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Research Proposal: Adverse Effect of the Janssen COVID-19 Vaccine

Abhinav Goyal

School of Nursing, University of San Diego

HCI 615: Advanced Health Care Analytics

Dr. Adriana Arcia

May 6, 2023
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Adverse Effect of the Janssen COVID-19 Vaccine

According to Johnson & Johnson (J&J; 2021), the U.S. Food and Drug Administration

(FDA) approved the J&J COVID-19 vaccine, also known as the Janssen vaccine, through an

Emergency Use Authorization (EUA) in February 2021. The J&J vaccine is a single-dose

vaccine, which means recipients only need to receive one dose to be considered fully

vaccinated. The J&J vaccine having one dose also makes it easier to distribute and administer

than the Pfizer and Moderna vaccines, which both vaccines require two doses. The Centers for

Disease Control and Prevention (CDC; 2020a) stated the J&J vaccine may be advantageous for

certain populations, such as those who have difficulty returning for a second dose or accessing

healthcare facilities for follow-up appointments.

According to Billingsley (2022), all three major COVID-19 vaccines (i.e., Pfizer, Moderna,

and J&J) were initially granted EUA. Without complete FDA approval, EUAs permitted the

vaccines’ use during the COVID-19 epidemic. The Pfizer and Moderna COVID-19 vaccines

received full FDA approval on August 23, 2021 and January 31, 2022, respectively. However,

the FDA has limited use of the J&J vaccine to certain individuals due to concerns about rare but

serious blood clotting events. As per the CDC (2020b), reported minor adverse events following

the J&J vaccine include headache, fatigue, muscle aches, and fever, which are common side

effects of many vaccines. These symptoms typically resolve on their own within a few days, and

the benefits of getting vaccinated against COVID-19 far outweigh the risks of adverse events.

The long-term safety and efficacy of the J&J vaccine are not yet fully known given its

permission for emergency use and the expedited research, development, and approval process.

Hence, it is important to monitor and conduct research to identify any potential adverse effects

or unforeseen complications that may arise because of its use. In this paper I focus on

conducting a literature review, identifying any gaps in current knowledge, stating the purpose of

the research, proposing hypotheses to be tested, and presenting of the methods and

discussion.
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Literature Review

According to Oliver et al. (2022), the J&J COVID-19 vaccine has demonstrated high

levels of safety and efficacy in clinical trials and real-world use but there have been reports of

adverse events. In April 2021, the CDC and FDA recommended a pause in the use of the J&J

vaccine due to rare cases of thrombosis with thrombocytopenia syndrome (TTS) and Guillain-

Barré syndrome (GBS) after vaccination. The report indicates a causal relationship between the

J&J vaccine and TTS. As of September 2021, there have been 43 confirmed cases of TTS

identified out of 15 million doses with a higher risk observed in women under 50. In addition,

cases of GBS, a rare muscle weakness disorder causing paralysis, have been reported after

J&J vaccination in men aged 50 years and older. The incidence of GBS was found to be 21

times higher than that observed after a Pfizer or Moderna vaccination. Despite these rare

adverse events, the vaccine was allowed to be used again with additional warnings and

precautions.

See et al. (2021) examined 12 cases of cerebral venous sinus thrombosis with

thrombocytopenia syndrome following vaccination with the Ad26.COV2.S vaccine (J&J) in the

United States. The limitations and gaps in the literature included a small sample size, lack of a

control group, limited generalizability, lack of information on risk factors, and no comparison with

other vaccines. See et al. (2022) examined TTS cases that occurred after COVID-19

vaccination in the United States from December 2020 to August 2021. The study’s limitations

include potential underreporting and incomplete follow-up of TTS cases, which may have led to

an incomplete understanding of the true incidence and outcomes of TTS associated with

COVID-19 vaccination.

Initially, limited data were available for research when studies were conducted soon after

the J&J vaccine was authorized for emergency use. The studies conducted earlier did not

provide a complete understanding of potential adverse effects.

Purpose Statement
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Since the release of the J&J vaccine 2 years ago, more people have been vaccinated;

therefore, a growing pool of data is available for research. The purpose of this study is to

compare and analyze the available data for J&J vaccine for adverse effects and complications.

By identifying and understanding any adverse effects associated with the J&J vaccine, this

study can help address concerns about vaccine safety, provide more information for public

health officials to adjust vaccine recommendations or develop new safety guidelines, and inform

the development of safer and more effective vaccines in the future.

