Established
Safety Surveillance for Smallpox Vaccine
Smallpox
Vaccine Adverse Events Monitoring Needs (22:V7:17)
Monitoring for
vaccine adverse events in a pre-outbreak vaccination program verses
a post-event outbreak control emergency vaccination program will
be different.
Pre-outbreak
program should focus on assuring the best possible safety profile
for the vaccine, characterize non-serious and serious AE profiles
to assist with post-event response planning, education, etc., identify
all unexpected AEs, instill confidence in program by assuring that
careful monitoring is being done and enhancing strategies to screen
for persons with contraindications to vaccination.
Post-event outbreak
AE monitoring may have to be adjusted to accommodate large numbers
of people being vaccinated in a short period of time. Emergency
response mode, limited resources, must focus on immediate needs
such as identifying most serious AEs that require medical resources.
Pre-Outbreak
Smallpox Vaccine AE Monitoring (22:V7:18)
A
pre-event program has to be as safe as possible as you are vaccinating
people for a disease that doesn’t exist naturally anymore
and for an un-definable risk of future exposure. It should screen
out people who may have potential problems, even if you would normally
allow vaccination in outbreak setting (e.g. people without definite
risk factors but who may have questionable risk factors).
At least in
early stages of program, a pre-event program must have a timely
and responsive system for monitoring in order to pick up problems
quickly. The program must also be able to treat individuals with
limited access medications (VIG) if needed. A successful pre-event
program needs to maintain confidence that authorities are being
as vigilant as possible to assure a safe program.
Additional studies
to define full scope of AEs (common and minor to more serious)
in current, older primarily vaccinated population so that will
have a better idea of what to expect in a post-event emergency
response vaccination program. The pre-event program will also assist
with training and education for post-event response. An opportunity
to “test-run” system in non-emergency setting to identify
needs to address in larger-scale post-event monitoring system is
also an important part of a pre-event program.
The pre-outbreak
setting also provides the opportunity to monitor any adverse events
resulting from the treatment of vaccine adverse events using VIG
or Cidofovir. Thus, we would have a comprehensive safety profiles
on the vaccine and AE treatments.
Safety
Steps at Time of Vaccination (22:V7:19)
In order to
help prevent adverse events from occurring in the first place,
participants should be carefully screened for contraindications.
Participants should be given extensive instructions on contraindications,
adverse events and where to seek evaluation, and site care before
vaccination.
Recognition
of a Problem Individual (22:V7:20)
Given the lack
of experience with smallpox vaccine in most healthcare communities,
even recognizing people who are having adverse events may be difficult.
The key for the pre-outbreak monitoring system is to be overly
sensitive. Vaccinees need to be told that they should have any
unexpected symptoms or serious side effects evaluated by a physician,
and vaccine recipients should be encouraged to report to the vaccination
clinic or healthcare provider if the vaccine site looks worse that
the pictures they are given of the expected vaccine take. Anyone
who develops more than the expected mild systemic illness expected
is also encouraged to call in.
Response
to a Problem Individual (22:V7:21)
When
a significant individual problem is identified/reported, vaccine
safety team personnel should begin an investigation; ensuring that
a VAERS form has been submitted and is filled out completely. More
serious adverse events would be referred to the established CDC
Clinical specialist who can consult on various aspects of vaccine
adverse events. The vaccine recipient is followed until the adverse
event has resolved and then for as long a year after depending
upon the vaccine complication.
Recognition
of a Problem Population [Population: unusual
reactions or high rates] (22:V7:22)
At the national
level, the CDC and the FDA reviews all the VAERS forms submitted
for smallpox vaccine. The CDC also reviews the follow-up information
obtained by the Clinical Consultation team. The CDC routinely calculates
rates and monitors for unusual reactions. This data is further
monitored by an expert committee composed of the Advisory Committee
on Immunization Practices (ACIP), Department of Defense (DoD) members,
and smallpox experts. The vaccination program overall is monitored
by the Institute of Medicine.
