Damian G. Walker

The iDSI reference case, originally published in 2014, aims to improve the quality and comparability of cost-effectiveness analyses (CEA). This study assesses whether the development of the guideline is associated with an improvement in methodological and reporting practices for CEAs using disability-adjusted life-years (DALYs). We analyzed the Tufts Medical Center Global Health CEA Registry to identify cost-per-DALY averted studies published from 2011 to 2017. Among each of 11 principles in the iDSI reference case, we translated all methodological specifications and reporting standards into a series of binary questions (satisfied or not satisfied) and awarded articles one point for each item satisfied. We then calculated methodological and reporting adherence scores separately as a percentage of total possible points, measured as normalized adherence score (0% = no adherence; 100% = full adherence). Using the year 2014 as the dissemination period, we conducted a pre-post analysis. We also conducted sensitivity analyses using: 1) optional criteria in scoring, 2) alternate dissemination period (2014–2015), and 3) alternative comparator classification. Articles averaged 60% adherence to methodological specifications and 74% adherence to reporting standards. While methodological adherence scores did not significantly improve (59% pre-2014 vs. 60% post-2014, p = 0.53), reporting adherence scores increased slightly over time (72% pre-2014 vs. 75% post-2014, p<0.01). Overall, reporting adherence scores exceeded methodological adherence scores (74% vs. 60%, p<0.001). Articles seldom addressed budget impact (9% reporting, 10% methodological) or equity (7% reporting, 7% methodological). The iDSI reference case has substantial potential to serve as a useful resource for researchers and policy-makers in global health settings, but greater effort to promote adherence and awareness is needed to achieve its potential.

Although there are many overlapping features, pediatric diarrheal diseases can vary in severity, duration, clinical manifestations and sequelae according to the causal pathogen, which in turn can impact the economic burden on patients and their families. We aimed to evaluate the household costs of diarrheal disease by pathogen in seven countries. We analyzed data from the Global Enteric Multicenter Study (GEMS), a prospective, age-stratified, matched case-control study of moderate-to-severe diarrheal disease among children aged 0-59 months in seven low income countries; four in Africa (Kenya, Mali, Mozambique, The Gambia), and three in Asia (Bangladesh, India, Pakistan). Demographic, epidemiological, economic, and clinical data were collected, and a stool sample was obtained for microbiological analysis at enrollment. We used a multivariate generalized linear model to assess the effect of rotavirus, Cryptosporidium, ST-producing enterotoxigenic E. coli (ETEC [ST only or LT plus ST]), Shigella, Campylobacter jejuni, norovirus GII, and Vibrio cholerae O1, age, gender, in/outpatient, and country on total costs to the patient/family. Household out-of-pocket costs were higher in Mali than any other country. Within countries, household cost differences between pathogens were minimal and not statistically significantly different. We found no significant differences in household costs by pathogen. Despite data limitations, understanding pathogen-specific household costs (or lack thereof) is useful as decision-makers could consider broader illness cost information and its relevance to a particular pathogen’s economic burden and contribution to poverty when deciding which pathogens to target for interventions.

Investing in global health and development requires making difficult choices about what policies to pursue and what level of resources to devote to different initiatives. Methods of economic evaluation are well established and widely used to quantify and compare the impacts of alternative investments. However, if not well conducted and clearly reported, these evaluations can lead to erroneous conclusions. Differences in analytic methods and assumptions can obscure important differences in impacts. To increase the comparability of these evaluations, improve their quality, and expand their use, this special issue includes a series of papers developed to support reference case guidance for benefit-cost analysis. In this introductory article, we discuss the background and context for this work, summarize the process we are following, describe the overall framework, and introduce the articles that follow.

