Abstract
Overview
Introduction
The Critical Care Community is currently at its most organized, and motivated, and on a mission to improve outcomes in sepsis. This is driving a rigorous assessment of care strategies which is gathering speed and showing results. This will yield many opportunities for developing products, but current interventions' roles will change, with impacts on how they are measured, used and valued.
Scope
- Insight into clinical and commercial developments tackling predisposition, infection, response and organ dysfunction
- A translation of the complex, multifaceted processes involved in sepsis into commercial realities for industry
- Perspectives from Contract Research, Biotech, Pharmaceutical and Diagnostics sectors and leading figures from the sepsis and critical care community
- Assessment of the impact of the Surviving Sepsis Campaign and the changes in its latest set of guidelines on prescribing physicians
Highlights
The critical care community' s rigorous assessment of current management strategies is now gathering speed and showing results, gaining more converts and highlighting new perspectives on sepsis-related processes
Current interventions used in sepsis are typically either repurposed from other disease areas, or based on nascent understandings of the processes in play
Whilst this improved understanding may yield many new opportunities for developing new interventions, the understanding of the roles of current interventions may be turned upside-down, with implications for how they are measured, used, and indeed, valued in improving outcomes
Reasons to Purchase
- Understand the clinical and commercial characteristics and priorities for an increasingly complex therapy area
- Identify the elements of strategies that will either kept players at the top of their field or fail completely
- Understand how these businesses and strategies relate to your interest in the market, and how to position your products and services accordingly
Table of Contents
- ABOUT DATAMONITOR HEALTHCARE
- About the Infectious & Respiratory Disease pharmaceutical analysis team
- CHAPTER 1 EXECUTIVE SUMMARY
- Objective of the analysis
- Datamonitor insight into sepsis
- A highly motivated Critical Care Community is gaining a singular momentum
- Old dogs, new tricks? Current interventions meet new thinking
- The new era: personalized medicine in infectious disease
- Related reports
- Upcoming related reports
- CHAPTER 2 BACKGROUND
- Catalyst
- Scope
- Acknowledgements
- CHAPTER 3 DEFINITIONS
- Sepsis defined - the lynchpin of progress
- Matching definitions to working criteria for clinical inclusion
- Taking an oncologist' s view of sepsis: the PIRO model
- CHAPTER 4 ORDER FROM CHAOS - THE IMPACT OF SEPSIS STAGING
- P is for Predisposition and Prophylaxis targets
- Age
- Co-morbidities
- Genetic predisposition
- I is for Infection - a plethora of pathogens
- The diagnostic shortfall
- Anti-infectives: trialed for infection, not sepsis indications
- Supply and demand: how do available anti-infectives stack up?
- Too much of a gram-positive focus
- Indication semantics - site of infection in sepsis
- Matching infection indications to sepsis sites of infection
- R is for Response to infection: when is too much and what to treat?
- Multiple pathways
- Beyond early goal directed therapy - current targets for new and novel
therapeutics
- Upstream versus downstream
- Early versus late onset
- Neither upstream, nor downstream
- Sepsis, severe sepsis and clinical trials
- Continuity of outcomes across progressive trials
- Recruitment
- Endpoints
- O is for Organ dysfunction
- Discrete organ dysfunction versus multiple organ dysfunction
- Modeling sepsis-related organ failure
- Measuring an outcome versus a target for intervention
- Binary versus linear scales
- With or without interventions
- P is for Predisposition and Prophylaxis targets
- CHAPTER 5 CASE STUDY: THE SURVIVING SEPSIS CAMPAIGN
- Mandate, leadership and direction
- Singular view
- Achievable principles versus specifics
- Ethical responsibility
- Legal liability
- Coherence and continuous improvement - the evolution of SSC Guidelines
- Backing
- Creating a balance through non-industry grants
- Diluting the "Lilly-effect" with more corporate sponsorship
- Private foundations and government funding
- New versus old guidelines
- Balancing consistency with improvement
- The big question: so what happened to Xigris recommendations?
- Xigris, the data
- Corticosteroids - CORTICUS prompts subtle changes
- Glycemic controls and vasopressors
- Vasopressin - more subtle changes, but why?
