Two major U.S. pharmaceutical companies racing to develop novel coronavirus vaccines have announced that their vaccines have been confirmed to be over 90% effective. But Masayuki Miyasaka, a leading immunologist at Osaka University, told the Mainichi Shimbun in a recent interview that even after these vaccines become available, he does not plan to receive them for the time being.
At a meeting of the Committee on Health, Labor and Welfare of Japan's House of Representatives on Nov. 17, Miyasaka stated, "There's no doubt that their effectiveness is quite high, but their safety is not guaranteed at all," sounding a word of caution about expectations for the vaccines.
In the following interview, Miyasaka explains how people should interpret a figure of "over 90% effective" and shares his concerns about the vaccines.
Question: Pfizer Inc. and Moderna Inc. both recently announced that their vaccines were over 90% effective. How should we interpret this?
Answer: People tend to misunderstand this. It doesn't mean that if you give the vaccine to 100 people, it will work on 90 of them. "Effectiveness" estimates how much the onset of illness will drop in vaccinated people if you set the rate of infections among unvaccinated people at 1 as a base figure. So "confirmed 90% effective" is equivalent to "90% of people who developed the disease without being vaccinated would not have gotten it had they been vaccinated."
Q: The effectiveness of influenza vaccines is said to be around 30 to 50%. We've heard from experts that it would be difficult to develop a coronavirus vaccine, so it's surprising to hear figures of "over 90%" being touted.
A: I'm also surprised to hear that. I had thought that even if they succeeded in developing a vaccine, it would have around the same level of effectiveness as influenza vaccines, or that it would be limited to preventing serious cases of the disease. But it appears that's not the case. I think we need to pay attention in the future to how such high figures emerged.
Q: During the lower house committee meeting, you said the methods in which clinical trial data of U.S. companies was released was in a "grey zone." What is the problem, specifically?
A: In the international development of vaccines, parties normally have to be extremely careful about releasing interim data from phase 3 trials, which represent the final stage. During phase 3 trials, recipients are divided into two groups, one of which is administered the vaccine and one of which receives a placebo, and neither doctors nor patients are told which is which when vaccinations take place. This is to prevent preconceptions and other forms of bias and confirm the effectiveness and safety of the vaccine. It is known as a "double blind" technique.
Methods of releasing information that speak directly about the results of clinical trials, like how the two firms did recently, are practically forbidden. There is a possibility that doctors and patients in the trial could find out the details, compromising the "blindness" of phase 3. This could affect the decision on whether or not to approve the drug.
The American companies may have thought they could more easily have the vaccines approved by creating the impression from an early stage that their vaccines are effective. Intense competition probably plays a part in this, but if one company does this, then the others will adopt the same approach. It's a cause for concern.
Q: The two firms said that they saw "no serious safety concerns" with the vaccines in early data. What do you think of this?
A: Usually, the frequency of serious side effects from vaccinations is in the range of several cases per million. The scale of the trial is currently in the range of tens of thousands of people, so unless you increase the scale to the hundreds of thousands, you likely won't know the real risks. Looking back on the history of the development of vaccines, only about 4% make it all the way from pre-clinical trials (on animals) to approval. So if there are 100 candidate vaccines, 96 of them will fall by the wayside. But this is not because they were unable to produce antibodies. Even if they are effective in triggering an immune response, the reality is that most of them are rejected due to side effects.
The current phase 3 trials are conducted on people who have not been infected with the novel coronavirus. With vaccines there is a risk of antibody-dependent enhancement (ADE), in which antibodies acquired through past infections or vaccinations behave abnormally, causing the ailment in the patient to become severe. But during phase 3 trials, you can't examine the possibility of ADE -- that can only be done after it goes on sale.
Q: During the lower house health committee meeting, you stated that medical workers should not be given priority in receiving vaccinations. Why is this?
A: This is because if you administer the vaccines to medical workers when the side effects remain unclear, then they could be knocked out before patients, which would make things difficult. When new types of influenza spread, medical workers were vaccinated first, but this was because influenza vaccines have a long history of development, and they know the frequency of side effects. However, when it comes to elderly people, while they have a low level of immunity, it's possible they will not develop major side effects because side effects are produced through an immune response. From that perspective there is significance in giving the elderly higher priority.
I take influenza vaccines, but I won't get the novel coronavirus vaccine for a while even after it becomes available. It's undoubtedly quite effective, but we shouldn't focus on that alone.
When it comes to administering vaccines, probably the most important thing is to give people the right to decide at what stage they should or shouldn't receive the vaccine, respecting individual opinions in light of the risks.
(Interviewed by Ai Yokota, Lifestyle and Medical News Department)