New Diagnostics for Neglected Diseases –
The Foundation for Innovative New Diagnostics (FIND)
Business Case
Research & Evidence Division,
Human Development Team
May 2013
1
INTERVENTION SUMMARY
What support will the UK provide?
DFID will provide £10,050,000 over 5 years (2013/14-2017/18) to the Foundation for Innovative
New Diagnostics (FIND) for the development of new diagnostics for neglected diseases of the
poor, including TB, sleeping sickness, leishmaniasis, malaria and non-malarial febrile illness.
Why is UK support required?
Neglected diseases, TB and malaria are major causes of mortality, illness and lack of economic
progress for the poorest. The UK is both one of the major supporters of work in this area, and
has some of the leading scientists and research groups globally. Each year these diseases
together cause 13.7million deaths and the loss of 377 million years of healthy and productive
life globally. While much of this ill health and death is preventable with existing tools, additional
tools are still required, particularly where active diagnosis of disease status is required before
treatment and existing methods rely on particularly cumbersome and/or invasive medical and
laboratory procedures (e.g. extraction of cerebrospinal fluid).
High quality diagnostics are required to reduce illness and death through improved patient
treatment outcomes (ensuring that the right people are getting the right drugs). They also
reduce substantial drug wastage (and the associated risk of emerging or increasing drug
resistance); for example without diagnostics the great majority of people given expensive antimalarials do not in fact have malaria. The cost-effectiveness of both new and old drugs
depends on better diagnostics being developed. Current products, even when available, are
either insensitive (miss cases), non-specific (many false positives), expensive, difficult to use in
clinics without power or are unstable in tropical climates. Diagnostic tests are essential to
provide reliable epidemiological data for programme decisions, disease-control programme
implementation and monitoring.
There are market failures around the development of new technologies for diseases of poverty
purely in the for-profit private sector, in large part because most individuals and countries with
these diseases are very poor making return on investment very uncertain. This extends to
diagnostics.
What are the expected results?
DFID’s investment in FIND will allow them to continue to contribute towards the impact goal of
reducing the global burden of neglected diseases and their impact on both patients and health
systems through enhanced disease diagnosis, treatment and control.
Working to accelerate diagnostics development across TB, sleeping sickness, leishmaniasis,
malaria and non-malarial febrile illness, and potentially in new disease areas, the main 5-year
outputs associated with this funding are:
 5+ neglected disease diagnostic tests developed and in use in disease endemic
countries
 Strong and balanced pipeline of diagnostics in development, including 3-5 fully
evaluated tests and another 4-6 for which technical feasibility has been established
 Strategic portfolio expansion into at least 1 new disease area
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STRATEGIC CASE
A. Context and Need for a DFID Intervention
Neglected tropical diseases (NTDs), TB and malaria are major causes of mortality, illness and
lack of economic progress for the poorest. The UK is both one of the major supporters of work
across these disease areas, and has some of the leading scientists and research groups
globally. Each year these diseases together cause 13.7million deaths and the loss of 377
million years of healthy and productive life globally. For example, half the world’s population is
at risk of malaria and around one third of them are currently infected with tuberculosis (TB),
sleeping sickness (Human African Trypanosomiasis – HAT), leishmaniasis or Chagas disease1.
Loss of productivity due to malaria is thought to reduce national incomes across much of subSaharan Africa by as much as 15-20%2 while the World Bank estimates that in disease
endemic countries (DEC) the burden of TB may result in 4-7% losses of Gross National
Product (GNP)3. The UK government invests heavily in global efforts to reduce these diseases
both through country programmes and indirectly through major contributions to organisations
such as the Global Fund. In 2012, the UK became signatories to the London Declaration of
Neglected Tropical Diseases and committed, with other donors, non-governmental
organisations (NGOs) and industry players, to support the WHO Roadmap for the elimination,
eradication and control of the NTDs by 2020. While much of the ill health and death associated
with TB, malaria and NTDsis preventable with existing tools, additional tools are still required,
particularly where existing treatments are difficult to use, ineffective or associated with adverse
events, and/or where we lack reliable tools for accurate disease detection and diagnosis.
The Need for New Neglected Disease Diagnostics
Diagnostics are a critical, oft overlooked, tool for improving global health. Appropriate, reliable,
high quality diagnostics are required to reduce illness and death through:
- evidence-based patient management and associated
o improved patient outcomes (ensuring the right people are treated for the right
diseases and /or severity of infection),
o reduced drug wastage
o reduced risk of emerging or increasing drug resistance
- screening for asymptomatic disease carriers (who may still be infectious),
- disease surveillance and outbreak investigations, and
- epidemiological studies to better understand disease burden and transmission, and
the efficacy of treatments and/or vaccines4.
Without reliable, affordable and appropriate diagnostics, patients in need of treatment may not
be detected while others may be misdiagnosed resulting in mistreatment. Misdiagnosis can
waste costly medicines placing unnecessary strains on already tight health budgets and
increase the risk of drug-resistance through mis- and/or over-treatment. Current diagnostic
products, even when available, are either insensitive (and miss disease cases) or non-specific
(falsely diagnosing uninfected individuals as infected), expensive, difficult to use in clinics
1
Norris J et al (2012) FULL REF. Hudson Institute Briefing Paper
Sachs J et al (2002) FULL REF. In Nature v415(6872): 680-5
3 Laxminarayan R et al FULL REF World Bank Policy Research Working Paper n.4295
4 Burgess, Wasserman & Dahl (2006) Foreword: Global Health Diagnostics. In ‘Determining
the Global Health Impact of Improved Diagnostic Technologies for the Developing World’. In
Nature S1:1-2
2
3
without power or are unstable in tropical climates. Significant efforts are required to develop
neglected disease diagnostics that do not require extensive laboratory infrastructure and can
be used by health workers with minimal training5. This is particularly true for neglected
diseases of the poor, an area in which the private biotech industry has little commercial
interest.
The following examples (cervical cancer, HIV, TB, malaria and sleeping sickness) serve to
illustrate the powerful public health impact the availability and use of appropriate disease
diagnostics can make.
The introduction of Pap smear test has reduced the number of cervical cancer deaths by up to
99% in those countries where women are now routinely tested6. Likewise, the risk of HIV and
hepatitis C transmission through blood transfusion has been reduced to less than 1 case per
million transfusions in those countries with well-regulated blood banks and associated donor
screening and blood testing7.
In the case of TB, the development and use of appropriate diagnostic tests and treatment has
had a huge impact on TB prevalence and mortality, even when only moderately reliable
diagnostics have been available8. For example the implementation of a systematic microscopybased diagnosis for TB is estimated to have saved 5.4 million lives between 1995 and 20099. In
spite of these gains, the significant growth of HIV-associated TB and the spread of multi-drug
resistant (MDR) TB has increased mortality rates in some populations and heightened the need
for improved diagnostics that outperform microscopy. Patients co-infected with HIV and TB
have high especially high short-term mortality in the absence of early TB infection detection
and treatment. In a study in Malawi, half of HIV patients with suspected TB but whose infection
could not be confirmed by microscopy died while waiting for definitive diagnosis10. This
example serves to illustrate the potential importance of rapid diagnostic tests (RDTs) in
averting treatment delays (and death) and interrupting further disease transmission.
Malaria causes high rates of mortality across sub-Saharan Africa and other endemic regions.
However, while the prevalence of malaria can be high, a reliance on syndromic management11
in the absence of appropriate, field-applicable diagnostics has historically resulted in overtreatment for malaria. Unfortunately, the clinical presentation of malaria is highly variable and
overlaps with a number of other common illnesses, including pneumonia, also associated with
significant disease burden and mortality12. Falling malaria incidence globally has meant that the
automatic treatment of fever as malaria has resulted in even more overtreatment. This
overtreatment has, in turn, contributed to huge drug wastage (at economic cost to health
systems). Even in sub-Saharan Africa, less than a quarter of all febrile patients (those with
5
Ibid.
DeMay RM (2000) In American Journal of Clinical Pathology v114: S48-51
7 Zou S (2010) In Transfusion v50: 1495-504
8 Subramani R et al (2008) Rapid decline of prevalence of pulmonary tuberculosis after DOTS
implementation in a rural area of South India. In International Journal of Tuberculosis and
Lung Disease v.12(8): 916-920
9 Glaziou P (2011) In Bulletin of the World Health Organisation v89: 573-582
10 Friend JH et al (2005) In Tropical Doctor v35(2): 93-95
11 Sydromic management = the diagnosis of disease status on the basis of clinical symptoms.
In the case of malaria, high fever is often the main symptom used to make presumptive
diagnosis though it is increasingly recognised that there are many other infections that share
this clinical symptom.
12 Kallander K et al (2005) In Acta Tropica v90(2):211-4
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fever) are infected with malaria13. Failure to use diagnostic evidence to guide therapy in cases
of suspected malaria has been shown to increase mortality rates due to mistreatment 14. The
development and routine use of rapid diagnostic tests for malaria has, in recent years, led to
significant improvements in patient management and treatment and associated large
decreases in anti-malarial drug wastage15.
Sleeping sickness is endemic in 36 African countries and is fatal if undetected and/or
untreated. Diagnosis remains a challenge particularly in the rural (and often fragile) settings in
which it is most commonly found. In early stage infection patients demonstrate few, if any,
disease symptoms making it impossible to diagnosis infection on the basis of clinical
symptoms. However, if undetected the disease progresses to a second stage of infection, at
which stage the disease enters the central nervous system (where it causes huge damage and
often death). At this stage of infection the disease is risky, difficult and expensive to treat. At the
current time there is no widely available point-of-use or rapid diagnostic test for sleeping
sicknesses which means that laboratory facilities and expertise are required for diagnosis.
