Qualitative indepth analysis of
gaps in drug
development

Final
__

August 16th 2023

2

Content
Executive summary

3

1. Background of the study

10

2. Research approach used

12

3. Selection of conditions

20

4. In-depth analysis of selected conditions

28

5. Answers to research questions and conclusions

41

6. Appendices

44

— Appendix A: Overview of organisations that participated in the surveys
— Appendix B: Survey questionnaires
— Appendix C: Gaps in drug development for anxiety disorders

© 2023 KPMG Advisory N.V., all rights reserved

Document Classification: KPMG Confidential

2

Executive
summary

4

Executive summary

Improved balance between financial and social benefits of drug
development is desirable
Background and purpose of the study
A study into the financial ecosystem of drug research & development (R&D) shows
that, logically, commercial potential is a key driver of drug research. However, drugs
with commercial potential are not necessarily drugs for conditions with the highest
burden of disease. That begged the question of to what extent R&D activity into new
drugs is answering the societal need (as expressed in burden of disease).1
As a result of a possible suboptimal alignment of drug development to the societal
need, there may be conditions for which pharmacological treatment is desirable, but
for which no or only limited medication is developed. In this study, this is referred to as
"gaps in drug development". Other terms often used to indicate the discrepancy
between the development of drugs and the societal need for drugs are unmet medical
need or pharmaceutical blind spots.

indications drugs are currently being developed.2 The quantitative study describes the
numbers of registered and expected new drugs. This report contains the results of
subsequent qualitative research, describing for which of these 33 conditions there are
gaps in drug development and what the pharmacological need for these conditions
consists of. The factors contributing to the emergence of these gaps and the possible
solutions are also explored in a qualitative manner.

33 conditions with the highest annual
burden of disease

The Dutch Ministry of Health, Welfare and Sport asked KPMG to study "gaps in drug
development". KPMG translated this into the following research questions:
Research question 1: For which conditions is R&D activity in imbalance with the
societal need? Can the need for medicines for these conditions be categorised?

1. Conceptual model

Research question 2: Can these conditions be broken down into subindications?

2. Surveys & desk research

Research question 3: What are the causes of limited R&D activity and what can the
government do to encourage R&D activity for these conditions?

Funnel approach to identify gaps in drug development
The above research questions were answered using the funnel approach. This
research approach is presented in Figure 1.

3. Interviews
4. Focus groups

Starting point of this study are the 33 conditions with the highest
burden of disease
In a previously conducted quantitative drug development study, 33 conditions with the
highest annual burden of disease were defined. For these conditions it was mapped
out which drugs had been newly registered in the period 1995-2021 and for which
Source:

Figure 1: Funnel study approach

1. The Financial Ecosystem of Pharmaceutical R&D
2. Output current R&D ecosystem
© 2023 KPMG Advisory N.V., all rights reserved

Document Classification: KPMG Confidential

4

5

Executive summary

Funnel approach for identifying gaps in drug development
Step 1: Conceptual model

Step 2: Desk research and survey

A conceptual model was drawn up to enable a comparison of the 33 conditions. This
conceptual model consists of three composite indicators that together define the gaps
in drug development. The three selected indicators are:

Approach

— Societal need (Y-axis)
The societal need is defined as burden of disease expressed in Disability Adjusted
Life Years (DALYs).
— Relative potential improvement in R&D activity (X-axis)
This indicator shows that more R&D activity is possible and that, given the state of
knowledge, this R&D activity is considered promising. Because there is no unit for
improvement in R&D activity and it concerns a mutual comparison, this is referred to
as 'relative' potential improvement in R&D activity.
— Potential improvement in pharmacological treatment (colour coding)
This indicator indicates whether better pharmacological treatment is possible because
there is no effective drug yet, or because there is a need for drugs with a different
form of administration or fewer side effects.This dimension has been made into a
categorical variable, where the categories are displayed in different colours.
The conceptual model is populated with the 33 conditions with the highest annual
burden of disease; an overview of these conditions is shown on page 14. The
populated conceptual model can be plotted as a graph. Conditions on the curve have
equal improvement potential based on societal need and relative potential
improvement in R&D activity. (The potential improvement in pharmacological
treatment is not included in this yet). The two variables are inversely related. That is
the reason why an inverse curve is used to identify gaps in drug development.
Conditions above the curve have the greatest improvement potential based on
societal need and the relative potential improvement in R&D activity.

© 2023 KPMG Advisory N.V., all rights reserved

The conceptual model is populated based on desk research and a survey Existing
data was used to fill in the societal need expressed in DALYs and for the initial
detailing of the other two indicators. Existing data was obtained using desk research.
For a qualitative analysis of the potential improvement in R&D activity and the
potential improvement in pharmacological treatment and to populate the rest of the
conceptual model, a survey was conducted. The organisations approached for this are
listed in Appendix A, the survey questions are included in Appendix B.
Results
A condition-specific survey was conducted among members of scientific associations
and patient associations. This survey was completed 102 times; the response rate is
77.9%. In addition, a general survey was conducted among members of coordinating
scientific associations and professors of pharmacology. This survey was completed 60
times; the response rate is 42.9%. The input from the surveys and desk research was
used to plot the conceptual model.
Conditions on the curve have equal improvement potential based on societal need
and relative potential improvement in R&D activity. (The potential improvement in
pharmacological treatment is not included in this yet). The two variables are inversely
related. That is the reason why an inverse curve is used to identify gaps in drug
development. The curve is placed at the position where it makes a clear distinction
visible, with some ten conditions above the curve (as such, it can be seen as a 'cut-off
curve', so to speak).

Document Classification: KPMG Confidential

5

Executive summary

The conceptual model shows 11 conditions with a possible gap in
drug development.
Explanatory list:

Gaps inUnmet
drug
development
medical
need

400.000

1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.

20

350.000

300.000

Societal
Socialneed
needininDALY’s
DALY’s

8
11

250.000

44

200.000

77
22

99
150.000

24
1
13

100.000

34
34

12

5
15

50.000 16

14
30
35

33
23

0

22

27

29
17

6 10

21

19

26

Low

31

3
25

32

28

18

Relative
potential
improvement
ininR&D
Relative
potential
imrovement
R&Dactivity
acitivty

High

Figure 2: graphic representation of results of conceptual model
Caption:
Y-axis:
X-axis:
Colour:
Low potential

Anxiety disorders
Arthrosis
Asthma
Stroke
Breast cancer
Contact eczema
COPD
Coronary heart disease
Dementia
Diabetes mellitus
Diabetes mellitys type II
Colon cancer
Hearing disorders
Eye disorders
Heart failure
Cardiac arrhythmias
Brain cancer

18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
33.
34.
35.

HIV infections
Skin cancer
Hypertension
Upper respiratory infections
Lower respiratory infections
Leukemia
Lung cancer NSCLC
Lung cancer SCLC
Multiple myeloma
Multiple sclerosis
Non-Hodgkin lymphoma
Pancreatic cancer
Prostate cancer
Rheumatoid arthritis
Schizophrenia
Oesophageal cancer
Mood disorders
Parkinson's disease

Explanation of figure 2:
‒ The interviews and the survey retrieved for which conditions there are subindications
for which a distinction must be made in the remainder of the study. This distinction has
been made for Diabetes Mellitus type I and type II and for small cell lung carcinoma
(SCLC) and non-small cell lung carcinoma (NSCLC).
‒ The 33 conditions with the highest annual burden of disease (35 conditions including
subindications) are presented in Figure 2. The 11 conditions above the curve were
included in a longlist of conditions for which a gap in drug development may exist.
Based on the interviews, five conditions were selected from this longlist for which a
qualitative in-depth analysis was carried out. These are the conditions that are printed
in bold and underlined in the explanatory list, and indicated with a blue circle in figure
2. Breast cancer was not selected for a further in-depth analysis on the basis of the
interviews; for a detailed explanation, see pages 22 to 27.
‒ For hypertension, only data on the indirect burden of disease is available. Because
hypertension is a risk factor for many other conditions, the indirect burden of disease is
high. It is estimated at 390,000 DALYs.
‒ For multiple myeloma no burden of disease expressed in DALYs is available for the
Dutch population. Every year, approximately 1,300 people are diagnosed with multiple
myeloma. There are some 6,500 people with this form of cancer. Multiple myeloma
was included in the previous quantitative study because of the large number of new
drugs.

Societal need in DALYS per year for the Dutch population
Relative potential improvement in R&D activity Relative measure, therefore no unit is shown on the x-axis.
Potential improvement in pharmacological treatment:
Medium potential

High potential

© 2023 KPMG Advisory N.V., all rights reserved

No results from survey

Selected for qualitative in-depth analysis
Document Classification: KPMG Confidential

6

7

Executive summary

A qualitative in-depth analysis was carried out for arthrosis,
stroke, COPD, dementia and mood disorders
Step 3: Interviews
Approach
The interviews were used to validate whether the 11 conditions on the longlist were
recognised and whether any other conditions had to be included in the list. We also
asked interviewees whether there are any subindications for the conditions studied,
the pharmacological need for these conditions, and the current level of R&D activity.
Subsequently, a selection was made from the longlist of conditions for which further
qualitative in-depth analysis was carried out.
Results
A total of seven interviews were held with representatives of the pharmacological
industry, investors, professors of pharmacology and interest representatives. The
conditions arthrosis, stroke, COPD, dementia and mood disorders were selected from
the longlist for further qualitative in-depth analysis.a

subindications, whether the need consists of an improvement of current medication
the development of new medication, and whether this medication is available on other
markets (e.g. Japan or China).
— What are the possibilities/impossibilities of drug development?
This addressed the current level of R&D activity. In the case of lagging R&D
activity, the reasons for this were explained, such as a lack of funding or the
current state of science.
— What potential solutions exist to better meet the pharmacological need?
This last theme included questions about concrete solutions that national and
international governments could facilitate.
Results
Below, the main findings from the qualitative in-depth analysis in the focus group are
described for each condition.
Arthrosis

Step 4: Focus groups with experts
Approach
For each of the five selected conditions, further qualitative in-depth analysis was
carried out in focus groups. For the focus groups, a heterogeneous group of experts
was invited to shed light on the different perspectives of the pharmacological need
and R&D activity. The following experts were invited for the focus groups:
patients/patient representatives; healthcare professionals pharmacists; professors of
pharmacology; representatives of the pharmacological industry and investors. Not all
experts were represented in every focus group. The results described are not
exhaustive, but only present the findings from the focus groups.
Three main themes were discussed in the focus groups:
— What is the pharmacological need for these conditions?
Questions included whether the need concerns the condition as a whole or specific
Note:

There currently is no preventive, curative or disease-modifying pharmacological
treatment for arthrosis. There is, therefore, no need for improvement of existing
medication, but a need for new therapies. Arthrosis has many different manifestations,
each of which requires its own form of treatment. Recognising these manifestations is
necessary for better treatment: there is a need for patient stratification. Enabling
patient stratification requires facilitating diagnostics, such as advanced imaging or use
of biomarkers.
To demonstrate the effectiveness of disease-modifying arthrosis therapies, major
long-term - and therefore expensive - trials must be conducted. It is advocated as a
starting point not to look for a solution for the entire patient population, but to first
demonstrate the effectiveness of pharmacological treatment for a selected subgroup
of patients: a proof of concept.
The availability of new drugs can be simplified by rationalising the regulatory
framework for the approval of experimental drugs. One suggestion that was put
forward is the conditional approval of promising experimental drugs being studied.

a. These are not by definition the five conditions with the greatest improvement potential, but conditions that have been selected for further qualitative in-depth analysis on the basis of the
outcomes of the conceptual model and validation with experts.
© 2023 KPMG Advisory N.V., all rights reserved

Document Classification: KPMG Confidential

7

8

Executive summary

Encouraging drug development requires customisation
Stroke
There have been a lot of developments in the treatment of the acute phase of stroke.
There currently is little need for improvement of medicines for the acute phase of
stroke. There is, however, a need for drugs that can limit brain damage in the phase
immediately afterwards, for instance for swelling or inflammation. Lowering the burden
of disease of a stroke for the largest group of patients requires other measures than
drug development. Most can be gained from preventing strokes, which requires
recognition of patients with risk factors and prevention.
COPD
To understand the drug need for COPD, a classification according to treatable traits is
necessary. These include inflammation, bronchoconstriction and mucus formation. A
total of twelve treatable traits have been defined.3 These treatable traits offer different
starting points for drug treatment.
In terms of new drugs, there is a need for disease-modifying drugs that prevent loss of
pulmonary tissue, such as biologicals. There is also a need for pharmacological
regeneration of pulmonary tissue.

economies of scale now.This can be enabled by more continuity in funding and a
more favourable research and investment climate.
Mood disorders
Mood disorders include both bipolar disorder and major depressive disorder. The
pharmacological need is greatest for depression, both unipolar and bipolar
depressions.
It is indicated that the treatment of mood disorders requires further development of
existing medication. There is a need for faster acting drugs with fewer side effects. It is
also indicated that there is a need for new drugs. These new drugs are quicker acting
and take effect in a different way. Drug repurposing of psychedelics is mentioned as
the most promising option.
Investing in setting up networks is mentioned as a precondition for more effective
treatment. These networks seek to collect patient data, such as patient characteristics,
treatment and course of the disease. These networks ultimately make it possible to
better predict which treatment will work for which type of patient on the basis of patient
characteristics.

