3.

Approaches to priority setting

3. Approaches to priority setting

See Background Paper 3 (BP3_Approaches.pdf)

3.1 Introduction
This chapter reviews the various approaches which have been used to set priorities for
health research — both at the international and national level — and explains the
rationale for the choice of methods used in this Project (see 2004 Report, Background
Paper 3 and present Report, Background Paper 3). The key message underlined in the
2004 Report and reiterated here is that all methods of priority setting have limitations
and that different methods need to be used, depending on the particular circumstances.
A combination of methods has therefore been used in this Report.

Priority setting is a challenge at all levels (global, national and local) and for all
contexts in health systems. Both consumers and funders are demanding greater
accountability for how limited health resources are used to meet health system goals.
As a result, public and private sector research funders have to make difficult decisions
about which fields and specific studies to support.

However, there is virtually no consensus regarding which, or whose, values should

guide decisions about allocation of research funding and how these values should
inform priority setting. In short, there is no “best practice” (see Viergever et al. 2010. A
checklist for health research priority setting 1 and Appendix 3.1).

There are two broad approaches to setting priorities for health research: the use of
technical analyses, which rely on quantifiable epidemiologic, clinical, financial or other
data; and the use of interpretive assessments, which rely on consensus views of
informed participants. Technical approaches depend on the availability of data, and
priorities tend to be based on measurable units such as diseases (burden of disease) or
interventions (with respect to their costs and use). The difficulty with quantitative
methodology is that it hides value judgments that might reflect those of stakeholders
not involved in the methodology, such as users and payers of health care services.
Interpretive or consensus stakeholder approaches relying on the subjective judgments
of participants are, in theory, capable of dealing with value judgments and
multifaceted assumptions, and they have been used for research priority setting in
large, governmental agencies like the United States National Institutes of Health
(NIH),2 the Science and Technology Council of Australia,3 or even large pharmaceutical
companies.

23
Priority Medicines for Europe and the World 2013 Update

3.2 Conceptual framework for the Priority Medicines Project

The conceptual framework for this updated 2013 Report has not changed. The Project
used different methods from the spectrum of possible approaches: evidence-based
approach (burden of disease and mortality data); future projections approach; risk
factor approach; and social solidarity approach. A framework for this kind of analysis
has been developed by the University of Colorado in the United States (see Figure
3.2.1).

Figure 3.2.1: A cognitive continuum framework

INTUITION
Quality of Quality of
Intuition Analysis
ANALYSIS

Least precise/explicit Most precise/explicit

MODE: 7 6 5 4 3 2 1

non- clinical expert descriptive case randomized laboratory

Knowledge cognitive judgement consensus models control controlled experiment
Generation judgement judgement study trial

non- clinical expert decision

Decision/ cognitive judgement consensus models
Policy Making judgement judgement

Source: Dowie J. In Health Care Priority Setting. Oliver A. ed. Nuffield Trust, UK

3.3 Approaches to priority setting

3.3.1 Overview of the literature post-2004

There have been several literature reviews in this fairly active area since 2008.1,4, 5, 6, 7, 8
Reports have evaluated priority setting against an ethical framework. The factors that
impact priority setting have been studied as well, such as amount and type of
stakeholder engagement, cultural factors supporting explicit priority setting, decision
maker/group composition (size and clarity of process, local ownership and awareness
and representation), and management of local politics. These are summarized in
Background Paper 3. A key conclusion of this review for the present updated report is

24
 3. Approaches to priority setting

that there is still very little information on how funding decisions are developed for
biomedical research.

3.3.2 Defining a priority medicine: the role of regulatory authorities

The regulatory authorities of the EU, Canada and the United States determine whether
a medicine should be a “priority” for regulatory purposes. The European Medicines
Agency (EMA) and the United States Food and Drug Administration (FDA) have
established categories of medicines, based on whether or not they demonstrate
improvement over existing medicines. Such a designation facilitates the registration
process. 9 Although not intended for use in prioritizing research, in practice this
designation is intended to reward successful research (see Background Paper 3).