Given the potential severity of second stage sleeping sickness and different treatment
regimens for the two stages of disease, all those testing positive for infection must undergo a
second test to determine their disease stage. Currently this second test involves the extraction
and testing of their cebrospinal fluid which can only be conducted by highly trained medical
personal at fully equipped tertiary level hospitals and is highly invasive and painful for the
patient. When testing positive for second stage sleeping sickness, patients must undergo long,
complex and expensive treatment and medical supervision to ensure parasite clearance. As
there is still no definitive test-of-cure available, patient treatment times currently stand at 2436months representing huge challenges for treatment compliance and causing huge strains on
the health system. A simple test-of-cure could conceivably reduce treatment duration to 36months. The lack of a sensitive and specific, field-adapted, diagnostic test for detecting both
stages of the sleeping sickness disease is possibly the biggest remaining barrier to controlling
this fatal disease16.
The identification and treatment challenges for leishmaniasis are also similar to those
described above for sleeping sickness – a long and toxic treatment regime necessitates
parasitological confirmation of disease status before drugs are administered, and the only
available quality diagnostics rely on microscopy and are highly invasive (they use lymph node,
bone marrow or spleen aspirates) making them difficult to perform in remote and resource-poor
settings, and failure to detect when the patient has been cured.17
The Case for Investing in Neglected Disease Diagnostics
The above sections highlighted the huge global burden of neglected diseases and the
importance of diagnostics in their effective management, control and surveillance. However,
while neglected diseases remain a major problem there has historically been little private
investment in the development of new diagnostics, treatments or vaccines associated with
them.
D’Acremont V et al (2010) In Malaria Journal v9:240
WHO (2008) World Malaria Report. WHO, Geneva.
15 D’Acremont V et al (2011) In Malaria Journal v10(1):107
16 Simarro PP et al (2008) Eliminating Human African Trypanosomiasis: Where Do We Stand
and What Comes Next. In PLoS Medicine v5(2): e55
17 FIND (2011) The Diagnostic Path to a Better World: Partnering for Better Diagnosis for All.
Geneva.
13
14
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Take, for example, drugs for neglected diseases: Of the 1,556 new drugs approved between
1975 and 2004, only 21 were specifically designed for tropical diseases including malaria and
TB, although they account for 11.4% of the global burden of disease. This represents just 1.3%
of the total number of new drugs registered by private sector pharmaceutical companies
globally18,19.In the case of diagnostics, while private sector investments in this market have
grown substantially in recent years, the vast majority of investments being made target submarkets for cancer, heart disease, other non-communicable diseases and personalised
medicine – high burden diseases in developed countries, where patients and governments can
afford and are prepared to pay much higher prices, presenting strong opportunities for profit
and return on investment.
In response to this market failure, the last 10years has seen significant increases in nonindustrial investments in neglected disease product (diagnostics, vaccines and drugs)
development, primarily through the form of product development partnerships (PDPs). PDPs
are designed to work like virtual pharmaceutical and/or biotechnology companies and have
been demonstrated to significantly lower both the costs of drug, vaccine and diagnostics
development and the lead time to market over those experienced when the private sector is
working alone20. This combination of increased public sector and philanthropic investments in
this area and the introduction of PDPs has resulted in a significant upsurge in product
development for neglected diseases – in the last 10 years alone 43 new products have been
registered, while another 350 are in development21.
While investment trends have been particularly promising with regards to investment in
neglected diseases drug and vaccine development, investment increases have been less
obvious diagnostics field in spite of significantly lower costs and, often, shorter product
development lead times for new disease diagnostics. Funding for malaria drug development,
for example, has been a massive 20x higher than that spent on diagnostics22.
The Role of FIND in Neglected Diseases Diagnostics Development
Formed in 2003 as a spin-off from the Tropical Disease Research (TDR) special research
programme at the World Health Organisation (WHO), FIND is a not-for-profit PDP focussed
solely on the development of new diagnostics for neglected diseases. Initially focussing on TB
and malaria, they now work to accelerate diagnostics development across these two disease
areas as well as sleeping sickness, leishmaniasis and Chagas disease.
FIND forms innovative partnerships with industry and public institutions, developing different
partnerships for different research and development needs, depending on the needs for access
to and use of technical expertise and technology. It targets cross-platform diagnostics that are
appropriate for use in integrated laboratories that serve health systems, rather than diseasespecific diagnostics. FIND fund and guide the development, clinical trials, and processes that
lead to WHO endorsement, while industry partners are responsible for manufacture, delivery
18
Chirac P & Torreele E (2006) Global Framework on Essential Health R&D. IN The Lancet
v367: 1560-1
19 Moran et al (2006) The new landscape of neglected diseases drug development. London.
Wellcome Trust.
20 Moran et al (2005) New EU Approaches to funding R&D for neglected diseases. London:
Pharmaceutical R&D Policy Project.
21 Policy Cures (2012) Saving lives and creating impact: EU investment in poverty-related
neglected diseases.
22 Moran M et al (2010) G-Finder Report. Policy Cures.
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and customer support of the final product. In parallel, FIND collaborates with Ministries of
Health, technical agencies, and other global and local partners to support the development of
laboratory infrastructure and capabilities, quality assurance systems, training and the other
components needed for successful implementation of its diagnostic products. These activities
together allow FIND to significantly contribute towards reducing the global burden of neglected
diseases through enhanced disease diagnosis, treatment and control.
Since its inception, FIND has made some significant advances in the field of neglected disease
diagnostics, including for example:
 5 new TB tests approved by the WHO and being scaled up in over 27 countries as part
of the Expand TB Programme
 Development of the first ever rapid diagnostic test for sleeping sickness
 Strengthened laboratory infrastructure in multiple countries including Lesotho, Uganda
and Ethiopia
Of particular note, working with the biotech firm, Cepheid Inc. and the Univeristy of Medicine
and Dentistry of New Jersey, FIND developed the Gene Xpert test for TB which was formally
endorsed by the WHO in 2010. Within two years of endorsement, two-thirds of countries with a
high TB burden and half of all cuontries with multi-drug resistant (MDR) TB had incorporated
the test into their national TB programme guidelines23. It is now available in 29 countries, over
2 million test cartridges have been sold globally, and a number of commercial companies have
since been applying for direct funding to develop similar tests since its launch (indicating
market stimulation). The Gene Xpert test is changing the landscape of TB diagnosis and
treatment – it can be used by healthcare workers with minimal training and/or laboratory
facilities, is associated with a 40% improvement in case detection rates, and, as a point of use
test, can provide test results for both TB and MDR-TB within 2 hours compared to a previous
wait of 6-8 weeks, and modelling suggests that use of the test could save up to 200,000 lives a
year24.
In spite of these developments however, significant diagnostic gaps remain and efforts are
further required to ensure that newly developed diagnostics are adopted in target populations,
allowing for correct diagnosis and treatment. In an effort to address some of these gaps,
looking forwards FIND intends to continue to work on expanding the availability and reach of
appropriate diagnostics for TB, malaria and neglected diseases including sleeping sickness,
leishmaniasis, Chagas disease and trachoma. They have ambitious targets for the future as
indicated by their expected 2018 results (see section B: Impact and Outcome that we expect to
achieve, p8 of this document).
Alignment with Wider DFID Priorities
The Coalition Government has taken a global leadership goal in the battles against malaria, TB
and the neglected tropical diseases. Most recently, in 2011, Ministers approved a plan for
DFID’s involvement in NTD control (as one of the ‘big’ three funder – DFID, USAID and the Bill
and Melinda Gates Foundation) with a commitment to an additional £195 million funding
between 2011 and 2015. This was formally announced at the event marking the launch of the
2012 London Declaration and the WHO NTD Control 2020 Roadmap. New improved
23
Lawn SD et al (2013) Advances in tuberculosis diagnostics: the Xpert MTB/RIF assay and
prospects for a point-of-care test. In The Lancet v13(4): 349-361
24 Keeler et al (2006) Reducing the global burden of tuberculosis: the contribution of improved
diagnostics. In Nature v444(S1): 49-57
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diagnostics will be of critical importance to achieving the goals for sleeping sickness, trachoma,
leishmaniasis and congenital Chagas disease. Targetted opulation screening to identify
asymptomatic carriers of malaria will also enhance global malaria control and eradication
efforts.
Supporting the rapid development of health technology innovation is a key strand of DFID’s
Structural Reform Plan (SRP) Pillar 1 – International commitments to support actions to
achieve the MDGs relevant to health and education. Health technology innovation is also an
area of high level political support and represents one of the UK commitments through the G8.
DFID Ministers have also reaffirmed their commitment to the use of evidence and new
technologies in DFID’s work in a number of speeches25.
Fit with DFID’s Research and Evidence Priorities
DFID’s investment in research has three main aims: 1) developing new technologies and
innovations that have impact on poverty or its effects, 2) finding better and more cost-effective
ways of delivering development to those who need it, including stopping things that do not
work, and 3) better understanding of key development questions and background to support
the best policy decisions. Investment in FIND’s portfolio of work directly contributes to the first
two of these aims, through the development of new drugs for neglected diseases and working
with regulators, host governments and implementing partners to work-out the most costeffective ways of ensuring these are delivered to those who need them the most.
B. Impact and Outcome that we expect to achieve
DFID’s investment in FIND will allow them to continue to contribute towards (outcome) reducing
the global burden of neglected diseases and through enhanced disease diagnosis, treatment
and control.
Working to accelerate diagnostics development across TB, sleeping sickness, leishmaniasis,
malaria and non-malarial febrile illness, and potentially in new disease areas, the main 5-year
outputs associated with this funding are:
 5+ neglected disease diagnostic tests developed and in use in disease endemic
countries
 Strong and balanced pipeline of diagnostics in development, including 3-4 fully
evaluated tests and another 4-6 for which technical feasibility has been established
 Strategic portfolio expansion into at least 1 new disease area
The diagnostics to be developed include rapid diagnostic tests for population screening for
sleeping sickness and asymptomatic carriers of malaria (both of which will contribute
significantly to disease control and eradication efforts, as well as case management); a
diagnostic for testing infants for congenital Chagas disease; disease staging and test-of-cure
diagnostics for sleeping sickness; triage tests for detecting individuals at high risk for TB at
primary care centres (enabling rapid referral for definitive diagnosis); a multi-drug resistant TB
test; tests to direct treatment and estimate risk of severe illness in patients, especially children,
with acute fever not associated with malaria; and molecular tests for case management and
surveillance of cutaneous and visceral leishmaniasis.
