Chapter 3: Priority Setting
Priority Medicines for Europe and the World
"A Public Health Approach to Innovation"
Background Paper
Priority Setting
Warren Kaplan, Ph.D., JD, MPH
7 October 2004
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Chapter 3: Priority Setting
Table of Contents
3.
Priority Setting ............................................................................................................................. 3
3.1 General Introduction to Priority Setting ....................................................................... 3
3.1.1
Subjective Methods ............................................................................................. 3
3.1.2
Using Burden of Disease as a Benchmark ....................................................... 3
3.1.3
Valuing Impact on Actual Clinical Practice .................................................... 3
3.1.4
Valuing Information Itself ................................................................................. 4
3.2 Definition of “Priority” Medicines ................................................................................ 4
3.2.1
Drug Regulatory Authority Priority Setting and Innovation ....................... 4
3.3 Public Sector Priority Setting: National Cancer Institute, Global Forum and
Others ................................................................................................................................... 6
3.4 Private Sector : Prioritizing Pharmaceutical R&D Private Sector “Unmet Needs”
Assessment .......................................................................................................................... 7
3.4.1
Pharmaceutical Company’s Product Development Strategy ....................... 7
3.4.2
Determining Unmet Medical Need: Company A........................................... 8
3.5 Prioritization in Other Contexts ...................................................................................... 8
3.5.1
Examples of Priority Setting at a Local Level ................................................. 8
a.
Hospital Formulary Committees ...................................................................... 8
b.
The Oregon Experiment ..................................................................................... 9
3.6 Prioritizing for the Priority Medicines Project ........................................................... 10
3.6.1
Background: Solving Problems and Making Decisions.............................. 10
3.6.2
Priority Setting as a Political Process ............................................................. 11
3.6.3
Putting Explicit Models in Perspective: Providing a “Menu” for Policy
Makers ................................................................................................................ 11
a.
The "Evidence Based" Approach (e.g., Acute Stroke, Chronic Obstructive
Pulmonary Disease, Alzheimer`s disease): Modes 1 and 2 in Figure 3.1 .. 11
b.
Priorities Based on Predictions and Probabilities (e.g., Antibacterial
Resistance, HIV): Modes 5, 6 and 7 in Figure 3.1. ........................................ 12
c.
Priorities Based on Social Justice (e.g., Orphans, special patient groups,
and the Neglected Diseases): Modes 5, 6 and 7 in Figure 3.1 ..................... 12
d.
Bringing the Evidence Base "Up to date": Modes 1, 2, 5, and 6 in Figure
3.1 ........................................................................................................................ 13
3.7 Conclusions ....................................................................................................................... 13
References ................................................................................................................................... 14
Annexes
Appendices
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Chapter 3: Priority Setting
3.
Priority Setting
See Annex 3
3.1
General Introduction to Priority Setting
Setting priorities for health research includes two broad approaches: technical analyses which
rely on quantifiable epidemiologic, clinical, financial or other data, and 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 these measurable units such as diseases
(burden of disease) or interventions (with respect to their costs and use). See, for example,
literature on clinical trial investments 1 or assessments of technology.2, 3 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 healthcare services.
Indeed, as will be discussed in Chapter 4, even measuring the burden of disease itself means
different things to different people. The funding priorities of the U.S. National Institutes of
Health (NIH) demonstrate this point rather well.4 See also Subsection 3.1.2.
Interpretive/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 U.S. National Institutes of Health ( NIH), 5 the Science and Technology Council
of Australia6 , or even large pharmaceutical companies .
3.1.1
Subjective Methods
In many cases of priority setting, if one carefully reviews the methodology, one sees that the
assessment of the importance of research is often based on subjective judgments of reviewers
and referees and the consensus that emerges from their various opinions. Such methods cannot
provide a truly objective judgment, nor can there be a replicable methodology for valuing
research and setting priorities since there is no formal measure of health research being
estimated. Such methods may be useful, however, to complement more evidence-based
approaches.
3.1.2
Using Burden of Disease as a Benchmark
The assumption in this method is that the higher the 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, the measure of burden ranging from
epidemiologic measures to combinations of mortality and morbidity (e.g., disability adjusted life
year or DALY). See Chapter 4.The assumption is that the burden of disease rankings can be
translated into a need for research. This assumption is not proven.