With regard to the need for improvement of existing medication, corticosteroids are
mentioned most often. These only work in some COPD patients and cause many side
effects. These patients need an effective anti-inflammatory.
There is also a need for anti-inflammatory drugs that effectively combat inflammation
without general immunosuppressive effect.
A possible solution put forward is encouraging the synergistic effect between
academia and industry.
Dementia
It has been indicated that there is a lot of R&D activity in the field of disease-modifying
treatment of dementia. There are several trials with positive results, as well as a few
approved medicines. However, the effect of these drugs is limited, the costs are high
and there are significant side effects. That is why it is emphasised to stimulate
Source:

3. Treatable traits: toward precision medicine of chronic airway diseases - PubMed (nih.gov)
© 2023 KPMG Advisory N.V., all rights reserved

Document Classification: KPMG Confidential

8

9

Executive summary

Patient stratification necessary for drug development for
different conditions
General views from focus groups on opportunities to stimulate drug
development
The focus groups mentioned several possible solutions to fill the gaps in drug
development for each condition. In addition to the condition-specific solutions, there
are a number of general solutions that were a recurrent theme in all focus groups.
Below is an overview of the possible solutions mentioned:
— Improving public-private partnership. Many good ideas originate in academia, but it
is usually the industry that has the investment power to scale up an idea.
Improving collaboration between the two will make it easier for universities and the
industry to jointly develop an idea up to the phase as a registered medicine. An
additional benefit would be that talented researchers can better be retained for
academia, where expertise in the current situation sometimes leaks away to,
among others, the pharmaceutical industry because it can offer more financial
security and there are more opportunities for further development of their ideas.
Agreements on intellectual property are mentioned as facilitator for improving
public-private partnerships.
— Simplifying the regulatory framework. The experts indicate that there is a culture in
the Netherlands in which the safety and rights of participants in scientific research
are properly safeguarded. However, the downside of this regulatory framework is
that it hinders conducting research in the Netherlands. International collaborations
in particular could increase sample sizes.

every healthcare institution has to deal with an increasingly selective patient
population. This affects the research populations in medical scientific research.
Access to complete and representative research populations and materials (such
as biobanks) must be guaranteed despite the centralisation of care.

Conclusions
Based on a funnel approach, this study identified for which conditions gaps in drug
development may occur. From these, five conditions were then selected for further
qualitative in-depth analysis. This shows that the emergence of gaps in drug
development is more complex than simply the lack of commercial potential of drugs.
Factors such as the state of knowledge, access to research populations and an
existing infrastructure for collaboration also play a key role. The extent to which each
of these factors applies varies per condition, is difficult to determine exactly and is also
subjective.
There are specific drug needs for the conditions mentioned. However, what all
selected conditions have in common is the need for patient stratification. In the past,
drugs for many conditions were developed for the patient group as a whole. However,
based on the current knowledge, it is clear that different conditions comprise different
subgroups that respond differently to treatments. There is a need to better recognise
these groups and develop treatments that target specific subgroups.

— More national and international control. For various conditions it is indicated that
other developments are preconditions for acceleration of drug development. These
include cooperation with primary care, the development of advanced diagnostics
and the possibility of patient stratification. Participants in the focus groups do not
expect that research into this will be initiated by the industry. That is why
international governments are called upon to take the helm.
— Improving the infrastructure. The Dutch research landscape is fragmented.
Improving the infrastructure would promote collaboration between universities,
authorities, primary care and patients. As a result of the concentration of care,

© 2023 KPMG Advisory N.V., all rights reserved

Document Classification: KPMG Confidential

9

1.

Background of the
study

1
1

The current R&D ecosystem results in gaps in the development of
medicines
Background
The study “The Financial Ecosystem of Pharmaceutical R&D”, published in 2022, has
shown that investors and industry weigh the commercial potential, the investment
costs and the potential of a medical breakthrough given the state of knowledge before
deciding on the development or further development of a drug.1 The relative
importance of the various factors can differ per investor and the stage of development
of the drug. This study shows that, logically, commercial potential is a key driver
determining whether a drug will be developed to launch. This makes the development
of new drugs in part dependent on the willingness of governments and insurers to pay
for these drugs.

selected conditions for which in-depth analysis was carried out on the basis of this
approach. Chapter 4 outlines the in-depth results for the selected conditions. Chapter
5 contains the recommendations. Appendix A provides an overview of all
organisations that were asked to participate in the surveys. Appendix B comprises the
complete surveys. Finally, Appendix C lists additional results for the condition ‘anxiety
disorders’.

However, drugs with commercial potential are not necessarily drugs for conditions
with the highest burden of disease. New drugs that are developed do not necessarily
meet the societal need for new drugs. As a result, there are conditions for which there
is a societal need for new medication but for which insufficient new drugs are
developed. In this study, the discrepancy between the drugs that are actually being
developed and the drugs for which there is a societal need is described “gaps in
drug development”.

Research questions
The Ministry of Health, Welfare and Sport has asked KPMG to conduct a study into
“gaps in drug development”. KPMG translated this into the following research
questions
Research question 1: For which conditions is R&D activity in imbalance with the
societal need? Can the need for medicines for these conditions be categorised?
Research question 2: Can these conditions be broken down into subindications?
Research question 3: What are the causes of limited R&D activity and what can the
government do to encourage R&D activity for these conditions?

Reader’s guide
Chapter 2 describes the research approach used. In Chapter 3, we explain how we
Source:

1. The Financial Ecosystem of Pharmaceutical R&D
© 2023 KPMG Advisory N.V., all rights reserved

Document Classification: KPMG Confidential

11

2.

Research
approach used

1
3

Identification of gaps in drug development by means of a funnel
approach
To identify gaps in drug development, we used a funnel approach, as presented in
Figure 3. Starting point were 33 conditions with the highest annual burden of disease.
This was followed by the following four steps:
1.

Development of a conceptual model for mutual comparison of the gaps in drug
development for these 33 conditions

2.

Plotting conditions in the conceptual model based on a survey and desk
research

3.

Validation and refinement of the outcomes of the conceptual model in various
interviews

4.

Qualitative in-depth analysis of a selection of conditions in focus groups

The steps in the study approach are discussed in more detail on this and the following
pages.

Starting point of this study are the 33 conditions with the highest
annual burden of disease
The 33 conditions with the highest annual burden of disease were taken as a starting
point for this study. These conditions follow from the research report “Output current
R&D ecosystem”. This report describes the number of market introductions of new
drugs between 1995 and 2021 for the 33 conditions with the highest annual burden of
disease. An overview of these conditions is presented on the next page.

33 conditions with the highest annual
burden of disease

1. Conceptual model
2. Surveys & desk research
3. Interviews
4. Focus groups

Rapportage
Figure 3: funnel study approach

© 2023 KPMG Advisory N.V., all rights reserved

Document Classification: KPMG Confidential

13

1
4

Overviewof the33 conditionswiththehighestannualburdenof
disease
Conditions with the highest annual burden of disease2, 4, a
1. Anxiety disorders

12. Hearing disorders

23. Lung cancer

2. Arthrosis

13. Eye disorders

24. Multiple myelomab

3. Asthma

14. Heart failure

25. Multiple sclerosis

4. Stroke

15. Cardiac arrhythmias

26. Non-Hodgkin lymphoma

5. Breast cancer

16. Brain cancer

27. Pancreatic cancer

6. Contact eczema

17. HIV infections

28. Prostate cancer

7. COPD

18. Skin cancer

29. Rheumatoid arthritis

8. Coronary heart disease

19. Hypertensionb

30. Schizophrenia

9. Dementia

20. Upper respiratory infections

31. Oesophageal cancer

10. Diabetes Mellitus

21. Lower respiratory infections

32. Mood disorders

11. Colon cancer

22. Leukaemia

33. Parkinson's disease

Source:
Note:

2. Output current R&D ecosystem
4. Burden of disease in 2018 via Vzinfo
a. This overview was created by selecting the forty conditions with the highest burden of disease. Of these, only those conditions were included in which pharmacological treatment plays at least a
reasonably large role. The overview was then extended by including conditions for which the burden of disease has fallen sharply due to the recent introduction of drugs. This resulted in an overview with
a total of 33 conditions.2
b. The disease burden for hypertension and multiple myeloma is not available via VZinfo. Hypertension has a high indirect burden of disease. Multiple myeloma is included in the overview because of the
large number of new drugs and the expected growth in the number of drugs.2
© 2023 KPMG Advisory N.V., all rights reserved

Document Classification: KPMG Confidential

14

1
5

33 disorders with the highest
annual burden of disease

1. Conceptual model

Step 1: A conceptual model with three indicators for mutual
comparison of the conditions
Conceptual model allows comparison of conditions

3. Interviews
4. Focus groups

The three indicators were plotted in a two-axis colour-coded model, as presented in
Figure 4 below. The following pages provide a more detailed explanation of each
indicator and how the input for each indicator was collected.

Conceptual model allows comparison of conditions
A conceptual model was drawn up to enable a comparison of the 33 conditions. The
conceptual model consists of three composite indicators that together define the gaps
in drug development. The three selected indicators are:
1.

Societal need, expressed in burden of disease based on DALYs

2.

The relative potential improvement in R&D activity

3.

The potential improvement in pharmacological treatment

Input

2. Survey & deskresearch

.

Output

Calculation

Display of the conceptual model output
Disease burden in DALY’s a year for
the Dutch population

Indicator 1 (y-axis):
Societal need

High

5

8

Extent of R&D activity into new drugs +
availability of logical explanation of any
low R&D activity
Availability of medication +
pharmacological treatment compared
to other treatment options

Potential improvement of existing
medication

Indicator 2 (x-axis)
Relative potential improvement in R&D
activity

Social need

10

12

4

11
7

Indicator 3 (color-coding):
Potential improvement in
pharmacological treatment

1

Low
Low

6

2

13

Relative potential improvement
in R&D activity

3

9
High

Caption color-coding: Indicator Potential improvement in
pharmacological treatment
Low potential

© 2023 KPMG Advisory N.V., all rights reserved

14

Medium potential

High potential

Document Classification: KPMG Confidential

15

1
6

33 disorders with the highest
annual burden of disease

Together, the three indicators of the conceptual model define
the gaps in drug development
Indicator 1: Societal need

Indicator 3: Potential improvement in pharmacological treatment

In this study, the societal need for drug development for a condition is expressed in
disease burden based on Disability-Adjusted Life Years (DALYs). The burden of
disease is the relative loss of health due to a condition. This includes loss of future
years of healthy life and loss of quality of life compared to a healthy person. One
DALY is equivalent to the loss of one year of life in complete health.5, 6 This study
looked at the total number of DALYs for the entire patient population in the
Netherlands, consisting of the burden of disease per patient times the number of
patients in the Netherlands. This information was collected by means of desk research
– see next pages.