Rt Hon Justine Greening Speeches 1) to Conservative Party conference, Tuesday, 9 October 2012; 2) Open
Up! Using technology to build open societies and make aid smarter Speech 13th November 2012 and 3)
Development in transition Speech on 7 Feb 2013
25
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APPRAISAL CASE
A. What are the feasible options that address the need set out in the strategic case?
A recent RED review of research models26 identified six basic models in common use across
DFID that aim to deliver a complementary mix of high quality relevant research, facilitate
research-into-use and strengthen capacity to undertake and use research:
1. Core funding to international research organisations;
2. Product Development Partnerships (PDPs) selected through open competition;
3. Research Programme Consortia (RPCs)27 selected through open competition;
4. Direct funding for defined areas of research (not through RPCs) selected through open
competition
5. Funding relationship with UK Research Councils;
6. Collaborations with other bilateral donors around research areas of mutual interest.
This business case falls under the second model identified above and a number of options
were explored to ensure the development of new drugs against neglected diseases of poverty.
The three most viable of these – direct funding to the pharmaceutical industry, direct funding to
academic R&D labs and portfolio funding to a Product Development Partnership (FIND) – were
considered alongside the ‘do nothing’ counterfactual.
Option 1: The do-nothing counterfactual
Under this option DFID would not invest in product development, leaving the development of
new global health technologies, including those for diseases of poverty, to the private sector
and/or other funding bodies.
Option 2: Direct funding to stimulate the diagnostics industry
Under this option DFID would seek to provide direct support to industry to attempt to stimulate
them to develop and ensure access to diagnostics for neglected diseases.
Option 3: Direct funding to academic R&D institutions
Under this option DFID would seek to provide direct support to academic R&D labs to develop
and ensure access to diagnostics for neglected diseases through an open competitive
tendering process.
Option 4: Invest in a portfolio of neglected disease diagnostics development through,
the product development partnership, the Foundation for Innovative New Diagnostics
(FIND) [Preferred Option]
Under this option DFID would invest in the Foundation for Innovative New Diagnostics (FIND)
pre-existing and emerging portfolio of diagnostics for neglected diseases of the poor. They
have, through open competition, been identified as a market leader in this field.
Product Development Partnerships (PDPs) are non-profit entities that act as virtual
pharmaceutical companies, coordinating the development of new health technologies (drugs,
vaccines, diagnostics) and drawing upon the respective strengths of academia, large and small
industry, at the different stages of the R&D and commercialisation process.
Piper J (2010) Working Paper. Research & Evidence Division, DFID Internal Document
RPCs represent consortias of primarily academic partners from across high and low-come countries working
together to explore a set of research questions around a common theme (e.g. nutrition, health systems,
reproductive health)
26
27
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Options Appraisal
In this section we use a core set of Critical Success Criteria (presented on p19) to frame a
qualitative analysis of each of the 4 presented options. Following the analysis of the strengths
and weaknesses associated with each option we present a summary table which compares the
performance of each option against these critical success criteria and present a summary
rationale for the preferred option.
Option 1: The do-nothing counterfactual
This was the default position until the inception of Product Development Partnerships (PDPs) in
the early 2000s. As indicated in the strategic case, prior to the formation of PDPs and
significant public investments in global health product R&D, few new diagnostics, vaccines or
treatments for neglected diseases of poverty were coming on stream, the pharmaceutical
industry lacking incentive to develop them due to the high costs of new drug development and
the extremely limited profit margins associated with making them available to patients in need.
Of 1,556 new drugs approved between 1975 and 2004, just 21 of these were specifically
designed to tackle neglected diseases of poverty (including TB and malaria), representing only
1.3% of the total number of drugs registered by private sector pharmaceutical companies in
that time period (while the diseases account for 11.5% of the total global burden of disease )28
29. The situation for diagnostics was even worse, major activity taking place in the area of noncommunicable diseases (e.g. heart disease, diabetes and cancer) where significantly more
potential developed country market, and profit potential, exists.
The argument for investing in diagnostics development is based on the lack of viable markets
for neglected diseases tests and associated market failures around the commercial investment
for R&D in this area. The main factor explaining this market failure relates to the status of
diagnostics for neglected diseases as global public goods whereby those in need of disease
diagnosis are too poor to be able to pay enough for tests to make it worthwhile for
pharmaceutical companies to invest the huge amounts required in the R&D process to develop
and produce them, particularly given the steep rises in costs and complexity of developing
pharmaceutical products seen over the years. Estimated out-of-pocket expenditure now
ranges between US$403 – US$873 million for drug development30 and as costs have
increased the number of products in development has fallen31. While the costs of diagnostics
development are lower than those seen in drug development similar trends of rising costs and
approvals are apparent.
Traditionally, Intellectual Property (IP) rights have been used to provide incentives for the
private sector to invest in risky and expensive R&D programmes by enabling monopoly pricing
of pharmaceutical products. The biotechonology and pharmaceutical industries rely heavily on
IP portfolios to protect their investments, provide signals to the investment community to
encourage future investment, provide incentives to enter a market (rather than wait) and to
justify prolonged expenditures in view of regulatory risk and market uncertainty. Research
funded by the pharmaceutical and biotechnology industries is made with the principle aim of
developing commercial products which can be protected by patents and licensing agreements
Chirac P & Torreele E (2006) Global Framework on Essential Health R&D. In The Lancet, v367:1560-1561
Moran et al (2006) The new landscape of neglected disease drug development. Wellcome Trust.
30 Paul SM et al (2011) How to improve R&D productivity: the pharmaceutical industry’s grand
challenge. In Nature Reviews: Drug Discovery iv10:328-329
31 David E et al (2010) New frontiers in pharma R&D investment. In McKinsey Quarterly.
28
29
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and which can be sold at a significant profit. However, the ability of industry to exploit
intellectual property with respect to neglected diseases is severely limited in large part because
the effective demand for these products is low (with neither patients nor their governments
being able to pay high enough prices for them). Thus, the combination of ever growing out-ofpocket expenditures associated with diagnostics development and the limited potential to
generate a profit from eventual diagnostics sales renders, leave no incentive for the private
sector to invest in R&D for tests for neglected diseases. This lack of commercial return is a
critical stumbling block which prevents industry from undertaking research for neglected
disease diagnostics without external financing and partnership to share costs and risks.
There is a clear market failure and it is readily accepted that public investment is required to
incentivise activity in neglected disease product development research.
Over the last 10years, governments, donors, philanthropic foundations and, increasingly
pharmaceutical companies (now that costs and risks are shared), have been increasing their
investments in the development of new diagnostics and other products for neglected diseases.
These increased investments, and associated partnerships, have led to the registration of 43
new products over this same time period, a significant productivity gain since public
investments commenced. Unfortunately, increases in even public investment in disease
diagnostics have been less marked in spite of the lower costs and shorter lead times involved
in their development. For example, funding for malaria drug development has been 20x higher
than that spent on diagnostics32.
Data from the 5th annual G-FINDER Report33 shows that while the public sector currently
provides nearly $2billion, or two thirds of all funding, for neglected diseases R&D, at the global
level government funding has continued to move away from product development and towards
more traditional, earlier stage, basic research, while industry or philanthropic investments in
this area have become either smaller and/or more focussed on only a narrow range of diseases
and products. Policy Cures argue that this might reflect a worrying retrograde step to a time
where the public sector funds only basic research, leaving product development to industry or
philanthropy and resulting in a subsequent lack of new medicines, vaccines or diagnostics for
neglected diseases reaching the market.
This analysis suggests that the do-nothing counterfactual is not a viable option.
The three remaining options all seek, in different ways, to stimulate R&D for new diagnostics
for neglected diseases of the poor.
Option 2: Direct funding to stimulate the pharmaceutical industry
One way to drive neglected diseases diagnostics R&D is to try to address the market failure by
trying to stimulate the private sector to invest in this area. In recent years an increasing number
of ‘pull’ mechanisms have been proposed in order to incentivise the pharmaceutical industry to
develop more health technologies (drugs, vaccines, diagnostics). Push mechanisms such as
subsidies for research, tax credits for R&D, expedited regulatory review are outside the scope
of DFID’s work. Subsidies for research and tax credits have been implemented in some
countries but have not made an appreciable difference to stimulating private sector activity in
32
Policy Cures (2012) Neglected Disease R&D. The Fourth Annual G-Finder Report.
Policy Cures (2012) Neglected Disease R&D: A Five-Year Review: The Fifth Annual GFinder Report.
33
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this area specifically. Another push mechanism, the PDP, however is discussed under option 4.
Pull mechanisms include Advanced Market Commitments and Prize Funds. These can be
used to incentivise private sector investment and risk bearing at different stages in the product
development, manufacturing and delivery value chain.
Advanced Market Commitments (AMCs)
AMCs are designed to mimic existing pharmaceutical incentive structures without altering their
current R&D model. An AMC works by providing industry with financial incentives and certainty
to develop new diagnostics for neglected diseases as they would tests for high prevalence
conditions in high income countries, thus mimicking the expected economic returns for a
blockbuster as viewed at the start of the R&D process (the time when the investment decision
is made) as opposed to at the time of sale. These financial incentives come in the form of
market guarantees, whereby the investors (likely donors, philanthropists or governments)
legally agree to buying a minimum quantity of the drug to be developed at a set price, thus
guaranteeing a minimum market size and profit margin to industry.
The first AMC, developed for pneumococcal vaccines (worth US$1.7billion), was launched in
February 2009, with investors (including DFID and a number of other donors) promising to buy
(and thus supply) 2 billion doses of vaccine in low- and middle-income countries by 203034.
However, while the AMC model is showing promise, when the AMC was introduced there were
already two pneumococcal vaccines in a late stage of development and GAVI has highlighted
that AMCs likely only work as an incentive to scaling up production capacity and as a
procurement mechanism for products in late-stage development rather than as a tool to driving
R&D across the full product development cycle35.
