Evaluation PDP III Fund 2015-2021
Final Report
Client: Ministry of Foreign Affairs
Rotterdam, 12 November 2021

Evaluation PDP III Fund 2015-2021

Final Report

Client: Ministry of Foreign Affairs

Wim Spit
Joost van der Meer (PHESTA)
Milda Saltenyte-Robbers
Tessa Huis in ‘t Veld
Hein Gietema (CSC Finance)
Zinovia Panagiotidou
Stef van Muiswinkel

Rotterdam, 12 November 2021

Table of contents

List of abbreviations

7

Conclusions and recommendations

9

Introduction

1

2

3

9

Main findings and recommendations on the individual PDPs during 2015-2021

9

Main findings and recommendations on the funding mechanism

10

Introduction

13

1.1

The PDP concept

13

1.2

The PDP III Fund

14

1.3

Scope of the evaluation

15

1.4

Evaluation questions

16

Methodology

17

2.1

Methodology used

17

2.2

Limitations

18

Findings

21

3.1

Review of the evidence from previous evaluations

21

3.2

Findings regarding the six PDPs

22

3.3

The funding mechanism

35

4

Discussion and recommendations

47

5

PDP Sheets

52

5.1

Drugs for Neglected Diseases Initiative (DNDi)

52

5.2

Foundation for Innovative New Diagnostics (FIND)

57

5.3

International AIDS Vaccine Initiative (IAVI)

62

5.4

International Partnership for Microbicides (IPM)

66

5.5

Medicines for Malaria Venture (MMV)

69

5.6

TB Alliance

74

The annexes are in a separate document.

Evaluation PDP III Fund 2015-2021t

5

List of abbreviations

ACT-A

Access to COVID-19 Tools Accelerator

AGYW

Adolescent Girls and Young Women

AIGHD

Amsterdam Institute for Global Health and Development

AMR

Antimicrobial Resistance

ARV

Antiretrovirals

BFF-DX

Biomarker based fever test

BMBF

German Ministry for Education and Research

BMGF

Bill & Melinda Gates Foundation

BPaL

Bedaquiline, Pretomanid and Linezolid

CAD

Computer-Aided Detection

cAg

Core antigen

CASPR

Coalition to Accelerate and Support Prevention Research

CE

Community Engagement

CHS

Centre for Health Security

CL

Cutaneous Leishmaniasis

DALY

Disability Adjusted Life Year

DFAT

The Department of Foreign Affairs and Trade of Australia

DFID

UK Department for International Development

DHSC

Directorates of Health and Social Care

DNDi

Drugs for Neglected Diseases Initiative

DR-TB

Drug-Resistant forms of Tuberculosis

DVR

Dapivirine Vaginal Ring

EDCTP

European and Developing Countries Clinical Trials Partnerships

EMA

European Medicines Agency

EUL

Emergency Use Listing Procedure

EVI

European Vaccine Initiative

FCDO

Foreign, Commonwealth and Development Office of UK

FDA

Food and Drug Administration

FDC

Fixed Dose Combination

FIND

Foundation for Innovative New Diagnostics

GPP

Good Participatory Practise

HAT

Human African Trypanosomiasis

HCV

Hepatitis C

HIC

High Income Countries

HIV

Human Immunodeficiency Virus

IAVI

International AIDS Vaccine Initiative

IOB

The Policy and Operations Evaluation Department

IPM

International Partnership for Microbicides

IVCC

Innovative Vector Control Consortium

KNCV

Dutch Tuberculosis Foundation

LMIC

Low- and Middle Income Countries

MAA

Marketing Authorization Application

MIC

Middle Income Countries

Evaluation PDP III Fund 2015-2021

7

MMV

Medicines for Malaria Venture

MNC

Multinational pharmaceutical Companies

MoFA

Ministry of Foreign Affairs

MPT

Multipurpose Prevention Technology

MSF

Médecins Sans Frontiéres

MSM

Men who have sex with men

NCE

New Chemical Entities

NEI

Netherlands Economic Institute

NGO

Non-Governmental Organisations

NIH

US National Institute of Health

NTD

Neglected Tropical Disease

OECD/DAC

Organisation for Economic Co-operation and Development/Development
Assistance Committee

8

PAHO

Pan American Health Organization

PDP

Product Development Partnerships

PKDL

Post-Kala Azar Dermal Lesions

POC

Point-Of-Care

POW PDP

Protection Options for Women Product Development Partnership

PRA

Pharmaceutical Research Associates

R&D

Research and Development

RDT

Rapid Diagnostic Test

RUNMC

Radboud University Nijmegen Medical Centre

RVO

The Netherlands Enterprise Agency

rVSV

recombinant Vesicular Stomatitis Virus

SDG

Sustainable Development Goals

SME

Small and Medium sized Enterprises

SRH

Sexual and Reproductive Health and Research

SRHR

Sexual and Reproductive Health and Rights

ST

Self-Testing

TB

Tuberculosis

ToC

Theory of Change

ToR

Terms of References

TPP

Target Product Profile

UHC

Universal Health Coverage

UNGA

United Nations General Assembly

VL

Visceral Leishmaniasis

WHO

World Health Organisation

WoCBP

Woman of Childbearing Potential

Evaluation PDP III Fund 2015-2021

Conclusions and recommendations

Introduction
In 2015 the Netherlands government awarded grants to the amount of €83.6 million to six Product
Development Partnerships (PDPs): public-private partnerships for research and development of
medicines, vaccines and diagnostics to combat poverty-related diseases and conditions related to
Sexual and Reproductive Health and Rights (SRHR). In 2020, the grant period was extended by
one year and topped up with an amount of €17.3 million. This report describes the findings of an
external evaluation of this funding, also known as the PDP III Fund.
The following PDPs have been co-financed under the PDP III Fund:
•

Drugs for Neglected Diseases Initiative (DNDi),

•

Foundation for Innovative New Diagnostics (FIND),

•

International AIDS Vaccine Initiative (IAVI),

•

International Partnership for Microbicides (IPM),

•

Medicines for Malaria Venture (MMV) and

•

TB Alliance.

The overall objective of the evaluation is to review the achievements of the six PDPs and inform
decision-making on continuation of the PDP Fund and future funding mechanisms and priorities.

Main findings and recommendations on the individual PDPs during 2015-2021
Relevance
The activities of the six PDPs are highly relevant, as they develop and bring to the market products
to combat or prevent poverty-related diseases1 and conditions associated with sexual and
reproductive health and rights (SRHR), which includes HIV/AIDS. Such products are highly needed,
as poverty-related diseases are still widespread in Low and Middle Income Countries (LMICs),
while they cause substantial loss of (quality of) life, and jeopardise public health. As the target
populations lack purchasing power and hence such markets are not commercially interesting for
private companies.
Effectiveness
PDPs have made substantial progress in terms of pipeline development of candidate products in
2015-2021. Even though not all activities have been carried out exactly according to the plans
submitted to the Ministry of Foreign Affairs (MoFA) in 2015, the adjustments made and the results
achieved are generally in line with the original objectives and goals. Since 2015 375 new products
are in the pipeline, in total 30 products of the six PDPs moved one phase in the development
process, while 12 products developed under PDP III funding have reached marketing stage and
have been registered with national authorities or international organisations such as WHO.2 These
products are available for: treatment of patients suffering from sleeping sickness (DNDi), for the

1
2

Poverty-related diseases comprise: HIV, TB, malaria and neglected tropical diseases as defined by WHO.
These 12 products are: fexinidazole, for the treatment of sleeping sickness (DNDi); TB Ultra Test, Xpert XDR and Omni,
for the diagnosis of tuberculosis; ProBio, Standard Q, for the diagnosis of COVID-19 (FIND); Dapivirine Vaginal Ring, for
the prevention of HIV (IPM); pyronaride-artesunate (Pyramax(R)) tablets and paediatric granules, artesunate rectocaps,
tafenoquine, for the treatment of various forms of malaria (MMV); pretomanid, as part of treatment for multidrug-resistant
tuberculosis (TB Alliance).

Evaluation PDP III Fund 2015-2021

9

diagnosis (FIND) and treatment (TB alliance) of tuberculosis, for the prevention of HIV (IPM) and for
the treatment of malaria (MMV).
Besides pipeline development, increasing the accessibility of the products is an important activity
for the PDPs. It is estimated that 2.4 billion people around the world have benefitted from the work
done by the PDPs. While some PDPs increasingly improve access for specific groups (in particular
women of childbearing age, and children), this effort is not seen systematically across all PDPs.
It is recommended that all PDPs follow a systematic approach to accessibility of products
for women and children; a cross-cutting standard for PDPs may be helpful in achieving such
a standard approach.
Flexibility
The COVID-19 pandemic has inevitably had an impact on operations of the PDPs. PDPs have
been successful in minimizing the impact of travelling restrictions and distancing measures, by
switching to remote methods of working e.g. in managing trials and keeping contacts with trial
participants. COVID-19 has had impact in terms of shifting the attention from donor funding away
from neglected tropical diseases (NTDs), as has happened with funding by the UK government.
This financial impact is far more important than the impact on operations. At the same time the
pandemic has created more attention for product development (particularly vaccines) and hence
has created opportunities for several PDPs with respect to the development of COVID-19 vaccines,
medicines, or diagnostic tests.

Main findings and recommendations on the funding mechanism
Relevance
Accessibility and pipeline development
The PDP III fund has focused predominantly on product pipeline development. However,
accessibility is equally important in order to achieve the desired impact of the funding. Accessibility
comprises all steps to reach end users, among which pricing, regulatory approval and reaching
communities. With many products now on the market or ready for market introduction, the
importance of optimal accessibility is growing.
It is recommended to explicitly include activities aimed at realising better access in the
scope of a future PDP Fund by adopting the end-to-end approach (i.e. the whole process
from identification of lead substances to the use of the end products by communities) to the
funding of PDPs.
Alignment with SRHR policy of the Netherlands
Products for the promotion of sexual and reproductive health constitute one of three priority themes
of the PDP III Fund (besides products in relation to poverty-related diseases, and products in
relation to new and recurring epidemics). In the present COVID-19 pandemic PDPs experience that
attention in funding is shifting. Two major donors, the Bill and Melinda Gates Foundation (BMGF)
and the government of the United Kingdom have recently reduced the financing for PDPs. There is
a risk of crowding out funding for SRHR and poverty-related diseases. Some PDPs already report
feeling the impact of this development.
It is recommended to focus a future PDP Fund on two areas: products for SRH and products
for poverty-related diseases.

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Evaluation PDP III Fund 2015-2021

A further focus in a potential future PDP Fund on products for SRH only would limit the possibilities
for product development by PDPs. Such a focus may be less limiting if it includes activities that are
related to safety of women during pregnancy and the lactating period, as some PDPs are already
doing, Thus, the relevance of product development for a large and hitherto underserved group
would increase.
It is recommended that, in case of a focus on SRH in a future PDP Fund, this focus is
interpreted broadly, by extending funding also to activities aimed at product development
and safety research for groups that are relevant for SRH, like pregnant and lactating women
and women of childbearing age.
Alignment with other Dutch funding mechanisms
The Ministry of Foreign Affairs manages several funding mechanisms besides PDP funding, for
instance Power of Voices and the SDG5 fund. Especially some funding mechanisms in the SDG5
fund address SRHR and, therefore, have potential synergies with PDP activities on increasing
access to essential medicines and diagnostics. Yet, the evaluators did not find evidence of a
systematic effort to enhance coherence and coordination between these funding mechanisms. This
is a lost opportunity.
It is recommended to explore the possibility to further strengthen the coherence between
the work of PDPs and other funding mechanisms of the Ministry of Foreign Affairs that have
potential synergies in working on increasing accessibility of the PDP products.
Effectiveness
According to an international survey, the financial contribution of the Netherlands during 2016-2020
equalled around 11% of total funding of all PDPs by bilateral donors. 3 Dutch funding covered
slightly over 3% of total expenditures of MMV and approximately 10% of those of IPM during 20162020. For the other four PDPs, the funding from PDP III Fund covered 5 to 6.5% of expenditures in
these years.
PDPs highly appreciate the characteristics of the Dutch funding under the PDP III Fund, such as it
being core funding, it’s flexibility in use and the long-term view in the funding. The flexibility for
instance complements project funding by other donors and enables the funding of activities that are
difficult to allocate to a particular project (like capacity building), or that other donors are not willing
to fund, such as exploring a new lead substance. Core funding also helps PDPs to obtain other
funding with a co-funding requirement, such as US Funds or ECDTP funds. Core funding is seen as
an important added value of Dutch funding.
It is recommended to keep the characteristics such as core funding, flexibility in use and a
long-term view in a future PDP fund.
In the past the Dutch government was visible as influencer in the PDP field, e.g. in advocating for
SRHR, and in strategy development within the PDP donor community. This role has diminished
over time and was significantly lower-key during PDP III years as compared to the level in the
beginning period of the PDPs, partly due to high turnover of Dutch government staff.
It is recommended that efforts are being made to step up the leadership role of MoFA in the
broader donor and international community regarding PDP funding and strategy (with a view
to further enhance PDP’s role in SRHR and explore innovative funding mechanisms).
PDPs intensively work together with commercial private sector partners in the discovery and
development of their products. In this cooperation, private partners normally participate on a
commercial basis. The work of PDPs attracts limited additional funds from commercial companies,
in many cases (in kind) as part of their CSR policy. From documents and interviews there appears
3

The funding from PDP III Fund started 1 October 2015. For this reason the year 2015 has not been taken into account.

Evaluation PDP III Fund 2015-2021

11

no increase in the investment of private sector in the work of PDPs during 2015-2021, whereas an
increase of such investments was an important assumption in the PDP III Fund Theory of Change.
All six PDPs work together with research institutes, in several LMICs. PDPs have been investing
actively in capacity building in LMICs and employ these institutes in clinical trials. PDP coalition
members have performed clinical research at more than 550 sites in more than 80 countries, mostly
in LMICs. When a trial is concluded, clinical trial sites experience discontinuity in their workload,
which can result in loss of valuable staff. More cooperation between PDPs and other stakeholders
in planning clinical trials can improve the sustainability of research capacity in LMICs.
It is recommended that PDPs improve their coordination of clinical trials in LMICs in order to
improve the long-term sustainability of the research capacity.
Efficiency
Over the years, the PDP model has proven to be a cost-effective way to develop products for
poverty related and neglected tropical diseases and conditions in relation to SRH. Their costeffectiveness is better than that of commercial pharmaceutical companies. The Lancet Commission
on Essential Medicines Policies states that industry-supported estimates of the cost for developed
medicines set the average at USD 2.5 billion per new product, whereas DNDi estimates the costs of
developing a new chemical entity at € 100-150 million, and the costs of improving a treatment at €
10-40 million. Alternative financing instruments (like direct funding of research institutes in LMICs;
or financing via multilateral organisations) are suboptimal in terms of scope and, therefore, potential
impact, as compared to the end-to-end approach of the PDP model.
Sustainability
The SWOT analysis shows that a main weakness of the funding mechanism is that it is financially
not sustainable without grant funding. Reduction of the dependence on donor grants by increasing
other funding would strengthen the sustainability. It is presently not clear to what extent this can be
successful. Various ways have been explored to improve the sustainability, such as the use of
impact bonds. A few possibilities have been identified to expand the funding basis. More research
will be needed to explore the viability of these opportunities.
It is recommended that MoFA explores the possibility, together with PDPs and other
funders, to create a common fund that is financed from impact bonds and/or from part of the
margin that pharmaceutical companies can make on selling newly developed products in
High Income Countries for which intellectual property rights are with PDPs.

12

Evaluation PDP III Fund 2015-2021

1

Introduction

1.1

Background
Only 10% of global health research is devoted to conditions that account for 90% of the global
disease burden – an imbalance that has been referred to as the 10/90 disequilibrium, and that
persists since the 10/90 report was published. In 2019, spending on neglected tropical diseases
and poverty-related diseases was 3,876 million USD, while total global spending on research and
development (R&D) for new medicines in that same year was estimated at 190 billion USD. Heavy
reliance on a highly competitive multinational drug industry has left the development of lifesaving
drugs largely to market forces. Currently, it is largely purchasing power that is defining research
agendas and priorities, which means that poor people’s health needs are not being met.
This means there is insufficient investment in research and development and innovation in the
areas of healthcare products and technologies specifically aimed at diseases and conditions related
to poverty and SRHR. Accordingly, such products and technologies are all but non-existent, or
unaffordable for the most vulnerable populations lacking access to adequate healthcare.
In 1990 the Product Development Partnerships (PDPs) have been introduced to accelerate the
development and availability of products which are unlikely to attract private investments while in
development. Since 2006, the PDP model has been deployed to promote research and
development and innovation in healthcare.

1.2

The PDP concept
A Product Development Partnership is a not-for-profit public–private partnership that is specifically
set up to overcome market failures and other barriers to product research and development PDPs
are used for a broad range of neglected diseases, among which the poverty-related diseases which
are within the scope of the PDP III Fund.4 PDPs develop products, such as medicines, vaccines,
microbicides, biologics, diagnostics, vector control products, devices, and multipurpose prevention
technologies.5 In a way, PDPs are not different from pharmaceutical companies in that they
organise the complete research and development process of new products. This process includes
all steps such as basic research, discovery, pre-clinical development, clinical development (phases
1, 2 and 3) and post-registration studies (phase 4).6 The main difference with commercial
pharmaceutical companies is that PDPs focus on the development of products and not on
production, and that they focus on products for which there is market failure. The specific failure in
this case is that there is an apparent need to prevent and/or cure diseases, but no supply of such
products, as their development is not seen as an attractive investment by commercial parties due to
expected low revenues.

4

5
6

From here on in this report we will use the term ‘poverty-related diseases’ to comprise HIV. Tuberculosis and malaria, as
well as neglected tropical diseases as defined by WHO, see https://www.who.int/health-topics/neglected-tropicaldiseases#tab=tab_1
Policy Cures Research, G-Finder 2019. Neglected Disease Research and Development: Uneven Progress, 2019
In each of the development phases clinical trials are used. Phase 1 trials focus on the safety and dose range of the
medicine; phase 2 trials on the efficacy of the medicine, phase 3 on the effectiveness of the treatment as compared to
normal treatment. Once phase 3 is concluded successfully, registration of the medicine can be requested with national
authorities and/or WHO. Once registered the product can be made widely available to patients. In this phase the effects of
long term use of the medicine are monitored, including possible long term side-effects.

Evaluation PDP III Fund 2015-2021

13

Once the clinical trials for a product are successfully concluded and the efficacy and added value of
the product is proven, PDPs take care of the registration process of developed products with
national authorities and for WHO pre-qualification. Once a product is allowed on a particular
market, the production and distribution are taken care of by commercial partners. To this end
agreements are made between the PDP and commercial partners, on the use of intellectual
property rights and product pricing, ensuring that products are affordable for users in LMICs.
In the development process PDPs use the knowledge of various partners, including commercial
partners, patient organisations, scientists, advocacy groups, etc., for instance on the specific needs
of patient groups. Financing is provided from a mix of sources, including donor funding from
national or philanthropic organisations, donations by private parties and, in some cases, revenues
from services provided to other parties.
PDPs operate a flexible model of working, which is inherent to the drug development process.
Development of substances that are deemed unsuitable for LMIC contexts are abandoned, and
new products are identified that enter the pipeline. PDPs have been adjusting their development
model over the years. As some of their products moved through the pipeline to the implementation
stage, PDPs increasingly included all aspects of access in their development model, ranging from
regulatory approval, via guideline development and –advocacy to training of health workers, and
community engagement.
Governance
PDPs are typically managed by a board of directors in which the various aspects of the work are
reflected including scientific research, access and external relations. Most PDPs also work with
external advisory committees comprising among others civil society organisations and independent
scientists. Typically, PDPs have their head office in the United States or Europe, and various
regional offices in LMICs.

1.3

The PDP III Fund
In the periods 2006-2009 and 2011-2014 the Dutch MoFA contributed EUR 150 million for the
development of medicines, vaccines and diagnostics to combat HIV/AIDS, tuberculosis and
malaria. After an evaluation of the PDP Fund II (2011-2014), the Minister for Foreign Trade and
Development Cooperation decided to make a third round of funding available.
In 2015, MoFA awarded EUR 83.6 million in grants to six PDPs. The grant was awarded for a
period of 5 years, from 2015 to 2020 (PDP III). In 2020, the grant period was extended by one year
to cover 2021 as well (EUR 17.3 million).Specifically, the PDP III Fund focuses on the development
and availability of affordable, effective medicines, vaccines, diagnostics and innovative products for
neglected diseases and conditions, with a view to combating poverty and inequality.
The following organizations received funding from the PDP III Fund in the period 2015-2021:

14

Evaluation PDP III Fund 2015-2021

1. The Medicines for Malaria Venture (MMV) - MMV’s mission is to reduce the burden of malaria in
disease-endemic countries by discovering, developing and delivering new, effective and
affordable antimalarial drugs to cure and protect vulnerable populations. www.mmv.org;
2. The International Partnership for Microbicides (IPM) - IPM’s mission is to provide women with
safe, effective and affordable products they can use to prevent HIV and protect their sexual and
reproductive health. www.ipmglobal.org;
3. The Drugs for Neglected Diseases initiative (DNDi) – DNDi’s mission is to improve the quality of
life and the health of people suffering from neglected diseases using an alternative model to
develop drugs for these diseases and by ensuring equitable access to new and field- health
tools. www.dndi.org;
4. The TB alliance - The TB Alliance’s mission is to dramatically impact the tuberculosis pandemic
by developing new, significantly improved, faster-acting and affordable TB treatments that are
available to those who need them. www.tballiance.org;
5. The International AIDS Vaccine Initiative (IAVI) - IAVI’s mission is to ensure the development of
safe, effective, accessible, preventive AIDS vaccines for use throughout the world.
www.iavi.org;
6. FIND - FIND’s mission is to turn complex diagnostic challenges into simple solutions to
overcome diseases of poverty and transform lives. www.finddiagnostics.org.
Table 1 summarises the activities and amounts per PDP disbursed within the PDP III fund.
Table 1
PDP

DNDi

Overview of funding provided under the PDP III Fund (million Euro)
Title of activities PDP III

Area of work covered by

Funding

Contracted

MoFA funding

2015-2020

amounts 2021

Support of global control and

Human African

elimination targets of poverty-

Trypanosomiasis (HAT),

related diseases

Leishmaniasis, Chagas

16.00

3.20

10.06

2.01

HIV/AIDS

16.00

3.20

HIV/AIDS

14.00

2.80

Malaria

14.94

2.99

Tuberculosis

15.30

3.06

86.3

17.26

Disease, Mycetoma
FIND

Smart diagnostic solutions to
drive effective treatment and

Tuberculosis, Malaria

elimination of poverty-related

Hepatitis C (HCV)

diseases
IAVI

Spurring Innovation to bring an
aids vaccine to the World

IPM

Developing Innovative Products
to enhance Women's Sexual
and Reproductive Health

MMV

Breaking the cycle in malaria:
prevention and protection for all

TB

Product Development for

Alliance

Tuberculosis Drug Regimens

Source: MoFA.