The indicator ‘potential improvement in pharmacological treatment’ addresses the
following questions:

Indicator 2: Relative potential improvement in R&D activity
The potential to improve R&D activity depends on two factors: The extent to which
there already is R&D activity and the extent to which there is a logical explanation for
any low R&D activity.a A low score for this indicator means:

1. Conceptual model
2. Survey & deskresearch
3. Interviews
4. Focus groups

1.

Is medication currently available, and is it the most appropriate treatment? (Or are
other treatments, such as surgery, physical therapy or lifestyle interventions more
appropriate?)

2.

Is there a need for improvement of existing medication? For example reducing
side effects or a more user-friendly form of administration.

This information was collected using desk research and a survey – see next pages.
Two methods were used to populate the conceptual model: desk research and a
survey. The information collected in this way was quantified and plotted in the
conceptual model. This is explained on the next pages.

— A great deal of R&D activity, as a result of which little improvement is possible; or
— Little R&D activity, for which there is a logical explanation. For example, because a
breakthrough is not considered promising on the basis of the current state of
knowledge or because drugs are already available in other markets (such as
Japan or China).
In that case, little improvement is possible. A high score for this indicator means that
there is little R&D activity and that there is no logical explanation for this low activity. In
that case, improvement is possible.
As it concerns a mutual comparison of the conditions, this is not expressed with its
own unit, but in terms of relative potential improvement in R&D activity. This
information was collected using desk research and a survey – see next pages.

Source:
Note:

5. Disability-adjusted life years (DALY's) (who.int)
6. Annexes to the report ‘Overview 50% of the Dutch disease burden: conditions with a lead in outcome information and suitable for shared decision-making’
a. The indicator ‘Relative potential improvement in R&D activity’ does not include the number of new market introductions in the past few years, as this does not properly reflect the improvement potential in
R&D activity. After all, the number of past market introductions cannot predict current R&D activity. It is possible, for example, that high R&D activity has not yet resulted in a new drug.
© 2023 KPMG Advisory N.V., all rights reserved

Document Classification: KPMG Confidential

16

1
7

33 disorders with the highest
annual burden of disease

Step 2: The conceptual model is populated using desk research
and surveys (1/2)
Initial population of conceptual model based on desk research
The conceptual model was populated as much as possible using the results of desk
research. This resulted in an initial overview of conditions for which there may be
potential for improvement in aligning supply and demand for pharmacological
treatment. To find the societal need (expressed in DALYs), the number of DALYs per
condition was retrieved from the VZinfo database. For the other two indicators, we
consulted the report ‘Output current R&D ecosystem’, the website of the National
Institute for Public Health and the Environment (RIVM) and nationally applicable
guidelines for the various conditions.2, 7

Subsequently, specialist knowledge of the conditions was collected
by means of a survey
After the initial population based on desk research, a survey provided more depth and
insight into whether, and if so where, there are gaps in drug development for the 33
conditions. The survey was distributed among members of patient associations,
members of scientific associations and professors of pharmacology. To obtain a
representative picture, five members of scientific associations and three members of
patient associations were approached for each condition. Appendix A lists the
organisations that were asked to participate in the survey. The questions of both
surveys are presented in Appendix B.
Two surveys to match the content with the expertise of the respondents The
survey was distributed among a heterogeneous group of respondents. In order to
match the content of the survey as closely as possible with the expertise of the
respondents, it was decided to draw up two different variants of the questionnaire.
1.

Condition-specific survey: This survey contained questions for one specific
condition and was distributed to members of the patient associations and
members of the scientific associations of the relevant condition. The survey was
completed 102 times and the response rate was 77.9%.a

2.

General survey: This survey contained questions for all 33 conditions, with
respondents having the option to complete them for the conditions they had
knowledge of. This general survey was distributed to experts with a broad view of

Source:
Note:

1. Conceptual model
2. Survey & deskresearch
3. Interviews
4. Focus groups

the pharmaceutical landscape, such as professors of pharmacology and
members of general scientific associations. This survey was completed 60 times;
the response rate is 42.9%.a

Translation of collected information to conceptual model
The collected information was finally translated into a value for each indicator plotted
in the conceptual model:
1.

Indicator societal need: The disease burden in DALYs was determined for all 33
conditions on the basis of the VZinfo.nl database.7 The DALYs for each condition
are presented as absolute values that are plotted directly on the Y-axis of the
conceptual model.

2.

Indicator relative potential improvement in R&D activity: In the surveys,
respondents were asked how they describe current R&D activity on new drugs by
biotech and pharmaceutical companies for the respective condition. It concerned
a multiple-choice question in which a score was assigned to each answer: a high
score means a lot of improvement potential, a low score means little improvement
potential. The average score of all respondents resulted in a value that was
plotted in the model. As there is no unit for potential improvement in R&D activity,
the term ‘relative’ was added to this indicator.

3.

Indicator potential improvement in pharmacological treatment: In the surveys,
respondents were asked how they would describe the current situation of
medicines on the market, and what proportion of patients treated with
pharmacological products can be effectively treated with that medication. These
were also multiple-choice questions to which scores were assigned. The scores
were categorised into ‘low’, ‘medium’ and ‘high’, after which the corresponding
colour coding was added.

2. Output current R&D ecosystem
7. Ziektelast in daly's | Ziektelast | Volksgezondheid en Zorg (vzinfo.nl)
a. Response rate is an approximation, calculated based on the number of times the questionnaire has been sent. The questionnaire may have been further distributed within participating organisations.

© 2023 KPMG Advisory N.V., all rights reserved

Document Classification: KPMG Confidential

17

1
8

33 disorders with the highest
annual burden of disease

Step 2: The conceptual model is populated using desk research
and surveys (2/2)

1. Conceptual model
2. Survey & deskresearch
3. Interviews
4. Focus groups

As there is an inverse relationship between indicator 1 and indicator 2, an inverse
curve is presented in the conceptual model to identify the conditions for which there
may be a gap in drug development. Conditions on the curve have equal improvement
potential based on societal need and relative potential improvement in R&D activity.
The curve is positioned such that it makes a clear distinction visible, with some ten
conditions above the curve (as such, it can be seen as a 'cut-off curve', so to speak).
Finally, the findings from the conceptual model were confronted with explanations
from the open answers from the survey and the desk research results. For a small
number of conditions, this resulted in manual adjustment of the positions of conditions
in the model.

© 2023 KPMG Advisory N.V., all rights reserved

Document Classification: KPMG Confidential

18

33 disorders with the highest
annual burden of disease

Step 3: Validation of outcomes of conceptual model in interviews
Step 4: In-depth analysis of selection of conditions in focus groups
Step 3: Findings from the conceptual model were validated in
interviews to create focus for conditions for qualitative in-depth
analysis
After populating the conceptual model based on desk research and the surveys, a
longlist of conditions with possible gaps in drug development was drawn up. The
longlist comprised conditions that are above the curve in the conceptual model and
have a medium to high potential for improvement in pharmacological treatment.
A total of seven interviews were conducted. The interviewees were representatives of
the pharmaceutical industry, investors in the pharmaceutical industry, professors of
pharmacology, pharmacists and patient representatives.
The results of the conceptual model were validated in the interviews with the various
experts. For the 33 conditions that were taken as a starting point, it was tested
whether subindications exist within these conditions and, if so, whether these
subindications should be investigated separately in the remainder of the study. Other
questions served to collect information on whether the conditions on the longlist were
recognised and whether any conditions had to be added to the list. The list of
conditions shows where the need lies and what the status of R&D activity is.
Throughout the study, we have worked as accurately as possible. Nevertheless, it is
virtually impossible to obtain a complete overview of R&D activity on drug
development. While the experts interviewed have extensive knowledge of drug
development, they do not always have a complete picture. It is therefore emphasised
that the research results in this report are only an approximation of reality.
Based on the insights from the interviews, the longlist was reduced to a selection of
five conditions for which further qualitative in-depth analysis took place through focus
groups.
Which five conditions were selected is described in the next chapter.

© 2023 KPMG Advisory N.V., all rights reserved

1. Conceptual model
2. Survey & deskresearch
3. Interviews
4. Focus groups

Step 4: In-depth analysis of five conditions in focus groups with
experts
A focus group was held for each selected condition. The purpose of the focus groups
was to analyse the selected conditions in more depth with experts and to better
understand what is going on in the field of drug development for the conditions in
question. Three main themes were discussed in a two-hour digital meeting:
1.

An in-depth look at the pharmacological needs of each condition, with, where
necessary, a distinction according to subindications.
Within this theme, it was asked whether the need concerns the condition as a
whole or specific subindications, whether the need consists of an improvement of
existing medication or the development of new medication and whether this
medication is available in other markets (e.g. Japan or China).

2.

An in-depth look at the possibilities/impossibilities of drug development for the
condition.
This addressed the current level of R&D activity. In the case of lagging R&D
activity, the reasons for this were explained, such as a lack of funding or the
current state of science.

3.

Exploration of the possible solutions to fill the gap in drug development for the
conditions in question.
This last theme included questions about concrete solutions that national and
international governments or the Ministry of Health, Welfare and Sport could
facilitate.

The results of the focus groups are described in Chapter 4. In the focus groups we
talked to only a limited number of experts. The information obtained from the focus
groups may not be exhaustive, but only reflects the findings obtained in this manner.

Document Classification: KPMG Confidential

19

3.

Selectionof
conditions

The conceptual model shows 11 conditions with a possible gap in
drug development
Explanatory list:

Gaps inUnmet
drug
development
medical
need

400.000

1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.

20

350.000

300.000

Societal
Socialneed
needininDALY’s
DALY’s

8
11

250.000

44

200.000

77
22

99
150.000

24
1
13

100.000

34
34

12

5
15

50.000 16

14
30
35

33
23

0

22

27

29
17

6 10

21

19

26

Low

31

3
25

32

28

18

Relative
potential
improvement
ininR&D
Relative
potential
imrovement
R&Dactivity
acitivty

High

Figure 4: graphic representation of results of conceptual model
Caption:
Y-axis:
X-axis:
Colour:
Low potential

Anxiety disorders
Arthrosis
Asthma
Stroke
Breast cancer
Contact eczema
COPD
Coronary heart disease
Dementia
Diabetes mellitus
Diabetes mellitys type II
Colon cancer
Hearing disorders
Eye disorders
Heart failure
Cardiac arrhythmias
Brain cancer

18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
33.
34.
35.

HIV infections
Skin cancer
Hypertension
Upper respiratory infections
Lower respiratory infections
Leukemia
Lung cancer NSCLC
Lung cancer SCLC
Multiple myeloma
Multiple sclerosis
Non-Hodgkin lymphoma
Pancreatic cancer
Prostate cancer
Rheumatoid arthritis
Schizophrenia
Oesophageal cancer
Mood disorders
Parkinson's disease

Explanation of figure 4:
‒ The interviews and the survey retrieved for which conditions there are subindications
for which a distinction must be made in the remainder of the study. This distinction has
been made for Diabetes Mellitus type I and type II and for small cell lung carcinoma
(SCLC) and non-small cell lung carcinoma (NSCLC).
‒ The 33 conditions with the highest annual burden of disease (35 conditions including
subindications) are presented in figure 4. The 11 conditions above the curve were
included in a longlist of conditions for which a gap in drug development may exist.
Based on the interviews, five conditions were selected from this longlist for which a
qualitative in-depth analysis was carried out. These are the conditions that are printed
in bold and underlined in the explanatory list, and indicated with a blue circle in figure
4. Breast cancer was not selected for a further in-depth analysis on the basis of the
interviews; for a detailed explanation, see pages 22 to 27.
‒ For hypertension, only data on the indirect burden of disease is available. Because
hypertension is a risk factor for many other conditions, the indirect burden of disease is
high. It is estimated at 390,000 DALYs.
‒ For multiple myeloma no burden of disease expressed in DALYs is available for the
Dutch population. Every year, approximately 1,300 people are diagnosed with multiple
myeloma. There are some 6,500 people with this form of cancer. Multiple myeloma
was included in the previous quantitative study because of the large number of new
drugs.