There have been no AMCs for early stage product development and as such their application is
limited. They are also unlikely to be applicable in the case of diseases such as sleeping
sickness (Human African Trypanosomiasis) where the remaining global disease burden is
small (hence limiting the potential market) and often associated with fragile states (potentially
limiting market reach) but the need for new drugs and diagnostics pronounced.
While AMCs might stimulate the production of global health products in late stage
development, in an era where the pharmaceutical industry itself has been questioning its
standard business model some have been challenging them more recently, particularly on the
grounds of efficiency and their reliance on strong intellectual property rights (held by
industry)36. Efficiency concerns relate, in particular, to evidence for high rates of product failure
in the (much more costly) later stages of development across the pharmaceutical and
biotechnology industries thought to be driven by incentives that encourage poor decisions to
pursue the development of technologies that have generated only weak evidence of
effectiveness at early stages of development and thus have an even higher risk of failure at
later stages37.
Prize Funds
34
Lahte J (2012) Is the pneumococcal vaccine advance market commitment motivating
invnovation and increasing manufacturing capacity? Some preliminary answers. In Vaccine
v30(14): 2462-6
35 Cernushi T et al (2011) Pneumococcal Advanced Market Copmmitment: Lessons Learnt on Disease and Design
Choices. GAVI White Paper.
36 Gold RG & Marin J-F (2012) Promising Trends in Access to Medicines. In Global Policy v3(2): 231-7
37 Editorial (2011) A Stronger Role for Science. In Nature Reviews: Drug Discovery v10:159
13
An alternative model to stimulate private sector R&D for health technologies for neglected
diseases is prize funds. Examples include the Health Impact Fund and the Medical Innovation
Prize Fund, where cash rewards are offered either for the development of new health
technologies or for achieving measurable health impacts occurring as a result of the availability
of new technologies. This approach changes the existing incentive structure for R&D, shifting
the R&D driver towards patient impact (and thus the health products that will have the largest
health impact per pound invested) rather than economic return on investment, and may result
in increased efficiencies in the R&D process, competitors seeking to lower their operating costs
in order to maximise potential profit. Unlike AMCs, prize funds could theoretically target the
development of multiple diagnostics for multiple diseases through a single channel.
While theoretically promising (and supported by a number of prominent economists) prize
funds are currently untested and there are a number of practical reasons why they are unlikely
to be an effective investment mechanism for developing neglected diseases diagnostics at this
point in time:
a) The proposals suggest that prize fund payments would be tied to measures based
upon available data relating to reported use of the diagnostics, outcomes and approval
processes while currently little such data exists creating real challenges to determining
payment models;
b) To be effective the prize funds need to be large (suggestions range from a minimum of
US$6 billion per year to a high of US$ 240 per year, though they may be lower in the
case of diagnostics) and currently there appears to be little political will amongst
potential donors to invest in an internationally managed funder over which they would
have little control. This is evidenced by the widespread lack of support (from either
donors or industry) for either the Health Impact Fund or the Medical Innovation Prize
Fund in their current form38;
c) In common with AMCs, while not yet proven, it is likely that prize funds would
disproportionately skew R&D towards later stage development.
Whichever pull mechanism is used to attempt to stimulate industry to work on technologies for
neglected diseases, one of their key advantages is that they shift the risk from the funder to the
R&D partner who only receives payment once the technology has been successfully
developed. However, as indicated by the pneumococcal vaccine AMC investment pot and the
proposed necessary budgets for effective prize funds, the financial ‘pull’ incentive may need to
be very large, particularly for those technologies that are earlier in the R&D cycle, scientifically
more complex to develop or associated with other substantial hurdles to industry engagement
(e.g. lack of expertise in conducting trials in developing countries). It is difficult to judge, in
advance, the optimal size of pull incentive required – creating a real danger of either
overpaying, in which case there is an element of unnecessary subsidy to industry, or
underpaying in which case the incentive will be ineffective.
Where a major pharmaceutical or biotech company is involved in developing products for
diseases of poverty, it is typically driven by corporate social responsibility (CSR) objectives
and, in some cases, because developing countries may be major markets and important
sources of revenue in the future. The CSR programmes of major companies usually revolve
around their expertise and existing products, currently aimed at the developing world. Often
these projects rely on single champions, with no corporate urgency to accelerate the project
38
Gold RG & Marin J-F (2012) Ibid
14
through the development process, and focused on developing single candidates39. This focus,
as opposed to a platform approach which seeks to use a single technology or diagnostic format
as the basis for a number of different disease tests, increases the overall risk of failure and also
has the impact of decreasing efficiency and increasing costs.
Option 3: Direct funding to academic R&D institutions through competitive tender
While direct funding to industry might be one way to stimulate pharmaceutical activity in later
stage R&D for neglected diseases much of the more basic research required takes place in
academic laboratories where more of the global expertise in tropical medicine is situated.
Indeed, one of the key strengths of academics working in neglected disease diagnostics
development is their early innovation and demonstrated capability and productivity in early
stage discovery (new potential diagnostics platforms or test types) a strength coupled with a
strong scientific reputation (gained largely through publication in peer-reviewed journals) which
allows them to effectively engage with the regulatory authorities and influence later-stage
development by other stakeholders.
While often highly successful at leveraging both public and private sector funding and
managing R&D costs within their grant parameters, academic institutions tend to take a very
project-based approach, working on extremely narrow product development activities rather
than taking a larger pipe-line or portfolio approach. This can both increase risks of failure (the
costs of failure being borne by the funder) and limit their ability to utilise promising early-stage
chemical entities for other potential uses. They can also lack the ‘translational’ capabilities to
ensure that promising new diagnostic platforms can be turned into viable field-adapted formats
for use in disease endemic countries. Further, a 2005 study suggests that the R&D that does
take place in academic institutions is often slower and more fragmented (with activities being
conducted in an interrupted fashion alongside other priority activities) than in either the
pharmaceutical industry or efforts led by Product Development Partnerships (PDPs) 40.
To enable the application of a single diagnostic technological platform across a range of
different diseases there would still need to be direct oversight by some organisation over the
disease portfolio as a whole. This could be problematic, where academic research groups
typically oversee work on one or a small number of diseases and could be met with reluctance
by investigators who value their autonomy. Opportunities to integrate the clinical and basic
programs could be lost and there may be duplication of investment to develop facilities that a
more coordinated approach could share.
A recent 5-year review of neglected diseases R&D, reports the a global trend of government
funding moving away from product development and towards traditional basic research, the
area academia is traditionally good at. The authors of the report suggest that this could reflect
a worrying retrograde step to a time where public sector funds basic research without a view to
product development and commercialisation41 and points to a need to maintain investments
across the product development cycle.
39
http://www.forbes.com/sites/sarikabansal/2011/11/22/top-five-ways-big-pharma-neglecteddiseases/
40 Moran M (2005) A Breakthrough in R&D for Neglected Diseases: New Ways to Get the
Drugs We Need. In PLoS Medicine v6
41 Policy Cures (2012) Neglected Disease R&D: A Five-Year Review. The 5th G-Finder
Report.
15
Option 4: Invest in a portfolio of neglected disease diagnostics development through,
the product development partnership, the Foundation for Innovative New Diagnostics
(FIND) [Preferred Option]
The Product Development Partnership (PDP) Mechanism
Jointly created and funded by governments, private foundations and/or industry, PDPs work
like “virtual” pharmaceutical companies with a small, central group of core staff coordinating the
development of a portfolio of new health products (e.g. vaccines, drugs, diagnostics) by
drawing on the respective strengths of academia, large pharma and smaller biotech companies
at various stages of the product development cycle. While academic R&D is driven by the
potential for high profile, peer reviewed publication, and industrial R&D by profit, as non-forprofit entities, PDPs are primarily driven by patient and service-provider need. In the case of
diagnostics, they further tend to utilise platform approaches whereby single technologies are
transferred and adapted across a range of different disease areas.
Both the portfolio and the platform approaches act to diversify risk, reduce the overall risk of
failure and reduce costs through the cross-application of single technologies to multiple
diseases, the selection of only the most promising technologies for later stage development,
and the leveraging of not only finance but technical expertise and infrastructure from a range of
different partners. Further, they work on all stages of the product development cycle from early
discovery through to product registration. As already cited, one analysis suggests that the
average cost of bringing a single new drug to market via a PDP is US$150 million compared to
US$800 million via an industrial pharmaceutical company alone. This same analysis suggests
that the speed of R&D is faster when coordinated by PDPs as opposed to when conducted by
either industry or academia alone42. Similar trends can be expected for diagnostics.
Over the past 10 years PDPs have been successful in the development of a wide range of new
health products for use in developing countries. During this time period there have been 43
new products registered with another 350 in development, PDPs being responsible for
approximately half of these43. The pharmaceutical industry has been a particularly active and
willing partner with them and in recent years (2007-11) the proportion of funding for neglected
disease R&D from the pharmaceutical industry has been rising. The private sector currently
contributes 13% of the total spending in this space though the percentage is lower in the subfield of diagnostics development44.
Representatives from the pharmaceutical and biotech industry have highlighted that PDPs play
an instrumental role in breaking down the institutional barriers between partners who otherwise
would not work together and allowing for R&D developments that would not previously have
been possible. In addition in areas where there is little or no commercial return, the private
sector see the role of the PDP as critical to avoid duplication and to focus on the most
promising candidates, wherever they originated from.
Acting as neutral, coordinating bodies, in many ways the funding of a PDP to deliver new for
neglected disease diagnostics represents a combination of options 2 (funding to industry) and 3
42
Moran M (2005) A Breakthrough in R&D for Neglected Diseases: New Ways to Get the
Drugs We Need. In PLoS Medicine v6
43 Policy Cures (2012) Saving Lives and Creating Impact: EU Investment in Poverty-related
Neglected Diseases.
