Policy Research Working Paper #13

June 2007

Forecasting Demand for Preventive HIV Vaccines in India
IAVI Public Policy Department and IAVI-India

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Forecasting Demand for Preventive HIV Vaccines in India Copyright © 2007 International AIDS Vaccine Initiative. All rights reserved. ISBN: 978-0-9792432-2-6 This paper was written by Gian Gandhi, Shilpa Vuthoori, and Pranay Lal (IAVI). The authors wish to thank Christoph Kaufmann, Dave Matheson, Wendy Woods, and Michael Yeh (Boston Consulting Group) for their significant contributions to all aspects of this research, particularly the modelling work and primary data collection. Special thanks to Paul Wilson (Columbia University) for his invaluable input to shape the methodology, validate the model, and strengthen this paper. Special thanks also to Jonathan Grund (IAVI) for his assistance with the synthesis and analysis of primary data that informs this research. The authors also wish to thank the advisors who helped steer this research: Martha Ainsworth, David Bishai, Ricardo Bitran, Laura Efros, Ruth Levine, Susan McKinney, Angeline Nanni, Patricia Roberts, Chutima Suraratdecha, and all of those who gave their time to be interviewed to inform this research (Appendix I). The authors are grateful to Vijay Samant, DCS Reddy, and Denis Broun, who reviewed our paper and provided valuable perspectives on the challenges of vaccine development, implementation of health care programmes, and the HIV/AIDS epidemic in India. Finally, the authors would like to thank Jean-Louis Excler, Tom Harmon, Robert Hecht, Sonali Kochhar, Eva Roca, Kate Taylor, and Holly Wong at IAVI for their clarifications and generous assistance with refining earlier drafts of this paper. This study and report were made possible in part by the generous support of the American people through the United States Agency for International Development (USAID) under Cooperative Agreement No. GPO-A-00-06-00006-00. The contents are the responsibility of the International AIDS Vaccine Initiative and do not necessarily reflect the views of USAID or the United States Government. Information in this document may be reproduced or copied without permission, provided the International AIDS Vaccine Initiative, Inc. (IAVI), is acknowledged as the source. However, reproduction of substantial portions of this report, or any use of the material other than for education or non-commercial purposes, requires prior authorization in writing. To request additional print copies of this working paper or other information from IAVI please contact: Publications Unit International AIDS Vaccine Initiative 110 William Street, 27th Floor New York, NY 10038 USA Tel: + 1.212.847.1111 Fax: + 1.212. 847.1112 Email: pubs@iavi.org Web: www.iavi.org The full text of this report is also http://www.iavi.org/India_Demand_Forecast available online at the IAVI website at:

IAVI’s mission is to ensure the development of safe, effective, accessible, preventive HIV vaccines for use throughout the world. Printed on recycled paper.

Forecasting Demand for Preventive HIV Vaccines in India

Policy Research Working Paper #13
June 2007

IAVI's Policy Research Working Paper series disseminates the findings of works in progress to promote the exchange of ideas about the effective development and global distribution of vaccines to prevent HIV infection.

Table of Contents
List of Tables List of Figures Acronyms Glossary Executive Summary I. Introduction 1.1 Background 1.2 Research overview and scope 1.3 Previous demand assessments for HIV vaccines in India II. Determinants of demand and methodological framework III. Expert consultation 3.1 Rationale and objectives 3.2 Interview methods and interviewee selection 3.3 Interview results IV. Demand forecasting model 4.1 Model overview 4.2 Public sector adoption and implementation assumptions 4.3 Private market modelling assumptions V. Results and discussion 5.1 Overview 5.2 Vaccine profile demand scenarios: public versus private markets 5.3 Results and implications for donors and policymakers 5.4 Revenue forecasts and implications for private industry 5.5 Sensitivity analyses VI. Summary/conclusions References Appendix I. Appendix II. List of interviewees and collaborators Vaccine profile specification 38 40 43 45 46 47 48 24 15 6 8 ii iii iv v 1 4

Appendix III. Interviewee categories, rationale and judgments Appendix IV. India’s country profile descriptor information and assumptions Appendix V. Algorithms to define endogenous country-level behavioural parameters

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List of Tables
Table 1. Table 2. Table 3. Table 4. Table 5. Table 6. Table 7. Table 8. Table 9. Key determinants of demand Minimum acceptable level of vaccine efficacy Ranges for the minimum acceptable levels of protective duration and maximum price per dose Target age range for populations at lower risk of exposure to HIV Efficacy and duration of protection, by scenario Prices of existing vaccines in India Summary of India’s country profile descriptor values Summary of India’s public sector adoption and implementation behaviours Summary of India’s private market adoption and usage behaviours 6 11 11 12 16 16 17 21 23 26 26 30 34 35 36 45 48 48 48 48 48 49 49 49 49 50

Table 10. Relative contribution to cumulative demand of private versus public initiatives Table 11. Volume of demand in India across scenarios Table 12. Policy-environmental scenario specifications and effects on demand Table 13. Cumulative and peak sales revenue in India Table 14. Relative contribution of private market versus public market programmes to revenue Table 15. Sensitivity analyses parameter values Table A1. Lower and upper bounds of vaccine profile Table A2. Efficacy-implementation threshold matrix for high-risk programme Table A3. Efficacy- implementation threshold matrix for general programme Table A4. Duration of protection- implementation threshold matrix Table A5. Price- implementation threshold matrix Table A6. Regulatory/licensure lag matrix Table A7. API-prevalence-GNI scores Table A8. Intermediate high-risk programme implementation lag value Table A9. Hepatitis B implementation Table A10. Intermediate low-risk programme implementation lag value Table A11. Upper age limit of low-risk target group matrix

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List of Figures
Figure 1. Figure 2. Figure 3. Figure 4. Figure 5. Figure 6. Figure 7. Figure 8. Figure 9. Methodological demand framework, from need to projected demand Is the AIDS epidemic plateauing in India? Behavioural disinhibition concerns with partial efficacy vaccines Total annual demand forecasts for India (given various vaccine profile assumptions) Total annual demand by vaccination strategy (Medium Scenario) Separating the effects of each vaccination strategy (Medium Scenario) Funded versus unfunded complete courses (for the Medium Scenario) Demand forecasts for policy-environmental scenario specifications Vaccine profile sales revenue forecasts 7 9 14 25 27 27 29 31 34 36

Figure 10. Change in cumulative demand from sensitivity analyses on model parameters

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Acronyms
AIDS API ARV/ART CAGR CSW EMEA EPI FDA FSW GAVI GDP GNI GOI HIV HPV HSV-2 IAVI IDU IEC MSM NACO NGO NPT NRA PPP PrEP R&D Rs SACS UIP UNAIDS UNDP VCTC VEI VEP VES WHO WTP WTV Acquired immunodeficiency syndrome AIDS program effort index Antiretroviral therapy Compound annual growth rate Commercial sex worker European Medicines Agency Expanded Programme on Immunizations U.S. Food and Drug Administration Female sex worker Global Alliance for Vaccines & Immunizations Gross domestic product Gross national income Government of India Human immunodeficiency virus Human papillomavirus Herpes simplex virus-2 International AIDS Vaccine Initiative Injecting drug user Information, education, and communication Men who have sex with men National AIDS Control Organisation (India) Nongovernmental organisation New preventive technology National regulatory authority Purchasing power parity Pre-exposure prophylaxis Research and development Indian rupees State AIDS Control Societies (India) Universal Immunisation Programme Joint United Nations Programme on HIV/AIDS United Nations Development Programme Voluntary counselling and testing centre Vaccine effect on infectiousness Vaccine effect on disease progression Vaccine effect on susceptibility World Health Organization Willingness to pay Willingness to be vaccinated

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Glossary
Term Adoption lag Definition / Explanation The time between licensure of the vaccine by the FDA or EMEA and licensure in India and the point at which the vaccine is licensed for use (at a minimum in private markets), in India. When vaccinated individuals believe they are protected from HIV infection and therefore engage in behaviours that put them at greater risk of exposure to HIV. A vaccination strategy aiming to vaccinate those missed or not eligible for a routine vaccination. A catch-up strategy targets any residual population outside of the routine recipient population(s). Enabling factors and constraints that facilitate or limit demand. The first set of preventive HIV vaccines that are licensed for use. Public vaccination programmes implemented to target (vaccinate) populations at greater risk of exposure to HIV. The time between licensure of a vaccine and commencement of a public vaccination programme. The level of total annual doses or courses of a vaccine at which demand is stable, (i.e., when there is no significant change from year to year in levels of demand). The proportion of those vaccinated who do not return for a needed revaccination. Public vaccination programmes targeting certain populations at lower risk of exposure to HIV. The year during the forecasting period when demand reaches its highest level. The total number of people who receive a complete course of the HIV vaccine within a given period. This is equivalent to the total number of courses (not doses) received. The level of policymaker support for public policy initiatives. The market for a vaccine that is not funded or subsidized by public funds and not implemented as a public health programme. In this analysis, the private market represents individual demand from those willing and able to pay for the vaccine and also willing to be vaccinated. See implementation lag above. Vaccine demand or utilisation funded by the public sector. The time between regulatory approval in the U.S. or Europe and national regulatory approval in India. The vaccination strategy employed to maintain protection when a vaccine with a limited duration is used.
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Behavioural disinhibition

Catch-up vaccination strategy

Determinants of demand First-generation preventive HIV vaccines High-risk vaccination programme Implementation lag Long-term stable demand

Loss to follow-up Low-risk vaccination programme Peak year of demand People fully vaccinated

Political will Private market

Programme implementation lag Public market Regulatory lag Re-vaccination strategy

Term Routine vaccination strategy

Targeting Vaccine profile

Wastage factor

Definition / Explanation The vaccination strategy employed to vaccinate new entrants to certain sub-populations as part of an annual programme. The routine vaccination strategy may vary in approach depending on the sub-population (e.g., schoolbased programmes for adolescents or vaccination, harm reduction programmes for injecting drug users (IDUs), or outreach/condom promotion programmes for sex workers. The selection of specific population groups for vaccination based on such criteria as risk of exposure, age, etc. The key vaccine characteristics that describe the vaccine, including efficacy, duration of protection, price per dose, dosing regime, and clade-specificity. The amount of vaccines lost due to inefficiencies in storage, transport, or usage (e.g., poor cold chain system, faulty syringes, etc.)

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Executive Summary
At the end of 2005, an estimated 5.2 million people were living with the human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) in India, representing 12-15% of the global burden of disease from HIV/AIDS. Vigorous prevention programmes are reported to be slowing the spread of the epidemic in parts of India. Despite these efforts, however, more than a quarter of a million people died of AIDSrelated illnesses and thousands of others were newly infected with HIV in India during 2005. Under these circumstances, there is an urgent need for stronger and more effective HIV prevention methods, including an HIV vaccine. Ongoing research and development (R&D) for HIV vaccines needs to remain a high priority in the search for new preventive technologies. The eventual launch of such a vaccine could make an enormous difference in reversing the epidemic and saving millions of lives. To make such an impact, however, an HIV vaccine needs to be widely available and accessible and must be implemented quickly. Demand forecasts for products still in an early stage of development, such as an HIV vaccine, can provide a valuable decision-making tool to help achieve these goals. A consultation was conducted in 2006 to assess the preferences and perceptions of Indian policymakers and policy influencers which could affect demand for a first-generation preventive HIV vaccine in India. The aim of the consultation was to understand (1) how the country might adopt and implement an HIV vaccine, and how public and private markets might react to an HIV vaccine with given characteristics, (2) which groups might be targeted by the government to receive such a vaccine, and (3) how quickly the vaccine might become available and be taken up in various population groups. The consultation findings suggested the following: Given the multiple regulatory approvals needed to secure licensure for an HIV vaccine in India, it is likely that it would take 2-3 years for the vaccine to be implemented in India after initial licensure in the United States and Europe (assuming the vaccine is effective across all strains of HIV-1). However, the regulatory review process in India might be expedited if India continues to participate in HIV vaccine clinical trials beyond the current Phase I trial. Based on the results of the consultations, it seems unlikely that the Indian public sector (national and state-level) would endorse the use of an HIV vaccine in its programmes if the efficacy or duration of protection is below certain levels, or if the price per course is above a certain value. Vaccine efficacy of at least 50% would be necessary to persuade the public sector to mount a vaccination programme for groups at higher risk of exposure to HIV -groups such as commercial sex workers and injecting drug users. Those consulted for the study indicated that an even higher level of efficacy -- at least 70% -- would be needed to convince the public sector to subsidize and promote the use of the vaccine in the broader adult population groups which face relatively lower risks of HIV infection. In this instance, epidemiological, behavioural, and cultural factors specific to India point to the fact that the government might decide to target only adolescents and young adults under 26 years of age, rather than promoting the vaccine for all sexually-active adults.