Societal need in DALYS per year for the Dutch population
Relative potential improvement in R&D activity Relative measure, therefore no unit is shown on the x-axis.
Potential improvement in pharmacological treatment:
Medium potential

High potential

© 2023 KPMG Advisory N.V., all rights reserved

No results from survey

Selected for qualitative in-depth analysis
Document Classification: KPMG Confidential

21

2
2

Validation of the longlist in interviews results in in-depth analysis of
arthrosis, COPD, mood disorders, stroke and dementia(1/6)
Based on the graph on page 21, a longlist of 11 conditions was drawn up. In in-depth
interviews, this longlist of conditions was presented to experts. The table below shows
for each condition what the most important findings were and why the condition was or
was not selected for further qualitative in-depth analysis. The selected conditions are
not necessarily the conditions with the greatest improvement potential. These are
Condition

conditions for which their position in the graph on page 21 shows that there are gaps
in drug development and for which, based on the interviews, there is also potential for
improvement. The findings described for the selected conditions mentioned also serve
as an example for the other conditions.

Key findings

Anxiety disorders

Societal need:

127,800 DALYs. The high number of DALYs can be explained by the large
patient population.

Potential improvement
in R&D activity:

Although the disease burden of anxiety disorders is slightly higher than
that of mood disorders, the potential improvement in R&D activity has
been reported to be greater for mood disorders.

Pharmacological
treatment:

There is a lot of improvement potential in terms of pharmacological
treatment. Because there is overlap with the treatment of mood disorders,
it was decided to discuss mood disorders in the focus groups.

Selected for further qualitative in-depth
analysis


Given the overlap in the treatment of
anxiety disorders and mood disorders, it
has been decided to study only one of the
two in more depth. In the mood disorders
focus group, similarities and differences
with anxiety disorders were briefly
discussed (see Appendix C).

Caption:


Selected for qualitative in-depth analysis



Partial qualitative in-depth analysis in combination with other condition

—

Not selected for qualitative in-depth analysis

© 2023 KPMG Advisory N.V., all rights reserved

Document Classification: KPMG Confidential

22

2
3

Validation of the longlist in interviews results in in-depth analysis of
arthrosis, COPD, mood disorders, stroke and dementia(2/6)
Condition
Arthrosis

Stroke

Key fndings

Selected for further qualitative in-depth
analysis

Societal need:

165,800 DALYs. Concerns a large population. Immobility due to arthrosis
has an additionally negative health effect.



Potential improvement in
R&D activity:

Now that it is becoming increasingly clear that arthrosis is more than wear
and tear, there are more targets for its treatment.

Pharmacological
treatment:

Only drugs for symptomatic treatment are available. No preventive,
modifying or curative treatment possible

Arthrosis was selected due to the high burden of
disease, increasing incidence and major direct
and indirect effects on other health aspects.
Arthrosis is also relevant given the new
treatment options created by recognition of
different subindications.

Societal need:

248,000 DALYs. Does not only affect a large group of patients, but also their
informal caregivers.



Potential improvement in
R&D activity:

A stroke can be divided into different phases. In the acute phase, there is a
need for anticoagulant medication and the possibility of reversing the effects
of prophylactic anticoagulant medication. There is also a need for
neuroprotective drugs.

Pharmacological
treatment:

Existing prophylactic medication cannot protect all patients yet. They also
have side effects. Existing medication can be improved and new drugs can
be developed.

Stroke has been selected due to the high burden
of disease. Based on the interviews there is
greater scope for potential improvement in
pharmacological treatment than the results from
the conceptual model suggested.

© 2023 KPMG Advisory N.V., all rights reserved

Document Classification: KPMG Confidential

23

2
4

Validation of the longlist in interviews results in in-depth analysis of
arthrosis, COPD, mood disorders, stroke and dementia(3/6)
Condition
Breast cancer

COPD

Key fndings

Societal need:

81,300 DALYs for all forms of breast cancer together. The disease burden at
population level for the triple negative variant of breast cancer only is low
compared to other conditions.

Potential improvement in
R&D activity:

There already is a lot of R&D activity with respect to most oncological
conditions. There is a need for more R&D activity in particular for the triple
negative variant of breast cancer.

Pharmacological
treatment:

Scope for improvement, primary treatment is still tumour resection.

Societal need:

188,500 DALYs. As a result of air pollution, the number of lung diseases
may increase further, so there is a growing need for the development of
drugs for the treatment of COPD.

Potential improvement in
R&D activity:

For COPD, it is indicated that there is a lot of overlap with the treatment of
asthma, despite the fact that the pathophysiology is different. No diseasemodifying treatment is available yet.

Pharmacological
treatment:

Current medication has side effects and is not always easy to titrate. In
order to better influence the disease and its consequences, the most
potential is seen in pharmacological treatment.

© 2023 KPMG Advisory N.V., all rights reserved

Selected for further qualitative in-depth
analysis

—
For most oncological conditions there is little
scope for improvement in R&D activity. As
regards breast cancer, there is scope for
improvement for the triple negative variant.
However, the disease burden of this specific
variant is relatively low compared to that of
other conditions. It was therefore decided not
to analyse breast cancer in more depth.


COPD has a high disease burden and there
is a lot of scope for improvement in R&D
activity. This was confirmed in the interviews,
which is why COPD was selected for indepth analysis.

Document Classification: KPMG Confidential

24

2
5

Validation of the longlist in interviews results in in-depth analysis of
arthrosis, COPD, mood disorders, stroke and dementia(4/6)
Condition
Coronary heart
disease

Dementia

Key fndings

Societal need:

271,300 DALYs; there is a great societal need because of the combination
of a large patient population and a high burden of disease.

Potential improvement in
R&D activity:

Based on the survey, R&D activity is low, which seems to be explained by
the treatment options that are already available and the expectation that the
greatest developments will come from non-pharmacological therapies.

Pharmacological
treatment:

It is indicated that compliance is a more limiting factor than the availability of
medication. In addition, more is expected from minimally invasive
interventions.

Societal need:

163,600 DALYs. In addition to the burden of disease in DALYs, there is also
a great need among informal caregivers of patients with dementia for new
and different pharmacological treatment.

Potential improvement in
R&D activity:

Investments made in recent years have not yet led to groundbreaking new
treatment.

Pharmacological
treatment:

There is a need for preventive, curative and disease-modifying treatment.

© 2023 KPMG Advisory N.V., all rights reserved

Selected for further qualitative in-depth
analysis

—
Despite the high disease burden, the
interviews show that the low R&D activity
can be explained. It has therefore been
decided not to analyse coronary heart
disease in more depth.


Dementia has a high disease burden. The
interviews show that the pharmacological
treatment of dementia is gaining momentum;
there is more scope for improvement in R&D
activity than appears from the surveys. It
was therefore decided to analyse dementia
in more depth.

Document Classification: KPMG Confidential

25

2
6

Validation of the longlist in interviews results in in-depth analysis of
arthrosis, COPD, mood disorders, stroke and dementia(5/6)
Condition

Key fndings

Diabetes Mellitus
Type II

Societal need:
Potential improvement in
R&D activity:
Pharmacological
treatment:

Hypertension

The disease burden of both types of diabetes together totals 201,000
DALYs. Diabetes Mellitus Type II has the greatest share in this.

—

Due to the great need in areas other than
It is indicated that there are relatively many treatment options, therefore
there is little room for improvement in R&D activity with regard to new drugs. drug development, it was decided not to
study Diabetes Mellitus Type II in more
depth.
The greatest need consists of other forms of administration of existing
medicines and treatments in the form of lifestyle adjustments.

Societal need:

No disease burden for hypertension itself can be determined. Hypertension
often underlies other conditions; the indirect burden of disease is estimated
at 390,000 DALYs.

Potential improvement in
R&D activity:

There are a lot of effective treatment options. Currently little scope for
improvement in terms of R&D activity.

Pharmacological
treatment:

For hypertension, it is indicated that no improvement potential is seen in
pharmacological treatment. There is room for improvement in terms of
lifestyle and adherence to therapy.

© 2023 KPMG Advisory N.V., all rights reserved

Selected for further qualitative in-depth
analysis

—
It is explicitly stated that the greatest need
for the treatment of hypertension is not
pharmacological but through other routes. It
was therefore decided not to analyse
hypertension in more depth.

Document Classification: KPMG Confidential

26

2
7

Validation of the longlist in interviews results in in-depth analysis of
arthrosis, COPD, mood disorders, stroke and dementia(6/6)
Condition

Key fndings

Lung cancer
(NSCLC)

Mood disorders

Selected for further qualitative in-depth
analysis

Societal need:

The disease burden of lung cancer is 165,800 DALYs Approximately 80% of
lung cancer cases concerns NSCLC.

—

Potential improvement in
R&D activity:

The surveys indicate that there is a need for more pharmacological
treatments specifically for NSCLC, but the interviews show that R&D activity
is high for almost all oncological diseases. Based on the interviews, there is
less room for improvement in R&D activity than previously thought.

Pharmacological
treatment:

In addition to surgical treatment, it is expected that there will be an
increasing role for pharmacological treatment.

Based on the interviews, there seems to be
less relative potential improvement in R&D
activity than the graph shows. It was
therefore decided not to analyse lung cancer
(NSCLC) in more depth.

Societal need:

98,200 DALYs. This is a little less than for anxiety disorders.

Potential improvement in
R&D activity:
Pharmacological
treatment:

© 2023 KPMG Advisory N.V., all rights reserved



There is relatively little understanding of the underlying pathophysiology. As Although the burden of disease is slightly
there is a lot to be gained in this area, relatively much potential is seen in the lower, so much more potential is seen in the
improvement of R&D activity.
improvement in R&D activity that it was
decided to analyse mood disorders in more
depth.
There is a lot of potential for improvement of existing medication.

Document Classification: KPMG Confidential

27

4.

In-depth analysis
of selected
conditions

2
9

Selected conditions were analysedin more depth in focus groups
Based on the outcomes of the conceptual model and the interviews, five conditions
were selected for further qualitative in-depth analysis. This was conducted in focus
groups. For all focus groups, a heterogeneous group of experts was approached
consisting of healthcare professionals, researchers, representatives of the
pharmaceutical industry, investors, patient representatives, hospital pharmacists and
professors of pharmacology.
In the focus groups, three main themes were discussed with the experts: the
pharmacological need, the possibilities and impossibilities of drug development and
an exploration of the solution options to fill the gap in drug development.
All the experts asked to participate had a broad view of trends and developments in
the field of drug development. Despite this, each focus group remains a
representation of the findings retrieved in a selected group. As such, the results are
subjective and possibly not complete.

