1. The projects described were supported by T32 AI007433, R01 AI058736, R01 AI093269 from NIAID, P30 AI060354 from HU CFAR, & NIH Fogarty International Center The contents are solely the responsibility of the author and do not necessarily represent the official views of the awarding offices Emily P. Hyle, MD Division of Infectious Diseases Massachusetts General Hospital Conflicts of interest: None HIV, Communicable, and Non-Communicable Diseases: Costs and Cost-Effectiveness of Integrated Care

2. 1.Global response to the HIV pandemic 2. Costs, cost-effectiveness, and modeling 3. Data needed to assess the value of integration Overview

3. Global Response to HIV Pandemic

4. Funding for the Global Response http://www.kff.org/globalhealth/upload/8002-05.pdf

5. Three Questions for Any Intervention 1.Is it effective? Does it work? ** If it is not effective, it is not cost-effective.** 2.Is it cost-effective? What is its value? 3.Where and how can it best be implemented? Is it affordable?

6. “Cost-Effective” = “Cheap” “Cost-Effective” = “Saves money” “Cost-Effective” = Additional benefit worth the additional cost Common Misconceptions

7. Formal methodology to assess the comparative value of at least 2 interventions Two different outcome measures: –Cost: $, Rand, Rupee –Effectiveness: Years of life saved (YLS) QALYs or DALYs Incremental cost-effectiveness ratio (ICER): Additional Resource Use Additional Health Benefits Cost-Effectiveness Analysis

8. The Commission on Macroeconomics and Health and WHO have suggested that interventions are: Cost-effective: the ICER is <3 x GDP per capita for that country Very cost-effective: the ICER is <1 x annual GDP per capita for that country Macroeconomics and Health: WHO 2001. WHO-CHOICE 2008. Cost-Effectiveness Thresholds

9. Examines the impact of a new intervention on one or multiple payers –Specific payer perspective –Specific site –Limited to a defined budgetary horizon Annual 5-year Budget Impact Analysis

10. Objective To project the cost-effectiveness of early compared to delayed ART for treatment and prevention in serodiscordant couples Analyses were conducted for two countries, South Africa and India, to assess regional differences in value Collaboration: HPTN 052/CEPAC-I Walensky et al., NEJM. 2013.

11. Mathematical model of HIV natural history and treatment Clinical and resource utilization data from South Africa and India Cohort and ART efficacy parameters from HPTN 052 trial (Cohen et al, NEJM 2011) Methods: CEPAC-International Model* *Funded by NIAID R37 AI42006, R01 AI058736, R01 AI093269

12. 1)Delayed ART (CD4 <250/µl) 2)Early ART (at presentation) Evaluate outcomes in: –Clinical benefit, cost and transmissions –5-year and lifetime horizons Methods: Two Strategies Walensky et al., NEJM. 2013.

13. Life expectancy (years) Costs (USD 2011) ICER † ($/YLS) Delayed ART13.815,100-- Early ART15.816,600590 † Including projected survival losses and cost increases associated with 1 st - and 2 nd -order transmissions per capita GDP in South Africa: $8,100 Walensky et al., NEJM. 2013. Results: Cost-Effectiveness (Lifetime, South Africa)

14. Data Needed: Cost-Effectiveness of Integrated Care Screening Treatment Costs Quality of Life Epidemiology Cost- Effectiveness Analysis

15. Effectiveness: Data Needed Epidemiology: –Prevalence –Incidence –Attributable mortality

16. Effectiveness: Data Needed Screening: –Test characteristics –Linkage to care after positive screening Treatment: –Effectiveness of management or cure –Adverse events Quality of life: –With or without symptoms –Effects of stigma

17. Resource Utilization: Data Needed Infrastructure: –Effects of using existing sites and personnel –Fixed vs. marginal costs –Impact of economies of scale Staff training: –In multiple domains –Decentralized vs. specialized sites Monitoring and evaluation: –Diversity of outcomes –Quality control

