I. Overview On January 22, 2020, Acting Health and Human Services Secretary Norris
Cochran declared COVID-19 a national public health emergency, an action that eventually
enabled emergency authorization for free COVID-19 vaccines, testing and treatments. This
public health declaration has been renewed seven times for 90-day intervals, as required
under section 319 of the Public Health Service (PHS) Act. Under this declaration over the
past two years, the US government has provided full support and distribution of COVID-19
vaccines and therapeutics (antibody therapies, remdesivir, and nirmatrelvir/ritonavir),
such that they have been widely available and free of charge to all Americans. Although
these measures have not, by any means, ended the pandemic, it is clear from multiple
epidemiologic modeling studies that they have decreased hospitalizations and saved
hundreds of thousands of lives. They have also led to a narrowing of the profound
morbidity and mortality disparities gap that was seen in minority populations in the
first two waves of the pandemic.

The PROCOVAXED trial was a multicenter study that sought to decrease COVID-19 vaccine
hesitancy and increase COVID-19 vaccine uptake through the use of vaccine messaging
platforms in the emergency department (ED). In this trial, investigators found that
implementation of our COVID-19 messaging platforms (videos, information sheets and
scripted, direct messaging) were associated with greater COVID-19 vaccine acceptance and
uptake among unvaccinated ED patients (Rodriguez RM, Nichol G, Eucker SA, et al. Effect
of COVID-19 Vaccine Messaging Platforms in Emergency Departments on Vaccine Acceptance
and Uptake: A Cluster Randomized Clinical Trial. JAMA Intern Med. 2023;183(2):115-123.
doi:10.1001/jamainternmed.2022.5909).

In January 2022, the investigators extended PROCOVAXED by shifting the focus to
vaccinated ED patients to examine the timely and critically important topic of booster
vaccine hesitancy in underserved ED populations. To better characterize COVID-19 booster
hesitancy, the investigators performed a cross-sectional study at five high-volume,
safety-net hospital EDs in four cities (San Francisco, Philadelphia, Seattle, and Durham,
NC) using survey tools to gather quantitative data on vaccination status, demographic
variables, usual source of care, and attitudes toward booster vaccination. Of 771
participants who had completed their full initial series, 316 (41%) had not received any
booster vaccine. Among these 316 non-boosted participants, 179 (57%, 95% CI 51-62) stated
they would decline or were unsure whether they would accept a booster vaccine if it was
offered to them (i.e., booster-hesitant). Investigators found the following associations
with booster vaccine hesitancy: age 35-49 years vs age 18-34 years (OR 1.16, 95% CI
0.99-1.36); Asian vs White race (OR 0.21, 95% CI 0.05-0.93); Hispanic/Latino vs White
ethnicity (OR 1.59, 95% CI 0.82-3.09); primary language non-English vs English (OR 2.35,
95% CI 1.49-3.71); and Republican vs Democrat party affiliation (OR 6.07, 95% CI
4.21-8.75). The three most common reasons for booster vaccine hesitancy were a preference
to wait for more information (25%), concerns about side effects and safety (24%), and "I
don't need one because I'm fully vaccinated" (20%).

Recognizing the ED as a unique opportunity to address COVID-19 booster vaccine hesitancy
in underserved populations, the investigators will launch the PROmotion of COVID-19
BOOSTer VA(X)ccination in the Emergency Department (PROBOOSTVAXED) trial as an extension
of the PROCOVAXED trial, seeking to increase COVID-19 booster vaccine acceptance and
uptake among vaccinated ED patients. Because of Omicron variant-associated surges during
the COVID-19 pandemic with corresponding research staff illness and ED overcrowding, the
investigators found wide week-to-week fluctuations in enrollment in the PROCOVAXED study.
To reduce this variability of enrollment, the investigators have changed the unit of
randomization from 1-week to 1-day in the PROBOOSTVAXED trial.

As of May 11, 2023, the COVID-19 public health emergency ended. Consequently, not only
are the costs for vaccines, testing, and treatments shifted to health insurers and
patients via commercial payment mechanisms, but COVID-19 vaccines are no longer available
in some EDs. Since our research focuses on the delivery and availability of vaccines to
underserved populations whose only health care access occurs in EDs, the team believes
that this represents a potential barrier to 30-day vaccine uptake in these populations.
The investigators have been informed that only some of the PROBOOSTVAXED study sites will
have COVID-19 vaccines available for distribution in the ED, and this availability is
subject to change throughout the study period. Nevertheless, the team will proceed with
the same research protocol, however, the investigators feel it is important to examine
how ED vaccine availability will affect 30-day vaccine uptake in underserved populations.
They will therefore be performing additional subgroup analyses that compare 30-day
vaccine uptake among sites with available COVID-19 vaccine to those without for the
intervention and control arms.They will also evaluate whether patient costs of vaccines
are a deterrent to acceptance and uptake.

While the sample size calculation for this research is derived from Aim 1, the
investigators emphasize that this is a pragmatic study in which they seek to evaluate the
fluid real-world changes in COVID-19 vaccine availability and funding. As stated above,
there have been (and likely will continue to be) changes in payment for and availability
of vaccines in EDs.

The investigators therefore have developed our protocol and aims below to assess the
impact of these changes.

Aim1: To determine whether implementation of COVID-19 booster vaccine trusted messaging
platforms is associated with increased booster vaccine uptake in ED patients. At five EDs
(Zuckerberg San Francisco General, UCSF Parnassus Medical Center [San Francisco, CA],
Thomas Jefferson University Hospital [Philadelphia, PA], Ben Taub Hospital [Houston, TX],
Duke University Medical Center [Durham, NC]), investigators will conduct a
cluster-randomized controlled trial of the implementation of PROBOOSTVAXED trusted
messaging platforms, with 30-day booster vaccine uptake as the primary outcome and
booster vaccine uptake in the ED as a secondary outcome. Hypothesis: Implementation of
PROBOOSTVAXED trusted messaging platforms in EDs will be associated with increased 30-day
booster vaccine uptake in vaccinated ED patients.

Aim 1a: To determine whether implementation of COVID-19 booster vaccine trusted messaging
platforms in EDs is associated with increased booster vaccine acceptance in ED patients.
For this aim, booster vaccine acceptance in the ED assessed via ED survey will be the
primary outcome. Hypothesis: Implementation of PROBOOSTVAXED trusted messaging platforms
in EDs will be associated with increased booster vaccine acceptance in ED patients.

Aim 2: To determine whether implementation of a protocol in which ED patients are asked
whether they will accept a COVID-19 booster vaccine in the ED is associated with
increased booster vaccine uptake in ED patients. Hypothesis: Implementation of an ED
protocol in which patients are asked whether they will accept a COVID-19 booster vaccine
will be associated with increased 30-day booster vaccine uptake in ED patients.

Aim 3: To compare vaccine uptake (during the index ED visit and 30 days post visit)
between sites that have COVID-19 booster vaccine available and those that do not.

Aim 3a: To compare vaccine acceptance and 30-day uptake among patients with health
insurance versus those without health insurance (evaluating the effects of patient
vaccine cost on acceptance and uptake).

Aim 4: To compare COVID-19 vaccine uptake in this current study with data gathered in our
previous COVID-19 vaccine messaging trial.

General Design: This is a three-arm cluster-randomized controlled trial (CRCT).