Investing in late-stage clinical trials and manufacturing of product candidates for five major infectious diseases: a modelling study of the benefits and costs of investment in three middle-income countries

BACKGROUND : Investing in late-stage clinical trials, trial sites, and production capacity for new health products could improve access to vaccines, therapeutics, and infectious disease diagnostics in middle-income countries. This study assesses the case for such investment in three of these countries: India, Kenya, and South Africa. METHODS: We applied investment case modelling and assessed how many cases, deaths, and disability-adjusted life years (DALYs) could be averted from the development and manufacturing of new technologies (therapeutics and vaccines) in these countries from 2021 to 2036, for five diseases—HIV, tuberculosis, malaria, pneumonia, and diarrhoeal diseases. We also estimated the economic benefits that might accrue from making these investments and we developed benefit–cost ratios for each of the three middle-income countries. Our modelling applies two investment case perspectives: a societal perspective with all costs and benefits measured at the societal level, and a country perspective to estimate how much health and economic benefit accrues to each middle-income country for every dollar invested in clinical trials and manufacturing by the middle-income country government. For each perspective, we modelled two scenarios: one that considers only domestic health and economic benefits; and one that includes regional health and economic benefits. In the regional scenarios, we assumed that new products developed and manufactured in India would benefit eight countries in south Asia, whereas new products developed and manufactured in Kenya would benefit all 21 countries in the Common Market for Eastern and Southern Africa (COMESA). We also assumed that all 16 countries in the Southern African Development Community (SADC) would benefit from products developed and manufactured in South Africa. FINDINGS : From 2021 to 2036, product development and manufacturing in Kenya could avert 4·44 million deaths and 206·27 million DALYs in the COMESA region. In South Africa, it could prevent 5·19 million deaths and 253·83 million DALYs in the SADC region. In India, it could avert 9·76 million deaths and 374·42 million DALYs in south Asia. Economic returns would be especially high if new tools were produced for regional markets rather than for domestic markets only. Under a societal perspective, regional returns outweigh investments by a factor of 20·51 in Kenya, 33·27 in South Africa, and 66·56 in India. Under a country perspective, the regional benefit–cost ratios amount to 60·71 in India, 8·78 in Kenya, and 11·88 in South Africa. INTERPRETATION : Our study supports the creation of regional hubs for clinical trials and product manufacturing compared with narrow national efforts.The Bill & Melinda Gates Foundation.https://www.thelancet.com/journals/langlo/homehttps://datahelpdesk.worldbank.org/knowledgebase/articles/906519-world-bank-country-and-lending-groupsam2023Graduate School of Technology Management (GSTM

Developing new health technologies for neglected diseases: a pipeline portfolio review and cost model [version 1; referees: 1 approved, 2 approved with reservations]

Background:  Funding for product development for neglected diseases fell from 2009-2015, other than a short-term injection of Ebola funding. One impediment to mobilizing resources is a lack of information on product candidates, the estimated costs to move them through the pipeline, and the likelihood of specific launches. This study aimed to help fill these information gaps. Methods: We conducted a pipeline portfolio review to identify current candidates for 35 neglected diseases. Using an adapted version of the Portfolio to Impact (P2I) financial modelling tool, we estimated the costs to move these candidates through the pipeline over the next decade and the likely launches. Since the current pipeline is unlikely to yield several critical products, we estimated the costs to develop a set of priority “missing” products. Results: We found 685 product candidates for neglected diseases as of August 31, 2017; 538 candidates met inclusion criteria for input into the model. It would cost about $16.3 billion (range$13.4-19.8B) to move these candidates through the pipeline, with three-quarters of the costs incurred in the first 5 years, resulting in about 128 (89-160) expected product launches.  Based on the current pipeline, there would be very few launches of complex new chemical entities; launches of highly efficacious vaccines for HIV, tuberculosis, or malaria would be unlikely. Estimated additional costs to launch one of each of 18 key missing products range from $13.6B-$21.8B, depending on product complexity. Over the next 5 years, total estimated costs to move current candidates through the pipeline and develop these 18 missing products would be around $4.5-5.8B/year. Conclusions: Since current annual global spending on product development is about$3B, this study suggests the annual funding gap over the next 5 years is at least $1.5-2.8B, which is probably an underestimate. The current portfolio is not balanced across health needs

Human Monkeypox Outbreak Caused by Novel Virus Belonging to Congo Basin Clade, Sudan, 2005

TOC Summary: This virus should be considered endemic to the wetland areas of Bentiu, Unity State, Sudan

ANALYSIS OF THE HEALTH PRODUCT PIPELINE FOR POVERTY-RELATED AND NEGLECTED DISEASES USING THE PORTFOLIO-TO-IMPACT (P2I) MODELLING TOOL

To estimate how much additional funding is needed for poverty-related and neglected disease (PRND) product development and to target new resources effectively, policymakers need updated information on the development pipeline and estimated costs to fill pipeline gaps. In this study, we analyze the product pipeline for PRNDs up to August 31, 2019 for 45 diseases and 6 multiple diseases and also conduct a comparison analysis with the product pipeline analysis we conducted for PRNDs in 2017 that included 35 diseases and 5 multiple disease categories

Phylogenetic and Ecologic Perspectives of a Monkeypox Outbreak, Southern Sudan, 2005

Identification of human monkeypox cases during 2005 in southern Sudan (now South Sudan) raised several questions about the natural history of monkeypox virus (MPXV) in Africa. The outbreak area, characterized by seasonally dry riverine grasslands, is not identified as environmentally suitable for MPXV transmission. We examined possible origins of this outbreak by performing phylogenetic analysis of genome sequences of MPXV isolates from the outbreak in Sudan and from differing localities. We also compared the environmental suitability of study localities for monkeypox transmission. Phylogenetically, the viruses isolated from Sudan outbreak specimens belong to a clade identified in the Congo Basin. This finding, added to the political instability of the area during the time of the outbreak, supports the hypothesis of importation by infected animals or humans entering Sudan from the Congo Basin, and person-to-person transmission of virus, rather than transmission of indigenous virus from infected animals to humans