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Consultations suggested that an HIV vaccine with an efficacy threshold as low as 30% efficacy could nevertheless be seen as acceptable and be taken up by paying individuals in the private market. Finally, a vaccine would need to have a duration of protection of at least three years and a price paid by the Government of India (GOI) to suppliers of US$20 (Rs 880) per course or less, in order for decision-makers to use the HIV vaccine in public programmes. Implementing HIV vaccine programmes could be delayed by safety concerns and fears about behavioural disinhibition, i.e., worries that vaccinated individuals would believe that they are fully protected from HIV infection and thus engage in riskier behaviour. Overcoming this worry could be crucial to ensuring rapid vaccine introduction and uptake in India. To do so, a partially efficacious vaccine may have to be introduced in tandem with vigorous informational, education, and communication (IEC) interventions to mitigate the anticipated adverse effects of behavioural disinhibition. Such interventions could be complex and costly to implement, and would add to the overall price tag for an HIV vaccination programme in India. On the basis of these qualitative interview findings, the International AIDS Vaccine Initiative (IAVI) and its consultants from the Boston Consulting Group developed a model to generate baseline forecasts and other scenario analyses which allow policy-makers to explore the effects of varying epidemiological, regulatory, and health systems assumptions on demand projections. For vaccines of medium and higher efficacy (50% and 70%, respectively), peak demand in India from public and private markets is projected to range between 15.2-41.5 million persons fully vaccinated per year. Total cumulative demand over three decades for such vaccines is estimated at 221-788 million complete courses -- these are robust levels of demand. If the efficacy of a first-generation vaccine falls below 50%, however, anticipated demand could drop significantly, since the GOI would not initiate a public sectorsponsored programme for a vaccine with such limited efficacy. Under these circumstances, demand is projected to be restricted to the private market and over 30 years is estimated to amount to only 24 million complete courses. Assuming tiered pricing between public and private markets (US$10 and $50 per dose, respectively), demand for medium and higher efficacy vaccines could generate annual sales revenues that peak at US$415-$911 million (Rs 1,831-4,017 crore) just seven years after launch. Even levels of demand for a low-efficacy vaccine (30%) could translate into significant revenues for suppliers, with average annual sale revenues projected to be about US$58 million (Rs 255 crore). These revenue projections suggest that under certain market conditions, a first-generation HIV vaccine could account for as much as 1.1-2.4% of expected total annual biopharmaceutical market sales in India. Given that the consultation findings depicted significantly divergent perceptions of the future HIV epidemic in India, we ran scenarios to assess the effect of various epidemiological changes on demand. These indicated that should HIV prevalence remain unchanged from today, average annual baseline demand would be 15 million complete course administered per year. Should the epidemic worsen significantly, the GOI might seek to use an additional 45 million complete course per year.

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Efforts to address regulatory, health systems delivery capacity, and political constraints could increase access to and use of an HIV vaccine by almost 46 million additional people each year over a 30-year period, compared to a vaccine with a medium efficacy. These efforts include strengthened and expedited regulatory processes, expanded capacity of the government health and vaccine delivery system, and greater political and public financial support for HIV vaccines. Without significant increases in financial investment by the GOI or international donors to fund such initiatives, almost two-thirds of the potential gains in access would not materialize. To achieve the aforementioned increases in demand and access, much lead time is required to foster dialogue and implement policy change. Since the search for an HIV vaccine is still likely to take several more years, there is an opportunity to engage vaccine developers, donors, and Indian health care system officials in such a dialogue now, using tools such as this forecasting model. Like all mathematical models, this forecasting model is limited by the quality and availability of data, the inherent uncertainty of the future, and the resulting assumptions that have been made. Over time, lessons can be learned and valuable data gathered as new vaccines such as that for the human papillomarivus (HPV) and other HIV preventive technologies are introduced in India. Richer information would enable more precise and reliable forecasts. In turn, these forecasts could lead to better-informed strategic decisions to prepare for and eventually maximise access to and use of a much needed HIV vaccine. IAVI and its partners are fully prepared to work with the Indian authorities to strengthen such forecasts over the coming years.

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I. Introduction
1.1 Background
Demand has historically been estimated for products that are close to, or already on, the market. Exploring demand forecasts for a product still in an early phase of research and development (R&D) (Longhi et al. 2006), such as a preventive HIV vaccine, is also important: x x x To provide product developers with credible estimates of future market potential and better evaluate the acceptability of pipeline candidates to guide R&D portfolio management and manufacturing investment decisions; To help donors design R&D incentives that include realistic market scenarios; and To provide information to national health officials to prepare delivery infrastructure for future vaccines well before they are introduced.

1.2 Research overview and scope
To assess the potential demand for a health intervention, an understanding of the determinants of demand as well as how a country may respond to these drivers is essential. The International AIDS Vaccine Initiative (IAVI) has undertaken policy research to identify the key determinants of demand for an HIV vaccine and to create a framework to conceptualize how these determinants affect demand (IAVI 2007a). To better understand how India might adopt and implement a first-generation preventive HIV vaccine, researchers interviewed experts to assess the preferences and perceptions of those who make and influence policy. These interview findings have been synthesized along with published data to tailor the conceptual framework and create a demand forecasting model capable of creating scenarios to assess demand and revenues associated with an HIV vaccine in India, given a variety of policy and market conditions in the country. This research does not attempt to address the following issues: x x x Second-generation "follow-on" HIV vaccines, the associated competitive dynamics, and the impact on market demand over time; The therapeutic use of an HIV vaccine designed, tested, and licensed for preventive use; The effect of other new preventive technologies (NPTs), such as microbicides, preexposure prophylaxis (PrEP), and herpes simplex virus (HSV-2) suppression therapies, on HIV vaccine demand — even though these other NPTs might be available in India by the time an HIV vaccine is launched; The social, epidemiological, and financial impacts of HIV vaccine introduction.

x

1.3 Previous demand assessments for HIV vaccines in India
Only one published study exists that assesses potential demand for an HIV vaccine in India (Seshadri et al. 2003). The study assesses the demand for a vaccine in the four
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southern states of Andhra Pradesh, Karnataka, Maharashtra, and Tamil Nadu, focusing on eight potential target groups, including children and early adolescents (newborn to 14 years old). Using estimates of coverage for existing HIV prevention programmes and other health care programmes for each target group, and assuming the ability of an HIV vaccination programme to capitalise on existing interventions, the study estimates demand as well as the financial implications of introducing a single-dose HIV vaccine that costs US$10 per dose. The study provides very useful insights into the potential demand for a preventive HIV vaccine, but its design and assumptions require reappraisal in light of changing scientific opinion. The study does not consider the impact of efficacy and duration of protection on demand for HIV vaccines. Furthermore, the study considers what now seem to be unlikely target groups (children) and overlooks more applicable populations at higher risk of exposure to HIV, such as injecting drug users (IDUs) and men who have sex with men (MSM). Finally, the regional focus of the study was useful at the time, since the HIV epidemic disproportionately affects Southern India (NACO 2004). However, given how fast the epidemic is growing in northern states (in particular Nagaland, Manipur, and Mizoram), a forecast for the entire subcontinent provides significant additional value (NACO 2004).

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II. Determinants of demand and methodological framework
Key determinants or drivers of demand (Table 1) were identified after a review of prior studies (IAVI 2005) and discussion with researchers as part of a wider global demand forecasting study (IAVI 2007a). These determinants were incorporated into a methodological framework (Figure 1), which informed the structure of the forecasting model. The framework was based upon the notion that the determinants act as constraining factors that limit final demand to some fraction of the total population in need.
Table 1. Key determinants of demand Key Determinant Description Population requiring the intervention (e.g., not already infected, at most Need risk, etc.) Vaccine characteristics Product profile Political will Policymaker support Capacity Health care system capacity and effectiveness Government (and donor) funding to pay for public sector vaccine Funding demand; or Private individuals' willingness to pay for the vaccine Acceptability Individual beliefs and attitudes: their willingness to be vaccinated The intended recipient population(s) for the public sector vaccination Targeting programme(s)

The need for an HIV vaccine depends upon the national epidemiological and demographic situation. Need is determined by the incidence, prevalence, and disease burden in a country. Countries with higher prevalence, large disease burdens, and growing epidemics are those with the greatest need for a preventive HIV vaccine. The vaccine's characteristics determine how well, for how long, and for whom the vaccine will work; how easy it will be to transport, store, and administer; and what it costs. These factors are important to policymakers because they influence both the social benefits and risks and the cost of vaccinating a population. Such information often guides public sector decisions about whether or not to use the vaccine, and if it is to be used, by whom. Political will is a crucial determinant of demand because it plays an important role in prioritizing and implementing public health initiatives. Amongst other things, a lack of political will can impede the licensure process of a vaccine, prevent rapid incorporation of a vaccine into national public health initiatives, and limit funding for purchasing vaccines or financing delivery costs. Capacity refers to the availability of resources (monetary or otherwise) available for use within the health care system to introduce public health programmes (e.g., vaccination campaigns) and deliver such health technologies as an HIV vaccine. Capacity determines the availability and ease of access to an HIV vaccine via public markets. From the introduction of other health care interventions, we know that capacity constraints can cause recipient populations in some countries to receive vaccinations years later than those in other parts of the world.

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Funding from national governments or from international donors is essential to guarantee that desired levels of demand in public markets can be financed in low- and middle-income countries. Funding constraints can affect the extent to which a public health care intervention is available and accessible. In privately funded markets, funding constraints are described by individuals' willingness to pay (WTP). The beliefs and attitudes of individuals play a large part in determining a vaccine's acceptability. Acceptability to individuals and the wider society is an important determinant of demand. Unless people are willing to be vaccinated, potential demand will not translate into actual demand and utilization. Lack of acceptance may impede voluntary vaccination (resulting in lower coverage) or limit completion of a full course of vaccination (resulting in lower compliance). The targeting and vaccination strategies employed by policymakers identifies the intended recipient population(s) for the vaccine and how to reach these populations, based on policymakers' perceptions of the extent of the epidemic and their preferences regarding the vaccine's profile (efficacy, safety, duration, price, etc.).
Figure 1. Methodological demand framework, from need to projected demand

x Future State of Epidemic

Number of people who would need an AIDS vaccine Driver: Epidemiological characteristics

x x x x x x x x x x x x

Efficacy Duration Dosing Price Cost Political will Adoption speed/lag Funding Capacity Implementation lags Reach/coverage Targeting

Number of people for whom a vaccine is appropriate given the product profile Driver: Vaccine characteristics

Number of people who can access vaccination Multiple drivers: 'Policy environment characteristics'

x Coverage x Compliance

Number of people likely to take vaccine given attitude and behaviour Driver: Acceptability

Final demand is a fraction of the population in need

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III. Expert consultation
3.1 Rationale and objectives
A consultation of experts was conducted to ensure that the demand forecasts incorporate "ground-level" attitudes and perceptions as well as the likely actions of stakeholders who determine or influence health and finance policy decisions across India. The aim of the expert interviews was to understand: x x x x x x Policymakers' preferences and reactions to first-generation vaccine profiles; Health care decision-making structure and prioritization in India; Health technology licensure/approval processes and implementation time frames; Policymakers' perceptions about the future state of the epidemic; Policymakers' preferences for targeting strategies if an HIV vaccine became available; and Strategies envisaged to deliver and fund future vaccination programmes.

3.2 Interview methods and interviewee selection
Forecasting demand for global public health products such as an HIV vaccine is a complex problem involving a plethora of unknown variables. In such instances, forecasting experts often break the problem down into its component parts and assess smaller parts of the bigger problem (MacGregor and Armstrong 1994). Following this methodology, assessing demand for an HIV vaccine was broken down into specific questions about the key determinants of demand described above. Questions about these determinants were then compiled into a semi-structured interview guide.1 To determine the likely range of vaccine characteristics that might describe a firstgeneration HIV vaccine, an initial consultation was conducted with HIV vaccine R&D experts from around the world. This identified several key vaccine characteristics: (1) efficacy, (2) dosing schedule, (3) duration of protection, and (4) price per full course of vaccination. In addition, other characteristics (e.g., safety, clade specificity, and delivery and storage requirements and associated costs) were also considered. However, for simplicity, it was assumed that the vaccine would be safe (with no serious adverse effects) and would confer cross-clade protection. Appendix II details the characteristics and range of hypothetical first-generation HIV vaccine profiles tested during the interviews. Individuals from multiple stakeholder groups in India representing those who might influence the adoption and implementation of an HIV vaccine were interviewed. In all, 43 interviews were conducted across stakeholder groups in India. The interviews were conducted in New Delhi (22), Chennai (7), and Mumbai (9), with five interviews conducted with stakeholders based in other parts of the country. The 43 interviews were divided amongst the following stakeholder groups: 13 civil society representatives; seven health technology developers, manufacturers, suppliers; five representatives of donor and

1

Available on request.

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multilateral institutions; seven government representatives; and 11 representatives of research and academic institutions (see Appendix III for further details). The findings from the expert consultations were synthesised and formed the basis of many of the forecasting model assumptions described in the next section.

3.3 Interview results
3.3.1 Perceptions of the future HIV epidemic in India Perceptions of the future nature of the HIV epidemic are important because they help show whether need will increase, decrease, or stay at the same level as today. The level of need is a crucial driver of demand, as described above. There were significantly divergent views among public sector stakeholders (government officials and policymakers), representatives of civil society, and representatives of donor and multilateral institutions about perceptions of the HIV epidemic in India and whether it has started to plateau, as has been suggested in recent research (Kumar et al. 2006) (Figure 2).
Figure 2. Is the AIDS epidemic plateauing in India?
100% No 33%

80%

No 43%

No 44% No 80%

Percent of Respondents

60%

No 90%

40%

Yes 67%

Yes 57%

Yes 56% Yes 20%

20% Yes 10% Civil Society

0% Government Industry Representatives Research & Academia Donor & Multilateral Community

Stakeholder Group

Most respondents across all stakeholder groups feel that the epidemic is unlikely to spread as virulently as it has in many parts of Africa. However, every respondent believes that HIV will remain a serious public health crisis in India, even if prevalence has already peaked.