3.1.3
Valuing Impact on Actual Clinical Practice
The impact of research on actual clinical practice has been used for prioritization, based on the
assumption that randomized clinical trials (RCTs) showing benefit of one treatment over another
(i.e., standard treatment vs. new treatment) is likely to change current practice, and thus
provide a net health benefit to the population.19 More often than not, RCTs providing such
"head to head" comparisons are not done (See Chapter 8.4). Moreover, there may be more ways
to modify current clinical practice than to conduct more clinical research.
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Chapter 3: Priority Setting
3.1.4
Valuing Information Itself
These models recognize the uncertainty in prioritization due to the uncertainty in the factors that
make up the decision. These decision-analytic methods provide some quantitative measure of
the uncertainty. Different parameters are assigned probability distributions that represent how
well we understand the parameters. Using, for instance, various computer simulations, the
models are iterated and expected costs and outcomes for treatments are calculated. Decisionanalytic methods have been proposed as a framework for decision making for the UK`s National
Institute of Clinical Excellence (NICE).19 Analysis and subjective/intuitive approaches can be
identified at various places on a ‘cognitive continuum’ that embodies changing ratios of analysis
to intuition. Figure 3.1 is taken from Appendix 3.5 and is based on the work of Kenneth
Hammond at the University of Colorado, Boulder CO. Our methodology for prioritization uses
this framework at several different places. See Subsection 3.6.
Figure 3.1: A Cognitive Continuum Framework
INTUITION
Quality of
Intuition
ANALYSIS
Least precise/explicit
MODE:
Knowledge
Generation
Decision/
Policy Making
Quality of
Analysis
7
6
Most precise/explicit
5
4
expert descriptive
nonclinical
cognitive judgement consensus models
judgement
judgement
clinical
expert
noncognitive judgement consensus
judgement
judgement
3
case
control
study
2
1
randomized laboratory
controlled experiment
trial
decision
models
Source: J. Dowie. In: Health Care Priority Setting. A. Oliver ed. Nuffield Trust, UK
3.2
Definition of “Priority” Medicines
3.2.1
Drug Regulatory Authority Priority Setting and Innovation
We briefly review how the drug regulatory agencies of the United States, the EU and Canada
define a “priority” medicine.
UNITED STATES
The classification system of the U.S. Food and Drug Administration (FDA) assigns all
new drug approvals to categories representing distinct levels of innovation, and this
classification is relevant for our purposes 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” because it is a 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
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Chapter 3: Priority Setting
U.S. market. An INCREMENTALLY MODIFIED DRUG (IMD) is one that relies on an
active ingredient present in a drug already approved for the U.S. market, or a closely
related chemical derivative of such an ingredient, and has been modified by the
manufacturer. “OTHER” drugs are drugs with 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 an NME, IMD or “other”. Most U.S.
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. 7
We further note that the Institute of Medicine (IOM) Report on the National Institutes of
Health (1998)8 investigated the research prioritization in the NIH. Research
prioritization at the Institutes within the NIH varies by Institute. The National Eye
Institute has a formal planning process although details are not known at this time. The
National Cancer Institute (NCI) plans, promotes, and carries out disease-specific
research, through advice from expert Progress Review Groups (PRGs) in an
interpretive/consensus stakeholder approach.
EUROPEAN UNION
EU Products are eligible for “priority review” by the European Agency for the
Evaluation of Medicinal Products (EMEA) if they claim to provide a significant
improvement compared to marketed products in the treatment, diagnosis, or prevention
of a disease. This is not the same as “fast track” status in which the license processing
time is approximately halved. The EU system grants this accelerated approval based on
the seriousness of the disease, the absence or insufficiency of an appropriate alternative,
and anticipation of high therapeutic benefit.
CANADA
“Priority” medicines in Canada are those for a serious, life-threatening or severely
debilitating illness or condition for which there is substantial evidence of clinical
effectiveness. Specifically, the drug must provide effective treatment, prevention or
diagnosis of a disease or condition for which no drug is presently marketed in Canada.
