About
The Evidence to Recommendations (EtR) frameworks describe information considered in moving from evidence to ACIP vaccine recommendations.
Summary
Question: Should the Novavax COVID-19 vaccine (2 doses, 5µg antigen + 50µg Matrix-M adjuvant, IM, 21 days apart) be recommended for persons ages 18 years and older under an Emergency Use Authorization?
Population: People 18 years of age and older
Intervention: Novavax COVID-19 vaccine NVX-CoV2373 (2 doses, 5µg antigen + 50µg Matrix-M adjuvant, IM, 21 days apart)
Comparison: No COVID-19 vaccine
Outcomes:
- Symptomatic lab-confirmed COVID-19
- Hospitalization due to COVID-19
- Death due to COVID-19
- Asymptomatic SARS-CoV-2 infection
- Serious Adverse Events (SAEs)
- Reactogenicity grade ≥3
Background
The emergence of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), in late 2019 has led to a global pandemic with dramatic societal and economic impact on individual persons and communities. In the United States, more than 89 million cases and more than 1 million COVID-19-associated deaths have been reported as of July 14, 2022. Persons of all ages are at risk for infection and severe disease. However, the risk for severe illness from COVID-19 is higher in people aged ≥65 years, those living in long-term care facilities, and those with chronic medical conditions. Additionally, there is a disproportionate burden of COVID-19 infections and deaths among racial and ethnic minority communities. Non-Hispanic Black, Hispanic/Latino (Hispanic) and American Indian/Alaska Native persons have experienced higher rates of disease, hospitalization and death compared with non-Hispanic White persons. This is likely related to inequities in social determinants of health that put racial and ethnic minority groups at increased risk for COVID-19, including overrepresentation among essential workers who have higher risk of exposure to COVID-19, lower incomes, reduced access to healthcare, or higher rates of comorbid conditions.
In the United States, the first vaccines to prevent COVID-19 received Food and Drug Administration (FDA) Emergency Use Authorizations (EUA): Pfizer-BioNTech on December 11, 2020, for persons aged 16 years and older, Moderna on December 18, 2020, for adults aged 18 years and older, and Janssen on February 27, 2021, for adults aged 18 years and older. On July 13, 2022, the FDA issued an EUA for the Novavax COVID-19 vaccine, Adjuvanted for the prevention of COVID-19 in persons ages 18 years and older.
Additional background information supporting the interim ACIP recommendation on the use of Novavax COVID-19 vaccine can be found in the relevant publication of the recommendation referenced on the ACIP website.
Problem
| Criteria | Work Group Judgements | Evidence | Additional Information |
|---|---|---|---|
| Is the problem of public health importance? | Yes | COVID-19 is a major global public health threat that dramatically disrupted all sectors of society worldwide. In the United States, COVID-19 has important associated morbidity and mortality.
Incidence:
As of July 14, 2022, there were 89,067,445 COVID-19 cases reported in the United States.1 In June 2022, unvaccinated people ages 5 years and older had 2.8X higher risk of testing positive for COVID-19 compared to people vaccinated with at least a primary series.2
Hospitalization:
Trends in weekly rates of new inpatient admissions by age group in the United States from August 1, 2020 – July 10, 2022, show that higher hospitalization rates occur in older age groups relative to other age groups.3 In May 2022, unvaccinated adults ages 18 years and older had 3.5X higher risk of COVID-19-associated hospitalization compared to people who have received a primary series and ≥1 booster dose.4
Mortality:
As of July 14, 2022, there were 1,018,578 COVID-19-associated deaths reported in the United States.5 In May 2022, unvaccinated people ages 5 years and older had 6X higher risk of dying from COVID-19 compared to people who have received a primary series. Additionally, unvaccinated people ages 12 years and older had 9X higher risk of dying from COVID-19 compared to those with a completed primary series and a booster dose.2
|
Vaccination: As of July 12, 2022, 20,802 total doses were administered with a 7-day average total of 154,423 doses daily.6 Not all people in the U.S. have received the benefits that COVID-19 vaccines provide. About 26–37 million US adults have not yet received a single dose of a COVID-19 vaccine and would benefit from starting a primary series.