© 2023 KPMG Advisory N.V., all rights reserved

Document Classification: KPMG Confidential

29

3
0

Arthrosis: A key prerequisite for optimisationof pharmacological
treatment is patient stratification (1/2)
In the Netherlands, approximately 1.5 million people suffer from arthrosis. This joint
disorder can present in one or more joints. Arthrosis affects the quality of the cartilage
and can cause inflammation of the tissues in the joint and changes in the bone at the
joint. Arthrosis is accompanied by pain and stiffness, affected joints can become
swollen and unstable and creak when moved.8 Arthrosis can lead to changes in
posture. As a result of the symptoms of arthrosis, patients often become less mobile,
which has an indirect negative effects on health.
Subindications
Arthrosis has long been considered a homogeneous form of joint wear. There are,
however, different manifestations (we do not speak of subindications, but of
manifestations). Patients can suffer from one or more manifestations of arthrosis, and
the manifestations can change over time in a patient. Examples are: inflammatory
arthrosis, post-traumatic arthrosis, arthrosis as part of metabolic syndrome or arthrosis
as a result of stress or strain.9, 10 In addition, there are probably even more undiscovered - forms of arthrosis.
1. Description of the need for drug development for arthrosis
The currently available treatment focuses solely on pain management. There is little
need for improvement of existing medication. At present, no preventive or curative
treatment of arthrosis is possible. In addition to prevention and cure, the need for
medical treatment of arthrosis consists of disease-modifying treatment. Diseasemodifying medication should enable inhibition of cartilage degeneration. Of the
different manifestations of arthrosis, the potential of pharmacological treatment is
greatest for inflammatory arthrosis.
2. Possibilities/impossibilities of drug development for arthrosis
— Patient stratification is a prerequisite for further development of medication

effective use of resulting treatments. To enable patient stratification, more research is
needed into different forms of diagnostics such as advanced imaging and the use of
biomarkers.
— Drug repurposing for disease-modifying medication is a promising option
Drug repurposing means that existing medicines are also used or investigated for
other indications. This concerns both registered and non-registered medicines. In the
past, a lot has been invested in the development of a generic treatment for arthrosis.
These drugs often proved ineffective in phase II research (exploratory and
therapeutic). As a result, development of many drugs foundered in this phase.
However, these drugs were tested for effectiveness in the patient population as a
whole. The experts indicate that when better patient stratification is possible, these
medicines can be administered in a more targeted manner to subgroups of patients
and may be effective. The experts see opportunities via this route for repurposing of
drugs that were originally developed for arthrosis. As the safety of these drugs has
already been demonstrated, phase I medicine research can be skipped. This could
lead to faster drug development at lower costs.
— Accelerated further development of medication due to proof of concept
The experts state that it is important to set realistic goals. There has been a long
search for a drug that can inhibit cartilage degeneration for the entire group of
patients. An action that could lead to a step forward in the treatment of arthrosis is a
proof of concept study, in which cartilage degeneration can be demonstrably inhibited
in a selected group of patients. Demonstrating effectiveness of disease-modifying
treatment in a selected group of patients increases confidence in the success rate. As
a result, investors will be more inclined to invest in further development of arthrosis
medication. In this way, a proof of concept can have a reinforcing effect on drug
development.

The different manifestations of the condition make the group of patients suffering from
arthrosis heterogeneous. The different manifestations have their own target for
treatment, and relatively much is known about possible targets for disease-modifying
treatment in arthrosis. However, patient stratification is an important precondition for
Source:

8. Artrose | Alles wat je moet weten • ReumaNederland
9. Artrose toch een inflammatoire aandoening? | NTvG
10. Living with Inflammatory Arthritis: What You Need to Know | HSS

© 2023 KPMG Advisory N.V., all rights reserved

Document Classification: KPMG Confidential

30

3
1

Arthrosis: A key prerequisite for optimisationof pharmacological
treatment is patient stratification (2/2)
3. Suggestions for improvement in R&D activity for arthrosis
— Improved national cooperation
The development of diagnostics to enable patient stratification is not expected to
come from the pharmaceutical industry. The experts indicate that coordination of
research to make this stratification possible should come from, for example, a national
arthrosis working group, in which various stakeholders are represented. In the
Netherlands, a great deal of tissue is available for research. To facilitate research,
good access to tissues via biobanks is a requirement.
— Simplifying research
The experts indicate that the duration of phase II drug research (exploratory and
therapeutic) is very long. That is why the experts in the focus groups advocate a
system in which experimental treatment is possible with a lower threshold under
controlled conditions.
— Alternative forms of reimbursement
Medicines are only reimbursed when they have been approved and registered. Due to
the long duration of phase II research into arthrosis medication, the experts from the
focus groups argue for an alternative form of (partial) reimbursement, whereby there is
already a reimbursement for the drug while Phase II or Phase I research is still
ongoing.

© 2023 KPMG Advisory N.V., all rights reserved

Document Classification: KPMG Confidential

31

3
2

Stroke: In order to reduce the burden of disease as a result of
stroke, there is a particular need for prevention (1/2)
Each year, approximately 43,000 people in the Netherlands suffer a stroke.11 Stroke
ranks second in the Netherlands in terms of disease burden.12 Another name for
stroke is CerebroVascular Accident (CVA).
Subindications
There are two different forms of CVA:
— Ischaemic CVA: as a result of a blockage of a blood vessel, the underlying brain
tissue does not receive oxygen. This may cause brain tissue damage. This form is
also called infarction or non-haemorrhagic CVA.11, 13
— Haemorrhagic CVA: as a result of a leaking or ruptured blood vessel in the brain.
The bleeding can also cause damage to the brain tissue.11, 13
Depending on the location in the brain, a stroke may have different symptoms. A
commonly used acronym to identify the main symptoms is FAS(T).14 The F stands for
‘Face’. Patients may have a drooping face. The A stands for ‘Arms’: the patient may
have paralysis in an arm or leg. The S stands for ‘Speech’: the patient's speech may
be slurred.
In addition to the distinction between ischaemic and haemorrhagic CVA, a distinction
can be made between different phases of a CVA, such as preventive, acute, semiacute, and rehabilitation phase. These phases have their own treatment routes.
1.

Description of the need for drug development for stroke

— Preventive phase - the phase prior to a stroke
The experts indicate that in terms of societal needs, the greatest gains can be made in
prevention. Prevention includes both pharmacological and non-pharmacological
interventions. Various risk factors have been defined for stroke, which result in a low
degree of suffering of the patient. It is therefore important for pharmacological
treatment that the side effects are minimal in order to still achieve good adherence to
the therapy. A lot of research is currently being done into anticoagulants categorised
as
Source:

factor XI inhibitors. These are expected to have less bleeding as a side effect.
— Acute phase: first few hours after stroke onset
Both an ischaemic and a haemorrhagic CVA lead to brain tissue death. In the acute
phase, it is therefore important to restore blood vessel patency as soon as possible in
the event of an ischaemic CVA, or to stop and/or relieve the bleeding in the event of a
haemorrhagic CVA. Some of the patients who develop an ischaemic CVA use
anticoagulants as prophylaxis. The treatment of an ischaemic CVA in the acute phase
may consist of administering a powerful anticoagulant to dissolve the blockage
(thrombolysis). To qualify for this treatment, the effect of the anticoagulants taken as
prophylaxis must first be reversed, because the combination of prophylactic
anticoagulation and thrombolysis together gives too great a risk of bleeding. In recent
years, many new anticoagulants have become available with associated reversal
agents. There is currently no need for new or different drugs in this area.
— Semi-acute phase: the period in which the stroke has already started, but there is
still room to limit the brain damage caused by the stroke as much as possible
Not every patient can be treated in the acute phase. And brain damage may occur
despite prompt treatment in the acute phase. There is a need for medication that can
limit brain tissue damage caused by a stroke; these are called neuroprotective drugs.
This treatment inhibits the local inflammatory process and swelling. Other targets for
treatment are glucose metabolism in the brain and influencing calcium influx.
To date, despite a great deal of research, there are no routinely used neuroprotective
drugs. There is a need for new drugs in this respect.
There may be drugs that are used for other conditions that can also have a
neuroprotective effect. GLP-1 agonists have been mentioned as an example. These
are used in the treatment of diabetes mellitus type II, but may also influence glucose
metabolism in the brain. This could be a promising form of drug repurposing.

11. Wat is een CVA? (beroerte) – Hersenletsel
12. Beroerte | Volksgezondheid en Zorg (vzinfo.nl)
13. Wat is een beroerte? - Hersenstichting
14. Stroke - NHS (www.nhs.uk
© 2023 KPMG Advisory N.V., all rights reserved

Document Classification: KPMG Confidential

32

3
3

Stroke: In order to reduce the burden of disease as a result of
stroke, there is a particular need for prevention (2/2)
— Late phase: the period focused on symptom control, rehabilitation and secondary
prevention
Improving quality of life is an important outcome measure in the late phase after
stroke. One in three patients develops a depression. There is a need to recognise
these patients so that treatment can be started in a timely manner. There is only
sporadic research into which antidepressants specifically work for this target group.
There is a need for drug repurposing alongside a possible improvement in R&D
activity.
2. Possibilities/impossibilities of drug development for stroke

that there is little time in the acute phase of a stroke to inform patients and their
families about participation in scientific research. When conducting research,
informing patients and obtaining their consent (informed consent) is mandatory. In
addition, patients are not always responsive when they arrive at the hospital, which
complicates the informed consent procedure. These factors make it difficult to conduct
research within this population, and it sometimes takes years before a sufficient
number of patients is included in a study. In order to speed up research, other forms
of research should be considered, in addition to randomised trials, to demonstrate the
effectiveness of medicines. This could include research with smaller groups of
patients, or accepting a different informed consent procedure for this population.

At the moment, regenerating brain tissue is not possible, and this does not seem
possible in the short term either. The greatest breakthrough is therefore expected from
drugs that can prevent or limit brain damage. In the past, a lot of research has been
done into neuroprotective drugs, but this has not yet led to a solution. The timely
administration of medication and getting the right dose to the brain (blood-brain
barrier) seem to be the biggest challenges. A breakthrough requires more
understanding of the underlying pathophysiology.
3. Suggestions for improvement in R&D activity for stroke
— To reduce the burden of disease at a population level, the risk group must be
recognised
The experts indicate that when looking at the greatest possible reduction in the burden
of disease, the main focus should be on prevention. Prevention can be more effective
by better recognising the risk group. Several risk factors have already been identified
for this. One possibility that was mentioned was recognition based on data in the
Electronic Patient Dossier (EPD) and General Practitioner Information System (HIS).
Research in this area will not be coordinated by the industry, but will have to be
stimulated by the government.
— Accepting other forms of research for populations in which research is difficult to
conduct
Starting treatment of stroke as soon as possible influences the outcome. This means

© 2023 KPMG Advisory N.V., all rights reserved

Document Classification: KPMG Confidential

33

3
4

COPD: For effective treatment, a change in thinking towards
treatable traits is desirable (1/2)
In the Netherlands, more than 600,000 people suffer from COPD. This leads to
approximately 200,000 COPD-related hospital admission days every year.15 Although
COPD is often seen as a disease related to smoking, the incidence is expected to
increase in the coming years, mainly as a result of air pollution. It is also possible that
COPD will occur in a different, younger population as a result of trends such as
electronic cigarettes and vaping.
Subindications
COPD is a collective name for chronic bronchitis and pulmonary emphysema.16 COPD
can be accompanied by all kinds of symptoms, the main ones being tightness of the
chest, coughing, coughing up mucus, shortness of breath, fatigue, low muscle
strength and weight change.17
In practice, the distinction between chronic bronchitis and pulmonary emphysema is
often no longer made. More important is recognising the treatable traits, such as
bronchoconstriction or inflammation.18 The distinction according to subindications has
not been made for COPD in the identification of gaps in drug development.
1. Description of the need for drug development for COPD
— Further development of existing medication
The current treatment of COPD consists of symptom control. Medication is often
administered as a combination preparation to treat bronchoconstriction and
inflammation. In the event of a lung attack, patients are instructed to take additional
medication if necessary. The combination of drugs increases the dosage of both,
while only the dosage of the drug used to treat bronchoconstriction needs to be
increased. There is a need for the possibility of more targeted treatment.
An important pillar of the treatment of COPD are anti-inflammatory drugs in the form of
corticosteroids. Corticosteroids do not work in all patients. There is a need for other
anti-inflammatory drugs that are effective in this group of patients. Moreover,
corticosteroids have an overall immunosuppressive effect, so that instead of having an
anti-inflammatory effect, they can actually encourage the development of pneumonia.
There is a need for anti-inflammatory drugs that have a local and specific action.
Source:

— Development of new medication
Timely treatment can prevent progression of the disease and thus the loss of lung
capacity. However, the experts indicate that when patients come with complaints, the
disease is already advanced. A great need therefore lies in the prevention of COPD
and its early detection. Another need exists for disease-modifying treatment that helps
prevent the loss of alveoli. A next step is medicinal regeneration of lung tissue.
In the treatment of asthma, some biologicals have a disease-modifying effect. It is
possible that these drugs can also be used in the right subgroup of patients with
COPD. This form of drug repurposing is considered promising.
2. Possibilities/impossibilities of drug development for COPD
— Thinking in terms of treatable traits is important for precision treatment
Current treatment focuses heavily on bronchoconstriction and inflammation. However,
research has identified twelve treatable traits. More effective treatment requires a
change in thinking. Only treat with an anti-inflammatory if there is actually an
inflammatory component. To stimulate precision treatment, other clinical readout
parameters must also be defined.
— Successful drug development and drug repurposing require patient stratification
There are different phenotypes within the group of patients suffering from COPD. A
treatment to regenerate lung tissue that works for all of them seems impossible. To
demonstrate the effectiveness of such drugs, it is necessary to be able to predict
which patients will respond to which type of drug. It is expected that biologicals can
play a role in the treatment of COPD, for which better patient stratification is a
prerequisite.