1.4

Scope of the evaluation
As per Terms of Reference (ToR; Annex A) this external evaluation focuses on whether the original
aims of the PDP III fund have been achieved during the funding period 2015 – 2021. It should
determine to what extent the PDPs and the used funding instrument – six individual grants over six
years – meet their specific objectives in support of their general objective/outcomes. In this

Evaluation PDP III Fund 2015-2021

15

assessment the large-scale effects of the COVID-19 pandemic on the achievements of the PDPs
are to be taken into account.
The Dutch funding covers activities of six PDPs working on eight different diseases in more than 40
countries with a considerable network of partners. After more than 16 years of continued funding
and in the highly changed context of the COVID-19 pandemic, it is important to evaluate the added
value of the PDPs and to evaluate whether the original focus on the six partnerships is still relevant
in light of both the Dutch policy objectives and –priorities and current global health context. The
overall objective and specific objectives of this evaluation are as follows:7
Overall objective
•

To inform decision-making on continuation of the PDP Fund and future funding mechanisms
and priorities.

Specific objectives
1. To assess the relevance, flexibility, coherence, effectiveness and sustainability of the individual
PDPs;
2. To assess to what extent follow-up was given to the recommendations made by the Mid- Term
Evaluation of March 2019;
3. To assess the relevance, efficiency and effectiveness of the funding mechanism in reaching the
(policy) goals for both the PDPs and the Dutch government – define added value of Dutch
funding;
4. To provide recommendations for future funding mechanisms and priorities to promote research
and product development to combat poverty-related diseases and conditions related to SRHR
based on current challenges.

1.5

Evaluation questions
This evaluation includes questions of relevance, effectiveness, efficiency, sustainability and
coherence, as laid down in the OECD/DAC evaluation criteria, as guiding criteria.8 This evaluation
also looks at the governance of the PDPs and how they engage with key external players and
stakeholders, whether they are institutions, organizations, networks, programmes, governments or
individuals.
Furthermore, this evaluation builds on the Theory of Change (ToC) that stands at the basis of the
PDP III funding mechanism (Figure 1, see section 3.3.1).
We have included questions around the added value of the PDPs in the landscape of product
development stakeholders, progress of the funding pipeline, and accessibility of the new products
for the target groups, while also taking into account the engagement of LMICs in the development
process, the role of creating awareness, and leveraging of funds from other donors and the private
sector. The evaluation matrix in Annex B shows all evaluation questions and their relationship to the
evaluation objectives and OECD/DAC criteria in full detail.

7
8

16

As per Terms of Reference.
https://www.oecd.org/dac/evaluation/daccriteriaforevaluatingdevelopmentassistance.htm

Evaluation PDP III Fund 2015-2021

2

Methodology

2.1

Methodology used
We have used a complexity-aware approach that acknowledges the complexity of the PDP
programme. A complexity-aware approach recognizes the very different types of outcomes in a
programme, and the different approaches that may be needed to properly evaluate each type of
outcome. A complexity-aware approach also takes into account that processes leading to outcomes
may not be linear, and looks at contribution rather than attribution of the evaluation subject.
Therefore, we consider this method suitable for a Theory of Change-based programme such as
PDP III Fund that recognises complexity, and the many processes and stakeholders that are
involved.
We have used two different approaches to evaluate the PDP III programme: 1) Sentinel Indicators
and 2) Stakeholder Feedback. We have used Contribution Analysis as the main approach to the
evaluation. Contribution Analysis is suitable to evaluate programmes that have a solid Theory of
Change that clearly articulates the assumptions underlying the intervention. It can therefore test if
these assumptions are valid and influential, and thus also test alternative hypotheses. One of the
key starting points in Contribution Analysis is, that it has to be verified that the programme has
produced (most) outcomes as intended. The PDP III Fund has some very well-defined and easily
verifiable outcomes, such as an increased product pipeline for individual PDPs and increased
contributions from the private sector. We also have calculated some indicators to provide evidence
for the extent to which planned outcomes have been achieved. These are based on available
internal or external information, such as estimated number of patients having access to a new
product, translated as the number of doses, treatments or tests being distributed.
Stakeholder feedback collected information from stakeholders directly. Using Contribution Analysis,
we included a focus on the more complex relationships between the programme and intended and
unintended outcomes of the programme, notably the ones related to levels of contribution by
various stakeholders or changes in donor policy, target country policies or policies of multilateral
organisations such as WHO, and tested whether these have materialised and what the contribution
of PDP III was. This left room to test alternative theories of change, for instance if changes in
contributions or policy have occurred by public or political pressure, rather than by existence of the
PDP III Fund.
For these two approaches, we have used a number of methodologies to collect evidence:
1) Document review (see Annex C for a list of reviewed documents and publications)
2) Key informant interviews (see Annex D for an overview of interviews by stakeholder)
3) a Validation workshop (see Annex F for a short report on the workshop).
With these methodologies a rich body of evidence has been obtained from different sources that
enabled us to triangulate the information and obtain robust results for the evaluation.
To formulate and examine alternative theories, we included stakeholders who likely have
knowledge of other donor initiatives directed at increasing access to medicines and diagnostics,
such as external experts in the field of PDP, staff at relevant global (health) organisations and
representatives from relevant research institutes, Civil Society Organisations (CSOs) and NonGovernmental Organisations (NGOs). This allowed us to reflect on the specific contribution of
comparable donor initiatives in relation to PDP III.

Evaluation PDP III Fund 2015-2021

17

A summary of the methodology can be found in the evaluation matrix (Annex B), in which the
evaluation questions are translated into criteria, indicators and information sources. The guide for
interviews is included in Annex E.

2.2

Limitations
Evaluating complex global health initiatives like PDPs requires three main pillars9 :
1) A Theory of Change that grounds the evaluation;
2) Using multiple methods to help address complexity;
3) Triangulation and synthesis to build confidence in evaluation findings.
There is a Theory of Change (ToC) that forms the basis of the PDP interventions. However, a
narrative that explains the thinking, mechanisms and assumptions in this ToC has been lacking.
All evaluation methodologies in a non-experimental setting have as limitation that the counterfactual
cannot be established. It is, therefore, tempting to seek a confirmation of results of ‘what is there’,
i.e., the contribution of the PDP-programme. Or, to the contrary, focus on what the programme was
not able to contribute to, without formulating alternative theories of change. We aimed to contribute
to alternative theories of change by explicitly exploring alternative mechanisms to support product
development during our interviews and discussions. While we have done so, more detail in the
background of the PDP ToC would have enabled us to more explicitly address underlying
mechanisms and assumptions of the PDP III funding by looking for evidence to support or refute
these mechanisms and assumptions. Thus, we would have been able construct alternative theories
of change based on the Ministry’s thinking, rather than our own.
A further main limitation of the evaluation is posed by the limited time span that was available for
the evaluation. This means that the time window available for data collection was approximately five
weeks. This has restricted the number of methodologies to those that could be implemented. For
instance, due to the limited time window, it has not been possible to use methods like surveys, or
network analysis by which a broader selection of stakeholders could have been included and thus
potentially had provided a more diverse and complete picture that would have done justice to the
complex nature of the evaluation subject.
The restricted timespan also limited the possibilities to collect data to construct quantitative
indicators and verify data that seem contradictory.
The limit to the number of methodologies for data collection decreased the potential for triangulation
of findings. The validation workshop has been the main tool to manage this limitation, next to
grading of evidence while triangulating data from interviews and document review.
Another limitation of the current evaluation approach is the sampling strategy. We have
purposefully (non-random) sampled stakeholders who know about the PDP III funding by MoFA,
and/or are likely to be familiar with the work of one or more PDPs. We have taken care to have
representation of all stakeholder groups: the donor, PDPs, Funding Group, industry partners,
research partners and civil society partners. To get access to these individuals, we relied on the
support of MoFA, RVO and the PDPs. Support by stakeholders with the selection of documents and
individuals for key informant interviews is indispensable, but may lead to bias when critical reports
or individuals will not be included in this evaluation. We have managed this bias to some extent by
9

18

Mookherji S, Meck K. How Can We Better Evaluate Complex Global Health Initiatives? Reflections From the January 2014
Institute of Medicine Workshop. Global Health Science and Practice 2015;3(2):174-179.

Evaluation PDP III Fund 2015-2021

triangulation of data, and by compiling a list of interviewees that was larger than the actual need.
The evaluation team has decided on the final selection of interviewees, and has included
independent experts that were not suggested by either the MoFA or the PDPs.

Evaluation PDP III Fund 2015-2021

19

3

Findings

This chapter presents the main findings from the evaluation. It starts with a short overview in
section 3.1 of four evaluations that have been carried out in recent years. Section 3.2 focuses on
the evaluation questions that concern the six individual PDPs. As far as possible, general
conclusions are drawn for the group of PDPs. In section 3.3 the focus is on the evaluation
questions regarding the PDP III fund as a mechanism of MoFA to realise the objective, being the
development and availability of affordable, effective medicines, vaccines, diagnostics and
innovative products for neglected diseases and conditions. Each section starts with a text box with
the relevant evaluation question(s) from the ToR.

3.1

Review of the evidence from previous evaluations
To ensure a complete and efficient implementation of the evaluation, we have built on the analyses
made in previous evaluations. In this section the key findings of relevant previous evaluations are
summarised.
Review of the Product Development Partnerships Fund 2011-2014 (2014) 10
In 2014 Technopolis Group carried out a review of the Dutch Ministry of Foreign Affairs PDP Fund II
for a period of 2011-2014, covering: Aeras, DNDi, FIND, IAVI, IPM, Sabin and POW PDP. The
evaluation concluded that PDPs successfully progressed in their R&D pipelines and stimulated the
development of local research capacity.
A number of recommendations to PDPs were provided, specifically:
•

The need for more formal structures to promote mutual learning and information sharing, in
relation to such themes as advocacy and capacity building;

•

Potential reduction of costs of non-core activities by sharing resources and streamlining
operations resources (e.g., clinical trial sites, manufacturing facilities, logistics);

•

Targeting policy and decision makers with a clearer communication and advocacy strategy.

The PDP II Fund was recognized as an effective funding mechanism, enabling PDPs to carry out
activities that would not have been possible otherwise. However, with many products still being
under development, it was too early to conclude that the PDP II Fund had achieved its objectives.
MoFA was recognized as a valuable partner, especially for the forward-looking and flexible funding
approach, which also helped receiving additional funding from other donors. Several
recommendations were made to MoFA regarding the PDP II fund and future priorities, including:
(1) consider PDPs with not just direct linkages to SRHR, but also connections to the broader
international development agenda and the Dutch Top Sector policy;
(2) identify where in the R&D value chain Dutch funding would have the greatest added
value;
(3) consider a need for long-term commitment.

10

Technopolis Group (2014). Review of the Product Development Partnerships Fund 2011-2014. Final report to the
Dutch Ministry of Foreign Affairs

Evaluation PDP III Fund 2015-2021

21

Mid-term Review of PDP III Fund (2019)11
In 2019 ACT for Performance conducted the mid-term review of the PDP III Fund, covering the
2015-2017 funding period. The mid-term evaluation concluded that PDPs’ pipeline development
was progressing according to plan and PDPs continued building capacity in LMICs. As in the
previous evaluation, flexibility was identified as the main strength of the Dutch funding. PDP III
funding was seen as leveraging attention from the PDPs for access and gender issues. The
evaluation team drafted several recommendations for MoFA/RVO. For more information see
section 3.2.6).
Evaluation of the Product Development Partnerships (PDP) funding activities (2015) 12
In 2015 evaluation was carried out to inform the UK Department for International Development
(DFID) and the German Ministry for Education and Research (BMBF) on the added value of their
investment in PDPs. It included the assessment of DNDi, FIND and the European Vaccine Initiative
(EVI), in the period of 2009- 2013. The overall recommendations included:
(1) for the governments involved to continue public funding of PDPs with the long-term financing,
which should mostly be unrestricted or semi-restricted;
(2) for PDPs to seek the diversification of their funding base in order to have flexibility and
ability to set their own strategy, instead of being driven by requirements of a particular
dominant funder.
Product development partnerships Fund: Mid-term review (2020)13
The Department of Foreign Affairs and Trade (DFAT) of the Australian government is currently
funding MMV, TB Alliance, FIND and the Innovative Vector Control Consortium (IVCC), for the
period of 2018-2023. A mid-term review of Australian Government’s support for PDPs, published in
2020, concluded that the PDPs sufficiently progressed against their planned activities. The PDP
model was identified as representing value for money, yielding large-scale health and economic
impacts. Yet, it was recognized that more can be done to address gender equality. PDPs’
increasing role in product access was also noted, acknowledging that access barriers can be
addressed by leveraging relative strengths of multiple actors.
Australian government was recommended to:
(1) continue funding PDPs at the same level, maintaining core or equivalent funding flexibility;
(2) identify critical pathways for specific product access and actors and focus more on end-to-end
solutions with demand-driven access activities;
(3) help PDPs to strengthen their ability to address gender equality.

3.2

Findings regarding the six PDPs

3.2.1 Relevance of individual PDPs
Relevance & flexibility
o What is the relevance of the PDPs for the beneficiaries of the developed
products?

11
12

13

22

ACT for Performance (2019). Mid-term review of PDP III Fund.
Boulton, I.; Meredith, S.; Mertenskoetter, T.; Glaue, F. Evaluation of the Product Development Partnerships (PDP) funding
activities. (2015) 71 pp. Retrieved:
https://assets.publishing.service.gov.uk/media/57a08971ed915d622c00020d/Evaluation_of_the_PDP_Funding_Activities_
of_DFID_and_BMBF_final.pdf.
Retrieved: https://indopacifichealthsecurity.dfat.gov.au/sites/default/files/PDPFund_MidTerm_Review_Report_2020.pdf?v=1606429211.

Evaluation PDP III Fund 2015-2021

All PDPs are making products that are relevant for the end-users in LMICs. These products are
relevant in several ways:
•

Some diseases represent a considerable loss of (quality of) life on a global scale, as is the case
with HIV and AIDS, tuberculosis and malaria, while LMICs bear the brunt of the global burden of
these diseases;

•

Other diseases represent a relatively modest disease burden globally, but have crippling effects
in communities affected by these diseases, like Human African Trypanosomiasis (sleeping
sickness), Chagas Disease, or Mycetoma;

•

Affordability, and acceptability in terms of side-effects, are among the main criteria in drug
development by PDPs, making these products highly relevant for communities with little
purchasing power and sparse health care facilities.

Table 2 gives an overview of the burden of disease for the individual diseases involved.
Table 2

Burden of diseases addressed under the PDP III fund

PDP

Disease

Burden of disease14

DNDi

Chagas disease

Chagas disease was responsible for 9 490 deaths (95% UI 5
500–16 500) and 275 000 DALYs15 (184 000–459 000) in
2019. Chagas is endemic in Latin American countries, but
cases are also found in other locations due to migration.

DNDi

Human African

The global burden of Human African trypanosomiasis (HAT)

Trypanosomiasis (HAT/

in 2019 was 82 600 DALYs (95% UI 37 600–156 000) and

sleeping sickness)

1360 deaths (95% UI 609–2580), a 98% decrease in deaths
since 1990, reflecting efforts to eliminate transmission and
improve case detection. Selected countries in Central Africa
(Democratic Republic of Congo, Central African Republic)
are among the most affected by HAT.

DNDi

Leishmaniasis (Visceral

Leishmaniasis was responsible for 5 710 deaths (95% UI

Leishmaniasis/VL, black fever /

1690–18 700) and 697 000 DALYs (375 000–1 620 000) in

kala azar; Cutaneous

2019. The main affected world regions are North Africa and

Leishmaniasis, tropical sore/CL;

the Middle East, Sub-Sahara Africa and Latin America.

post-kala azar dermal
lesions/PKDL).
DNDi

Mycetoma

The global burden of mycetoma is unknown. It is endemic in
tropical and subtropical areas in the so called 'Mycetoma
belt', which includes the Bolivarian Republic of Venezuela,
Chad, Ethiopia, India, Mauritania, Mexico, Senegal, Somalia,
Sudan, Thailand, and Yemen.16

FIND

COVID-19

To date, approximately 247 million people have had COVID19 since the outbreak of the pandemic, COVID-19 caused 5
million deaths world-wide. Among the or geographical entities
win the top-10 of highest mortality rate is only one with highincome: Taiwan. Yemen, Peru and Sudan are in the top 3 by
death rate.17

14

15

The Lancet. Global Burden of Disease. GBD cause and risk summaries. https://www.thelancet.com/gbd/summaries
Accessed on 26 October, 2021.
One DALY represents the loss of the equivalent of one year of full health. DALYs for a disease or health condition are the
sum of the years of life lost to due to premature mortality (YLLs) and the years lived with a disability (YLDs) due to
prevalent cases of the disease or health condition in a population. https://www.who.int/data/gho/indicator-metadataregistry/imr-details/158 Accessed 8 November, 2021

16

https://www.who.int/news-room/fact-sheets/detail/mycetoma Accessed 26 October, 2021.

17

https://coronavirus.jhu.edu/ Johns Hopkins University Coronavirus Resource Center. Accessed 1 November, 2021.

Evaluation PDP III Fund 2015-2021

23

PDP

Disease

Burden of disease14

FIND

Fever

No estimate available. However, FINDs diagnostics of fever
aim to distinguish between viral infections and bacterial
infections. As an example, it would be important to
distinguish between a viral and bacterial cause lower
respiratory tract infections, such as pneumonia. In 2019,
there were 489 million new cases of lower respiratory tract
infections, causing 2.49 million deaths and 97.2 million
DALYs. Lower respiratory tract infection is the number 5
leading cause of death in LMICs. The largest disease burden
occurs in sub-Sahara Africa and in countries in South and
Central Asia. Latin America also contributes substantially to
the burden of lower respiratory tract infections.

FIND

HCV (Hepatitis C)

Globally, 113 million people are estimated to be infected with
Hepatitis C in 2019. 542 000 have died of hepatitis C related
causes that same year. Hepatitis C resulted in 15.3 million
(95% UI 13.3–17.5) global DALYs in 2019 and 0.6% (0.5–
0.7) of total global DALYs. Acute hepatitis, cirrhosis, and liver
cancer contributed 1.7% (0.9–2.5), 79.5% (76.1–82.7), and
18.9% (15.9–22.2) to DALYs due to hepatitis C, respectively.

FIND,

Tuberculosis

Globally in 2019, tuberculosis was one of the leading causes

TB

of death by a single pathogen. Among HIV-negative

Alliance

individuals, the number of deaths was 1.18 million (95% UI
1.08–1.29) and the number of new cases of tuberculosis was
8.50 million (7.45–9.73). 1.8 billion people are estimated to
be exposed to tuberculosis. Among the regions with the
highest burden are sub-Sahara Africa, South and South-East
Asia, and Eastern Europe and Central Asia. Drug-resistant
tuberculosis is an increasing problem in many of these
countries.

IAVI,

HIV

IPM

Globally in 2019, the number of people living with HIV was
36.8 million. HIV-related deaths were 864,000 (95% UI
786,000–996,000) and the number of new HIV infections was
1·99 million (1·76–2·26). People living with HIV have an
increasing susceptibility to tuberculosis, and visceral
leishmaniasis. The majority of burden was seen in subSaharan Africa, which had 74.0% (71.4–76.9) of global HIVrelated deaths in 2019. Numbers of new infections are still
rising in Eastern Europe and Central Asia, as well in the
Middle East and North Africa. Populations most at risk are
adolescent girls and young women (highest burden: subSahara Africa), men who have sex with men, and
transgender women (highest burden: Latin America), sex
workers (highest burden: South East Asia), people who inject
drugs and incarcerated people (highest burden: Eastern
Europe and Central Asia).

24

Evaluation PDP III Fund 2015-2021

PDP

Disease

Burden of disease14

MMV,

Malaria

In 2019, there were 231 million new cases of malaria. Malaria

FIND

was responsible for 643 000 deaths (95% UI 302 000–1 150
000) in 2019. 356 000 deaths (169 000–626 000) occurred in
children under 5 years, comprising 7.1% (4.0–10.4) of total
deaths in that age group. These numbers comprise infection
by the two most prevalent types of malaria parasites
(Plasmodium falciparum and Plasmodium vivax).
Endemic countries comprise most sub-Sahara African
countries, as well as countries in South and South-East Asia.

Source: The Lancet

The six PDPs have developed several products that are being used in the diagnosis, prevention
and/or cure of these diseases or to improve sexual and reproductive health. This implies that
patients are actually being reached. An overview of volume of products distribution is presented in
Section 3.2.2.
3.2.2 Effectiveness of individual PDP’s
Effectiveness
o What is the progress of the individual PDPs in this period in terms of pipeline
development?
o How does this progress compare with the objectives set out in the original grant
proposals to the Dutch Government?
o To what extent has the COVID-19 pandemic been an enabling or hindering factor
in the achievements of results of the PDPs?
o How do the results/activities so far contribute to increased access for the target
group and accelerating delivery of effective products to people most in need? Do
all beneficiaries benefit equally from the increases access to products and
services?
o What unintended effects/results/outcomes (positive and negative) are being
achieved by the PDPs besides the development of the product pipeline (gender
equality, jobs created, people trained, etc.).

Pipeline development
Table 3 presents the information on the achievements of the PDPs in terms of pipeline
development during 2015-2021; the full overview can be found in Annex G. The table shows that
five PDPs together saw 30 products progress at least one phase in the development process.
Some 375 new products are reported to be in the pipeline.18 Some PDPs, such as DNDi, even
managed to develop 23 new chemical entities (NCEs), of which now one has led to a marketed
drug (fexinidazole),19 which, according to one PDP representative, and one external publication20
was initially considered outside the scope and capacities of a PDP.
Table 3 also presents the milestones in regulatory approval that are likely to have an impact on
access. Most PDPs had a major breakthrough in 2015-2021 in that (one or more of) their products
received a positive scientific opinion or approval from EMA, FDA, or an LMIC regulatory authority,
and/or received WHO pre-qualification or were included in the list of essential medicines of the
WHO.

