Supplemental Evidence and Data Request on Safety of Vaccines Used for Routine Immunization in the United States
| Published date | 20 April 2020 |
| Citation | 85 FR 21855 |
| Record Number | 2020-08331 |
| Section | Notices |
| Court | Agency For Healthcare Research And Quality,Health And Human Services Department |
Federal Register, Volume 85 Issue 76 (Monday, April 20, 2020)
[Federal Register Volume 85, Number 76 (Monday, April 20, 2020)]
[Notices]
[Pages 21855-21858]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2020-08331]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Agency for Healthcare Research and Quality
Supplemental Evidence and Data Request on Safety of Vaccines Used
for Routine Immunization in the United States
AGENCY: Agency for Healthcare Research and Quality (AHRQ), HHS.
ACTION: Request for Supplemental Evidence and Data Submissions
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SUMMARY: The Agency for Healthcare Research and Quality (AHRQ) is
seeking scientific information submissions from the public. Scientific
information is being solicited to inform our review on Safety of
Vaccines Used for Routine Immunization in the United States, which is
currently being conducted by the AHRQ's Evidence-based Practice Centers
(EPC) Program. Access to published and unpublished pertinent scientific
information will improve the quality of this review.
DATES: Submission Deadline on or before 30 days after the date of this
publication in the Federal Register.
ADDRESSES:
Email Submissions: [email protected].
Print Submissions:
Mailing Address: Center for Evidence and Practice Improvement;
Agency for Healthcare Research and Quality, ATTN: EPC SEADs
Coordinator, 5600 Fishers Lane, Mail Stop 06E53A, Rockville, MD 20857.
Shipping Address (FedEx, UPS, etc.): Center for Evidence and
Practice Improvement; Agency for Healthcare Research and Quality, ATTN:
EPC SEADs Coordinator, 5600 Fishers Lane, Mail Stop 06E77D, Rockville,
MD 20857.
FOR FURTHER INFORMATION CONTACT: Jenae Benns, Telephone: 301-427-1496
or Email: [email protected].
SUPPLEMENTARY INFORMATION: The Agency for Healthcare Research and
Quality has commissioned the Evidence-based Practice Centers (EPC)
Program to complete a review of the evidence for Safety of Vaccines
Used for Routine Immunization in the United States. AHRQ is conducting
this systematic review pursuant to Section 902(a) of the Public Health
Service Act, 42 U.S.C. 299a(a).
The EPC Program is dedicated to identifying as many studies as
possible that are relevant to the questions for each of its reviews. In
order to do so, we are supplementing the usual manual and electronic
database searches of the literature by requesting information from the
public (e.g., details of studies conducted). We are looking for studies
that report on Safety of Vaccines Used for Routine Immunization in the
United States, including those that describe adverse events. The entire
research protocol is available online at: https://effectivehealthcare.ahrq.gov/products/safety-vaccines/protocol.
This is to notify the public that the EPC Program would find the
following information on Safety of Vaccines Used for Routine
Immunization in the United States helpful:
[ssquf] A list of completed studies that your organization has
sponsored for this indication. In the list, please indicate whether
results are available on ClinicalTrials.gov along with the
ClinicalTrials.gov trial number.
[ssquf] For completed studies that do not have results on
ClinicalTrials.gov, a summary, including the following elements: study
number, study period, design, methodology, indication and diagnosis,
proper use instructions, inclusion and exclusion criteria, primary and
secondary outcomes, baseline characteristics, number of patients
screened/eligible/enrolled/lost to follow-up/withdrawn/analyzed,
effectiveness/efficacy, and safety results.
[ssquf] A list of ongoing studies that your organization has
sponsored for this indication. In the list, please provide the
ClinicalTrials.gov trial number or, if the trial is not registered, the
protocol for the study including a study number, the study period,
design, methodology, indication and diagnosis, proper use instructions,
inclusion and exclusion criteria, and primary and secondary outcomes.
[ssquf] Description of whether the above studies constitute ALL
Phase II and above clinical trials sponsored by your organization for
this indication and an index outlining the relevant information in each
submitted file.
Your contribution is very beneficial to the Program. Materials
submitted must be publicly available or able to be made public.
Materials that are considered confidential; marketing materials; study
types not included in the review; or information on indications not
included in the review cannot be used by the EPC Program. This is a
voluntary request for information, and all costs for complying with
this request must be borne by the submitter.
The draft of this review will be posted on AHRQ's EPC Program
website and available for public comment for a period of 4 weeks. If
you would like to be notified when the draft is posted, please sign up
for the email list at: https://www.effectivehealthcare.ahrq.gov/email-updates.