Alternatively, the drug must provide a significant increase in efficacy and/or significant
decrease in risk such that the overall benefit/risk profile is improved over existing
therapies. The benefit/risk evaluation in Canada may include:

Improvement in one or more of the serious outcomes

A favorable effect on a serious symptom of the condition for which there is no existing
therapy;

A clinical benefit in individuals unable to tolerate, or unresponsive to, existing therapies;

Demonstration of effectiveness in combination with other critical agents, where no
information is available;

Demonstration that the new agent is able to provide clinical benefits that are similar to
existing therapies while a) avoiding serious toxicity present in existing therapies and/or
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Chapter 3: Priority Setting
b) avoiding less serious toxicity, common to the therapy, which results in the
discontinuation of treatment for a serious disease. See Canadian Ministry for Health. 9
3.3
Public Sector Priority Setting: National Cancer Institute, Global Forum and
Others
Over the past decade, attempts at priority setting for healthsector research have been made by
public sector organizations such as the NIH, the Global Forum for Health Research, TDR, other
WHO collaborations. We provide brief summaries of a few of such attempts.
The Commission on Health Research for Development (COHRD: 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. The idea of country-specific research became
manifest as the Essential National Health Research (ENHR) concept. 10 See Appendix 3.1.
The World Development Report (WDR) 11 was the 16th in a series of World Bank reports and
was prepared in conjunction with the WHO. Probably the greatest value-added was the use of
the Disability Adjusted Life Year (DALY) – arguably a major advance in methodology- to help
guide resource allocations towards reducing the greatest burden of disease and for which there
are cost effective responses. See Appendix 3.2.
The Ad Hoc Committee on Health Research 12 (1996) was established under WHO auspices and
was formed based on the previous conclusions of the WDR as well as the interests of funders
and foundations in health R&D. The Committee focussed on needs of low to middle income
countries but realized that “private sector” product development considerations (magnitude of
the problem, basing cost-effectiveness of new therapies and products on scientific judgment) can
inform debate about priorities for public sector R&D as well. A major contribution of this
document was the identification of specific high priority product development opportunities
using a systematic “ 5 step” process.
The WHO Advisory Committee on Health Research is the primary expert WHO advisory body
on scientific research and practices and their role is to analyse health status to guide a global
health research agenda.13 Their methodology for setting research criteria is written in only the
broadest terms. See Appendix 3.3.
The Global Forum for Health Research 14 has 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. This framework is a very useful way of organizing information.
It identifies gaps in knowledge and future challenges. In part, its value is in its ability to help set
priorities for national, regional or global diseases. See Appendix 3.6.
The framework allows identification of “common factors” by looking across diseases or risk
factors. Completing the matrix should highlight the “blank areas”, i.e., where there are gaps in
information needed to make rational decisions. We have based our approach, in part, on this
methodology (See Section 4.3).
The Special Programme for Research and Training in Tropical Diseases (TDR) prioritizes
research using an expansion of the Global Forum matrix to include information on TDR's
comparative advantages and, based on this, provides conclusions as to TDR's strategic research
emphasis. Prioritization is done on a disease-by disease basis. TDR has completed this
prioritization exercise for African trypanosomiasis, Dengue, Leishmaniasis, Malaria,
Schistosomiasis, Tuberculosis, Chagas disease, Leprosy, Lymphatic filariasis, and
Onchocerciasis. For each disease, the analysis was undertaken by the TDR in consultation with
outside experts.15 See Appendix 3.4.
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Chapter 3: Priority Setting
WHO-IFPMA ROUND TABLE 16 : In 2000/2001, a joint task force comprising members of the
WHO and the pharmaceutical industry convened to establish a working list of infectious
diseases and review disease burden as a way of directing research priorities. The criteria used
for assessing disease impact included, in addition to disability adjusted life years (DALYs):
mortality, societal costs, likelihood of treatment and forward trends. They then reviewed
existing interventions on the basis of availability and any limitations of medicines. Current
levels of industry activity for each disease were assessed. A judgment on the need for additional
medicines R&D was therefore made both on the basis of the current or likely future availability
of medicines and of other treatment approaches. Altogether a combination of 17 assessment
criteria were used. See Appendix 3.7.