18
19
20

Netherlands Enterprise Agency, The impact of the Product Development Partnerships. PDP III Programme 2015-2021.
DNDi (2021). Summary Report PDPIII 2015-2020.
Grace C. (2010). Product Development Partnerships (PDPs): Lessons from PDPs established to develop new health
technologies for neglected diseases. DFID human development resource centre (hdrc)

Evaluation PDP III Fund 2015-2021

25

Although PDPs have made substantial progress in terms of pipeline development in 2015-2021,
their reports on the achievements in 2015-2020 show that not in all cases all activities have been
carried out according to the plans that they had submitted to MoFA in 2015. However, the reports
also show that the adjustments made and the results achieved are generally in line with the original
objectives and goals.
Table 3

Summary of pipeline development under PDP III: number of substances that moved at least
one phase in the development process and regulatory milestones

PDP

No.

Diseases

Regulatory milestones21

DNDi

7

HAT: improved combination

2018: fexinidazole receives a positive

treatment

opinion from EMA.

VL, CL: improved combination

2019: WHO includes fexinidazole as first-

treatment

line treatment into the new WHO-HAT

Chagas disease: treatment for

treatment guidelines, and adds fexinidazole

children

to the 2019 WHO-Essential Medicines List.
2020: Democratic Republic of Congo
(2018), Guinea, Central African Republic,
Chad, Angola, Equatorial Guinea and
Gabon approved fexinidazole for the
treatment of HAT and updated treatment
guidelines.
2021 Ravidasvir, a new drug for treatment
of Hepatitis C, receives conditional
registration from the Malaysian
government.

FIND

11

Tuberculosis: improved tests, tests

2017: TB Ultra test recommended by WHO

for drug resistant TB, tests for TB in

2020: European Commission (CE) approval

patients with HIV

for Xpert XDR and Omni for TB and MDR-

Malaria: rapid diagnostic test for a

TB; WHO approves two COVID-19 tests

specific form of malaria (P. vivax);

under the Emergency Use Listing

test to distinguish Malaria and other

Procedure (EUL): Panbio, Abbott Rapid

fever

Diagnostics and STANDARD Q, SD

Fever: biomarker-based test

Biosensor Inc.

Hepatitis C: rapid test
COVID-19: rapid test
IAVI

5

HIV: vaccine candidates; antibody

(No products at the marketing stage)

products
IPM

1

HIV: dapivirine vaginal ring (DVR)

2020: EMA Issues a Positive Opinion for

as HIV prevention for women

the monthly DVR.
2021: WHO Prequalifies the DVR: and
received WHO recommendation for use in
addition, WHO adds the DVR to the WHO
clinical guidelines as a choice for women at
substantial risk for HIV infection.

MMV

21

26

4

Malaria: treatments adapted to

The updated WHO Guidelines for Malaria

children; prevention of relapse of P.

(February 2021) confirm that pyronaridine-

As reported by the PDPs in their Annual PDP Funder Reports. List is non-exhaustive, as it focuses on products developed
under PDP III funding.

Evaluation PDP III Fund 2015-2021

PDP

No.

Diseases

Regulatory milestones21

vivax malaria; treatment of severe

artesunate (Pyramax®) is considered a

malaria before referral

safe and efficacious combination therapy
for treatment of uncomplicated malaria in all
malaria-endemic areas.
2020: Adult tablet formulation registered in
29 countries; paediatric granule formulation
registered in 19 countries,
Pyronaridine- artesunate Listed in the
national treatment guidelines of Cameroon,
Côte d’Ivoire, Guinea, Niger, Nigeria and
Republic of Congo.
Artesunate rectal capsules for severe
malaria in children > 6 months old are WHO
prequalified and registered in 17 countries.
2020: marketing authorization application
(MAA) approved for tafenoquine in Peru,
with regulatory dossiers under review in six
additional P. vivax-endemic countries.

TB Alliance

2

Multidrug-resistant tuberculosis: new

Approval of pretomanid (Pa) in a

and shorter treatment; new target

combination regimen (BPaL) with

substance directed against drug-

bedaquiline (B) and linezolid (L) for the

resistant TB.

treatment of people with highly drugresistant forms of TB (DR-TB) by the U.S.
FDA, the EMA, and the Drug Controller
General of India, as well as its incorporation
into WHO guidelines.

Source: PDP annual funder reports, various years

Impact of COVID-19
Relevance & flexibility
o To what extent have the PDPs been able to adjust to changing contexts, including
the COVID-19 pandemic?

The COVID-19 pandemic inevitably meant a change in the way the PDPs conduct their operations.
The most direct impacts were due the restrictions in travelling and physical contacts. These
restrictions have affected the development process as they affected all aspects of the work of
PDPs, including clinical trials. For instance, DNDi reported delays in recruiting patients for a
Leishmaniasis trial in Uganda,22 and this example is consistent with reports from other PDP staff
and PDP research affiliates. Another impact has been on the availability of medical supplies due to
the high demand that suppliers were facing. All in all, the COVID-19 pandemic resulted in
temporary interruptions in the work and projects of the PDPs.
PDPs have reacted to these restrictions in various ways and have been successful in minimizing
the impact of the restrictions on the activities and results. For instance, much greater use has been
made of digital tools and platforms for tracking the situation of patients. Meetings with research

22

DNDi. Annual Report, 2020.

Evaluation PDP III Fund 2015-2021

27

partners were held digitally.23 According to a recent report by RVO, most of the activities are
running and back on track.24 This was confirmed in the interviews with PDP representatives.
COVID-19 has caused Ministries of Health in LMICs to focus on the COVID-19 response, at the
expense of poverty-related diseases. In addition, COVID-19 has had a huge impact in terms of
shifting the attention from donor funding away from poverty-related diseases, as has happened with
funding by the UK government (FCDO).25 Some PDPs already report feeling the impact of this
development. In interviews, PDP representatives confirmed that the impact of the pandemic on
donor policies and funding is far more important than the impact on operations.
On the other hand, COVID-19 has created more attention for product development (particularly
vaccines) and thus has proven the value of the research and development structures developed by
PDPs in LMICs. This R&D infrastructure for instance enabled PDPs to carry out clinical trials in
LMICs for COVID-19 vaccines. As the RVO report summarizes: “For example, FIND invested in
possibilities for COVID-19 testing, MMV focused on vulnerable children that are affected and DNDi
shared their knowledge and network regarding chemical entities against infectious diseases by
creating the ANTICOV research platform in 13 African countries. And IAVI leveraged its core
technology platforms and expertise in mounting a COVID-19 program to develop antibodies for
SARS-CoV2 (currently in the preclinical stage).”26 These and other achievements were confirmed in
the interviews with staff of the individual PDPs. In Chapter 5 more details can be found on the
impact of COVID-19 on operations of each PDP.
Increased access
Distribution of products developed by PDPs
Not only have PDPs brought forward products in the development process, most of them have
been able to register newly developed with authorities in LMICs, get them included in treatment
guidelines and/or had them included on the WHO list of essential medicines or WHO guidelines.
This has been the start of sales of these products. As the products are produced and marketed by
commercial partners, sales data are confidential. There are estimates that 2.4 billion people around
the world have benefitted from the work done by the PDPs.27 At the request of the evaluation team,
PDPs have provided information on sales of products in recent years. The following table
summarizes this information, more details can be found in the PDP sheets (see chapter 5).
Table 4

Market distribution of products developed by PDPs

PDP

Product (group)

Number distributed

First year

DNDi

ASAQ for malaria

over 500 million treatments

2003

ASMQ for malaria

over 1.3 million treatments

2008

NECT for HAT

100% of all stage-2 patients
are now treated with NECT

Paediatric benznidazole for Chagas disease

11,457 children treated

HIV-TB Super-booster therapy

Guidelines improve
concurrent HIV and TB
treatment for 1 million
children

Fexinidazole for HAT
23
24
25

26
27

28

134 patients treated

2020

E.g. as IAVI reported in the PDP Funders Report 2020
Netherlands Enterprise Agency, The impact of the Product Development Partnerships, PDP III Programme, 2021.
Davies, L. (2021). ‘A very cruel exit’: UK’s aid cuts risk rapid return of treatable diseases. The Guardian, 13 September
202
IAVI Funder Report., p. 27.
Netherlands Enterprise Agency, The impact of the Product Development Partnerships, PDP III Programme, 2021.

Evaluation PDP III Fund 2015-2021

PDP

Product (group)

FIND

Over 95 million products to LMICs

IAVI

IAVI does not yet have products in the

Number distributed

First year
No details

implementation stage
IPM

The monthly dapivirine ring is now in the process
of approval in several African countries. Data on
the distribution of the ring are not yet available.

MMV

TB

3 day cure malaria

Approximately 3 billion

2008/2019

Seasonal malaria chemoprevention:

355 million

2013

Pre-referal in severe malaria

3.8 million rectocaps

2017

Severe malaria

175 million vials

2010/18

RH 75/50 2 FDC DT

1,021,226 treatment courses

RH 13 FDC DT

1,011,051 treatment courses

Alliance
Source: Information provided to the evaluation team by the PDPs (for more details see Chapter 5 of this report)

Actions aimed at increasing accessibility
Besides pipeline development, increasing the accessibility of the products for the patients in need is
an important task for the PDPs. Given that more and more products become available now, even
more efforts will be required in the next few years to optimise accessibility of medicinal products in
LMICs.
From the interviews and documentation provided, evaluators conclude that PDPs do considerable
efforts to secure access, and equity in access, for instance for women and children, by taking into
account suitability of products for use during pregnancy and lactation, and acceptability or
palatability for young children. All PDPs, albeit to varying degrees, now apply the end-to-end
approach in product development in which securing accessibility already starts in the early, basic
research stages.
For instance, DNDi includes pricing in the Target Product Profiles (TPPs), as well as access for
women and children in terms of suitability for use in pregnancy, and palatability of the formulation. .
Also, for FIND an access strategy for any specific intervention is a consideration in the earliest
phases of project planning, which includes in-country delivery and uptake. IAVI aims to ensure
access to a licensed AIDS vaccine for those individuals and communities who are most vulnerable
and at greatest risk of HIV infection. IPM has an access advisory committee to provide strategic
guidance to help ensure the dapivirine vaginal ring’s successful introduction and uptake in subSaharan Africa, where women face the greatest risk for HIV. IPM sees engagement with the
community as crucial to realise access to IPM’s products. MMV’s access strategy is built around
supporting introduction of new products (including messaging, education, and mobilising
advocates), enhancing reach of marketed products, gathering marketing intelligence and informing
R&D such that unmet needs are addressed. TB Alliance worked on multiple fronts to improve
access of tuberculosis treatments. It devoted significant resources to facilitate and ensure global
adaptation, availability, and affordability of the bedaquiline(B), pretomanid (Pa) and linezolid (L)
(BPaL) treatment regimen. It has also made a considerable contribution to addressing a gap in the
paediatric TB market.
Intellectual property
All PDPs have particular Intellectual Property (IP) policies that ensure non-exclusive licensing, price
limits or other provisions that ensure accessibility and affordability of their products.

Evaluation PDP III Fund 2015-2021

29

DNDi has an intellectual property policy.28 DNDi aims to secure, non-exclusive, sub-licensable,
royalty-free licenses to ensure sustainable manufacturing and distribution at the lowest possible
price in endemic countries.
FIND has a Global Access Strategy.29 FIND considers IP is essential to ensure that the cost
structure of new products befits LMICs and is in line with the objective to support affordable
products, as well as to maximize freedom for others to use the outputs of our development projects.
IP discussions may cover patent-protected intangibles, copyrights, trademark, trade secrets and
data rights, for instance.
IAVI’s IP management policies and practices are designed to share the results of its research
broadly to help enable other researchers in the field, secure IP rights for vaccine candidates in its
portfolio to ensure freedom to operate and incentivise collaboration with future industry partners
and to ensure ultimate global and equitable access to an HIV/AIDS vaccine.
IPM has secured intellectual property rights to a portfolio of compounds that IPM is working on to
develop into various microbicide formulations. IPM is the owner of the intellectual property
associated with dapivirine vaginal ring (DVR). Therefore, it has freedom to make changes to
manufacturing operations and logistics as needed to achieve the lowest possible cost while
maintaining regulatory and quality standards. Generic manufacturers may also be explored for
markets outside of the initial target geographical areas.
Management of IP is a key driver of the MMV partnership model. Negotiation of IP value attracts
and enables successful collaboration agreements with pharmaceutical partners and researchers,
‘de-risking’ the venture and guarding against misuse of innovation. For compounds with a novel
mechanism of action, MMV or its partners will often seek patent protection in case the compound
has application for a profitable indication outside malaria, and to provide control over the quality of
manufacture. In turn, there is an understanding that pharmaceutical partners will operate on a ‘no
profit, no loss’, or low-margin “cost-plus” basis, and that patent protection will not extend to malariaendemic countries (except for India, China and Brazil).
TB Alliance holds the IP to pretomanid, and has licensed its production to pharmaceutical company
Mylan. According to its website TB Alliance is committed to ensure access though wide adoption,
ensure that products are available and reach those in need, and are affordable to those with TB
and their health systems.
Criticism of efforts made by PDPs
Some publications, and at least one interviewee, express concerns as to whether PDPs do enough
to ensure affordable prices, or have criticised a lack of transparency about licensing.30 31 32 Others
have raised the question to what extent products developed by PDPs are accessible in very

28

29

30

31

32

30

DNDi Intellectual Property Policy
https://dndi.org/wp-content/uploads/2018/03/DNDi_Intellectual_Property_Policy.pdf
Maximizing the health impact of diagnostic solutions. https://www.finddx.org/wp-content/uploads/2018/02/FIND_AccessStrategy-Web.pdf Accessed 8 November, 2018.
MSF Access Campaign. Pretomanid - third new TB drug in over half a century must be affordable.
https://msfaccess.org/pretomanid-third-new-tb-drug-over-half-century-must-be-affordable
Muñoz, V., et al. (2015). "Can medical products be developed on a non-profit basis? Exploring product development
partnerships for neglected diseases." Science and Public Policy 42(3): 315-338.
Pratt, B. and B. Loff (2013). "Linking Research to Global Health Equity: The Contribution of Product Development
Partnerships to Access to Medicines and Research Capacity Building." American Journal of Public Health 103(11): 19681978

Evaluation PDP III Fund 2015-2021

privatised health care systems, where private services are excluded from concessional pricing
schemes, but that are nonetheless used by many patients from poor communities.33 34
Factors hindering access
Despite their actions to ensure access, PDPs report that there are various factors that hinder equity
in access. Some of these are beyond their reach, such as the organisation of the health care
system, national government policies (or a change in government official), the availability of health
care centres and health workers in remote areas, logistical challenges or the availability of other
essential infrastructure.
While some PDPs increasingly improve access for specific groups (in particular women of
childbearing age, and children), we do not see this effort being done systematically across all
PDPs. Therefore, a systematic approach to accessibility of products for women and children is most
desirable; a cross-cutting standard for PDPs may be helpful in achieving such a systematic
approach and could further enhance the relevance of the products entering and leaving the pipeline
of the PDPs.
Unintended effects
PDPs rarely report unintended effects. The identified effects were very mixed. Among positive
unintended effects on the level of individuals that have been mentioned are job creation, and more
knowledge of trial participants about their own body and HIV prevention, resulting in empowerment
and behaviour change. On an organisational level, the fact that PDPs emphasise more and more
the importance of access to their products from the beginning of the development process, has led
to policy change with pharmaceutical companies to include access in their product development as
well.35 Glaxo, Sanofi and Novartis were mentioned in interviews as big pharmaceutical companies
that are now planning systematically about access to their products in an early phase of
development. Another unintended influence of PDPs on big pharmaceutical companies is the
transparency about the costs of drug development e.g., from DNDi, that according to one of the
interviewees, brought about a discussion about the best way of financing research and
development with the pharmaceutical industry, and also opened a dialogue on how to spur
innovation in other ways than charging high prices for newly developed drugs.
Negative unintended consequences mentioned during interviews were, that in a busy development
landscape PDPs sometimes had a competitive rather than collaborative relationships with particular
(research) partners. Interviewees mentioned uncertainty of funding as a factor contributing to
attrition and turnover of (sometimes very experienced) PDP staff, as well as staff at clinical
research centres.
3.2.3 Efficiency of PDPs
Over the years the PDP model has proven to be a cost-effective way to develop medicinal products
for poverty-related diseases and conditions in relation to SRH. Asked about cost-effectiveness, one
PDP representative stated that their cost-effectiveness was better than that of the commercial
pharmaceutical industry, which was backed up by one of the independent experts interviewed as
well as by a peer-reviewed report by the Lancet Commission on Essential Medicines Policies. This
report states that industry-supported estimates set the average cost for medicines developed at
USD 2.5 billion per new product, whereas DNDi estimates the development of a new chemical

33
34

35

Pratt et al., 2013
Puri, L., et al. (2016). "Xpert MTB/RIF for tuberculosis testing: access and price in highly privatised health markets." The
Lancet Global Health 4(2): e94-e95.
Access to Medicines Foundation. Access to Medicines Index 2021.

Evaluation PDP III Fund 2015-2021

31

entity to cost € 100-150 million, including the costs of failure,36 and the costs of improving a
treatment at € 10-40 million.37
The six PDPs report on the breakdown of their expenditures in their annual reports to funders.
Generally these reports show that the vast majority of expenditures is related to research and
development and accessibility. Management generally takes 8 to 10% of the total expenditures. 38
3.2.4 Coherence of PDP’s
Coherence
o How and to what extent are the PDPs engaging with key external players and
stakeholders and what is their specific added value?
Coherence is generally understood as the compatibility of the intervention with other interventions
in a country, sector or institution. Focus in this section is on external coherence, which considers
the consistency of the intervention with other actors’ interventions in the same context. 39 Internal
coherence, the consistency of PDPs with Dutch policies and standards, will be dealt with in Chapter
4 of this report.
We operationalise the external coherence of PDPs as how PDPs utilise their (many) partnerships.
PDPs have 70 to nearly 500 partnerships (see also table 6). All of them are engaged with donors,
research institutions (from basic research to applied research), commercial companies, regulatory
authorities, WHO, Ministries of Health, health professionals and community organisations. They are
the hub that connects a vast spectrum of information to serve the entire chain of development of
health products for LMICs: from identification of lead substances to ensuring access and availability
in communities. Some PDPs and external researchers see this ‘spider in the web model’ as their
very essence and added value as ‘system integrators’40 over other research organisations or
product developers, which is very well compatible with the OECD notion of external coherence.
PDPs sometimes also partner with each other, as is the case of FIND working closely with DNDi,
TB Alliance and MMV to provide companion diagnostics for the introduction of new treatment
regimens as well as advocating for better tools for LMICs. MMV has also collaborated with DNDi
and taken several antimalarials from DNDi in its portfolio. These are partnerships directly related to
the development of particular products for particular diseases. PDPs do not report broader
collaboration or partnerships among each other, e.g., in coordination of clinical trial capacity,
sharing experience with regulatory approvals, or setting standards in the field of not-for-profit
product development.

36
37
38
39

40

32

Wirtz, V. J., et al. (2017). Essential medicines for universal health coverage. The Lancet 389(10067): 453.
DNDi (2015). PDP Annual Funder Report.
Funders reports of the PDPs, various years.
OECD DAC. Evaluation Criteria.
https://www.oecd.org/dac/evaluation/daccriteriaforevaluatingdevelopmentassistance.htm#coherence-block Accessed 8
November, 2021.
Muñoz, V., et al. (2015). "Can medical products be developed on a non-profit basis? Exploring product development
partnerships for neglected diseases." Science and Public Policy 42(3): 315-338.

Evaluation PDP III Fund 2015-2021

3.2.5 Sustainability of individual PDP’s
Sustainability
o What is the added value of and dependency on Dutch funding in terms of
sustainability of results and financial sustainability of the individual PDPs? What
other donors are supporting the PDP’s?
o What other stakeholders have joined the PDP Funders Group – an informal
network of donors of which the Dutch MoFA is an active member – during the
period the PDPs have received support from the Dutch MoFA?
In applying for funding from the PDP III Fund, the PDPs have put forward proposals. These clearly
describe for what activities financing is requested and what outcomes are to be expected. There is
variation between the PDPs in terms of the part of total activities for which financing is sought, and
the level of co-financing requested for those activities. In general terms, the co-financing rate
ranges from 10-20% in case a major part of the activities of the PDP are put forward for cofinancing, to 50-90% in case the co-financing relates to a smaller part of the activities of the PDP.41
The Dutch co-financing thus has a substantial role in the activities put forward for co-financing.
When related to the total expenditures of the PDPs in the years 2016-2020, the Dutch funding
under PDP III was responsible for approximately 3% in the case of MMV, to up to 10% in the case
of IPM; for the four other PDPs this share was 5 to 6.5 %.42
Under the PDP III Fund MoFA provides core financing to the PDPs. This characteristic is broadly
appreciated by the PDPs for its flexibility. This was already found in previous evaluations of the
PDP Fund and was confirmed by the interviews for this evaluation. The core financing in principle
makes it easier for PDPs to complete the financing plan. As many donors use project financing this
leaves some activities potentially uncovered that are deemed necessary for the portfolio approach
of the PDPs. Core funding can then be used to fill in the gaps.
The PDPs do not see the conditions as valid under the financing as a problem to use the funding.
They all complied with at least one of the priority themes described in the administrative rules, i.e.
products for SRHR, products for neglected tropical diseases or products for new or recurring
epidemics.
All PDPs have a large portfolio of donors. Although at overall level (all PDPs together) the top 12
financing organisations are relatively stable, at the level of individual PDPs shifts occur in the donor
financing regularly. PDPs report annually on the status of the (newly attracted) donor funding.
These report show a broad range of donors, with varying levels of financing. For instance the DNDi
Funders Report for 2020 shows a list of 37 grants that were already secured before 2020 and
grants secured in 2020. Grant sizes for DNDi range from GBP 40.000 up to GBP 64 million.43 The
Dutch grant under PDP III is among the larger individual grants for DNDi. The lists of grants of other
PDPs show a similar picture.
Most of the PDPs are wholly or predominantly dependent on donor funding. In the case of FIND the
revenue basis was expanded substantially due to the revenues generated by the work carried out in
relation to the COVID-19 pandemic. However, in all other cases PDPs continuously have to acquire
new funding. The long term financial sustainability is therefore seen as a weakness (see also
section 3.3.3). For instance, in the past IPM has temporarily halted development of a product due to
insufficient funding (see section 5.4).
41
42

43

Based on the information contained in the proposals submitted by the PDPs to MoFA in 2015.
Calculated from the information based in the annual PDP Funder Reports submitted by the PDPs and the actual cofinancing received.
See: DNDi, PDP Annual Funder Report 2020.

Evaluation PDP III Fund 2015-2021

33

3.2.6 Mid-Term Evaluation
Relevance & flexibility
o To what extent follow-up was given to the recommendations made by the MidTerm Evaluation of March 2019.
In the Mid-Term evaluation of 2019 various recommendations were drafted aimed at various
parties: PDPs, Funders Group and the Dutch government (see text box). It is noted that the
Steering Committee of this Mid-Term Evaluation did not endorse all recommendations.44 The
committee in particular expressed doubts on recommendations I (stronger focus) and IV
(earmarking of funds for few specific products) and questioned details of recommendation VIII (in
particular regarding the levies on products and services).
Main recommendations
i.