Research Question

With this study, I seek to explore the following research question: What is the incidence

of long-term adverse events (e.g., autoimmune disorders and thrombosis following vaccination)

among individuals 18 years of age or older who have received at least one dose of the J&J

vaccine or booster dose between February 2021 to February 2023 compared to unvaccinated

individuals based on electronic health records (EHR) and vaccine registry data in California?

This study will use a quantitative research design. The null hypothesis for this study is

there is no significant difference in the incidence of long-term adverse events (e.g., disorders,

and thrombosis) between individuals who have received at least one dose of the J&J vaccine or

booster dose and those who have not received any COVID-19 vaccine in California. The

alternate hypothesis would be the incidence of long-term adverse events is lower among

vaccinated individuals compared to unvaccinated individuals.

Conclusion

In summary, researching the adverse effects of the J&J vaccine is important to ensure

the safety of individuals who have received the vaccine, inform public health policy and vaccine

recommendations, increase public confidence in the vaccine, and improve the development of

future vaccines.
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Research Methods

The study design for this research is a quantitative retrospective cohort study. The study

will examine the incidence of adverse events in individuals who received the J&J vaccine or

booster dose compared to those individuals who did not receive any COVID-19 vaccine. Data

for the study will be collected from EHR and vaccine registry databases in California.

Participants

The study will include all individuals aged 18 years or older at the start of the study, who

received one dose of J&J vaccine or booster between February 2021 to February 2023. The

inclusion criteria will also specify participants must have complete medical records available in

EHR data up to 90 days after the vaccination or booster dose. The exclusion criteria include

individuals who have received mRNA vaccines (i.e., Pfizer or Moderna), had preexisting

autoimmune disorders or thrombosis, or have received any other vaccination within 90 days

before or after the date of the J&J vaccination. The participants will be identified from EHR and

vaccine registry data based on the inclusion and exclusion criteria.

Sampling

The study will use a convenience sample, and participants will be identified from EHR

and vaccine registry data based on the inclusion and exclusion criteria. Sample size will be

determined based on the available data in the EHR and vaccine registry databases. The

common identifiers (i.e., date of vaccination), will be used in conjunction with patient or provider

ID to link the EHR and vaccine registry datasets and to remove any duplicate entries.

Instruments

The independent variable for this study is vaccination status. The dependent variable is

the incidence of adverse events identified using ICD-10 codes. The descriptive variables include

age, gender, race/ethnicity, date of vaccination, and medical history (i.e., preexisting conditions

and medications identified by ICD-10 codes). The period from the date of vaccination to
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mortality or booster vaccination (for first dose analysis) or 90 days after vaccination or February

2023, whichever comes first will be measured.

Proper authorization will be obtained for accessing EHR and vaccine registry data from

relevant healthcare organizations or institutional review board and state or local public health

departments or immunization registry. Data for eligible participants will be collected and stored.

Datasets from EHR and vaccine registries will be linked using common identifiers such as

patient ID, name, date of birth along with date of vaccination. The incidence of adverse events

in vaccinated individuals will be compared to that of unvaccinated individuals.

Data Analysis

Descriptive statistics will be used for the demographic characteristics of the study

sample including age, gender, and race or ethnicity. Frequency distributions will be used to

show the percentage of individuals in each category. Means and standard deviations will be

used to describe the central tendency of age and its distribution. The total number of adverse

events in vaccinated and unvaccinated groups will be calculated.

Inferential statistics will be used to compare the incidence of adverse events among

individuals who received the J&J vaccine to those who did not. An independent t-test will be

done to compare the adverse events among people who got the J&J vaccination and those who

did not get any vaccines. A paired t-test will be used to compare vaccination incidence rates

within individuals, indicating whether the J&J vaccine has a significant impact on the incidence

of adverse events within the same individual.

Table 1 will show the mean number of adverse events, standard deviation, and sample

size. When comparing the incidence of adverse events between the vaccinated and

unvaccinated groups, if the independent t-test indicates a statistically significant difference (p-

value less than or equal to 0.05), it would suggest the J&J vaccine may be associated with an

increased risk of adverse events.

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Table 1

t-test

Mean No. of Standard Sample Size

Adverse Deviation
Events
J&J vaccine

No vaccine

J&J vaccine as first dose

J&J vaccine as booster dose

Ethical Considerations

A waiver will be requested from institutional review board for permission to access and

use vaccination data of individuals for this research. After merging the datasets, any personally

identifiable information such as name and social security number will be removed from the data.

