1. MANDATE Maternal and Neonatal Directed Assessment of Technology http://www.mnhtech.org GBCHealth November 29, 2011

2. MANDATE OVERVIEW MANDATE’s GOAL and OBJECTIVES APPROACH PRETERM BIRTH EXAMPLE NEXT STEPS

3. MANDATE OBJECTIVE Mortality impact on individuals : Mothers Fetuses Neonates Mortality impact on individuals : Mothers Fetuses Neonates Where and how to allocate product development resources to have the greatest impact on pregnancy-related mortalities? Impact in different settings : Hospitals Clinics Homes Impact in different settings : Hospitals Clinics Homes What types of technologies or packages: Preventatives Diagnostics Therapeutics What types of technologies or packages: Preventatives Diagnostics Therapeutics Impact in high- mortality regions : Sub-Saharan Africa India Impact in high- mortality regions : Sub-Saharan Africa India Provide a tool for quantitative assessment of where innovation might have the greatest potential to reduce maternal, fetal and neonatal mortality

4. CRITICAL CONDITIONS ASSOCIATED WITH MATERNAL, FETAL AND NEWBORN MORTALITY Sepsis Syphilis Malaria Abruption Previa Laceration Ret products Atony Eclampsia Preeclampsia Hypertension Short cervix IUGR Fetal distress Twins Breech Bacterial sepsis Omphalitis Neonatal Infection Syphilis Malaria Tetanus Obstructed labor Maternal hemorrhage Continuing Pregnancies Maternal hypertension High risk pregnancy Shock Neonatal Asphyxia Seizure Poor feeding RD/RDS Preterm Birth IVH NEC Pregnancies (India, Sub-Saharan Africa) Abortions Ectopic Pregnancy Maternal infection Maternal Conditions Neonatal Conditions

5. MANDATE team developed condition maps and populated them with prevalence and case fatality rates ORGANIZING PRINCIPLE: CONDITION MAP - HEMORRHAGE Maternal Fetal Neonatal Death Rates Pregnant Women No HemorrhageHemorrhage Antepartum Postpartum Maternal Fetal Neonatal Death Rates Previa Abruption Retained Products Laceration Atonic Uterus Ruptured Uterus

6. Maternal Fetal Neonatal Death Rates Pregnant Women No HemorrhageHemorrhage Antepartum Postpartum Previa Abruption Retained products Laceration Atonic uterus Ruptured uterus C-Section Screen for risk Hemoglobin Suturing Surgery IV Fluid Blood repl a cement Misoprostol Oxytocin Suction C-Section Screen for risk (US) Misoprostol ORGANIZING PRINCIPLE: CONDITION MAP- HEMORRHAGE

7. TECHNOLOGY IMPACT FACTORS Penetration: availability in setting Utilization: appropriate use by health provider Efficacy: Success in intended purpose - with ideal use – Prevention – Diagnosis – Treatment Coverage

8. Underlying Population Deaths Treated Not Treated Treated Not Treated Treated Not Treated “-” “+” “-” “+” “-” “+” Diagnosed Not Diagnosed Diagnosed Not Diagnosed Diagnosed Not Diagnosed Clinic Home Hospital Condition PositiveCondition Negative Diagnostic Intervention Treatment Intervention Penetration Utilization Penetration Utilization Penetration Utilization Efficacy Penetration Utilization Penetration Utilization Penetration Utilization Efficacy The MANDATE decision support tool allows user to change penetration, utilization, and efficacy of a technology intervention. CONDITION FLOW Prevention Intervention

9. Deaths Treated Not Treated Deaths Treated Not Treated Clinic Hospital Deaths Treated Not Treated Home Home to Clinic Home to Hospital Clinic to Hospital “-” “+” “-” “+” “-” “+” Diagnosed Not Diagnosed Diagnosed Not Diagnosed Diagnosed Not Diagnosed Diagnostic Intervention Setting Intervention Clinic Home Hospital Home to ClinicHome to Hospital Clinic to Hospital Underlying Population Clinic Home Hospital Condition PositiveCondition Negative All variables and assessments are captured as ranges. MANDATE reflects movement between treatment settings and allows user to change transfer rates CONDITION FLOW Prevention Intervention Setting Intervention Treatment Intervention

10. RDS IS THE MOST COMMON RESPIRATORY DISORDER OF PREMATURE NEWBORNS 1 million deaths are due to prematurity – ~80% of those deaths are attributed to RDS Current treatment for RDS: oxygen; CPAP; surfactant; ventilation, advanced NICU Current RDS Diagnostic: clinical exam, pulse oximetry, chest X-ray Prevention of RDS: corticosteroids Prevention of Premature Birth: progesterone 10

11. Failed Tx Not Treated Treated 107,433 Penetration: 80% Utilization: 80% 72,691 32,230 Death Rate: 40% Tx Efficacy: 25% Tx Failure Rate = 30% Failed Tx Treated Not Treated 29,576 Penetration: 25% Utilization: 75% 8,873 Death Rate: 40% Tx Efficacy: 25% Tx Failure Rate = 30% 176,544 Not Treated Failed Tx Treated Setting Transfer Expected change in setting for patients diagnosed with RD Efficacy: 95% 74,8783,941 Efficacy: 95% 209,29911,016 Efficacy: 95% 93,8434,939 52,415 157,741 167,864 Clinic Home Hospital Home to Clinic: 15% Home to Hospital: 15% Clinic to Hospital: 30% 1 st Line Treatment (oxygen) 0 Penetration: 0% Utilization: 0% 371,632 0 Death Rate: 40% Tx Efficacy: 25% Tx Failure Rate = 30% 78,819 Penetration: 50% Utilization: 40% 315,276 220,315 Penetration: 90% Utilization: 95% 37,363 Respiratory Distress Diagnostic 98,782 Penetration: 98% Utilization: 95% 7,321 “-” “+” “-” “+” “-” “+” Diagnosed Not Diagnosed Diagnosed Not Diagnosed Diagnosed Not Diagnosed 757, 876 (in 2008) Number of Preterm Infants born with Respiratory Distress in Sub-Saharan Africa 394,096257,678106, 103 Clinic Home Hospital 52%34% 14% Interventions Observation of Distress Note: Values shown are single base case values. All MANDATE variables are assessed as ranges to capture the uncertainty inherent in the data. Assessment source: RTI clinical expertise based on RTI table of RDS incidence and case fatality rates Respiratory Distress with current care in Sub-Saharan Africa. MANDATE CONDITION FLOW EXAMPLE

