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[Federal Register Volume 89, Number 228 (Tuesday, November 26, 2024)]
[Notices]
[Pages 93293-93296]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2024-27679]

[[Page 93293]]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Agency for Healthcare Research and Quality

Supplemental Evidence and Data Request on Prehospital EMS Blood 
Transfusion and Fluid Interventions for Hemorrhagic Shock

AGENCY: Agency for Healthcare Research and Quality (AHRQ), HHS.

ACTION: Request for Supplemental Evidence and Data Submission

-----------------------------------------------------------------------

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 Prehospital EMS 
Blood Transfusion and Fluid Interventions for Hemorrhagic Shock, 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 Access to published and unpublished pertinent 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 December 26, 2024.

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: Kelly Carper, Telephone: 301-427-1656 
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 Prehospital EMS Blood 
Transfusion and Fluid Interventions for Hemorrhagic Shock. AHRQ is 
conducting this review pursuant to Section 902 of the Public Health 
Service Act, 42 U.S.C. 299a.
    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 Prehospital EMS Blood Transfusion and Fluid 
Interventions for Hemorrhagic Shock. The entire research protocol is 
available online at: https://effectivehealthcare.ahrq.gov/products/ems-blood-transfusion/protocol.
    This is to notify the public that the EPC Program would find the 
following information on Prehospital EMS Blood Transfusion and Fluid 
Interventions for Hemorrhagic Shock helpful:
    [ssquf] A list of completed studies that your organization has 
sponsored for this topic. 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, if 
relevant: 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 topic. In the list, please provide the 
ClinicalTrials.gov trial number or, if the trial is not registered, the 
protocol for the study including, if relevant, 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 topic 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 topics 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://effectivehealthcare.ahrq.gov/email-updates.
    The 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

    a. What are the benefits and harms of transfusion of whole blood 
for patients requiring prehospital hemorrhagic shock resuscitation?
    b. Are the benefits and harms modified by:
    i. EMS protocols (including but not limited to transfusion volume, 
adjuvant medication coadministration such as tranexamic acid [TXA] and 
calcium salts, or crystalloid fluid coinfusion; transfusion equipment, 
and transfusion route)?
    ii. Patient characteristics (including but not limited to age, sex, 
comorbidities, preexisting medications [anti-platelets, anti-
coagulants, heart rate control medications], or mechanism of injury/
condition)?
    iii. Characteristics of the EMS system (including air/helicopter 
medical ambulance, ground ambulance, EMS clinician certification, or 
service delivery model [such as fire-based, private, third service], 
and logistics related to blood administrations [intercept model, blood 
stored on ambulance])?

KQ 2

    a. What are the benefits and harms of transfusion of PRBCs for 
patients requiring prehospital hemorrhagic shock resuscitation?
    b. Are the benefits and harms modified by:
    i. EMS protocols (including but not limited to transfusion volume, 
adjuvant medication coadministration such as TXA and calcium salts, or 
crystalloid fluid coinfusion; transfusion equipment, and transfusion 
route)?
    ii. Patient characteristics (including but not limited to age, sex, 
comorbidities, preexisting medications [anti-platelets, anti-
coagulants, heart rate control medications], or mechanism of injury/
condition)?
    iii. Characteristics of the EMS system (including air/helicopter 
medical ambulance, ground ambulance, EMS clinician certification, or 
service delivery model [such as fire-based, private, third service], 
and logistics related to blood administrations [intercept model, blood 
stored on ambulance])?

KQ 3

    a. What are the benefits and harms of transfusion of plasma for 
patients

[[Page 93294]]

requiring prehospital hemorrhagic shock resuscitation?
    b. Are the benefits and harms modified by:
    i. EMS protocols (including but not limited to transfusion volume, 
adjuvant medication coadministration such as TXA and calcium salts, or 
crystalloid fluid coinfusion, transfusion equipment, and transfusion 
route)?
    ii. Patient characteristics (including but not limited to age, sex, 
comorbidities, preexisting medications [anti-platelets, anti-
coagulants, heart rate control medications], or mechanism of injury/
condition)?
    iii. Characteristics of the EMS system (including air/helicopter 
medical ambulance, ground ambulance, EMS clinician certification, or 
service delivery model [such as fire-based, private, third service], 
logistics related to blood administrations [intercept model, blood 
stored on ambulance])?