|
Benefits and Harms
| Criteria | Work Group Judgements | Evidence | Additional Information |
|---|---|---|---|
| How substantial are the desirable anticipated effects? | Large | Risk of symptomatic COVID-19 and severe COVID-19, used as a surrogate for hospitalization due to COVID-19, were reduced among persons receiving two doses of the Novavax COVID-19 vaccine rather than placebo (GRADE Tables 3a and 3b).
The clinical trial for the Novavax COVID-19 vaccine demonstrated high efficacy of the 2-dose regimen against symptomatic, laboratory-confirmed COVID-19 during a time of Alpha variant predominance.1,2 The overall efficacy was 89.6% (95% Confidence Interval [CI]: 82.4%, 93.8%). Efficacy >75% was observed across age, race, ethnicity, and among those at risk for severe COVID-19.
Four persons in the placebo group and none in the vaccine group experienced severe COVID-19.2 Vaccine efficacy against severe COVID-19 was 100% (95% CI: 0%, 100%). No hospitalizations or deaths due to COVID-19 were reported in the per protocol population.3
Efficacy was assessed a median of 2.5 months after receipt of the second dose.
|
Direct evidence of efficacy against severe outcomes is not expected from Phase III studies. Vaccine efficacy in preventing hospitalizations and deaths may be inferred from observed high efficacy against symptomatic COVID-19. |
| How substantial are the undesirable anticipated effects? | Small |
Risk of serious adverse events was low and similar between the vaccine and placebo groups. Grade ≥3 reactogenicity was increased among persons receiving 2 doses of the Novavax COVID-19 vaccine compared with placebo (GRADE Table 3c and Table 3d). Solicited local and systemic reactions within 7 days after vaccination were frequent and mostly mild to moderate. Solicited reactions were generally more frequent in the younger age group (18-64 years) compared with the older age group (≥65 years) and after dose 2 compared with dose 1. Local reactions were reported by 80.9% of participants ages 18 to <65 years and 61.7% of participants ages ≥65 years, following dose 2. The most frequent local symptom was injection site pain or tenderness (82.2% in ages 18 to <65 and 63.4% in ages ≥65 years). Solicited systemic reactions were reported by 72.1% of participants ages 18 to <65 years and 48.7% of participants ≥65 years, following dose 2. In participants ages 18 to <65 years, the most common solicited systemic reactions after any dose were fatigue (62.0%), headache (52.9%), and muscle pain (54.1%). In participants ages ≥65 years, the most common solicited systemic reactions after any dose were fatigue (39.2%), headache (29.2%), and muscle pain (30.2%). The median onset of systemic reactions was 2 days post-vaccine receipt; reactions resolved after a median duration of 1 day.
Severe (grade ≥3) solicited adverse reactions (pain/tenderness, erythema, and swelling at the injection site; headache, fatigue/malaise, muscle pain, joint pain, fever, and nausea/vomiting) occurred more commonly with the vaccine (16.3%) compared with placebo (4.0%). Generally, grade ≥3 reactions were more commonly reported after the second dose than after the first dose and were more prevalent in younger than older participants.
Serious adverse events were reported in similar proportions among recipients of vaccine (1.0%) and placebo (1.1%); they represented medical events that occur in the general population at similar frequency as observed in the study.
|
Safety data showed an acceptable safety profile.1,2
Post-marketing surveillance will be critical to detect any rare serious adverse events, which were not identified in the clinical trial.
