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  • 9 20 To assert that a program is cost-effective, it must be defended by some sort of analysis whereby both costs and effectiveness are measured. Effectiveness is generally measured in terms of years of life saved or quality-adjusted years of life saved. Once you have both of these measures for all programs or treatments to be compared, you create what is called a CE ratio with incremental costs in the numerator and incremental health benefits in the denominator. The next questions are, are resources limited and what are we willing to pay?
  • To address these objectives, we used the CEPAC-International model. This is a first-order Monte Carlo state transition model of HIV disease and treatment. The CEPAC International model has been adapted from a US-based model for resource-limited settings where CD4 counts and HIV RNA may not be available, and where, clinical data have been derived from South Africa. Model outcomes are denominated for this analysis in undiscounted mean projected life expectancy
  • Based on the Commission on Macroeconomics and Health, the World Health Organization suggests that interventions are “very cost-effective” if they have cost-effectiveness ratios less than the Gross Domestic Product (GDP) per capita of that country, or $803 for Cote d’Ivoire and “cost-effective” if they have ratios less than 3 times the per capita GDP of that country, or $2,409 for Cote d’Ivoire. We used these definitions in this analysis.
  • When long term outcomes are projected, the two ART strategies result in mean life expectancy of 10.33 years with deferred ART, and 11.03 years with earlier ART. Per person lifetime costs of deferred ART are $10,820, compared to $11,660 with earlier ART. The incremental cost effectiveness of deferred ART compared to no treatment is $1,110/life year saved and of earlier ART compared to deferred ART is $1200/life years saved.
  • Good morning. The question of “when to start” antiretroviral therapy, or ART, in HIV-infected patients has drawn interest globally. Especially in resource-limited setting, this question must be addressed in the context of limited available ART regimens, in addition to an increased incidence of opportunistic infections and tuberculosis at comparatively higher CD4 cell counts.
  • When long term outcomes are projected, the two ART strategies result in mean life expectancy of 10.33 years with deferred ART, and 11.03 years with earlier ART. Per person lifetime costs of deferred ART are $10,820, compared to $11,660 with earlier ART. The incremental cost effectiveness of deferred ART compared to no treatment is $1,110/life year saved and of earlier ART compared to deferred ART is $1200/life years saved.
  • Model-generated survival curves also diverge for the three ART strategies. No treatment, in blue, has 50% survival at 4.2 years. By year 3, earlier ART maintains a consistent 5% absolute increase in the proportion alive.
  • Our objectives were to examine alternative ART rollout scenarios in South Africa to: First, forecast the number of lives lost while awaiting therapy among treatment-eligible patients, and the number of patients in treatment over the next several years; Second, to project when total ART need would be met; And third, to inform decisions regarding the life-saving value of alternative treatment expansion scenarios.
  • We examine four different growth scenarios for ART rollout. These scenarios are similar to proposals made by the Actuarial Society of South Africa, or ASSA, and the South African Joint Task Team on HIV/AIDS. They range from a zero-growth scenario, which provides 750,000 new treatment slots by 2010, to a rapid growth scenario, which provides 2.8 million treatment slots by 2010.
  • This results slide shows the percent ART need met by year. On the horizontal axis is the year, and on the vertical axis, the percent of ART need met. All scenarios begin with the same number of patients treated in 2007, and hence the same percent of coverage; they then diverge in subsequent years. Treatment coverage under the zero growth scenario, shown in white, decreases steadily through 2012 at which time 28% of people in need of therapy will receive it. In the constant growth scenario, shown in yellow, treatment rates stay relatively unchanged to achieve 52% of necessary coverage by 2012. In the moderate growth scenarios, shown in orange, treatment coverage increases steadily to reach 97% of those in need by 2012. The rapid growth scenario, shown in purple, achieves full treatment coverage by 2011.
  • This table shows the number of AIDS deaths and patients alive on ART for 2005 to 2010, as we total the deaths for each year from the previous slide. The number of AIDS deaths ranges from 2,197,000 in the zero growth scenario, down to 1,161,000 in the rapid growth scenario. The number of patients alive and receiving therapy ranges from 693,000 in the zero growth scenario to 2,572,000 in the rapid growth scenario.
