Policy Update 097

Benefit-Risk Analysis of COVID-19 Vaccination at the Individual Level

YOSHIDA Yasuhiko
Vice Chairman, RIETI

As a main pillar of the fight against the COVID-19 pandemic, vaccination is underway around the world. In Japan as well, the government and medical institutions are actively promoting vaccination based on the argument that generally speaking, although some side effects may be caused by COVID-19 vaccines, they are outweighed by the benefits. In fact, as of July 26, 2021, the number of elderly people in Japan who are fully vaccinated reached 23.53 million people, accounting for 66.3% of the total number of elderly people. Of the total population of Japan, 31.47 million people, or 24.8%, are fully vaccinated (the website of the Prime Minister's Office). As indicated by these numbers, COVID-19 vaccination has made significant progress in Japan, due to efforts by relevant organizations and people.

On the other hand, in many countries where vaccination has made more progress than in Japan, a slowdown of the pace of vaccination on a nationwide basis has been seen. The rate of rise in the vaccination rate has tended to slow down after reaching around 50%, although the figure may vary from country to country (the website of Medical Genome Sciences, Research Institute for Frontier Medicine, School of Medicine, Sapporo Medical University). While there are problems such as difficulty in securing vaccine supplies, media reports indicate that the slowdown mainly reflects the presence of people with a negative attitude toward vaccination. Regarding the situation in Japan as well, the possibility has been pointed out that it will become necessary to promote an initiative to encourage the public, particularly the youth, to receive vaccinations.

Indeed, according to a survey on what sorts of people are likely to feel a reluctance towards vaccination conducted by RIETI Senior Fellow Mr. Yoichi Sekizawa, jointly with Mr. Sora Hashimoto, Dr. Sae Ochi, Professor Mirai So, and Professor Kenzo Denda, a negative attitude toward vaccination tended to be more prevalent among people with low socioeconomic status, people with a distrustful disposition, and people with depressive or anxious tendencies, as well as among women and elderly people (Sekizawa, Hashimoto, Ochi, So, and Denda (2021)). More specifically, the research team conducted an internet survey in late April 2021 and asked unvaccinated participants about their willingness to receive a vaccine, providing three potential answers, namely, "willing to receive," "not willing to receive," and "not decided," and based on the results, the team conducted a multinominal logistic regression analysis. The explanatory variables used in the analysis are gender, age, level of academic education, composition of a cohabiting family, employment status, household income, amount of savings, body mass index (BMI), health status, the most preferred source of information, generalized trust, depressive or anxious tendencies, COVID-19 phobia, and location of residence. The three answer choices were used as outcome variables. Respondents who chose the answer "willing to receive" were used as the reference group.

The results were as follows. First, of the unvaccinated participants (11,637 people), 60.9% were willing to receive vaccination, 30.1% had not yet made a decision, and 9.0% were not willing to receive vaccination. Being female, having a lower level of education, a low household income, and a low amount of savings, a low body mass index, and being depressive or generally anxious were positively associated with the choices "not decided" or "not willing to receive." Older age, living only with a spouse, having hypertension or dyslipidemia, having a trusting disposition, regarding TV (NHK) as the most important source of information on COVID-19, and having a phobia related to COVID-19, were negatively associated with the choices "not decided" or "not willing to receive."

Why are there people who are reluctant to receive a vaccine? The tendency to avoid vaccination, known as "vaccine hesitancy," has been an international topic of discussion since before the COVID-19 pandemic. A report written by a WHO working group pointed out that a theoretical model adopting the 3Cs, or confidence, complacency (the sense of being satisfied with the current, unvaccinated situation) and convenience as the determinant factors of vaccine hesitancy, is useful in understanding the complexity of this problem (WHO Strategic Advisory Group of Experts on Immunization Working Group (2014)). The report also classified the determinant factors of vaccine hesitancy into three categories—(i) contextual influences, (ii) individual and group influences, and (iii) vaccine/vaccination-specific issues—and identified factors in each category. Meanwhile, a pilot survey of European countries in 2014 found that the three greatest factors of vaccine hesitancy are (i) beliefs, attitudes, and motives regarding health and prevention, (ii) risks and benefits of vaccines (risk perception and experiences (empirical rules)), and (iii) communication and the media environment, and that the main challenges are fears about the side effects of vaccines, distrust of vaccines, lack of awareness about the risks of diseases that can be prevented through vaccination, and the impact of negative media reports about vaccination. Regarding COVID-19 as well, it is desirable to conduct an appropriate analysis and formulate appropriate responses by taking advantage of the abovementioned findings.