This will ensure de-identification of data.

Discussion

The proposed study has several strengths. As the design of the study is a retrospective

cohort, it will be cost effective and time efficient to conduct because the data already exists.

There will be no need to follow up with the participants. Two-year data in the EHR and vaccine

registry databases for California should be enough for the sample.

One major limitation of this study design is the data is prone to bias. As the study will be

conducted using data from California only, findings may not be generalizable to other

populations. The study may be limited by incomplete or inaccurate documentation of medical

records in the EHR or vaccine registry. Finally, the results are not applicable to other COVID-19
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vaccines. The study’s ethical implications are minimal, as all data will be de-identified to protect

participant privacy.

This study will help determine any association between the J&J vaccine and adverse

events. It is important to understand the safety profile of the vaccine as the J&J vaccine has

been authorized for emergency use only. The results of the study will inform healthcare

providers and policymakers on the safety of the J&J vaccine. This study will also help in

evidence-based decision making for future vaccine recommendations. Furthermore, the study

findings may help to reassure individuals who have received the J&J vaccine or booster dose

about its safety.

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References

Billingsley, A. (2022, December). FDA COVID-19 vaccine approval: Live updates on Pfizer,

Moderna, J&J, and more. GoodRx Health.

https://www.goodrx.com/conditions/covid-19/fda-covid-19-vaccine-approval-updates

Centers for Disease Control and Prevention. (2020a, February 11). Overview of COVID-19

Vaccines. https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/

overview-COVID-19-vaccines.html?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov

%2Fcoronavirus%2F2019-ncov%2Fvaccines%2Fdifferent-vaccines%2Fjanssen.html

Centers for Disease Control and Prevention. (2020b, February 11). Selected adverse events

reported after COVID-19 vaccination.

https://www.cdc.gov/coronavirus/2019-ncov/vaccines/safety/adverse-events.html

Johnson & Johnson. (2021, February 27). Johnson & Johnson COVID-19 vaccine authorized by

U.S. FDA for emergency use - First single-shot vaccine in fight against global pandemic.

https://www.jnj.com/johnson-johnson-covid-19-vaccine-authorized-by-u-s-fda-for-

emergency-usefirst-single-shot-vaccine-in-fight-against-global-pandemic

Oliver, S. E., Wallace, M. J., See, I., Mbaeyi, S., Godfrey, M., Hadler, S. C., Jatlaoui, T. C.,

Twentyman, E., Hughes, M., Rao, A. K., Fiore, A. E., Su, J. C., Broder, K. R.,

Shimabukuro, T. T., Lale, A., Shay, D. K., Markowitz, L. E., Wharton, M., Bell, B. P., . . .

Daley, M. F. (2022). Use of the Janssen (Johnson & Johnson) COVID-19 vaccine:

Updated interim recommendations from the advisory committee on immunization

practices — United States, December 2021. Morbidity and Mortality Weekly Report,

71(3), 90–95. https://doi.org/10.15585/mmwr.mm7103a4

See, I., Su, J. C., Lale, A., Woo, E. J., Guh, A., Shimabukuro, T. T., Streiff, M. B., Rao, A. K.,

Wheeler, A. P., Beavers, S. F., Durbin, A. P., Edwards, K. M., Miller, E. T., Harrington,

T., Mba-Jonas, A., Nair, N., Nguyen, D., Talaat, K. R., Urrutia, V. C., . . . Broder, K. R.

(2021). US case reports of cerebral venous sinus thrombosis with thrombocytopenia

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after Ad26.COV2.S vaccination, March 2 to April 21, 2021. JAMA, 325(24), 2448–2456.

https://doi.org/10.1001/jama.2021.7517

See, I., Lale, A., Marquez, P., Streiff, M. B., Wheeler, A. P., Tepper, N. K., Woo, E. J., Broder,

K. R., Edwards, K. M., Gallego, R. C., Geller, A. I., Jackson, K. A., Sharma, S., Talaat,

K. R., Walter, E. B., Akpan, I. J., Ortel, T. L., Urrutia, V. C., Walker, S. C., . . . Shay, D.

K. (2022). Case series of thrombosis with thrombocytopenia syndrome after COVID-19

vaccination—United States, December 2020 to August 2021. Annals of Internal

Medicine, 175(4), 513–522. https://doi.org/10.7326/m21-4502