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3.3.2 Health care decision-making structure in India Indian health care system policies and programmes are both vertical and horizontal in nature: The vertical GOI-controlled programmes address diseases of national concern and are grouped under what is known as the "Union List." Approximately 75% of all vaccinations in India are distributed through vertical programmes, with the remaining 25% distributed through private market channels. As a political priority, a vertical programme determined by the National AIDS Control Organisation (NACO) carries out HIV treatment and prevention policy. These national policies are administered by 38 State AIDS Control Societies (SACS), which operate in all states of India and Union Territories, as well as in three large cities. The consultation results suggest that if an HIV vaccine is licensed in India, policy is likely to be set by the NACO programme. Additionally, there may be horizontal programme components administered via SACS as part of a wider initiative (e.g., associated counselling). Nonetheless, these findings suggest that delivery of future HIV vaccines is likely to be determined at a national level via a vertical programme and suggest that the forecasting model should take a national (as opposed to regional or state-specific) perspective. 3.3.3 Health technology approval processes and adoption timeframes Responses seem to suggest that approval from the U.S. Food and Drug Administration (FDA) or the European Medicines Agency (EMEA), and possibly World Health Organization (WHO) prequalification, would be required to secure approval in India. In the absence of Indian Phase III trials, bridging studies (safety and immunogenicity) in an Indian population would also be required. Approval from the Recombinant DNA Committee and the Genetic Engineering Approval Committee might be required, depending on the vaccine technology. Given the multiple levels of approval both internationally and nationally, these findings suggest that an HIV vaccine would be licensed for use in India (adopted) at least two to three years after initial licensure in the U.S. and the European region. Most respondents feel that HIV vaccine regulatory approval would be expedited if India continues to participate in HIV vaccine discovery and development beyond current Phase I trial activities. One biopharmaceutical industry representative suggests: The key to faster adoption would be to include Indian participants in Phase III trials … Then the need for bioequivalent studies would be negated and the developers would actually save themselves the time required for the additional study plus could also reduce approval time by the Drug Controller General to less than one year. Researchers outside the private biopharmaceutical industry also commented on the importance of involving India in the development and manufacturing process. For example, one says: A 'Made in India' stamp is important for faster adoption. If a vaccine is developed in partnership with India or is being manufactured in India, it would make a difference.

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It will also help overcome the 'Guinea Pig Syndrome' to which Indians are very sensitive. 3.3.4 Minimum acceptable level of vaccine efficacy There was significant variation of opinion among stakeholder groups about the minimum acceptable level of vaccine efficacy (Table 2). Efficacy was understood to mean two things: First, the vaccine prevents infection in those vaccinated prior to exposure by a fixed percentage (known as the 'vaccine effect on susceptibility', VES); and second, the vaccine also lowers transmissibility if infected after being vaccinated (known as the 'vaccine effect on infectiousness', VEI) by the same magnitude as VES. For further details, refer to Appendix II.
Table 2. Minimum acceptable level of vaccine efficacy Stakeholder Group Civil society Donors/multilaterals Government Research & academia Industry representatives Average Average Minimum Acceptable Level of Vaccine Efficacy Populations at Higher Risk Populations at Low Risk 30% 60% 40% 70% 50% 80% 50% 80% 60% 70% 50% 70%

Most agree that efficacy levels will be major determinants of the target populations. Overall, responses suggest that the minimum acceptable threshold of efficacy must be 50% before the GOI would sanction use of an HIV vaccine for populations at higher risk of exposure to HIV, while in populations at lower risk of exposure, the minimum acceptable efficacy threshold might be as high as 70%. 3.3.5 Minimum acceptable duration of protection and maximum acceptable price Most stakeholder groups feel that a vaccine with a duration of protection of at least three years will be necessary. Across all stakeholder groups, the range for prices deemed to be acceptable to the public sector is between US$1-$10 per dose (Table 3), assuming a twodose vaccine. Unlike efficacy, these do not vary much when respondents consider different target groups.
Table 3. Ranges for the minimum acceptable levels of protective duration and maximum price per dose Stakeholder Group Civil society Donors/multilaterals Government Research & academia Private sector industry
a

Minimum Acceptable Duration of Protection (Years) 1-5 years 1-3 years 5 years 3-5 years 3-5 years

Maximum Acceptable Price Per Dosea (US$) $1-2 $1-2 $1-10 $1-2 $1-10

Assumes a two-dose vaccine.

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3.3.6 Targeting Most stakeholder groups feel that the GOI would favour targeting populations at higher risk of exposure to HIV first and foremost and only consider targeting populations at lower risk if vaccine efficacy is high (t70%). When populations at lower risk are considered, only adolescents and young adults (13- to 26-year-olds) will be targeted (Table 4). This is because there seems to be a prevailing view amongst those interviewed that once an Indian is married (typically by the age of 26), the risk of contracting HIV significantly diminishes, thereby removing the need for an HIV vaccine.2
Table 4. Target age range for populations at lower risk of exposure to HIV Target Age Range for Populations at Stakeholder Group Lower Risk Civil society 13- to 26-year-olds Donors/multilaterals 16- to 21-year-olds Government 14- to 25-year-olds Research & academia 16- to 26-year-olds Private sector industry 15- to 19-year-olds Overall age range 13- to 26-year-olds

3.3.7 Implementation lag and uptake speed There is uncertainty about the likely speed of implementation of HIV vaccine programmes and the subsequent uptake of the vaccine in India following regulatory approval. Respondents cited a host of confounding factors that could slow or expedite implementation and uptake. These include:

x x x

Concerns about potential behavioural disinhibition (see subsection 3.3.9); The fact that HIV is a key political priority and hence political will would ensure appropriate resourcing and no delays; and India's continued involvement in HIV vaccine clinical research would ease safety concerns, provide experience in the use of the vaccine, and ensure relatively rapid implementation and uptake.

As such, there was no clear view amongst respondents about implementation lags and the speed of uptake. 3.3.8 Coverage Civil society and multilateral representatives are doubtful about the ability of public sector HIV vaccination programmes to reach and cover populations at higher risk of exposure because these populations are unlikely to present themselves at state-run institutions. As such, nongovernmental organisations (NGOs) may represent the only viable delivery channels for interventions (education, condoms) targeting populations at higher risk.
2

That said, some stakeholders, particularly from civil society groups and multilateral organisations, feel that social norms are changing and that married women are increasingly being infected by husbands who are not monogamous. They feel that broader prevention (and vaccination) programmes may be necessary to protect these increasingly vulnerable populations.

12

The obvious place to administer an HIV vaccine to adolescents would be through schools and colleges. However, access to high schools and higher education, as well as high dropout rates, suggest that such vaccination programmes might not adequately cover large portions of this target population. All of this suggests that the target populations for an HIV vaccine are likely to be hard to reach. We thus conclude that maximum coverage rates in India are likely to be no greater than 40%. 3.3.9 Other implementation issues Many respondents stressed concerns about behavioural disinhibition. Behavioural disinhibition refers to the increase in high-risk sexual behaviour among vaccine recipients in response to perceptions of safety conferred by the vaccine as a protective barrier. For example, a public health expert said: A 70 percent efficacy is acceptable, 50 percent is the bare minimum, but the greater the inefficacy, the greater the negative effects of behavioural disinhibition. Future studies should continue to assess the likelihood of behavioural disinhibition and add to the growing body of evidence demonstrating that such concerns are minimal or unfounded (Aral 2006; Bartholow et al. 2005). A significant number of stakeholders feel that in the absence of data to the contrary, behavioural disinhibition would occur if a partially efficacious vaccine were launched and suggest that the vaccine would therefore need to be introduced in tandem with other IEC interventions to mitigate the expected risk (Figure 3). A vaccine that is not highly efficacious will have strong challenges for an educational effort both to address partial efficacy as well as to address behavioural disinhibition. People are looking for a substitute for condoms rather than for something in addition to their use. (industry/private sector stakeholder) Several experts, particularly those from civil society organisations, say that the necessary health outreach and communication could be undertaken alongside current IEC services. However, many note that many existing IEC programmes are under-funded and require additional resources to build capacity if they are to become effective. Respondents across all stakeholder groups mention that many current service promotion communications do not reach intended audiences, and in particular, key populations at higher risk. Several point to voluntary counselling and testing centres (VCTCs) across India that have been unable to effectively reach the majority of potential beneficiaries and remain under-utilized. For these reasons, many feel that serious communications challenges must be addressed in tandem with the wide-scale implementation of any partially effective vaccine.

13

Figure 3. Behavioural disinhibition concerns with partial efficacy vaccines
60%

Percent of Stakeholders Expressing Concern

50%

National Average Across All Stakeholder Groups 40%
Researchers & Academics 50% Civil Society 50%

40%

30%

Donors & Multilateral Institutions 40%

Government & Policy Makers 40%

20%

10%

Industry Representatives 0%
0%

Stakeholder Group

14

IV. Demand forecasting model
4.1 Model overview
IAVI created a model to estimate global demand based upon the aforementioned key determinants of demand and findings from the expert consultation. This model aims to reflect how India might respond to the availability of an HIV vaccine. It also provides a national picture of HIV vaccine demand, with outputs defined according to whether demand originates in public or private markets. Assessing public and private demand is important because these markets respond differently to the determinants of demand. The timing, volume, and value of demand from each market may differ significantly and should be viewed separately. Public market demand is described by two programmes: (1) the high-risk population programme and (2) the low-risk population programme. The private market is viewed as a single programme. The contribution to demand by each of the programmes is determined by three types of information: vaccine profile descriptors, country profile descriptors, and country-level behavioural parameters. The model allows users to change the values for the descriptors and the parameters. Its flexibility enables users to explore the effects of changing the assumptions, the underlying data, and the predictive algorithms of the model. 4.1.1 Vaccine profile descriptors Three key vaccine characteristics have been identified: efficacy, duration of protection, and cost (vaccine plus delivery costs). Different combinations of these characteristics were used to produce three vaccine profile scenarios (Table 5). These scenarios — Low, Medium (baseline), and High — were assembled to represent the broad array of product profile characteristics that a first-generation preventive HIV vaccine might take. In the Low Vaccine Profile Scenario (hereafter the Low Scenario), we assume that the vaccine has a 30% level of efficacy, which vaccine experts regard as the lowest level that might be acceptable to regulators, and a duration of protection of three years. In the Medium Scenario, which also represents our baseline scenario, the efficacy is assumed to be 50%. In the High Scenario, we assume that efficacy is 70% and the duration of protection is five years. These vaccine profile scenario assumptions represent realistic and achievable but also aspirational goals. The ranges of efficacy and duration are certainly in line with current scientific expectations, although there is little certainty about the dosing regimen or the delivery and storage requirements. Ideally, the vaccine would require as few doses as possible and be stable at room temperature. However, scientific thinking suggests that first-generation HIV vaccines will require a prime plus boost combination (i.e., at least two doses). Many vaccines also require some sort of refrigeration. In each of these scenarios, it is assumed that India's public market price is fixed at US$10 per dose, which would be borne by the GOI (possibly with support from donors), while the private market price is assumed to be US$50 per dose (except in the High Scenario, in

15

which the private market price is assumed to be US$10 per dose). The private market price is what consumers not patronising GOI-sponsored vaccination programmes would pay. The prices chosen for the analysis are based on current pricing structures for newly licensed vaccines (Table 6). For simplicity, no price decline is assumed over time in either the public or private markets.
Table 5. Efficacy and duration of protection, by scenario
Vaccine Profile Scenarios Low Vaccine efficacya Duration of protection Dosing schedule (for a full vaccination course) Private market Price per dose Public Market Delivery/storage requirements (upon which delivery costs are loosely based) Private market
b

Medium 50% 3 years 2-dose prime-boost combination

High 70% 5 years

30% 3 years

US$50/dose (Rs 2,200/dose)

US$50/dose (Rs 2,200/dose) US$10/dose (Rs 440/dose)

US$10/dose (Rs 440/dose)

Single vial/cold chain of 2-8ºC

US$0.01/dose (Rs 0.44/dose) Delivery costb US$3.00/dose Public market: high risk per dose (Rs 1.3/dose) US$2.00/dose Public market: low risk (Rs 0.88/dose) a The vaccine's efficacy is assumed to be effective against all HIV strains or subtypes. b Based on conversion using exchange rate as of January 1, 2007, of US$1 = 44.12Rs (OANDA n.d.). This conversion and rate of exchange is used throughout the rest of the report.