Recognition
of a Problem Population Response (22:V7:24)
If a problem
is identified, the CDC will begin an investigation to determine
if this indicates a previously unknown contraindication, or some
issue with screening criteria. This is also an opportunity to review
other possible causes of the condition and to possibly improve
the vaccine. The response includes:
- Identify
groups at risk for VAE; new contraindications, screening for
contraindications not consistent, unavoidable VAEs (e.g. person
with contraindication was also high-risk contact in post-outbreak
setting).
- Determine
if VAEs differ by lot, clinic, etc.
- Determine
if AE resulted from treatment of vaccine reaction (e.g. renal
failure from Cidofovir).
- Investigate
pathophysiology of VAE.
- Develop new,
safer vaccine.
Smallpox
Vaccine Safety Workgroup/Advisory Committee on Immunization Practices
To provide an
additional level of oversight, a committee of clinical experts
can review data on a regular basis in order to monitor the program
and help to formulate medical policy. It is composed of a standing
committee of clinical and public health experts from the CDC’s
immunization advisory group, DoD’s Armed Forced Epidemiology
Board and other designated smallpox experts and specialty consultants.
The workgroup functions as medical monitor for smallpox vaccine
program as IND protocols (VIG and Cidofovir). They review and assess
VAE data from multiple sources (VAERS, Diary Cards, Epidemiology
Studies), as well as AEs associated with IND medications for treatment
of smallpox vaccine AEs.
Post-Outbreak
Smallpox Vaccine AE Monitoring (22:V7:25)
The
ability to monitor AEs in a post-event emergency setting will most
likely be limited and must focus on the more serious adverse events
that require utilization of medical resources. One of the post-outbreak
tasks is adapting pre-existing monitoring system to meet increased
demands and post-event priorities. Since those using the monitoring
system would be more familiar with existing systems, it makes sense
to modify those existing systems than to have people learning a
new system under the duress of an outbreak. Another task is to
establish monitoring system priorities. Identification and immediate
reporting of serious, known AEs requiring hospitalization and/or
treatment (VIG) would be a top priority. Also, the identification
and immediate reporting of serious unexpected AEs would also be
a high priority. Establishing a method and frequency of data communication:
Web-based, Publications, or Daily or weekly totals.
Smallpox
Vaccine Safety System
The
following information is a detailed description of the current,
pre-outbreak responder smallpox vaccine safety monitoring program
in the United States. (22:V7:26-41)
During the early
phases of smallpox vaccination, vaccination clinics and healthcare
providers should report clinically significant and unexpected adverse
events to their state health department. The state health department
will, in turn, report such adverse events to the CDC. A VAERS
report should also be filed for clinically significant and
unexpected adverse events. The VAERS report can be submitted by
the clinic, provider, vaccinee, or state health department. Although
any adverse event can be reported to VAERS, it is most important
to report the clinically significant or unexpected adverse events,
ideally within 48 hours. Clinically significant being; serious
adverse events, events that result in death, hospitalization, permanent
disability, or are life-threatening. Adverse events that prompt
a visit to a healthcare provider may also be considered clinically
significant; however, that is left to the judgment of the healthcare
provider. Adverse events other than unexpected or clinically significant
can be reported to VAERS within 7 days.
Smallpox Adverse
Events to Report:
- Eczema
vaccinatum
- Erythema
Multiforme major/Steven Johnson
- Fetal
vaccinia
- Generalized
vaccinia
- Inadvertent
inoculation
- Myocarditis/pericarditis
- Ocular
vaccinia
- Post
vaccinial encephalitis
- Progressive
vaccinia
- Pyogenic
infection of vaccination site
- Vaccinia
transmission to contacts
- Vaccination
of person with a contraindication
- Other serious
AEs and any AE of concern to a clinician/patient
Reporting
Adverse Events Following Smallpox Vaccine
Anyone can report
to VAERS:
vaccinees, healthcare providers, vaccine manufacturers, and, of
course, state health departments. For smallpox vaccine, state health
departments should make sure that VAERS reports have been filed
for the clinically significant and unexpected adverse events. Reports
can be sent to VAERS via the web, FAX, or mail.