18. Integrated clinical care for HIV patients could offer opportunities to improve outcomes for good value Model-based budget impact and cost- effectiveness analyses are critical to understanding how to expand or integrate care, especially when resources are limited Data are needed to inform such analyses, which can help to prioritize resources and scale-up to improve patient outcomes Conclusions

19. United States Nalini Anand, JD, MPH Wafaa El-Sadr, MD, MPH, MPA Paolo Miotti, MD KM Venkat Narayan, MD, MSc Sten Vermund, MD, PhD South Africa Kogie Naidoo, MBChB Linda-Gail Bekker, MD, PhD Keren Middlekoop, MBChB, PhD Robin Wood, MBBCh, MMed Acknowledgements MGH Medical Practice Evaluation Center Ingrid Bassett, MD, MPH Andrea Ciaranello, MD, MPH Kenneth Freedberg, MD, MSc N. Kaye Horstman, PhD, MPH Robert A. Parker, ScD, Cstat Rochelle Walensky, MD, MPH Jordan Francke Michael Girouard Melanie Gaynes Margo Jacobsen Sarah Park Marion Robine Amanda Su

20. Is It Worth It? Comparison of Strategies     Incremental Health Benefits Incremental Cost Yes No (Evaluate ICER) Evaluate ICER

21. ParameterInput Mean CD4 (cells/μL)449 48-wk virologic suppression92% Loss to follow-up rate (/100 py)3.4 Average partners (/mo) South Africa0.014 India0.007 Transmission rate (/100 py)0.103-1.483 Model Input Parameters: Cohort, Treatment, and Transmission

22. South AfricaIndia ART (/mo)13 11 OI treatment300-1,00040-300 Routine care300-2,40090-311 per capita GDP*8,1001,500 1 WHO Global Price Reporting Mechanism *WHO thresholds: “Very cost-effective”: <1x per capita GDP *“Cost-effective”: <3x per capita GDP Model Input Parameters: Costs (2011 US$)

23. Results: Cost-effectiveness (Lifetime) Life expectancy (years) Costs (USD 2011) ICER † ($/YLS) South Africa Delayed ART13.815,100-- Early ART15.816,600590 India Delayed ART14.27,300-- Early ART15.88,400530 † Including projected survival losses and cost increases associated with 1 st - and 2 nd -order transmissions per capita GDP: South Africa ($8,100); India ($1,500) Walensky et al. NEJM. 2013.

24. The “Tutu Tester” Cape Town, South Africa 4,000 people, 2010- 2012 HIV prevalence 10.2% Hypertension 38.2% Diabetes 4.1% Govindasamy et al, PLoS One. 2013. PEPFAR Supplement to AI 058736

25. Cost-effectiveness Ratios for Other Screening Programs C-E ratio Screening Program ($/QALY)* Reference HIV screening inpatients $38,600Walensky AJM 2005 HIV screening every 5 years high risk patients $50,000Paltiel NEJM 2005 Breast cancer screeningSalzmann Annual mammogram, 50–69 y/o $57,500Ann Intern Med 1997 Colon cancer FOBT + SIG q5y, adults 50–85 y/o $57,700 Frazier JAMA 2000 Diabetes Mellitus, Type 2 fasting plasma glucose, adults >25 y/o $70,000CDC JAMA 1998 *All costs adjusted to 2001 US dollars

26. C-E Ratio Intervention Agent ($/QALY)*Reference PCP/Toxo proph. TMP-SMX $2,800 Freedberg JAMA 1998 ART AZT/3TC/EFV $11,700 Freedberg NEJM 2001 Resistance Test ---$20,200 Weinstein Annals 2001 Resistance Test (naïve) --- $23,900 Sax CID 2005 Inpt HIV screening --- $38,600 Walensky AJM 2005 MAC proph.Azithromycin $43,300 Freedberg JAMA 1998 HIV screening q5y --- $50,000P altiel NEJM 2005 high risk patients high risk patients Cost-effectiveness Ratios for HIV Care *All costs adjusted to 2001 US dollars