44 Policy Cures (2012) Neglected Disease R&D: A Five-Year Review: The Fifth Annual GFinder Report.
16
(funding to academia), allowing DFID to capitalise on the strengths of each partner. Further,
funding of PDPs allows us to manage a wide portfolio of R&D activities via a single
organisation (rather than via a number of smaller contracts for individual activities with different
partners). The neutrality of PDPs (and lack of profit drive) further enables them to develop
strong relationships with developing country governments and the appropriate (global and
national) regulatory agencies which increases their ability to conduct clinical trials in disease
endemic environments and to ensure the timely WHO endorsement, national registration and
use of new diagnostics in countries where they are most needed.
Product Development Partnerships have a range of different IP agreements with their industry,
and other, partners, using the guiding principle of developing global public goods45, i.e. that
access to treatments should be equitable and treatments should be affordable to those who
need them. Where the PDPs do not control the IP related to each of their products they
negotiate appropriate licensing rights (e.g. non-exclusive and sub-licensing rights) to enable
them to deliver products to patients at cost in low income countries. In some cases the private
sector partner can commercialise in high income countries, if a market exists. The private
sector has a history of sharing IP with PDPs, and acknowledges that they will not commercial
returns in this area of their work.
For some products (e.g. vaccines for TB and HIV) modelling studies have identified a potential
commercial market, once products are available. These studies highlight the need for push
funding in the near future, with the potential for differential pricing at later stages, and the funds
realised can then be used to support future developments46.
PDPs collaborate with the public and private sectors in developing countries to improve
capacity building for research into product discovery, development and manufacture. The
technology transfer can lead to sustainable production of new technologies and result in new
jobs being created in developing countries.
The main identified risk associated with funding via the PDP mechanism relates to the issue of
funding sustainability. Drug, vaccine and diagnostic development is lengthy and uncertain
leading to a need for stable long-term financing. However, PDPs are largely funded by the
public and philanthropic sectors whose funding tends to be short-term (five years and under)
and unpredictable. Much of this funding can also be in the form of targeted can prevent grants
for specific institutions to work on specific projects. This lack of flexibility can prevent PDPs
from being able to use and move funds strategically across their portfolios to the most
promising projects47. For this reason, DFID favours core-funding over ear-marked investments
to PDPs, giving them more flexibility to make strategic investment choices.
FIND
Utilising a highly productive platform approach, FIND is currently the only PDP that focuses all
its efforts on diagnostics development. In common with other PDPs they have a wide-ranging
portfolio (including TB, malaria and neglected tropical diseases) that balances short- to longerterm projects and early and late stage developments. Their overall goal is to provide patients
Changing with the times – doing the right things in the right places in the right way –
presentation to DFID EMC May 2013
46 Aeras and TBVI: TB Vaccine Research and Development: A Business Case for Investment:
2013
47 Hecht R, Wilson P & Palriwala A (2009) Improving Health R&D Financing for Developing
Countries: A Menu of Innovative Policy Options. In Health Affairs v28(4): 974-985
45
17
and disease control programmes in developing countries with the means to effectively
diagnose infectious diseases to improve patient care and provide surveillance information to
support disease control. This entails the careful and strategic selection of diseases and
diagnostics development for greatest impact, the maintenance of a flexible portfolio of best-inclass technologies, and strong partnerships (with academic, biotech companies, the WHO,
governments and disease control stakeholders) and operational mechanisms to drive solutions
through all the R&D stages including diagnostics endorsement and in-country registration and
adoption. In their approach to partnership they actively seek to ensure that, for any given
project, they combine the specific skills and resources from each partner in such a manner that
enables them to achieve the greatest impact and best value for money as quickly as possible.
Their platform approach not only reduces costs but reduces diagnostics development lead
times and makes in-country adoption easier through the use of a single technology type to test
for multiple diseases.
Their strong performance in diagnostics development is best exemplified by the development of
the multi-award winning Xpert test for T:. Building upon the Gene Xpert platform and working
with the biotech firm, Cepheid Inc. and the University of Medicine and Dentistry of New Jersey,
FIND developed the Xpert MTB/RIF point-of-us TB test, which was endorsed by the WHO for
the simultaneous rapid detection of TB and multi-drug-resistant TB in 2010. Within two years
of endorsement, two-thirds of countries with a high TB burden and half of all countries with
MDR-TB had incorporated the test into their national TB programme guidelines48. It is now
available in 29 countries and biotech companies in India have expressed an interest in full
commercialisation of later iterations at lower cost. Modelling suggests that the Xpert MTB/RIF
test will save up to 200,000 lives a year49
Concluding Rationale for Preferred Option, Funding the FIND PDP
The below table presents a quantitative comparison of the three options discussed against a
series of 5 critical success criteria. Building on the options appraisal above, we give each
option a score between 1 (low/poor) and 5 (high/good) for each of these criteria and then sum
these to give an overall score. Beneath the table we present a succinct narrative to explain
why, on the basis of these criteria, funding to FINDi is the preferred option.
Critical Success Criteria
Able to deliver effective, safe,
affordable and appropriate
neglected disease diagnostics
to those populations that need
them most
Ability to bring together the
right partners
Costs are proportionate and
manageable
Ability to manage risk of failure
Leveraging of wider resources
Option 2 (fund
industry) score
3
Option 3 (fund
academia)
2
Option 4 (fund FIND
PDP)
5
3
2
5
2
2
4
2
1
1
2
4
48
Lawn SD et al (2013) Advances in tuberculosis diagnostics: the Xpert MTB/RIF assay and
prospects for a point-of-care test. In The Lancet v13(4): 349-361
49 Keeler et al (2006) Reducing the global burden of tuberculosis: the contribution of improved
diagnostics. In Nature v444(S1): 49-57
18
Total Score
11
9
23
FIND’s ability to broker partnerships across the full range of players necessary to ensure
successful diagnostics development (from product profiling and technical feasibility testing
through registration and uptake) is demonstrated through a long list of strategically chosen
partners (which include industry and academia as well as other PDPs). Furthermore this
partnership model allows them to limit core costs and approach diagnostics development in a
flexible and cost-effective manner which results in significantly lower costs and shorter lead
times for diagnostics development than seen in the private sector or academia.
By adopting a portfolio of activities, utilising platform approaches, across a range of diseases
and ensuring a balance between core and earmarked funding, FIND are also well-placed to
minimise the risk of failure. In order to support this strategic approach to portfolio management,
DFID proposes to continue to core fund FIND. The strong decision-gates further mean that only
the most promising candidates move from earlier to later stage development, both reducing
risks of failure and increasing operating efficiencies and value for money.
B. Assessing the Strength of the Evidence Base for each Feasible Option
In contrast to most development interventions, there is limited published evidence comparing
the effectiveness of different funding models for delivering new products. Therefore it is not
possible to present formal evidence ratings for each option using the DFID standard criteria.
Instead, the decision on which funding model to use is based largely on qualitative
assessments and critiques of different models for stimulating global health product
development (e.g. Gold & Morin 201250), external evaluations of the various PDPs operating in
the global health space, the personal viewpoints of other stakeholders (including other R&D
funders and pharmaceutical partners), and DFID’s own judgement and expertise in managing
research. This is in line with recent guidance from the Quality Assurance Unit51.
A recent analysis of a number of PDPs52 suggests four reasons why PDPs such as FIND are
particularly effective in securing increased industry engagement to accelerate product
development:



50
51
PDPs have skills and resources, such as infectious disease expertise and access to
developing country clinical trial sites, that companies may lack
PDP funding is crucial to the development of a ‘no profit no loss’ model, particularly at
the stage of large scale clinical trials, making ‘public good’ activities more acceptable in
board rooms and to shareholders. PDPs act as a ‘push incentive’ as they significantly
reduce R&D costs for industry because of sharing costs with the PDP;
PDPs can provide an important source of revenue for smaller industry partners, either
as a commercial contractor of services or as a grant funder for technology research
(often without diluting equity as venture capitalists would). PDPs can also help broker
partnerships with larger companies that may be needed to undertake large clinical
trials or scale up manufacturing processes. This may include technology transfer to
and partnerships with developing country pharmaceutical companies; and
Gold RE & Morin J-F (2012) Promising Trends in Access to Medicines. In Global Policy v3(2): 231-237
QAU Report Violence against Women and Girls’ Research and Innovation Fund. See p.28
52
London School of Economics and Political Science, The New Landscape of Neglected Disease Drug
Development (London: Wellcome Trust, September 2005).
19

PDPs have been successful in raising the issue of future access to new products by
developing countries with donors and potential recipient countries. Addressing access
issues may be difficult and politically sensitive for companies to take on by themselves
(as they are seen as having vested commercial interests). However, it is essential for
industry engagement that mechanisms are in place for any successful new product to
be used.
Evidence ratings for the options discussed in the business case
Option
Evidence rating
1
2
3
4
Do nothing
Weak
Weak
Medium
C. For Each Feasible Option, What is the Assessment of Local Capacity? Is the
Intervention Likely to Strengthen Capacity in a Durable Manner?
The development of new diagnostics for neglected diseases necessitates the conduct of clinical
trials in disease-endemic countries where research capacity is often weak. Industry can find it
particularly challenging to both enter and work in these contexts, where governments can be
wary of large global companies and where poor in-country infrastructure can make accessing
research sites and conducting trials particularly difficult. While academics may find it easier to
enter these countries to conduct research they often lack access to pre-established clinical trial
sites and associated laboratory facilities. FIND on the other hand have a strong presence in
both India and Uganda and have strengthened lab-testing capabilities in an additional 30
disease endemic countries. FIND continues to invest significantly in conducting in diagnostics
development activities in disease endmic countries and also partner with another PDP, the
Drugs for Neglected Diseases Initiative (DNDi), who now have a presence in 40 countries and
have, over the years, invested heavily in the development of local R&D capacity (both in terms
of infrastructure and staffing). Where possible, both FIND and DNDi leverage previous
investments in capacity-building through the conduct of multiple trials at single sites.
D. What is the Likely Impact (Positive or Negative) on Climate Change & Environment for
Each Feasible Option?