3.4
Private Sector : Prioritizing Pharmaceutical R&D Private Sector “Unmet Needs”
Assessment
3.4.1
Pharmaceutical Company’s Product Development Strategy
Based on discussion with industry executives, we would describe the general process used by
the industry as follows: For the pharmaceutical industry, there is no “generic” method for
determining unmet medical need and for creating a product development profile, as each
organization has different needs and agendas. However, most companies combine commercial
market research, competitive intelligence, therapeutic strategies with scientific development to
determine their therapeutic product profile. Decisions about new drugs are generally made
within a set of four different contexts, scientific opportunity, market assessment, available and
required resources and medical need. 17 From a marketing viewpoint, a “classic” market-based
series of steps might occur as follows:

Review the marketplace to identify unmet medical needs. This involves reviewing the
therapeutic area to understand the state of practice and to identify key market openings
that reflect this unmet medical need. This task requires interpreting complex
epidemiological and economic data “ … where there are not accepted definitions of
need.”17 How does one compare the “need” for new treatments for rare, fatal conditions
with need for palliatives for common diseases that produce disability but not death? See
Subsection 3.4.2

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.
Often, companies seek to introduce more indications and line extensions earlier in a
product “lifecycle” so as to maximize a molecule’s lifetime economic value;

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 so that
commercial perspectives are embedded early on in the product development cycle. The
goal of market research at this point would be to find a product profile that physicians
would prescribe at levels needed to justify further development; Assemble market
research to profile key geographic markets to ensure product success;

Create an ideal new product launch profile since marketers note the importance of
identifying characteristics that would enable a fast-uptake launch for the new product.
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Chapter 3: Priority Setting
There are numerous tools and tactics to make these assessments. These include, among others,
structured processes to guide teams through critical discussions, milestones and decisions,
sophisticated decision trees and complex econometric forecasting to integrate several decision
factors with use of historical benchmarks of past project from similar areas. We note that overly
complex and financially driven models can provide a false sense of certainty into an inherently
risky endeavour.
3.4.2
Determining Unmet Medical Need: Company A
One of the largest innovative pharmaceutical companies shared their approach to determining
“unmet medical needs” with us. They have found that determining and measuring unmet needs
is not straightforward. Many factors, conscious and unconscious, contribute to a person’s
perception of unmet needs and these will vary between people and between different diseases.
Recognising this, the company established a systematic method in the 1990s to measure
perceptions of unmet needs amongst its customers. The process started with qualitative market
research among doctors in the US and Europe to determine what they believed were the key
components of unmet medical need. These varied from the extent of physical or psychological
suffering the disease imposed on the patient, to the financial impact of the disease, the likelihood
of complications and the effect on careers. In total, 18 major classes of factors were identified.
The company discovered that healthcare providers in the US and Europe view unmet medical
needs in the same way. Hence the company developed their unmet need model with US doctors
but with the understanding that the model would also be appropriate in the European setting.
Following the initial qualitative phase, the company embarked on a major piece of quantitative
market research whereby over 700 doctors (primary care and specialist) in the US have ranked
over 600 conditions against these 18 factors. The end result of this process is that an unmet need
“score” can now be associated with any disease from the prescriber’s perspective. In this way
the company can determine which are the more significant diseases in terms of unmet needs as
perceived by primary care and specialist prescribers.
In addition, by further studying the data the company has been able to determine the drivers of
the unmet need for each disease so they are able to direct their research efforts. Finally, using a
decision tree approach, the company is able to determine the extent to which the unmet need
might be reduced if a new therapy were introduced. The company has repeated this market
research routinely because it is recognised that unmet need is not static. As new treatments are
introduced, perceptions of unmet needs will change and these need to be continually monitored.
3.5
Prioritization in Other Contexts
3.5.1
Examples of Priority Setting at a Local Level
Albeit on a different scale than the EU, the issues raised in priority setting for pharmaceuticals in
hospital formularies and the state of Oregon are illustrative and we briefly discuss these below .
a.
Hospital Formulary Committees
Priority setting for new drugs in a hospital context such as in a hospital drug formulary
committee 16 is based on a complex array of factors that include clinical evidence, adverse
reactions, availability of alternate drugs, ease of administration, cost of the drug as compared to
current drug cost, and , comparative advantages of over drugs. Formulary committees do not
review all these factors, but rely on clusters relevant to each decision. Thus, in this case, decision
making is highly dependent on “context.”