These pricing assumptions may reasonably reflect the cost of investments and risks to producers of an HIV vaccine and are also in line with what is being charged in private markets for some of the newer vaccines in India (Table 6). However, these prices are very high compared to what the GOI is used to paying for vaccines implemented through public programmes.
Table 6. Prices of existing vaccines in India
Vaccine Anti-rabies vaccines Brand Name Rabivax, Raksharab Rabipur GeneVac-B Engerix B Varilix Havrix Quadrimeningo BCG OPV M-VAC Sii
c d

Private Market Retail Price Range US$6-10 (Rs 293-437)/coursea US$45 (Rs 2,000)/courseb US$35 (Rs 1,550)/coursec US$20-30 (Rs 875-1,400)/ coursed US$1-3 (Rs 70-180)/ coursee US$0.20-1 (Rs 8-45)/coursef US$25-30 (Rs 1120-1345)/ coursee US$13-16 (Rs 598-712)/ coursee US$11-15 (Rs 510-650)/ coursee

Estimated Public Market Price US$6 (Rs 300)/ coursea

Hepatitis B vaccine JE vaccine Chickenpox vaccine Hepatitis A Meningococcal vaccine TB vaccine Oral polio vaccine Measles vaccine
a b

US$0.55 (Rs 25)/ coursee US$1.65 (Rs 73)/ coursee US$0.75 (Rs 33)/ coursee
e f

Chennai Online 2004 Belgaumkar 2007

Maya 2006 Tribune News Service 2002

Dhanasiri et al. 2007 Ramachandran 2006

16

4.1.2 Country Profile Descriptors The country descriptors underpin the model, describing the demographic, epidemiological, political, and financial situation in India. These descriptors comprise data from published sources on:

x x x x x x

Demography: population, subpopulation sizes; HIV/AIDS epidemiology: prevalence, burden; Political will: AIDS program effort index (API) score; Ability to pay: purchasing power parity (PPP)-adjusted Gross National Income (GNI) per capita; Health care system capacity: PPP-adjusted GNI per capita; and Funding: projected government and donor funding.

The demographic information is used to estimate the size of target populations. The epidemiological information is used to capture the extent of the epidemic and describe the need for the vaccine. Given that political will is difficult to quantify, the API score is an approximate measurement of a country's level of effort to implement AIDS treatment and HIV prevention programmes. Income as measured by PPP-adjusted GNI per capita is used as a proxy for ability to pay, as well as a measurement of health care capacity. Finally, projected government funding is based on a proportion of national income, a proxy for budgetary constraints that might limit achievable demand (Table 7).
Table 7. Summary of India’s country profile descriptor values (See Appendix IV for details on sources and assumptions) Criterion
Demography

Proxies
N/A

Value(s) for India
In 2015, the following populations in India are estimated to be: o High-risk: 131 million o Low-risk (13-26 yrs): 237 million o Low-risk (13-49 yrs): 614 million o Total: 1,280 million Assumed to have a low prevalence (0.5%) in 2015. (Equivalent to an absolute prevalence of around 6.6 billion people) API score of 59; (i.e., medium political will) Income per capita of $1,292 (i.e., medium income/capacity/ability to pay) In 2015, the corresponding hypothetical funding allocations are as follows: 1.19% of GDP spent on health: US$1,656.0 billion 1% of health budget spent on HIV/AIDS: US$19.7 billion 25% of HIV/AIDS budget available for spending on HIV vaccine: US$49.3 million o If Low Scenario, 15% of HIV/AIDS budget spent on vaccine: US$7.4 million o If Medium Scenario, 50% of HIV/AIDS budget spent on vaccine: US$24.6 million o If High Scenario, 73% of HIV/AIDS budget spent on vaccine: US$36.0 million

Need

Prevalence per capita

Political will Capacity and ability to pay Projected GOI funding for health care budget & predicted allocation to HIV/AIDS programmes & HIV vaccine

AIDS Program Index (API) National income per capita - PPP adjusted National income

17

The country descriptor data assume static values, some of which are categorized according to their value (high, medium, or low) (Appendix IV). This categorization is necessary for applying the algorithms (Appendix V) that define the behavioural parameters. 4.1.3 Country-level behavioural parameters The behavioural parameters describe India's public sector adoption (licensure) and implementation behaviour, as well as private market demand and utilisation behaviour. The public sector adoption and implementation behaviour parameters describe the:

x x x x x x x

Minimum acceptable levels of key vaccine characteristics (efficacy and duration) below which countries would not license and/or implement the vaccine; Maximum acceptable price above which countries would not license and/or implement the vaccine; Time to local regulatory approval; Time to initiate public vaccination programmes; Vaccination strategy; Levels of achievable coverage; and Time it takes each country to achieve these levels of coverage.

The private demand and utilisation behaviour variables describe the:

x x x

Willingness to pay (WTP) for the vaccine; Willingness to be vaccinated (WTV); and Compliance.

The behavioural parameters can be defined by the user or by a set of algorithms (internal to the model) described in Appendix IV. The parameters that are used in the baseline analyses presented here are based on a mixture of all three and are described in more detail in the following sections.

4.2 Public sector adoption and implementation assumptions
4.2.1 National regulatory approval time The model assumes that approval occurs first in North America and Europe through the FDA and EMEA in 2015. But assuming the U.S. and European licensure processes occur before India's overlooks the possibility that a vaccine might be developed outside of the U.S. or Europe or that a clade C-specific vaccine might be developed. In either case, Indian biomedical regulatory authorities might license the vaccine ahead of the FDA and EMEA (if these licensing authorities license such a vaccine at all). Should FDA/EMEA approval take place first, the baseline regulatory approval time for India is assumed to be two years after this point. Compared to historical lags in approval and implementation, this fast approval time is justified by the political prioritisation of AIDS, as well as the presence of HIV vaccine clinical trials in India, which would likely remove the need for local bridging studies.

18

The model assumes that the approval time depends on the vaccine's efficacy level. Vaccines with an efficacy of 30% or less have an approval time of one year longer, while vaccines with 70% or better efficacy would have an approval time of one year less than the baseline. National regulatory authorities (NRAs) may approve highly efficacious products more quickly because the clinical and scientific evidence is stronger and requires less scrutiny and time to assess. We assume that the vaccine would need to demonstrate a minimum level of efficacy of 30% in any particular target population in order to be licensed anywhere in the world. 4.2.2 National implementation decisions Although implementation decisions are based on a variety of factors, including the riskbenefit profile of the intervention and the implications of this profile for cost-effectiveness and affordability, the model assumes that public sector implementation decisions are based solely on the acceptability of the vaccine's profile (in terms of efficacy, duration, and price per dose). If the vaccine profile meets minimum acceptable thresholds across all three profile dimensions, the GOI will implement it in a particular target population. The model assumes that the minimum acceptable level of efficacy (efficacy threshold) varies by target population. Therefore, given a particular level of vaccine efficacy, the GOI might implement the vaccine in only the populations at higher risk of exposure to HIV as opposed to more broadly in lower risk populations. Based on the findings from the expert consultation, the model assumes that these implementation thresholds are set at 30% and 70% efficacy (for high-risk and low-risk programmes, respectively), with a minimum duration of protection of three years and a maximum acceptable price to the public sector of US$10 (Rs 440) per dose. 4.2.3 Vaccination programmes: recipient populations Because current scientific opinion assumes that preventive HIV vaccines would be administered to HIV-uninfected individuals, the population to be vaccinated includes those confirmed as HIV-negative. However, since HIV testing prior to vaccination will be logistically difficult and expensive, the starting population in this model is the total population. This assumes two distinct population groupings: populations at higher risk of exposure to HIV, and populations at lower risk of exposure. Populations at higher risk of exposure to HIV It is assumed that the populations at higher risk include female sex workers (FSWs), IDUs, and MSMs. The size of these populations is based on three UNAIDS-commissioned studies of prevalence in each of these populations (FSWs: Population Division of the Department of Economic and Social Affairs n.d.; IDUs: Vandepitte et al. 2006; MSM: Aceijas et al. 2004). These populations have been estimated to total almost 131 million persons in India by 2015 (Table 7). Although other groups might also be target recipients (e.g., migrant workers, truck drivers, health care workers), they are not included in our model, due to a lack of available data. Populations at lower risk of exposure to HIV Interview findings suggested that the GOI is likely to target certain populations at lower risk of exposure to HIV: adolescents and young adults who are not yet married. Young adults who have married are deemed to no longer be a target population because they are

19

assumed to be at such low risk of exposure that it is no longer necessary to vaccinate them. For purposes of the baseline analysis, low-risk populations are defined as those outside the high-risk populations 13 to 26 years old, which is estimated to be about 237 million persons in 2015 (Table 7). This age range seems appropriate given social norms in India: the average age of sexual debut is 13 to 15 years old (WHO 2004), while the average age of marriage is 18.7 years for females and 23.4 years for males (UNFPA 2005), and 91% of women live with their husbands by 25 years of age (International Institute for Population Sciences 2000). 4.2.4 Programme implementation lags Even after a vaccine has been approved for licensure by national regulatory authorities, there may be secondary implementation lags that further delay product emergence in public markets. These delays would occur because officials are waiting to learn from the experience of implementation in other countries or because of the time it takes for them to adequately scale up delivery infrastructure. Within the model, the lag to implement a particular public-sector vaccination programme depends upon the population targeted. High-risk population programmes would presumably be initiated first, as suggested in the interview findings. These would then be followed by low-risk population programmes. With no clear view about how long these lags might be, we assume that experience from clinical trials and continued political impetus will prevail and ensure that implementation lags are relatively short (i.e., two years to initiate high-risk programmes and three years to initiate low-risk programmes after licensure). 4.2.5 Post-licensure decision uptake speed Separate from the licensure approval decision and implementation lags is the speed or intensity with which the implementation of the vaccination strategy might occur. The uptake speed describes the time to achieve the maximum achievable rate of coverage. It is assumed that India would be able to achieve the maximum expected coverage five years after initiating the high-risk programme and five years after initiating the low-risk programme. 4.2.6 Vaccination strategy In this model, three types of vaccination strategy are considered: a primary routine annual vaccination strategy, a catch-up vaccination strategy, and a re-vaccination strategy. x Routine vaccinations refer to the approach employed to vaccinate new entrants to certain sub-populations in an annual programme. For example, if adolescents 13 to 16 years old are the sole target group, then a routine strategy might involve a schoolbased programme that vaccinates every 13-year-old in school each year. Alternatively, a routine strategy targeting IDUs might focus on individuals using needle exchange programmes who had not already received an HIV vaccination. Catch-up vaccinations involve vaccinating those missed or not eligible for a routine vaccination. The catch-up strategy targets any residual population outside the routine recipient population(s). To continue the example from above, if adolescents 13 to 16 years old are the target group, then the catch-up strategy would attempt to vaccinate those 13-year-olds missed by the routine vaccinations offered that year, as well as

x

20

those 14 to 16 years old who weren't vaccinated when they were eligible for a routine vaccination.
x

Re-vaccinations are required when vaccines have a limited duration. If an HIV vaccine is assumed to provide five years of protection, individuals will need to be re-vaccinated every five years while they are in the eligible population. If a primary routine programme involves an adolescent group 15 to 19 years old, with a five-year duration of protection, no re-vaccination is required. On the other hand, if the general population, aged 15 to 49 years, is targeted, then a vaccine with a five-year duration would involve up to seven re-vaccinations for each individual.

Two further assumptions regarding re-vaccination have been made. First, in the absence of clinical evidence, re-vaccination is assumed to require only a single dose. Second, only 75% of people requiring a re-vaccination are assumed to return. 4.2.7 Coverage, vaccine acceptability, compliance, and wastage The model is designed to enable analysis of demand with respect to coverage, vaccine acceptability, compliance, and wastage by target population as well as by vaccination strategy. However, due to lack of available data, we consider only coverage and wastage in the analyses presented here. In addition, the coverage rate assumed, which describes the proportion of the target population who receive a full course of vaccination, accounts to some extent for imperfect compliance to a multi-dose vaccination course. Coverage rates in the model for target populations at lower and higher risk of exposure for both routine annual strategies and catch-up strategies are both assumed to be 40%. We assume a wastage factor of 10% within the model. Hence for every ten people who are fully vaccinated, one course is wasted.
Table 8. Summary of India's public sector adoption and implementation behaviours Adoption/implementation behaviour
Minimum acceptable level of vaccine efficacy Minimum acceptable level of vaccine duration Minimum acceptable price per dose Local regulatory approval lag after FDA/EMEA approval in 2015 Programme implementation lag

High-risk (vulnerable population) programme
50% 3 years US$10.00 (Rs 440)

Low-risk (adolescent/general population) programme
70% 3 years US$10.00 (Rs 440)

2 years (therefore approved in India in 2017) 2 years (beyond local regulatory approval lag; i.e. high-risk programme implemented in 2019) 16-49 years 5 years 25% 10% 40% 3 years (beyond local regulatory approval lag; i.e. low-risk programme implemented in 2020) 13-26 years 5 years

Eligible age range of target population Time to peak coverage (following programme implementation) Loss-to-follow-up rate Wastage factor Maximum coverage rate

21

4.3 Private market modelling assumptions
The private market for a vaccine is neither funded nor implemented by the public sector. It is driven by individuals who are willing and able to pay for the vaccine, and is likely to include firms purchasing the vaccine for their employees as part of health care benefits. However, due to a lack of information on all potential private markets, only individual private demand is considered here. Licensure (Adoption) Decision: The efficacy and duration thresholds in the private market are set to the minimum levels realistic for a first-generation vaccine: 30% and three years, respectively. It is assumed that if a vaccine achieves these minimum standards, it would be licensed, and individuals would be able to buy the product via private markets, even in the absence of public programmes. An individual is assumed to be willing to pay a specified proportion of his or her income, irrespective of the vaccine profile. This threshold is set in the baseline so that the cost of a full course of the vaccine in the private market is always 50% or less of an individual's weekly income. In the Low and Medium (baseline) scenarios, the vaccine price in the private market is set at US$50 per dose (Rs 2,200). An individual would need to have an annual income of at least US$10,400 (Rs 4.6 lakhs) to buy vaccine via the private market. The proportion of persons demanding the vaccine via the private market would be those 16 to 49 years old at or above that income level. If the private market price drops to US$10 per dose (Rs 440), as is the case in the High Profile Scenario the minimum annual income necessary to afford the vaccine would be US$2,080 (Rs 0.9 lakhs). It is assumed that if a low-risk public programme is initiated, then 50% of those 13-to-26year-olds willing and able to pay for the vaccine via the private market will demand the vaccine via the public programme, since rational individuals will seek to minimize their expenditures. Although the GOI could introduce means testing to avoid to ensure that the programme is used only by lower-income individuals, this option has been ignored for the purposes of this model. Regulatory Lag: For the private market, the regulatory lag is the same as for public initiatives: If the FDA or EMEA approves the technology in 2015, the HIV vaccine will be licensed about two years later in India. Private Programme Lag: The model assumes no private programme implementation lag. Willingness to be Vaccinated (WTV): The proportion of Indians WTV in the private market represents those who believe they need the vaccine and are willing and able to pay for it. This proportion of people who might believe they need the vaccine is set at 10%, the same percentage used to describe the size of the populations at higher risk of exposure to HIV. Maximum Coverage: In the private market, we assume that 100% of those who are willing to be vaccinated can be covered.