Myocarditis:
In evaluation of potential harms, cases of myocarditis or pericarditis were detected during Novavax COVID-19 clinical trials and reports of myocarditis or pericarditis were identified during postauthorization use of Novavax COVID-19 vaccine in countries outside the United States. These reports underscore the critical importance of ongoing vaccine safety surveillance in the United States and internationally to help assess the possible risk of Novavax COVID-19 vaccine-associated myocarditis or pericarditis. |
| Do the desirable effects outweigh the undesirable effects? | Favors intervention | The Work Group decided that the desirable effects of the Novavax COVID-19 vaccine outweigh the undesirable effects. | |
| What is the overall certainty of this evidence for the critical outcomes? | 1 (high) for prevention of symptomatic COVID-19
3 (low) for hospitalization
1 (high) for SAEs
|
For the critical outcomes, the certainty of evidence was high for prevention of symptomatic COVID-19, low for prevention of hospitalizations due to COVID-19 assessed using the surrogate of severe COVID-19, and high for serious adverse events. For important outcomes, the certainty of evidence was high for reactogenicity. No deaths due to COVID-19 occurred in the per-protocol population of the trial and no data were available to evaluate asymptomatic SARS-CoV-2 infection. |
Values
| Criteria | Work Group Judgements | Evidence | Additional Information |
|---|---|---|---|
| Does the target population feel that the desirable effects are large relative to undesirable effects? | Varies | In a survey designed by the CDC and University of Iowa/RAND Corporation to assess vaccination intentions for a protein-based COVID vaccine with or without adjuvant among unvaccinated Americans, 16% of unvaccinated respondents reported that they “probably” or “definitely” would get an adjuvanted protein-based COVID-19 vaccine. Additionally, vaccination intentions were significantly higher among men (21.9%) than among women (11.9%). However, vaccine intentions did not vary by US region, metropolitan status, age, or education.1
In a survey conducted June 18-23, 2022, among a representative sample of 1,788 unvaccinated U.S. adults, some unvaccinated groups were less adamantly against traditional vaccines than others. Those in urban areas, adults under 35 and Black and Hispanic adults were all less likely than the average unvaccinated American to say they would skip a traditional protein-based vaccine. The survey also picked up on the concern over mRNA technology, as 8% of vaccinated adults and 39% of unvaccinated adults view mRNA vaccines as unsafe. Whereas, nearly 3 in 10 unvaccinated adults view traditional protein-based vaccines as safe.2
|
The survey collected data from January 27 – February 2, 2022, with a sample size of 541 respondents.1 |
| Is there important uncertainty about or variability in how much people value the main outcomes? | Probably important uncertainty or variability | In relation to vaccination intentions for a protein-based COVID vaccine with or without adjuvant among unvaccinated Americans, 52% of unvaccinated respondents reported that they “probably” or “definitely” would not get an adjuvanted protein-based COVID-19 vaccine. Additionally, vaccination intentions were significantly lower among non-Hispanic White adults (9.6%) than among non-Hispanic Black adults (20.1%) or among Hispanic adults (19.5%).1
As it pertains to the Novavax protein-based COVID vaccine survey, 72% of unvaccinated adults reported side effects as their top concern and a major reason why they wouldn’t get a protein-based COVID-19 vaccine. Regarding vaccine safety, 17% of unvaccinated respondents viewed mRNA vaccines as a safer option; and were far less likely than vaccinated adults to view either type of vaccine (i.e., protein-based or mRNA) as safe.2
|
Acceptability
| Criteria | Work Group Judgements | Evidence | Additional Information |
|---|---|---|---|
| Is the intervention acceptable to key stakeholders? | Probably yes | A survey conducted April 13-26, 2022, among a nationally representative random digit dial telephone sample of 1,889 adults ages 18 and older found that personal doctors are the most trusted source for COVID-19 vaccine information, with 85% of adults saying they trust their personal doctor “a great deal” or “a fair amount.”1
CDC works with national, state, tribal, territorial, local, and community partners to promote COVID-19 vaccination. To support these partnerships, CDC has provided funding for organizations, which includes:
