no cases of severe disease in their vaccinated groups compared to placebo, resulting in a vaccine efficacy of 100 percent for preventing severe disease. No one expects any of these vaccines to perform as well as this in real practice, but if properly used, the vaccine effectiveness on rollout against severe disease will be quite high and will save many, many lives. This is especially true among the most vulnerable groups such as the elderly and frontline healthcare workers among whom up to 10 percent of those infected can die.

Finally, herd immunity is currently not guaranteed for any of the COVID-19 vaccines. To prove transmission interruption, even asymptomatic people will have to be swabbed periodically and asymptomatic infection rates compared between those who were vaccinated versus placebo. This is much harder to demonstrate and will take a longer time. Moderna is doing some of these studies and early data shows that it may block up to 2/3 of transmission of COVID-19. This is less certain for the other vaccines.

To get or not to get vaccinated

There are over 200 vaccines in development and at least 10 have gotten some form of EUA or an equivalent designation. In the Philippines, only the Pfizer vaccine has gotten an EUA. An absolute requirement for the EUA in the Philippines is complete Phase 3 clinical data with a minimum length of safety follow-up. Among the vaccines that have this data are Pfizer, Moderna, Astra, and Sinovac. Pfizer and Moderna have published their results in peer-reviewed journals. Astra has published interim results but it has not published its final clinical trial results. Sinovac recently released partial data from its completed clinical trial in Brazil in a press conference, but the publicly available details remain sparse.

The two vaccines that will most likely get here by the end of February are the Pfizer vaccine and Sinovac. The Pfizer vaccine is via the WHO Covax facility and Sinovac has committed 50,000 doses for the end of February. Only Pfizer, however, currently has an EUA and it is not certain whether Sinovac will get an EUA by then.

Unless you are a frontliner, it is unlikely that you will be offered the vaccine as part of the government program in February. If there is enough supply to cover all frontliners nationwide, the next priority group will be seniors. If you belong to either of these groups, you should take whatever vaccine is offered unless you have a specific contraindication. This is because Pfizer is 95 percent clinically effective and reduces the risk of severe COVID-19 by 89 percent.

If only Sinovac is available, it may still be worthwhile because even though it is only 50.4 percent clinically effective against mild disease, it completely protected against severe disease in the clinical trial population. Remember that high risk groups have a 10 percent chance of dying and so holding out for a better vaccine may be too late.

More vaccines, including Astra and Moderna, may arrive in the second and third quarter of 2021. Both Astra and Moderna completely protected against severe disease in its clinical trials, and clinical efficacy was 62 percent and 94 percent respectively. People who will be eligible for this will include the remaining frontliners and seniors, people with comorbid conditions and essential workers. More shipments of Pfizer and Sinovac may arrive and more vaccines may already be granted EUAs by then. There may also be more data regarding transmission-blocking effects and also which vaccines work best against the new variants.

If you do not belong to the high-risk priority groups, don’t feel bad. The more time there is to observe the effects of the vaccines in a bigger population, the safer it will be for you. You may also have a wider array of vaccines to choose from, and some of them may be safer and more efficacious with a longer duration of protection. In the meantime, it is important to stick to the minimum health standards to decrease the risk of infection and of passing on the disease to other people.

In the end, the kind of vaccine that may be best for you comes down to clinical efficacy, availability, the ability to prevent severe disease, and the risk group you belong to. If you are in a high-risk group, getting the first available vaccine that can protect you from severe disease and dying is paramount. If you are not in the severe risk group, waiting for better vaccines isn’t a bad thing. Either way, the end of the pandemic is in sight so let’s ensure as many of us get there alive and healthy.