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.

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We aimed to compare clinical outcomes, health-related quality of life (HRQOL) and work status associated with olanzapine and haloperidol treatment in patients with bipolar disorder. This double-blind, randomized controlled trial, comparing flexible dosing of olanzapine (5-20 mg/day, n = 234) to haloperidol (3-15 mg/day, n = 219), consisted of a 6-week acute phase, followed by a 6-week continuation phase. Symptomatic remission rates were similar for olanzapine- and haloperidol-treated patients at weeks 6 and 12. At week 6, significant changes in five dimensions of the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) [general health (P = 0.010), physical functioning (P < 0.001), role limitations due to physical problems (P < 0.001), social functioning (P < 0.05) and vitality (P < 0.01)] and the SF-36 physical components summary score were found in favour of olanzapine compared to haloperidol. At week 12, olanzapine treatment maintained the significantly favourable HRQOL changes. At the end of week 12, patients on olanzapine showed significantly greater improvement than haloperidol in work activities impairment and household activities impairment scores on the Streamlined Longitudinal Interview Clinical Evaluation from the Longitudinal Interval Follow-up Evaluation (SLICE/LIFE) activities impairment scores. Subgroup analyses revealed that olanzapine treatment significantly increased a proportion of employed patients and their weekly paid working hours. In conclusion, compared to haloperidol, olanzapine treatment was comparably effective in the remission of bipolar mania and significantly improved HRQOL and work status in patients with bipolar I disorder.

BackgroundGAVI’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.MethodsA 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.ResultsSerches 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.ConclusionIn 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12889-015-2521-8) contains supplementary material, which is available to authorized users.

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BackgroundTo 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.MethodsThis 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.ResultsExisting 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.ConclusionsThe 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 ...

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.