22

Uptake Speed: We assume that the uptake speed in the private market depends on the GOI's decision to implement the vaccine. If the vaccine is implemented in public programmes, then we assume that uptake is fast (three years to achieve maximum coverage following licensure in India). If the GOI does not implement the vaccine, as is the case for low-efficacy vaccines (30%), then we assume uptake speed will be slow: six years to achieve maximum coverage following licensure. These assumptions are based on the premise that without GOI endorsement, private individuals may be more cautious about using a low-efficacy vaccine. Compliance: We assume that 80% of those who choose to purchase an HIV vaccine through a private health care provider will complete a course of two or more doses. Re-vaccinations: Like the public initiatives, the baseline forecasts in the model assume that 25% of those who require re-vaccination are lost to follow-up, and those who are revaccinated require only a single dose.
Table 9. Summary of India's private market adoption and usage behaviours Adoption/usage behaviour Local regulatory approval lag (years after FDA or EMEA) Minimum acceptable level of vaccine efficacy Minimum acceptable duration of protection WTP threshold (for $50/dose vaccine) WTP threshold (for $10/dose vaccine) Programmatic implementation lag Uptake speed Switching from private to public market programmes when latter become available Compliance rate Re-vaccination loss-to-follow- up rate Private market 2 years (same as public markets) 30% 3 years Annual income > $10,400 Annual income > $2,080 N/A 3-6 years (depending on vaccine profile) 50% 80% 25%

23

V. Results and discussion
5.1 Overview
India-specific demand forecasts are generated from expert consultation findings and the model described above. They highlight the relative importance of the key determinants of demand and illustrate the types of analyses that can be undertaken using the demand forecasting model. We did not intend to generate a single estimate or number to reflect demand. Rather, generating various forecasts illustrates the magnitudes of demand given a range of assumptions about the future technical, epidemiological, economic, and socio-political environment that India might face when a first-generation HIV vaccine becomes available. The results of the vaccine profile scenario are considered first, comparing the relative contributions of the public and private markets in India. These are then considered in revenue terms from the perspective of private industry (i.e., vaccine developers, manufacturers, and suppliers). Finally, the results are considered from the perspective of the GOI, donors, and other multilateral institutions. Future GOI funding scenarios, the future epidemic scenarios, and the policy intervention scenarios are also described and discussed.

5.2 Vaccine profile demand scenarios: public versus private markets
The three vaccine profile assumptions (Table 5) describe vaccine efficacy and duration of protection and its price in the public and private markets. Figure 4 illustrates how these vaccine profile scenarios affect the demand forecasts for India over a 30-year time horizon. In general, more favourable vaccine profiles (higher levels of efficacy and duration) result in higher levels of demand in India.

24

Figure 4. Total annual demand forecasts for India (given various vaccine profile assumptions)
45

40

Number of Complete Courses (Millions)

35

High Vaccine Profile (70% efficacy, 5 year duration, Price=WTP)

30

25

20

15
Medium Vaccine Profile (50% efficacy, 3 year duration, Tiered pricing)

10

5

Low Vaccine Profile (30% efficacy, 3 year duration, Tiered pricing)

0 0 5 10 15 20 25 30

Years Since FDA/EMEA Licensure

The forecasts illustrated throughout this report measure national demand in terms of complete courses received. We assume that all vaccine profiles are based on a two-dose (prime-boost) regimen. To convert the number of complete courses into doses, the assumptions regarding a 10% wastage factor should be noted. This means that the total number of doses demanded is more than twice the total number of courses. The forecasts indicate low levels of demand in the Low Vaccine Profile Scenario, modest levels of demand in the Medium Vaccine Profile Scenario, and high levels of demand in the High Vaccine Profile Scenario. The variability in the magnitude of demand can be explained: – by the acceptable thresholds of vaccine characteristics by market type (public or private) and target population (high or low risk) as described in Tables 8 and 9; and – by the relative contribution to cumulative demand of private versus public initiatives described in Table 10. (NB: The acceptable thresholds of vaccine characteristics in India mean that a vaccine must be at least 50% efficacious for the GOI to implement it in high-risk populations and 70% efficacious for implementation in low-risk populations; see section 4.2 for further details). The model assumes that the GOI would not be willing to use low-efficacy vaccines (30% efficacy) in public markets. Therefore, in the Low Vaccine Profile Scenario, all of the demand forecasted (100%) originates from the private market. In the Medium Vaccine Profile Scenario, where the vaccine efficacy is 50%, there is demand from both the private

25

market (11%) as well as the public high-risk population programme (89%). However, only in the High Vaccine Profile Scenario, where vaccine efficacy is assumed to be 70%, does the demand for an HIV vaccine in India comprise private (6%), high-risk (21%), and low-risk (73%) population components. Since the low-risk programme targets a broad population (all 13- to 26-year-olds), the volume of demand in the High Vaccine Profile Scenario is significantly higher than in the other scenarios.
Table 10. Relative contribution to cumulative demand of private versus public initiatives
Vaccine Profile Scenarios Millions of courses (% of market) Millions of courses (% of market) Millions of courses (% of market) Low 24.0 (100.0%) Medium 24.4 (11.1%) 196.6 (88.9%) High 49.8 (6.3%) 162.9 (20.7%) 575.6 (73.0%)

Private market High-risk population programme Low-risk population programme

Public market

In all three vaccine profile scenarios, demand peaks seven to eight years after vaccine launch (Table 11). This is due to a combination of regulatory and implementation lags and the time to achieve maximum coverage.
Table 11. Volume of demand in India across scenarios
Vaccine Profile Scenarios Low Peak year of demand (year of maximum annual courses demanded) Demand during peak year, in millions of courses Cumulative total demand over 30-year period, in millions of courses Average annual "steady-state" demand over 30 years, in millions of courses 8 1.2 24.0 0.8 Medium 7 15.2 221.1 7.1 High 7 41.5 788.3 25.4

5.3 Results and implications for donors and policymakers
5.3.1 Composition of demand by vaccination strategy Figure 6 provides a breakdown of the relative contribution of the three different vaccination strategies (routine, catch-up, and re-vaccination) for the Medium Vaccine Profile Scenario over the 30-year period. The first years after vaccine licensure are dominated by the catch-up strategy, which comprises more than 50% of total demand for the first 10 to 12 years. However, after year 12, the catch-up vaccination strategy no longer contributes to demand, at which point India’s demand is made up entirely by the other two strategies, particularly re-vaccinations. The re-vaccination strategy accounts for the oscillating peaks and troughs visible in the Medium and High forecasts in Figure 5, as demand increases and decreases with each re-vaccination cycle. These peaks are more pronounced in the earlier years reflecting the steep rise and fall first experienced as a result of the initial catch-up strategy (Figure 5). The initial effect of the catch-up strategy and subsequent effects on the re-vaccination strategy are more clearly apparent when the three strategies are separated out (Figure 6).
26

Figure 5. Total annual demand by vaccination strategy (Medium Scenario)
Re-vaccination Strategy Primary Routine Vaccination Strategy Catch-up Strategy
14 16

Figure 6. Separating the effects of each vaccination strategy (Medium Scenario)

16

14

12

12

10

10

8

8

6

6

Number of Complete Courses (Millions)

2

2

0
10 15 20 25 30

0 0 5 10 15 20 25 30

0

5

Year since EMEA/FDA Licensure

Number of Complete Courses (Millions)
4

4

27 27

It may be important for policymakers to understand the effect of these different strategies on demand over time, particularly if different delivery mechanisms are required for each of these strategies. For example, routine vaccinations may occur at schools for populations at lower risk and at sexual health clinics or VCTCs for populations at higher risk. Catch-up vaccinations, on the other hand, might be delivered via some mass campaign-based vaccination approach that moves from town to town attempting to capture all those missed or not eligible for routine vaccination. Analysis of forecast volumes over time better enables policymakers to prepare for the initial introduction of large-scale catch-up strategies and to ensure that the health care system has the adequate delivery capacity for routine and re-vaccination strategies in subsequent years. Finally, if health programme officials have control over the coverage and hence the annual numbers of people vaccinated via the catch-up strategy, they might spread the catch-up vaccination programme out over a longer period to avoid the initial peak and subsequent decline. This would ensure that vaccination delivery capacity was not stretched thin in the short term and possibly underused in the longer term. 5.3.2 Funding While projections of demand in India provide valuable information to decision-makers, it should be noted that the forecasts illustrated assume no funding constraints. The model framework is capable of assessing the effect of funding constraints on demand, however, because donor and government future funding allocations for HIV and AIDS in India have not been considered as part of our baseline analyses. More realistic forecasts of demand will require an understanding of the effect of a funding-constrained environment. This is important because the cost of the vaccine to the GOI might exceed its ability to pay, in which case access to an HIV vaccine may be limited, and only a proportion of the projected demand will materialise. The GOI's financial capacity and funding allocations are described in Table 7. This suggests that up to US$123 million (Rs 542 crore) annually would be available to spend on an HIV vaccine, although the actual amount spent would depend on the quality of the vaccine. To contextualize these funding estimates, in 1999-2000 the GOI spent US$44 million (Rs 194 crore) on vaccines, salaries, maintenance, supplies and consumables, transportation and associated IEC for all childhood Expanded Programme on Immunizations (EPI) interventions; e.g. BCG, DTP3, and measles vaccines (GAVI Alliance 2001). Assuming GOI spending on EPI vaccines grows at the same rate as India's gross domestic product (GDP), i.e. 6.9% annually, then spending in 2015 on these vaccines will reach US$120 million (Rs 530 crore). This means that if an HIV vaccine received the allocations described above, the GOI's immunisation budget would need to double. Using the basic assumptions for GOI funding (Table 7 and Appendix IV), and assuming no additional funds from donors, the scenario illustrated in Figure 7 compares demand for the Medium Vaccine Profile Scenario in a funding-constrained versus -unconstrained environment. The funding-constrained scenario considers the magnitude of funding necessary to cover the costs of the vaccine itself as well as its delivery. (The assumed costs of both vaccine and delivery are described in Table 5). The shortfall in funding occurs during the eight years around peak demand and results in a cumulative total of 47.1 million courses being unfunded in this time period. This suggests that the GOI and

28

international donors might need to prepare to address significant funding challenges to realise the desired levels of demand suggested by these forecasts. In the past, the GOI has consistently financed over 95% of routine immunisation costs. The remaining proportion, covering supplementary campaigns and evaluation surveys, is paid for by such donors as UNICEF and USAID (IAVI 2007b). If immunisation budgets require dramatic increases, the GOI and international donors will need to significantly increase their funding commitments. Finally, the scenarios modelled assume a cost of US$2-3 per dose delivery, based on the presumption that each dose of the vaccine is stored and delivered using a single vial under conditions that meet cold chain delivery and storage refrigeration requirements of 2 to 8ºC. However, some of the current vaccines in clinical testing must be stored at -70ºC and may involve three or more doses. Clearly, actual delivery costs may turn out to be significantly higher than those modelled here, and funding challenges may be even greater.
Figure 7. Funded versus unfunded complete courses (for the Medium Scenario)
16 14

Number of Complete Courses (Millions)

12 10 8 6 4 2 0 0 5 10 15 20 25 30 Unfunded Total Funded Total

Year Since EMEA/FDA Approval

5.3.4 Policy changes to strengthen demand Changes in the regulatory process, political environment, and health care system might also significantly impact future demand for an HIV vaccine. Specifically, expedited regulatory approval, expedited public programme introduction, improved political will, and increased coverage could improve the delivery of an HIV vaccine to those who need it most. The model specifications used to reflect these types of policy-environmental changes and resulting four demand scenarios for India are described in Table 12 and Figure 8. The baseline scenario in this scenario analysis and subsequent sensitivity analyses is synonymous with the “Medium Vaccine Profile Scenario” in the vaccine profile scenarios above.