KQ 4

    a. What are the benefits and harms of infusion of crystalloid 
fluids for patients requiring prehospital hemorrhagic shock 
resuscitation?
    b. Are the benefits and harms modified by:
    i. EMS protocols (including but not limited to volume infused, or 
adjuvant medication coadministration such as TXA and calcium salts, or 
transfusion equipment and transfusion route)?
    ii. Patient characteristics (including but not limited to age, sex, 
comorbidities, preexisting medications [anti-platelets, anti-
coagulants, heart rate control medications], or mechanism of injury/
condition)?
    iii. Characteristics of the EMS system (such as air/helicopter 
medical ambulance, ground ambulance, personnel certification, or 
service delivery model [such as fire-based, private, third service], 
and logistics related to blood administrations [intercept model, blood 
stored on ambulance])?

KQ 5

    a. What are the benefits and harms of different strategies 
(therapeutic, logistical, or both combined) and interventions (whole 
blood, PRBCs, plasma, and crystalloid fluid) for patients requiring 
prehospital hemorrhagic shock resuscitation?
    b. Are the benefits and harms modified by:
    i. EMS protocol (including but not limited to transfusion volume, 
adjuvant medication coadministration such as TXA and calcium salts, or 
crystalloid fluid coinfusion, and transfusion equipment and transfusion 
route)?
    ii. Patient characteristics (including but not limited to age, sex, 
nature of illness, comorbidities, preexisting medications [anti-
platelets, anti-coagulants, heart rate control medications], or 
mechanism of injury/condition)?
    iii. Characteristics of the EMS system (including air/helicopter 
medical ambulance, ground ambulance, EMS clinician certification, or 
service delivery model [such as fire-based, private, third service], 
logistics related to blood administrations [intercept model, blood 
stored on ambulance])?

KQ 6

    What specific areas of future research are essential for closing 
existing evidence gaps surrounding prehospital hemorrhagic shock 
resuscitation and prehospital blood transfusion? What are the precise 
scientific questions, optimal study designs, targeted study 
populations, and the various transfusion intervention protocols that 
need to be studied?

Contextual Question (CQ)

CQ 1

    What are the barriers to and facilitators of implementation of 
effective prehospital blood product transfusion programs utilizing a 
systems-level approach? Barriers and facilitators could include EMS 
agency costs, EMS agency reimbursement, cost effectiveness, blood 
product maintenance and logistics, partnerships with blood banks, 
medical oversight including real-time medical direction, and diagnostic 
tools.

PICOTS (Populations, Interventions, Comparators, Outcomes, Timing, and 
Setting)

                       Preliminary PICOTS Criteria
------------------------------------------------------------------------
                                                            Exclusion
            PICOTS                Inclusion criteria        criteria
------------------------------------------------------------------------
Populations...................   Patients       
                                 requiring prehospital   Individuals who
                                 hemorrhagic shock       do not require
                                 resuscitation treated   prehospital
                                 in the prehospital      hemorrhagic
                                 setting by emergency    shock
                                 medical services        resuscitation.
                                 clinicians.            
                                                         Individuals not
                                                         treated by
                                                         emergency
                                                         medical
                                                         services
                                                         clinicians.
Intervention..................   KQ1: whole      Other
                                 blood.                  types of
                                                         resuscitation.
                                 KQ2: PRBCs...
                                 KQ3: plasma
                                 (e.g., fresh frozen,
                                 liquid, dried, etc.).
                                 KQ4:
                                 crystalloid fluids.
                                 KQ5:
                                 strategies as
                                 specified in each
                                 publication.
                                 KQ6: NA......
                                 CQ1: NA......
Comparator....................   KQ1 to 4.....   KQ1 to
                                                         KQ5: no
                                                         comparison.
                                   [cir] Head-to-head
                                    comparisons
                                    between
                                    transfusion
                                    options to treat
                                    prehospital
                                    hemorrhagic shock
                                    patients.
                                   [cir] Comparison to
                                    usual care as
                                    specified in each
                                    publication in
                                    another group or
                                    time period.
                                 KQ5:
                                 strategies as
                                 specified in each
                                 publication.
                                 KQ6: NA......
                                 CQ1: NA......
Outcomes......................  Patient Health           Cost-
                                 Outcomes (highest       effectiveness,
                                 priority).              other outcomes.
                                 Mortality/
                                 survival.
                                   [cir] To arrival at
                                    hospital.
                                   [cir] To hospital
                                    discharge.
                                   [cir] Any period
                                    less than or equal
                                    to 30 days post-
                                    emergency.
                                 Morbidity
                                 after discharge.