The climate change and environmental impacts are likely to be similar for all three feasible
options (though it is possible that negative impacts will be slightly reduced via the FIND option
due to enhanced operating efficiencies associated with their collaborative model). Therefore a
single climate and environment assessment (CEA) is presented here.
Option
Climate change and
environment risks and
impacts, Category (A, B,
C, D)
1 Do nothing
C
2 Support
B
commercial research
Climate change and environment
opportunities, Category (A, B, C, D)
C
B
20
group
3 Develop new
partnerships
4 Support PDPs
B
B
B
B
The activities that will be implemented/funded as part of this intervention are unlikely to have
any major environmental impact or involve any serious/substantial risks to environmental and
human health. However there are still a number of issues associated with all kinds of medical
research that need some level of consideration and adequate management. The disposal of
medical and/or bio-hazardous waste is one of them as improper disposal can have very
serious impacts on the environment, ecosystems and human health53,54,55.
Responsible environmental management is included in various international and regional
standards and regulatory requirements such as those set by the International Conference on
Harmonisation of Technical Requirements for the Regulation of Pharmaceuticals for Human
Use56 and in the WHO Good Laboratory and Good Manufacturing guidelines57. Such guidelines
further lay strict standards for the use of animal and human subjects in research as initially laid
out in the World Medical Association’s 1964 Helsinki Declaration. PDPs and their partners
reflect these strict international safety standards, as well as national environmental standards
and regulations, in their own Standard Operating Procedures (SOPs) which include
environmental impact reduction (in particularly associated with waste disposal). Where disease
endemic country partners do not have existing SOPs, PDPs provide technical support to
develop these. New drugs and diagnostics will not pass through the WHO or national
regulatory process without demonstrating strong adherence to international, regional and
national standards, and the European Medicines Evaluation Agency (EMEA) in particular now
requires a full environmental risk assessment for all new medical devices.
Additionally, all diagnostics trials must obtain ethical approval both from their host institutions
and within the countries within which they are conducted; such approval will include adherence
to national environmental and safety legislation. To this end all PDPs have or are developing
environmental policies and safety guidelines in place.
FIND is committed to ensuring that the environmental impact of its diagnostic tools is
minimised. For instance, they are working with the developer of their most recent TB test, the
Xpert MTB/RIF, to reduce packaging and optimise waste disposal. They are also working on
the development of solar-powered alternatives to power certain diagnostic equipment to avoid
reliance on strained electricity systems. This will have the co-benefit of increasing the use of
green energy.
They already have environmental checklists and measures58 in place to try to minimise the
environmental impact of diagnostics manufacturing, transport and use and are in the process of
developing environmental assessment tools for identifying and minimising potential
Hossain MS et al (2011) Clinical solid waste management practices and its impact on human health and
environment--A review. In Waste Management v.31(4):754-66.
54 Johannessen LM et al (2000) Health Care Waste Management Guidance Note. World Bank. Washington.
55 Prüss A et al (2000) Safe management of wastes from health-care activities. WHO. Geneva.
56 See www.ich.org for further information
57 See http://www.who.int/medicines/areas/quality_safety/quality_assurance/production/en/ for documentation
58 For example manufacturing partners are asked to document opportunities and strategies for minimising the
environmental impact of product shipping and use e.g. use of biodegradable or recyclable training materials,
carbon-minimal shipping, local sourcing of materials.
53
21
environmental risks earlier in the product development cycle. As such they include
environmental considerations (such as use of toxic materials in assays, product disposal
requirements, power consumption requirements in use) in the initial product description. They
are currently exploring the development of environmental thresholds that might render a
potential product unacceptable; however these thresholds will need to be offset against its lifesaving potential.
More broadly the development and adoption of new, improved diagnostic tools will allow for
better patient management and more targeted treatment which may help minimise overtreatment and reduce the environmental impacts associated drug packaging and generic waste
disposal. The increased availability of point-of-use diagnostic tests further has the potential to
reduce the carbon footprint associated with patient travel and or the transport of specimens to
centralised health clinics and laboratory facilities.
From an operational perspective, PDP operations are likely to have significant carbon
footprints, particularly associated with international travel for meetings, workshops, conferences
and field activities. As business class flights are about three times more carbon intensive per
flight than for economy seats59, DFID will recommend that all travel (associated with this
funding) is undertaken in economy class as routine procedure, irrespective of staff seniority,
unless there are specific and exceptional reasons to the contrary.
E. If Any, What are the Likely Major Impacts on Social Development?
Neglected diseases affect the poorest, hardest to reach people, who often live in remote or
conflict-affected areas with minimal access to formal healthcare services. Part of the rationale
for controlling these diseases is to help break the poverty cycle and improve economic
prospects for the poor. Preventing prolonged morbidity from neglected diseases will, through
earlier and better diagnosis, reduce out-of-pocket expenditures on treatment and contribute to
increased school attendance and economic productivity.
The development of new neglected disease diagnostics will thus have a disproportionate
impact on the health and economic productivity of the poorest, most marginalised peoples
across the globe.
F. For Fragile and Conflict-Affected Countries, What are the Likely Major Impacts on
Conflict and Fragility, If Any?
The burden of some of the diseases contained within FIND’s portfolio, particularly sleeping
sickness, is especially high in fragile African states such as the Democratic Republic of Congo
and South Sudan. The development of new diagnostics, particularly point-of-care and test-ofcure tests, could have a particularly marked impact in these places.
G. What are the Likely Costs and Benefits of Each Feasible Option? Identify the
preferred option.
DFID Business Cases require a cost-benefit analysis to be conducted for each feasible delivery
option. This requires the identification, quantification of monetary value to costs and benefits.
However, applying a formal cost-benefit analysis to research and development investments is
59
UK Department for Forestry and Rural Affairs (2009)
22
difficult as while target product profiles are developed for each desired new product a) it is
difficult to predict early in the product development what the precise final diagnostic sensitivity
and applicability and/or costs will be and b) it is beyond the scope of the product developer to
ensure that diagnostics produced reach all patients in need of treatment.
There is limited publically-available evidence on the relative cost-effectiveness of PDPs versus
industry models in particular. This is driven in part by the commercially-sensitive nature of
industry data, but even more so by the reality that most of industry now conduct the majority of
their neglected disease R&D activity through partnerships with PDPs such as FIND rather than
alone in-house.
Given these data challenges it is not possible to perform a full cost-benefit analysis of the
options discussed in this business case. Such an analysis would be based on too many
assumptions and lack credibility. However, 2005 study suggests that the PDP model is a costeffective mechanism for neglected diseases product R&D, especially when compared with
standard commercial product development. They reviewed the work of 4 PDPs, which together
had a combined portfolio of 40+ projects, representing 75% of all identified on-going product
development. They estimate that the cost of bringing a new drug to market via a PDP is
US$150 million compared to US$800 million via an industrial pharmaceutical company working
alone. While the costs involved in diagnostics development are significantly lower than those
necessary for new drug development, the same trends can be seen in this field. This
discrepancy in costs reflects a combination of factors including the ability of PDPs to leverage
substantial in-kind inputs from a large range of partners (an unpublished analysis by one of the
PDPs suggests that for each $1 of public investment they are able to leverage $1.5-$2.5 from
the private sector). The same analysis suggests that R&D is slower and more fragmented in
the academic sector than in the private sector or when coordinated by PDPs60.
Comparing Core Cost Components across Different Delivery Mechanisms
Commissioning and managing a programme of product development entails 4 broad cost
categories:
 Core costs – including central management, monitoring and research, information
dissemination and overhead costs;
 Implementation costs – including resource materials, equipment costs, experimental
research and development activity, travel expenses and consultants’ fees;
 DFID management costs – the costs of DFID oversight, programme design and
management;
 External evaluation – including costs of assessing the impact of the programme
The table below briefly and qualitatively compares these different cost categories across the
three main options considered in this business case (not including the counter-factual):
Core Costs
60
Option 2: Direct
Funding to Industry
High
 Higher operating
cost-base
(associated with
higher staff costs).
Option 3: Direct
Funding to Academia
Medium
 Lower staff costs
than biotechs and
strong ability to
manage costs
Option 4: Funding to
FIND PDP
Low
 Supple
organisational
structure, with small
core team and
Moran M et al (2006) The New Landscape of Neglected Diseases Drug Development. Wellcome Trust.
23

Capital-base
model creating
additional
expenditures
associated with
things such as IP
and liability
management.
Implementation High
Costs
 Emphasis on
research
conducted to
international
regulatory
standards
 Trials usually
(more expensively)
conducted in
developed country
contexts
DFID
Management
Costs

within grant
parameters,
however

Universities tend to
charge full
economic costings
with high

overheads
Medium to high
 Lower cost
research than
biotechs but higher
cost than FIND
Further they
experience
challenges in
conducting phase
2-3 trials and lack
of understanding
or regulatory
standards creating
challenges for
translation of
research into use
Medium
High
 Likely to be
 Likely to involve a
increased
large number of
compared to PDPs
contracts as
due to the need to
individual
manage multiple
academic
separate contracts
institutions tend to
work on very
 In early years likely
specific stages of
to involve much
the R&D process
staff inputs from
for single diseases
other parts of DFID
(including private
 Additional DFID
sector,
staff support likely
procurement)
to be required to
link academics
with other partners
including
regulators and
potential
open model
reduces costs
Lower salaries for
core staff than in
industry reduces
running costs
Regional
management
structure further
reduces staff costs
Medium
 Can be high
relative to
academia but this is
offset by the
conduct of research
to international
regulatory
standards
 Costs lowered by
use of trial sites, lab
facilities and staff
capacity a) in
disease endemic
countries (where
costs are lower)
and b) developed
for previous product
development
activities
Low
 Portfolio approach
reduces the
number of
individual contracts
to be managed
 PDP model
capitalises on
partnerships that
allow in-house
management and
implementation of
the full R&D
pipeline reducing
the need for
external
management
support from DFID
 Transparent
24
manufacturing
partner
External
Evaluation
High
 Difficult to conduct
meaningfully as
dealing with
commerciallyprotected
information
structures make for
easier external
contract
management and
progress tracking
Medium
Low
 Increased costs
 Relatively
compared to PDPs
transparent
due to fragmented
operating and
nature of
reporting allow
investments across
meaningful
a number of
evaluation, though
different contracts
there may be some
held with different
commercial
institutions.
sensitivities
associated with
particular activities
and pharma
partners
 Costs of conducting
external
evaluations shared
with a number of
other donors (the
PDP Donor group)
Programme costs for the preferred option.