29

Table 12. Policy-environmental scenario specifications and effects on demand

30
Model Specification
a

Scenario

Peak year demand

Cumulative demand (Years 1- 10) Courses Courses 7.1m 7.3m 66.7m 86.3m 226.4m 221.1m Courses Courses (% change) -0.4m (-3%)

Total cumulative demand

Average annual demand (over 30year period) Change from baseline peak year demand

Change from baseline cumulative demand

Courses 14.7m 15.1m

Courses (% change) 5.3m (+2%)

Baseline scenario

Expedited regulatory approval processes

Expedited public vaccination programme introduction & improved political will 41.2m 235.1m 964.2m

31.1m

26.1m (+173%)

743.1m (+336%)

Increased coverage and funding 34.0m

123.2m

360.5m

11.6m

18.9m (+125%)

139.4m (+63%)

Combined policy changes

Reduce regulatory lag in public and private markets from 2 years to 1 year Decrease the time to introduce public vaccination programmes (following national regulatory approval) from 2-3 years to 1-2 years; increase political will classification from medium to high (changing the API score, a proxy for political will, from 57 to 67) Double GOI funding available for an HIV vaccine from 1% to 2% of the projected total annual health care budget; increase maximum coverage rate across all programmes from 40% to 65% All of the above modifications 81.7m 478.1m 1,633.2m 52.7m

66.6m (+441%)

1412.2m (+639%)

a

Only specifies variables where different from baseline values.

30

Figure 8. Demand forecasts for policy-environmental scenario specifications

90

80
Combined policy changes

70

60

50
Improved coverage & improved funding

40

Number of Complete Courses (Millions)

30
Expediting the time to programme introduction & improved political will

20

10
Baseline Expedited regulatory approval processes

0 5 10

0

15

20

25

30

Years Since EMEA/FDA Licensure

31 31

Expedite regulatory approval processes: Expediting regulatory approval has relatively little effect on overall demand (an additional 5.3 million complete courses demanded in India over the 30-year period), though it does cause a shift in the demand curve; in this scenario, the uptake pattern commences two years earlier than the baseline scenario. Perhaps the most significant implication of this is that volume of demand increases by approximately 30% during the first 10 years of this scenario compared to the baseline scenario, even though cumulative demand for the entire forecast is relatively unchanged. Since the first 10 years following product launch are likely to be a period of market exclusivity, expediting regulatory approval can significantly increase the already substantial market potential of HIV vaccines. Expediting regulatory approval might be achieved by India's continued participation in discovery and development activities of first-generation HIV vaccines beyond current Phase I trial involvement, because data generated in India would be immediately available for review. In addition, national and international regulatory processes might be streamlined using measures similar to those employed by the FDA to allow drugs for serious and life-threatening diseases to reach the market earlier. For example, policies could encourage early interactions between vaccine developer/sponsor and the GOI's regulatory agencies, resulting in improved trial design and data collection and reducing delays in regulatory submission reviews. Expediting public vaccination programme introduction and increased political will: These changes have the largest single impact — an increase of 336% — on cumulative demand over the baseline scenario. They increase peak year demand by 173% over the baseline scenario, resulting in demand during the peak year of 41.2 million courses. Expediting the public vaccination programme introduction creates demand sooner and demand peaks earlier. This increases the cumulative volume of demand during the 30-year period over baseline levels. Increasing political will has the same effect. Expediting the time to public vaccination programme introduction might be possible through advanced planning and preparation for HIV vaccines and through learning from the experience of introducing and implementing other preventive and therapeutic technologies. For example, there are lessons to be learned from India's Universal Immunisation Programme's (UIP) system of procurement and distribution, including both its successes and failures. And while an HIV vaccine programme is unlikely to utilise the established childhood immunisation system, it could perhaps be integrated into the extensive network of voluntary counselling and testing and antiretroviral therapy (ART) centres. Combining the three prevention and treatment interventions could offer significant synergies (IAVI 2007b). Strengthening political will might require policymakers to increase focus and relative prioritization on HIV vaccine introduction. This might mean an HIV license application is prioritized by regulators, and additional funding may be made available for purchasing vaccines or financing delivery costs. Some of the responsibility for generating stronger political support lies with advocates, community leaders, scientists, and others who can educate and influence policymakers about the importance of an HIV vaccine programme. Increased coverage: Increased coverage also has a marked effect — an increase of 63% — on demand in the scenario analysis above. Increasing coverage doesn't reduce the

32

regulatory lag and doesn't change when the vaccine is introduced in India. However, it does increase the rate of uptake of the vaccine and the maximum achievable coverage (from 40% to 65%). This therefore translates into significantly higher demand. Increased coverage might be achieved by scaling up delivery and outreach infrastructure for the expected target populations of an HIV vaccine. Since health services for populations at higher risk of exposure to HIV are often delivered by NGOs, increasing coverage for an HIV vaccine used in these populations might improve the resources available to some NGOs that do outreach. For the 13- to 26-year-old populations at lower risk of exposure who might be targeted, it might be necessary to create or adapt appropriate delivery infrastructure. This might use and build upon infrastructure developed for the new HPV vaccine if this is targeted toward adolescent populations. The combination of all of these policy changes profoundly impacts demand forecasts, resulting in a six-fold increase (639%) over the baseline forecasts. Improving political will positively affects the regulatory approval speed and the level of achievable access (coverage) and also shortens the time to begin national vaccination programmes (i.e., it reduces programme implementation lags). However, 64% of cumulative demand over the 30-year period would not be covered by GOI funds, given current funding assumptions. Therefore, in order to realise the potential gains, policymakers and international donors alike need to strategically plan how to address potential funding constraints that might otherwise limit demand and access.

5.4 Revenue forecasts and implications for private industry
As a rapidly growing economy, India's market for health technologies is still growing fast and hence provides increasing opportunities for suppliers. The market opportunity for future HIV vaccines in India has, until now, not been adequately quantified. Elucidating the potential market magnitude might help multinational R&D organisations determine whether to include trial participants from a country like India, or in the future, might inform investment decision-making to determine manufacturing scale. The sheer magnitude of India's population means that gaining a good understanding of market demand and revenue potential in this market alone is an important consideration for biopharmaceutical and investment analysts in the context of the wider global picture. 5.4.1 Revenue scenarios Revenue scenarios3 were generated on the basis of the demand forecasts for the vaccine profile scenarios above and the pricing assumptions described in Table 5. The results of these projections are illustrated in Figure 9 and described in Table 13 below.

3

All revenue scenarios described in this section are undiscounted.

33

Figure 9. Vaccine profile sales revenue forecasts
1000
Potential Pre-Generic Market Exclusivity Period

900 800 700 600 500 400 300 200 100 0 0 5 10 15 20 25 30
MEDIUM Vaccine Profile Revenue Scenario

Annual Sales Revenue (Millions $USD)

HIGH Vaccine Profile Revenue Scenario

LOW Vaccine Profile Revenue Scenario

Years Since EMEA/FDA Licensure

Table 13. Cumulative and peak sales revenue in India
Vaccine Profile Scenarios Peak revenue in US$ millions (Indian rupees) Average annual sales revenue in US$ millions (over years 0-10) (Indian rupees) Average annual sales revenue in US$ millions (over years 0-30) (Indian rupees) Cumulative sales revenue in $US millions (over 30-year period) (Indian rupees) Cumulative total demand in doses (millions) Low $124.7 (Rs 550 crore) $54 (Rs 239 crore) $58 (Rs 255 crore) $1,792 (Rs 7,906 crore) 35.8 Medium $415.0 (Rs 1,831 crore) $163 (Rs 721 crore) $153 (Rs 677 crore) $4,754 (Rs 20,977 crore) 329.5 High $910.5 (Rs 4,017 crore) $322 (Rs 1,423 crore) $428 (Rs 1,888 crore) $13,263 (Rs 58,519 crore) 1,326.3

Peak annual revenue is reached seven years after launch in India for all three vaccine profile scenarios. In these peak years, revenue from vaccine demand in India reaches US$124.7 million (Rs 550 crore) in the Low Scenario, US$415 million (Rs 1,831 crore) in the Medium Scenario, and US$910.5 million (Rs 4,017 crore) in the High Scenario. To put these figures into context, market research conducted last year estimated India's biopharmaceuticals market value at US$8.8 billion in 2005 (Espicom Business Intelligence

34

Market Report 2007) and is expected to reach US$20.8 billion4 in 2015 and US$38.1 billion in 2022, the year of peak sales revenues (Research And Markets 2005). This means that in the years of peak sales for the Medium and High scenarios, HIV vaccine revenues would represent 1.1% and 2.4%, respectively, of total Indian pharmaceutical market sales, a significant amount for a single product. The revenue forecasts underline the significant market potential of HIV vaccines, irrespective of vaccine profile. During the first 10 years following product launch, which is likely to be the period of market exclusivity or patent protection in India, average annual sales revenues range between US$54 million to US$322 million (Rs 239-1,423 crore). These revenue estimates highlight the importance of being the first entrant to take advantage of the value and opportunities in both public and private markets. Table 14 below describes the relative contribution of private and public demand to sales revenue. When compared with Table 10, this breakdown underscores the fact that even low levels of demand from the Low Scenario can generate significant revenue. Although the private sector contributes only 11% of total demand in the Medium Scenario, it accounts for nearly 40% of revenue.
Table 14. Relative contribution of private market versus public market programmes to revenue
Vaccine Profile Scenarios Low Private Market High-risk (vulnerable) population programme Public Market Low-risk (adolescent) population programme Average annual US$ value of private market (Indian rupees) Average annual US$ value of public market(s) (Indian rupees) 100.0% $57.8m (Rs 255 crore) Medium 38.4% 61.6% $58.9m (Rs 260 crore) $47.3m (Rs 417 crore) High 5.9% 19.3% 74.8% $25.3m (Rs 171 crore) $201.3m (Rs 1,162 crore)

5.5 Sensitivity analyses
Sensitivity analyses help us understand how our baseline assumptions (acceptable levels of vaccine characteristics, coverage rates, targeting, political will, and epidemiology in India) might affect projected demand. Table 15 presents the baseline assumptions and the upper and lower boundaries of the model parameters tested in the sensitivity analysis. Figure 10 depicts the results of these analyses in comparison to the baseline scenario.

4

Assuming 9% growth per annum (IAVI 2007a).

35

Table 15. Sensitivity analyses parameter values
Original Baseline Values Model Parameter High-risk Programme 50% 40% Constant prevalence (at 0.9%)
Low-risk Programme

Sensitivity Analyses Values High-risk Programme Upper Lower Value Value 70% 60% Increase in prevalence 30% 20% Decrease in prevalence Low-risk Programme Upper Value 95% 60% Increase in prevalence Lower Value 50% 20% Decrease in prevalence

Minimum acceptable level of efficacy Maximum achievable coverage rate Epidemic character (flat vs. increasing/ decreasing prevalence)

70%

(NB: The sensitivity of demand to both licensure/adoption and implementation lags has not been assessed since these lags will affect only the timing of peak demand. Furthermore, since lags only come into effect after acceptable vaccine characteristics have been met, unless these thresholds are altered simultaneously in a two-way sensitivity analysis or scenario assessment, the effect of changing lags alone will be minimal.)
Figure 10. Change in cumulative demand from sensitivity analyses on model parameters
700% 600% 500% 400% 300% 200% 100% 0% -100% -200% 5.5.1: Changing Efficacy Thresholds 5.5.2 Changing Maximum Achievable Coverage 5.5.3: Changing Epidemic Trajectory Upper Value 51% Lower Value 0% Upper Value 621%

Percent Change in Cumulative Demand from Medium Scenario

Lower Value 317%

Upper Value -89%

Lower Value -49%

Model Parameter

36

5.5.1 Effects of changing the minimum acceptable level of efficacy Setting the minimum acceptable levels of efficacy for the low- and high-risk programmes to the upper values (defined in Table 15) decreases demand by 89% because neither set of public programme thresholds is met by the baseline vaccine profile and only private market demand remains. Using the lower values for vaccine efficacy thresholds, demand significantly increases because the low-risk programme is now implemented, whereas in the baseline, it is not. These analyses underscore the importance of policymaker preferences with respect to vaccine profiles. HIV vaccine advocates, including vaccine developers themselves, might consider illustrating to policymakers the value and benefits of partially efficacious vaccines (for example, through epidemiological modelling). This may enable policymakers to make more informed decisions about what constitutes acceptable levels of efficacy. 5.5.2 Effects of changing maximum achievable coverage rates The upper and lower bounds for coverage rates increase and decrease demand by around 50%, respectively. These results suggest that Indian policymakers should focus on improving delivery mechanisms to achieve higher rates of coverage for future adult and adolescent vaccines. This might occur through efforts to strengthen national health care capacity, improve and expand outreach services to high-risk populations, and improve the effectiveness of distribution systems for low-risk populations. 5.5.3 Effects of changing the epidemic's trajectory The stakeholder interviews highlighted the divergent opinions that exist amongst Indian experts about the future of the HIV epidemic. The hepatitis B vaccine in India demonstrated how controversy over prevalence and diverging perceptions of public health need can hinder the adoption and implementation of a new health technology, which resulted in a 10-year lag between the WHO recommendation to start a hepatitis B vaccination programme in India and its actual launch (IAVI 2007b; Steinbrook 2007). Current estimates and projections of the HIV epidemic in India are far from perfect, despite the expansion of surveillance sites (Chandrasekaran et al. 2006; Dandona et al. 2006). The current uncertainty and conflicting perceptions of prevalence and need highlight the importance of sensitivity analyses of varied HIV prevalence projections. Results suggest that no change in demand occurs if the epidemic trajectory declines. In this instance, need is lower, but not significantly lower to dampen demand for the vaccine for high-risk populations. However, as prevalence increases, the model suggests that demand increases more than in any of the other sensitivity analyses (i.e., by 621% over the baseline case). This translates into 1.6 billion cumulative courses over the 30-year period. Should the epidemic worsen, the GOI would seek to vaccinate an additional 45.7 million people per year, requiring a huge investment in delivery capacity and a quantum leap in funding.