European Union

In November 2005, one year after the publication of the 2004 Priority Medicines Report,
accelerated assessment was introduced by revised EU pharmaceutical legislation.
Companies can request accelerated assessment provided they are able to demonstrate
that their product responds to unmet medical needs or constitutes a significant
improvement over the available methods of prevention, diagnosis or treatment of a
condition. 10 An accelerated assessment is conducted in a maximum of 150 days
although if major objections to this are uncovered during the assessment, the timing is
reverted to the normal timetable for the centralized procedure, which allows a
maximum assessment period of 210 days. In 2007, the medicinal product, eculizumab,
from Alexion Europe SAS, was the first medicinal product for which an accelerated
assessment procedure was concluded successfully.

Two other pathways to address 'unmet medical needs' are the conditional approval
and the exceptional approval pathway.11,12 In case of conditional approval, marketing
authorization is granted based on a smaller package of clinical data, with follow-up
obligations to submit additional clinical efficacy and safety evidence of the product.
For some products, such as certain orphan medicinal products for extremely rare
diseases, it will usually never be possible to assemble a full dossier. These products
may be approved under an ‘exceptional approval’ scheme, without further post-
approval obligations.

The United States

The classification system of the FDA assigns all new drug approvals to categories
representing distinct levels of innovation, and this classification is of particular
relevance here as it highlights the different meanings of the term innovation. The FDA
reviews new drug applications (NDAs) and awards priority status based on chemical
type and therapeutic potential. With regard to the latter, a drug qualifies for priority
review if it offers a potentially significant improvement over marketed products. With
regard to the former, a new molecular entity (NME) is a drug whose active ingredient
has never before been approved by the FDA for the USA market. An incrementally

25
Priority Medicines for Europe and the World 2013 Update

modified drug (IMD) is one that relies on an active ingredient present in a drug already
approved for the USA market (or a closely related chemical derivative of such an
ingredient), and has been modified by the manufacturer. Drugs are classified as other if
they rely on an active ingredient that is already available in an identical marketed
product. A standard drug is a product that does not qualify for priority review and it
can be a NME, IMD or other. Most United States observers would view priority NMEs
as the most innovative type of new drug.

The FDA has also granted priority status to some IMDs, indicating that they provide
therapeutic advances even though they are derivatives. Priority IMDs are also
moderately innovative. The FDA, however, rates many NMEs as standard and,
although based on new compounds, these drugs usually have the same mechanism of
action and outcomes as other drugs on the market. Standard NMEs may have different
safety and efficacy profiles from other marketed drugs in the same class. Thus,
standard NMEs may enhance clinical outcomes even if they do not demonstrate
significant improvement over other medicines already available.13

The FDA’s fast track process is designed to facilitate the development, and expedite
the marketing review, of drugs that both target “serious” diseases and fill an “unmet
medical need”. Determining whether a disease is “serious” is generally based on
whether the drug will have an impact on factors such as survival, day-to-day
functioning, or the likelihood that the disease, if left untreated, will progress from a
less severe condition to a more serious one. Filling an “unmet medical need” is defined
as providing a therapy where none exists or providing a therapy which may be
potentially superior to existing therapy. If there are existing therapies, a fast track drug
must show some advantage over available treatment, such as: showing superior
effectiveness; avoiding serious-side effects of an available treatment; improving the
diagnosis of a serious disease where early diagnosis results in an improved outcome;
or decreasing the clinically significant toxicity of an accepted treatment. Most products
that are eligible for “fast track” designation are likely to be considered appropriate to
receive a priority review. A drug that receives “fast track” (and probably also priority
review) designation is eligible in effect for more frequent contact with the FDA as well
as eligibility for a third component of prioritisation, “accelerated approval” i.e.,
marketing approval on an effect on a surrogate, or substitute endpoint reasonably
likely to predict clinical benefit. All of these procedural measures indicate a willingness
of the FDA to `prioritize` applications to accelerate regulatory review prior to market
authorization.

