1. Introduction to the Project
Priority Medicines for Europe and the World
"A Public Health Approach to Innovation"
Background Paper
Introduction to the Project
Warren Kaplan, Ph.D., JD, MPH
7 October 2004
Table of Contents1.Introduction to the Project
1.1Background to the Project
1.2Objective of the project
1.3Priority Medicines
1.4Populations and the Epidemiological Transition (Commonality of Interest)
1.5Pharmaceutical Gaps
1.6Public Health Perspective
1.7Conceptual Framework
1.8Issues not Addressed by the Present Study
1.9Target Audience
References
Annexes
Appendices
1.Introduction to the Project
1.1Background to the Project
The Government of the Netherlands has requested WHO to identify "priority medicines" (defined below) for certain high-burden priority diseases with reference to opportunities afforded within the European Union (EU). Targeted research funding has been available since 1984 through the various European Framework Programmes (See Background Chapter 2). More recently, the EU has opportunities for encouraging innovation through possibilities for supporting clinical trials such as through the European Developing Countries Clinical Trial Partnership and supporting product development through the European Investment Bank. At present, targeted research funding is available through the EU 6th European Framework Programme, which includes the development of effective interventions for diseases of poverty, suchas HIV/AIDS, malaria and tuberculosis.[1]
The Government of the Netherlands is interested in creating a public-health-based medicines development agenda, for support by the EU as part of the EU 7th Framework Programme for 20072010. To address populations in developing countries that also need "priority medicines", the WHO has been asked to also identify disease conditions where there is a commonality of interest with the rest of the world.
1.2Objective of the Project
The objective of the project as described in the initial proposal (See Annexes toSection2) is:
to prepare a public-health-based medicines development agenda, for support by the EU in the immediate (20052006) and medium-term (20072010) future, and to develop a systematic methodology in this regard.
Within the context of tackling preventive and therapeutic gaps for the citizens of Europe, special emphasis will be put on identifying those research needs which are also relevant for countries in economic transition (including several new EU members) and, if possible, also for developing countries – so that a maximum benefit may be derived from a "commonality of interest". In addition, needs regarding better delivery mechanisms/formulations of existing preventive and therapeutic medicines, will be identified.
1.3Priority Medicines
It seems beyond question that for even the most developed countries, the demand for healthcare outweighs the supply of resources allocated to finance it. As a result, the ability of national policy makers to set priorities for their health care system, or for new technologies within the health care system, is most often conducted in the face of varying degrees of evidence about the safety, effectiveness, and appropriateness of particular interventions. Thus, priority setting is a real challenge for every health care system in the world. As yet, it is safe to say that there are no widely accepted models for legitimate and fair priority setting in health care.
During the past decade, various priority setting exercises have included the Commission on Health Research for Development,[2]the World Development Report (1993),[3]the Ad Hoc Committee on Health Research (1996),[4]the WHO Advisory Committee on Health Research (1997),[5]the Global Forum for Health Research (2000),[6] the joint initiative of the UN Development Program/World Bank/ World Health Organization- the Special Program on Research and Training in Tropical Diseases (TDR) (2002)[7] and the joint WHO-IFPMA Roundtable(See Appendix 3.7). With the exception of the TDR initiative and the joint WHO-IFPMA Roundtable exercise, we note that much of this work has been directed to identifying “gaps” in existing healthcare delivery interventions, and not in identifying “gaps” in pharmaceutical research and development (R&D). See alsoBackground Chapter 3and accompanying documentation.
In May 2004, ten countries joined the European Union (EU) and some of these countries have unique public health issues that the rest of the EU will have to face. For a number of diseases that affect all members of the EU, no effective and safe medicinal treatment is yet available (e.g. Alzheimer disease and several cancers). For some diseases, potentially large markets exist for medicines (e.g. breast cancer) and associated pharmaceutical research is likely to be intensive for certain therapeutic classes. For other categories of medicines, the number of patients is low (e.g. cystic fibrosis) or the market-driven pharmaceutical industry has failed to pursue R&D (i.e., new medicines for tuberculosis).