The estimation of costs for the preferred option (funding to FIND) needs to take into account all
aspects of its operations that will have implications on resources needed to deliver on its
objectives.
The total costs of delivering FIND’s overall portfolio of diagnostics development over the next 5
years are estimated to be £129,928 million. This cost includes all activities from market
analysis through feasibility testing, diagnostics development and trialling through to product
registration registration, endorsement and adoption. Their projected overhead is relatively low
at around 15% of total expenditure and they are actively seeking ways to improve their
organisational efficiency and management.
Their broad pattern of spend across different stages of diagnostics development cycle and
overall operations are displayed in the table below.
We proposed to provide FIND with £10million over a 5 year period. DFID have also allocated
an additional £50,000 for an external evaluation of FIND at some point over the 5year period.
GBP 000s Year 1
Year 2
Year 3
Year 4
Year 5
Total
25
Expenditure Area
Feasibility
Development
Clinical Trials
Piloting & Intervention
Product Uptake &
Comms
Administration
Total
DFID Contribution
10,642
3,568
3,404
2,925
566
8,664
5,249
5,253
2,175
604
6,400
7,221
6,885
1,500
640
5,113
8,043
8,134
1,500
618
2,786
6,233
12,904
1,500
463
33,605
30,313
36,580
9,600
2,891
3,258
24,361
2,000
3,323
25,268
2,000
3,388
26,033
2,000
3,453
26,861
2,000
3,518
27,405
2,000
16,939
129,928
10,050
Expected Benefits
DFID’s renewed contribution to FIND will play a critical role in supporting the treatment and
control of malaria, TB and neglected tropical diseases, while enhancing health system
efficiencies through better disease diagnosis, reduced drug wastage and burden on tertiary
health and laboratory facilities and staff. An investment of £10,050,000 over 5 years will allow
them to further roll-out the diagnostics they have already developed, ensure the development
and use of at least 5 new diagnostics in disease endemic countries, maintain a strong and
balanced pipeline of diagnostics in development and strategically expand their portfolio into at
least 1 new disease area.
The diagnostics to be developed include rapid diagnostic tests for population screening for
sleeping sickness and asymptomatic carriers of malaria (both of which will contribute
significantly to disease control and eradication efforts, as well as case management); a
diagnostic for testing infants for congenital Chagas disease; disease staging and test-of-cure
diagnostics for sleeping sickness; triage tests for detecting individuals at high risk for TB at
primary care centres (enabling rapid referral for definitive diagnosis); a multi-drug resistant TB
test; tests to direct treatment and estimate risk of severe illness in patients, especially children,
with acute fever not associated with malaria; and molecular tests for case management and
surveillance of cutaneous and visceral leishmaniasis.
H. Theory of Change for the Preferred Option (Funding to FIND)
DFID’s investment to find will ultimately support FIND to achieve the impact goal of reducing
the global burden of neglected diseases and their impact on both patients and health systems,
through enhanced disease diagnosis, treatment and control. The overall pathway to achieving
this impact is illustrated below:
26
Inputs
Processes
Outputs
•Founding partners & Governance
•Alternative PDP model based on patient needs
•Qualified staff with complementary backgrounds
•Diverse funding pool including £10,050,000 from DFID
•Market analysis and target product profiling on a patient-needs basis
•Portfolio and pipeline management
•Partnership and capacity building, including endemic country stakeholder engagement
•R&D Operations
•WHO endorsement
•5+ neglected disease diagnostic tests developed and in use in disease endemic countries
• Strong and balanced pipeline of diagnostics in develompent, including 3-5 fully evaluated tests and another
4-6 for which technical feasibility has been established
•Portfolio expanded to include at least one new disease area
•Improved neglected disease management and control iniitatives (achieved through
increased availability and use of new, appropriate and affordable field-adapted
Outcome diagnostics for use in resource-constrained settings)
• Reduced global burden of neglected diseases and their impact on
Impact both patients and health systems
This pathway to impact is based upon some of the below mentioned assumptions:
Outcome to Impact:
 Improved neglected disease management reduces disease burden
 Improved neglected disease management reduces the strains on the health system
Outputs to Outcome:
 Improved diagnostics are adopted by disease endemic countries
 Improved diagnostics enable correct treatment and improved case management
 Improved diagnostics support wider disease control initiatives not only through
improving case management but through their use in active case finding and disease
surveillance
Processes to Outputs:
 A patient-needs based approach and disease endemic country government
engagement maximises the likelihood of developing appropriate products that will,
ultimately be adopted
 Partnerships contribute to more effective operations
 Capacity-building within developing countries supports the development of relevant
research, sustainable research capacity, and facilitates the rational use and uptake of
new neglected disease diagnostics
 WHO endorsement is critical to disease endemic country adoption of new products
 A portfolio approach maximises the likelihood of ensuring appropriate diagnostics are
developed in a cost-effective manner
FIND and partners’ development of the Xpert test for TB provides a strong example of the
results chain illustrated above. Following a patient-needs approach and recognising the need
27
for a reliable, point-of-use, test for TB, they adapted the Gene Xpert platform for detecting TB
and multi-drug resistant TB. The resultant diagnostic test, Xpert MTB/RIF, was endorsed by the
WHO in 2010 and within two years two-thirds of high burden TB countries had incorporated use
of the test into their National TB Control Guidelines. By 2012, over 2 million test cartridges had
been sold globally (across 29 countries). The Xpert MTB/RIF test is changing the landscape of
TB diagnosis and treatment – it can be used by healthcare workers with minimal training and/or
laboratory facilities, is associated with a 40% improvement in case detection rates, and, as a
point of use test, can provide test results for both TB and MDR-TB within 2 hours compared to
a previous wait of 6-8 weeks, and modelling suggests that use of the test could save up to
200,000 lives a year61
I.
What Measures can be used to monitor Value for Money for the Intervention?
In their patient-needs driven approach to R&D, FIND (and other PDPs) work with a diverse
range of partners to ensure the most appropriate and cost-effective approach to the
development of new drugs. ICAI (2011)62 suggests that to represent value for money,
programmes receiving support from DFID should:
 Ensure they have realistic and appropriate objectives and a clear plan for achieving
their intended impact,
 Have robust delivery arrangements to support the desired objectives and demonstrate
good, transparent governance and management through the delivery chain,
 Demonstrate a transformational, positive and lasting impact on the lives of the intended
beneficiaries,
 Incorporate learning to improve future aid delivery.
In order to ensure investments in FIND continue to represent good value for money for DFID
we have worked with them to develop a set of possible indicators against which they will report
annually. The final set of indicators will be agreed with them if this business case is approved
but they are likely to be selected from those illustrated in the table below which sets them out
against the core VfM indicators of economy, efficiency, effectiveness and cost-effectiveness.
Where possible these indicators are taken from FIND’s pre-existing performance assessment
and reporting frameworks.
Criteria
Economy – getting the best
value from inputs
Efficiency – maximising the
outputs for a given level of
inputs
Metric
 Proportion of co-funding/ in-kind contributions leveraged from partners
 Evidence of leveraging of other PDPs for drug or vaccine trial platforms
(usually by “piggy-backing” on trials or by adding critical mass, so metric
would be number of trials we can “top up” or share)
 Cost reduction in FIND target markets compared to high income countries
 Proportion of programmatic spend out of total spend (consistently lean wrt
running/admin costs)
 Number of biomarker- and product development and validation projects
enabled through use of FIND clinical platform (incl. specimen banks)
and mentorship programme
 Number of products successfully developed (meeting target product
profiles)
 Number of technologies assessed through systematic technology
scouting and selection process
61
Keeler et al (2006) Reducing the global burden of tuberculosis: the contribution of improved
diagnostics. In Nature v444(S1): 49-57
62 ICAI (2011) ICAI’s Approach to Effectiveness and Value for Money.
28
Effectiveness - ensuring
that the outputs deliver the
desired outcome
Cost-effectiveness
Overall, how much does
your programme of
activities contribute to your
impact goal (e.g. reduced
global burden of infectious
disease) relative to the
investments made?









 Number of tests approved by WHO or regulatory authorities
Number of national programmes that are implementing FIND co-developed
tests in disease control or elimination efforts
Number of co-developed tests sold in disease endemic countries (uptake)
Shortened time to treatment
Quality assurance data informs procurement leading to use of higher quality
tests (extent to which large scale global health programmes procure tests
based on whether or not they’ve been QA’d through FIND-partners
processes)
Number of cited open access research publications with FIND authorship
High cost-effectiveness of new tools and reduction of
transmission/incidence demonstrated through mathematical modeling and
large scale trials
Proportion of donor and national funding devoted to implementation of FIND
co-developed products
Money saved through avoidance of misdiagnosis and overtreatment
Number of patients appropriately treated per dollar of donor funding
J. Summary Value for Money Statements for the Preferred Option
The preferred option is to fund the Foundation for Innovative New Diagnostics product
development partnership to develop a range of new diagnostic tests for neglected diseases.
This delivery mechanism is associated lower costs and shorter lead times than either the
private or academic sectors alone, resulting in the greatest number of lives saved at the best
value for money.
Further supporting statements are offered in the table below.