The evaluation team recommends the PDPs to consider for the future a stronger focus on a
fewer products and diagnostic tools that have a irrefutable potential to service vulnerable
populations, which may strengthen even further the effectiveness of PDP III funding;

ii.

Continued work could be done to ensure reporting is streamlined and coordination is reinforced;

iii.

The recommendations from PDP II, as well from this mid-term review and any future evaluation,
may be provided to the grantees with a strong advice to apply these in their work, and with a
monitoring mechanism (e.g. mandatory section in progress reports);

iv.

The evaluation team recommends MoFA to continue its funding to the PDPs while strengthening
the earmarking of its funds for a few specific products relevant for SRHR and vulnerable
populations. A notional earmarking is suggested, keeping the funding flexible (not earmarked on
expenditures but on process results, hence providing flexibility in re-allocation of funds), while
agreeing on targets related to the products;

v.

MoFA could develop a communication strategy, in close collaboration with the grantees, to better
inform the Dutch public and Parliament on PDP III and its concrete results;

vi.

Forward looking, the evaluation team recommends MoFA to strengthen the relevance of PDP III
(or a possible PDP IV) by paying more attention to neglected tropical diseases (NTDs), relatively
underfunded compared to malaria, TB, and HIV;

vii.

MoFA could start discussions with like-minded donors to develop a common (pooled) fund that
finances the next phase of a PDP fund. A common fund will reduce the transaction costs for the
grantees;

viii.

The PDPs and the Funder’s Group could start a joint study and initiate reflections on a
sustainable funding mechanism that is less dependent on aid flows, such as an air levy system, a
small tax on drugs and vaccines, or an additional levy on unhealthy industries, such as tobacco
and soft drinks industries.
Source: ACT for Performance, 2019, p X (summarised by Ecorys).

In our interviews it appeared that most, if not all, PDP representatives and government officials
were not aware of these recommendations. The evaluators also did not find evidence that anyone
of the recommendations had been implemented.
Nevertheless, it is acknowledged that some of the recommendations touch upon issues that are still
relevant, such as those with respect to communication strategy of the Dutch government (V) and
exploring ways to improve financial sustainability (VII, VIII).

44

34

See: Management response to the Mid-Term Review of the PDP III Fund.

Evaluation PDP III Fund 2015-2021

3.3

The funding mechanism

3.3.1 Introduction
The PDP III Fund
With the PDP III Fund the Dutch government made EUR 86.3 million available for the period 20152020 to PDPs that adhered to the criteria of the fund. PDPs could submit proposals for co-financing
for the whole period. In 2020 an additional EUR 17.3 million was made available for 2021. By this
the time span of the funding was effectively prolonged up to 31 December 2021.
Proposals from PDPs for financing were in principle eligible for funding if they met the following
criteria:
•

the products to be developed are specifically meant for use in countries that are included in the
List of Recipients of Official Development Assistance;

•

the activities proposed for financing could relate to any phase of the project development cycle;

•

the subsidy was to be used for the development of at least one of the following types of
products:
-

Promotion of sexual and reproductive health;

-

Treatment, prevention and diagnostics of poverty-related diseases;

-

Treatment, prevention and diagnostics of potentially new and recurring epidemics.

Theory of change
The overall objective of the PDP III fund is defined as: “to promote the development of medicines,
vaccines, diagnostics and other devices to prevent, diagnose and treat diseases and conditions
related to poverty and SRHR more quickly, cheaply, effectively and simply”. 45
By promoting the development of such medicinal products (main objective), the PDP III fund aims
to realise the following (additional) objectives46:
A.

Increased investment in R&D and innovation in these areas by other donors (public and
private);

B.

Increased interest in and/or contributions from the private sector towards product development
for poverty-related diseases and conditions related to SRHR;

C.

Increased involvement and active participation of developing countries in product development
partnerships;

D.

Increased R&D capacity in the target countries regarding the research and production of
medicines, vaccines and diagnostics for diseases and conditions related to poverty and SRHR;

E.

More investment in and awareness of diseases and conditions related to poverty and SRHR,
as well as a coherent policy approach towards this topic.

In defining these main and additional objectives, the Terms of Reference deviates somewhat from
the administrative rules, as published in the Staatscourant in 2015, as well as the Theory of Change
(ToC) that accompanies the ToR (see Figure 1).

45
46

As stated in the Annexe to the publication of the grant in the Staatscourant.
See Annexe to: Order of the Minister for Foreign Trade and Development Cooperation of 20 April 2015, no. MinBuza2015.BZ-2015.198527, laying down administrative rules and a ceiling for grants awarded under the Ministry of Foreign
Affairs Grant Regulations 2006 (Product Development Partnerships III Fund).

Evaluation PDP III Fund 2015-2021

35

Figure 1

Theory of Change of the PDP III Fund

Source: MoFA.

In the administrative rules the above-described objectives (main; A-E) are called results. A
distinction is made between primary results (pipeline development; A-C) and secondary results (D
and E). In the ToC these results areas are divided over outputs (D and E; considered outputs of the
activities of the PDPs and PDP III Fund respectively) and outcomes (pipeline development; A to C).
In addition, it is noted that the administrative rules define two other results, which are neither
mentioned in the ToR nor in the ToC, namely:47
•

Primary result: Strengthened image of the Netherlands as a country with expertise in povertyrelated diseases and conditions;

•

Secondary result: Increased access for Dutch businesses and knowledge institutes to
international public and private funding for product development in the areas of SRHR and/or
poverty-related diseases.

For this evaluation a slightly revised ToC has been drafted. The core of the ToC is that the activities
of the PDPs that are co-financed are being seen as the Activities, which lead to progress in the
R&D product pipeline (output). In being able to carry out their activities PDPs use additional funds
from other donors (A), private parties (B) and target countries (C), and develop and use R&D
capacity in target countries (D). Next to pipeline development the PDPs develop activities which
increase accessibility of the developed medicinal products, among others by raising awareness (E).
In this respect pipeline development (objective 1) and increased awareness (objective 2E) are seen
as outputs of the work of PDP’s whereas results relating to A-D are seen as direct outcomes.
In other words, our interpretation of the Terms of Reference and the Theory of Change is that the
main objective of the PDP III Fund is to stimulate the development of medicinal products by
financing activities of PDPs in terms of pipeline development and in terms of advocacy. These are

47

36

Ibid.

Evaluation PDP III Fund 2015-2021

the two main outputs of the funding of the PDPs. In realising these outputs progress may be made
in realising objectives A to D as described above, which should be seen as expected outcomes of
the financing of the PDP’s during 2015-2021.
The expected impact of the PDP III Fund is that the greater availability of suitable products and
treatments and the increased awareness result in an increase in their accessibility for target groups,
thereby having an impact on the number of people suffering from diseases such as malaria,
HIV/AIDS and tuberculosis. This slightly revised ToC is shown in Annex I.
The following sections should be read with this conclusion in mind. It for instance means that the
expected results and impacts are to be rather seen as a result of the financed activities of PDPs
and not so much as a direct consequence of the PDP III Fund itself as the Theory of Change
suggests.
3.3.2 Relevance
Relevance
o What is the relevance of the PDPs regarding the current SRHR ToC and SRHR
Results Framework of the MoFA?
o To what extent are the PDPs aligned to the current Dutch (SRHR) policy
objectives and priorities?
o To what extent are the PDPs aligned to the current global health agenda and
the Dutch Top Sector policy?

The relevance of the PDP III Fund has been assessed with a view to the policies of the Dutch
Ministry of Foreign Affairs, the life sciences and health top sector and the European Commission.
SRHR policy: policy objectives and priorities, results framework
The SRHR policy of the Dutch Ministry of Foreign Affairs has the following four objectives:
1. Better information and greater freedom of choice for young people about their sexuality;
2. Improved access to SRH and HIV/AIDS medicines and commodities;
3. Better public and private health care for family planning, pregnancies and childbirth, including
safe abortions;
4. The sexual and reproductive rights of all people, including those belonging to marginalized
groups, are institutionally respected & protected.
In the SRHR Results Framework these objectives have been translated in several objectives for
each result areas with accompanying indicators. The framework comprises in total 10 objectives
(see Annex H). For these objectives the Framework defines in total 27 indicators.
Relation of PDP III Funded activities with SRHR policy
One of the three themes for which PDPs could propose financing relates to promotion of sexual and
reproductive health. Three of the PDP’s have defined their application as relating to this theme,
such as IPM, FIND and IAVI. For others, such as MMV, TB Alliance and DNDi the focus of their
application for PDP III funding is not on this theme specifically.
As the PDPs are mainly aimed at product development and accessibility, the main relation of the
output and impact of their activities is with two of the 10 objectives, namely:
•

Objective D: Support innovation for SRH and HIV/AIDS medicines and commodities

•

Objective E: Promote access to and correct usage of safe, effective, quality and affordable
medicines and commodities for:

Evaluation PDP III Fund 2015-2021

37

1. Safe pregnancy and delivery, modern family planning, post-abortion care and safe abortion;
2. Prevention and treatment of HIV/AIDS.
None of the other objectives appear to be directly affected by the results of the PDP III Fund. Of
course, the availability of diagnostics and medicinal products can help to stimulate the availability of
services to the target group of SRHR policy (women of child bearing age, youths), but this relation
is more indirect and it would not directly affect any of the other indicators in the framework.
The PDP III Fund is thus relevant in terms of contributing to one of the four policy objectives of the
SRHR policy. Therefore, the PDP III Fund is considered to be to some extent relevant for the SRHR
policy, given that part of the PDP’s activities are beyond the scope of the policy, whereas the policy
focus is much broader than availability of medicinal products.
Top sector policy
The goal of the international strategy of the Dutch Life Science and Health Top-sector (HealthHolland) is increasing the competitiveness of the sector, thereby increasing the size and impact of
their international activities. 48 One of the ambitions of the strategy is to contribute to the
development of solutions for global health problems in realising the sustainable development goals.
The strategy poses that the Dutch health sector has much to “Ensure healthy lives and promote
well-being for all at all ages” as described in SDG3. It states: through international cooperation the
Netherlands can help partner countries with knowledge and technology transfer. This cooperation is
expected to be also beneficial for the Netherlands, in terms of gathering new insights and
strengthening the earning capacity.
The work of the PDP’s fits well with this policy and several Dutch companies and research institutes
are active in the various PDPs (see section 3.3.3). This is not to say that these links are the result
of the PDP III Fund, as partnerships with Dutch entities would most likely have been established
also in absence of the Dutch funding through the PDP III Fund. Nevertheless, it can be concluded
that the PDPs fits well with the Dutch top sector policy.
Alignment of PDPs to the global health agenda
The mission of all PDPs directly supports the global health agenda, including the Sustainable
Development Goals (SDGs) and WHO’s Universal Health Coverage (UHC). All PDPs align with
SDG3: Ensure healthy lives and promote wellbeing for all at all ages.
Within SDG3 all PDPs particularly align with the following SDG3 health targets:
•

3.3 By 2030, end the epidemics of AIDS, tuberculosis, malaria and neglected tropical diseases
and combat hepatitis, water-borne diseases and other communicable diseases;

•

3.8 Achieve universal health coverage, including financial risk protection, access to quality
essential health-care services and access to safe, effective, quality and affordable essential
medicines and vaccines for all;

•

3.b Support the research and development of vaccines and medicines for the communicable
and non-communicable diseases that primarily affect developing countries, provide access to
affordable essential medicines and vaccines, in accordance with the Doha Declaration on the
TRIPS Agreement and Public Health, which affirms the right of developing countries to use to
the full the provisions in the Agreement on Trade-Related Aspects of Intellectual Property
Rights regarding flexibilities to protect public health, and, in particular, provide access to
medicines for all.

48

38

Health-Holland, Strategie Internationaal 2020-2023, p 3.

Evaluation PDP III Fund 2015-2021

The PDPs that focus on developing products directly related SRH, like IPM, are also aligned with
target 3.7:
•

3.7 By 2030, ensure universal access to sexual and reproductive health-care services, including
for family planning, information and education, and the integration of reproductive health into
national strategies and programmes.

The PDPs that develop products targeted for children also contribute to SDG target 3.2:
•

3.2 By 2030, end preventable deaths of new-borns and children under 5 years of age, with all
countries aiming to reduce neonatal mortality to at least as low as 12 per 1000 live births and
under-5 mortality to at least as low as 25 per 1000 live births.

PDPs have a significant role in achieving SDG3, by realising access to quality medicines through
their contacts with large donors such as the Global Fund to fight AIDS, tuberculosis and malaria,
PEPFAR/USAID. The Netherlands is the tenth largest public donor of The Global Fund, with a total
contribution of €1,077 million to date.49 Once a product is WHO approved and included in
guidelines, these large actors can wield major influence on the availability of new products. The
Global Fund can do so by procuring new products to (national) programmes in LMICs that it funds.
3.3.3 Effectiveness
Effectiveness
o
Have there been significant developments in expenditure, costs and investments for
PDPs by other donors?
o
Has the funding mechanism provided leverage for Dutch policy priorities in
international fora?
o
What is the relative contribution of the Netherlands to the funding of other donors
in terms of both finance and influence?
o
Is there an increased interest in and/or are there investments from the private sector
in product development for poverty-related diseases and conditions related to SRHR?
And how and to what extent are the 6 PDPs contributing to that?
o
Is there increased involvement and participation of developing countries in product
development partnerships? And how and to what extent are the 6 PDPs contributing
to that?
o
Is there an increase in R&D capacity in target countries (training and job creation
are important overall indicators for many of the programmes funded by MoFA)?
o
Is there more investment in (see point E), and awareness of disease related to
poverty and SRHR, as well as a coherent policy approach towards this topic? As the
aspect of awareness is difficult to measure, suggested evaluation questions are:
o
Has the visibility of the PDP III Fund in the Netherlands increased?
o
Has the number of Dutch companies and knowledge institutes involved in the
PDPs increased?

Trends in financing of research and development of neglected diseases
The annual G-Finder report is an important source of information on the overall financing of PDPs
and the role of the Dutch PDP III Fund in this. The table below shows some relevant data for the
years 2015-2019 (data on 2020 not yet available). In interpreting these data, it should be kept in
mind that the G-Finder report covers a broader range of neglected diseases in developing countries
than the PDP III Fund.
The table shows that almost all of the funding of PDPs comes from 12 large donors, and that the
share of this group has even grown over the years. The Dutch contribution to PDPs accounted for 4

49

https://www.theglobalfund.org/en/government/profiles/netherlands/ Accessed 9 November, 2021

Evaluation PDP III Fund 2015-2021

39

to 5% of the total funding of all PDPs in 2016-2019. The low share in 2015 is due to the fact that
PDP III Fund only started late 2015. Since 2016 the Netherlands has been among the top 12
funders. The G-Finder reports also show that in recent years no new bilateral donor has emerged
with a substantial additional contribution.
Table 5

Funding of PDPs (million US Dollar) a)
2015

2016

2017

2018

2019 b)

Total financing PDPs

508

467

526

553

492

Of which by top 12 funders

484

449

504

537

n.a.

Idem as % of total

95%

96%

96%

97%

n.a.

Of which PDP III Fund

5

24

24

20

19

Idem as % of total

1%

5%

5%

4%

4%

Private investments MNC

410

418

466

598

500

Private investments SME

86

106

110

96

13

Source: G-Finder 2019 Final Report; G-Finder 2020 Final Report.
a: NB: the scope of the G-Finder survey includes all PDPs, also those not co-financed from the PDP III Fund.
b: note that the data for 2015-2018 are in US dollars of 2019; data for 2019 are in US dollars of 2019.

These figures illustrate that the PDP III Fund is an important source of financing for the PDPs. It
also shows the decline in overall funding in 2019, which is attributed to lower contributions from for
instance Gates Foundation and UK Government (previously DFID, now DHSC).
The G-Finder report also shows investment by private companies with respect to neglected
diseases. These relate to the investments for own account of these companies (multinational
pharmaceutical companies – MNCs; small and medium sized enterprises- SMEs) in relation to
neglected diseases and are thus not related to investments in relation to the activities of PDPs. The
vast majority (71%) of this financing is related to clinical development and post registration studies,
while only 20% is devoted to early stage research.50 In addition, the majority of private investments
(64 to 76% in 2015-2019) were related to three diseases: HIV/AIDS, malaria and tuberculosis; an
additional 10% to neglected tropical diseases as identified by WHO. Despite their high level of
investments, MNCs are responsible for only 16% of total investments in neglected tropical
diseases. 51
Involvement of developing countries
The review of the achievements of the six PDPs reveals that they have established many
partnerships over time. A differing number of the partnerships are with organisations within LMICs.
The following table presents a partial overview.
Table 6

Overview of partnerships of PDPs

PDP

Number of

Idem in LMICs

partnerships
DNDi

Over 200

FIND

332

IAVI

190

Among which research

Dutch knowledge

institutes in LMICs

partners in PDP

52% of research partners

7

are in LMICs
17
34

IPM

70

26

4

MMV

323

51

7

TB Alliance

482

94

8

Source: various documents provided by the PDPs. See also PDP sheets in chapter 5.

50
51

40

4

G-Finder 2019, Final report, p. 9.
Ibid., p 11.

Evaluation PDP III Fund 2015-2021

Among these partnerships there are research institutes in target countries. The level to which PDPs
have been instrumental in setting up or increasing the capacity of these institutes differs
considerably between them. This is partly due to the emphasis in their activities. For instance,
phase 2 and phase 3 clinical trials are more frequently organised in LMICs than phase 1 trials.
Another factor that explains the difference relates to the character or scope of the PDPs. DNDi and
IPM, for instance, put substantial effort in capacity building in developing countries.
The overall view from the documentation and interviews is that PDPs have had a substantial impact
on R&D capacity in LMICs. PDP coalition members have performed clinical research at more than
550 sites in more than 80 countries, mostly in LMICs, according to the Netherlands Enterprise
Agency.52 In various cases, clinical research capacity in LMICs was available for testing newly
developed COVID-19 vaccines. Interviewees also pointed out, though, that the lack of continuity in
clinical trials is a potential threat for the continuity of these research centres.
Despite their capacity to generate much-needed interventions for neglected diseases, PDPs are not
without their critics. It has been suggested that the paradigm perpetuates research disparities and
power inequities between high-income countries and LMICs. Financial control and decision making
power within PDPs rest with first-world head offices and senior staff primarily from the United States
and Europe,53 and many production partners who can benefit from work of PDPs are
pharmaceutical companies in high-income countries. Some PDP representatives acknowledged
that PDPs could step up their role for instance in enhancing phase 1 research capacity and
manufacturing capacity, particularly in Africa.
Dutch policies
With respect to the leverage of Dutch policies in international fora, frequently interviewees
mentioned that the Dutch focus on SRHR is generally well known and highly appreciated. With
respect to the role of PDPs in tackling global health issues in general or in tackling neglected
tropical diseases, the long-standing presence of the Netherlands is most telling. In this area,
though, it is noted that the input by the Netherlands has been less prominent in recent years than it
has been in the earlier years of PDPs
Investments in poverty-related diseases and products for SRH
According to the G-Finder survey of 2020, total investments in R&D for neglected diseases
increased from 3.4 billion US dollars in 2015 to 3.9 billion US dollars in 2019.54 It should be noted,
though, that over 75% of all investments are geared to three diseases: HIV/AIDS, malaria and TB.
These data are therefore not representative for investments in diseases related to poverty. The
report also shows, for instance that only a small part of total investments is related to neglected
tropical diseases:55
“Global R&D funding for neglected tropical diseases […] included in the G-FINDER survey scope
has been stagnant for a decade, and this situation continued in 2019. After adjusting for
participation, funding for NTDs increased by just $7.5m (2.4%), to $328m [..], marginally above the
record-low share of overall neglected disease funding they received in 2018. [..] In addition to
seeing little overall change, most NTDs saw little change to their individual funding levels in 2019,
although the majority received small increases.”

52
53

54
55

Netherlands Enterprise Agency, The impact of the Product Development Partnerships PDP III Programme, 2015-2021
Pratt, B. and B. Loff (2013). "Linking Research to Global Health Equity: The Contribution of Product Development
Partnerships to Access to Medicines and Research Capacity Building." American Journal of Public Health 103(11): 19681978.
Policy Cures Research, G-FINDER 2020, Neglected disease research and development: where to now?
Ibid, p. 14. Note that not all NTDs recognised by the WHO are included in the survey.

Evaluation PDP III Fund 2015-2021

41

Visibility and involvement of Dutch companies
Among the partnerships shown in Table 6 there are various Dutch companies and knowledge
institutions. The number reported in recent years is slightly higher than as was reported in 2015,
with many partnerships that were present in 2015 still being in place.56 It is thus concluded that the
cooperation with Dutch knowledge partners has been quite stable over time. The role of PDP III
Fund in this is assessed to be limited, based on the interviews.
The number of partnerships may not be the best metric to look at the Dutch input into product
development. Most of these relations either were already established earlier, or are driven by the
knowledge and capabilities that the Dutch partners can bring for the PDP’s development processes.
Also, the we have not found indications from interview partners that the visibility of the PDP Fund in
the Netherlands has grown vis-à-vis the previous funding period.
3.3.4 Efficiency
Efficiency
o What are the strengths and weaknesses of the current funding mechanism? What
are threats and opportunities?
o What is the role of the European & Developing Countries Clinical Trials
Partnership (EDCTP) and how efficient is the collaboration between EDCTP and
the Netherlands MoFA regarding the PDPs?
Alternative financing instruments
As explained in section 3.2.3, the PDP model is a cost effective way of developing medical products
for poverty-related diseases and making them accessible for the people in need in LMICs. By cofinancing the activities of six PDPs, the PDP III Fund contributes to this development and
accessibility, thereby realising the expected impact. Although are alternative financing instruments
can be envisaged to stimulate development and/or accessibility of products for poverty-related
diseases, most of these alternatives would address only part of the activities of PDPs, and may
therefore have more limited outcomes and impact.
One alternative to PDP co-financing would be direct funding of research institutes, either in LMICs
or elsewhere. In this way Dutch financing would concentrate on the development phase of
products, without necessarily adding to increased accessibility. Also the funding might involve more
partners, each with a narrow scope in terms of products. Another alternative would be to directly
fund multilateral organisations that stimulate development or accessibility of products for povertyrelated diseases. Also in this situation the focus would be on only a part of the development and
accessibility process, thereby limiting the scope of outcomes and impact.
SWOT of the PDP mechanism
Despite its cost-effectiveness, the PDP model has some drawbacks. For this evaluation an analysis
has been made of the strengths, weaknesses, opportunities and threats of the PDP model from a
financial and government point of view.