With respect to vaccine hesitancy concerning COVID-19, this article will discuss a benefit-risk analysis of vaccination, which was raised as an important point of discussion at the WHO working group. More specifically, regarding the argument that vaccination is desirable because the benefits of vaccination outweigh the risks of side effects, which was mentioned at the beginning of this article, there is concern that vaccine hesitancy may be attributable in part to a lack of awareness on sufficient evidenced-based information as to whether vaccination is desirable not only for public health but also for individuals. From the viewpoint of this concern, I will offer my thoughts on evidence, information provision, and communication.

It has been pointed out that there are differences across age groups in terms of the case rate of COVID-19, the serious symptom rate, the mortality rate and the rate of occurrence of vaccine side effects. In the sample of people diagnosed with COVID-19, the serious symptom rate is 80% lower among people aged 10 to 19 and 70% lower among people aged 20 to 29 compared with the rate among people aged 30 to 39. The rates for the 10 to 19 and 20 to 29 age groups are much lower than the rates among people aged 60 to 69 people and 70 to 79, which are 25 times and 47 times higher, respectively, than the rate for the 30 to 39 age group. Regarding mortality rate, in the sample of people diagnosed with COVID-19 since June 2020, the rate among people aged 59 or younger is 0.06%, and in particular, the rates among people aged 10 to 19 and 20 to 29 are much lower (the website of the Ministry of Health, Labour and Welfare).

It is emphasized that achieving herd immunity through vaccination is important for preventing further spread in society. However, given the significant differences across age groups in the benefits gained from vaccination, it is important to make it clear and publicize that the benefits of COVID-19 vaccines outweigh the risks regardless of age at the individual level in order to ensure widespread understanding on that point. At least as far as what can be surmised from information to which this author has had access is concerned, it remained questionable that accurate information as to the balance of benefits and risks for young individuals, for whom the rate of serious symptoms and mortality are generally considered to be low, has been disseminated.

When I investigated this point of discussion, I learned that at a meeting on June 23, 2021, of the Advisory Committee on Immunization Practices (ACIP (Note 1)), held at the U.S. Centers for Disease Control and Prevention (CDC), there was a report based on a comparison of the benefits and risks of messenger RNA (mRNA) vaccines for COVID-19 (Note 2) for the youth that was conducted in reference to the situation in the United States (Wallace and Oliver (2021), Shimabukuro (2021), et al. (Note 3). Below, I will report on interesting data included in that report. With respect to the side effects of vaccination, the United States has introduced the Vaccine Adverse Event Reporting System (VAERS). Under this system, medical personnel are obligated to report on side effects, and parents and patients are also able to submit reports. As a result, if patients complain of side effects, their experiences are fed back directly to the health authorities (the website of the U.S. Department of Health and Human Services).

In the United States, it was reported that Pfizer's mRNA vaccine for COVID-19 provides 95% efficacy against COVID-19 symptoms for people aged 16 or older, while Moderna's equivalent vaccine provides 94.1% efficacy for people aged 18 or older. Meanwhile, regarding the infection situation in the United States, the number of reported infection cases per 100,000 persons was higher among people aged 12 to 29 than among any other age group in the period from April 1 to June 11, 2021, with at least a total of 7.7 million infection cases reported in this age group since the onset of the COVID-19 pandemic (Note 4). Among the infection cases of people aged 12 to 29 in the United States, 2,767 deaths related to COVID-19 were reported (Note 5) (although cases of continued symptoms after the acute period were also mentioned at the ACIP meeting, data concerning those cases are omitted here). At the meeting, a study was introduced, which reports that among 1,597 competitive athletes (affiliated with universities belonging to the Big 10 Conference) with COVID-19 infection, 2.3% were diagnosed with myocarditis related to COVID-19 (Daniels, Rajpal, Greenshields, et al. (2021)) (however, how to treat cases diagnosed at the subclinical level among those cases (two-thirds of the total) is considered as a topic for further discussion by some scholars (Clark, Parikh, Dendy, et al. (2021)).