- APPENDIX A - EPIDEMIOLOGY DATA
- Sepsis by pathogen
- Sepsis by deaths pathogen
- Sepsis sites of infection
- APPENDIX B - SSC GUIDELINE OUTLINES
- Initial Resuscitation
- Initial resuscitation (first 6 hours)
- Diagnosis
- Antibiotic Therapy
- Source identification and control
- Hemodynamic Support and Adjunctive Therapy
- Fluid Therapy
- Vasopressors
- Inotropic therapy
- Steroids
- Recombinant human activated protein C (rhAPC)
- Blood product administration
- Mechanical ventilation of sepsis-induced acute lung injury (ALI)/Adult Respiratory Distress Syndrome (ARDS)
- Sedation, analgesia, and neuromuscular blockade in sepsis
- Glucose control
- Renal replacement
- Bicarbonate therapy
- Deep vein thrombosis (DVT) prophylaxis
- Stress ulcer prophylaxis
- Consideration for limitation of support
- Initial Resuscitation
- APPENDIX C - PIPELINE DATA
- Cell Signalling Targets
- Coagulation Cascade Targets
- Endotoxin Targets
- Immodulation Targets
- APPENDIX D
- Bibliography
- Definitions
- Epidemiology
- Websites
- Clinical trial data
- Contributing experts
- Clinical
- Industry
- Report methodology
- About Datamonitor
- About Datamonitor Healthcare
- About the Infectious & Respiratory Disease analysis team
- About the Infectious Disease analysis team
- Key therapy team members
- Holger Rovini, Head of Respiratory and Infectious Diseases
- Disclaimer
- List of Tables
- Table 1: Evidence based preventative strategies for Septic Shock
- Table 2: Candidate genes and severe sepsis
- Table 3: Examples of microbial diagnostic tests
- Table 4: Signs and symptoms of organ dysfunction
- Table 5: Sponsors of the SSC Guidelines
- Table 6: Relative frequency of sepsis by pathogen
- Table 7: SOAP trial - mortality by pathogen type, and ICU/hospital attribution
- Table 8: Site of infection in Sepsis Patients - SOAP study outcomes
- Table 9: The Sepsis Pipeline: Cell-signaling targets by development stage
- Table 10: The Sepsis Pipeline: Coagulation cascade targets by development stage
- Table 11: The Sepsis Pipeline: Endotoxin targets by development stage
- Table 12: The Sepsis Pipeline: Immunomodulation targets by development stage
- Table 13: The Sepsis Pipeline: Specific Mediator targets by development stage
- Table 14: The Sepsis Pipeline: Unknown targets by development stage
- List of Figures
- Figure 1: Defining Sepsis - the ACCP, SCCM, ATS, ESICM and SIS consensus conference 2001
- Figure 2: The PIRO model
- Figure 3: Increasing importance of the over 65s as a high risk group for sepsis, 1979-2001
- Figure 4: Over 65s and sepsis - higher incidence, higher mortality rates
- Figure 5: Co-morbidities in sepsis patients stratified by age
- Figure 6: Pathogen, site, origin - the complexities of infection
- Figure 7: Impact of timing of antimicrobial initiation on survival in sepsis
- Figure 8: Diagnostic capabilities - different roles in assisting treatment strategy decisions
- Figure 9: Stratifying diagnostic tools for sepsis
- Figure 10: Top five marketed brand and pipeline coverage of antibiotics by indication, 2007
- Figure 11: Site of infection in sepsis patients according to the onset from routine postoperative monitoring of sepsis
- Figure 12: Stylized and simplified - sepsis progression
- Figure 13: Main effector pathways for sepsis
- Figure 14: The sepsis pipeline by target and stage of development, 2008
- Figure 15: Theories of pathogenesis
- Figure 16: Organ failure by type, 2000
- Figure 17: SOFA, MODS and LODS - Parameters and scores used in assessing organ dysfunction
- Figure 18: Key elements of the Barcelona Declaration
- Figure 19: Can' t comply, won' t comply - barriers to uptake and facilitators of change
- Figure 20: Early Goal Directed Therapy in Sepsis
- Figure 21: Relative frequency of sepsis by pathogen
- Figure 22: SOAP trial - mortality by pathogen type, and ICU/hospital attribution
- Bibliography