56

42

The overview of Dutch partners of the six PDPs was derived from Netherlands Enterprise Agency (RVO).

Evaluation PDP III Fund 2015-2021

Figure 2 A SWOT analysis of the PDP delivery model from a finance (and governance) perspective
Strength:

Weakness:

1.

1.

2.

Proven PPP model with long term (complex)

R&D and;

Mitigation / repair of ‘market failure’ (medicines

•

resulting medicines / products;

are developed for financially unattractive

•

product delivery (uptake/access), and

•

‘impact’ (public health indicators)

markets)
3.

4.

Relative indirect relation between funding of

partnerships between private and public sector

Mitigated product development risks for private

2.

Not sustainable without grant funding

sector

3.

Portfolio approach requires freedom of

Track-record of product delivery

manoeuvring (less focus on specific medicines /
diseases)

Opportunity:

Threat:

1.

Provide core and long-term budget support

1.

(Other/ non-NL) Donor grants fall away

2.

Strengthen / extending ‘delivery chain’

2.

Weak governance / deviation of focus of donor

3.

Secure revenue upside (via development fund)

4.

Social impact bonds

3.

‘Control’ over ‘trust’ (micro managing PDPs)

5.

Direct funding other players in ‘delivery chain’

4.

Short-term budgeting

6.

Combined donor approach

5.

Overhead squeeze

administrations

One of the weaknesses of the PDP mechanism is its high dependency on donor financing. Due to
reducing financing by some of the donors (UK, Gates Foundation), as well as the shifting focus due
to the COVID-19 pandemic, this weakness is becoming a serious threat.
In this respect the PDP III Fund contributes to this weakness as it provides financing for 5 years,
which is quite short given the time it takes to develop new medicinal products, which can easily take
up to 20 years or more. This drawback is somewhat counterbalanced by the way in which the Dutch
financing works. The core financing applied by the PDP III Fund provides flexibility for the PDPs
which is relatively unique among donor organisations.
Dutch PDP funding has leveraged other funding, according to PDP staff. Sometimes it is not very
tangible, when interviewees say the Dutch government has a good reputation as a donor, and
therefore getting Dutch money is a good sign for your organisation. More concretely, more than one
interviewee has mentioned that for some EDCTP or US funding calls, co-funding was required, in
which case the PDP brought up the unearmarked Dutch money that helped them attract the
EDCTP or US funding.

Evaluation PDP III Fund 2015-2021

43

Figure 3 Synergy in Dutch funding of product development

Dutch funding not only creates major synergies in product development through its in-kind funding
of EDCTP and PDPs, but also in market-shaping through its contribution to The Global Fund to fight
AIDS, tuberculosis and malaria as the Fund’ 10th largest donor (see Figure 3). Once the Global
Fund includes a product in its procurement system, a substantial number of orders can be expected
and therefore places a new product firmly on the market.
Nevertheless, a broadening of the financing basis for the PDPs is required in order to increase their
financial sustainability. Various options have been explored to increase the financial sustainability,
by means of a development fund or by making use of social impact bonds.
Possible opportunity: Secure possible revenue upside (via development fund)
In principle, PDPs address a market failure that arises from a low revenue expectation in a certain market
in developing countries. It may however be possible that a product/medicine is relevant in other more
affluent markets as well (a HIV medicine for instance) which could create additional revenue returns for a
PDP. A PDP could agree with its associated pharmaceutical companies a premium on the sale price for
any product that is sold outside the developing countries market. Such upside revenue sharing mechanism
could stimulate PDPs and their partners to also cease these market opportunities.
The premium could be secured in a designated ‘development fund’ that provides future R&D budgets for
PDPs. Those budgets would enhance the sustainability and capacity of PDPs to deliver the required health
/ societal impact objectives. Such fund may ideally be linked to a group of PDPs, otherwise individual PDPs
may prefer developing only medicines that also have a market potential in developed markets. Which
would be a partial return to the market failures PDPs were designed for to overcome.
Recommendation: explore whether donors and PDPs would consider this as a proper incentive, then
explore the development fund’s governance principles.

Possible opportunity: Social Impact bonds
Social Impact Bonds have been in use in various sectors to help donors, social entrepreneurs and
investors with measuring, financing and enhancing societal impact. See the figure below for an overview of
a social impact bond structure. It is structured around a contract (1) between an outcome payer (donor), an
impact investor and a social entrepreneur (read a PDP). The investor pays out working capital budgets (2)
for the PDP to perform their activities (3). An outcome payment (5) is eventually made if an independent
third party (4) acknowledges that the impact is realised.

44

Evaluation PDP III Fund 2015-2021

Social Impact Bond structure

1) contract

Outcome Payer
(donor)

5) Outcome payment

1) contract

Investor
2) payments

Social entrepreneur
(PDP)

4) Impact assessment

3) activities

Social impact
(health)

These bonds could be instrumental for further enhancing the impact of PDPs and / or for attracting other
investor groups into the sector. Social impact bonds may be more relevant for the latter than for the former
objective; PDPs have shown to be effective and efficient whilst the present funding mechanism is input and
best effort based. It may be opportune to at least further explore whether a social impact bond for this
sector is relevant for attracting other investor groups.
Recommendation: Explore whether a social bond structure is feasible for this sector, whether investors are
available and whether donors and PDPs see opportunities for this type of support.

EDCTP
Part of the Dutch financing of PDPs is earmarked as a contribution “in kind” of the Netherlands for
the work of EDCTP. This contribution is matched by a similar extra funding by the European
Commission. Based on these funding EDCTP finances capacity building and clinical trials in Africa,
thereby giving extra financing opportunities to PDPs.
The PDP III Fund thus fits well in with and strengthens the activities of the EDCTP. PDP staff
mentioned more than once the positive contribution of EDCTP in strengthening their work (“We
would not have the support we needed on many products without them“). Interviewees also
wondered whether such a good partnership could not be extended to other continents outside
Africa.
On a more critical note, more than once interviewees also commented on the quite heavy
bureaucracy at EDCTP, especially when something in the project changes – as often happens,
particularly when the pandemic struck.

Evaluation PDP III Fund 2015-2021

45

4

Discussion and recommendations

In this chapter recommendations are formulated on the basis of the evidence presented and
findings formulated in the previous chapter. In line with the ToR, the recommendations focus on
future funding mechanisms and priorities to promote research and product development to combat
poverty-related diseases and conditions related to SRHR based on current challenges. Also
aspects that might become relevant in the future are taken into account.
The recommendations address the following questions from the ToR:
o

o

What can be done to improve the relevance, efficiency and effectiveness of a
new PDP funding mechanism, taking into account the current policy focus of the
Dutch Ministry of Foreign Affairs, in specific the policies related to SRHR and the
balance between aid and trade?
Is the instrument of the PDP the most appropriate to stimulate research and
product development to combat poverty-related diseases and conditions related
to SRHR or are there any other instruments recommended?

Recommendations on a new PDP funding mechanism
On the focus in funding: accessibility and pipeline development
Although the criteria for the PDP III Fund are broadly described, the fund has focused
predominantly on product pipeline development. However, accessibility is equally important in order
to achieve the desired impact of the funding. Whereas pipeline development stimulates supply of
products (medicines, vaccines, diagnostics, etc.), accessibility deals with the demand for these
products.
Accessibility comprises all steps to reach end users, among which pricing, regulatory approval and
reaching communities. This means that the product needs to be approved for marketing, needs to
fit the conditions of the specific patient groups (e.g. children, women of childbearing age), need to
be user friendly for these groups, etc. It also means that national governments need to stimulate the
use and health professionals need to be aware of the value of the products and how they need to
be applied.
Over time the PDPs have developed new products for specific patient groups. With more products
becoming available or ready for market introduction, the importance of optimal accessibility is
growing. Based on these observations:
It is recommended to explicitly include activities aimed at realising better access in the
scope of a future PDP Fund by adopting the end-to-end approach (i.e. the whole process
from identification of lead substances to the use of the end products by communities) to the
funding of PDPs.
On the relation between PDP’s and SRHR policy
Products for the promotion of sexual and reproductive health constitute one of three priority themes
of the PDP III Fund (besides products in relation to poverty-related diseases, and products in
relation to new and recurring epidemics). While there is a clear need for innovative products directly
related to SRHR, particularly an effective AIDS vaccine, the needs for innovative medicinal

Evaluation PDP III Fund 2015-2021

47

products for poverty-related diseases remain in a context where new and recurring epidemics have
an impact on the funding landscape for poverty-related diseases.
In the present COVID-19 pandemic PDPs experience that attention in funding is shifting. Two major
donors, the Bill and Melinda Gates Foundation (BMGF) and the government of the United Kingdom
have recently reduced the financing for PDPs. There is a risk that COVID-19 is crowding out
funding for SRHR and poverty-related diseases. Some PDPs already report feeling the impact of
this development. In the past, funding for diseases new and recurring epidemics has been
considerable, once such an epidemic occurred. For instance, when Ebola hit West Africa in the
previous decade, $165 million were made available for R&D, masking the general decline in
funding for poverty-related disease and making Ebola the fifth-best funded neglected diseases,
directly behind HIV, tuberculosis, malaria and diarrhoeal diseases.57 Therefore, based on current
and past trends in funding for new and recurring epidemics, one can conclude that such diseases
will be able to attract sufficient R&D funding when circumstances so dictate. Based on these
observations:
It is recommended to focus a future PDP Fund on two areas: products for SRH and products
for poverty-related diseases.
A further focus in a potential future PDP Fund on products for SRH only would limit the possibilities
for product development by PDPs. Such a focus may be less limiting if it includes activities that are
related to safety of women during pregnancy and the lactating period, as some PDPs are already
doing, Thus, the relevance of product development for a large and hitherto underserved group
would increase.
It is recommended that, in case of a focus on SRH in a future PDP Fund, this focus is
interpreted broadly, by extending funding also to activities aimed at product development
and safety research for groups that are relevant for SRH, like pregnant and lactating women
and women of childbearing age.
Coherence between future PDP fund and other Dutch funding mechanisms
Accessibility for all patient groups to the newly developed products is important to realise their full
impact. PDPs have been increasing their efforts into the access of their products in recent years
(end-to-end approach). Increasing accessibility of the products can improve the effectiveness of the
PDPs.
The Ministry of Foreign Affairs manages several funding mechanisms besides PDP funding, for
instance Power of Voices and the SDG5 fund. Especially some funding mechanisms in the SDG5
fund address SRHR and, therefore, have potential synergies with PDP activities on increasing
access to relevant essential medicines and diagnostics. Yet, the evaluators did not find evidence of
a systematic effort to enhance coherence and coordination between these funding mechanisms.
This is a lost opportunity.
It is recommended to explore the possibility to further strengthen the coherence between
the work of PDPs and other funding mechanisms of the Ministry of Foreign Affairs that have
potential synergies in working on increasing accessibility of the PDP products.

57

Ebola funding boost hides ongoing decline in neglected disease R&D
https://www.ghtcoalition.org/blog/ebola-funding-boost-hides-ongoing-decline-in-neglected-disease-r-d

48

Evaluation PDP III Fund 2015-2021

On funding characteristics
PDPs highly appreciate the characteristics of the Dutch funding under the PDP III Fund, such as it
being core funding, it’s flexibility in use and the long-term view in the funding. The flexibility for
instance complements project funding by other donors and enables the funding of activities that are
difficult to allocate to a particular project (like capacity building) or that other donors are not willing
to fund, such as exploring a new lead substance. Core funding also helps PDPs to obtain other
funding with a co-funding requirement, such as US Funds or ECDTP funds. Core funding is seen as
an important added value of Dutch funding.
It is recommended to keep the characteristics such as core funding, flexibility in use and a
long-term view in a future PDP fund.
On the PDP instrument
Effectiveness of PDP III Fund in realising the desired impact
As described in section 3.3.1, the objective of the PDP III Fund is to reduce the burden of povertyrelated diseases and improve the availability and accessibility of products related to sexual and
reproductive health. The evidence presented in this report underlines that indeed more products,
which were developed by the PDPs co-financed from the PDP III Fund, have become available for,
and have been distributed to, patients since 2015. Other products advanced in the product
development cycle of the PDPs.
Over the years, the PDP model has proven to be a cost-effective way to develop products for
poverty related and neglected tropical diseases and conditions in relation to SRH. Their costeffectiveness is better than that of commercial pharmaceutical companies. The Lancet Commission
on Essential Medicines Policies states that industry-supported estimates of the cost for developed
medicines set the average at USD 2.5 billion per new product, whereas DNDi estimates the costs of
developing a new chemical entity at € 100-150 million, and the costs of improving a treatment at
€ 10-40 million. Alternative financing instruments (like direct funding of research institutes in LMICs;
or financing via multilateral organisations) are suboptimal in terms of scope and, therefore, potential
impact, as compared to the end-to-end approach of the PDP model.
The PDPs are thus effective in reaching the goal of product pipeline development for povertyrelated diseases and conditions in relation to SRH. Alternative financing instrument (such like direct
funding of research institutes in LMICs; or financing via multilateral organisations) are suboptimal in
terms of scope and potential impact, as compared to the PDP model, mostly because such models
would address only part of the product development and accessibility pipeline. They would either
stimulate part of product development or focus on increasing accessibility.
Although the PDP III Fund has contributed to this success, it is difficult to exactly pinpoint what part
of that success is due to this financing. If the PDP III Fund would not have been available, it is not
likely that other donors would have stepped in. Each donor makes an individual appraisal and there
is no sign found that donors directly react on each other’s actions. For instance, there is no
indication that the recent reductions in PDP funding by BMGF and UK government has been
reason for other new donors to step in or for existing donors to increase their funding.
Given this, and given the way in which PDPs manage their portfolios of donors and activities, it is
more likely that fewer activities would have taken place if the PDP III Fund had not been available.
In practice this most probably means that fewer new products would have been explored and that
development of products would slow down. Also, without Dutch funding the PDPs could not have
applied for funding for some EDCTP funding applications for which co-funding was a requirement,

Evaluation PDP III Fund 2015-2021

49

as the Dutch funding has been used as co-funding. The same holds true for applications to some
US donors.
It therefore seems fair to conclude that without PDP III Funding less would have been achieved in
terms of product development, and therefor in terms of (future) availability of products for people in
need. Although an exact estimate of the impact of PDP III funding is not possible, some tentative
remarks can be made. The funding provided by the Netherlands government in 2015-2021 equalled
just over € 100 million Euro. Given this funding and the cost estimates presented above from DNDi,
the size of the budget of the PDP III Fund is slightly below the cost of one successful new product
development or equal to 2.5 to 10 improved treatments. This does not yet take into account the
synergy that is realised via EDCTP and the Dutch contribution to the Global Fund.
Alternatively, the Dutch funding catered for approximately 5 to 6 percent of total expenditures over
the past 5 years. This may indicate that due to Dutch funding 5 to 6 percent of the results of the
PDPs have been realised, i.e. 5 to 6 percent of the products that progressed one stage (30), or of
products that were brought to the market (12), or of other outcomes such as research capacity
developed and persons trained.
At the same time there is pressure on financing and the risk of crowding out financing by COVID-19
is substantial. This would limit the possibilities for PDPs and negatively affect the realisation of
impact.
Given the above observations the evaluators conclude that, in case developing and making
accessible products to combat poverty-related diseases or conditions relating to sexual and
reproductive health remains a policy priority, the PDP model potentially is the optimal instrument to
realise this, provided that potential threats can be successfully addressed, such as with respect to
financial sustainability.
Explore possibilities to improve financial sustainability
The SWOT analysis shows that a main weakness of the funding mechanism is that it is financially
not sustainable without grant funding. Reduction of the dependence on donor grants by increasing
other funding would strengthen the sustainability. It is presently not clear to what extent this can be
successful. Various ways have been explored to improve the sustainability. A few possibilities have
been identified to expand the funding basis. More research will be needed to explore the viability of
these opportunities.
It is recommended that MoFA explores the possibility, together with PDPs and other
funders, to create a common fund that is financed from impact bonds and/or from part of the
margin that pharmaceutical companies can make on selling newly developed products in
High Income Countries for which intellectual property rights are with PDPs.
Reintroduce thought-leadership of Dutch government
In the past the Dutch government was visible as influencer in the PDP field, e.g. in advocating for
SRHR, and in strategy development within the PDP donor community. This role has diminished
over time and was significantly lower-key during PDP III years as compared to the level in the
beginning period of the PDPs, partly due to high turnover of Dutch government staff. The leadership
role in the recent past of the Dutch government in strategic issues has been acknowledged and
appreciated by the PDPs. In addition, PDP representatives feel that the Dutch government, with
like-minded partners such as the Swiss government, could play a leadership role in the donor
community and the PDP Funders Group in advocacy on issues like core funding.

50

Evaluation PDP III Fund 2015-2021

It is recommended that efforts are being made to step up the leadership role of MoFA in the
broader donor and international community regarding PDP funding and strategy (with a view
to further enhance PDP’s role in SRHR and explore innovative funding mechanisms).

Recommendations to PDPs
Besides pipeline development, increasing the accessibility of the products is an important activity
for the PDPs. While some PDPs increasingly improve access for specific groups (in particular
women of childbearing age, and children), this effort is not seen systematically across all PDPs.
It is recommended that all PDPs follow a systematic approach to accessibility of products
for women and children; a cross-cutting standard for PDPs may be helpful in achieving such
a standard approach.
All six PDPs work together with research institutes, in several LMICs. PDPs have been investing
actively in capacity building in LMICs and employ these institutes in clinical trials. When a trial is
concluded, clinical trial sites experience discontinuity in their workload, which can result in loss of
valuable staff. More cooperation between PDPs and other stakeholders in planning clinical trials
can improve the sustainability of research capacity in LMICs.
It is recommended that PDPs improve their coordination of clinical trials in LMICs in order to
improve the long-term sustainability of the research capacity.

Evaluation PDP III Fund 2015-2021

51

5

PDP Sheets

In this chapter summarised information is presented for each of the six PDPs financed under the
PDP III Fund. The information is based on documentation received from the PDPs, such as Annual
Funder Reports and the Applications for financing under PDP III, and documentation received from
Netherlands Enterprise Agency (RVO). The sections are organised along the various evaluation
criteria and contain information that is used in the main report. Some sections, in particular those
relating to relevance, are based on additional research and assessments by the evaluation team.

5.1

Drugs for Neglected Diseases Initiative (DNDi)
MoFA Awards to DNDi
DNDi-1

Grant of € 3 million for the period 2006-2009

DNDi-2

Grant of € 14 million for the period 2011-2014

DNDi-3

Grant of € 16 million for the period 2015-2020

Extension 2021

Grant of € 3.2 million for 2021

Source: Netherlands Enterprise Agency (RVO)

Relevance
Relevance of the developed products for the individuals in need
The Drugs for Neglected Diseases initiative’s (DNDi) mission is to save lives and improve the
health of people living with neglected diseases by using an alternative model to develop drugs for
these diseases, and by ensuring equitable access to treatment. Table 7 shows the burden and
geographical spread of the diseases for which DNDi has been developing products under the PDP
III fund. These diseases mainly affect LMICs and are diseases which disproportionately impact the
poorest and most vulnerable.
Table 7

Burden and geographical spread of diseases targeted by DNDi

Disease

Burden of disease58

Leishmaniasis (Visceral Leishmaniasis/VL, black fever /

Leishmaniasis was responsible for 5 710

kala azar; Cutaneous Leishmaniasis, tropical sore/CL;

deaths (95% UI 1690–18 700) and 697 000

post-kala azar dermal lesions/PKDL).

DALYs (375 000–1 620 000) in 2019. The main
affected world regions are North Africa and the
Middle East, Sub-Sahara Africa and Latin
America.

Chagas disease

Chagas disease was responsible for 9 490
deaths (95% UI 5 500–16 500) and 275 000
DALYs (184 000–459 000) in 2019. Chagas is
endemic in Latin American countries, but cases
are also found in other locations due to
migration.

Human African Trypanosomiasis (HAT/ sleeping

The global burden of human African

sickness)

trypanosomiasis (HAT) in 2019 was 82 600
DALYs (95% UI 37 600–156 000) and 1360
deaths (95% UI 609–2580), a 98% decrease in

58

52

The Lancet. Global Burden of Disease. GBD cause and risk summaries. https://www.thelancet.com/gbd/summaries
Accessed on 26 October, 2021.

Evaluation PDP III Fund 2015-2021

Disease

Burden of disease58
deaths since 1990, reflecting efforts to eliminate
transmission and improve case detection.
Selected countries in Central Africa
(Democratic Republic of Congo, Central African
Republic) are among the most affected by HAT.

Mycetoma

The global burden of mycetoma is unknown. It
is endemic in tropical and subtropical areas in
the so called 'Mycetoma belt', which includes
the Bolivarian Republic of Venezuela, Chad,
Ethiopia, India, Mauritania, Mexico, Senegal,
Somalia, Sudan, Thailand, and Yemen.59

Source: The Lancet

Relevance regarding SRHR policy of MoFA
DNDi has not developed products directly related to SRH or to HIV/AIDS under PDP III funding.
The only direct relationship to SRH in DNDi’s overall portfolio is the development of paediatric
formulations for antiretrovirals used in HIV, to improve quality of life for children living with HIV.
One of DNDi’s current strategic imperatives in its Strategic Plan 2021-2028 is to “contribute to
building a proactive agenda for maternal and child health and gender-responsive R&D”60.
Therefore, more broadly speaking there is alignment with the SRHR Theory of Change and Results
Framework (especially pillar 2 and 3) of the Netherlands Ministry of Foreign Affairs.
Alignment Dutch Top Sector policy
The innovative character of PDPs such as DNDi is fully aligned with one of the Dutch Top Sector
policy’s foundations, i.e. innovation. DNDi’s collaboration with selected Dutch knowledge institutes
and partners contribute to the Dutch Top Sector policy. Dutch partners of DNDi include:
•

Amsterdam UMC;

•

Netherlands Cancer Institute;

•

MSF-Netherlands;

•

Rotterdam Centre for Tropical Medicine;

•

Free University Amsterdam;

•

Radboud University Medical Center;

•

Erasmus Medical Center.

Effectiveness
Pipeline and original targets
Figure 4 shows the progression of the funding pipeline from 2015 – 2021 funded under PDP III,
with a projection for 2022. At least 7 products moved one phase or more through the pipeline. It is
expected that an additional four products move one phase up in 2022, including two to
implementation after registration and/ or national guideline change.

