"No Regrets" Purchasing in a pandemic: making the most of advance purchase agreements.

"No regrets" buying - using Advance Purchase Agreements (APAs) - has characterized the response to recent pandemics such as Avian flu, Zika Virus, and now COVID-19. APAs are used to reduce demand uncertainty for product developers and manufacturers; to hedge against R&D and manufacturing risks; and to secure availability of products in the face of spiking demand. Evidence on the use of APAs to buy vaccines, medicines, diagnostics, and personal protective equipment during recent pandemics illustrates how these contracts can achieve their intended objectives for buyers. But, transferring risk from suppliers to buyers - as APAs do - can have consequences, including overbuying and overpaying. Furthermore, the widespread use of APAs by high-income countries has contributed to the striking inequities that have characterized the Swine flu and COVID-19 responses, delaying access to vaccines and other supplies for low- and middle-income countries (L&MICs).We identify seven ways to address some of the risks and disadvantages of APAs, including adoption of a global framework governing how countries enter into APAs and share any resulting supplies; voluntary pooling through joint or coordinated APAs; a concessional-capital-backed facility to allow international buyers and L&MICs to place options on products as an alternative to full purchase commitments; greater collection and sharing of market information to help buyers place smarter APAs; support for a resale market; building in mechanisms for donation from the outset; and transitioning away from APAs as markets mature. While a binding global framework could in theory prevent the competitive buying and hoarding that have characterized country/state responses to pandemics, it will be very challenging to put in place. The other solutions, while less sweeping, can nonetheless mitigate both the inequities associated with the current uncoordinated use of APAs and also some of the risks to individual buyers.Analysis of recent experiences can provide useful lessons on APAs for the next pandemic. It will be important to keep in mind, however, that these contractual instruments work by transferring risk to the buyer, and that buyers must therefore accept the consequences. In the spirit of "no regrets" purchasing, having bought what hindsight suggests was too much is generally preferable to having bought not enough.

Shaping markets to benefit global health - A 15-year history and lessons learned from the pentavalent vaccine market.

Market shaping for health products used in lower-income countries strives to benefit public health. As a funder of vaccines, Gavi, The Vaccine Alliance (Gavi) has goals for its market shaping efforts, achieved through a strategy developed and implemented by the Gavi Secretariat, UNICEF, the World Health Organization (WHO) and the Bill & Melinda Gates Foundation (BMGF). A case-study of Gavi's fifteen-year engagement with a vaccine against diphtheria, tetanus, pertussis, hepatitis B and haemophilus influenzae type b (pentavalent) provides evidence of the benefits and potential risks of trying to influence markets. During 2001-18, Gavi disbursed US$3.5 billion to support use of 50 million pentavalent doses annually before 2005, increasing to ∼300 million doses annually by 2016. During this time, eight manufacturers invested in vaccine development and manufacturing and the first two manufacturers have subsequently ceased production. Following its strategy, Gavi implemented coordinated market interventions including technical assistance to manufacturers, improving market information transparency, risk-sharing agreements and innovative procurement aiming to stimulate and capitalize on a competitive market. In 2018 supply allows ∼80 million children per year to be immunised, a sixteen-fold increase from 2005, with vaccine-related costs per child for donors and countries of one-quarter the 2005 level. Lessons learned include the importance of frameworks and strategies; the need to adjust interventions with changing conditions; the important role of manufacturers; and the potentially powerful effects of interconnected markets. This case study is limited by its focus on a single health product in a specific market, however the lessons can inform other market shaping efforts when taken in context. While countries and children have improved vaccine access, risks of financial sustainability and continued manufacturer investment in Gavi vaccine markets are being monitored. Gavi should continue implementing a market shaping strategy, adjust with market conditions and expect and measure unintended consequences.

Charting the evolution of approaches employed by the Global Alliance for Vaccines and Immunizations (GAVI) to address inequities in access to immunization: a systematic qualitative review of GAVI policies, strategies and resource allocation mechanisms through an equity lens (1999-2014).