The systematic review will answer the following questions. This
information is provided as background. AHRQ is not requesting that the
public provide answers to these questions.
Key Questions (KQ)
KQ 1: What is the evidence that vaccines included in the
immunization schedule recommended for adults in the United States
(https://www.cdc.gov/vaccines/schedules/hcp/imz/adult.html) are safe in
the short term (within 42 days following immunization) or long term
(>42 days after immunization)?
[[Page 21856]]
KQ1a. What adverse events (AEs) are collected in clinical studies
(Phases I-IV) and in observational studies containing a control/
comparison group?
KQ1b. What AEs are reported in clinical studies (Phases I-IV) and
in observational studies containing a control/comparison group?
KQ1c. What AEs are associated with these vaccines?
1. For each AE associated with a particular vaccine, what is the
average severity and frequency?
2. For AEs without statistically significant associations with a
particular vaccine, what is the range of possible effects?
3. For each AE associated with a particular vaccine, what are the
risk factors for the AE (including age, sex, race/ethnicity, genotype,
underlying medical condition, whether a vaccine is administered
individually or in a combination vaccine product, schedule of vaccine
administration, adjuvants, and medications administered concomitantly)?
KQ 2: What is the evidence that vaccines included in the
immunization schedules recommended for children and adolescents in the
United States (https://www.cdc.gov/vaccines/schedules/hcp/imz/child-adolescent.html) are safe in the short term (within 42 days following
immunization) or long term (>42 days after immunization)?
KQ2a. What AEs are collected in clinical studies (Phases I-IV) and
in observational studies containing a control/comparison group?
KQ2b. What AEs are reported in clinical studies (Phases I-IV) and
in observational studies containing a control/comparison group?
KQ2c. What AEs are associated with these vaccines?
1. For each AE associated with a particular vaccine, what is the
average severity and frequency?
2. For AEs without statistically significant associations with a
particular vaccine, what is the range of possible effects?
3. For each AE associated with a particular vaccine, what are the
risk factors for the AE (including age, sex, race/ethnicity, genotype,
underlying medical condition, whether a vaccine is administered
individually or in a combination vaccine product, schedule of vaccine
administration, adjuvants, and medications administered concomitantly)?
KQ 3: What is the evidence that vaccines recommended for pregnant
women in the United States are safe in the short term (within 42 days
following immunization) or long term (>42 days after immunization) for
both the woman and her fetus/infant?
KQ3a. What AEs are collected in clinical studies (Phases I-IV) and
in observational studies containing a control/comparison group?
KQ3b. What AEs are reported in clinical studies (Phases I-IV) and
in observational studies containing a control/comparison group?
KQ3c. What AEs are associated with these vaccines?
1. For each AE associated with a particular vaccine, what is the
average severity and frequency?
2. For AEs without statistically significant associations with a
particular vaccine, what is the range of possible effects?
3. For each AE associated with a particular vaccine, what are the
risk factors for the AE (including age, sex, race/ethnicity, genotype,
underlying medical condition, whether the vaccine is administered
individually or in a combination vaccine product, the schedule of
vaccine administration, adjuvants, and medications administered
concomitantly)?
KQ3d. What AEs are associated with these vaccines in the fetus/
infant?
1. For each AE associated with a particular vaccine, what is the
average severity and frequency?
2. For AEs without statistically significant associations with a
particular vaccine, what is the level of certainty?
3. For each AE associated with a particular vaccine, what are risk
factors for the AE (including age, gender, race/ethnicity, genotype,
underlying medical condition, whether vaccine administered individually
or in a combination vaccine product, vaccine schedule of
administration, adjuvants, medications administered concomitantly)?
PICOTS (Populations, Interventions, Comparators, Outcomes, Timing, Settings)
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Domain Inclusion Exclusion
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Population......................... Human participants of all Studies in animals or
ages for whom the vaccines are mechanistic/in vitro studies.
recommended in the United States. Studies exclusively in
populations for whom the vaccine is
not approved or is contraindicated.
Interventions...................... All KQs.............................. Studies of vaccines not on
Individual vaccines included the United States recommended
in the immunization schedule schedules, including brands/
recommended for adults, children and formulations not available in the
adolescents, and pregnant women, as United States, or no longer used.
well as combination vaccines
available in the United States..
Vaccines for adults (KQ1)............