  • This shows the impact of the availability of CD4 monitoring on the number of deaths. In the absence of CD4 monitoring, decisions on treatment initiation and switching are based solely on clinical criteria. The number of AIDS deaths with CD4 monitoring available from 2007 to 2012 is the same as on the previous slide, shown here in the left column. The number of deaths with no CD4 monitoring available is substantially higher in every scenario. In the zero growth scenario, deaths increase from 2,465,000 with CD4 monitoring to 2,568,000 with no CD4 monitoring. This effect is even more pronounced in the rapid growth scenario, where deaths increase from 1,232,000 with CD4 monitoring to 2,218,000 with no CD4 monitoring. Compared to corresponding scenarios where CD4 monitoring is available, the lack of CD4 monitoring results in 103,000 to 986,000 increased deaths.
  • This figure depicts the timeline of major HIV interventions we considered and when they became standard of care in the US. We include prophylaxis for Pneumocystis jiroveci pneumonia (or PCP), starting in 1989 and add Mycobacterium avium complex, or MAC, prophylaxis starting in 1993. Prevention of mother to child transmission with AZT began in 1994 . 1996 marks the beginning of highly active antiretroviral therapy. We characterize the improvements in ART efficacy over time by dividing ART into 4 eras, beginning in 1996, 1998, 2000 and 2003.
  • This figure shows model-based survival curves for patients diagnosed in the first year of each of the six treatment eras (1989, 1993, 1996, 1998, 2000, 2003) and untreated disease, shown in gray. The area between the curves illustrates the improvement in AIDS-associated survival in the US over time. Median survival was 1.7 years for the PCP era shown in yellow, 7.5 years for ART 1 shown in light blue, and 14.1 years for ART 4, the upper most curve shown in pink.
  • In conclusion, we find that earlier initiation of ART in South Africa improves both short-term and long-term survival, and is cost-effective by international standards. The addition of TLTBI to both deferred and earlier ART strategies leads to a small survival benefit, but is cost-saving. While awaiting the results of clinical trials on the “when to start” question, the results of this study indicate that earlier ART initiation with the addition of TLTBI should be the treatment goal in South Africa.
  • In conclusion, we find that earlier initiation of ART in South Africa improves both short-term and long-term survival, and is cost-effective by international standards. The addition of TLTBI to both deferred and earlier ART strategies leads to a small survival benefit, but is cost-saving. While awaiting the results of clinical trials on the “when to start” question, the results of this study indicate that earlier ART initiation with the addition of TLTBI should be the treatment goal in South Africa.
  • And also, but a terrific modeling group, we fondly call the cost-effectiveness of preventing AIDS complications or CEPAC investigators. This group is led by Kenneth Freedberg and has the generous support of the CDC, NIMH, and NIAID. Thank you.

Wesat2203 Wesat2203 Presentation Transcript

  • Scaling up antiretroviral therapy in resource poor countries: The impact of speed on survival Rochelle P. Walensky, MD, MPH Associate Professor of Medicine Harvard Medical School Divisions of Infectious Disease Massachusetts General Hospital Brigham and Women’s Hospital Supported by NIAID, NIMH, and Doris Duke Charitable Foundation
    • $48 billion
    • Is this too much? Not enough?
    • How can we measure the value when dollars are spent?
    PEPfAR Reauthorized July 2008
    • Methods of cost-effectiveness analysis
    • What is the value of :
      • Antiretroviral therapy (C ô te d’Ivoire)?
      • Second-line therapy (India)?
      • Earlier treatment initiation (South Africa)?
    • What is the projected impact of PEPfAR funding over the next 5 years?