Criteria
Economy – getting the
best value from inputs
Funding the FIND PDP
Management costs are included in the funding from DFID. The
PDP works with and manages a wide range of partners across all
stages of the pipeline, runs open competitions for innovations to
include in the pipeline. All projects in the portfolio are subject to a
detailed cost assessment by the PDP and its governance
structures (scientific and technical advisory committees, Boards)
at different milestone stages along the development chain. Can
leverage funding from private sector partners, work with
developing country industrial partners and negotiate favourable
costs and conditions to keep costs low. FIND is also seeking
increasing partnerships with other PDPs to allow them to share
field sites and associated running costs.
Efficiency - maximising The PDPs are able to develop portfolios using the best candidates
the outputs for a given
developed anywhere in the world. They make strong, rigorous
level of inputs
decisions at predefined go/no go stages in the development chain
and only progress candidates with a high degree of efficacy at
each stage, thus decreasing risk of failure at each stage.
Effectiveness - ensuring PDPs act as neutral brokers, bringing together a wide range of
that the outputs deliver
partners, to work together. Some commercial partners would not
the desired outcome
be able to work together under other circumstances. Able to
leverage in a wide range of in-kind support from different partners
and have access to private sector and in-country development
29
Cost-effectiveness
partners. Able to reach researchers, policy makers and regulatory
authorities in developed and developing countries.
Acting as ‘virtual’ organisations PDPs use resources and
knowledge from a wide range of partners. They are able to
develop new technologies without the high overhead costs of
maintaining complex infrastructure or a large workforce.
30
Commercial Case: Delivery through a third party (multilateral organisation; civil
society organisation)
What assurance has been obtained on the organisation’s capability and capacity to
deliver?
The Foundation for Innovative New Diagnostics (FIND) was selected for funding following a
global open competition calling for the development of new global health technologies
(vaccines, drugs, diagnostics, vector control and family planning commodities). 47
organisations (including academic, industrial and public-private partnerships) submitted
expressions of interest, 17 of which were invited to submit full proposals which all went through
a formal process of scientific, technical, commercial, financial and policy peer review,
discussions with other funders, private sector stakeholders, community stakeholders and
researchers.
A substantial number of staff employed by the PDP are from the private sector, including
pharmaceutical and biotechnology industries and bring with them good knowledge and
practices in the field.
Core competences of organisation to deliver in country
FIND has a track record of working efficiently with numerous partners in many countries.
Stringent portfolio management systems are employed which ensure that only the most
promising leads are pursued. There are strict go/no-go decision points in the management of
their portfolio of products .This means that they are able to close out projects quickly that are
unlikely to produce the desired outcome. They have partnerships with organisations involved
in the delivery of new technologies; to ensure that once developed they can be made available
to those who need them.
Procurement capability
The organisation has demonstrated robust procurement systems and has a proven record in
supply chain management and attaining economies of scale. Robust due diligence assessment
has provided further assurance that procurement practices are undertaken professionally and
in line with recognised best practice.
FIND’s procurement processes and risk are regularly assessed by their own boards, and by
funders, as part of the due diligence for providing support, by independent reviews of the
organisation and members of the Multi Donor PDP Funders Group.
Is there an opportunity to negotiate on the organisation’s anticipated costs?
PDPs have been shown to deliver new products faster, and at lower cost, than the public or
private sectors alone. They are able to leverage in resources, knowledge and expertise, from a
range of different partners. The organisation will be constantly looking for potential savings that
can be made during the term of the programme. The portfolio management enables the
organisation to focus closely on products where there is a higher chance of success Based on
an analysis of the workplan, objectives and following discussions with other technical funders,
our assessment is that there is an opportunity to invest up to £10 million in FIND with
increasing returns. This amount is lower than the amount requested by FIND in their proposal.
DFID Relationship
DFID has been a supporter of PDPs for some time and, based on previous experience and
long-term relationships with them, is viewed as a global leader in this area. DFID has worked
31
with other funders, and the PDPs themselves, to leverage support from other donors. The
donor group (PDP Funders Group), currently chaired by DFID, has played a major role in
influencing PDP governance, structure and financial planning. Donor input is welcomed by
PDPs and donor harmonisation on reporting has created efficiencies.
Financial Case
What are the costs, how are they profiled and how will you ensure accurate forecasting?
The proposed budget for FIND is £10,050,000 over 5 years (2013 –2018). The anticipated
breakdown of core funding by DFID financial year is as follows but will be subject to negotiation
with FIND based on need and avoiding payment in advance of need. The total amount includes
an allocation for an external review of FIND, the timing of which has not yet been decided.
2013/14
£2,000.000
2014/15
£2,000,000
2015/16
£2,000,00
2016/17
£2,000,000
2017/18
£2,000,000
Total
£10,050,000.
How will it be funded: capital /programme/admin?
Funding will be made available from programme funds through a Memorandum of
Understanding from the Human Development Team in Research and Evidence Division.
How will funds be paid out?
Support will be through a Memorandum of Understanding with FIND. Payments will be
provided in June and November each year on production of appropriate claim forms.
What is the assessment of financial risk and fraud?
FIND will administer and account for DFID, and other funders’ contributions in accordance with
its financial regulations and other applicable rules and procedures and practices.
FIND has a proven record of strong financial management and probity employing international
standards of financial management and accountability. The risk has been assessed as Low.
Conditions will be included in the MOU to ensure that FIND have appropriate fraud and conflict
of interest policies in place.
How will expenditure be monitored, reported and accounted for?
FIND will be required to submit Annual Audited Accounts for each of the years covered by the
DFID grant. Harmonised annual reporting to donors will include detailed information on
finances, in addition to technical, organisational and governance issues.
32
Management Case
What are the management arrangements for implementing the intervention?
The MOU will be managed by the Human Development Team in DFID’s Research and
Evidence Division. They will have oversight through routine financial and performance
reporting and review, including at regular donor meetings, when all donors will discuss the
organisations scientific, technical, governance, organisational, operational and financial
management.
Within DFID a Health Adviser and Research Manager in the Human Development Team will
provide the lead technical and project management roles, overseeing the relationship with
FIND. A Deputy Programme Manager will be responsible for the day to day administration of
the grant including financial tracking, compliance and other administrative functions.
FIND is overseen by a Governing Management Board and a Scientific Board of experts both of
which meet on a regular basis.
What are the risks and how these will be managed?
Overall the level of risk associated with this business case is Medium to High.
FIND’s model is characterized by several distinguishing features including (a) an unwavering
patient-centered, needs-driven approach, (b) a commitment to both open access to knowledge
and equitable access to treatment for patients, (c) financial and scientific independence, and
(d) building and sustaining of solid alliances. They are currently in the process of exploring
options for considerably improving their operating efficiencies.
FIND undertake regular risk assessments and the Board has a role in the detailed scrutiny of
risk. The follow table provides a view of the major technical, organizational and financial risks
for the organization which is reviewed internally throughout the year and will be reviewed
annually by DFID at the time of their annual review.
Probability
Impact
(low/med/high)
(low/med/high)
Medium
High
 Perform detailed
market/landscape analysis and
reassess strategic direction of all
programmes
 Work to strengthen core
competencies
 Actively communicate
organization’s on-going value and
impact
Current technical
infrastructure in FIND
becomes overwhelmed
with the requirements of
meeting additional grant
obligations
High
High
 Implement longer term plan to
address staffing needs to improve
efficiency, effectiveness, and
responsiveness to grants.
 The current structure is expected
to be able to fully deliver on
upcoming grant obligations
Current absence of
permanent CEO creates
Medium
Medium
 More frequent internal monitoring
 Maintain transparency in
Risk
Organisational
Changing diagnostic
development landscape
and increasing
competition affect long
term sustainability
Mitigation Measures
33
Risk
Probability
Impact
(low/med/high)
(low/med/high)
Organisational
loss of momentum and
focus
Mitigation Measures
communications with all staff
 Current interim measure
functioning well (Executive
Committee that carries out
Executive functions)
 Identify full-time CEO within 3-9
months.
Financial
Short-to-medium term
funding inadequate to
cover organisational
costs
Medium
High
 Continue implementation of
stringent indirect cost-reduction
programme
 Improved efficiencies
 Examine effects of relocation,
including office or service sharing
options
 Investigate potential partnerships
and/or operating models to
broaden product offering and/or
capture operational efficiencies
Longer term risk of
narrowing of donor
funding base
Medium
Medium
 Proactively attempt to broaden
donor base and bring on a wider
range of funding partners
 Identify sources of sustainable
revenue to support programs (as
currently planned)
 Targeted resource mobilization to
balance core and programme
funding
Medium
Medium
 Examine multiple options to
integrate an automated samplehandling platform specifically for
LAMP assays.
High
High
 Support the development, through
a Gates Foundation grant, of
multiple new biomarkers for TB
that adequately distinguish
patients that require TB treatment
from those which do not.
Medium
Medium
 Use a quantitative mechanism to
assess which disease and testingindication offer the greatest
chance of health impact per unit
of investment.
 Maintain an oversight of other
potential new disease areas for
strategic portfolio expansion
Technical
No manual fluid handling
mechanism can be found
that would be simple
enough to implement in
the periphery of the
health system
Biomarkers will not be
found for tuberculosis that
adequately distinguish it
from LTBI and pulmonary
disease of other causes
Risk that sexually
transmitted infections
(STIs), the current lead
disease area for
expansion, will have too
weak a treatment
infrastructure, or too
complicated diagnostic
requirement, for FIND to
meet program needs
34
What conditions apply (for financial aid only)?
Not applicable.
How will progress and results be monitored, measured and evaluated?
FIND has a detailed performance framework which is used internally to monitor their progress
and report to the Board, Scientific Advisory Board and other funders. Internally all projects are
monitored using strict go/no-go decisions and those that are not making their milestones are
stopped.
Evaluation
DFID have allocated £50,000 for external evaluation activities. External reviews and/or
evaluations are likely to be undertaken jointly with other donors. In addition it is worth noting
that the Board of Governors and the Scientific Advisory Board have a constant overview of the
technical work being undertaken
Logframe (draft available at Quest Link: 4029997)
FIND has a detailed performance framework which they use to manage their performance
internally and with their other donors. The logframe is specific to DFID and will be discussed
and agreed with FIND if DFID funding is agreed.
35