CDC also works with the Federal Retail Pharmacy Program to conduct community-based activities and use data to ensure COVID-19 vaccines are accessible in all communities2
Furthermore, impressions from a jurisdictional partner listening session on July 7, 2022, indicate that most participants (19 out of 26) would order Novavax, if it were available, whereas 7 participants were unsure. Participants expressed high interest in support related to Novavax, including:
Intent of use varied substantially, including:
|
Feasibility
| Criteria | Work Group Judgements | Evidence | Additional Information |
|---|---|---|---|
| Is the intervention feasible to implement? | Yes | There are a variety of barriers that are likely to limit the feasibility of implementing the Novavax COVID-19 vaccine including:
The Novavax COVID-19 vaccine is the fourth COVID-19 vaccine with an Emergency Use Authorization (EUA). Although the current recommendation for Novavax is not complex, which solely entails a primary series for individuals ages 18 years and older, the remaining three vaccines (i.e., Moderna, Pfizer-BioNTech and Janssen/Johnson & Johnson) authorized under an EUA entail more complex recommendations including: Moderna EUA
Pfizer-BioNTech EUA
Janssen/Johnson & Johnson EUA
Vaccine storage and handling requirements also influence feasibility. The Novavax COVID-19 vaccine, Adjuvanted is supplied in a carton containing 10 multiple-dose vials. Each multiple-dose vial contains a maximum of 10 doses of 0.5 mL each. Unpunctured multi-dose vials of the Novavax COVID-19 vaccine, Adjuvanted should be stored in a standard refrigerator at 36–46℉ (2–8℃). The vial should be stored in the original carton to protect from light and should not be frozen. After the first needle puncture, the vials should be stored at 36–77℉ (2–25℃) for up to 6 hours. The vial should be discarded if the vaccine is not used within 6 hours after first puncture. Additionally, the vaccine is preservative free and does not require reconstitution or dilution.1 Furthermore, the Novavax COVID-19 vaccine, Adjuvanted vial and carton do not have an expiration date. To find the expiration date, access www.NovavaxCovidVaccine.com, navigate to the United States Healthcare Professional section of the website, and enter the lot number printed on the carton or vial into the “Expiry Date Checker” tool.2 Financial barriers to receiving the Novavax COVID-19 vaccine will be reduced because the vaccine is being provided free of charge to the U.S. population. However, health systems or health departments could incur costs for COVID-19 vaccine implementation, clinics, outreach, and education. Furthermore, financial hardship may arise if vaccine recipients need to take time off to receive the vaccine or experience post-vaccination reactogenicity that prevents them from working. Vaccine supply in the United States is sufficient for implementation of the intervention. As of July 13, 2022, over 599 million doses of COVID-19 vaccine have been administered in the United States, demonstrating that the vaccine per se is feasible to implement broadly.3 Purchase of Novavax COVID-19 vaccine includes 3.2 million doses to date, with intent to distribute following ACIP recommendation. In regard to qualitative logistical comparisons of Novavax COVID-19 vaccine with current COVID-19 vaccines, there are logistical advantages and disadvantages of Novavax. Relative logistical advantages of Novavax COVID-19 vaccine entail:
Relative logistical disadvantages of Novavax COVID-19 vaccine entail:
|
Equity
| Criteria | Work Group Judgements | Evidence | Additional Information |
|---|---|---|---|
| What would be the impact of the intervention on health equity? | Probably no impact | Disparities in COVID-19 outcomes are both a manifestation of longstanding inequities and a contributor to continued and future inequities. We need to do everything we can to reduce health inequities – this is fundamental to our mission in public health. No single vaccine has the ability to overcome all disparities. Neither the vaccine under discussion (i.e., Novavax), nor any other single vaccine. It is critical to continue to investigate persistent health inequities and do everything necessary to resolve them. Any inequity in COVID-19 vaccine access or use has the potential to further exacerbate disparities in COVID-19 disease impact. 1,2