    Overview
  • Cost-effectiveness: Common Misconceptions
    • “ Cost-Effective” = “Cheap”
    • “ Cost-Effective” = “Saves Money”
    • “ Cost-Effective” = Additional benefit worth the additional cost ($/YLS)
  • Cost-effectiveness is about Value for Money
    • Two different outcome measures
      • Cost in dollars
      • Effectiveness: years of life saved (YLS)
            • quality-adjusted life years (QALYs)
    • Cost-effectiveness ratio:
    • Additional Resource Use ($)
    • Additional Health Benefits (YLS)
  • Cost-effectiveness of Preventing AIDS Complications (CEPAC)-International
    • CEPAC is a simulation model of HIV disease and treatment that incorporates CD4 count, HIV RNA, ART, OIs
    • Clinical data are from Côte d’Ivoire, India, and South Africa
    • Model provides outcomes measured in:
      • Mean projected life expectancy
      • 1-, 5-, 10-yr morbidity and mortality
      • Mean projected per person costs
    • Designed to address the most critical questions in resource-limited settings
    Funded by NIAID/NIMH/DDCF
  • Methods: Cost-effectiveness Thresholds
    • The Commission on Macroeconomics and Health of the WHO have suggested that interventions are:
        • Very cost-effective : the CE ratio is <1X Gross Domestic Product (GDP) per capita for that country
          • $803 for C ô te d’Ivoire
          • $590 for India
          • $5,300 for South Africa
          • $43,000 for US
        • Cost-effective : the CE ratio is
        • <3 x GDP per capita for that country
    Macroeconomics and Health: WHO 2001
  • Data from C ô te d’Ivoire
    • Collaborators: Xavier Anglaret, MD, PhD, ANRS 059
    • Mean age 33 yr, 40% male
    • Mean CD4 count 331/ µl
    • ART 52-week efficacy/annual cost:
      • First-line (NNRTI): 51% suppression, $292/yr
  • Model Validation: Data from C ô te d’Ivoire Cumulative Incidence Goldie et al NEJM 2006
  • Cost-effectiveness of ART: C ô te d’Ivoire Goldie et al NEJM 2006 GDP: $803 -- 780 31.4 -- -- -- No Treatment 1,180 3,420 69.6 90% in CD4 count CD4<200, CD4<350 and 1 severe OD, or 1 OD Yes T/S + ART 1,060 2,260 57.9 5 ODs 1 OD No T/S + ART 890 2,170 56.8 3 ODs 1 OD No T/S + ART 620 1,720 50.7 1 OD 1 OD No T/S + ART 590 1,230 41.4 1 OD 2 ODs No T/S + ART 240 810 32.8 -- -- No T/S alone C-E Ratio ($/yr life saved) Costs ($) Life Expectancy (mo) ART Stop Criteria ART Start Criteria CD4 Test Strategy
  • But what about expensive second-line therapy?
  • Data from India
    • YRG Care, N. Kumarasamy, MD
    • Mean age: 32.6 yr, 66% male
    • Mean CD4 count: 318/ µl
    • ART 48-week efficacy/annual cost:
      • First-line (NNRTI): 55% suppression, $222/yr
      • Second-line (PI): 65% suppression, $1,435/yr
  • The value of two lines of ART: India *All costs in 2005 US$, converted using GDP deflators & the mean exchange rate between the Rupee & US$ Freedberg et al., AIDS 2007, World Bank GDP: $590 1,850 84.8 4,980 Two lines ART (NNRTI/PI) (<200/ µl) 450 62.4 1,540 One line ART (NNRTI) (<200/ µl) -- 35.9 580 No treatment C-E Ratio ($/YLS) Survival (months) Lifetime cost ($)* Strategy
  • When to Start?
    • The question of “when to start” ART has drawn interest globally
    • In resource-limited settings, this question is crucial:
      • Limited available ART regimens
      • Increased incidence of opportunistic infections (OIs) and tuberculosis (TB) at higher CD4 counts
    • A clinical trial may be well-suited to address the “when to start” question
    • Results from such a trial will not be available for at least 5 years; two trials are currently enrolling
  • Data from South Africa
    • CTAC/Gugulethu Cohorts
      • Robin Wood, FCP, MMed, DTM&H , U CapeTown
    • Mean age 33 yr, 55% male
    • Mean CD4 count 375/ µl
    • ART 48-week efficacy/annual cost:
      • First-line (NNRTI): 84% suppression, $288/yr
      • Second-line (PI): 71% suppression, $564/yr
  • “ When to Start” ART: South Africa *All costs in 2006 US$, converted using GDP deflators & the mean exchange rate between the SA Rand & US$ Walensky et al CROI 2008 [abstract] GDP: $5,300 1,200 11.03 11,660 Earlier ART (<350/ µl or OI) 1,110 10.33 10,820 Deferred ART (<250/ µl or OI) -- 3.83 3,620 No treatment C-E Ratio ($/YLS) Survival (years) Lifetimecost ($)* Strategy
  • Results: Proportion Alive at 5 Years Deferred ART Earlier ART No ART Walensky et al CROI 2008 [abstract]
  • ART Roll Out: The impact of speed on survival
    • Alternative ART rollout scenarios in South Africa OR what might more PEPFAR funds mean?