BACKGROUND: GAVI's focus on reducing inequities in access to vaccines, immunization, and GAVI funds, - both between and within countries - has changed over time. This paper charts that evolution. METHODS: A systematic qualitative review was conducted by searching PubMed, Google Scholar and direct review of available GAVI Board papers, policies, and program guidelines. Documents were included if they described or evaluated GAVI policies, strategies, or programs and discussed equity of access to vaccines, utilization of immunization services, or GAVI funds in countries currently or previously eligible for GAVI support. Findings were grouped thematically, categorized into time periods covering GAVI's phases of operations, and assessed depending on whether the approaches mediated equity of opportunity or equity of outcomes between or within countries. RESULTS: Serches yielded 2816 documents for assessment. After pre-screening and removal of duplicates, 552 documents underwent detailed evaluation and pertinent information was extracted from 188 unique documents. As a global funding mechanism, GAVI responded rationally to a semi-fixed funding constraint by focusing on between-country equity in allocation of resources. GAVI's predominant focus and documented successes have been in addressing between-country inequities in access to vaccines comparing lower income (GAVI-eligible) countries with higher income (ineligible) countries. GAVI has had mixed results at addressing between-country inequities in utilization of immunization services, and has only more recently put greater emphasis and resources towards addressing within-country inequities in utilization to immunization services. Over time, GAVI has progressively added vaccines to its portfolio. This expansion should have addressed inter-country, inter-regional, inter-generational and gender inequities in disease burden, however, evidence is scant with respect to final outcomes. CONCLUSION: In its next phase of operations, the Alliance can continue to demonstrate its strength as a highly effective multi-partner enterprise, capable of learning and innovating in a world that has changed much since its inception. By building on its successes, developing more coherent and consistent approaches to address inequities between and within countries and by monitoring progress and outcomes, GAVI is well-positioned to bring the benefits of vaccination to previously unreached and underserved communities towards provision of universal health coverage.

Updating the evidence base on the operational costs of supplementary immunization activities for current and future accelerated disease control, elimination and eradication efforts.

BACKGROUND: To achieve globally or regionally defined accelerated disease control, elimination and eradication (ADC/E/E) goals against vaccine-preventable diseases requires complementing national routine immunization programs with intensive, time-limited, and targeted Supplementary Immunization Activities (SIAs). Many global and country-level SIA costing efforts have historically relied on what are now outdated benchmark figures. Mobilizing adequate resources for successful implementation of SIAs requires updated estimates of non-vaccine costs per target population. METHODS: This assessment updates the evidence base on the SIA operational costs through a review of literature between 1992 and 2012, and an analysis of actual expenditures from 142 SIAs conducted between 2004 and 2011 and documented in country immunization plans. These are complemented with an analysis of budgets from 31 SIAs conducted between 2006 and 2011 in order to assess the proportion of total SIA costs per person associated with various cost components. All results are presented in 2010 US dollars. RESULTS: Existing evidence indicate that average SIA operational costs were usually less than US$0.50 per person in 2010 dollars. However, the evidence is sparse, non-standardized, and largely out of date. Average operational costs per person generated from our analysis of country immunization plans are consistently higher than published estimates, approaching US$1.00 for injectable vaccines. The results illustrate that the benchmarks often used to project needs underestimate the true costs of SIAs and the analysis suggests that SIA operational costs have been increasing over time in real terms. Our assessment also illustrates that operational costs vary across several dimensions. Variations in the actual costs of SIAs likely to reflect the extents to which economies of scale associated with campaign-based delivery can be attained, the underlying strength of the immunization program, sensitivities to the relative ease of vaccine administration (i.e. orally, or by injection), and differences in disease-specific programmatic approaches. The assessment of SIA budgets by cost component illustrates that four cost drivers make up the largest proportion of costs across all vaccines: human resources, program management, social mobilization, and vehicles and transportation. These findings suggest that SIAs leverage existing health system infrastructure, reinforcing the fact that strong routine immunization programs are an important pre-requisite for achieving ADC/E/E goals. CONCLUSIONS: The results presented here will be useful for national and global-level actors involved in planning, budgeting, resource mobilization, and financing of SIAs in order to create more realistic assessments of resource requirements for both existing ADC/E/E efforts as well as for new vaccines that may deploy a catch-up campaign-based delivery component. However, limitations of our analysis suggest a need to conduct further research into operational costs of SIAs. Understanding the changing face of delivery costs and cost structures for SIAs will continue to be critical to avoid funding gaps and in order to improve vaccination coverage, reduce health inequities, and achieve the ADC/E/E goals many of which have been endorsed by the World Health Assembly and are included in the Decade of Vaccines Global Vaccine Action Plan.