[[Page 21857]]
Hepatitis A (HepA;
Havrix, Vaqta); hepatitis B
(HepB; Engerix-B, Recombivax HB,
HEPLISAV-B); HepA-Hep B
(Twinrix); Haemophilus influenzae
type b (Hib; PedvaxHIB, ActHIB,
Hiberix); human papillomavirus
(HPV, HPV9; Gardasil 9);
inactivated influenza (IIV;
Afluria Quadrivalent, Flucelvax
Quadrivalent, Fluarix
Quadrivalent, Flulaval
Quadrivalent, Fluzone High Dose,
Fluzone Quadrivalent, Fluad);
live attenuated influenza (LAIV;
FluMist Quadrivalent);
recombinant influenza (RIV;
Flublok Quadrivalent); measles,
mumps, rubella (MMR; M-M-R II);
meningococcal (Menactra [MenACWY-
D], Menveo [MenACWY-CRM]);
Meningococcal B (MenB; Bexsero
[MenB-4C], Trumenba [MenB-FHbp]);
pneumococcal conjugate vaccine
(PCV13; Prevnar 13); pneumococcal
polysaccharide vaccine (PPSV23;
Pneumovax); tetanus, diphtheria,
& acellular pertussis (Tdap;
Adacel, Boostrix); tetanus,
diphtheria (Td; TDVAX, Tenivac);
varicella (VAR; Varivax); zoster
(recombinant, RZV; live, ZVL;
Shingrix, Zostavax).
Children and Adolescents (KQ 2)......
Vaccines for children and
adolescents will include
diphtheria, tetanus, & acellular
pertussis (DTaP; Daptacel,
Infanrix); hepatitis A (HepA;
Havrix, Vaqta); hepatitis B
(HepB; Engerix-B, Recombivax HB);
Haemophilus influenzae type b
(Hib; PedvaxHIB, ActHIB,
Hiberix); human papillomavirus
(HPV, HPV9; Gardasil 9);
inactivated polio vaccine (IPV;
IPOL); inactivated influenza
(IIV; Afluria Quadrivalent,
Fluarix Quadrivalent, Flulaval
Quadrivalent, Fluzone
Quadrivalent, Flucelvax
Quadrivalent); live attenuated
influenza (LAIV; FluMist
Quadrivalent); measles, mumps,
rubella (MMR; M-M-R II);
meningococcal (MenACWY-D, Men-
ACWY-CRM; Menactra [MenACWY-D],
Menveo [MenACWY-CRM]);
meningococcal B (MenB; Bexsero
[MenB-4C], Trumenba [MenB-FHbp]);
pneumococcal conjugate vaccine
(PCV13; Prevnar 13); pneumococcal
polysaccharide vaccine (PPSV23;
Pneumovax); rotavirus (RV;
Rotarix, RotaTeq); tetanus,
diphtheria, & acellular pertussis
(Tdap; Adacel, Boostrix);
varicella (VAR; Varivax); DTaP-
HepB-IPV (Pediarix); DTaP-IPV/Hib
(Pentacel); DTaP-IPV (Kinrix,
Quadracel); MMR-V (ProQuad); DTaP-
IPV-Hib-HepB (Vaxelis).
Vaccines for pregnant women (KQ3)....
Hepatitis B (HepB;
Engerix-B, Recombivax HB,
HEPLISAV-B); inactivated
influenza (IIV; Afluria
Quadrivalent, Flucelvax
Quadrivalent, Fluarix
Quadrivalent, Flulaval
Quadrivalent, Fluzone
Quadrivalent); recombinant
influenza (RIV; Flublok
Quadrivalent); tetanus,
diphtheria, & acellular pertussis
(Tdap; Adacel, Boostrix).
Comparators........................ Active comparators (e.g., Studies without
other vaccines or other vaccination intervention comparator.
schedules) and inactive comparators
(e.g., no vaccine).
Outcomes........................... Adverse events identified in Studies reporting only on
participants, and, in the case of effectiveness outcomes.
pregnant women, in their fetuses/
infants (including the presence and
the absence of harms, toxicities,
transient side effects, and
unintended adverse health effects).
Timing............................. Short term (within 30-42 No exclusions apply.
days following immunization) as well
as long term (>42 days after
immunization) effects.
Setting(s)......................... No restrictions with regard
to settings.
Study design....................... Controlled studies Studies without comparator
(randomized and non-randomized (e.g., case studies *).
controlled clinical trials, cohort
studies comparing two or more
cohorts, case-control studies, self-
controlled case series).
Other limiters..................... English language scientific Studies published in
journal publications and trial abbreviated form only (e.g.,
records with published results. letters, conference abstracts).
Studies reported only in
non-English publications.
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* Case studies are outside the scope of the review because they do not include unvaccinated individuals for
comparison.
[[Page 21858]]
Dated: April 15, 2020.
Virginia Mackay-Smith,
Associate Director, Office of the Director, AHRQ.
[FR Doc. 2020-08331 Filed 4-17-20; 8:45 am]
BILLING CODE 4160-90-P