Assessing the risk for COVID-19 infection, hospitalization, and death by race and ethnicity as presented in age-adjusted rate ratios from various data sources including state and territorial jurisdictions, COVID-NET, the National Center for Health Statistics (NCHS) and the National Vital Statistics System (NVSS) show that American Indian and Alaska Native, Black, and Hispanic or Latino persons have elevated risk of COVID-19 cases, hospitalizations and death compared to White, non-Hispanic persons.3
As it pertains to data from the May 2022 National Immunization Survey-Adult COVID-19 Module on the percent of adults ages 18 years and older who report not yet receiving a COVID-19 vaccine by race and ethnicity, 22% of persons of other or multiple races, 20% of persons who are American Indian or Alaska Native persons, 14% of persons who are Hispanic and 14% of persons who are White have yet to receive a COVID-19 vaccine. Looking at the same data from the National Immunization Survey on US adults by metropolitan statistical area, a higher percentage of US adults living in rural areas remain unvaccinated as compared to those living in suburban and urban areas. Furthermore, a higher percentage of US adults with incomes <$75,000 or living in poverty have not yet received a COVID-19 vaccine compared to adults with higher incomes. Additionally, a higher percentage of US adults who do not have a regular primary care provider or health insurance have not yet received a COVID-19 vaccine compared to those with a regular provider and those who are insured. These are both markers of access to health care.4
According to the December 2021 U.S. Census Bureau Household Pulse Survey, adults who had not received any doses of the COVID vaccine differed from those who had received at least one dose of a COVID vaccine across several measures. Unvaccinated adults were younger, had lower levels of education, were more likely to be non-White, were more economically disadvantaged and were more likely to report a disability.5
In an effort to make advancements toward vaccine equity for all, in 2020, CDC launched the Partnering for Vaccine Equity program focused on increasing equity in adult immunization. Through the Partnering for Vaccine Equity program and broader adult immunization efforts, CDC aims to improve equity in adult immunization across disproportionately affected populations, including racial and ethnic minority groups, individuals living with disabilities, rural communities, older adults, individuals with chronic conditions, and more through partnerships that drive community-level action. The partner network includes 500+ total partners and 300+ local chapters, affiliates, and community-based organizations located in 225+ cities in 50 states. Individuals can visit the Partnering for Vaccine Equity’s Home | Vaccine Resource Hub to access hundreds of free and accurate educational materials to support COVID-19 vaccination in their community.6
|
Work Group Interpretation Summary
Novavax COVID-19 vaccine had high efficacy against symptomatic COVID-19 disease in settings of Alpha predominance. However, there were reports of myocarditis after Novavax COVID-19 vaccine during clinical trial and early post-authorization data. Based on available data, vaccine efficacy or myocarditis rates for Novavax and mRNA COVID-19 vaccines cannot be directly compared. However, post-authorization monitoring for both vaccine efficacy and safety will be important. All things considered, vaccination remains the best way to protect against SARS-CoV-2 and rare cardiac risks of COVID-19 disease.
As always, the top priority remains vaccination of unvaccinated individuals. An additional COVID-19 vaccine, utilizing traditional vaccine technology, will provide an additional option for unvaccinated individuals. Overall, the benefits of Novavax COVID-19 vaccine outweigh the risks.
Balance of consequences
Desirable consequences probably outweigh undesirable consequences in most settings.
Is there sufficient information to move forward with a recommendation? Yes.
Draft recommendation (text)
On July 19, 2022, ACIP voted (12-0) in favor of recommending:
A two-dose Novavax COVID-19 vaccine, adjuvanted primary series for persons ages 18 years and older under the EUA issued by FDA
Final deliberation and decision by ACIP
Final ACIP recommendation
ACIP recommends the intervention.
The Novavax COVID-19 vaccine is recommended for individuals ages 18 years and older under an Emergency Use Authorization.