Projections of costs, financing, and additional resource requirements for low- and lower middle-income country immunization programs over the decade, 2011-2020.

The Decade of Vaccines Global Vaccine Action Plan has outlined a set of ambitious goals to broaden the impact and reach of immunization across the globe. A projections exercise has been undertaken to assess the costs, financing availability, and additional resource requirements to achieve these goals through the delivery of vaccines against 19 diseases across 94 low- and middle-income countries for the period 2011-2020. The exercise draws upon data from existing published and unpublished global forecasts, country immunization plans, and costing studies. A combination of an ingredients-based approach and use of approximations based on past spending has been used to generate vaccine and non-vaccine delivery costs for routine programs, as well as supplementary immunization activities (SIAs). Financing projections focused primarily on support from governments and the GAVI Alliance. Cost and financing projections are presented in constant 2010 US dollars (US$). Cumulative total costs for the decade are projected to be US$57.5 billion, with 85% for routine programs and the remaining 15% for SIAs. Delivery costs account for 54% of total cumulative costs, and vaccine costs make up the remainder. A conservative estimate of total financing for immunization programs is projected to be $34.3 billion over the decade, with country governments financing 65%. These projections imply a cumulative funding gap of $23.2 billion. About 57% of the total resources required to close the funding gap are needed just to maintain existing programs and scale up other currently available vaccines (i.e., before adding in the additional costs of vaccines still in development). Efforts to mobilize additional resources, manage program costs, and establish mutual accountability between countries and development partners will all be necessary to ensure the goals of the Decade of Vaccines are achieved. Establishing or building on existing mechanisms to more comprehensively track resources and commitments for immunization will help facilitate these efforts.

Demand forecasting for preventive AIDS vaccines: economic and policy dimensions.

BACKGROUND: An AIDS vaccine could play a very significant role in reversing the HIV pandemic, saving millions of lives. For a vaccine to have such an impact, it must be widely available and adopted and taken up rapidly in the countries most affected. A demand-forecasting model provides a valuable tool that can guide R&D spending decisions and identify policy actions to help achieve these goals. OBJECTIVE: To identify the key determinants of vaccine demand, model global adoption and uptake dynamics, estimate potential demand and revenues associated with future preventive AIDS vaccines, and to conduct sensitivity analyses to assess the impact of each parameter on demand. METHODS: A discrete, deterministic, linear, predictive mathematical model based on stratified population averages with a 30-year time horizon was developed to assess scenarios of future demand. This forecasting model was used to explore the effects of vaccine characteristics and a variety of regulatory, political, financial and health service factors on future demand and revenues. The intervention modelled was a preventive AIDS vaccine (efficacy: 30-90%; duration of protection: 3-5 years; in a two-dose prime-boost combination). The main outcome measure was the number of complete courses of vaccine administered. RESULTS: The model suggests that demand for a preventive AIDS vaccine with a medium efficacy (50%) and duration of protection (3 years) would average 68 million courses annually over a 30-year period. Under different scenarios, demand would peak at 38-152 million courses annually. On the basis of tiered pricing across public and private markets ($US2-100 per dose), these levels of peak demand would translate into $US2.5-5.5 billion in peak annual sales revenues. Private markets and high-income countries account for small volumes but large shares of projected revenues, while low-income countries account for large volumes and more modest, but still significant, sales revenues. Vaccinations to 'catch-up' those who are missed or not eligible for routine annual programmes (whether adolescent or high-risk populations) would account for 20-35% of cumulative vaccination courses across all scenarios. Demand was found to be sensitive to vaccine efficacy, duration of protection and price. Efforts to expedite regulatory review processes, improve immunization infrastructure and reduce political constraints could increase demand for an AIDS vaccine by 40 million additional courses a year compared with the medium efficacy (baseline) vaccine forecast. CONCLUSIONS: Our model can provide vaccine developers with credible estimates of market potential for an AIDS vaccine, and with a tool that can be used to improve forecasts over time as AIDS vaccine science progresses. It can also help governments to identify and pursue those policies that could best strengthen demand and uptake of a safe and effective preventive AIDS vaccine.