Another FDA initiative, priority review vouchers are, in essence, a prize incentive for
companies to invest in new drugs and vaccines for neglected tropical diseases. A
provision of the Food and Drug Administration Amendments Act (HR 3580) awards a
priority review voucher to any company that obtains approval for a treatment for a
neglected tropical disease. The voucher, which is transferable and can be sold, also
entitles the bearer to a priority review for another product.

26
 3. Approaches to priority setting

3.4 Public sector priority setting for research and development

The United States National Institutes of Health (NIH), the largest public funder of
biomedical research in the world, has identified five criteria that play a critical role in
decisions about funding biomedical research: (1) public health needs; (2) scientific
merit of specific study proposals; (3) potential for advances in a particular area; (4)
distribution across diverse research areas (since it is impossible to predict exactly
where advances will occur); and (5) national training and infrastructure needs. The first
of these criteria, public health needs, is determined on the basis of five considerations:
the number of people with a specific disease; the number of deaths attributable to a
specific disease; the degree of disability caused by a specific disease; to what extent a
specific disease shortens the average human lifespan; the financial and social costs of a
specific disease; and threats posed to others by contagious disease. According to the
NIH in 1997, these five considerations for determining “public health needs” were of
equal importance in allocating research resources.14

At the time of the 2004 Report, only four institutes of the NIH - the National Cancer
Institute (NCI), the National Institute of Child Health & Human Development (NICHD,
the National Institute on Aging (NIA) and the National Institute of Environmental
Health Studies (NIEHS) - had the facility to retrieve bibliometric data to track the
publications and assess the potential public health impact of their grantees. Of these,
three institutes (NIEHS, NICHD and NIA) have collaborated to develop a database to
improve the priority-setting process.15 The Office of Portfolio Analysis (OPA) was only
recently established in 2011 by the NIH as a whole to “enable NIH research administrators
and decision makers to evaluate and prioritize current, as well as emerging, areas of research
that will advance knowledge and improve human health.”16

With regard to the practical output of awarding NIH grants, there is still inadequate
linkage between NIH awards and literature/citation data. Some preliminary
bibliometric analysis suggests that the effect of a publication’s “impact factor” is more
predictive of the fate of R01 grants than the number of subsequent citations of the
investigators. At a Portfolio Analysis Workshop in July 2012, a survey of over 500
participants showed that 47% thought that measuring the impact of NIH grants would
be the most important task in the work of the OPA.16

Since the late 1980s, there have been many attempts by various international
organizations and less formal groups to develop methods for prioritizing health
research (see also 2004 Report Chapter 3, Annex 3.1). During the 1990s, a series of
commissions undertook studies aimed at priority setting for health or for health
research, but none of these specifically focused on pharmaceutical research. The
studies are summarized below in roughly chronological order:

The Commission on Health Research for Development (1990) was an independent

international initiative formed in 1987 with the aim of improving the health of people
in developing countries through a focus on research (see 2004 Report, Chapter 3
Appendix 3.1).

27
Priority Medicines for Europe and the World 2013 Update

The Essential National Health Research (ENHR) approach was developed to define:
who sets priorities and how to get participants involved; the potential functions, roles
and responsibilities of various stakeholders; information and criteria for setting
priorities; strategies for implementation; and indicators for evaluation. It was designed
to not only specify broad research areas but also give a detailed listing of priority
possibilities/options as well as to involve a broad range of stakeholders and significant
engagement with experts. Significantly, discussion and decisions on funding are
supposed to be based on tapping the skills and knowledge of scientists from a wide
range of disciplines.17

The World Development Report (1993) was produced by the World Bank in
conjunction with the WHO and used a key measure of the burden of disease and
disability called the Disability Adjusted Life Year (DALY), which has also been used in
this Project (see Background Paper 4).18

The Ad Hoc Committee on Health Research (1996) was established in 1994 by the
WHO. It identified a systematic “five-step” process which is the basis of the conceptual
model used in this project.19 Briefly, these five steps include: 1. Calculate the burden of
the conditions or risk factor (look at the magnitude); 2. Identify the reason why the
disease burden persists (look at determinants); 3. Judge the adequacy of the current
knowledge base (assay knowledge); 4. Assess whether new R&D would improve
population health and at what cost (understand cost and effectiveness); 5. Assess the
adequacy of the current level of effort.

