Open Source Drug Discovery in Practice: A Case Study

Background: Open source drug discovery offers potential for developing new and inexpensive drugs to combat diseases that disproportionally affect the poor. The concept borrows two principle aspects from open source computing (i.e., collaboration and open access) and applies them to pharmaceutical innovation. By opening a project to external contributors, its research capacity may increase significantly. To date there are only a handful of open source R&D projects focusing on neglected diseases. We wanted to learn from these first movers, their successes and failures, in order to generate a better understanding of how a much-discussed theoretical concept works in practice and may be implemented. Methodology/Principal Findings: A descriptive case study was performed, evaluating two specific R&D projects focused on neglected diseases. CSIR Team India Consortium's Open Source Drug Discovery project (CSIR OSDD) and The Synaptic Leap's Schistosomiasis project (TSLS). Data were gathered from four sources: interviews of participating members (n = 14), a survey of potential members (n = 61), an analysis of the websites and a literature review. Both cases have made significant achievements; however, they have done so in very different ways. CSIR OSDD encourages international collaboration, but its process facilitates contributions from mostly Indian researchers and students. Its processes are formal with each task being reviewed by a mentor (almost always offline) before a result is made public. TSLS, on the other hand, has attracted contributors internationally, albeit significantly fewer than CSIR OSDD. Both have obtained funding used to pay for access to facilities, physical resources and, at times, labor costs. TSLS releases its results into the public domain, whereas CSIR OSDD asserts ownership over its results. Conclusions/Significance: Technically TSLS is an open source project, whereas CSIR OSDD is a crowdsourced project. However, both have enabled high quality research at low cost. The critical success factors appear to be clearly defined entry points, transparency and funding to cover core material costs

An International Legal Framework to Address Antimicrobial Resistance

Antimicrobial resistance is a growing threat to global health. Currently it accounts for approximately 700,000 deaths annually, but is predicted to cause as many as 10,000,000 deaths by 2050 if nothing is done to address it. To effectively deal with this problem three areas must be addressed simultaneously: access, conservation, and innovation. However, solving issues of access, conservation and innovation at the same time requires new coordination and financing mechanisms, some of which must be organized globally. This bulletin outlines the possible role that a binding international legal framework can play in the fight against antimicrobial resistance

Using European travellers as an early alert to detect emerging pathogens in countries with limited laboratory resources

BACKGROUND: The volume, extent and speed of travel have dramatically increased in the past decades, providing the potential for an infectious disease to spread through the transportation network. By collecting information on the suspected place of infection, existing surveillance systems in industrialized countries may provide timely information for areas of the world without adequate surveillance currently in place. We present the results of a case study using reported cases of Shigella dysenteriae serotype 1 (Sd1) in European travellers to detect "events" of Sd1, related to either epidemic cases or endemic cases in developing countries. METHODS: We identified papers from a Medline search for reported events of Sd1 from 1940 to 2002. We requested data on shigella infections reported to the responsible surveillance entities in 17 European countries. Reports of Sd1 from the published literature were then compared with Sd1 notified cases among European travellers from 1990 to 2002. RESULTS: Prior to a large epidemic in 1999–2000, no cases of Sd1 had been identified in West Africa. However, if travellers had been used as an early warning, Sd1 could have been identified in this region as earlier as 1992. CONCLUSION: This project demonstrates that tracking diseases in European travellers could be used to detect emerging disease in developing countries. This approach should be further tested with a view to the continuous improvement of national health surveillance systems and existing European networks, and may play a significant role in aiding the international public health community to improve infectious disease control

Antibiotic research and development: business as usual?

This article contends that poor economic incentives are an important reason for the lack of new drugs and explains how the DRIVE-AB intends to change the landscape by harnessing the expertise, motivation and diversity of its partner

Remdesivir and three other drugs for hospitalised patients with COVID-19: final results of the WHO Solidarity randomised trial and updated meta-analyses.