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                                   [cir] Glasgow
                                    Outcome Scale,
                                    Glasgow Outcome
                                    Scale Extended,
                                    Modified Rankin
                                    Scale, Cerebral
                                    Performance
                                    Category.
                                 Length of
                                 stay.
                                   [cir] Hospital free
                                    days.
                                   [cir] ICU free days
                                Intermediate Outcomes
                                 in the prehospital or
                                 ED setting.
                                 Physiological
                                 indicators (including
                                 but not limited to
                                 the following).
                                   [cir] Systolic
                                    blood pressure.
                                   [cir] Diastolic
                                    blood pressure.
                                   [cir] Mean arterial
                                    pressure.
                                   [cir] Heart rate...
                                   [cir] Respiratory
                                    rate.
                                   [cir] Respiratory
                                    failure.
                                   [cir] ROSC.........
                                   [cir] Shock index..
                                   [cir] Body
                                    temperature.
                                   [cir] End tidal CO2
                                    (EtCO2).
                                   [cir] Level of
                                    Consciousness.
                                     [ssquf] GCS......
                                     [ssquf] AVPU.....
                                   [cir] Blood lactate
                                    level.
                                Process Outcomes......
                                 Time from EMS
                                 arrival to initial
                                 transfusion of blood
                                 product or infusion
                                 of crystalloid fluid.
                                 Amount of
                                 blood product
                                 transfused or
                                 crystalloid fluid
                                 infused (total:
                                 prehospital and
                                 hospital) vs.
                                 (hospital only).
                                Adverse Events/Harms
                                 (including but not
                                 limited to the
                                 following).
                                 Allergic
                                 reaction.
                                 Febrile
                                 nonhemolytic reaction.
                                 Acute
                                 hemolytic reaction.
                                 Transfusion-
                                 related acute lung
                                 injury [TRALI].
                                 Transfusion-
                                 associated
                                 circulatory overload
                                 [TACO].
                                 Infection....
                                 Fluid
                                 overload.
                                 Citrate
                                 toxicity.
                                 Delay to
                                 definitive care based
                                 on arrival time.
                                
                                 Isoimmunization.
                                 Hemolysis....
                                 Harms related
                                 to the method of
                                 administration.
                                 Risk of
                                 clotting when
                                 Ringer's lactate
                                 solution combined
                                 with blood.
Timing........................   Outcomes up    
                                 to 30 days post-        Outcomes more
                                 injury.                 than 30 days
                                                         post-injury.
Setting.......................   Prehospital..   ED.
                                 US and         
                                 International studies   Inpatient,
                                 published in English    surgery.
                                 language from Very      Studies
                                 High and High HDI \a\   conducted in
                                 countries..             countries rated
                                                         less than High
                                                         in the HDI \a\.
Study Design..................   RCTs.........  
                                                         Systematic
                                                         reviews (we
                                                         will use
                                                         reference lists
                                                         to identify
                                                         studies for
                                                         possible
                                                         inclusion).
                                 Prospective     Case
                                 comparative studies.    series.
                                 Retrospective  
                                 comparative studies.    Descriptive
                                                         studies.
                                 Case control    Letters
                                 studies.                to the editor.
                                 Before/after    Opinion
                                 studies.                papers.
                                 Time series..   Studies
                                                         published prior
                                                         to 1990, to
                                                         focus on
                                                         contemporary
                                                         evidence and
                                                         practices
                                                         relevant to
                                                         current
                                                         prehospital
                                                         hemorrhagic
                                                         shock
                                                         resuscitation
                                                         protocols.
                                 For CQ1 only:
                                 qualitative studies
                                 that specifically
                                 collect data about
                                 barriers to and
                                 facilitators of
                                 implementing
                                 prehospital blood
                                 product transfusion
                                 programs (e.g.,
                                 descriptive case
                                 studies, evaluations,
                                 QI reports),
                                 interviews, focus
                                 groups.
------------------------------------------------------------------------
Abbreviations: AVPU = Alert, Voice, Pain, Unresponsive; CQ = Contextual
  Question; ED = emergency department; EMS = emergency medical services;
  GCS = Glasgow Coma Scale; HDI = Human Development Index; ICU =
  intensive care unit; KQ = Key Question; NA = not applicable; PICOTS =
  population, interventions, comparators, outcomes, timing, and setting;
  PRBC = packed red blood cell; QI = quality improvement; RCT =
  randomized controlled trial; ROSC = return of spontaneous circulation.
\a\ United Nations Development Programme. Human Development Index.
  Retrieved from https://hdr.undp.org/data-center/human-development-index#/indicies/HDI.

[[Page 93296]]

    Dated: November 21, 2024.
Marquita Cullom,
Associate Director.
[FR Doc. 2024-27679 Filed 11-25-24; 8:45 am]
BILLING CODE 4160-90-P
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