15. Van wens naar werkelijkheid: 25% minder ziekenhuisopnamedagen voor COPD-patiënten | Activiteit | Zorginstituut Nederland
16. Wat is COPD? | Longfonds
17. Symptomen van COPD | Longfonds
18. Treatable traits: toward precision medicine of chronic airway diseases - PubMed (nih.gov)

© 2023 KPMG Advisory N.V., all rights reserved

Document Classification: KPMG Confidential

34

3
5

COPD: For effective treatment, a change in thinking towards
treatable traits is desirable (2/2)
3. Suggestions for improvement in R&D activity for COPD
— Intensification of cooperation with primary care
Many COPD patients are treated by their GP. In order to reach and treat the largest
group of patients, it is important to involve GPs in drug development research.
— COPD higher on the public agenda
Because patients have often already lost lung capacity at the time of their diagnosis,
early recognition is important. In order to improve recognition, more attention must be
generated for COPD, which is why, according to the experts, the condition should be
placed higher on the public agenda.
— Encouraging the synergistic effect in public-private partnerships
The experts emphasise that many good ideas originate in academia. Encouraging
public-private partnerships increases the chances that these ideas can be realised.
Optimising this synergistic effect requires close collaboration between public and
private, but also between different research bodies.
— Early involvement of patients
In order to respond to societal needs, it is emphasised that it is necessary to involve
patients in all stages of drug development. Patients are in an ideal position to indicate
which new medicines are needed. In addition, patients can indicate what are clinically
relevant outcome measures for them in follow-up research.

© 2023 KPMG Advisory N.V., all rights reserved

Document Classification: KPMG Confidential

35

3
6

Dementia: Drug development at a tipping point, scaling up and
investing are important right now (1/2)
In the Netherlands, a total of approximately 290,000 people suffer from dementia.
800,000 Dutch people provide informal care to someone with dementia.19 The
incidence of dementia is only expected to increase further in the coming years.
Subindications
Dementia is a collective name for over 50 different brain diseases. Most common in
the Netherlands are Alzheimer's disease, vascular dementia, frontotemporal dementia
and Lewy Body dementia.20The forgetfulness often referred to as dementia is in fact a
symptom of all of these brain diseases. In addition, patients suffering from dementia
may experience problems with daily activities, confuse time or place, develop
language problems, lose things, have poor judgement, withdraw from social activities,
and show changes in behaviour and character.21
1.

Description of the need for drug development for dementia

— Further development of existing medication
At the moment, no preventive or curative pharmacological treatment is possible. A
limited number of drugs have been registered that can have a short-term diseasemodifying effect in Alzheimer's disease and Lewy Body Dementia. In the field of
prevention, cure and disease modification, there is therefore a particular need for the
development of new medication.
In addition to the treatment of the condition itself, it is important that the quality of life
in patients with dementia is as good as possible. That is why there is a need for the
further development of medicines to combat clinical features that arise as a result of
dementia, such as anxiety or depression. Now, medicines are often borrowed from
other conditions. There is a need for the possibility of treating these secondary
manifestations of disease specifically aimed at patients with dementia.
— Development of new medication
Prevention, cure or disease modification are not possible. Much is clear about the
pathophysiology of the different forms of dementia; the need now consists of
translating the pathophysiology into pharmacological treatment options.
Source:

2. Possibilities/impossibilities of drug development for dementia
Dementia is already a collective name for various brain diseases, but different
subtypes can also be defined within, for example, Alzheimer's disease. It is impossible
to treat dementia as a single condition and diagnosing the different subtypes is an
important precondition for successful treatment. New diagnostic methods can
increasingly facilitate patient stratification.
In the past, a lot has been invested in the development of pharmacological treatment
of dementia in general. These drugs proved ineffective in this context. It is possible
that these drugs, when used in the right subgroup of patients, will still prove to be
effective. This form of drug repurposing is considered promising.
There are several trials with positive results, as well as a few approved medicines that
appear to have a disease-modifying effect. These are Lecanemab, Aducanumab and
Donanemab. However, their effect appears to be limited, the costs are high and the
drugs have side effects.22 There are a relatively large number of trials on new diseasemodifying treatments from which positive results are expected. The experts
emphasise that this can act as a catalyst for the development of other treatment
options.
The experts indicate that there are different views as to what dementia actually is.
Some see it as a disease of old age, others as a deadly brain disease, the so-called
disease paradigm. When you see dementia as a deadly brain disease, you are
prepared to accept different or more side effects than when you see dementia as a
disease of old age in a vulnerable target group.
In view of the ageing population, there is a need for the prevention of dementia. This
requires identifying patients who will develop dementia, or diagnosing dementia early
on in the disease process.
This does not seem promising at the moment due to ethical concerns. Because
although people can know through screening that they may develop the condition, no
effective treatment is available yet. As such, this knowledge can have a negative
effect on the quality of life, making early diagnosis undesirable.

19. Factsheet cijfers en feiten over dementie | Alzheimer Nederland (alzheimer-nederland.nl)
20. Soorten dementie | Alzheimer Nederland (alzheimer-nederland.nl)
21. Herkennen en symptomen van dementie | Alzheimer Nederland (alzheimer-nederland.nl)
22. Nieuw medicijn remt verloop van alzheimer klein beetje af - NRC

© 2023 KPMG Advisory N.V., all rights reserved

Document Classification: KPMG Confidential

36

3
7

Dementia: Drug development at a tipping point, scaling up and
investing are important right now (2/2)
3. Suggestions for improvement in R&D activity for dementia
— Improving public-private partnership
The experts indicate that better public-private partnership is needed. Many good ideas
originate in academia, but due to complex regulations regarding, for example,
intellectual property, it is not always possible to follow up on these ideas. Researchers
at universities often leave for the industry.
A more entrepreneurial climate could attract new investors and contribute to the
retention of researchers.
— Simplifying the regulatory framework
The Netherlands has a solid but complex research infrastructure. The safety of
participants in studies is guaranteed by Medical Ethical Review Committees (MRECs)
and the Central Committee on Research Involving Human Subjects (CCMO). The
downside of this is that it hinders foreign organisations from conducting research in
the Netherlands. The experts indicate that it is precisely this type of collaboration that
can accelerate research.
— Scaling up
Lecanemab is the first disease-modifying agent in the treatment of Alzheimer's
disease approved in the United States. The experts indicate that with the first positive
results from trials, drug development for Alzheimer's may be at a tipping point. That is
why scaling up and investing are essential right now.

© 2023 KPMG Advisory N.V., all rights reserved

Document Classification: KPMG Confidential

37

3
8

Mood disorders: Effectiveness of treatment may be increased by
patient stratification
Every year, about 10% of the Dutch population suffers from some form of a mood
disorder.23 These include both patients who are being treated by their general
practitioner and those who receive mental health care.
Subindications
Mood disorders include both depressive disorders, which represent by far the largest
group with approximately 1.1 million Dutch people, and bipolar disorders, which affect
approximately 150,000 Dutch people annually.a
The experts indicate that the greatest burden of disease for patients is caused by
depressive episodes. Mania and depression are treated differently. The results
described here therefore focus on the drug requirement in bipolar and unipolar
depression.
1. Description of the need for drug development in mood disorders
— Further development of existing medication
Several pharmacological options are available for the treatment of mood disorders.
Various areas are mentioned in which there is a need to improve the current
pharmacological treatment. For example, current drugs affect glucose metabolism and
have cardiovascular side effects. There is a need for drugs with fewer side effects. In
addition, it sometimes takes several weeks for drugs to reach their maximum
therapeutic effect and even longer before they also achieve their maximum
prophylactic effect. There is a need for quicker acting drugs.
— Development of new medication
Psychedelics can give quick results in both bipolar and unipolar depression. Although
psychedelics were not developed for this purpose, they can play a role in the
treatment of depression. Drug repurposing with psychedelics for the treatment of
depression is considered promising.
The focus group only discussed the treatment of mood disorders in adults. However,
the experts indicate that there is a great need within child and adolescent psychiatry
for targeted treatment, as opposed to treatment with the same drugs as for adults in
adjusted doses.

Source:
Note:

2. Possibilities/impossibilities of drug development for mood disorders
The experts indicate that there are subgroups within the large group of patients with
mood disorders. For effective drug treatment, it is important to be able to recognise
these subgroups. However, recognising subgroups based on pathophysiological
characteristics is difficult, which is why it is argued to reverse the process: setting up
large databases that enable pattern recognition. Based on these patterns, it would be
easier to predict how certain subgroups of patients will respond to treatment. The
experts indicate that patients with both bipolar and unipolar depression should be
included in the same database.
3. Suggestions for improvement in R&D activity for mood disorders
— Encouraging public-private partnerships
The experts indicate that research can be accelerated by collaborating more. The
United States is mentioned as an example, where the government drives medicine
research more.
— Investing in networks
Patient stratification is mentioned several times as an important precondition for more
effective treatment, which requires the creation of a national database that enables
pattern recognition. In the past, many studies have been done into the treatment of
mood disorders in general, but the drugs studied often turned out to be ineffective.
This makes it difficult to secure investment for large-scale studies. When the
effectiveness of new medicines can be demonstrated in a subgroup, this can give a
new impetus to the necessary investments.
— Need for better treatment monitoring
The experts indicate that we still do not know much about the optimal duration of
treatment and the prevention of side effects. Patients sometimes use drug treatment
for prolonged periods of time, without this treatment being monitored. To gain more
knowledge about optimal treatment duration and side effects, it is necessary to
continue to monitor patients after their successful initial treatment.

23. Depressie en andere stemmingsstoornissen | Leeftijd en geslacht | Volksgezondheid en Zorg (vzinfo.nl)
a. In addition to mood disorders, anxiety disorders also cause a high burden of disease. Anxiety disorders were on the longlist of conditions. The experts who participated in the focus group on mood
disorders were also asked about the similarities and differences in drug development gaps with respect to anxiety disorders. The findings are included in Appendix C.

© 2023 KPMG Advisory N.V., all rights reserved

Document Classification: KPMG Confidential

38

3
9

Overview of possibilities/impossibilities in R&D activity for
conditions that were analysedin more depth
The focus groups discussed three main themes: the need for medicines for each
condition, the possibilities/impossibilities of drug development for the condition and an
exploration of the possible solutions to fill the gap in drug development for the
condition in question. The table below provides an overview of the most important
findings for the pharmacological need and the possibilities/impossibilities of drug
development.

