Joint Hemostatics In-Progress Review: Introduction 25 April 2012

Background: Causes of Death on the Battlefield All Deaths Potentially survivable: 19% Other Central Nervous System Airway Compromise Non-survivable: 81% Potentially Survivable Deaths: 75% KIA and 25% DOW Non-survivable injuries: Catastrophic TBI Cardiac laceration / puncture Thoracic great vessel injury Intra thoracic tracheal injury Open pelvis Top cause of preventable DOW*: Hemorrhage 76% Burn 13% TBI 6% MOF 3% Airway 1% *DOW: Died of Wounds at Role 3+ Hemorrhage: 84% 33% Tourniquetable 67% Non-compressible/ non-tourniquetable (internal injuries) Kelly et al., 2008

DoD Joint Program Committee for Combat Casualty Care Top Three Needs 1. Improved ability to diagnose, resuscitate, and stabilize casualties with survivable wounds 2. Improved ability to stop internal bleeding and external bleeding 3. Improved therapy for hemorrhagic shock and head injury

DoD Hemorrhage and Resuscitation Program/Portfolio Scope and Purpose Scope: The Hemorrhage and Resuscitation R&D program includes DoD efforts in the general areas of hemorrhage control, fluid resuscitation, blood products, transfusion, and pathophysiologic responses to traumatic hemorrhage, with a view ranging from basic and discovery research through clinical develoment Purpose: Conduct research and development to provide improved methods, drugs, and devices to stop bleeding, restore lost blood volume, and mitigate the consequences of hemorrhage. Reduce mortality by up 16% overall.

Steering Committee Role The present combination of Service programs, major Defense Health Program initiatives, significant CSI efforts, and numerous smaller initiatives make coordination extremely important Joint/Interagency Steering Committee Role: Advise the JPC-6 and Service R&D programs Review overall program and provide recommendations Develop (and update) a DoD-level strategic plan Produce recommendations and position papers regarding significant strategic level issues relevant to the program Facilitate harmonization of research requirements, objectives, and programs; ensure that Service-unique requirements are also met Promote communication and cooperation among programs

Strategic Approach: Major Efforts Goal Improved Blood Products Develop safer and more logistically supportable blood products for transfusion Damage Control Resuscitation Identify the best ways to use existing and newly developed blood products, drugs, and fluids (Including Transfusion Practice using existing products-CPGs) Coagulopathy of Trauma Elucidate mechanisms to identify diagnostic and therapeutic targets for the development of rapid diagnostics and drugs to prevent or treat coagulopathy of trauma Immune/Inflammatory Modulation Evaluate promising approaches and identify key mechanisms leading to the long-term ability to modulate inflammatory responses of the patient Metabolic and Tissue Stabilization Evaluate promising approaches and identify key mechanisms leading to long-term ability to modulate/stabilize metabolic responses (Including oxygen delivery) Hemostatics Evaluate/identify existing products and develop new products or procedures to control bleeding

DoD Activities in Hemostatics The major gaps in hemostatics: Non-compressible and Junctional bleeding Areas of research and testing in hemostatics DARPA Wound Stasis Program to develop a field treatment for intracavitary bleeding Hemostatic drugs Devices for junctional bleeding (CROC; hemostatic pellets) Other approaches to noncompressible hemorrhage (e.g. abdominal tourniquet) Endovascular hemostasis Improved topical hemostatics (Internal Use) Improved topical hemostatics (External Use) Improved limb tourniquets Primarily R&D Primarily Testing

DoD Hemorrhage R&D Investment By Major Effort ($M) FY10 FY11 FY12 FY13 Improved Blood Products 62.00 42.86 37.30 43.37 Damage Control Resuscitation 55.61 16.33 11.26 24.08 Coagulopathy of Trauma 12.06 10.72 6.68 5.56 Inflammatory Modulation 5.71 8.08 3.09 3.39 Metabolic and Tissue Stabilization 16.73 20.52 17.75 12.78 Hemostatics 19.56 22.21 15.55 8.75 Total 171.67 120.73 91.63 97.92 DoD Spending on hemostatics has been ~$15-20M/year and declining