BACKGROUND World Health Organization expert groups recommended mortality trials of four repurposed antiviral drugs - remdesivir, hydroxychloroquine, lopinavir, and interferon beta-1a - in patients hospitalized with coronavirus disease 2019 (Covid-19). METHODS We randomly assigned inpatients with Covid-19 equally between one of the trial drug regimens that was locally available and open control (up to five options, four active and the local standard of care). The intention-to-treat primary analyses examined in-hospital mortality in the four pairwise comparisons of each trial drug and its control (drug available but patient assigned to the same care without that drug). Rate ratios for death were calculated with stratification according to age and status regarding mechanical ventilation at trial entry. RESULTS At 405 hospitals in 30 countries, 11,330 adults underwent randomization; 2750 were assigned to receive remdesivir, 954 to hydroxychloroquine, 1411 to lopinavir (without interferon), 2063 to interferon (including 651 to interferon plus lopinavir), and 4088 to no trial drug. Adherence was 94 to 96% midway through treatment, with 2 to 6% crossover. In total, 1253 deaths were reported (median day of death, day 8; interquartile range, 4 to 14). The Kaplan-Meier 28-day mortality was 11.8% (39.0% if the patient was already receiving ventilation at randomization and 9.5% otherwise). Death occurred in 301 of 2743 patients receiving remdesivir and in 303 of 2708 receiving its control (rate ratio, 0.95; 95% confidence interval [CI], 0.81 to 1.11; P = 0.50), in 104 of 947 patients receiving hydroxychloroquine and in 84 of 906 receiving its control (rate ratio, 1.19; 95% CI, 0.89 to 1.59; P = 0.23), in 148 of 1399 patients receiving lopinavir and in 146 of 1372 receiving its control (rate ratio, 1.00; 95% CI, 0.79 to 1.25; P = 0.97), and in 243 of 2050 patients receiving interferon and in 216 of 2050 receiving its control (rate ratio, 1.16; 95% CI, 0.96 to 1.39; P = 0.11). No drug definitely reduced mortality, overall or in any subgroup, or reduced initiation of ventilation or hospitalization duration. CONCLUSIONS These remdesivir, hydroxychloroquine, lopinavir, and interferon regimens had little or no effect on hospitalized patients with Covid-19, as indicated by overall mortality, initiation of ventilation, and duration of hospital stay. (Funded by the World Health Organization; ISRCTN Registry number, ISRCTN83971151; ClinicalTrials.gov number, NCT04315948.)

Assessing implementation mechanisms for an international agreement on research and development for health products

The Member States of the World Health Organization (WHO) are currently debating the substance and form of an international agreement to improve the financing and coordination of research and development (R&D) for health products that meet the needs of developing countries. In addition to considering the content of any possible legal or political agreement, Member States may find it helpful to reflect on the full range of implementation mechanisms available to bring any agreement into effect. These include mechanisms for states to make commitments, administer activities, manage financial contributions, make subsequent decisions, monitor each other’s performance and promote compliance. States can make binding or non-binding commitments through conventions, contracts, declarations or institutional reforms. States can administer activities to implement their agreements through international organizations, sub-agencies, joint ventures or self-organizing processes. Finances can be managed through specialized multilateral funds, financial institutions, membership organizations or coordinated self-management. Decisions can be made through unanimity, consensus, equal voting, modified voting or delegation. Oversight can be provided by peer review, expert review, self-reports or civil society. Together, states should select their preferred options across categories of implementation mechanisms, each of which has advantages and disadvantages. The challenge lies in choosing the most effective combinations of mechanisms for supporting an international agreement (or set of agreements) that achieves collective aspirations in a way and at a cost that are both sustainable and acceptable to those involved. In making these decisions, WHO’s Member States can benefit from years of experience with these different mechanisms in health and its related sectors

Developing Health Technology Assessment to address health care system needs

Garrido MV, Gerhardus A, Rottingen J-A, Busse R. Developing Health Technology Assessment to address health care system needs. HEALTH POLICY. 2010;94(3):196-202.This article discusses the development of Heath Technology Assessment methods and HTA institutions. in regards to meeting the information needs of all levels and fields of health policy-making. On the one hand, HTA needs to expand and develop its methods. Although health products and health care services have been its preponderant focus to date, HTA should develop to increase its focus on the "technologies applied to health care" (i.e. the regulatory and policy measures for managing and organizing health care systems) and on policies in non-health care sectors. Such a knowledge synthesis for health policy should not necessarily be called HTA or conducted by narrowly defined HTA agencies. However, the trends observed in several European HTA agencies indicate the recognition of these development needs. Countries embarking on HTA should not consider establishing separate agencies for HTA, quality development, performance measurement, and health services development, but should rather combine these functions and goals into a common knowledge strategy for evidence-informed decision-making on health care and the health system. (C) 2009 Elsevier Ireland Ltd. All rights reserved

Future challenges for HTA in Europe.

Rottingen JA, Gerhardus A, Velasco Garrido M. Future challenges for HTA in Europe. In: Velasco Garrido M, Kristensen FB, Palmhøj Nielsen C, Busse R, eds. Health Technology Assessment and Health Policy-Making in Europe: Current status, challenges and potential. World Health Organization; 2008: 161-181