For the conditions for which a qualitative in-depth analysis was carried out, there is a
particular need for new medicines. For arthrosis, COPD and mood disorders, it is
indicated that the development of new medicines by means of drug repurposing is
considered promising.
Some general solutions to fill gaps in drug development are discussed on page 40.

Need
Condition

Improvement of existing
medicines

New medicines

Possibilities/impossibilities in R&D activity

Arthrosis

—



Patient stratification necessary
Proof of concept

Stroke

—



Largest gains in disease burden reduction can be achieved
with prevention (recognition of patients with a risk profile)

COPD



a



Patient stratification necessary
Treatable traits

Dementia

—



Patient stratification necessary
Proof of concept
Wish for upscaling following first promising results

Mood disorders





National networks for recognition of subgroups

Note:

b

a. Fewer side effects of anti-inflammatory drugs and precision treatment.
b. Faster effects
© 2023 KPMG Advisory N.V., all rights reserved

Document Classification: KPMG Confidential

39

4
0

The focus groups have revealed four general suggestions for
encouraging drug development (1/2)
The focus groups mentioned several possible solutions to fill the gaps in drug
development for each condition. In addition to the condition-specific solutions, there
are a number of general solutions that were a recurrent theme in all focus groups.
Below is an overview of the possible solutions mentioned:

— More national and international control
The study expressed a need for national and international steering in various areas:
•

For various condition, it is indicated that better patient stratification is a
precondition for the further development of pharmacological treatment. This
requires new diagnostic studies, or databases of patients with which different
subgroups can be recognised based on patterns. As such initiatives will not be
coordinated from within the industry, there is a desire to manage them centrally.

•

It has also been mentioned that an acceleration in drug development can be
achieved through access to larger patient samples. This can be achieved through
international cooperation.

•

International guidance is preferred for both points, because the Netherlands alone
has such a small scale that it is not attractive for research and industry. Joining
forces at European level is therefore crucial in this respect.

•

Finally, it is indicated that in addition to pharmacological treatment, there is a great
need for prevention and early recognition of conditions. This requires close
cooperation with primary care. Due to the existing pressure on primary care, this is
only possible if these conditions are also high on the public agenda. This at any
rate applies to COPD and stroke.

— Improving public-private partnership
For all conditions, it was indicated that improving public-private partnerships would
benefit drug development. It must become easier for universities and industry to jointly
develop an idea into a registered medicine. Agreements on intellectual property are
mentioned as facilitators.
When public-private partnerships become more common, it will be easier to retain
talented researchers for universities. The collaboration can also contribute to greater
continuity of research funding. If researchers are less dependent on short-term grants,
they will need to spend less time securing funding for their research. This would allow
them to bring more focus to their work, which could lead to an acceleration of
research.
— Simplifying the regulatory framework
It is indicated that a lot of high-quality research is being done in the Netherlands.
However, the complex regulations make it difficult for foreign organisations to
participate in Dutch research. In the Netherlands, the rights and safety of participants
in scientific research are guaranteed by regulations implemented by the METC and
the CCMO. Research must meet strict requirements before participants can be
recruited, which is at the expense of rapid research progress. International
collaborations can increase the sample size, with which research can be accelerated.
The experts also indicate that due to the complexity of the regulations, drug research
often has a long lead time. As a result, promising drugs take a long time to become
available to patients. This process can be accelerated by simplifying the regulatory
framework for the approval of experimental drugs. The experts have suggested a
system in which experimental treatment with a lower threshold is possible under
controlled conditions.

© 2023 KPMG Advisory N.V., all rights reserved

— Improving the infrastructure
It has been mentioned several times that facilitating a good infrastructure contributes
to drug development. An example mentioned in this study are the biobanks. To
facilitate research, access to research material such as tissues from biobanks must be
guaranteed. This requires improvement of the infrastructure.
The experts indicated that research is often fragmented in terms of both conditions
and research bodies. Close collaboration between universities, government, primary
care and patients is necessary to fill the gaps in drug development.

Document Classification: KPMG Confidential

40

5.

Answers to
research
questions and
conclusions

4
2

There are gaps in the development of drugs for several conditions,
including arthrosis, stroke, COPD, dementia and mood disorders
For 33 conditions with the highest annual burden of disease, this study provided
answers to three research questions by means of a funnel approach. The answers to
each research question are described below, followed by the resulting conclusions.
Answers to research questions
Research question 1: For which conditions is R&D activity in imbalance with the
societal need? Can the need for medicines for these conditions be categorised?
A longlist of conditions with improvement potential has been drawn up on the basis of
a conceptual model populated through desk research and surveys. This longlist was
validated in interviews with experts, after which five conditions were selected for
further qualitative in-depth analysis. These are arthrosis, stroke, COPD, dementia and
mood disorders.
The need for drug development for each condition was analysed in more depth in
focus groups. These focus groups led to a specific need for each conditions. This
need cannot be categorised.
For the conditions arthrosis, COPD and dementia, almost exclusively symptom control
is currently available. There is a need for disease-modifying treatments. A second key
finding that emerged for all selected conditions is the need for patient stratification.
The selected conditions consist of heterogeneous subgroups of patients. With patient
stratification, the different subgroups can be identified and a specific treatment can be
developed, which is expected to improve the effectiveness of the treatment.
Following on from the need for patient stratification, the possibilities for drug
repurposing are also mentioned. Drug repurposing is considered promising for
arthrosis, COPD and dementia. In the past, drug repurposing has been studied for the
patient population as a whole, which often proved ineffective. These drugs may have
potential if they are prescribed to specific subgroups of patients, which can be
identified with patient stratification.
Research question 2: Can these conditions be broken down into subindications?
In all focus groups a distinction was made according to possible subindications, in
order to subsequently validate with the experts whether this classification was correct
and whether it contributed to identifying the need for medicines. The subindications, if
any, for each of the conditions are shown below.
© 2023 KPMG Advisory N.V., all rights reserved

— Arthrosis
There are different manifestations. Patients can have multiple manifestations of
arthrosis at the same time, and the manifestation of arthrosis in a patient can change
over time. It is important to recognise that these manifestations exist and that there is
a need for patient stratification in the treatment of arthrosis. There is currently no
distinction between subindications.
— Stroke
Ischaemic and haemorrhagic CVA differ in terms of pathophysiology. This
subindication is needed to describe the need for medicines.
— COPD
COPD is the official collective name for chronic bronchitis and pulmonary
emphysema. However, the distinction between these subindications is no longer
made in practice. More important for the treatment of COPD is to distinguish between
treatable traits (such as bronchoconstriction). A total of 12 treatable traits have been
defined.
— Dementia
There are various subindications of dementia. In this study, the most common
subindications of dementia in the Netherlands have been examined in depth:
Alzheimer's disease, vascular dementia, frontotemporal dementia and Lewy Body
dementia.
No other subindications can be distinguished within Alzheimer's disease, but the
experts indicate that Alzheimer's disease concerns a heterogeneous group of patients,
where there is a need for patient stratification.
— Mood disorders
Mood disorders include the subindications bipolar disorder and major depressive
disorder. Bipolar disorder can be a depressive disorder or a manic disorder. This
study analysed the subindications bipolar depressive disorder and unipolar depressive
disorder in more depth.

Document Classification: KPMG Confidential

42

4
3

The lagging behind of R&D activity has different causes for each
condition
Research question 3: What are the causes of limited R&D activity and what can the
government do to encourage R&D activity for these conditions?
For the conditions for which a qualitative in-depth analysis was made, the focus
groups identified causes why R&D activity is lagging behind, with associated specific
solution options.
— Arthrosis
The disappointing research results from the past, when a single drug was sought for
the entire patient population, are cited as the cause of lagging R&D activity. As a
possible solution, more focus on research that encourages patient stratification is
requested.
— Stroke
In the past, many studies of neuroprotective drugs proved unsuccessful. The experts
indicate that the greatest need lies in the prevention of strokes. This requires better
recognition of patients with risk factors, which in turn requires close cooperation
between primary and secondary care.
— COPD
For COPD, it is indicated that research into disease-modifying treatments is taking
place, but lags behind the R&D activity for asthma. No clear explanation can be given
for this. Collaboration with general practitioners and patient participation is necessary
to ensure that drug development for COPD meets the need. The experts are calling
on the government to put COPD high on the public agenda.
— Dementia
The experts indicate that R&D activity in itself does not lag behind, it is rather that the
results of this activity are not forthcoming. Many studies are currently under way into
new disease-modifying treatments from which positive results are expected, and an
appeal is being made to invest in scaling up right now.

© 2023 KPMG Advisory N.V., all rights reserved

— Mood disorders
A large proportion of patients with mood disorders are treated in primary care. Due to
the pressure on mental health care, it is virtually impossible for primary care providers
to participate in scientific research. This hinders scientific research among a
representative patient population. There is an appeal to facilitate setting up large
research networks.
Conclusion
This study used a funnel approach to identify conditions for which gaps in drug
development may occur. From these, five conditions were then selected for further
qualitative in-depth analysis. This qualitative in-depth analysis concerned arthrosis,
stroke, COPD, dementia and mood disorders. This qualitative in-depth analysis shows
that the emergence of gaps in drug development is more complex than simply the lack
of commercial potential of drugs.
Previous research concluded that commercial potential is the main driver for drug
research. Other contributing factors described are the state of knowledge, access to
research populations and an infrastructure for collaboration. This study confirms that
the emergence of gaps in drug development is more complex than just commercial
potential. For five selected conditions, the extent to which each of the factors applies
has been examined in more detail. The role of other factors differs for each condition,
is difficult to determine exactly and is, moreover, subjective.
There are specific needs for medicines for arthrosis, stroke, COPD, dementia and
mood disorders. However, what all selected conditions have in common is the need
for patient stratification. In the past, drugs for many conditions were developed for the
patient group as a whole. However, based on the current knowledge, it is clear that
different conditions comprise different subgroups that respond differently to
treatments. There is a need to better recognise these groups and develop treatments
that target specific subgroups.

Document Classification: KPMG Confidential

43

6.

Appendices

4
5

Appendix A: Overview of organisationsthat were asked to
participate in surveys (1/3)
Condition

Patient associations

Scientific associations

1. Anxiety disorders

Angst, Dwang en Fobie Stichting

Nederlandse Vereniging voor Psychiatrie (Dutch Association for Psychiatry)

ReumaNederland

Nederlandse Vereniging voor Reumatologie (Dutch Rheumatology Association)

Vereniging Reumazorg Nederland

Nederlandse Orthopaedische Vereniging (Dutch Orthopaedic Association)

2. Arthrosis

Vereniging Fysiotherapie & Wetenschap (Physical Therapy & Science Association)
3. Asthma

Longfonds

Nederlandse Vereniging van Artsen voor Longziekten en Tuberculose (Dutch Society of
Physicians for Pulmonary Diseases and Tuberculosis)

4. Stroke

Hersenletsel.nl

Nederlandse Vereniging voor Neurologie (Dutch Association for Neurology)

Harteraad

Nederlandse Vereniging voor Medische Oncologie (Dutch Association for Medical Oncology)

5. Breast cancer

Borstkankervereniging Nederland

6. Contact eczema

Vereniging voor mensen met Constitutioneel Eczeem

Nederlandse Vereniging voor Dermatologie en Venereologie (Dutch Society for Dermatology
and Venereology)

7. COPD

Longfonds

Nederlandse Vereniging van Artsen voor Longziekten en Tuberculose (Dutch Society of
Physicians for Pulmonary Diseases and Tuberculosis)

8. Coronary heart disease

Harteraad

Nederlandse Vereniging voor Cardiologie (Dutch Society of Cardiology)

Alzheimer Nederland

Nederlandse Vereniging voor Neurologie (Dutch Association for Neurology)

9. Dementia

Verenso

10. Diabetes Mellitus

Diabetesvereniging Nederland

Nederlandse Internisten Vereniging (Netherlands Association of Internal Medicine)