The Global Forum for Health Research (2000) created a framework (Combined
Approach Matrix) which brings together in a systematic manner all information
(current knowledge) related to a particular disease or risk factor 20 (see 2004 Report
Chapter 3, Appendix 3.6).

WHO-IFPMA Round Table (2000-2001) was a joint task force, comprising

representatives of the WHO and the International Federation of Pharmaceutical
Manufacturers Associations (IFPMA), convened to establish a working list of infectious
diseases and to review disease burden as a way of directing research priorities. The
task force also used additional criteria such as mortality, societal costs, likelihood of
treatment, and future trends. (See 2004 Report Chapter 3, Appendix 3.7).

The UNICEF-UNDP-World Bank-WHO Special Programme for Research and

Training in Tropical Diseases (TDR) prioritized research by using an adapted version
of the Global Forum’s framework for priority setting, expanded to include information
on the comparative advantages of the TDR. 21 (See 2004 Report Chapter 3, Appendix
3.4).

28
 3. Approaches to priority setting

3.5 Approaches to priority setting post-2004

Priority Setting Methodologies in Health Research (2008) was the theme of a
workshop held at the WHO in Geneva, Switzerland in April 2008. The overall objective
was to develop practical proposals for user-friendly methodologies for priority setting
in health research, for application in developing countries. Specifically, the workshop
(1) reviewed the main priority-setting methodologies utilized to date; (2) reviewed and
assessed case studies of priority setting in various countries and for various topic areas;
and (3) developed a framework of guiding principles and a practical approach to
priority setting by bringing together salient elements of existing methodologies (see
Background Paper 3 and Annexes).

The Child Health and Nutrition Research Initiative (CHNRI) (2007) approach
emphasized principles of legitimacy and fairness and provided a detailed listing of
individual research questions scored against pre-defined criteria. Technical experts
independently scored each research option against these five criteria. As in other
methods, stakeholder input was sought and used to rank the five criteria from the most
important to the least important. These rankings were then adjusted to provide relative
“weights” that determined the importance of the research option. Everything is
recorded, is repeatable, can be reviewed, and can be challenged and revised at any
time based on feedback, so this is a very dynamic process. The role of non-experts was
limited to selecting and weighing criteria. Once consensus is reached on areas of
research there is no further stakeholder involvement.22,23

3.6 Private sector prioritization methods

Methods of prioritization in the pharmaceutical industry vary from company to
company depending on their history and strategic vision. Decisions about new
medicines are generally made within a set of four different contexts: scientific
opportunity, market assessment, available and required resources, and medical need.
The common steps taken are to:
 Review the marketplace to identify unmet medical needs.
 Benchmark competitor products to understand the competitive landscape.
 Identify the market segments and patient populations a product will target.
 Identify all possible additional indications that might make the compound more
valuable.
 Create a dosing and delivery profile to provide optimal dosing and delivery
mechanisms.
 Understand the broad market preferences for the key characteristics of the product.
The goal of market research at this point would be to find a product profile which
payers are willing to pay for and which provides a sufficient return on investment
(for example, is the product profile such that physicians would prescribe it at the
levels needed to justify further development?).
 Assemble market research to profile key geographic markets to ensure product
success.

29
Priority Medicines for Europe and the World 2013 Update

The strength of this approach is that it clearly identifies products that the "market" is
willing to pay for and that will ensure an adequate return on investment.
Unfortunately, this approach will ignore diseases which mainly affect the poor in low-
income countries.

3.7 Prioritizing for the Priority Medicines Project

An assumption in the methods used in this report is that the higher the disease burden,
the greater the cost to society of the disease, and the greater the need for research.
Priorities are then set based on: the relative contribution of each disease to the total
burden; and the measure of burden, ranging from epidemiologic measures to
combinations of mortality and morbidity (such as the Disability Adjusted Life Year
(DALY)). A version of this approach is used in the present method (see Background
Paper 4).

