What does Vaccine Efficacy mean in COVID-19 Vaccine’s Clinical trials?
Understanding the difference between vaccine efficacy and vaccine effectiveness.
Since past couple of weeks, every media channels and sites is bombarded with the news about ongoing vaccine trials. These vaccines may be our key to fight and prevent deadly COVID-19. With the latest update about Pfizer and BioNTech announcing their vaccine (BNT162b2) efficacy rate of 95% (p<0.0001), Moderna announcing efficacy of its vaccine as 94.1% and COVID-19 vaccine developed in the UK by Oxford University and AstraZeneca having 70.4% efficacy, few questions have obviously sparked in the curious minds. What is vaccine efficacy? Is it similar to vaccine effectiveness? And why various vaccines have different results?
Vaccine Efficacy
Generally, for any vaccine to pass approval, it needs to show promising results during the three stages of clinical trials. These trials aim to assess short-term safety, ability to generate an immune response, and efficacy. According to the CDC,
- In Phase I, small groups of people receive doses of the trial vaccine.
- In Phase II, the clinical study is expanded and the vaccine is given to people who have characteristics (such as age and physical health) similar to those for whom the new vaccine is intended.
- In Phase III, the vaccine is given to thousands of people and tested for efficacy and safety.
Sometimes, vaccines may have to undergo Phase IV trials, after the vaccine is approved and licensed.
Efficacy refers to the difference between the people who fell sick after vaccination and those who fell sick without it. It is measured during the Phase III period, where researchers vaccinate some people and give a placebo to others. After that, the test subjects are monitored over several months to see whether the people receiving the vaccine get infected at a lower rate than people who get the placebo, on average. So, suppose a COVID-19 vaccine has an efficacy of, say, 75%. In that case, it implies, if 100 people who were not previously infected by the coronavirus are given the vaccine, on average 75 of them will not get COVID-19. Since, an efficacious vaccine is crucial to preventing further morbidity and mortality, the greater the vaccine efficacy, the greater is the percentage reduction of illness in the vaccinated group.
As per Pfizer, the company had recruited 43,661 volunteers, out of which 170 contracted COVID-19. From the 170 test volunteers, 162 had received placebo and the remaining 8 received the two-dose vaccine. Moderna which earlier received 94.5% efficacy in the preliminary tests results, 95 infections were recorded, two weeks after the volunteers received second dose. Here, only five were in the vaccine group, and the remaining 90 belonged to the placebo group. Meanwhile, the Oxford-AstraZeneca vaccine trials on 23,000 volunteers in Brazil and the UK, had complicated results. Although the AZD1222 or ChAdOx1 nCoV-19 vaccine candidate appeared to be 90% and 62% effective for the two dose regimens having 2,741 and 8,895 individuals in the two groups, respectively.
A WHO (World Health Organization) document released on 9th April noted two success benchmarks for vaccines. The vaccine should have at least a 70% efficacy on a population basis with durability for at least a year for reactive use in an outbreak and/or protection for those with a high ongoing risk. The lower success bar is about 50% efficacy with at least a six-month durability.
The Food and Drug Administration has said that once a vaccine is shown to be safe and at least 50% efficacy, it could be approved for use in the US.
According to a research article by Science, these trials typically focus on a primary endpoint of virologically confirmed, symptomatic disease to capture the vaccine’s direct benefit that forms the basis for regulatory decisions. And secondary endpoints, like infection or viral shedding, provide supporting data, along with analyses of vaccine efficacy in subgroups. It also suggests that to improve the precision of efficacy estimates in high-risk subgroups, regulators could insist for interim analyses to be performed only after a certain number of confirmed disease cases occur in these subgroups, in addition to existing monitoring of the overall number of events in the study. Further, these trials are often double-blinded so the participants don’t know which vaccine they received.
Vaccine Effectiveness
While efficacy is measured during clinical trials, effectiveness is measured when the vaccine is approved for use in the general population. A vaccine’s effectiveness can be influenced by multiple, unpredictable factors like the rate of spread of a virus, the number of people adhering to the optimum dosing schedule and timetable, storage temperature of the vaccine and more. Other important data parameters include vaccine performance for different groups (age, ethnic background, other conditions), duration of protection (duration of immunity and effectiveness against evolving virus strains), the balance of benefit against harms, etc.
No vaccine is 100% effective. This is because there are chances that the given vaccines may not work for a small percentage of people, mainly due to immune suppression. It is also possible that for people who were sheathed by vaccine protection, the vaccine effectiveness may diminish over time. For instance, the measles vaccine has an efficacy of 95-98 percent, however only 96% of the time, the vaccine offers life-long protection.
Takeaway
While most of the vaccine trials are focused on number of people getting sick (Pfizer), they don’t say much about the asymptomatic COVID-19 cases. So, even with 95% efficacy, there is no absolute guarantee of protection for any particular individual. Thus, the fear of transmission still remains. Till now only, AstraZeneca has showed signed of preventing virus transmission. Moreover, the vaccine’s effectiveness matters. For instance, if close to 0% of the US population has been infected by the time a COVID-19 vaccine is ready, computer simulations show that a vaccine could eradicate the virus if the vaccine is at least 70% effective and 75% of the population gets vaccinated. So, if only 5% of the population are infected with coronavirus, an 85% effectiveness could mean an 80% reduction in peak cases even if only 50% are vaccinated. This points out that while vaccines can provide us a chance to fight this pandemic, the success of vaccination programs, speed of vaccine discovery and vaccine effectiveness will play a huge role in minimizing the cases.