For a given disease condition, wecan define "priority medicines" in several ways.
- Priority medicines are essential medicines which should be developed to treat conditions where few, or none, effective treatments exist. These are medicines that would fill pharmaceutical "gaps" (as defined below") and would be useful in Europe and anywhere in the World where the diseases exist that need effective treatments.
- We further define "priority medicines" as being those essential medicines that have not been developed yet for conditions that will be important public health concerns in Europe and the rest of the world. Such conditions needing as-yet undeveloped medicines include antibacterial resistance, pandemic influenza.
3."Priority" medicines as those medicines needed for neglected patient groups (patients having "orphan" diseases, elderly, children, and women: Background Chapters7.5,7.2.7.3 and 7.4, respectively) and the so-called "neglected" diseases of primarily tropical origin.[8](See Background Chapter 6.9).
1.4Populations and the Epidemiological Transition (Commonality of interest)
This project focuses on the requirements of different populations, all of whom are undergoing important social, demographic and epidemiological changes. Europe encompasses the twenty five countries of the new European Union. This includes the ten new members who show a rapidly aging population.See Background Chapter 5. The "world" encompasses the remaining population of the earth, including the twenty five countries of the European Union. Many parts of this population outside the EU is particularly influenced by the large numbers of people who are undergoing their epidemiologic and demographic transitions. This means that their healthcare systems are faced with aging populations and ever-increasing chronic diseases associated with life style and economic changes. We live in a world where a commonality of interests means that the vast majority of chronic disease conditions affecting the EU such as cancers, heart and cerebrovascular disease as well as osteoarthritis will also be occurring in the "developing" world in the future. In addition, large portions of the world's poorest population also face the onslaught of AIDS combined with neglected diseases such as malaria, trypanosomiasis and tuberculosis.
1.5Pharmaceutical Gaps
“Priority medicines” are designed to fill pharmaceutical “gaps”. The project is thus focused on diseases for which treatments do not exist or are inadequate, and threats such as antibacterial resistance or pandemic influenza, for which present treatments or preventive measures are unlikely to be effective in the future. In addition, the project addresses obstacles where effective medicines could be better delivered to the patient. We have chosen to emphasize certain fixed dose combination medicines as worthy of further research and development. Finally this project looks at particular groups such as children, women and the elderly who have frequently been ignored in the scientific or drug development process.
This study therefore focuses on "pharmaceutical gaps." It is encouraging to note that in the past, major pharmaceutical gaps have been closed. For example, prior to 1975 surgery for peptic ulceration was one of the most common forms of surgery. Following the development of H2 antagonists after a long period of focused research, effective medical treatment was discovered. This discovery, when combined with the development of proton pump inhibitors and the discovery that most ulceration was associated with infection by Helicobacter pylori which could be easily treated by a combination of generic antibiotics, rendered surgery unnecessary. (See Annex to Chapter 1 and textbox).
1.6Public Health Perspective
This project uses a public health perspective when addressing "pharmaceutical gaps." This involves considering the greatest good for the greatest number, the value of promoting healthy behavior, prevention where possible, and ensuring that access is assured to all who would benefit. We do address some diseases having a high burden such as lung cancer, chronic obstructive pulmonary disease (COPD), alcohol dependence and alcoholic liver disease where pharmaceutical gaps exist in spite of the fact that these conditions are in principle preventable. Health promotion, prevention and ensuring access will remain very high priorities for the future although this report will focus on pharmaceutical interventions. From a public health perspective, a pharmaceutical “gap” can be filled with an innovative medicine having a new mode of action, an existing medicine with a less harmful side effect profile, or a medicine (whether or not innovative) that can be delivered to the patient with a better delivery system (i.e., fixed dose combinations).