Background Congenital syphilis continues to be a substantial public health problem in many parts of the world. Since the first use of penicillin for the treatment of syphilis in 1943, which was a notable early success, it has remained the preferred and standard treatment including for congenital syphilis. However, the treatment of congenital syphilis is largely based on clinical experience and there is extremely limited evidence on the optimal dose or duration of administration of penicillin or the use of other antibiotics. Objectives To assess the effectiveness and safety of antibiotic treatment for newborns with confirmed, highly probable and possible congenital syphilis. Search methods We searched the Cochrane STI Group Specialized Register, CENTRAL, MEDLINE, Embase, LILACS, WHO ICTRP, ClinicalTrials.gov and Web of Science to 23 May 2018. We also handsearched conference proceedings, contacted trial authors and reviewed the reference lists of retrieved studies. Selection criteria Randomised controlled trials (RCTs) comparing antibiotic treatment (any concentration, frequency, duration and route) with no intervention or any other antibiotic treatment for neonates with confirmed, highly probable or possible congenital syphilis. Data collection and analysis All review authors independently assessed trials for inclusion, extracted data and assessed the risk of bias in the included studies. We resolved any disagreements through consensus. We assessed the quality of the evidence using the GRADE approach. Main results Two RCTs (191 participants) met our inclusion criteria and none of these trials was funded by the industry. One trial (22 participants) compared benzathine penicillin with no intervention for infants with possible congenital syphilis. Low‐quality evidence suggested that benzathine penicillin administration may not have decreased the rate of neonatal death due to any cause (risk ratio (RR) 0.83, 95% confidence interval (CI) 0.06 to 11.70), and showed a possible reduction into the proportion of neonates with clinical manifestations of congenital syphilis (RR 0.12, 95% CI 0.01 to 2.09). Penicillin administration increased the serological cure at the third month (RR 2.13, 95% CI 1.06 to 4.27). These results should be taken with caution, because the trial was stopped early because there were four cases with clinical congenital syphilis in the no treatment group and none in the treatment group. Interim analysis suggested this difference was significant. This study did not report neonatal death due to congenital syphilis or the frequency of serious or minor adverse events after therapy. We downgraded the quality of evidence because of imprecision and risk of bias. One trial (169 participants) compared benzathine penicillin versus procaine benzylpenicillin. High‐ and moderate‐quality evidence suggested that there were probably no differences between benzathine penicillin and procaine benzylpenicillin for the outcomes: absence of clinical manifestations of congenital syphilis (RR 1.00, 95% CI 0.97 to 1.03) and serological cure (RR 1.00, 95% CI 0.97 to 1.03). There were no cases of neonatal death due congenital syphilis; all 152 babies who followed up survived. This study did not report on the frequency of serious or minor adverse events after therapy. We downgraded the quality of evidence because of serious risk of bias. Authors' conclusions At present, the evidence on the effectiveness and safety of antibiotic treatment for newborns with confirmed, highly probable or possible congenital syphilis is sparse, implying that we are uncertain about the estimated effect. One trial compared benzathine penicillin with no intervention for infants with possible congenital syphilis. Low‐quality evidence suggested penicillin administration possibly reduce the proportion of neonates with clinical manifestations of congenital syphilis, penicillin administration increased the serological cure at the third month. These findings support the clinical use of penicillin in neonates with confirmed, highly probable or possible congenital syphilis. High‐ and moderate‐quality evidence suggests that there are probably no differences between benzathine penicillin and procaine benzylpenicillin administration for the outcomes of absence of clinical manifestations of syphilis or serological cure.

The Disease Control Priorities (DCP) publications have pioneered new ways of thinking about investing in health. We agree with Norheim, that a useful first step to advance efforts to translate DCP’s global evidence into local health priorities, is to develop a clear Theory of Change (ToC). However, a ToC that aims to define how global evidence (DCP and others) can be used to inform national policy is too narrow an undertaking. We propose efforts should be directed towards developing a ToC to define how to support progressive institutional development to deliver on universal health coverage (UHC), putting the client at the center. Enhancing efforts to meet the new global health imperatives requires a shift in focus of attention to move radically from global to local. In order to achieve this we need to reorganize the nature of technical assistance (TA) along three major lines (1) examine and act to clarify the mandates and roles to be played by multilateral normative and convening agencies, (2) ensure detailed understanding of local institutions, their needs and their demands, and (3) provide TA over time and in trust with local counterparts. This last requirement implies the need for long-term local presence as well as an international network of expertise centers, to share scarce technical capabilities as well as to learn together across country engagements. Financing will need to be reorganized to incentivize and support demand-led capacity strengthening.

Introduction: The Global Financing Facility (GFF) was launched to accelerate progress towards the Sustainable Development Goals (SDGs) through scaled and sustainable financing for Reproductive, Maternal, Newborn, Child and Adolescent Health and Nutrition (RMNCAH-N) outcomes. Our objective was to estimate the potential impact of increased resources available to improve RMNCAH-N outcomes, from expanding and scaling up GFF support in 50 high-burden countries. Methods: The potential impact of GFF was estimated for the period 2017–2030. First, two scenarios were constructed to reflect conservative and ambitious assumptions around resources that could be mobilised by the GFF model, based on GFF Trust Fund resources of US$2.6 billion. Next, GFF impact was estimated by scaling up coverage of prioritised RMNCAH-N interventions under these resource scenarios. Resource availability was projected using an Excel-based model and health impacts and costs were estimated using the Lives Saved Tool (V.5.69 b9). Results: We estimate that the GFF partnership could collectively mobilise US$50–75 billion of additional funds for expanding delivery of life-saving health and nutrition interventions to reach coverage of at least 70% for most interventions by 2030. This could avert 34.7 million deaths—including preventable deaths of mothers, newborns, children and stillbirths—compared with flatlined coverage, or 12.4 million deaths compared with continuation of historic trends. Under-five and neonatal mortality rates are estimated to decrease by 35% and 34%, respectively, and stillbirths by 33%. Conclusion: The GFF partnership through country- contextualised prioritisation and innovative financing could go a long way in increasing spending on RMNCAH-N and closing the existing resource gap. Although not all countries will reach the SDGs by relying on gains from the GFF platform alone, the GFF provides countries with an opportunity to significantly improve RMNCAH-N outcomes through achievable, well-directed changes in resource allocation.