Status We currently effective hemostatic dressings and limb tourniquets that are largely effective The major technology gaps in hemostatics are Non-compressible and Junctional bleeding We continue to test new dressings and tourniquets (for “tourniquetable” and compressible hemorrhage)

Issues Lack of agreement on why (what gap are we trying to fill?) Disagreements on what dressings and tourniquets to test and how to test them Need improved coordination and communication to enhance efficiency Funding is declining – need to ensure we are focusing (limited) resources on the right priorities “Testing” takes away resources from research and development efforts – need alternative funding and need focus Frustration - user community that we are not testing dressings of interest Frustration - research community – why use S&T funds?

Some Recent Progress Recent efforts to establish consensus testing approaches (with Inter-Service Agreement) DHP funding for FY12 – Dressings and Tourniquets Possible DHP 6.7 funds Improved coordination still needed

Approach Joint In-progress Review on Hemostatics This will be the first of a series of recurring meetings (probably 1x/yr in person and 1x/yr conference call) Recommended by the Joint Program Committee for Trauma (JPC-6) Endorsed by: Principal Assistant for Acquisition, USAMRMC (Dr. Bertram, SES) Army Combat Casualty Care Research Program (RAD2; COL Hack) Defense Medical Materiel Program Office DoD Hemorrhage and Resuscitation Research and Development Steering Committee Others

Goals of the Conference Agree on a framework for linking needs, testing, and acquisition processes for hemostatic dressings and limb tourniquets Establish an agreed list of hemostatic dressings and limb tourniquets (and related topical hemostatics) that require testing in FY13 Share latest testing data for hemostatic dressings and tourniquets Define/confirm standardized models for testing Identify organization(s) that will/propose to perform testing for FY13 (Not-directive – requires chain of command approval, etc.) Identify funding source for testing Define/revise desirable characteristics for new topical hemostatics and limb tourniquets Improve integration with acquisition processes Provide a predictable forum for dissemination of information and planning 

Key Coordinating Partners Defense Medical Materiel Program Office DoD Hemorrhage and Resuscitation R&D Steering Committee USA Medical Materiel Acquisition Activity

Defense Medical Materiel Program Office Mission: To recommend clinical, logistics, and program policy, as well as to support medical materiel development and acquisition processes across the four Services Purpose: To promote standardized medical supplies and equipment, joint interoperability of operational medical capabilities, and efficiency in the acquisition and lifecycle management of medical materiel

Questions/Comments

Discussion Define/revise desirable characteristics for hemostatic dressings and tourniquets What are the gaps that we are trying to fill for Limb Tourniquets and Hemostatic Dressings?

Potentially Salvageable Deaths Up to 16% of all combat deaths could be saved with new technologies to control or treat bleeding Of these: >half non-compressible (intracavitary) bleeding ~one-fifth compressible (axilla, groin, neck) but junctional or otherwise difficult ~one-third tourniquetable Source: Kelly JF, et al. Injury severity and causes of death from Operation Iraqi Freedom and Operation Enduring Freedom: 2003-2004 versus 2006. J Trauma. 2008;64(2):S21-S27.

Desirable characteristics/technology gaps for improved dressings and tourniquets? Efficacy Weight Size Durability Ease of use Cost Flexibility/versatility Effective with coagulopathy Additional functions Other 1

Characteristics (Continued)

Discussion List of Hemostatic Dressings and Related Topical Hemostats for FY13 Testing

Generalized testing process Two-part Screening Government organization (e.g. lab) assesses available data to determine if a screening test is warranted Limited number/scope Military experts provide early reality check and assessment Company may be required to pay for screening Joint Military Efficacy Testing (JMET) Must be FDA approved (or near approval) Must be successful in screening using relevant model Must be on the Joint list Consideration What are you testing versus what is the desirable characteristic (e.g. a dressing may be lower cost but the same efficacy)?

Lists Recommended List for Screening Recommended List for JMET Recommended List for R&D

List of Dressings to Test Screening 1 JMET 1 R&D 1

Discussion List of LimbTourniquets for FY13 Testing

List of Limb Tourniquets to Test Screening 1 JMET 1 R&D 1