12. Sepsis Syphilis Malaria Retained products Previa Laceration Abruption Atony Eclampsia Preeclampsia Hypertension Short cervix IUGR Fetal distress Twins Breech Bacterial sepsis Omphalitis Neonatal Infection Syphilis Malaria Tetanus Obstructed labor Maternal infection Maternal hemorrhage Continuing Pregnancies Maternal hypertension High risk pregnancy Shock Neonatal Asphyxia Seizure Poor feeding RD/RDS Preterm Birth IVH NEC Treat ConditionPrevent ConditionPrevent Primary Condition Pregnancies (India and Sub-Saharan Africa) Abortions Ectopic Pregnancy OPPORTUNITIES TO REDUCE MORTALITY

13. Condition (prevalence) Sub-Saharan Africa Pregnancies resulting in birth31,996,058 Live Preterm Births (~12%  ?)3,638,757 Preterm Infants with RD (~21%  ?)757,876 Deaths in Preterm Infants with RD (~38%  ? with a better care) 287,117 ? = level of reduction dependent on efficacy, penetration, and utilization of the intervention 0 2, nCPAP, Surfactant Corticosteroids Ultrasound & Progesterone Prevent Preterm Births Prevent Preterm RD Treat Preterm RD RESPIRATORY DISTRESS INTERVENTION OPPORTUNITIES

14. RD at Birth Diagnostic Transfer Care Setting Given Diagnosis of RD 5 th Line RD Treatment 4 th Line RD Treatment 3 rd Line RD Treatment 2 nd Line RD Treatment 1 st Line RD Treatment Lives Saved:0 A working scenario is created to compare a new condition intervention scenarios against the current standard care. RD in Sub-Saharan Africa in 2008 Technology Intervention Points Setting Transfer Intervention Points Better Treatment Scenario Visual Observation of RD Diagnosed With Respiratory Distress Expected change in Setting for RD Diagnosis Advanced NICU Care Ventilator Surfactant nCPAP Oxygen, pulse oximetry, antibiotic Setting where preterm babies with RD are born RD TECHNOLOGY INTERVENTION SUMMARY DIAGRAM COMPARE A NEW INTERVENTION TO CURRENT CARE MANDATE DECISION SUPPORT TOOL

15. RD at Birth Diagnostic Transfer Care Setting Given Diagnosis of RD 5 th Line RD Treatment 4 th Line RD Treatment 3 rd Line RD Treatment 1 st Line RD Treatment RDS in Sub-Saharan Africa in 2008 Prevent RD in preterm infants Increase coverage of antenatal steroids in hospital, clinic and the home to 80% Treatment technology remains same as current care 11% mortality Lives saved = 30,784 Improve the ability to diagnose ‘preterm risk’ in the home and in the clinic (80% coverage, 70% efficacy) Visual Observation of RD Diagnosed With Respiratory Distress Expected change in Setting for RD Diagnosis Advanced NICU Care Ventilator Surfactant nCPAP Setting where preterm babies with RD are born Technology Intervention Points Setting Transfer Intervention Points 22% mortality Lives saved = 64,104 Oxygen, pulse oximetry, antibiotic RD TECHNOLOGY INTERVENTION SUMMARY DIAGRAM COMPARE A NEW INTERVENTION TO CURRENT CARE 2nd Line RD Treatment

16. PROVIDING INSIGHT ON THE IMPACT OF INNOVATION Web-Based Tool for the Global Health Community Assess impact of technologies – A technology across conditions – Comparative impact of alternate technologies – A technology in different care settings and patient transfer between settings – Impact of a package of interventions Inform strategic planning with “What If” scenarios

17. MANDATE: NEXT STEPS Enhance technology parameter data -- establish/ apply a methodology for analysis of technology parameters Validate data and model for each condition -- expand model and data sources -- run multiple scenarios -- include as examples on web site Expand user access -- provide training and technical support -- improve interface http://www.mnhtech.org

19. CONDITION AND TECHNOLOGY DATA DataSource Population birth rates by country UN estimated live birth rates (LiST) Health care settingDHS, in-country studies, Global Network Mortality rates by conditionWHO/IHME maternal mortality CHERG neonatal mortality Lancet series stillbirth Mortality for sub-conditionsLiterature review →ongoing review of literature, white papers, etc Field data → in-country surveys and studies Expert review → content and concepts TechnologyEfficacy → Cochrane, other meta-analyses Penetration, utilization→ literature, DHS, in- country studies

20. Respiratory Distress Treatment Estimated Mortality Rate in LMIC No Treatment40% Oxygen30% Oxygen and nCPAP15% Oxygen, nCPAP, and Surfactant10% Current treatment for RD/RDS in high-income countries includes oxygen, nCPAP, surfactant, ventilation, and advanced NICU therapies  Mortality now rare RD/RDS TREATMENT