Background: The iDSI reference case, originally published in 2014, aims to improve the quality and comparability of cost-effectiveness analyses (CEAs). This study assesses whether the development of the guideline has improved the reporting and methodology for CEAs using disability-adjusted life-years (DALYs). Methods: We analyzed the Tufts Medical Center Global Health CEA Registry to identify cost-per-DALY averted studies published from 2011 to 2017. Among each of 11 principles in the iDSI reference case, we translated all reporting standards and methodological specifications into quantifiable yes/no questions and awarded articles one point for each item satisfied. We then separately calculated reporting and methods scores, measured as percent adherence (0%=no adherence, 100%=full adherence). Using the year 2014 as the dissemination period, we conducted a pre-post analysis. Additionally, we conducted an analysis stratified by the 11 principles and examined different scoring strategies and dissemination periods in sensitivity analyses. Results: Articles averaged 74% adherence to reporting standards and 60% adherence to methodological specifications. Adherence to reporting standards increased slightly over time (72% pre-2014 vs. 75% post-2014, p<0.01), but methodological adherence did not significantly improve (59% pre-2014 vs. 60% post-2014, p=0.53). Overall, reporting adherence scores exceeded methodology adherence scores (74% vs. 60%, p<0.001). Articles seldom addressed budget impact (9% reporting, 10% methodology) or equity (7% reporting, 7% methodology). Conclusions: The iDSI reference case has substantial potential to serve as a useful resource for researchers and policy-makers in global health settings, but greater effort to promote adherence and awareness is needed to achieve its potential.

In an environment of constrained resources, policymakers must identify solutions for financing and delivering health services that are efficient and sustainable. However, such solutions require that policymakers understand the complex interaction between household utilization patterns, factors influencing household medical decisions, and provider performance. This study examined whether and under what conditions out-of-pocket, transportation, and time costs influenced Kenyan households’ choice of medical provider for childhood diarrhoeal illnesses. It compared these decisions with the actual cost and quality of those providers to assess strategies for increasing the utilization of high quality, low-cost primary care. This study analyzed nationally-representative survey data through several multinomial nested logit models. On average, time costs accounted for the greatest share of total costs. Households spent the most time and transportation costs utilizing public care, yet were more likely to incur catastrophic time and out-of-pocket costs seeking private care for their child’s diarrhoeal illness. Out-of-pocket, transportation, and time costs influenced households’ choice of provider, though demand was cost inelastic and households were most responsive to transportation costs. Poorer households were the most responsive to changes in all cost types and most likely to self-treat or utilize informal care. Many households utilized informal care that, relative to formal care, cost the same but was of worse quality—suggesting that such households were making poor medical decisions for their children. To achieve public policy objectives, such as financial risk protection for childhood illnesses and equitable access to primary care, policymakers could focus on three areas: (1) refine financing strategies for further reducing household out-of-pocket costs; (2) reduce or subsidize time and transportation costs for households seeking public and private care; and (3) increase transparency of costs and quality to improve household decisions.

To estimate the economic impact likely to be achieved by efforts to vaccinate against 10 vaccine-preventable diseases between 2001 and 2020 in 73 low- and middle-income countries largely supported by Gavi, the Vaccine Alliance. We used health impact models to estimate the economic impact of achieving forecasted coverages for vaccination against Haemophilus influenzae type b, hepatitis B, human papillomavirus, Japanese encephalitis, measles, Neisseria meningitidis serogroup A, rotavirus, rubella, Streptococcus pneumoniae and yellow fever. In comparison with no vaccination, we modelled the costs - expressed in 2010 United States dollars (US$) - of averted treatment, transportation costs, productivity losses of caregivers and productivity losses due to disability and death. We used the value-of-a-life-year method to estimate the broader economic and social value of living longer, in better health, as a result of immunization. We estimated that, in the 73 countries, vaccinations given between 2001 and 2020 will avert over 20 million deaths and save US$ 350 billion in cost of illness. The deaths and disability prevented by vaccinations given during the two decades will result in estimated lifelong productivity gains totalling US$ 330 billion and US$ 9 billion, respectively. Over the lifetimes of the vaccinated cohorts, the same vaccinations will save an estimated US$ 5 billion in treatment costs. The broader economic and social value of these vaccinations is estimated at US$ 820 billion. By preventing significant costs and potentially increasing economic productivity among some of the world's poorest countries, the impact of immunization goes well beyond health.