By HENRY OWINO (Senior Correspondent)
The Drugs for Neglected Diseases initiative (DNDi) Organization has for the 15 years of experience accumulated, discovered, developed, and delivered new and improved treatments for neglected patients. These include new drugs, diagnostics, or vaccines to address pressing health needs in resource-limited settings and the list continues.
Yet when DNDi was founded, in the late 1990s or early 2000s as not-for-profit entities to conduct and coordinate research and development (R&D) in health sector, many were sceptical that a not-for-profit approach to R&D could succeed.
DNDi has been an ‘experiment in innovation both in what it does, develop urgently needed treatments for neglected populations and how it does so: testing an alternative virtual R&D model, based not on profit maximization but on patient needs, which aims to promote the broadest possible sharing of research knowledge and data through a collaborative approach,
It also seeks to ensure both innovation and affordable access to new and improved treatments with the desire to develop drugs as public goods wherever and whenever possible.
Over the past 15 years, a number of new initiatives and new policies have favoured the sharing of data and IP and a greater diffusion of knowledge, a movement which has impacted global health – through, for example, the creation the Medicines Patent Pool as well as multiple other sectors.
DNDi is committed to exploring the potential contributions of open and collaborative science. This is because the organization considers that publicly or philanthropically funded R&D ought to be carried out in the public interest, be as transparent as possible, and shared as broadly and equitably as possible.
DNDi also believes in the intrinsic advantages of sharing and collaborating, which can attract additional researchers to a neglected field, enable more and different results, and potentially accelerate the R&D process by reducing duplication as well as make R&D activities more efficient and less expensive. DNDi’s approach is focused on areas where bottlenecks exist, and where openness and collaboration could have the greatest impact for neglected patients.
Distinctive Features of DNDi Achievements
DNDi recognizes the importance of contributing to scientific knowledge by sharing data whether positive or negative, collected through its clinical trials, in order to improve the lives of neglected patients whose needs are often overlooked in research.
In May 2017, DNDi adopted a policy on the Sharing of Clinical Trial Data and signed on to the WHO Joint Statement on Public Disclosure of Results from Clinical Trials.8 DNDi has also committed itself to registering all trials in a publicly available register, such as the US National Institutes of Health (NIH) clinicaltrials.gov or the Pan-African Clinical Trials Registry, promptly reporting trial results 12 months after completion of the trial, and publishing findings in open access journals.
Various policies now push for scientific findings to be openly accessible, from the 2008 US NIH Public Access Policy, to the Plan S initiative launched in 2018 in Europe, with backing from numerous funding bodies, calling for free access to all scientific papers at the point of publication.
DNDi commits to contributing to public databases and open-access journals, to “support the timely communication of all research it sponsors (discovery, pre-clinical, clinical), and facilitate the rapid and accurate communication of DNDi-sponsored research and clinical trial results to the wider scientific and medical communities”. In 2018, 85% of the 26 peer-reviewed scientific articles published by DNDi authors were open-access.
Pooling Clinical Data to Overcome the Fragmentation of Research
Pooling and standardizing the data generated by different trials allows for improved understanding of clinical outcomes and can guide the design of future trials. The Infectious Diseases Data Observatory (IDDO) seeks to assemble global clinical, laboratory and epidemiological data on a collaborative platform that can be shared across the research and humanitarian communities.
DNDi collaborates with IDDO by sharing fully anonymized data from its visceral leishmaniasis trials in a data platform launched in 2017. In 2019, IDDO and DNDi created a Chagas Clinical Data Sharing Platform to collate and standardize data, enabling comparisons of efficacy between drugs, regimens and regions, which is almost impossible from publications.
DNDi Best Science for the Most Neglected
DNDi stresses the value of academic and public research centres as well as industry to the early research phase, but as the organization is often not engaged until the discovery phases (screening, hit to lead, lead optimization) or pre-clinical phases, it cannot place an exhaustive and reliable economic value on early research costs. Industry costing models often have a similar limitation, as costs incurred prior to lead optimization cannot be attributed to specific compounds, and industry studies often aggregate data at this level to assess costs per drug for R&D incurred prior to human testing. In addition, industry cost models do not capture public investments at this early stage of research.
There is no “market price” methodology that can serve as a valuation benchmark to determine the value of a compound at the discovery stage secured from an industry partner. When DNDi secures the license to a compound for a neglected indication, the economic value (defined as potential for financial returns, as distinct from the historical cost) of that compound for that indication is considered as very limited or null. The only exception occurs when the compound development could lead to a Priority Review Voucher.
In such cases, the industry partner and DNDi negotiate collaboration on the principle of fair distribution of possible economic benefits commensurate with investments, and past investments by the IP holder are factored into the equation.
Post-registration additional studies and access costs are not included here. DNDi investments in implementation vary widely from project to project depending on what is needed to secure wide access to a treatment developed (see page 24). It is therefore challenging to define average ranges of costs. Furthermore, while DNDi designs its development activities with access in mind from the outset, the full roll-out and implementation is a domain where DNDi more commonly looks to other organizations to co-lead.
DNDi’s ultimate objective is to contribute to new innovation ecosystems, driven by scientific leaders in LMICs that will fundamentally change how research priorities are defined and where end-to-end health R&D in the public interest is conducted.
A virtual, collaborative R&D organization can only succeed with strong partnerships and alliances and a global network. Leadership from the public sector, particularly in LMICs, is essential to ensuring sustainable innovation ecosystems.
Proximity to the needs of affected communities and patients is critical and can only be achieved through building trusting and equal partnerships with local clinicians, scientists, and experts, as well as patient and community/civil society groups in affected countries.
In LMICs, innovative partnerships throughout the R&D process leverage and strengthen existing research capacity, facilitate needs definition, promote scientific exchange, and enable access. In addition, targeted investments in training and health infrastructure improvements, including in remote settings, are critical for success.
Since 2003, five disease-specific clinical research platforms and networks have been created. By bringing together key actors, including health ministries, national disease control programmes, regulatory authorities, WHO, academia, civil society groups, as well as clinicians and health professionals, these ‘knowledge hubs’ promote scientific exchange, and facilitate access and delivery of new tools.
Looking to the future, existing R&D capacity in LMICs, and the desire to support and enhance this potential, should be harnessed to address national, regional, and global health priorities while ensuring the needs of the most vulnerable are met. Achieving this goal will require the active participation of medical and scientific communities, civil society, as well as national and regional political leadership and financing.
Trial Sizes and Location
As DNDi studies focus on diseases for which treatment options are usually limited, the number of patients and volume of studies required to show statistically significant improvements over the standard of care is lower than for many industry trials looking to show only incremental improvements over previously approved drugs. Furthermore, as DNDi patients are in LMICs, costs of clinical trials are usually lower than in HICs.
However, logistics and trial coordination are more complex, and as part of its mission, DNDi invests 5% of its overall expenditures (2018 data) in strengthening existing clinical research capacities to increase the ability of neglected disease-endemic countries to respond to their own research needs.
Finally, patient recruitment varies considerably (for a drug intended to facilitate the sustainable elimination of a disease, patient recruitment may require many sites, sometimes across several countries, whereas patient recruitment is easier for trials with sites in highly endemic areas) and this has a bearing on DNDi costs.