On the other hand, regarding the side effects of mRNA vaccines for COVID-19, post-vaccination side effects such as dizziness, headache, nausea, fever, fatigue, chills, pain, syncope, sweating and vomiting were reported at the ACIP meeting. Myocarditis and related events, including pericarditis, were identified as adverse events requiring particular consideration in relation to the side effects. It was reported that myocarditis tends to be observed as an acute condition during around the first week after the second shot of an mRNA vaccine, particularly among men aged 29 or younger (Note 6). According to reports regarding post-vaccination myocarditis issued to date, acute symptoms (mostly chest pains) are benign. Although there were many cases of hospitalization, only short-term hospitalization was required in most cases. Indeed, according to data regarding the occurrence of myocarditis and pericarditis as of June 11, of the 484 preliminarily reported cases of myocarditis and pericarditis, 323 cases were confirmed to meet the definition of those conditions as currently applied by the CDC. Of that number, 309 cases were hospitalized, and 295 of them were discharged from the hospital (218 are known to have recovered from their symptoms at the time of the report), with only nine cases still hospitalized (two of them in intensive care units). No deaths were reported (regarding five cases, classification data was not available).

Summarizing the abovementioned situations, Drs. Wallace and Oliver presented the estimation shown below in their report at the ACIP meeting.

Table: Estimated Benefits and Risks to be Gained During a 120-day Period after Vaccination Per Million Shots of the Second dose of mRNA Vaccine for COVID-19
(The figures for avoidance of hospitalization, ICU treatment and death are based on data for the week of May 22.)
Benefits Risks
Sex (age group) Avoidance of COVID-19 infection (cases) Avoidance of hospitalization Avoidance of ICU treatment (cases) Avoidance of death (cases) Myocarditis (cases)
Female (12-17) 8,500 183 38 1 8-10
Male (12-17) 5,700 215 71 2 56-69
Female (18-24) 14,000 1,127 93 13 4-5
Male (18-24) 12,000 530 127 3 45-56
Female (24-29) 15,000 1,459 87 4 2
Male (24-29) 15,000 936 215 13 15-18

In light of the above estimation, Drs. Wallace and Oliver observed that currently, the benefits of the mRNA vaccines for COVID-19 clearly outweigh the risks in the case of the youth while mentioning the need to collect further data and to continue monitoring.

The number of infection cases per 1 million people in the past one month in the United States was four times as high as the number in Japan (the website of Medical Genome Sciences, Research Institute for Frontier Medicine, Sapporo Medical University, School of Medicine). In Japan, in the sample of people diagnosed with COVID-19 since June 2020, the serious symptom rate was around 1.6% and the mortality rate was around 1.0% (0.06% among people aged 59 or younger and 5.7% among people aged 60 or older). In the sample of people diagnosed with COVID-19 in June-August 2020, both the serious symptom rate and the mortality rate were at 0.00% among people aged 10 to 19, while among people aged 20 to 29, the serious symptom rate was 0.03% and the mortality rate was 0.01% (the website of the Ministry of Health, Labour and Welfare). Therefore, in Japan as well, the mRNA vaccines for COVID-19 are expected to bring significant benefits, although they may be less than the benefits indicated by the estimation concerning the results in the United States. On the other hand, there is a suspected causal relationship between mRNA vaccination and myocarditis. In Japan, the occurrence risk of post-vaccination myocarditis is 0.5 cases per 1 million doses in the case of Pfizer's mRNA vaccine for COVID-19 and 1.0 case per 1 million doses in the case of Moderna's equivalent vaccine (Note 7) (Ministry of Health, Labour and Welfare (2021)). As for the specific risks of myocarditis, the symptoms are mild in most cases. In all cases of young males for whom there was a suspected causal relationship between vaccination and myocarditis in Japan, the patients recovered fully or sufficiently to be discharged. In view of the above, with respect to the two mRNA vaccines for COVID-19 now in use in Japan, namely the Pfizer and Moderna vaccines, it may be assumed that at the individual level, the benefits generally outweigh the risks even among younger generations.

In order to overcome vaccine hesitancy, making accurate evidence available, and the methods of providing information to and communicating with the public are important. Given the need for the public to have access to convincing information if the vaccination rate is to rise further, it is important to obtain sufficient understanding of benefit-risk analysis at the individual level, by ensuring that relevant data is fully disseminated. Even though what was reported at the ACIP meeting attracted interest in some quarters in Japan, it is apparently not widely known. Regarding the situation in Japan, updated information on suspected cases of side effects is published in the form of reference materials of the Health Science Council, which summarize reports not only on myocarditis-related events but also on suspected cases of anaphylaxis and other conditions. I hope that information like this will be fully disseminated to the public.