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Chapter 3: Priority Setting
Studies have described decisions regarding new drugs as being based on: “thresholds”
determined from information on effectiveness 17, generic substitution principles 18, or other,
somewhat limited survey information or decision making techniques. 19
b.
The Oregon Experiment
In the late 1980s Oregon (a state in the northwestern part of the United States) decided to expand
Medicaid coverage for low-income individuals, to a greater number of people. Oregon
formulated an explicit process for setting priorities in health services. The Oregon methodology
used five primary care physicians, a public health nurse, a social worker and four members of
the public and they were to draw up a list of services ranked according to priority of importance,
based on considerations of clinical effectiveness and social values. Panels of physicians rated
the clinical effectiveness of approximately 1000 condition-treatment pairs. Public input was
sought to integrate social values into the priority list. i There was widespread criticism of some
of the rankings. This was related in part to the poor data on effectiveness20 and probably on how
people view health “utilities”.ii
We have reviewed the Oregon priority list . Pharmaceutical interventions, in decreasing order
of ranking are listed below. Those conditions in bold are also found in our preliminary list for
developing “priority medicines” (See Chapter 5).
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
Type 1 diabetes mellitus
Peritonitis
Acute glomerulonephritis
Tuberculosis
Pneumoccocal pneumonia, other bacterial pneumonia
Pertussis and diphtheria
Acute bacterial meningitis
Hodgkin’s disease
Liver abcess
Pancreatic cancer
Non diabetic hypoglycaemic coma
Acute osteomyelitis
Acute mastoiditis
Pyogenic arthritis
Acute inflammation of the heart
Peripheral vascular disease
Septicemia
Necrotizing enterocolitis in fetus or newborn
Neonatal thyrotoxicosis
Respiratory conditions of fetus and newborns
Low birth weight
Fetal hemorrhage
Cystic fibrosis
End stage renal disease
Liver cirrhosis, polycystic liver disease,
i
Public preferences for a variety of health states were obtained by a random telephone survey. Meetings were held
across the state to assess the public's values regarding various health services. Public meetings were held to allow
input from special interest groups regarding specific services.
ii Hypothetical choices about severe medical conditions elicit different responses when the choices are placed in a
social context as people tend to give such conditions much more weight (See endnote 18).
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Chapter 3: Priority Setting
26.
27.
28.
29.
30.
31.
32.
33.
34.
35.
36.
37.
38.
39.
40.
41.
42.
43.
44.
45.
46.
47.
48.
49.
50.
51.
Diabetes insipidus
Asthma
Pneumonia due to respiratory syncitial virus
Schizophrenia
Recurrent Major depression
Bipolar disorders
HIVOpportunistic
HIV infections
Malaria
Heart failure
Single episode of depression
Attention deficit disorders
Hypertension
Ulcers, gastritis
Uterine cancer
Breast cancer
Ovarian cancer
Transient cerebral ischaemia
Lung cancer
COPD
Stroke
Acute bronchitis
Type 2 diabetes mellitus
Rheumatoid arthritis
Acute otitis media
Alcoholic liver disease
3.6
Prioritizing for the Priority Medicines Project
3.6.1
Background: Solving Problems and Making Decisions
If we agree that resources for pharmaceutical R&D are substantially fixed and the needs and
demands for health interventions are not, then all decisions regarding R&D resource allocation
decisions are rationing decisions. Rationing in this situation implies that, because of cost and
other constraints, not every disease condition will get every medicine that is needed, wanted,
or even deserved. Prioritizing, fixing agendas, setting goals and designing actions are usually
called “problem solving” and evaluating and choosing among alternative actions is called
“decision making”.
Many problems (e.g., designing a building, creating a public health based pharmaceutical R&D
prioritisation) have complex, ambiguous goals and are constantly shifting or transforming in the
course of exploring the problem. Much of the research about organizational decision-making in
management studies, industrial sociology and organizational psychology reveals that
organizational decision-making is often messy, implicit, intuitive and ill-defined.21
The goals of a public health care system are a complex amalgamation of a number of other goals,
not all of which are readily defined. Thus, the use of any one tool to set priorities within such a
complex entity may be overly simplistic. 22 Indeed, evidence shows that allocations of research
funds by the NIH through largely informal and unstructured processes turn out to be consistent
with measurements of disease burden (a criteria used on more formal priority setting models). 23
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Chapter 3: Priority Setting
This complexity is further underscored by Holmstrom (1999), who stated that
“… priority-setting is a complex interaction of various decisions at diverse levels in the organization.