References
Problem:
- CDC COVID Data Tracker. https://covid.cdc.gov/covid-data-tracker/#trends_dailycases Accessed July 14, 2022
- CDC COVID Data Tracker. https://covid.cdc.gov/covid-data-tracker/#rates-by-vaccine-status Accessed July 15, 2022
- Unified Hospital Dataset: https://covid.cdc.gov/covid-data-tracker/#new-hospital-admissions Accessed July 13, 2022
- CDC COVID Data Tracker. https://covid.cdc.gov/covid-data-tracker/#covidnet-hospitalizations-vaccination Accessed July 11, 2022
- CDC COVID Data Tracker. https://covid.cdc.gov/covid-data-tracker/#trends_dailydeaths Accessed July 13, 2022
- CDC COVID Data Tracker. https://covid.cdc.gov/covid-data-tracker/#vaccination-trends Accessed July 18, 2022
Benefits and harms:
- Food and Drug Administration (FDA). FDA briefing document Novavax COVID-19 vaccine. https://www.fda.gov/media/158912/download. Accessed June 7, 2022.
- Grading of Recommendations, Assessment, Development, and Evaluation (GRADE): Novavax COVID-19 Vaccine for Adults Aged ≥18 Years. Grading of Recommendations, Assessment, Development, and Evaluation (GRADE): Novavax COVID-19 Vaccine | Advisory Committee on Immunization Practices (ACIP) | CDC.
- Novavax, 2022 personal communication, May 11 – June 3, 2022.
Values:
- CDC and University of Iowa/RAND survey, unpublished
- Morning Consult. July 5, 2022. Novavax Protein-Based COVID Vaccine Survey. https://morningconsult.com/2022/07/05/novavax-protein-based-covid-vaccine-survey/ Accessed July 18, 2022
Acceptability:
- KFF COVID-19 Vaccine Monitor (April 13-26, 2022). https://www.kff.org/coronavirus-covid-19/poll-finding/kff-covid-19-vaccine-monitor-april-2022/ Accessed July 7, 2022
- CDC. COVID-19 Vaccine Equity for Racial and Ethnic Minority Groups. www.cdc.gov/coronavirus/2019-ncov/community/health-equity/vaccine-equity.html Accessed July 7, 2022
Feasibility:
- Novavax HCP Fact Sheet 07132022 (fda.gov). Accessed July 14, 2022
- CDC. Novavax COVID-19 Vaccine Adjuvanted FAQs for CDC
- CDC COVID Data Tracker. https://covid.cdc.gov/covid-data-tracker/#vaccinations_vacc-total-admin-rate-total Accessed July 18, 2022
Equity:
- CDC Newsroom. Media Statement from CDC Director Rochelle P. Walensky, MD, MPH, on Racism and Health. www.cdc.gov/media/releases/2021/s0408-racism-health.html
- CDC. COVID-19 Vaccine Equity for Racial and Ethnic Minority Groups. www.cdc.gov/coronavirus/2019-ncov/community/health-equity/vaccine-equity.html
- CDC. Risk for COVID-19 Infection, Hospitalization, and Death by Race/Ethnicity. www.cdc.gov/coronavirus/2019-ncov/covid-data/investigations-discovery/hospitalization-death-by-race-ethnicity.html Updated June 24, 2022. Accessed July 14, 2022
- COVIDVaxView. Estimates produced by NORC at the University of Chicago using CDC's National Immunization Survey-Adult COVID-19 Module (NIS-ACM). www.cdc.gov/vaccines/imz-managers/coverage/covidvaxview/interactive/adults.html Accessed July 14, 2022
- United States Census Bureau. Who Are the Adults Not Vaccinated Against COVID? https://www.census.gov/library/stories/2021/12/who-are-the-adults-not-vaccinated-against-covid.html Accessed February 24, 2022
- CDC Vaccines & Immunizations. Equity in Adult Vaccination. www.cdc.gov/vaccines/health-equity/index.html Accessed July 1, 2022