Frequency of hospitalisations and inpatient care costs of manic episodes: in patients with bipolar I disorder in France.

BACKGROUND: Bipolar disorder is a chronic illness that may involve multiple relapses and result in substantial psychosocial impairment. However, very few recent studies have investigated the economic burden of the disease. OBJECTIVE: To assess the frequency of hospitalisation and the inpatient care costs associated with manic episodes in patients with bipolar I disorder in France. METHOD: A cost-of-illness study was conducted based on available data using a hospital payer perspective. The lifetime prevalence of manic episodes was estimated from published epidemiological data using a random-effects meta-analysis. Data were obtained by a computerised literature search using the main scientific and medical databases. Additional epidemiological references were identified from published studies and textbooks. Data on frequency of hospitalisation and length of stay were collected from a large psychiatric university hospital. Data on unit costs for inpatient care were obtained from the accounting system of the largest hospital group in Paris, France for the year 1999. RESULTS: Extrapolating from international data on the average prevalence of bipolar I disorder, the proportion of rapid cycling patients and the average cycle duration, we estimated the annual number of manic episodes in patients with bipolar I disorder to be around 265,000 in France. Based on hospital data in Paris, the proportion of manic episodes that require hospitalisation was estimated to be around 63%. The average length of stay was 32.4 days and the hospitalisation-related costs were estimated to be around 8.8 billion French francs (Euro 3 billion) [1999 values]. CONCLUSION: Our study highlights the lack of medical and economic data on the frequency and hospitalisation-related costs of manic episodes in patients with bipolar I disorder in France. As the lifetime prevalence of bipolar I disorder may be as high as 3% among adults, further studies are required in order to provide representative national data and to allow economic evaluations of costs related to bipolar I disorder in France.

Costs of bipolar disorder.

Bipolar disorder is a chronic affective disorder that causes significant economic burden to patients, families and society. It has a lifetime prevalence of approximately 1.3%. Bipolar disorder is characterised by recurrent mania or hypomania and depressive episodes that cause impairments in functioning and health-related quality of life. Patients require acute and maintenance therapy delivered via inpatient and outpatient treatment. Patients with bipolar disorder often have contact with the social welfare and legal systems; bipolar disorder impairs occupational functioning and may lead to premature mortality through suicide. This review examines the symptomatology of bipolar disorder and identifies those features that make it difficult and costly to treat. Methods for assessing direct and indirect costs are reviewed. We report on comprehensive cost studies as well as administrative claims data and program evaluations. The majority of data is drawn from studies conducted in the US; however, we discuss European studies when appropriate. Only two comprehensive cost-of-illness studies on bipolar disorder, one prevalence-based and one incidence-based, have been reported. There are, however, several comprehensive cost-of-illness studies measuring economic burden of affective disorders including bipolar disorder. Estimates of total costs of affective disorders in the US range from $US30.4-43.7 billion (1990 values). In the prevalence-based cost-of-illness study on bipolar disorder, total annual costs were estimated at $US45.2 billion (1991 values). In the incidence-based study, lifetime costs were estimated at $US24 billion. Although there have been recent advances in pharmacotherapy and outpatient therapy, hospitalisation still accounts for a substantial portion of the direct costs. A variety of outpatient services are increasingly important for the care of patients with bipolar disorder and costs in this area continue to grow. Indirect costs due to morbidity and premature mortality comprise a large portion of the cost of illness. Lost workdays or inability to work due to the disease cause high morbidity costs. Intangible costs such as family burden and impaired health-related quality of life are common, although it has proved difficult to attach monetary values to these costs.