59
60

https://www.who.int/news-room/fact-sheets/detail/mycetoma Accessed 26 October, 2021
DNDi Strategic Plan 2021-2028 – 25 treatments in 25 years

Evaluation PDP III Fund 2015-2021

53

Figure 4

Pipeline DNDi

DNDI
Disease
Human African Trypanosomiasis (HAT= sleeping sickness)

Treatment Category
Improved combination treatment
First oral treatment on the market

Candidate/Entity
NECT
Fexinidazole for T.B.gambiense

Phase 3/4

First oral treatment on the market
Single- dose treatment

Fexinidazole for T.B. rhodesiense
Acoziborole (SCYX-7158)

Phase 1

SCYX-1330682
SCYX-1608210

Leishmaniasis

VL (Visceral Leishmaniasis = black fever)
CL (Cutaneous Leishmaniasis = tropical sore)

Improved combination treatment
Improved combination treatment

Improved treatment guidelines
Improved treatment guidelines

Chagas Disease (American Trypanosomiasis)

Mycetoma (Fungal disease)

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Evaluation PDP III Fund 2015-2021

Treatment for children

2015

DNDI-6174
GSK3494245/DDD1305143
Aminopyrazoles
S07 series
CF series
Benznidazole (Paediatric Dosage Form)

2022

Implementation

Phase 3/4

Discovery
Discovery

Implementation
Implementation
Phase 3/4
Phase 3/4

Implementation

Phase 3/4

Implementation

Phase 3/4
Phase 2
Phase 2

Phase 3/4

Phase 1
Phase 1

Preclinical

Phase 2

Phase 1
Phase 1

Phase 2

Phase 1
Phase 1

Preclinical

Phase 1
Preclinical
Discovery

Discovery
Discovery

Implementation

New Benz Regimens

Phase 2

Fexinidazole
DNDI-6148

Phase 2

Biomarkers
Oxaborole profiling
UW series
Daichi Sankyo series
Fosravuconazole

2021

Phase 3/4

SSG&PM (Africa)
New VL Treatments (Asia)
MF/Paromycin combo for Africa
New treatments for PKDL
New treatments for HIV/VL
VL treatment Latin America
New CL Combos
Fexi/MF combo
Anfoleish
DNDi-6148
DNDi-0690
GSK3186899/DDD853651
Novartis LXE408
CpG-D35 for CL
GSK245 DDD1305143

2020
Implementation

Phase 3/4
Phase 2
Phase 1
Preclinical
Discovery

Discovery
Discovery
Phase 3/4

The PDP III funding proposal anticipated assessment of 5-6 preclinical candidates from internallydriven programmes, supplemented by 1-2 in-licensing opportunities for Chagas disease and
Leishmaniasis. Figure 4Error! Reference source not found. shows 8 substances in the discovery
phase and 4 substances as Preclinical, which means that with 12 substances in initial phases,
DNDi outperforms the original targets. In addition, 3 substances from external sources have
entered the development process.
Two of the aforementioned preclinical candidates for Leishmaniasis moved up in the pipeline to
phase 1 studies, while one of them is anticipated making it until phase 2 trials at the beginning of
2022. This meets the originally planned target in the funding proposal, which was to obtain 2 new
drug candidates for clinical development in leishmaniasis, with one of them entering phase 2
studies. The latter was anticipated for 2018 instead of 2022, as seems to be the case now.
As to HAT, finalizing development of fexinidazole for the two types of Trypanosoma parasite is on
track, as well as completion of clinical development of acoziborole. All substances are in the in
phase 3 or 4 trials or fully in the implementation phase.
For Mycetoma, the PDP III proposal plans clinical trials of an already developed substance, which
is in accordance with the reported funding pipeline.
Impact of COVID-19
The COVID-19 pandemic has partly hampered DNDi’s work, but also provided opportunities.
During the beginning of the pandemic DNDi has had weekly meetings with support teams in
countries and to assess how to best monitor activities remotely.
Opportunities
•

In response to the COVID-19 pandemic and inequities in research and access, DNDi launched
into action to address the underserved and specific challenges of resource-constrained
countries with fragile health systems.

•

DNDi’s core attributes placed it in a prime position to contribute its expertise and leverage its
networks for COVID-19. DNDi was called to contribute to the ACT-A therapeutic partnership,
notably in therapeutic selection and clinical trials in low-resource settings. DNDi established the
COVID-19 Clinical Research Coalition, which has grown to nearly 700 members including close
to 200 member institutions (including: Amsterdam UMC, and Radboud UMC), and launched
ANTICOV, the largest clinical trial in Africa testing multiple early treatment options for COVID19.61

Challenges
•

DNDi has secured access to sizable compound libraries to feed its discovery pipeline. In 2020
the numbers of compounds processed from commercial sources decreased due to the delays
experienced by partners during the COVID-19 lockdowns.

•

The DNDi PDP III Final Report expresses concerns around funding because of the pandemic
situation. With limited resources, objectives to combat the COVID-19 pandemic and the fight
against neglected tropical diseases, both might compete with one another – and NTDs may lose
traction on the global agenda. This may have a negative influence on donor contributions to be
expected for DNDi’s work.

Access for the target groups and equity in access
DNDi has realised multiple actions to improve and realise access to new treatments. Below are
some examples of actions geared towards improving access, without pretending to be exhaustive.

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PDP III Final Report. DNDi, 2020.

Evaluation PDP III Fund 2015-2021

55

Pricing
TPPs take into account the concept of affordable pricing. Contracts with pharmaceutical companies
stipulate affordable pricing arrangements. As part of its commitment to cost transparency and fair
pricing of medicines, DNDi publishes its drug R&D costs based on its latest historical data set.
Regulatory approval and clinical guidelines
Fexinidazole has been included as first-line treatment into the new WHO-HAT treatment guidelines
and added to the 2019 WHO-Essential Medicines Lists for adults and children.
The paediatric formulation of benznidazole for Chagas disease was registered in two countries
during the evaluation period (USA (2017) Argentina (2018)). The drug was already registered in
Brazil and included on the WHO Model List of Essential Medicines for Children prior to the period.
DNDi is working with Ministries of Health of affected countries in Africa to adapt guidelines for HIV
/VL co-infection to novel drug combinations.
DNDi provides training of health workers in new guidelines. For example, DNDi has provided
training of 1519 health workers on Good Clinical Practice and Leishmaniasis during the evaluation
period.
Equity
DNDi has put effort in ensuring access of children and women to new products. For instance,
special drug dosing studies in children have been done for Leishmaniasis products, as well as
DNDi’s continued efforts to expand testing and treatment of children with Chagas disease. DNDi
plans to conduct at least 6 new studies
on indications for paediatric use in its next work period (2021-2028). DNDi also has a gender
strategy to help increase gender-inclusive data and research for the development of drugs and
diagnostics, including proposals for a safe, ethical framework for the recruitment of women of
childbearing age in clinical trials of new drugs for NTDs. DNDi developed a proposal for a safe,
ethical framework for the recruitment of women susceptible to becoming pregnant in clinical trials of
new drugs against NTDs. DNDi has advocated to the WHO for inclusion of the framework into the
WHO’s Global Strategy for Women’s, Children’s and Adolescents’ Health (2016−2030).
Advocacy
DNDi has participated in various advocacy activities for equitable access to medicines for NTDs
within the global health agenda. DNDi realised this, for instance, within UNGA High Level Meeting
on UHC, and in the 2019 G20 Health Ministerial Declaration.
Distribution of developed products
Over the years DNDi has developed 9 products and/or improved treatments which have been
introduced into health systems. Exact distribution or uptake numbers are not available from DNDi
as much of the distribution is in the hands of its partners (WHO, PAHO, National health agencies,
pharmaceutical manufacturers). A recent overview received from DNDi shows that since 2015 three
products were registered (and made available to patients). One of these products (paediatric HIV)
is registered in one country (South Africa, 2016), one product (regarding HAT) in 7 countries in
Africa (2019), and the third product (hepatitis C, 2021) has received a conditional registration in
Malaysia. The market introductions before 2015 concern six products. These treatments are
registered or in treatment guidelines in 79 countries in Africa, Asia and the Americas.
Patients reached (2003-2020 cumulative):
ASAQ for malaria: over 500 million treatments distributed since 2007
ASMQ for malaria: over 1.3 million treatments distributed since 2008
NECT for HAT: 100% of all stage-2 patients are now treated with NECT

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Evaluation PDP III Fund 2015-2021

Patients reached (2003-2020 cumulative):
Paediatric benznidazole for Chagas disease: 11,457 children treated 2017-2020 (approximately 25-50% of
number of infants born with Chagas disease)
HIV-TB Super-booster therapy: Guidelines improve concurrent HIV and TB treatment for 1 million children
Fexinidazole for HAT: 134 patients treated in 2020 (over 20% of all diagnosed patients; all others treated
with NECT).

Involvement and increase in R&D capacity of LMICs
DNDi supports four regional clinical research platforms. These “knowledge hubs” promote scientific
exchange, identify patients’ needs and R&D gaps, strengthen and sustain clinical research
capacity, facilitate access to new treatments, and advocate for an enabling policy and regulatory
environment for needs-driven R&D.
The disease platforms have been integral in supporting DNDi operations, and in particular its
clinical trials and in access activities. In total DNDi trained almost 4500 people during the evaluation
period through these platforms. During the years 2015-2020 DNDi conducted an average of 18
clinical trials each year in over 18 countries. Through DNDi’s clinical work over 17,000 people were
enrolled in DNDi clinical studies in the five-year period. DNDi prepared or maintained around 60
trial sites on average annually during the evaluation period, in countries like Bolivia, Brazil, DRC,
Guinea, Panama, Peru, Ethiopia, Kenya, Sudan and Uganda.
Sustainability
DNDi secured EUR 56 million in new funding in 2020. The 2020 Annual Report shows a large,
varied number of donors, in line with DNDi’s Fundraising Policy which does not allow any one
donor to contribute over 25% of all donations. This diminishes the risk of depending on one (or a
few) donors, thus contributing to sustainability of the organisation. Besides the Netherlands Ministry
of Foreign Affairs, the report lists 17 other public institutional donors, and includes 33 named
private donors, some of which are institutional donors. DNDi also receives funding from anonymous
individual donors.
In DNDi’s 2021-2028 Strategic Plan it reports DNDi raised EUR 630 million since 2003 and
estimates a projected budget of EUR 600 million for the strategic plan through 2028.
DNDi receives substantial unrestricted funding. While unrestricted funding comprised 52% of total
funding in 2020, it is a decrease from 71% in 2018.

5.2

Foundation for Innovative New Diagnostics (FIND)
MoFA Awards to FIND
FIND-1

Grant of € 7.9 million for the period 2006-2009

FIND-2

Grant of € 10.2 million for the period 2011-2014

FIND-3

Grant of € 10.1 million for the period 2015-2020

Extension 2021

Grant of € 2.0 million for 2021

Support to ACT-A/ Covid-19

Grant of € 5.0 million for 2021

Source: Netherlands Enterprise Agency (RVO)

Relevance
Relevance of the developed products for the individuals in need
FIND, the global alliance for diagnostics, takes on the roles of connecting communities, funders,
decision makers, healthcare providers and developers to advance diagnostic innovation, to ensure
equitable access to reliable diagnosis around the world. The goal is to strengthen testing at primary

Evaluation PDP III Fund 2015-2021

57

health care level for the vulnerable populations in LMICs, by removing the barriers that prevent
accurate and timely diagnosis and providing access to diagnostic tools that are available and
affordable.
Table 8

Burden of disease of FIND’s PDP III portfolio

Disease

Burden of disease

HCV (Hepatitis C)

Globally, 113 million people are estimated to be infected with Hepatitis C in
2019. 542 000 have died of hepatitis C related causes that same year.
Hepatitis C resulted in 15.3 million (95% UI 13.3–17.5) global DALYs in 2019
and 0.6% (0.5–0.7) of total global DALYs. Acute hepatitis, cirrhosis, and liver
cancer contributed 1.7% (0.9–2.5), 79.5% (76.1–82.7), and 18.9% (15.9–
22.2) to DALYs due to hepatitis C, respectively.

Tuberculosis

Globally in 2019, tuberculosis was one of the leading causes of death by a
single pathogen. Among HIV-negative individuals, the number of deaths was
1.18 million (95% UI 1.08–1.29) and the number of new cases of tuberculosis
was 8.50 million (7.45–9.73). 1.8 billion people are estimated to be exposed
to tuberculosis.
Among the regions with the highest burden are sub-Sahara Africa, South and
South-East Asia, and Eastern Europe and Central Asia. Drug-resistant
tuberculosis is an increasing problem in many of these countries.

Fever

No estimate available. However, FINDs diagnostics of fever aim to
distinguish between viral infections and bacterial infections. As an example, it
would be important to distinguish between a viral and bacterial cause lower
respiratory tract infections, such as pneumonia. In 2019, there were 489
million new cases of lower respiratory tract infections, causing 2.49 million
deaths and 97.2 million DALYs.
Lower respiratory tract infections is the number 5 leading cause of death in
LMICs. The largest disease burden occurs in sub-Sahara Africa and in
countries in South and Central Asia. Latin America also contributes
substantially to the burden of lower respiratory tract infections.

COVID-19

To date, approximately 247 million people have had COVID-19 since the
outbreak of the pandemic, COVID-19 caused 5 million deaths world-wide.
Among the or geographical entities win the top-10 of highest mortality rate is
only one with high-income: Taiwan. Yemen, Peru and Sudan are in the top 3
by death rate.62

Source: The Lancet (Hepatitis C, Tuberculosis, Fever); John Hopkins University (COVID-19)

Within the PDP III, FIND facilitates access to diagnostics, focusing on Hepatitis C, TB, and
malaria/fever management. In addition, FIND has received financial support from the Dutch
government to support FIND’s COVID-19 work within Access to COVID-19 Tools Accelerator (ACTA). Table 8 shows the burden and geographical spread of these diseases.
Relevance regarding SRHR policy of MoFA
FIND has not developed products directly related to SRH or to HIV/AIDS under PDP III funding,
although its wider product portfolio includes products directly related to SRH, such as a test to
detect gonorrhoea resistance to antibiotics, a test to distinguish gonorrhoea from chlamydia in
primary care, and a test to detect recent HIV infection.

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Evaluation PDP III Fund 2015-2021

FIND also contributed to the evaluation of a sex-based treatment algorithm for the malaria
treatment (P. vivax malaria with tafenoquine) as a new strategy to accelerate policy changes for P.
vivax radical cure using available tools.
Three studies have been conducted on high sensitivity RDTs to detect malaria in pregnancy, which
show that low-density infections, detected by these tests, are linked to increased risk of anaemia in
pregnant women.
In 2020 FIND co-hosted the event together with G20 Health and Development Partnership, Women
Political Leaders, and the International Council of Nurses, titled “Test to exit COVID-19: Engaging
women political leaders as champions for testing”63, which focused on highlighting women
leadership and engagement as champions for testing. The event was hosted on 22 June with 120+
participants from across the world.
As defined in the high-level workplan for the next 36 months, included in PDP Annual Funder
Report of 2020, FIND also covers women and children as a specific field of focus and defines
multiple objectives, e.g. improving antenatal NCD testing; increasing access to testing for women
targeting HIV, syphilis, malaria and hepatitis B testing in antenatal care; support malaria elimination
by improving tools for P. vivax.
With all aforementioned activities in mind, FIND is aligned in a broad sense with the SRHR ToC

and Results Framework (especially results areas 2 and 3) of the Netherlands Ministry of
Foreign Affairs.
Alignment Dutch Top Sector policy
FIND has been working with various Dutch partners with respect to academic research, policy and
advocacy. Below is the overview of Dutch partners that FIND has been working with:

Source: “Achievements FIND PDPIII 2015-2020"

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Evaluation PDP III Fund 2015-2021

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Effectiveness
Pipeline and original targets
Figure 5 shows the progression of the funding pipeline from 2015 – 2021, with a projection for
2022, which covers three disease areas supported by the PDP III fund: Tuberculosis, Malaria/Fever
and Hepatitis C. FIND has made progress in each of these focus areas. The majority of diagnostic
tools that FIND started with in 2015 and those that got introduced at a later stage progressed
through at least one phase through the pipeline.
Figure 5

Pipeline FIND

Source: Netherlands Enterprise Agency (RVO)

Tuberculosis
•

FIND has supported the development of next-generation TB LAM and point of care urine tests.
Together with partners FIND developed a suite of superior reagents for a prototype next
generation unite test to detect TB in HIV-negative people.

•

To inform the WHO screening guidelines, FIND conducted evaluations of three computer-aided
detection (CAD) for chest X-ray tools as a class of technology for triage and screening. This
technology is now formally recommended by WHO. FIND also conducted a landscape
assessment of the portable and ultra-portable X-ray systems regarding CAD implementation for
TB programs, to support CAD implementation in LMICs.

•

FIND has contributed to improving the detection of drug resistant TB, by partnering with
Cepheid to develop and evaluate the Xpert MTB/XDR test.

•

During the PDP II funding period, FIND has also started to develop a biomarker database which
allows identification of the best biomarkers for test development, which helps solving the siloed
research at individual institutions level.

Malaria and fevers
FIND has been supporting novel molecular tools for P. vivax and lead the development of a
serology P. vivax rapid test (RDT) for identification of patients with liver stage infections. It has also
worked on developing and validating tests for malarial and non-malarial fevers, covering tools to
differentiate bacterial and viral fevers. This has included work on Biomarker based fever test (BFFDX), which aims at improving care in non-sever patients in low resource settings. By 2020 the study
has collected data from Brazil and Malawi for approx. 10 host biomarkers. FIND has also
progressed with Malaria/CRP DUO test to support care of patients with fever in LMICs. In 2020
CRP-Malaria combo test evaluation study was conducted in India. Th results have been made
available to manufacturers in order to support the test registration in India. Further impacts studies

60

Evaluation PDP III Fund 2015-2021

have been carried out in Myanmar and Cambodia and early CRP implementation studies in
Vietnam, Thailand and Myanmar.
Hepatitis C
•

Since 2017 FIND delivered two point-of-care (POC) molecular tests. Together with partners
FIND has identified 4 quality assured rapid diagnostic tests (RTDs) for screening and selftesting (ST) for WHO pre-qualification clearance.

•

10 studies have been conducted on HCV self-testing to collect evidence on feasibility,
acceptability, and usability, to be used by WHO for HVC self-testing recommendation, with a
focus on marginalized populations.

•

FIND together with partners successfully completed cAg RDT prototype development, which
facilitates cheap and simple confirmatory test using the HCV core antigen (cAg) as a marker.

Impact of COVID-19
The COVID-19 pandemic presented not only challenges for FIND, but also substantial
opportunities. As described FIND is presently a main actor in the diagnostic response as a coconvenor with the Global Fund of the ACT-A Diagnostic Pillar. The ACT-Accelerator offers a
springboard for accelerated diagnostics innovation and implementation. For instance, FIND works
in ACT-A to develop capacity for sequencing of new health threats, variants and resistant bacteria
(AMR) globally. The strong focus on COVID-19 since February 2020 has not negatively affected
the effort to address diagnostic needs for the other diseases.
Access for the target groups and equity in access
FIND has a global access policy that is shaped around the “four A’s”, which means that diagnostics
developed by FIND are Available, Appropriate, Affordable and Adopted. Developing a global
access strategy for any specific intervention is a consideration in the earliest phases of project
planning, which includes in-country delivery and uptake. The importance of access has evolved in
the past years in FIND. Since 2015 there is an access team and program. That program focuses on
making sure that tests not only are used but then are linked to health outcomes that lead to
treatments or prevention interventions. This approach has been used in the development of tests
for HAT, together with DNDi, as a contribution to eradicating HAT.
By working on ensuring equitable access to diagnostics for poverty-related diseases as well as
COVID-19, FIND has undertaken multiple activities in order to improve access for vulnerable
groups including women and girls. Together with Women in Global Health, FIND gathered the
evidence on women’s access to testing and explored the potential role of women as drivers of
change in health systems, which resulted in the report published in 2020 “Health in their hands:
testing & women’s empowerment means better health for all”64.
In terms of special target groups for access to diagnostics, FIND is developing diagnostic tests for
TB in children, for which there are very few good tools to date. Besides, FIND is developing a fever
screening tool that has great relevance for children.
FIND has a gender equality policy. The gender equality policy addresses the organisation itself, as
well as programmatic activities. The latter includes assessments ‘to identify gender dynamics that
affect the disease and its control that will better enable the creation of innovative solutions’. In
addition, FIND commits to provide gender disaggregated data ‘for all interventions, to indicate
if/how gender impacts outcomes’. See the section ‘Relevance regarding Sexual and Reproductive
Health and Rights (SRHR) policy of MoFA’ for an overview of FIND’s activities to foster genderequity in diagnostics development.
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Distribution of developed products
FIND reports in its review of activities over 2015-2021 that it has provided “over 95 million products
[….] to LMICs. Of the supported products, 10 were in use in LMICs by end 2020, 67% of the
target”.65 No details are available on the type of products, timing and/or geographic spread of these
distributions.
Involvement and increase in R&D capacity of LMICs
In 2020, FIND trained 2 318 health workers (48% women) and strengthened 233 laboratories or
testing sites. In 2015, the number of trained health workers was 1 786. While FIND doesn’t state
where these health workers were situated, it is assumed that the majority of them come from LMICs
given FIND’s product portfolio.
FIND representatives have stressed the bi-directional relationship in their capacity building
activities.
FIND staff report a gap in local manufacturing capacity, while the need to enhance the actual
production of diagnostic tests is clearly there. COVID-19 has accelerated this need.

Sustainability
The FIND Annual lists 18 institutional donors in 2015. The latest annual report published, over
2019, reports 14 institutional donors. In this period, the total of contributions received by FIND
(USD 63.0 million) more than doubled. In 2019, the UK government (DFID) was the single largest
donor contributing to over one-fourth of FINDs budget that year. FINDs growing budget and its role
in developing diagnostics for the current COVID-19 pandemic is likely to contribute to its
sustainability, within the restrictions that PDPs face in developing products for which the patients or
consumers have no purchasing power.

5.3

International AIDS Vaccine Initiative (IAVI)
MoFA Awards to IAVI
IAVI-1

Grant of NLG 5 million for 1999

IAVI-2

Grant of NLG 45 million over four years awarded in 2000

IAVI-3

Grant of * over three years awarded in 2004

IAVI-3 suppl.