Finally, appropriately providing information to and communicating with the public will become more and more important in the future, and therefore, I will mention matters that may provide useful insights in this respect.

First, at the abovementioned ACIP meeting, experts held discussions, with relevant reference materials published. Moreover, the U.S. Department of Health and Human Services issued a press release on the same day, and leading doctors, nurses, pharmacists, and public health leaders issued a joint statement on the benefits of vaccination as a message to the American people (Levine, Walensky, Stewart, et al. (2021)).

In addition, as Dr. Anthony Fauci, Director of the National Institute of Allergy and Infectious Diseases, pointed out in an interview during a U.S. Public Broadcasting Service program, in order to encourage more people to receive COVID-19 vaccines, it is important that people who can serve as trusted messengers, such as community doctors, healthcare service providers, religious leaders, and community leaders, engage in public communication rather than government officials (an interview with NIAID Director Dr. Fauci).

RIETI Faculty Fellow Professor Fumio Ohtake, (who is also a specially appointed professor at Osaka University), together with Professor Shusaku Sasaki and Dr. Tomoya Saito, conducted research on what sorts of nudge-based (Note 8) messages are effective in strengthening people's willingness to receive COVID-19 vaccines without impeding their autonomous decision-making (Sasaki, Saito and Ohtake (2021)). Specifically, in March 2021, they conducted an online survey with 1,595 respondents in Japan and found that the message "Your vaccination behavior can encourage the vaccination behavior of people around you" is effective in increasing the number of elderly people who are willing to receive vaccines. It was also found that the message "If you do not receive the vaccine, the people around you also may not do so," which conveys similar information to the above messages through loss framing, and the message "X out of 10 people in your age group answered they would receive this vaccine" makes elderly people who were already inclined to receive vaccines more willing to do so. However, the survey also indicated the possibility that messages using loss framing may increase viewers' emotional burden.

In reference materials presented at a meeting of the Health Science Council in October 2020, the Ministry of Health, Labour and Welfare stated: "When proceeding with vaccination, it is necessary to provide information in a way that makes it possible to make decisions regarding vaccination from a comprehensive perspective in view of the risk of COVID-19 infection based on the age, medical records and other attributes of prospective vaccinees in addition to the characteristics of the vaccine." It also stated that regarding the efficacy and safety of the vaccines, efforts should be made to understand the public's perception of the vaccines and obtain widespread public understanding on the importance of vaccination through appropriate and careful communication (Ministry of Health, Labour and Welfare (2020)). I am looking forward to the continuation of successful provision of information and public communication as an important means of dealing with the COVID-19 pandemic.

*The opinions expressed in this column are those of the author alone, and not those of RIETI.

The original text in Japanese was posted on July 27, 2021.

  1. ^ The Advisory Committee on Immunization Practices (ACIP) gives advice and presents proposals to the Secretary of Health and Human Services and the director of the Centers for Disease Control and Prevention.
  2. ^ TBoth of the vaccines for COVID-19 developed by Pfizer and Moderna that are in use in Japan are messenger (mRNA) vaccines.
  3. ^ All reference materials used at the day's meeting are available at the following URL.
  4. ^ Regarding the risk of COVID-19 infection, the situation in the United States does not necessarily apply in Japan, because the situation may be significantly affected by behavior patterns, or other factors.
  5. ^ Regarding the risk of developing serious symptoms after contracting COVID-19 and the risk of death, the situation in the United States does not necessarily apply in Japan, because the risks may be affected by the quality of and access to medical services, and other factors.
  6. ^ Generally speaking, myocarditis is a disease that may cause cardiac symptoms, such as signs of heart failure, chest pains due to pericardium stimulation, heart block, and arrhythmia (Japanese Circulation Society (2009)).
  7. ^ The figures are based on data concerning vaccination of the general public until June 27. The figure for the Pfizer vaccine represents the ratio of reported cases of myocarditis/pericarditis to the total sum of the numbers of first and second injections, 26,238,793 and 12,979,993, respectively, while the figure for the Moderna vaccine represents the ratio of reported cases of myocarditis/pericarditis to the total sum of the numbers of first and second injections, 936,696 and 22,469, respectively.
  8. ^ Regarding nudge theory, the relevant paper cited its definition as "any element of a choice architecture that changes human behavior in a predictable manner without prohibiting choice or significantly changing economic incentives." The report goes on to explain that nudges may contribute to measures to encourage people to voluntarily undergo vaccination, which is a socially desirable choice.

September 2, 2021

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