A recent study by Catala-Lopez et al examined whether efforts to develop innovative

medicines in Europe are focusing on the most relevant conditions from a global public
health perspective.24 The authors reviewed the information on new medicinal products
approved by the EU centralized procedure from 1995 to 2009 and evaluated the
association between authorized medicinal products and burden of disease measures,
based on DALYs in the EU and worldwide. They considered 520 marketing
authorizations for medicinal products and 338 active ingredients. There was a positive,
high correlation between DALYs and new medicinal product development (r = 0.619, p
= 0.005) in the EU, and a moderate correlation for low- and middle-income countries (r
= 0.497, p = 0.030) and worldwide (r = 0.490, p = 0.033).

Figure 3.7.1 shows a plot of the DALY burden of the then EU25 countries versus the
proportion of total new chemical entities (NCEs) attributed to that condition (see
Catalá-López et al. Population Health Metrics, 2010 24).

The size of the “bubble” is the weighted fraction of each condition to the total DALY
burden. The black line is the 1:1 situation where the fraction (%) of NCEs for that
condition matches the proportional DALY burden for that condition. In the EU25,
infectious and parasitic diseases, blood and endocrine disorders, diabetes mellitus and
genitourinary diseases were all relatively over-represented with regard to NCEs in
relation to the disease burden they generate (points above the 1:1 line in Figure 3.7.1),
while the most under-represented conditions were neuropsychiatric diseases,
cardiovascular diseases, respiratory diseases, sense organ conditions and digestive
diseases (points below the 1:1 line). At the global level (data from the same source, not
presented here), the most under-represented conditions were perinatal conditions,
respiratory infections, sense organ conditions, respiratory diseases and digestive
diseases.

30
 3. Approaches to priority setting

Figure 3.7.1: Bubble plot representing disability-adjusted life years (DALYs)

for EU-25 and active ingredients (NCEs)

Source: Catalá-López et al. Population Health Metrics, 2010, 8:34

Note: The areas of the bubbles are DALYs’ weighted contribution of each disease
condition(s) to the total burden of disease. 1: Other neoplasms; 2: Unintentional injuries
(poisoning); 3: Congenital anomalies; 4: Digestive diseases; 5: Respiratory diseases; 6:
Skin diseases; 7: Respiratory infections; 8: Maternal conditions; 9: Perinatal conditions

3.8 Providing a menu of complementary priority setting

approaches
As in the 2004 Report, the present report uses several complementary approaches for
establishing priorities for biomedical research. Where adequate data are available on
burden of disease and on the efficacy or lack of efficacy of treatments, an evidence-
based approach has been used (Modes 1-2 in Figure 3.2.1). Where data on burden of
disease or efficacy do not exist, projection or trend analysis methods have been used
(Modes 4-6 in Figure 3.2.1). For rare diseases and neglected diseases or where market
failures occur, principles of social solidarity have been applied (Modes 4-7 in Figure
3.2.1). (See Background Paper 3). Where it is clear that risk factors play a role in the
development of multiple disease states (mainly noncommunicable diseases), risk
factors (obesity, smoking) have themselves been used as a priority condition (Modes 4-
7 in Figure 3.2.1).

In order to bring complementary information to this approach, the framework

developed by the Global Forum has also been used to ask additional questions about
the current state of diseases of interest. This framework can be seen in the templates
developed for determining pharmaceutical gaps in Chapter 6. As these are different
though complementary methods the outcomes of each approach cannot be directly

31
Priority Medicines for Europe and the World 2013 Update

compared. All four approaches have been presented to give a comprehensive overview
of “pharmaceutical gaps” that can be prioritized for research.

3.8.1 Priorities based on evidence-based approach

(For example, acute stroke, chronic obstructive pulmonary disease (COPD),
Alzheimer disease: Modes 1 and 2 in Figure 3.2.1)
For this approach, burden of disease analysis has been used to determine a preliminary
list of high burden diseases and conditions. The combination of burden of disease and
clinical efficacy provides a preliminary list of conditions which have pharmaceutical
gaps (see also Background Paper 5).