37

VI. Summary/conclusions
Consultations were conducted amongst multiple stakeholder groups, including policymakers, academics, biopharmaceutical executives, and donors, to assess how India might adopt and implement a first-generation preventive HIV vaccine. Interviews were conducted across the country to ascertain how both public and private markets might react to an HIV vaccine, which potential target groups might receive the vaccine, and how quickly the vaccine might eventually be made available. The consultation and interview findings suggest the following:
ƒ

Licensure/Adoption Process: Given the multiple levels of approval necessary both internationally and nationally to secure licensure in India, it is possible that an HIV vaccine would be approved in India at least two to three years after initial licensure in the U.S. and Europe. However, an HIV vaccine could be expedited through the regulatory review process via a number of policy interventions contingent on India's continued participation in HIV vaccine clinical trials, negating the need for local bridging studies. Acceptable Vaccine Characteristics: The level of efficacy necessary for India to license an HIV vaccine is likely to vary by target population. Thresholds will be lower (50% efficacy) if a vaccine is to be used solely in populations at higher risk of exposure to HIV, and higher (70% efficacy) if it is also used in populations at lower risk. Furthermore, a vaccine must have a duration of at least three years to secure use in public markets, and such a vaccine would only be acceptable if prices are between US$1 to $10 per dose. Targeting and Delivery: Populations at higher risk of exposure to HIV are likely to be the initial target recipients of publicly funded vaccination programmes. If populations at lower risk are targeted, it is likely that only adolescents and young adults (those under 27 years old) will be recipients. If a partially efficacious vaccine is launched in India, delivery programmes may need to include educational interventions to prevent behavioural disinhibition. This may significantly increase health care capacity needs and costs for implementing simultaneous vaccination and education programmes.

ƒ

ƒ

IAVI created a model to estimate global demand based upon the key determinants of demand and the expert consultation findings. The model provides a national picture of HIV vaccine demand and revenue.
ƒ

Demand and Revenue Forecasts: Baseline forecasts suggest that demand in India for an HIV vaccine with an efficacy of 50 to 70% could range from 15.2 million to 41.5 million courses in the peak year. Assuming tiered pricing between public and private markets (US$10 to $50 per dose), these levels of demand could result in peak year sales revenues of US$415.0 to 910.5 million (Rs 1,831 to Rs 4,017 crore). These results imply that under certain market conditions, a first-generation HIV vaccine could account for up to 1.1 to 2.4% of the total Indian pharmaceutical market value. Scenario Analyses: Should the prevalence of HIV remain unchanged in India from its current 0.9%, average annual baseline demand over 30 years is projected at 15.2 million persons fully vaccinated per year. Should the epidemic worsen significantly, the GOI might seek to vaccinate an additional 45.7 million people per year over baseline

ƒ

38

levels to halt further increases in new infections. Efforts to address regulatory, infrastructural, and political constraints could increase access to and use of an HIV vaccine by up to 45.6 million additional people each year over a 30-year period. Potential Benefits of this Research To achieve these increases in demand and access, much lead time is required to implement policy change. Since the search for an HIV vaccine is still likely to take several more years, an opportunity currently exists to engage vaccine developers, donors, and Indian health care system officials with their R&D, funding, and preparatory endeavours. This forecasting model could help decision-makers in both Indian and international institutions develop both immediate and longer-term strategic action to streamline regulatory systems, improve health care capacity and infrastructure, and increase political will and financial commitment. Such policy changes will help to ensure the development of and eventual access to safe, effective, accessible, preventive HIV vaccines for use in India and throughout the world. Next Steps Consultation and Feedback: Consultation with key stakeholders and users of the model will enable a more sophisticated assessment and approach to modelling many of the key determinants of demand in future research. Consideration of the Complex Epidemiological Landscape and Other Target Populations: Due to current data limitations, the forecasting model presented here overlooks a number of target groups especially important in India. These include migrant workers, truck drivers, clients of sex workers, health care workers, military personnel, and private employers. Identifying and incorporating reliable estimates of the size of these groups and how a vaccine might be delivered to them would improve the model's ability to more accurately assess demand for an HIV vaccine across India. Moreover, since this model provides a national picture based upon national inputs, it does not address the regional variability of HIV. Regional and local data are important inputs to efforts to plan and implement HIV vaccine programmes. Consideration of Other New Preventive Technologies: The forecasting model assumes that only existing HIV interventions are available in India at the time of HIV vaccine introduction. The demand estimates for a future HIV vaccine will need to be refined once the timing and magnitude of demand for other new preventive technologies now in development, such as microbicides and PrEP, become clearer. Progressing from Demand/Impact to Cost-Effectiveness: Both developers and public health policymakers are concerned about cost-effectiveness as they make strategic and tactical decisions. These demand scenarios can be combined with future impact modelling for India along with future cost modelling to generate cost-effectiveness estimates. Lessons Learned from the Introduction of Other New Vaccines: IAVI hopes to learn from the implementation of new vaccines such as the HPV vaccine to improve our understanding of health system issues in India that must be addressed for successful preparation and implementation, particularly in adult and adolescent populations.

39

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Appendix I. List of interviewees and collaborators
Title, First, Surname Dr. Dinesh Agarwal Dr. Dan Barth-Jones Prof. Ramesh Bhat Dr. Lori Bollinger Dr. Nirupa Borges Dr. Denis Broun Dr. Prakash P. Doke Mr. Ravi Duggal Dr. Jose Esparza Mr. A.K. Ganesh Ms. Vidhya Ganesh Prof. N.K. Ganguly Mr. Gopi Gopalakrishnan Ms. Anjali Gopalan Mr. Anand Grover Dr. Indrani Gupta Dr. M.D. Gupte Dr. Raymond Hutubessy Dr. Shahid Jameel Dr. Amar Jesani Dr. S.V. Kapre Dr. Ashok Khar Dr. P. Krishnamurthy Dr. Raj Kumar Dr. Sanjeev Kumar Dr. Homayoun Madjrouh Mr. G. Manoj Dr. P. Manorama Dr. R.A Mashelkar Mr. Rajiv Misra Dr. S.N. Misra Position / Affiliation Team Leader and Technical Advisor, Reproductive Health, UNFPA, New Delhi Assistant Professor, Center for Healthcare Effectiveness Research and the Department of Internal Medicine at the Wayne State University, School of Medicine, Detroit Professor, Finance and Accounting and Public Systems Group, Indian Institute of Management, Ahmedabad Vice President Futures Institute, Glastonbury Project Director, Mumbai District AIDS Control Society, Mumbai Country Coordinator, UNAIDS, New Delhi Director, Health Services, Government of Maharashtra, Mumbai Coordinator, CEHAT, Centre for Enquiry into Health and Allied Themes (CEHAT), Mumbai Senior Advisor, HIV Vaccines, HIV, TB, & Reproductive Health, The Bill and Melinda Gates Foundation, Seattle, Project Manager, YRG Care for AIDS Research and Education, Chennai Chief, HIV/AIDS, UNICEF, New Delhi Director General, Indian Council of Medical Research, New Delhi Country Director, Janani/DKT International, Mumbai Executive Director, NAZ Foundation, New Delhi Project Director, Lawyers Collective HIV/AIDS Unit, New Delhi Head, Health Policy Research Unit, Institute of Economic Growth, New Delhi Director, National Institute of Epidemiology, Chetpet, Chennai Economist, WHO, Immunizations, Vaccines & Biologicals, HIV Vaccines, Geneva Group Leader, Mammalian Biology and Virology, International Centre for Genetic Engineering and Biotechnology, New Delhi Coordinator, Centre for Research in Ethics and Rights, Mumbai Executive Director, Serum Institute of India, Pune Head (R&D), Shanta Biotech, Hyderabad Project Director, AIDS Prevention and Control Project, Chennai Director, Immunisation - PATH India, New Delhi Head, Social Consulting, Hindustan Latex Family Planning Promotion Trust, New Delhi Managing Director, Sanofi Pasteur, New Delhi CEO, Hindustan Latex Family Planning Promotion Trust, Hyderabad Director, Community Health Education System, Chennai Former Director General & Secretary, Council of Scientific & Industrial Research, New Delhi Former Secretary, Health, Ministry of Health and Family Welfare, Government of India, New Delhi Deputy Director, Clinton Foundation, New Delhi

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Title, First, Surname Dr. Pem Namgyal Dr. Jean-Marie Okwo-Bele Dr. Saladin Osmanov Dr. R.K. Pal Dr. Samiran Panda Mr. Manoj Pardesi Dr. Mrudula Phadke Lt. Gen. D. Raghunath Mr. Askok Row Kavi Ms. Supriya Sahu Dr. N.M. Samuel Dr. Sanjay Sawant Mr. D.G. Shah Mr. Ranjit Shahani Dr. Suneeta Singh Dr. Suniti Solomon Dr. Chutima Suraratdecha Dr. Soumya Swaminathan Dr. A. Vaidyanathan Dr. Ravi K. Verma Dr. Neff Walker Dr. Roy Widdus Dr. Paul Wilson

Position / Affiliation Medical Officer, Immunization and Vaccine Development, WHOSEARO, New Delhi Director, WHO Department of Immunization, Vaccines and Biologicals, Geneva Acting Coordinator, WHO-UNAIDS HIV Vaccine Initiative. WHO, Geneva National Programme Officer (Hep. B), WHO-India, New Delhi Vice President, SPARSHA, Kolkata President, NMP+, New Delhi Vice Chancellor, Director, Medical Education & Research, Mumbai Principal Executive, Sir Dorabji Tata Centre for Research In Tropical Diseases, Bangalore Chairman, The Humsafar Trust, Mumbai Joint Secretary, Department of Health and Family Welfare, Government of Tamil Nadu, Chennai Professor and Head of Department, Dept. of Experimental Medicine, The Tamil Nadu Dr. M.G. R. Medical University, Chennai Deputy Secretary (Employment), Government of Maharashtra, Mumbai Secretary General, Indian Pharmaceutical Alliance, Mumbai Vice Chairman & Managing Director, Novartis India Limited, Mumbai Senior Public Health Specialist, The World Bank, New Delhi Director, YRG Care for AIDS Research and Education, Chennai Health Policy and Economics Officer, PATH Japanese Encephalitis Project PATH, Seattle Deputy Director, Tuberculosis Research Centre, Chennai Former Director of Madras Institute of Development Studies, Chennai Senior Programme Associate, Horizons – Population Council, New Delhi Senior Project Officer, Strategic Information Section, UNICEF, New York Project Manager, Initiative Public-Private Partnership Projects Global Health Futures Network, London Assistant Clinical Professor of Population and Family Health, Mailman School of Public Health, Columbia University, New York

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Appendix II. Vaccine profile specification
Table A1 describes the lower and upper bounds of vaccine characteristics to describe possible first-generation vaccines. These were developed through informal discussion with scientific experts and were used to guide discussion during the expert consultations.
Table A1. Lower and upper bounds of vaccine profile Parameter
Efficacy & mechanism of action 1. 2.

Assumptions
Vaccine is imperfect (partially efficacious) Vaccine prevents infection in those vaccinated prior to exposure by a fixed percentage (VES) Vaccine also lowers infectiousness after being infected (VEI) by same magnitude as VES Assume VES/VEI effects work differentially in low- and high-risk groups

Vaccine Characteristic Lower Bounds
VES/VEI = 30% efficacy in preventing infection in low-risk groups

Upper Bounds
VES/VEI = 70% efficacy in preventing infection in low-risk groups

3.

4.