Federal Health
Authorities (CDC) Roles and Responsibilities
Vaccine safety
roles and responsibilities of the different participants in the
vaccine program:
- At the Federal
level, CDC is responsible for tabulating the reported adverse
events, by number and type of adverse event, determining the
reported frequency of known serious adverse events to estimate
whether the reported rates are consistent with the historically
reported rates, and reviewing VAERS reports and information from
the states and providers on a daily basis to monitor for unexpected
adverse events.
- If there
are any unusual adverse events, such as type of event, geographic
location, or population distribution, CDC will conduct special
studies to further investigate any risk factors.
- CDC will
make Vaccinia Immune Globulin or VIG and Cidofovir available
under Investigational New Drug (IND) protocols for selected adverse
events.
CDC provides
technical assistance to state public health authorities to support
the safest possible use of smallpox vaccine. For example, CDC provides
assistance for questions regarding screening, contraindications,
vaccination technique, and adverse events. CDC will also provide
technical consultation to clinicians in the diagnosis and management
of adverse events after smallpox vaccination, especially if the
adverse events are moderate to severe, unexpected, or are not following
an expected clinical course. CDC works directly with the Food and
Drug Administration (FDA) to closely monitor VAERS reports.
State Health
Authorities Roles and Responsibilities
State Health
authorities are responsible for developing a plan to assure monitoring
of adverse events among vaccinees (state-based response team members)
in their state smallpox vaccination program. As part of that plan,
State Health authorities must identify an individual to oversee,
establish, and coordinate state vaccine safety monitoring. State
Health Authorities must communicate with medical organizations,
media, and public on vaccine safety issues before, during, and
after the vaccination program.
Although states
may designate or recommend certain medical facilities for the assessment
of adverse events, in practice, vaccinees could enter the healthcare
system at many points. Therefore, should make sure healthcare providers
are aware of the vaccination program and know who to contact if
they need to assess, refer, or treat a person with a potential
vaccine adverse event.
At the state/local
level a system should be developed for rapid reporting and local
assessment of adverse events in vaccinees or their contacts. This
system should provide coverage for answering questions posed by
vaccinees and clinician 24 hours a day, 7 days a week. This system
should assure prompt reporting to Federal officials (CDC) for clinically
significant and unexpected adverse events; VIG or Cidofovir requests;
and for the clinical outcome following treatment.
Hospital
Roles and Responsibilities
The hospitals
with smallpox response teams must provide follow-up of their own
team vaccinees, including 24/7 coverage for vaccine adverse event
assessment. Hospitals should identify subspecialists to assist
with assessment of suspected adverse events in other persons who
may present for evaluation. Subspecialty categories would ideally
include: Dermatology, Infectious diseases, Neurology, Ophthalmology
and Allergy/Immunology.
Hospital staff
should know the system and requirements for reporting AEs to the
state health authorities and requesting VIG and other treatments
or recommendations for serious AEs. Hospitals should promptly notify
their state health department of any clinically significant or
unexpected adverse events and should submit a case report to the
health department.
Vaccine Clinic
Roles and Responsibilities
Vaccination
clinics should be prepared to treat rare, immediate adverse events,
such as anaphylaxis or syncope. The clinics should be able to educate
vaccinees on vaccination site care, such as with written instructions.
Vaccine clinics should assure that vaccinees have instructions
for follow up, such as for vaccine take checks.The clinics should
know the reporting process for adverse events for their own reporting
purposes, and should also provide vaccinees with information on
who to contact for suspected adverse events. Clinics should keep
track of the number of persons vaccinated. This is helpful for
evaluating clinic operations, monitoring vaccine use, and, for
vaccine safety purposes, it facilitates calculating the rate of
reported adverse events.
Individual
Providers Roles and Responsibilities
Individual health
care providers should at least be able to recognize possible smallpox
vaccine adverse events. Many of the adverse events will be mild
and can be managed by primary care physicians. For moderate, severe,
or unusual adverse events, healthcare providers should know how
to refer patients as clinically indicated to an appropriate specialist.
For clinically significant and unexpected adverse events, the provider
must report to the state health department and to VAERS. If a provider
needs to treat a vaccinee or contact with VIG or Cidofovir, the
provider must seek consultation with Federal authorities and comply
with the IND protocol requirements for the administration of these
medications.
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