3.8.2 Priorities based on projections and trends

(For example, antimicrobial resistance (AMR), pandemic influenza: Modes 4-
7 in Figure 3.2.1)
Looking ahead, what are the emerging diseases that could affect the EU and the world?
The answers to these questions form the second prioritization method and are based
primarily on consensus judgements and observational and clinical evidence. Although
AMR is not a disease or condition per se, its importance as a threat to global public
health is expected to continue to grow. The same holds true for pandemic influenza.

3.8.3 Priorities based on social solidarity

(For example, rare or neglected diseases: Modes 4-7 in Figure 3.2.1)
The ethical and moral aspects of priority setting have been selected as the third
prioritization method along the continuum of Figure 3.1. Ethics and moral values are
often invoked to mobilize support for various health initiatives, and theories of social
justice (for example, the fair and equitable treatment of people) have been applied to
justify medicine and public health as a special "social good" (see 2004 Report,
Background Paper 3). Many European countries have a long history of social solidarity.
This has been demonstrated by the creation of universal social security systems and of
national health systems which are intended to ensure universal access to medical care
and pharmaceuticals.

In the EU and elsewhere, governments have enacted legislation to protect the interests
of people suffering from rare (“orphan”) diseases. This requires society to spend
substantial funds on a limited number of people who suffer from rare diseases. At a
global level, based on principles of global solidarity, similar efforts are needed to
address neglected diseases, which mainly affect the poor in low-income countries, as
well as other poor populations. In response, orphan diseases and neglected diseases
have been selected as priority diseases, even though the former affect small numbers of
patients and the latter affect patients living outside the EU. Special patient groups (the
elderly, women and children) are also considered since these groups often lack
effective medicines.

32
 3. Approaches to priority setting

3.8.4 Priorities based on risk factors

(For example, smoking, obesity: Modes 4-7 in Figure 3.2.1)
The most critical disease risk factors that will affect the EU countries and the world
going forward were selected as the fourth prioritization method along the continuum
of Figure 3.2.1. The answers to these questions are based on data generated by the
WHO’s Global Burden of Disease: 2004 Update and by the analyses of the more recent and
distinct Global Burden of Disease Study 2010 (see Chapter 4 and associated Background
documents). Obesity and tabacco use are risk factors for major chronic
noncommunicable diseases (NCDs) that influence both length and quality of life. More
specifically, obesity and smoking are well-established independent risk factors for
cardiovascular diseases. While all of these risk factors can and should be addressed
through prevention and health promotion activities, possible opportunities for
pharmacotherapeutic approaches exist. As a result, these risk factors were added to the
Preliminary List.

3.9 Conclusions
In this report, four complementary approaches to prioritization are used in an effort to
overcome the inadequacies of any one of these approaches when used exclusively. For
those decision makers who would like to use only evidence-based approaches, it
should be noted that absence of evidence does not necessarily mean there is no threat
or need. For those who would prefer to use a consensus-based expert opinion
approach, it should be pointed out that such expert groups have often missed
important developments. And while an approach based on the use of projections and
trends is critical in efforts to prepare for future threats to global public health, it
inevitably involves the use of judgments made on the basis of uncertain information.
For those who would use social solidarity as the sole criterion for prioritization, it is
important to note that there are many people, both rich and poor, from developed and
developing countries, who have benefited substantially from medical advances
achieved as a result of approaches based on evidence or projections and trends.

In this report a combination of methods have been used to achieve a balanced and
optimal result. By using these four approaches together, the health needs of both
Europe and the world have been taken into account in addressing pharmaceutical gaps
for diseases of current and future public health importance.