VES/VEI = 15% efficacy in high-risk groups

VES/VEI = 35% efficacy in high-risk groups

Vaccine doubles time of disease progression to AIDS after being infected (VEP). Duration of protection (and effect on revaccination) 1. 2. 3. 4. Price per dose 1. Duration of effect would be 2 years or longer Vaccine effect lasts for a certain number of years and doesn't wane before then Revaccination would be required every 2-5 years Assume that for revaccination, only a single dose is required Based on pricing of a range of old and new existing vaccines

VEP = 200%a 2-year duration 5 doses for 5-year protection 5-year duration 2 doses for 5-year protection

US$2

US$50

2. Assessed global prices for hepatitis B vaccine (HBV), new pneumococcal conjugate vaccine, and EPI vaccines 3. No price decline from launch needs to be assumed Two dosing schedules hypothesized x x x Clade specificity 3-dose vaccine represents less favourable dosing profile 2-dose schedule is viewed as more optimistic of the two scenarios 1-dose re-vaccination

Dosing schedule (including revaccination requirements)

Prime + 2 boosters 0-, 1-, 6- month schedule

Prime + 1 booster 0-, 1- year schedule

All vaccine profiles considered would be effective against any strain prevalent in any country No serious adverse effects

Complete and uniform cross-clade protection for all countries and populations Similar to a placebo US$1 per full vaccination course (McGreevey et al. 2004) US$6 per full vaccination course (CIA n.d.)

Safety Delivery/ storage requirements and delivery costs

Single vial/cold chain of 2-8ºC

During the consultation interviews, it became clear that many respondents found it difficult to appreciate the different mechanisms of vaccine effect (VEI, VES and VEP) - and as such, disease modifying effects (VEP) were removed and are not considered within these analyses.

a

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Appendix III. Interviewee categories, rationale, and judgments
Interviewee Category
Country- or regionspecific policymakers

Description & Rationale for Approaching
These were often government officials in the Ministry of Health or Ministry of Finance. A range of individuals were targeted, encompassing advisors to senior officials, but not the elected officials themselves. It was assumed that it would be the senior civil servants whose technical expertise would influence and shape future policies by providing expert advice to elected officials. Academics, particularly those who serve as advisors to the government, were targeted because of their influential role in policymaking.

Judgments sought on the following issues…
x Criteria governments use when considering adoption of health technologies x What characteristics for an AIDS vaccine would be acceptable for their country x Funding for vaccine and HIV/AIDS prevention x Targeting of an AIDS vaccine x Distribution mechanisms

Academics

x x x

Local HIV/AIDSrelated NGO leaders and staff

Key opinion leaders, advisors, and HIV/AIDS experts Local & international vaccine developers & biotechnology groups

NGO representatives working specifically in the field of HIV and AIDS or with the populations affected by HIV were approached given their intimate knowledge of capacities and challenges in dealing with these communities and getting treatment and prevention programs to them. These interviewees generally held academic posts and either advised policymakers directly or through their research. Developers understand the local licensure, implementation and delivery processes and have views on the size of the market today and in the future

x x x x x x x x x x x x x x x x x x x x x x x x x

Insight into the future epidemiological, economic, and social trends within a country (dependent on their areas of expertise) Criteria a country uses to make health technology adoption decisions Targeting policies that might be recommended for an AIDS vaccine Political will with respect to AIDS treatment and HIV prevention Need for a vaccine, particularly among vulnerable populations Perceptions of the future state of the epidemic The country’s ability to reach vulnerable populations Levels of achievable coverage in various risk groups Insight into lag time between adoption and implementation of programmes (time to scale-up) Future states of the epidemic in their country/region Political will with respect to HIV treatment and prevention Criteria used to decide whether to adopt a vaccine Vaccine targeting Level of achievable coverage Vaccine profile and market opportunity and commercial viability in particular country or region Insight on adoption and implementation patterns of other technologies Local regulatory requirements Lags between product development, licensure, and rollout Importance of clinical trials Health care delivery systems Anticipated future local "biopharma" market developments Global and regional financing for vaccine or AIDS prevention programmes Fast vs. slow adopters/implementers of new health technologies Regional epidemiological trends

Global and regional policymakers (e.g., WHO, UNAIDS, UNDP etc.)

These interviewees were thought to be able to provide broader regional perspective on the epidemiological need, the effectiveness of other vaccination campaigns, HIV prevention, and AIDS treatment programmes.

Representatives from the donor community

Future funding scenarios Criteria used to decide whether to fund a vaccine Perceptions of the future states of the epidemic in their country/region Political will with respect to treatment and prevention

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Appendix IV. India’s country profile descriptor information and assumptions
Source(s)
Assumes a compound annual growth rate (CAGR) of 1.5% per annum to calculate population magnitudes in 2015. With current scientific opinion assuming that preventive AIDS vaccines would be administered to uninfected individuals, the starting population constitutes those whose HIV status has been confirmed as HIV-negative. However, pre-vaccination HIVtesting is likely to be logistically difficult and expensive. Therefore, the starting population in the model is derived from the total population, irrespective of HIV-status (CIA n.d.).

Criterion

Proxies

Assumptions and/or Cut-offs (High/Medium/Low)

Value(s) for India
In 2015, the following populations in India are estimated to be: Total: 1,280 million High-risk: 131 million Low-risk (13-26 yrs): 237 million Low-risk (13-49 yrs): 614 million

Demography

N/A

Need

Pre-valence per capita

CIA World Factbook (CIA n.d.), UN Population Division World Population Prospects (Population Division n.d.); Sexually Transmitted Infections Supplement on the Data, Methods, & Tools Used to Produce the 2005 UNAIDS / WHO HIV/AIDS estimate (Vandepitte et al. 2006, Aceijas et al. 2004, Caceres et al. 2006) UNAIDS-WHO: 2006 Report on the Global AIDS Epidemic (UNAIDS 2006)

Assumed to have a low prevalence (0.5%) in 2015.

Political will

AIDS Program Index (API) World Bank data (World Bank n.d.)

UNAIDS-USAID-WHO-POLICY Project; 2003 (USAID 2003)

(Equivalent to an absolute number of around 6.6 million people). API score of 59; (i.e., Medium Political Will)

Capacity and ability to Pay

National income per capita - PPP adjusted World Bank data (World Bank n.d.)

Income per capita of $1,292 (i.e. medium income/capacity/ability to pay)

Projected GOI funding on health care budget & predicted allocation to HIV/AIDS and HIV vaccine

National income

In 2015, the corresponding hypothetical funding allocations are as follows: x US$49,300,000,000 x US$493,000,000 x US$123,000,000

Assumes a flat CAGR for rate in 2015 x High: >5% x Medium: between 1%-5% x Low: between 0.2%-1% x Very Low: 0.2% Scores vary between 0 and 100 x High: API 67 x Medium: API 55 - 66 x Low: API 54 Assumes a CAGR of 6.9% per annum for rate in 2015. Based on World Bank cut-offs for 2005 in US$: x High: $10,066 x Medium: $826-10,065 x Low: $825 Assumes: x 6.9% GDP growth per annum x 1.19% of GDP spent on health x 1% of health budget spent on HIV/AIDS x Maximum of 25% of HIV/AIDS budget spent on AIDS vaccine x Based on government attitudes about the vaccine profile, some proportion of the AIDS vaccine funding "pot" is actually spent on vaccine. On the basis of the vaccine profiles described in Table 5 above: x Low profile = 15% of funds spent on the HIV vaccine x Medium profile = 50% of funds spent on the HIV vaccine x High profile = 73% of funds spent on the HIV vaccine

x US$19,000,000 x US$62,000,000 x US$90,000,000

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Appendix V. Algorithms to define endogenous country-level behavioural parameters
Tables A2 to A5 describe how the model transforms the Country Profile Descriptors to define the Country Behavioural Parameters for the minimum acceptable thresholds of efficacy and duration of protection and maximum acceptable level of price for government implementation of an HIV vaccine.
Table A2. Efficacy-implementation threshold matrix for high-risk programme
Political Will (API Score) Low Medium High ” 54 55 - 66 • 67 Very Low <0.20% 50% 50% 50% Prevalence (%) Low Medium 0.20 - 0.99% 1.00 - 4.99% 50% 50% 50% 30% 50% 30% High >5.00% 50% 30% 30%

Table A3. Efficacy- implementation threshold matrix for general programme
Political Will (API Score) Low Medium High ” 54 55 - 66 • 67 Very Low <0.20% 90% 80% 70% Prevalence (%) Low Medium 0.20 - 0.99% 1.00 - 4.99% 80% 70% 70% 50% 50% 50% High >5.00% 50% 50% 30%

Table A4. Duration of protection- implementation threshold matrix
Political Will (API Score) Low Medium High ” 54 55 - 66 • 67 Very Low <0.20% 5 yrs 3 yrs 3 yrs Prevalence (%) Low Medium 0.20 - 0.99% 1.00 - 4.99% 3 yrs 3 yrs 3 yrs 2 yrs 2 yrs 1 yrs High >5.00% 3 yrs 1 yrs 1 yrs

Table A5. Price- implementation threshold matrix
Income (PPP-adjusted GNI/capita) Low Medium High ”$825 $826-10,065 • $10,066 Very Low <0.20% $1 $2 $50 Prevalence (%) Low Medium 0.20 - 0.99% 1.00 - 4.99% $2 $10 $10 $10 $50 $50 High >5.00% $10 $10 $50

Table A6 describes how the model transforms the Descriptors (in this case, need [prevalence] and political will [API score]) to define the regulatory lag by country.
Table A6. Regulatory/licensure lag matrix
Political Will (API Score) Low Medium High Very Low Prevalence (%) Low Medium High

54 55 - 66 67

<0.20% 5 years 4 years 4 years

0.20 to 0.99% 5 years 3 years 2 years

1.00 to 4.99% 4 years 2 years 1 years

>5.00% 3 years 1 years 1 years

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Tables A7 to A9 describe the calculation process for determination of the high-risk programme implementation lag. The model takes a composite score, derived by adding values for levels of political will (API), need (prevalence), and income (GNI/capita).
Table A7. API-prevalence-GNI scores API Score Value Prevalence Very Low Low 1 Low Medium 2 Medium High 3 High

Value 1 2 3 4

GNI/capita Low Medium High

Value 1 2 3

This composite score informs an intermediate lag value.
Table A8. Intermediate high-risk programme implementation lag value Composite Intermediate Lag Score Value #1 1 6 years 2 6 years 3 6 years 4 5 years 5 4 years 6 3 years 7 2 years 8 1 year 9 1 year 10 1 year

A second intermediate lag value is derived from the year of hepatitis B vaccine implementation.
Table A9. Hepatitis B implementation Year of Intermediate Lag Implementation Value #2 1900 0 yrs 1997 1 yr 2003 2 yrs

The summation of these two intermediate lag values provides the high-risk programme lag. Table A10 describes the low risk programme implementation lag calculation. A third intermediate lag value is derived from the API, prevalence, and GNI values only (listed above) and used to inform the low-risk programme lag.
Table A10. Intermediate low-risk programme implementation lag value Composite Intermediate Lag Score Value #3 1 3 years 2 2 years 3 1 year

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The low-risk programme lag is the sum of the intermediate lag value#3 and the high-risk lag (described on the previous page). Table A11 describes how the model transforms the Descriptors (in this case, need [prevalence] and political will [API score]) to define the upper age limit of the low-risk target group.
Table A11. Upper age limit of low-risk target group matrix
Political Will (API score) Low Medium High ” 54 55 - 66 • 67 Very low <0.20% 26 years 26 years 26 years Prevalence (%) Low Medium 0.20 - 0.99% 1.00 - 4.99% 26 years 49 years 26 years 49 years 26 years 49 years High >5.00% 49 years 49 years 49 years

50

Notes

Notes

IAVI Public Policy Publications Series
Policy Research Working Papers
#1 #2 #3 #4 #5 #6 Global Investment and Expenditures on Preventive HIV Vaccines: Methods and Results for 2002 Promoting R&D in Preventive Health Technologies: Opportunities for the Indian Pharmaceutical and Biotechnology Sector Demand for a Preventive HIV Vaccine: A Review of the Literature Estimating the Global Impact of an AIDS Vaccine Modeling the Impact of AIDS Vaccines: A Review of the Literature Methodologies for Modeling the Impact of a Preventive AIDS Vaccine in Developing Countries: Recent Studies An Advance Market Commitment for AIDS Vaccines: Accelerating the Response from Industry The Impact of an AIDS Vaccine in Developing Countries: A New Model and Preliminary Results A Review of European Commission Funding for HIV/AIDS, Tuberculosis and Malaria Health Technology R&D HIV Vaccine Research & Development: Modeling the Path to Speedier Success Accelerating AIDS Vaccine R&D in India: An Assessment of Obstacles and Possible Solutions The Introduction of New Health Technologies in India Forecasting Demand for Preventive HIV Vaccines in India September 2004 March 2005 April 2005 October 2005 October 2005 October 2005 May 2006 October 2006 December 2006 December 2006 April 2007 May 2007 June 2007

#7
#8 #9 #10 #11 #12 #13

Policy Discussion Papers
#1 #2 Speeding the Manufacture of an HIV Vaccine: Policy Issues and Options Putting it Together: AIDS and the Millennium Development Goals January 2005 September 2005

Joint Publications
Adding It All Up: Funding for HIV Vaccine and Microbicide Development, 2000 to 2005 AIDS Vaccine Development in Japan: Challenges and Opportunities August 2006 May 2006

IAVI also publishes a series of Public Policy Briefs on these and other topics. For a complete list of IAVI published materials, please see www.iavi.org.