11. Colon cancer

Stichting Darmkanker

Nederlandse Vereniging voor Medische Oncologie (Dutch Association for Medical Oncology)

12. Hearing disorders

Stichting Hoormij

KNO-vereniging

13. Eye disorders

Oogvereniging

Nederlandse Oogheelkundig Gezelschap (Netherlands Ophthalmological Society)

14. Heart failure

Harteraad

Nederlandse Vereniging voor Cardiologie (Dutch Society of Cardiology)

© 2023 KPMG Advisory N.V., all rights reserved

Document Classification: KPMG Confidential

45

4
6

Appendix A: Overview of organisationsthat were asked to
participate in surveys (2/3)
Condition

Patient associations

Scientific associations

15. Cardiac arrhythmias

Harteraad

Nederlandse Vereniging voor Cardiologie (Dutch Society of Cardiology)

16. Brain cancer

Brain tumour contact group

Nederlandse Vereniging voor Medische Oncologie (Dutch Association for Medical Oncology)

Hiv Vereniging

Nederlandse Vereniging voor Neurologie (Dutch Association for Neurology)

17. HIV infections

Nederlandse Vereniging voor Internist-infectiologen

18. Skin cancer

Stichting Melanoom

Nederlandse Vereniging voor Medische Oncologie (Dutch Association for Medical Oncology)

19. Hypertension

Harteraad

Nederlandse Vereniging voor Cardiologie (Dutch Society of Cardiology)

20. Upper respiratory infections

Longfonds

Nederlandse Vereniging van Artsen voor Longziekten en Tuberculose (Dutch Society of
Physicians for Pulmonary Diseases and Tuberculosis)

21. Lower respiratory infections

Longfonds

Nederlandse Vereniging van Artsen voor Longziekten en Tuberculose (Dutch Society of
Physicians for Pulmonary Diseases and Tuberculosis)

Hematon

Nederlandse Vereniging voor Medische Oncologie (Dutch Association for Medical Oncology)

22. Leukaemia
Nederlandse Vereniging voor Hematologie
Longkanker Nederland

23. Lung cancer

Nederlandse Vereniging van Artsen voor Longziekten en Tuberculose (Dutch Society of
Physicians for Pulmonary Diseases and Tuberculosis)
Nederlandse Vereniging voor Medische Oncologie (Dutch Association for Medical Oncology)

24. Multiple myeloma
25. Multiple sclerosis
26. Non-Hodgkin lymphoma

Hematon

Nederlandse Vereniging voor Medische Oncologie (Dutch Association for Medical Oncology)
Nederlandse Vereniging voor Hematologie

Multiple Sclerose Vereniging

Nederlandse Vereniging voor Neurologie (Dutch Association for Neurology)

Hematon

Nederlandse Vereniging voor Medische Oncologie (Dutch Association for Medical Oncology)

© 2023 KPMG Advisory N.V., all rights reserved

Nederlandse Vereniging voor Hematologie

Document Classification: KPMG Confidential

46

4
7

Appendix A: Overview of organisationsthat were asked to
participate in surveys (3/3)
Condition

Patient associations

27. Pancreatic cancer

Living With Hope

28. Prostate cancer

Prostaatkankerstichting

29. Rheumatoid arthritis
30. Schizophrenia

ReumaNederland
Ypsilon

31. Oesophageal cancer

Stichting SPKS Leven met maag- of slokdarmkanker

32. Mood disorders
33. Parkinson's disease

Depressie Vereniging
Parkinson Vereniging

Scientific associations

Nederlandse Vereniging voor Heelkunde (Association of Surgeons of the Netherlands)
Nederlandse Vereniging voor Medische Oncologie (Dutch Association for Medical Oncology)
Nederlandse Vereniging voor Urologie (Dutch Urological Association)
Nederlandse Vereniging voor Medische Oncologie (Dutch Association for Medical Oncology)
Nederlandse Vereniging voor Reumatologie (Dutch Rheumatology Association)
Nederlandse Vereniging voor Psychiatrie (Dutch Association for Psychiatry)
Nederlandse Vereniging voor Medische Oncologie (Dutch Association for Medical Oncology)
Nederlandse Vereniging voor Heelkunde (Association of Surgeons of the Netherlands)
Nederlandse Vereniging voor Psychiatrie (Dutch Association for Psychiatry)
Nederlandse Vereniging voor Neurologie (Dutch Association for Neurology)

General Scientific associations
Koninklijke Nederlandse Maatschappij ter bevordering der Pharmacie (Royal Dutch Society for the Advancement of Pharmacy, KNMP)
Nederlandse Vereniging van Ziekenhuisapothekers (Dutch Hospital Pharmacists' Association, NVZa)
Nederlands Huisartsen Genootschap (Dutch College of General Practitioners, NHG)
Nederlandse Vereniging voor Klinische Geriatrie (Dutch Geriatrics Society, NVKG)

Professors of pharmacology
Professors of pharmacology were personally invited to participate in the survey. Professors from all UMCs were asked to participate.

© 2023 KPMG Advisory N.V., all rights reserved

Document Classification: KPMG Confidential

47

4
8

Appendix B: Questionnaire of condition-specificsurveya
1a. How would you describe the situation with respect to medicines on the
market for this condition?

o
o
o

40-60%
60-80%

o

Pharmacological treatment is not preferred (other interventions such as
lifestyle, surgery, etc. are more applicable)

o

Better pharmacological treatment is available in other markets (e.g. Japan,
China or Russia), but not available in the Netherlands

o
o

No medication available, while medication could be a treatment option

o

Pharmacological treatment available, but need for better drug (e.g. simpler
administration, fewer interactions, fewer side effects, greater effectiveness,
etc.)

No or limited research is being done into new drugs, but that is understandable
given the current state of knowledge, since the chance of success is small

o

o

Good, all or almost all patients with this condition can be treated properly with
existing medicines

No or too limited research is being done into pharmacological treatment, while
the current state of knowledge would give rise to more R&D activity, since
research is promising

o

Research into pharmacological treatment is being done, but no suitable remedy
has yet emerged

o

Other, i.e.: …

1b. Please explain your answer to the previous question here.
[Space for free text]
2a. What proportion of the patients in the Netherlands with this condition can –
in your estimation – be treated with the medicines currently on the international
market?

o
o
o
o
o

<20%

o
o

<20%

3a. How would you describe the R&D activity of biotech and pharmaceutical
companies on new drugs for this condition?

[Space for free text]

3b. Please explain your answer to the previous question here.
[Space for free text]
4. If you think that pharmacological treatment can be further optimised, can you
please explain where you think this potential improvement can be achieved and
where the greatest need for improvement lies?

20-40%
40-60%

[Space for free text]

60-80%
>80%

2b. In what proportion of these patients – in your estimation – is the
pharmacological treatment effective?

Note

>80%

5. Are there (sub)indications for this condition that differ in terms of (1) the
possibility of pharmacological treatment, (2) the availability of pharmacological
treatment and/or (3) the degree of R&D activity for new drugs? If so, please
indicate here which (sub)indications this concerns and provide an explanation
of any differences.
[Space for free text]

20-40%

a. The condition-specific survey was conducted among members of scientific associations and patient associations.
© 2023 KPMG Advisory N.V., all rights reserved

Document Classification: KPMG Confidential

48

4
9

Appendix B: Questionnaire of generalsurveya
1. How would you describe the situation with respect to medicines on the
market for this condition?

o

Pharmacological treatment is not preferred (other interventions such as
lifestyle, surgery, etc. are more applicable)

o

Better pharmacological treatment is available in other markets (e.g. Japan,
China or Russia), but not available in the Netherlands

o
o

No medication available, while medication could be a treatment option

o

Good, all or almost all patients with this condition can be treated properly with
existing medicines.

Pharmacological treatment available, but need for better drug (e.g. simpler
administration, fewer interactions, fewer side effects, greater effectiveness,
etc.)

2. Please explain your answer to the previous question here.
[Space for free text]

4. Please explain your answer to the previous question here.
[Space for free text]
5. If you think that pharmacological treatment can be further optimised, can you
please explain where you think this potential improvement can be achieved and
where the greatest need for improvement lies?
[Space for free text]
6. Are there (sub)indications for this condition that differ in terms of (1) the
possibility of pharmacological treatment, (2) the availability of pharmacological
treatment and/or (3) the degree of R&D activity for new drugs? If so, please
indicate here which (sub)indications this concerns and provide an explanation
of any differences.
[Space for free text]

3. How would you describe the R&D activity of biotech and pharmaceutical
companies on new drugs for this condition?

o

No or limited research is being done into new drugs, but that is understandable
given the current state of knowledge, since the chance of success is small

o

No or too limited research is being done into pharmacological treatment, while
the current state of knowledge would give rise to more R&D activity, since
research is promising

o

Research into pharmacological treatment is being done, but no suitable remedy
has yet emerged.

o

Other, i.e.: …

Note:

[Space for free text]

a. The general survey was conducted among members of coordinating scientific associations and professors of pharmacology.
© 2023 KPMG Advisory N.V., all rights reserved

Document Classification: KPMG Confidential

49

5
0

Appendix C: Gaps in drug development for anxiety disorders
In the Netherlands, 15% of adults develop some form of anxiety disorder every year.24
This concerns all adults aged 18 to 75 who have had one or more anxiety disorders in
the past 12 months.
The anxiety disorders can be subdivided into generalised anxiety disorder, panic
disorder, specific phobia, social phobia and agoraphobia.25
Anxiety disorders and mood disorders share many similarities in pharmacological
treatment. The disorders themselves are closely related and may cross over. Two key
needs for drug development have been identified:
— Need for patient stratification
The experts indicate that there is a need for better patient stratification for anxiety
disorders. As it concerns a heterogeneous group of conditions, there is a need to be
able to treat subgroups of patients more specifically. Again, the identification of
subgroups based on pathophysiology is difficult. That is why there is a need for large
databases that enable pattern recognition. Based on these patterns, it is easier to
predict which subgroups of patients will respond to a particular treatment. Due to the
close relationship between mood disorders and anxiety disorders, it is indicated that it
is preferable to include patients suffering from either condition in the same database.
— Need for drugs with fewer side effects
Anxiety disorders are often treated using drugs that are effective, but can also have an
addictive effect, such as benzodiazepines. There is a need for medication with the
same effectiveness, but less addictive effect. In addition, as current treatment often
has side effects such as glucose intolerance and cardiovascular side effects, there is
a need for drugs that do not have these side effects or have them to a lesser extent.

Source:

24. Angststoornissen | Volksgezondheid en Zorg (vzinfo.nl)
25. Angststoornissen | Leeftijd en geslacht | Volksgezondheid en Zorg (vzinfo.nl)
© 2023 KPMG Advisory N.V., all rights reserved

Document Classification: KPMG Confidential

50

5
1

Contact details:
David Ikkersheim, Partner
KPMG Health
T +31 6 41 83 96 26
E ikkersheim.david@kpmg.nl

Petra Roeleveld, Manager
KPMG Health
T +31 6 15 68 58 18
E roeleveld.petra@kpmg.nl

kpmg.com/socialmedia
© 2023 KPMG N.V., a Dutch limited liability company and a member firm of the KPMG global organization of
independent member firms affiliated with KPMG International Limited, a private English company limited by
guarantee. All rights reserved.
This report is intended solely for the information and use of VWS and is not intended to be and should not be used
by anyone other than these specified parties. Any other party that obtains a copy and chooses to rely on it in any
capacity does so at its own risk. KPMG accepts no responsibility or liability for the use of this report other than for
the purpose for which it has been prepared and accepts no responsibility or liability to other parties than VWS.
The terms and conditions of the agreement under which this report has been drawn up are exclusively governed by
Dutch law, and the court in the district within which the office is situated has exclusive jurisdiction with respect to
any disputes arising under or in connection with that agreement