References

1 Viergever et al. 2010. A checklist for health research priority setting: nine common themes of
good practice. Health Research Policy and Systems, 2010, 8:36. Available at http://www.health-
policy-systems.com/content/8/1/36
2 Institute of Medicine. Health Services Research. Washington DC, National Academy of Sciences,

33
Priority Medicines for Europe and the World 2013 Update

1979.
3 Stocker JW. Priority Matters. Canberra: Department of Industry, Science and Tourism, 1997.
4 Vuorenkoski L, Toiviainen H, Hemminki E. Decision-making in priority setting for
medicines—A review of empirical studies. Health Policy, 2008, 86, 1–9.
5 Bahl et al. Research Priorities to Reduce Global Mortality from Newborn Infections by 2015.
Pediatr Infect Dis J, 2009, 28: S43–S48
6 Youngkong et al. Setting priorities for health interventions in developing countries: a review of
empirical studies. Tropical Medicine & International Health, 2009, 14(8): 930–939
7 Rudan et al. Evidence-Based Priority Setting for Health Care and Research: Tools to Support
Policy in Maternal, Neonatal, and Child Health in Africa. PLoS Med, 2010, 7(7): e1000308.
8 Guindo et al. From efficacy to equity: Literature review of decision criteria for resource
allocation and healthcare decision making. Cost Effectiveness and Resource Allocation, 2012, 10:9
9 Fast track, priority review and accelerated approval. U.S. Food and Drug Administration, 2004.
Available at http://www.accessdata.fda.gov/scripts/cder/onctools/Accel.cfm Last accessed 12
March 2004.
10 Guideline on the procedure for accelerated assessment persuant to article 14 (9) of Regulation (EC) No
726/2004. European Medicines Agency, 2006. (EMEA/49127/05) Available at
http://www.ema.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_guid
eline/2009/10/WC500004136.pdf Last accessed 27 May 2013
11 Commission Regulation (EC) No 507/2006 of 29 March 2006 on the conditional marketing
authorisation for medicinal products for human use falling within the scope of Regulation
(EC) No 726/2004 of the European Parliament and of the Council. Available at
http://ec.europa.eu/health/files/eudralex/vol-1/reg_2006_507/reg_2006_507_en.pdf Last
accessed 27 May 2013
12 Guideline on Procedures for the granting of a marketing authorisation under exceptional circumstances,
pursuant to Article 14 (8) of Regulation (EC) NO 726/2004. EMEA/357981/2005. European
Medicines Agency, 2005. Available at
http://www.ema.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_guid
eline/2009/10/WC500004883.pdf Last accessed 27 May 2013
13 U.S. Food and Drug Administration, Glossary of Terms. Available at
http://www.fda.gov/drugs/informationondrugs/ucm079436.htm
14 Setting Research Priorities at the National Institutes of Health. National Institutes of Health, 1997.
15 Office of Portfolio Analysis. Atlanta, Center for Disease Control and Prevention. Available at
http://dpcpsi.nih.gov/council/pdf/COC-portfolio_analysis.pdf
16 National Institute for Health. Office of Portfolio Analysis. Available at
http://dpcpsi.nih.gov/opa/index.aspx
17 A Strategy for Action in Health and Human Development. Task Force on Health Research for
Development Secretariat, 1991. Available at http://www.cohred.org/downloads/526.pdf
18 World Bank. World Development Report 1993: Investing in Health. New York, Oxford
University Press, 1993. Available at
http://mednet3.who.int/prioritymeds/report/append/33b_apx.pdf

34
 3. Approaches to priority setting

19 Ad Hoc Committee on health research relating to future intervention options. Investing in health
research and development. Geneva, World Health Organization, 1996. (TDR/Gen/96.1).
20 Global Forum for Health Research. Available at http://www.globalforumhealth.org Last
accessed 12 March 2004.
21 The UNICEF-UNDP-World Bank-WHO Special Programme for Research and Training in
Tropical Diseases (TDR). Geneva, World Health Organization. Available at
http://www.who.int/tdr Last accessed 8 March 2004.
22 Tomlinson M et al. Setting priorities in child health research investments for South Africa.
PLoS Med, 2007, 4: e259.
23 Rudan I et al. Childhood pneumonia and diarrhoea: Setting our priorities right. Lancet Inf Dis,
2007, 7: 56–61.
24 Catala-Lopez et al. Does the development of new medicinal products in the European Union
address global and regional health concerns? Population Health Metrics, 2010, 8:34. Available at
http://www.pophealthmetrics.com/content/8/1/34

35