1.7Conceptual Framework
We conceptualize the fact that no effective and safe medicinal curative treatment are yet available for certain conditions as the existence of an obvious “pharmaceutical gap” between burden of disease and clinically effective medicine. Funding for pharmaceutical research, in relation to preventive and curative gaps with considerable public health impact, should therefore be considered. Figure 1.1 (adapted from Figure 1.1 of the Combined Approach Matrix developed by the Global Forum for Health Research (See Appendix 3.6) has a vertical axis that is the combined efficacy of all pharmaceutical interventions used for a particular disease condition, whether cost effective or not. The point labelled “Z” is an arbitrary level of combined efficacy for all pharmaceutical interventions for the particular disease. The horizontal axis represents the proportion of the total population with that condition that is covered by the available mix of interventions. “X” and “Y” are arbitrary levels of population coverage. One can attempt to identify “pharmaceutical gap” labelled as: BOX 4 - where there is not yet any intervention at all (whether or not cost effective) or BOX 3- where an existing intervention can be improved in either or both a cost-effectiveness and/or therapeutic sense. For instance, eliminating a situation where there is not yet any intervention for a disease with a large global burden would be treating and diagnosing Alzheimer disease. Eliminating a “gap” where existing interventions can be improved might happen if a new delivery system for proteins were developed or heat-stable insulin were formulated or innovative treatments for certain “orphan” diseases were found.
Source: Adapted from the Report of the Ad Hoc Committee on Health Research Relating to Future Intervention Options, WHO, 1996
1.8Issues not Addressed by the Present Study
With regard to Figure 1.1, this study focuses on BOXES 3 and 4, and not on the others. This means that the study does not address health system "access"issues where the disease condition is avertable with improved healthcare system “efficiency.” We recognize that in many cases effective medicines exist but are not fully utilized for many reasons. When the reason is a difficulty in physical delivery we address this but where it relates to logistic l or sociological access we have not considered this at all. We have also not addressed conditions which can be considered major underlying causes of morbidity or mortality such as obesity. The study hardly mentions diagnostics or devices and does not address issues related to Intellectual Property as this topic is looked at by the WHO Commission on Intellectual Property Rights, Innovation and Public Health.[1] If this present study were to be repeated at a national level we would encourage these topics be covered.
1.9Target Audience
This report aims to address different audiences. The primary audience is the decision-makers working in the European Commission, Parliament and Council who will be responsible for defining the 7th Framework Programme. Another crucial group are the directors of research in the pharmaceutical industry. While their priority setting may be strongly influenced by market forces the reality is that these market forces particularly in Europe are driven by public health realities. Members of the European Investment Bank, policy makers and politicians at national and regional level may also find this report and the background documents useful for their decision making. Researchers who are deciding where to put their future efforts may find the methods and conclusions useful for their decisions. Patient groups and payers have a common interest in identifying which research may be prioritized. The level of text in the background documents is primarily geared towards technically-oriented stakeholders, whereas the level of text in the final report is primarily geared towards policy-makers.
References
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[1]
[1]6th Framework website for diseases of poverty.Available at Last accessed 8 March 2004.
[2] COHRED Results of the Commission’s work were published as Health Research: Essential Link to Equity in Development. New York: OxfordUniversity Press (1990).
[3] World Bank. World Development Report 1993: Investing in Health.New York: OxfordUniversity Press; 1993.
[4] Published as Ad Hoc Committee on Heath Research Relating to Future Intervention Options. Investing in Health Research and Development. WHO, Geneva, 1996 (TDR/Gen/96.1)
[5] World Health Organization, Advisory Committee on Health Research. A Research policy agenda for science and technology to support global health development. Geneva: World Health Organization; 1997.At Report No.: WHO/RPS/ACHR/97.3
[6] Global Forum for Health Research.At Last accessed 11 March 2004.
[7] UNICEF/UNDP/World Bank/WHO. Special Program for Research and Training in Tropical Diseases. At Last accessed 8 March 2004.
[8] Trouillier, P. et al. Drug development for neglected diseases: a deficient market and a public-health policy failure. Lancet 2002;359:2188-2194.