There is no self obvious set of ethical principles or scientific tools to determine what decisions we should
take at various levels, nor is there an easy or obvious way to determine what decisions we should take at
various levels, nor is there an easy or obvious way to resolve the dilemma of the increasing gap between
what we can and would like to do on one hand and the resources on the other”.24
There is no one correct answer; indeed there may not even be an answer. At a minimum., there
will be moral disagreements over the decisions that are made. 25 For example, setting
pharmaceutical research priorities based on principles of efficiency may lead to very costeffective interventions that cannot be offered to everyone because of the expense, thereby
violating the principles of equity.
3.6.2
Priority Setting as a Political Process
The question then becomes whether priority setting is, or can be, a truly rational undertaking 26
or whether it is essentially a value-based political process.18 Priority setting in health care at the
level of the European Union involves inadequate information, uncertainty, and conflicting
interests among many people, many goals and many values. Ultimately, it must be essentially a
political process which involves “pluralistic bargaining between different lobbies, modified by
shifting political judgements made in the light of changing pressures.” 24 Under such
circumstances, it may be that what is required is an explicit framework that allows stakeholders
to debate about what values should be used to set priorities. This suggests that a truly
comprehensive process of priority setting requires public input (to understand individual and
societal principles) and accountability (to make explicit the rationale for decisions). 27
3.6.3
Putting Explicit Models in Perspective: Providing a “Menu” for Policy Makers
We believe there is no “best” way to prioritise pharmaceutical R&D in a public health context
and such prioritisation should be viewed, not as a problem to be solved, but as a
multidimensional “dilemma” iii.
There are principles of allocation which can be thought of as a series of non- exclusive items on
the continuum of Figure 3.1 as a “menu” that policy makers might consider. We briefly discuss
these allocation principles and then summarize how policy makers might use them in
prioritisation of pharmaceutical R&D.
a.
The "Evidence Based" Approach (e.g., Acute Stroke, Chronic Obstructive
Pulmonary Disease, Alzheimer`s disease): Modes 1 and 2 in Figure 3.1
We have combined burden of disease analysis and an assessment of clinical efficacy of
interventions for diseases using rankings for burden of disease and the Cochrane Reviews of
randomized clinical trials. See Chapter 4 for further details of the burden of disease method and
the clinical trial reviews. Each of the burden of disease and clinical efficacy analyses has
important limitations which are further discussed in Chapter 4. At best, the combination of
burden of disease and clinical efficacy provides a preliminary, retrospective review of
pharmaceutical "gaps", in particular because newer and very old therapeutic interventions will
not be found in the Cochrane Reviews (See Chapter 4). While we have analyzed the risk of side
effects, we have been unable to incorporate this data into our priority setting as the quality of the
data was so uneven. See Chapter 5 and the Annexes to Chapter 5.
Dilemma: “ Any situation necessitating a choice between unpleasant alternatives”, Webster’s New
World Dictionary, 1960, World Publishing Company, USA
iii
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Chapter 3: Priority Setting
b.
Priorities Based on Predictions and Probabilities (e.g., Antibacterial Resistance,
HIV): Modes 5, 6 and 7 in Figure 3.1.
What are the emerging diseases that will affect the European Union and the world going
forward? What existing diseases or risk factors will grow in importance? The answers to these
questions form our second prioritization method and are based primarily on consensus
judgments and observational and clinical evidence. Clearly, antibacterial resistance is not a
disease condition per se, but we believe its importance as a threat to global public health will
continue to grow. Few, if any, clinical trial reviews on HIV or diabetes have yet found their way
into the Cochrane database. As a result, we have relied on the predictive power of other
evidence and the views of experts in the field to develop priorities.
c.