      • To forecast
        • Number of lives lost awaiting therapy
        • Number of patients in treatment
      • To project when total ART need would be met
      • To inform decisions regarding the life-saving value of alternative treatment expansion scenarios
  • 4 Growth Scenarios Walensky et al., JID 2008 --- 2,400,000 Rapid growth SA Joint Task Team 2,100,000 Moderate growth ASSA 600,000 Constant growth --- 100,000 Zero growth Source New ART Slots by 2012  
  • Percent ART Need Met by Year Rapid Moderate Constant Zero Year % ART Need Met Walensky et al., JID 2008
  • Projected Deaths and Patients Alive on ART: 2007-2012 Walensky et al., JID 2008 2,523,000 1,232,000 Rapid growth 2,306,000 1,449,000 Moderate growth 1,595,000 2,160,000 Constant growth 1,290,000 2,465,000 Zero growth Alive on ART AIDS Deaths  
  • Impact of No CD4 Monitoring on Deaths Decisions on treatment initiation and switching based on clinical criteria Walensky et al JID 2008 2,218,000 2,237,000 2,436,000 2,568,000 No CD4 Monitoring 986,000 1,232,000 Rapid growth 788,000 1,449,000 Moderate growth 276,000 2,160,000 Constant growth 103,000 2,465,000 Zero growth Increased Deaths CD4 Monitoring  
  • Timeline of Major HIV Interventions Walensky et al., JID 2006
  • AIDS Survival by Era Walensky et al., JID 2006
  • Future Directions
    • What are the next most important questions?
    • The clinical and economic value of CD4 and/or HIV RNA laboratory monitoring?
    • The cost-effectiveness of genotype testing?
    • The clinical and economic impact of routine HIV screening?
    • Which of these results are country-specific? Which are generalizable around the globe?
  • Conclusions
    • In resource-limited settings, quantitative assessments of value for money are critical, given multiple treatment strategies.
    • Cost-effectiveness analyses have demonstrated the value of 1 st and 2 nd -line therapy, of earlier ART initiation, and of the need for increasingly rapid ART roll-out in international settings.
    • HIV simulation modeling is a powerful tool to inform health policy and to understand survival, costs and cost-effectiveness of alternative clinical interventions.
  • CEPAC (and other) Investigators: US
    • Harvard Medical School
    • Ingrid Bassett, MD, MPH
    • Melissa Bender, MD, MPH
    • Sarah Chung
    • John Chiosi
    • Andrea Ciaranello, MD
    • Kenneth Freedberg, MD, MSc
    • Louise Ivers, MD
    • Elena Losina, PhD
    • Ben Linas, MD, MPH
    • Zhigang Lu, MD
    • Brandon Morris
    • Paul Sax, MD
    • Caroline Sloan
    • Heather Smith
    • Lauren Uhler
    • Rochelle Walensky, MD, MPH
    • Bingxia Wang, PhD
    • Harvard SPH
    • Sue Goldie, MD, MPH
    • Kara Cotich
    • Callie Scott
    • George Seage, III DSc, MPH
    • Milton Weinstein, PhD
    • April Kimmel, MSc
    • Cornell
    • Bruce Schackman, PhD, MBA
    • Yale
    • David Paltiel, PhD
    • Lille, France
    • Yazdan Yazdanpanah, MD, PhD
  • CEPAC Investigators: International
    • C ô te d’Ivoire
    • Xavier Anglaret, MD, PhD
    • Eugene Messou, MD
    • Catherine Seyler, MD, PhD
    • Siaka Tour é , MD, MPH
    • South Africa
    • Neil Martinson, MBBCh, MPH
    • James McIntyre, MBChB,MRCOG
    • Lerato Mohapi, MBBCH
    • Robin Wood, MD
    India N. Kumarasamy, MBBS, PhD Tim Flanigan, MD Kenneth Mayer, MD OECS Kathleen Allen-Ferdinand, MD Paul Ricketts, MD Hazel Williams-Roberts, MD
  •