Document headings vary by document type but may contain
                    the following: the agency or agencies that issued and signed a document
the number of the CFR title and the number of each part
                      the document amends, proposes to amend, or is directly
                      related to
the agency docket number / agency internal file number
the RIN which identifies each regulatory action listed in
                      the Unified Agenda of Federal Regulatory and Deregulatory
                      Actions See the
                    Document Drafting Handbook
                    for more details.
 Department of Health and Human Services Agency for Healthcare Research and Quality
 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 Access to published and unpublished pertinent scientific information will improve the quality of this review.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: epc@ahrq.hhs.gov* *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: 
                        *epc@ahrq.hhs.gov.*


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: 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.* *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. *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. 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 
                    ( print 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
PICOTS
Inclusion criteria
Exclusion criteriaPopulations
• Patients requiring prehospital hemorrhagic shock resuscitation treated in the prehospital setting by emergency medical services clinicians
• Individuals who do not require prehospital hemorrhagic shock resuscitation.
                             • Individuals not treated by emergency medical services clinicians.Intervention
• 
                            *KQ1:*
                             whole blood
• Other 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:*
                             NAComparator
• 
                            *KQ1 to 4*
• KQ1 to KQ5: no comparison.○ Head-to-head comparisons between transfusion options to treat prehospital hemorrhagic shock patients○ 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:*
                             NAOutcomes
*Patient Health Outcomes (highest priority)*
• Cost-effectiveness, other outcomes.• Mortality/survival○ To arrival at hospital○ To hospital discharge○ Any period less than or equal to 30 days post-emergency• Morbidity after discharge( print page 93295)○ Glasgow Outcome Scale, Glasgow Outcome Scale Extended, Modified Rankin Scale, Cerebral Performance Category• Length of stay○ Hospital free days○ ICU free days*Intermediate Outcomes*
                             in the prehospital or ED setting• Physiological indicators (including but not limited to the following)○ Systolic blood pressure○ Diastolic blood pressure○ Mean arterial pressure○ Heart rate○ Respiratory rate○ Respiratory failure○ ROSC○ Shock index○ Body temperature○ End tidal CO2 (EtCO2)○ Level of ConsciousnessGCSAVPU○ 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 bloodTiming
• Outcomes up to 30 days post-injury
• Outcomes more than 30 days post-injury.Setting
• Prehospital
                             
                                • US and International studies published in English language from Very High and High HDI a
                                 countries.
• ED.
                             • Inpatient, surgery. 
                             
                                • Studies conducted in 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 comparative studies
• Case series.• Retrospective comparative studies
• Descriptive studies.• Case control studies
• Letters to the editor.• Before/after studies
• Opinion 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 groupsAbbreviations: 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.*
 Dated: November 21, 2024. Marquita Cullom, Associate Director.


[FR Doc. 2024-27679 Filed 11-25-24; 8:45 am] BILLING CODE 4160-90-P