Priorities Based on Social Justice (e.g., Orphans, special patient groups, and the
Neglected Diseases): Modes 5, 6 and 7 in Figure 3.1
There are many perspectives one can take with regard to pharmaceutical research priority
setting in terms of the Priority Medicines Project. One can conceptualise priority setting within
a legal context as emphasizing universal rights to health care, or within a medical perspective as
relying on evidence-based medicine, or within an economics perspective as emphasising costeffectiveness analysis. Recently, many have argued that priority setting is an ethical exercise that
requires moral reasoning28 29. Accordingly, various ethical theories have guided priority setting.
30
We have chosen to emphasize the ethical and moral aspects of priority setting as our third
prioritization method along the continuum of Figure 3.1. Many European countries have a long
history of social solidarity. This has been demonstrated by the creation of universal social
security systems and national health systems which ensure that everyone in that society should
have access to medical care and pharmaceuticals. The USA and Europe have chosen to pass
legislation for "orphan diseases" which require the society to spend substantial funds on a
limited number of afflicted individuals who suffer from rare diseases.. At a global level we
would suggest that based on principles of global solidarity, similar efforts should be made to
cure "neglected" diseases which afflict poor people in poor countries.
Ethical and moral values are invoked to mobilize support for various health initiatives. There
are several schools of moral concepts that have explained this approach and two are briefly
summarized.
“Utilitarianism” is based on providing the greatest good for the greatest number and is usually
defended in terms of efficiency. Across all individuals in a society, the ideal condition is one that
maximizes health because health generates "utility" directly (such as generating increased
economic growth, and thus enhancing aggregate income). Therefore, under a strict
interpretation of utilitarianism, research funds would be distributed to diseases or specific
interventions in such a way as to maximize the net well-being of everyone. The WHO
Commission on Macroeconomics and Health estimated the costs and benefits of disease burdens
and asserted that investing in health would generate economic growth. 31
"Equity" is a relational concept and much important work has been done to clarify what health
equity really is. 32 An equity based evaluation should consider not only allocation of a fixed set
of health resources but the allocation of resources generally between health and other objectives.
The basic idea is that burdens (e.g., morbidity, mortality, costs of healthcare) and benefits (e.g.
health, well being, a chance to recover) are distributed fairly across individuals and groups.
The “equity” principle underlies priority setting based on either need, age or treatment
effectiveness. For example, the use of need for priority-setting might rank research into health
promotion programs very poorly 33 although from a utilitarian viewpoint, promotion programs
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Chapter 3: Priority Setting
might have more “bang for the buck.” Equity remains the presumptive principle in debates
over democracy, the social welfare state, and the distribution of income and other goods.
Powerful arguments based on equity have been raised such as the call to expand funding for
antiretroviral therapies for people living with HIV and AIDS in poor countries.
We note that such aspects, given human nature, will inevitably find themselves discussed even
using purely evidence based methods.
In this regard, we have applied this relational concept of "equity" and have prioritized orphan
diseases (Chapter 7.5), diseases of special patient groups (Chapter 7.2, 7.3 and 7.4) and
"neglected diseases" (6.9) as those worthy of examination by the European Union, even though
they affect small numbers of patients and, in the case of neglected disease, affect patients living
outside the EU.
d.
Bringing the Evidence Base "Up to date": Modes 1, 2, 5, and 6 in Figure 3.1
In order to bring these various methodologies "up to date", we have then used aspects of the
framework developed by the Global Forum for Health Research to ask additional questions
about the current state of diseases of interest. See Section 6.8. We have obtained information
about the present "state of the science", the drug pipelines, and the funds appropriated towards
various therapeutic interventions for the conditions identified using our evidence based
approach. Completing the questions highlights the “blank areas”, i.e., where there are gaps in
information needed to make rational decisions.
3.7
Conclusions
Bearing in mind all of the above discussion about priority setting, we have decided to use more
than one pragmatic public health based criterion for setting priorities for pharmaceutical
research for Europe and the World. The key evidence-based criteria used are the Burden of
Disease (as measured by DALYS and mortality) and evidence of a lack of efficacy for treating
specific conditions. The other approaches are based on a consensus view about emerging public
health issues and ethical/moral views from a patient-centered perspective. Authorities under
differing circumstances may use different source data or weight the data in different ways and
may produce different results.
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Chapter 3: Priority Setting
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