Supplementary grant of € 4 million

IAVI-4

Grant of € 16.2 million for the period 2006-2009

IAVI-5

Grant of € 13.3 million for the period 2011-2014

IAVI-6

Grant of € 16 million for the period 2015-2020

Extension 2021

Grant of € 3.2 million for 2021

Source: Netherlands Enterprise Agency (RVO)

Relevance
Relevance of the developed products for the individuals in need
IAVI is a Product Development Partnership established in 1996 to develop safe, effective,
accessible, preventive HIV vaccines for use throughout the world. IAVI has applied for PDP III
funding to advance the clinical development of HIV vaccine candidates working in close
collaboration with public and private partners worldwide, especially in Africa, to deliver the
Programme Goal of an expanded pipeline of novel HIV vaccine candidates, as well as other
biomedical HIV prevention methods, developed, designed and tested by IAVI and partners across

65

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Evaluation PDP III Fund 2015-2021

the world, which meet the needs of those most vulnerable to and disproportionately affected by
AIDS. Africa is the continent still disproportionally affected by HIV, with 1.4 million (93%) of all new
HIV infections globally each year occurring in SSA and women and girls accounting for 63% of
those new infections in 2020; there is still a global burden with LMICs on each continent harbouring
different key populations most at risk for HIV (and AIDS), see Table 9 for more details.
Table 9

Burden and geographical spread of HIV

Disease

Burden of disease66

HIV

Globally in 2019, the number of people living with HIV was 36.8 million. HIV-related deaths were
864,000 (95% UI 786,000–996,000) and the number of new HIV infections was 1·99 million
(1·76–2·26). People living with HIV have an increasing susceptibility to tuberculosis, and visceral
leishmaniasis.
The majority of burden was seen in sub-Saharan Africa, which had 74.0% (71.4–76.9) of global
HIV-related deaths in 2019. Numbers of new infections are still rising in Eastern Europe and
Central Asia, as well in the Middle East and North Africa.
Populations most at risk are adolescent girls and young women (highest burden: sub-Sahara
Africa), men who have sex with men, and transgender women (highest burden: Latin America),
sex workers (highest burden: South East Asia), people who inject drugs and incarcerated people
(highest burden: Eastern Europe and Central Asia).

Source: The Lancet

Relevance regarding SRHR policy of MoFA
The SRHR policy priority of the Netherlands MoFA includes HIV/AIDS. As such, IAVI fully aligns
with the current Theory of Change and Results Framework of this policy, particularly the result
“Support innovation for SRH and HIV/AIDS medicines and commodities” (result area 2, objective
D).
Alignment Dutch Top Sector policy
In spurring its vaccine development, IAVI has liaised with the following Dutch organisations amidst
of its 190 partners from academia, biotechnology, and pharmaceutical sector, as well as civil
society and global health initiatives:
•

Amsterdam Medical Centre;

•

Crucell/Janssen Pharmaceutical Companies;

•

Batavia Biosciences;

•

Erasmus University Medical Centre.

In addition, IAVI has long-standing advocacy partnerships with Aidsfonds, Share-Net, AIGHD and
KNCV.
Effectiveness
Pipeline and original targets
The pipeline (Figure 6) shows that IAVI has advanced a pipeline of 5 novel HIV prevention
approaches including those designed to ensure a durable and broad cellular and antibody
response. It also shows that one of these candidates progressed to phase 2b studies. This is in line
with the expected result in the project proposal, that anticipated 5-6 such novel vaccine
approaches, and to support the most advanced candidates towards phase 2b efficacy trials.
Additionally, in early 2021, IAVI and Scripps scientists released results from a germline targeting
vaccine (eOD GT 60mer) that successfully initiated the complex process of development of broadly
neutralizing antibodies (bnAb) in a Phase I clinical trial. Building on these positive results, IAVI will
66

The Lancet. Global Burden of Disease. GBD cause and risk summaries. https://www.thelancet.com/gbd/summaries
Accessed on 26 October, 2021.

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leverage mRNA technology to advance an mRNA eOD GT8 60mer vaccine later in 2021 in Phase
1 testing with an aim to ultimately generate potent and broadly protective antibodies.
Figure 6

IAVI’s product pipeline 2015-2022

Source: Netherlands Enterprise Agency (RVO)

Moreover, IAVI advanced four broadly neutralizing antibodies to preclinical development with three
first generation antibodies having completed evaluation in Phase I trials. With IAVI’s partner, the US
National Institute of Health (NIH), having established proof of concept in early 2021 for antibodybased prevention through the Phase IIb AMP trial, it is anticipated that antibody-based prevention
and the development of vaccines designed to generate such antibodies, can be accelerated.
Impact of COVID-19
As with most PDPs, the COVID-19 pandemic provided some opportunities and posed some
challenges for IAVI.
Opportunities
•

In the initial phase of the pandemic, February 2020, IAVI scientists responded rapidly and
began applying one of its HIV vaccine technologies — recombinant vesicular stomatitis virus
(rVSV) as a vaccine vector — to COVID-19.

•

While initial results of the candidate rVSV vaccine were disappointing, this has urged the
organisation to go back to the design lab to make improvements (ongoing) To strengthen
protective immune responses and apply formulations that can be especially suited to use in
resource-low settings. IAVI also applied its knowledge on neutralizing antibodies to identify
potent neutralizing antibodies from recovered COVID-19 patients. This portfolio of antibodies is
the foundation of a program designed to develop affordable and accessible antibodies with
potential application to COVID-19 and to new coronaviruses that may arise.

Challenges
•

COVID-19 presented a set of challenges for enrolment in and conduct of ongoing clinical trials.
The IAVI clinical research team and their partners met these challenges with new solutions, by
quickly deploying tools and methods to move many site monitoring visits and participant followup visits to virtual platforms with the aim of protecting the health and safety of staff, partners,
and participants. Direct data capture to reduce paper handling is also being increasingly used
and is improving efficiencies in data management for trials.

•

While some trials and trial sites experienced slower or lower enrolment due to the pandemic,
most trial targets are back on track, thanks to creative adaptations to local situations. IAVI
implemented other creative methods such as having trial staff contact volunteers by telephone
or WhatsApp for follow up. Planned in-person meetings, trainings and travel were also adapted
to virtual platforms where possible to ensure study activities continued.

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Evaluation PDP III Fund 2015-2021

Access for the target groups and equity in access
IAVI pays attention to gender balance in trial participation, having succeeded through gendermainstreaming in its actions to increase the participation by women to an average of 53.8%.
Through participation in the Coalition to Accelerate and Support Prevention Research (CASPR),
IAVI is strengthening the capacity of African CSOs representing adolescent girls and young women
(AGYW) and female sex workers (FSW) to champion their rights to exercise greater involvement in
decision making that affects them and creating an enabling environment for these female
populations to participate in the development of acceptable and needed HIV prevention tools (incl.
multi-purpose prevention technologies) to close critical gaps in women’s prevention toolkit/options.
Several IAVI publications address special issues of key populations for their effective involvement
in HIV research. IAVI’s approach to community engagement is essential to conduct safe and ethical
HIV research in a way that avoids the potential for social harm such as discrimination, genderbased violence and stigma to study participants, especially those most vulnerable, including
AGYW, men who have sex with men (MSM), transgender women, and fishing communities.
IAVI is also participating in research among key populations at risk for HIV and vulnerable
communities, garnering research insights in these communities that are relevant to guide policy
making in the AIDS response and for future product development. For instance, IAVI, in partnership
with the Uganda AIDS Commission, has developed guidelines and a road map for delivering HIV
and AIDS services in vulnerable Ugandan fishing communities; and helped develop National
Implementation Guidelines for HIV and STI Programming Among Young Key Populations, in
Kenya.
Distribution of developed products
As Figure 6 shows, IAVI does not yet have products in the implementation stage.
Involvement and increase in R&D capacity of LMICs
IAVI has forty clinical research partners in Africa and India as of 2020, including 11 state-of-the-art
clinical research centre partners with 12 GCLP-accredited laboratories capable of conducting
clinical research at international standards.
As part of the IAVI-led ADVANCE programme, that drives IAVI’s HIV Prevention & Community
Engagement work, IAVI collaborates through the CASPR Advocacy network of strategic
partnerships and activities toward supporting and strengthening India- and Africa-led biomedical
HIV prevention research, implementation, and advocacy. The CASPR network, led by AVAC,
brings together several Africa- and India-based partners — including the Wits Reproductive Health
and HIV Institute, WACI Health, HIV/AIDS Vaccine Ethics Group, the New HIV Vaccine and
Microbicide Advocacy Society, and Advocacy for Prevention of HIV and AIDS — to accelerate HIV
prevention research in Africa and India.
IAVI and partners published a total of 333 scientific publications during PDP III period with an
increase in articles co-authored or lead by African researchers from 29% to 64%. On average 28%
were female author. Through its Capacity Building Program, scientists in Africa were strengthened
in their basic science research skills to be able to more meaningfully contribute to HIV vaccine
design and become qualified scientists through degree training (Masters/PhD) with a total of 42
individuals supported by the International Training Program to date. Twenty-nine HIV vaccine
candidates have been advanced to clinical trials across 11 countries. To date, Phase I trials are
rarely conducted in LMICs, for regulatory and capacity reasons. IAVI managed its first ever Phase I
trials in Kenya, Rwanda, Zambia, India, (and Germany) in 2001. IAVI trained 970 Scientists in

Evaluation PDP III Fund 2015-2021

65

LMICs in Good Clinical Practices and GCLP to international standards for conducting clinical trials
in the years 2018 - 2020.
Sustainability
The 2020 IAVI Annual Report mentions across IAVI’s entire portfolio, 40 governments, foundations
and other donors, of which 12 government institutional donors. At December 31, 2020, grants from
U.S. Government agencies and foreign government agencies represented approximately 20% and
61% of grants receivable, respectively. In 2020, Dutch funding represented about 3% of total HIVrelated revenue, and about 4.6% of governmental donor funding.

5.4

International Partnership for Microbicides (IPM)
MoFA Awards to IPM
Core Funding to IPM of € 10 million for the period 2002-2008
IPM-1

Grant of € 12 million for the period 2006-2009

IPM-2

Grant of € 9.4 million for the period 2011-2014

IPM-3

Grant of € 14 million for the period 2015-June 2021

Extension 2021

Grant of € 2.8 million for 2021

Source: Netherlands Enterprise Agency (RVO)

Relevance
Relevance of the developed products for the individuals in need
Since its inception in 2002, IPM is dedicated to preventing HIV/AIDS and improving women’s
sexual and reproductive health by developing new HIV prevention and multipurpose prevention
technologies (MPTs). IPM works to improve women’s health by accelerating the development and
availability of safe, effective products women could use discreetly to protect themselves against
HIV, addressing a critical gap in the HIV prevention strategies currently available.
Table 10

Burden and geographical spread of HIV

Disease

Burden of disease

HIV

Globally in 2019, the number of people living with HIV was 36.8 million. HIV-related deaths were
864 000 (95% UI 786 000–996 000) and the number of new HIV infections was 1.99 million
(1.76–2.26). People living with HIV have an increasing susceptibility to tuberculosis, and visceral
leishmaniasis.
The majority of burden was seen in sub-Saharan Africa, which had 74.0% (71.4–76.9) of global
HIV-related deaths in 2019. Numbers of new infections are still rising in Eastern Europe and
Central Asia, as well in the Middle East and North Africa.
Populations most at risk for HIV are adolescent girls and young women (highest burden: subSahara Africa), men who have sex with men, and transgender women (highest burden: Latin
America), sex workers (highest burden: South East Asia), people who inject drugs and
incarcerated people (highest burden: Eastern Europe and Central Asia).

Source: The Lancet

IPM has advanced HIV prevention products for women that harness potent antiretrovirals (ARVs) to
address the urgent need for prevention methods that women can control themselves. Every minute
6 people under the age of 25 become infected with HIV. Among newly infected 15 –25 year olds in

66

Evaluation PDP III Fund 2015-2021

LMICs, females outnumber males two to one.67 This highlights the need for affordable, effective,
female-controlled HIV prevention methods such as the ones under IPM’s development.
Relevance regarding SRHR policy of MoFA
The SRHR policy priority of the Netherlands MoFA includes HIV/AIDS. As such, IPM fully aligns
with the current Theory of Change and Results Framework of this policy, particularly the result
“Support innovation for SRH and HIV/AIDS medicines and commodities” (result area 2, objective
D). IPM’s focus on female-controlled HIV prevention, which is hitherto underrepresented in product
development, is also broadly aligned with the result area 1 “Better information and greater freedom
of choice for young people about their sexuality”.
Alignment Dutch Top Sector policy
IPM has an extensive partnership network of 68 organisations. Among these, IPM lists the following
Dutch organisations:
•

Aidsfonds;

•

Global Network of People Living with HIV (GNP+);

•

Pharmaceutical Research Associates (PRA);

•

Venn Life Sciences (formerly Kinesis Pharma B.V.).

Effectiveness
Pipeline and original targets
IPM’s current product pipeline has moved the dapivirine vaginal ring from Phase 3 trials to
marketing stage. Further development focuses on products closely related to this ring, such as a
combination with a contraceptive, and a longer-acting dapivirine ring that could be used for 3
months instead of 1 month. Active development of the other 6 products in the pipeline has been
halted.
Figure 7

Pipeline IPM

Source: Netherlands Enterprise Agency (RVO)

Testing the dapivirine vaginal ring beyond Phase III trials to obtain priority regulatory approvals, and
provide early access to the ring to Phase III trial participants, is within the original objectives as
stated in the PDP III funding proposal.
The planned subsequent implementation and market introduction and delivery programs in at least
four African countries to support access to the dapivirine ring is also largely within the original
objectives as stated in the PDP III funding proposal. Approval has been received in Zimbabwe and
is pending in: Botswana, Eswatini, Kenya, Lesotho, Malawi, Namibia, Rwanda, South Africa,
Tanzania, Uganda and Zambia. Reportedly, four of these countries have also approved the ring
without yet having made their decision public.

67 UNAIDS. Gender & AIDS fact sheets: HIV/AIDS and young people.

https://data.unaids.org/topics/gender/youngpeople_en.pdf Accessed 28 October, 2021.

Evaluation PDP III Fund 2015-2021

67

Further development of the 3-month dapivirine-levonorgestrel ring for HIV prevention and
contraception to Phase III trials and the 3-month dapivirine-only ring to clinical trials, as outlined in
the PDP III funding proposal, has not been achieved. This is due to technical challenges related to
the ring device. Phase I safety-trials of the 3-month ring have been completed.
The planned preclinical/nonclinical studies on products based on various ARVs that were
mentioned in the PDP III proposal have been put on hold in response to advise from IPM’s
Scientific Advisory Board to focus IPM’s limited resources on:1. The monthly DVR (the licensure
program); 2. Dapivirine-contraceptive ring (MPT ring); and 3.
Impact of COVID-19
The impacts of COVID-19 on IPM’s work were monitored throughout 2020 across IPM’s
departments. Given IPM’s virtual work model and that there were no IPM-led clinical trials ongoing,
the impact on IPM’s programs was manageable. Some examples of the impact of COVID-19 and
how negative impacts were managed:
•

COVID-19 Impact on Regulatory and Quality Affairs Activities: Given imposed remote working
conditions, there were continued delays in compiling and transferring essential information for
drug regulators. IPM has put strategies in place to overcome and manage these delays.

•

COVID-19 Impact on Community Engagement Activities: In-person community outreach
activities - which form a significant part of IPM’s outreach activities - were halted in line with
country guidelines. To ensure continued outreach, IPM supported community-based partners
efforts to revise workplans so educational and support activities could progress, albeit on a
smaller scale.

•

COVID-19 provided an opportunity to examine how work and outreach could be continued
without face-to-face engagement. In response to the COVID-19 the situation, IPM provided
partners with non-pharmaceutical interventions (masks and hand sanitizers) and technical
support to host engagements using virtual platforms. Many successful engagements, trainings,
and dialogue sessions were implemented remotely. In 2020, 2,379 people (1,885 women and
494 men) attended community level training and skills building events. Online community
activities were hampered in rural and poor communities, where connectivity was limited
because people cannot afford smart phones or large data bundles.

Access for the target groups and equity in access
IPM has an access advisory committee to provide strategic guidance to help ensure the ring’s
successful introduction and uptake in sub-Saharan Africa, where women face the greatest risk for
HIV.
By developing and delivering safe, effective and affordable prevention products for women, IPM
incorporates demographic, geographic and gender equity in all its work.
To achieve maximum public health impact, equity is a necessary and vital component of any future
rollout strategy of IPM microbicide products. IPM conducts market and end-user research that
includes analysis by age, sex, geographic location and socioeconomic status, to address potential
inequities in product access and use.
IPM sees engagement with the community as crucial to realise access to IPM’s products. Womancentred healthcare can only be effective if women are part of the process. To support adolescent
girls and young women to stay informed and engaged, IPM continued to sponsor and utilize Inside
My Purse, a blog for and by young women in Africa to discuss topics of SRH and well-being in a
non-judgmental environment. This is just one example of ways IPM stays engaged with the
communities where the monthly dapivirine ring trials took place and market introduction is
expected.

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Evaluation PDP III Fund 2015-2021

IPM has started an engagement with health care workers, particularly making sure that they don’t
become the barrier for the ring for young people. According to IPM, a judgmental attitude about sex
may hamper access to HIV-prevention methods such as the dapivirine ring.
Distribution of developed products
As explained above the monthly dapivirine ring is now in the process of approval in several African
countries. Data on the distribution of the ring to the target group in these countries are not yet
available.
Involvement and increase in R&D capacity of LMICs
IPM has actively focused resources to build research capacity in sub-Saharan Africa. Over the
course of IPM’s clinical research, achievements included:
•

Increasing and developing physical infrastructure and strengthening human resource capacity
at research centres;

•

Developing research centre capability to conduct ethical and high-quality clinical trials

•

Providing professional development opportunities for research centre staff, including doctors,
nurses, counsellors, laboratory technicians, finance, community and administrative staff, among
others

•

During 2015-2020 IPM published 67 articles in peer-reviewed journals, of which 21 were LMICled.

Sustainability
In 2015 IPM reported having 10 grants for their work, from 8 different donors. In 2020 IPM reports 7
grants, by 7 donors (including PDP III). Although IPM planned to receive a new donor funding
commitment by the end of 2020, this did not materialise. IPM reports having submitted two funding
applications that could result in such a commitment. IPM staff report that the funding situation
currently is difficult. Taking all this into account, the funding situation and hence the sustainability of
IPM is a known risk that is included in IPM’s risk analysis and mitigation plan.

5.5

Medicines for Malaria Venture (MMV)
MoFA Awards to MMV
MMV

Grant of € 14,942,667 for the period 2015–2020

Extension 2021

Grant of € 2,988,533 for 2021

Source: Netherlands Enterprise Agency (RVO)

Relevance
Relevance of the developed products for the individuals in need
Medicines for Malaria Venture (MMV) is a Product Development Partnership (PDP) established as
a Not-for-Profit Swiss foundation in 1999. Its mission is to reduce the burden of malaria in diseaseendemic countries by discovering, developing and delivering new, effective and affordable
antimalarial drugs for vulnerable and under-served populations. Infants and women of childbearing
potential (WoCBP) currently represent two of the most vulnerable and underserved groups,
between them carrying the majority of the global malaria disease burden. Pregnant women are
more likely to bitten than other women, and are more likely to suffer severe consequences of
malaria, in part because pregnancy reduces a woman’s immunity, and also because the placenta
provides a location where malaria parasites can reside. A variable level of access to healthcare
decreases women’s access to malaria prevention and treatment and increases their vulnerability.

Evaluation PDP III Fund 2015-2021

69

Table 11

Burden and geographical spread of Malaria

Disease

Burden of disease68

Malaria

In 2019, there were 231 million new cases of malaria. Malaria was
responsible for 643 000 deaths (95% UI 302 000–1 150 000) in 2019.
356 000 deaths (169 000–626 000) occurred in children under 5 years,
comprising 7.1% (4.0–10.4) of total deaths in that age group. These numbers
comprise infection by the two most prevalent types of malaria parasites
(Plasmodium falciparum and Plasmodium vivax).
Endemic countries comprise most sub-Sahara African countries, as well as
countries in South and South-East Asia.

Source: The Lancet

Relevance regarding SRHR policy of MoFA
Although MMV does not develop products with a direct relationship with SRH, MMV’s mission
aligns with Ministry of Foreign Affairs’ objectives to support the development of innovative and
novel medicines designed for use in the most vulnerable patients (such as pregnant women and
very young children) and reduce maternal mortality rates. There is a clear focus on the main target
groups of the Dutch policy on SRHR (women of childbearing age; youths) and there is a direct link
with the SRHR Results Framework, since malaria treatment and prophylaxis during pregnancy
contributes to safe pregnancy and delivery in results area 2, objective E “Promote access to and
correct usage of safe, effective, quality and affordable medicines and commodities for: 1. Safe
pregnancy and delivery, modern family planning, post-abortion care and safe abortion 2. Prevention
and treatment of HIV/AIDS.”
Alignment Dutch Top Sector policy
Throughout the 5-year reporting period, MMV successfully collaborated with a number of Dutch
research organizations to complete the planned activities for PDP III, including:
•

TropIQ Health Sciences, Nijmegen;

•

Radboud University Medical Center, Nijmegen;

•

Pivot Park Screening Centre, Oss;

•

Lygature, Utrecht;

•

Biomedical Primate Research Centre, Rijswijk;

•

Mercachem, Nijmegen;

•

Consultants, e.g. Hermkens Consultancy.

These organizations assisted with the development and completion of drug screenings and
mosquito feeding assays, evaluation of mosquitocidal compounds, training of African scientists
and/or project management.
Effectiveness
Pipeline and original targets
Ten components or treatments for malaria moved up the pipeline one phase or more. This includes
transmission blocking agents mentioned in the PDP III funding proposal, developed in partnership
with Dutch partner TropIQ. Further progress during the funding period includes replenishing the
pipeline with the eyes on the emerging artemisinin resistance. This includes next generation tools
to replace today’s artemisinin-based therapies in Africa, and repurposing tools for severe malaria
as replacement for artemisinin monotherapies used today.

68

70

The Lancet. Global burden of disease. GBD cause and risk summaries. https://www.thelancet.com/gbd/summaries
Accessed 27 October, 2021.

Evaluation PDP III Fund 2015-2021

Figure 8 Pipeline MMV

Disease

Indication/treatment category*

Malaria

3 day cure, uncomplicated malaria, artemisinin-based combination therapy
Severe malaria
Severe malaria
3 day cure, uncomplicated malaria, artemisinin-based combination therapy
3 day cure, uncomplicated malaria, artemisinin-based combination therapy
3 day cure, uncomplicated malaria, artemisinin-based combination therapy
3 day cure, uncomplicated malaria, artemisinin-based combination therapy
3 day cure, uncomplicated malaria, artemisinin-based combination therapy

Malaria

Candidate/Entity/Manufacturer
Coartem® dispersible (artemether-lumefrantine), Novartis

2015

Larinate® 60 mg for injection (artesunate for injection), Ipca
Artesun® (artesunate for injection), Fosun Pharma
Eurartesim ® (dihydroartemisinin - piperaquine), Alfasigma

2021

2022

Implementation
Implementation

Pyramax ® (pyronaridine-artesunate), Shin Poong
Pyramax® granules pediatric (pyronaridine-artesunate), Shing Poong
ASAQ Winthrop® (artesunate-amodiaquine), Sanofi
ASMQ (artesunate-mefloquine), Cipla
SPAQ-CO™ dispersible (sulfaxodine-pyrimethamine+amodiaquine),
Seasonal Malaria Chemoprevention
Fosun Pharma
Seasonal Malaria Chemoprevention
Supyra® (sulfaxodine-pyrimethamine+amodiaquine), S Kant
DHA-PQP dispersible (dihydroartemisinin-piperaquine dispersible),
3 day cure, uncomplicated malaria, artemisinin-based combination therapy
Alfasigma
P.vivax relapse prevention
Tafenoquine (Kozenis/ Krintafel), GSK
Pre-referal in severe malaria
Artesunate Rectocaps (artesunate rectal capsules), Cipla
Pre-referal in severe malaria
Artecap™ (artesunate rectal capsules), Strides Pharma
Intermittent preventive treatment of malaria in pregnancy (IPTp)
Sulfaxodine- pyrimethamine, Universal Corporation
Sulfaxodine- pyrimethamine, S Kant
Intermittent preventive treatment of malaria in pregnancy (IPTp)
Sulfaxodine- pyrimethamine, Swhipha/Biogaran
Intermittent preventive treatment of malaria in pregnancy (IPTp)
Sulfaxodine-pyrimethamine, Emzor Pharmaceutical Industries Ltd.
3 day cure, uncomplicated malaria, artemisinin-based combination therapy for patients < 5kgArtemether-Lumefantrine for <5kg, Novartis
P. vivax relapse prevention
Tafenoquine paediatric, GSK
2-3 day cure, uncomplicated malaria, non-artemisinin based
Ganaplacide/Lumefantrine, Novartis
Non-artemisinin treatment for severe malaria
Cipargamin, Novartis
1-3 day cure, uncomplicated malaria, non-artemisinin based
M5717, Merck KGaA
Prophylaxis
Atoquanil, Ipca
1-3 day cure, uncomplicated malaria, non-artemisinin based; potential for severe malaria MMV533
ZY19489 (MMV253), Zydus Cadila
1-3 day cure, uncomplicated malaria, non-artemisinin based
MMV371, Janssen
Prophylaxis
1-3 day cure, uncomplicated malaria, non-artemisinin based
INE693, Novartis
Transmission blocking, 1-3 day cure, uncomplicated malaria, non-artemisinin based
MMV183, TropIQ
Uncomplicated malaria treatment for single-exposure radical cure (SERC) and/or
resistance management (TPP-1)

2020
Implementation

Implementation
Implementation
Implementation
Implementation

Implementation
Implementation

Implementation
PQ'd

Regulatory submission
Phase 3/4

Implementation

Development

Implementation

Development

Implementation

Manufacturing partnership in Progress
PQ'd
Manufacturing partnership in Progress
Phase 2

Development

Reg. review
Phase 2

Phase 2
Phase 1

Phase 2
Phase 1

Phase 1
Phase 1
Preclinical
Precl inical

Phase 1

Phase 2
Phase 1

Phase 2

Preclinical

Phase 1

Preclinical

Phase
1

GSK701, GSK

Source: MMV

Evaluation PDP III Fund 2015-2021

71

Not reflected in the funding pipeline but significant for the PDP III grant as it was mentioned in the
original funding proposal, is the research to establish the safety of artemisinine combination
treatments (ACTs) in early pregnancy. This includes setting up a registry, in cooperation with the
Liverpool School of Tropical Medicine, to monitor the use of different antimalarials during pregnancy
with an emphasis on the first trimester. This project started in 2020, with Dutch funding from 2021.
Impact of COVID-19
The global COVID-19 pandemic resulted in massive and unprecedented disruptions to all forms of
global industry, including scientific research and medical care. Main impacts on the activities of
MMV included:
•

many nations were forced to adopt strict restrictions on travel, which has limited the
collaboration of international research staff, preventing site visits and in-person training
activities.

•

Disruptions in global health supply chains and shortages of key medical products have been
experienced due to competition for manufacturing capacity between COVID-19 interventions
and other global health commodities, blocking and suspension of imports and exports of goods,
fluctuations in demand and panic buying.

•

The pandemic has placed a particular burden on the already restricted healthcare infrastructure,
staff, supply and storage facilities of resource-limited countries. As many of these countries are
also endemic for malaria, there have been significant concerns that pandemic-induced
shortages might oblige governments to shift their limited healthcare resources (financial and
human) to COVID-19 emergency care. This is predicted to result in a significant increase in the
number of cases and deaths for malaria. To illustrate this: 73% of malaria programmes have
been reported as disrupted.

MMV was nonetheless able to move a lot of its projects forwards. An important factor in this respect
was the global nature of MMV’s portfolio. In order to further mitigate the impact of the pandemicinduced challenges, various approaches had to be implemented:
•

For some partners doing experimental or clinical work there have been periods where scientists
working with MMV have been unable to do practical work, because of strict restrictions and
lockdowns. They focused on doing their work in other ways, just not experimentally.

•

Careful diligence of some of MMV’s CRO partners who had proactive measures in place,
resulted in hardly any days of work and productivity lost.

•

MMV helped establish medication stockpiles to mitigate shortages in antimalarial treatments
and preventative therapies.

•

At WHO’s request, MMV coordinated a multi-partner workstream to monitor on a weekly basis
any global risks to supply chain production and distribution of key antimalarial commodities
(primarily medicines, LLINs, diagnostics) as well as PPE.

•

Compounds from MMV’s portfolio with predicted antiviral activity were shared with researchers
free of charge as part of efforts to identify novel COVID-19 treatments. Consequently, two
treatments that have displayed good distribution to the lung and promising activity against
SARS-CoV-2 are currently being evaluated in clinical trials in South Africa.

•

MMV collaborated with organizations such as the WHO Global Malaria Programme, the
Wellcome Trust and the Bill & Melinda Gates Foundation to develop malaria/COVID-19
response policies designed to minimize the impact of the pandemic on malarial elimination
efforts.

•

Several nations were able to adapt existing malaria programmes to respond to the challenges
presented by COVID-19. In Zambia, healthcare workers were able to make use of
communication skills learned through MMV-sponsored training programmes to disseminate
public health messages on COVID-19 safety. In Ethiopia, two medical centres equipped with

72

Evaluation PDP III Fund 2015-2021

state-of-the-art laboratory equipment by MMV were transformed into fully functional COVID-19
testing facilities operated by MMV-trained clinical staff.
Access for the target groups and equity in access
MMV partners with ‘last-mile organisations’ who work hand in hand with the Ministries of Health to
build access strategies and routine systems that allow regular delivery of Malaria case
management. Examples are Catholic Relief Services, Clinton Health Access Initiative and the
Malaria Consortium. MMV has used data from malaria indicator surveys to make (very
conservative) estimates about patient impact of its medicines, by analysing each step of the access
delivery challenge: (a) drugs delivered to country, (b) drugs being available at the point of care
where needed; (c) at point of care, drugs being used correctly for malaria versus incorrectly for
something else.
Distribution of developed products
The pipeline of MMV shows 13 different products that are ready to be marketed (registration
obtained) or already being marketed. Six of these products were brought to the market after 2015
Total disbursements to date are higher for the eight older products. Table 12 gives a summary
overview. The older products have been registered in 10 to 50 countries (average: 27 countries).
For newer products the number of countries in which the products are registered is lower, at 1 to 13
countries.
Table 12

Distribution of products developed by MMV
Year
Approved

Treatments
distributed since
Launch

Data Source

Estimated Annual
Cases requiring
treatment

Data Source(s)

230 million
uncomplicated malaria
cases per annum

World Malaria Report 2020

3 day cure, uncomplicated malaria, artemisinin-based
combination therapy:
Coartem® dispersible (artemether-lumefrantine), Novartis
Generic copies of Coartem Dispersible ( by Ajanta, Cipla,
Ipca, Strides Pharma, Macleods, Mylan )

2011 7.8 million

Generic copy of Eurartesim (Guilin)
Pyramax ® (pyronaridine-artesunate), Shin Poong
Pyramax® granules pediatric (pyronaridine-artesunate), Shing
Poong

2019 3.5 million
2012 ~1 million

ASAQ Winthrop® (artesunate-amodiaquine), Sanofi

2008 537 million

ASMQ (artesunate-mefloquine), Cipla

Unitaid ACT Forecast and
additional analysis from GF
PQR database

2009-2021 1,530 million

Eurartesim ® (dihydroartemisinin - piperaquine), Alfasigma

Generic copies of ASAQ (Generics by Ajanta, Cipla, Fosun
Pharma, Ipca, Strides Pharma, Macleods)

MMV website:
https://www.mmv.org/node/1
1210/overlay

2008 430 million

MMV website:
https://www.mmv.org/node/1
1211/overlay
Global Fund dashboard
Company data

2015 ~1 million

Company data

MMV Website:
https://www.mmv.org/node/1
1529/overlay
Unitaid ACT Forecast and
additional analysis from GF
PQR database

2009-2021 419 million

2012 1.3 million

MMV Website:
https://www.mmv.org/node/1
1530/overlay

2013 355 million

MMV Website:
https://www.mmv.org/node/1
1531/overlay

Seasonal Malaria Chemoprevention
SPAQ-CO™ dispersible (sulfaxodinepyrimethamine+amodiaquine), Fosun Pharma

39 million children per
year

"Estimating the potential public health impact
of seasonal malaria chemoprevention in
African children"
DOI: 10.1038/ncomms1879

P.vivax relapse prevention
Tafenoquine (Kozenis/ Krintafel), GSK

no full product launch yet -2018 only small scale feasibility
studies to date

7 million cases per year

WHO MWR 2020

Pre-referal in severe malaria

Artesunate Rectocaps (artesunate rectal capsules), Cipla
2017

3.8 million rectocaps total

MMV website:
https://www.mmv.org/node/1
1235/overlay

MMV website:
https://www.mmv.org/node/1
2560/overlay

Artecap™ (artesunate rectal capsules), Strides Pharma

10 million severe malaria
cases per annum

Severe malaria
Larinate® 60 mg for injection (artesunate for injection), Ipca

2018 8.9 million vials

Artesun® (artesunate for injection), Fosun Pharma

2010 166 million vials

Most recent multi-country model/ survey about
prevalence of severe malaria establishes
estimate of 4.5%:
https://assets.researchsquare.com/files/rs32066/v1/6665691e-2834-4f2b-a680544b44f0dd9f.pdf?c=1631842221

MMV website:
https://www.mmv.org/node/1
2997/overlay
MMV website:
https://www.mmv.org/node/1
1206/overlay

Source: MMV

Evaluation PDP III Fund 2015-2021

73

Involvement and increase in R&D capacity of LMICs
MMV has built up a network of 107 clinical and discovery centres, increasing the research capacity
of 30 malaria-endemic countries.
Sustainability
The Dutch financing has been responsible for 1.4 to 4.7% of total income of MMV over the years
2015-2020. The total contribution of € 14.9 million represented about 9% of total governmental
funding during these years. Other governmental donors comprise United Kingdom, Germany,
Switzerland, Ireland, United States, Australia, Korea, Monaco and Norway.

5.6

TB Alliance
MoFA Awards to TB Alliance
TB Alliance-1

Grant of € 2 million awarded in 2005

TB Alliance-2

Grant of € 2 million awarded in 2006

TB Alliance-3

Grant of € 8 million for the period 2006-2009

TB Alliance-4

Grant of € 15.3 million for the period 2015-2020

Extension 2021

Grant of € 3.1 million for 2021

Source: Netherlands Enterprise Agency (RVO)

Relevance
Relevance of the developed products for the individuals in need
Since TB Alliance was established in 2000, it has led the global search and development of new
tuberculosis (TB) medicines, leveraging cross-sector partnerships to advance urgently needed TB
drug development. TB Alliance sees as their core mission to develop new, faster-acting and
affordable tuberculosis treatments for those in need, especially for the most vulnerable populations,
and in doing so have a considerable impact on the tuberculosis pandemic. TB Alliance defines as
their ultimate goal the development of “an ultra-short “universal” treatment that can cure all forms of
TB”69.
Table 13 shows the burden and geographical spread of tuberculosis, for which TB Alliance has
been developing treatments under the PDP III fund.
Table 13

Burden and geographical spread of tuberculosis

Disease

Burden of disease70

Tuberculosis

Globally in 2019, tuberculosis was one of the leading causes of death by a single
pathogen. Among HIV-negative individuals, the number of deaths was 1·18 million (95%
UI 1·08–1·29) and the number of new cases of tuberculosis was 8·50 million (7·45–
9·73). 1.8 billion people are estimated to be exposed to tuberculosis.
Among the regions with the highest burden are sub-Sahara Africa, South and South-East
Asia, and Eastern Europe and Central Asia. Drug-resistant tuberculosis is an increasing
problem in many of these countries.

Source: The Lancet

Relevance regarding SRHR policy of MoFA
There is no direct link between the actual products that TB Alliance develops, and SRHR.
Tuberculosis is still the leading cause of death of people living with HIV, and TB/HIV co-infection is

69
70

74

Achievements report: Achievements TB Alliance PDPIII 2015-2020
The Lancet. Global Burden of Disease. GBD cause and risk summaries. https://www.thelancet.com/gbd/summaries
Accessed on 26 October, 2021.

Evaluation PDP III Fund 2015-2021

common, certainly in sub-Sahara Africa where the new drug-resistant TB treatments will be
deployed.
The TB Alliance reports that it participated in a learning exchange led by MMV on the topic of R&D,
gender, and pregnant and lactating women. TB Alliance aims to contribute to this discussion, to
ensure that pregnant and lactating women are safely included into clinical studies according to
internationally defined legal, ethical, medical, safety, and scientific standards.
Based on the aforementioned actions, there is some, albeit indirect, alignment with the SRHR
Theory of Change and Results Framework (especially result 2 and 3) of the Netherlands Ministry of
Foreign Affairs.
Alignment Dutch Top Sector policy
TB Alliance has developed an extensive network of partnerships with Dutch parties, collaborating
with Dutch partners on execution of clinical trials, including clinical trial site for first-ever Phase 1
study of the compound TBAJ- 587 in the Netherlands (partner QPS Holdings LLC in Groningen), as
well as conducting market and costing analysis of TB products. Dutch partners include:
•

Erasmus University Medical Center;

•

KNCV Royal Netherlands Tuberculosis Association;

•

Médecins Sans Frontières Netherlands-Artsen Zonder Grenzen (MSF);

•

Radboud University Nijmegen Medical Centre (RUNMC);

•

Sonsbeek Pharma Consultancy B.V.;

•

Stichting Amsterdam Institute for Global Health and Development (AIGHD);

•

TropIQ Health Sciences;

•

VU Medical Center.

Effectiveness
Pipeline and original targets
Figure 9 shows the progression of the funding pipeline from 2015 – 2021 funded under PDP III, with
a projection for 2022. The most notable achievement is the approval of a new chemical entity
developed by TB Alliance pretomanid (Pa) as part of the BPaL regimen with bedaquiline (B) and
linezolid (L) for the treatment of people with highly drug-resistant forms of TB (DR-TB). It has been
approved by the U.S. Food and Drug Administration (FDA), the European Commission (EMA), the
Drug Controller General of India and incorporated into World Health Organization (WHO)
guidelines. TB Alliance reported that taking into account multiple approvals and guidelines, in 2020
pretomanid was available in 150 countries worldwide.
Figure 9

Pipeline TB Alliance

Source: Netherlands Enterprise Agency (RVO)

Since 2015 TB Alliance executed late-stage Phase 3 pretomanid containing trials including Nix-TB,
ZeNix-TB, and SimpliciTB, potentially shortening DR-TB treatment from between 9-18 months to six

Evaluation PDP III Fund 2015-2021

75

months and drug-susceptible TB treatment from six to four months. Regarding the earlier stage
clinical portfolio, in 2020 TB Alliance had five Phase 1 / 2 stage entities, namely TBA-7371 DprE1,
Sutezolid/oxazolidinone, TBI-223/oxazolidinone, TBAJ-587/diarylquinoline and TBA-J876/diarylquinoline.
TB Alliance also made progress in Paediatric Fixed Dose Combination (FDC) initiatives for drugsusceptible tuberculosis, although it was not directly supported by the DGIS funding. In 2020
Rifampicin / Isoniazid / Pyrazinamide were in Phase 4 phase.
These pipeline achievements of TB Alliance are broadly in line with the proposed objectives for
receiving the PDP III fund set out in 2015.
Impact of COVID-19
The outbreak of COVID-19 presented challenges to many aspects of TB Alliance work. Yet, TB
Alliance was able to respond quickly and adapt to the changing circumstances in order to continue
the planned activities. Various areas got impacted by the evolving COVID-19 pandemic situation
across regions:
Operations
The COVI-19 pandemic placed TB Alliance staff, contractors and consultants in difficult situation in
terms of the workload and uncertainly about the security. TB Alliance utilized already existing virtual
infrastructure to ensure the most effective way of working for personnel.
Pre-clinical activities and drug discovery
Since many of the TB Alliance’s pre-clinical partners are in Asia, the discovery and innovation
activities were impacted early on. TB Alliance responded to the situation by making use of the
partner model and quickly moving work to other partners (e.g. when China went into the lock down
at the beginning of 2020, the situation was mitigated by temporarily moving the research projects to
U.S, which then later on got moved back to China, once labs there got reopened.)
Clinical trials
Clinical trial activities faced multiple challenges, such as shipping drug products, transporting
samples to labs, and performing medical monitoring, which were addressed by regular meeting of
all Principle Investigators to find the needed solutions. TB Alliance also had to address disruptions
in continuation of community engagement, interruptions in supply chain, staff retention, travel
restrictions, increased costs of supplies and equipment.
New ways of patient retention and community support were created (e.g. ad-hoc dialogue groups
on COVID-19). When TB hospitals were shut down, for different clinical studies TB Alliance had to
modify protocols and find new techniques to continue the activities, e.g. telephonic meetings and
monitoring instead of in-person, delivery of drugs directly to patient’s homes, consolidating testing
schedules to minimize time at a clinic.
Financial uncertainty
TB Alliance also expressed the difficult financing climate caused by COVID-19 pandemic and its
economic impact on countries’ economies more generally, which translates into uncertain future of
PDP funding particularly coming from bilateral donors.
Access for the target groups and equity in access
TB Alliance worked on multiple fronts to improve access of tuberculosis treatments. It devoted
significant resources to facilitate and ensure global adaptation, availability, and affordability of BPal
regimen. TB Alliance progressed in BPaL registration and rollout. In 2020 TB Alliance (1) secured

76

Evaluation PDP III Fund 2015-2021

marketing authorization from European Commission for pretomanid in BPal, (2) its
commercialization partner Viatris secured approval in India, (3) BPaL was also included in WHO
treatment guidelines for DR-TB. Operational research to accelerate BPal implementation is planned
in key countries across Africa, Asia, Eastern Europe.
TB Alliance adopted a unique commercialization strategy within a broader PDP field, by recognizing
that generic pharmaceutical suppliers are needed to obtain high-quality and affordable (low-cost)
manufacturing. To that end by 2020 TB Alliance already made commercialization agreement with
three partners, which have complementary market reach but foster competition, to make sure that
the regimen is affordable, accessible and widely available. By bringing together industry partners
and procurement institutions like the Global Drug Facility and the Global Fund, TB alliance seeks to
ensure that countries can get access to new treatments at affordable prices.
TB Alliance addresses marginalized groups (e.g. people with disabilities, people living with
HIV/AIDS, groups who identify as having same-sex partners), by making sure that trial recruitment
plans consider these vulnerable populations.
TB Alliance also made a considerable contribution to addressing a gap in the paediatric TB market.
New TB cures for children in the appropriate dose and form were introduced by TB alliance in 2016.
By 2020 these child-friendly TB treatments have been ordered by 116 countries, covering 75% of
the estimated global childhood TB burden.71
In 2019 a paediatric investigation plan (PIP) for Pretomanid was submitted to the EMA. TB Alliance
is working together with the U.S government funded International Maternal Paediatric Adolescent
AIDS Clinical Trials Network (IMPAACT) to develop a paediatric pharmacokinetic and safety study
protocol for Pretomanid, 72 making this new product available for children with TB.
In high-burden countries in Sub-Saharan Africa, Eastern Europe, South and Southeast Asia new
TB regimens have to be tested which also provides access to special populations. TB Alliance
follows clinical research standards enrolling women in all its clinical trials (ranging from 30-50 % of
women participants). By following Good Participatory Practice (GPP), TB Alliance also puts
emphasis on community participation in clinical trials including women.73
Distribution of developed products
TB Alliance provided information on the supplies ordered by LMICs over the last five years for two
groups of products, namely 2 FDC DT (Rifampicin/Isoniazid (paediatric formulations) and 3 FDC DT
(including Rifampicin / Isoniazid / Pyrazinamide (paediatric formulations). It shows that a growing
number of countries have ordered such supplies since 2016-17 until 2019-2020. The number of
products ordered increased by more than 50% in these years, from roughly 1 million to 1,6 million
doses.
Table 14

Supplies ordered (in thousands) and number of LMICs ordering products developed by TB
Alliance

product

# of tablets sold

Packs of 84 sold

Treatment courses

RH 75/50 (2FDC DT)

367,641,288

4,376,682

1,021,226

RHZ 75/50/150 (3FDC DT)

182,007,168

2,166,752

1,011,151

Source: TB Alliance

71
72
73

Achievements report: Achievements TB Alliance PDPIII 2015-2020
Achievements report: Achievements TB Alliance PDPIII 2015-2020
PDP Funder Reporting 2020

Evaluation PDP III Fund 2015-2021

77

Involvement and increase in R&D capacity of LMICs
Most of TB Alliance’s clinical trial sites are located in LMICs, which means setting up trial capacity,
training and brining in the equipment to be able to carry out trials to the global standards that meet
registration requirements.
TB Alliance is working with clinical trial sites, coordinators and communities on the ground. It runs
Community Engagement (CE) programs, which provide technical assistance, skills training, and
small grant initiatives to the trial communities. Strong emphasis is put on research literacy and
dialogue with key local stakeholders, including trial participants.
Sustainability
During the PDP III grant period of 2015-2020 TB Alliance continued diversification of funding by
securing new donors and partnerships. Prior to 2015 TB Alliance funding was based on a few key
donors (such as BMGF, UK FCDO, USAID and US FDA). Since then donor base expanded and TB
Alliance added nine new donors, including both government bilateral funding agencies and private
foundations. In 2020 TB Alliance the total donor funding amounted to approx. US$62.5 million. The
graph below shows the donors and the percentage of their respective funding.

78

Evaluation PDP III Fund 2015-2021

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