Proposal for a Council Decision adopting a specific research, technological development and demonstration programme in the field of biomedicine and health (1994-1998) (94/C 228/09) (Text with EEA relevance) COM(94) 68 final - 94/0087(CNS)

(Submitted by the Commission on 30 March 1994)

THE COUNCIL OF THE EUROPEAN COMMUNITIES,

Having regard to the Treaty establishing the European Community, and in particular Article 130 I (4) thereof,

Having regard to the proposal from the Commission,

Having regard to the opinion of the European Parliament,

Having regard to the opinion of the Economic and Social Committee,

Whereas, by its Decision . . ./. . ./EC, the Council and the European Parliament adopted a Fourth Framework Programme for Community activities of research, technological development and demonstration (hereinafter RTD), for the period 1994 to 1998, specifying, in particular, the activities to be pursued in the field of biomedicine and health research; whereas this Decision should be taken in the light of the grounds set out in the preamble to the aforesaid Decision;

Whereas Article 130 I, paragraph 3 of the Treaty stipulates that the Framework Programme is to be implemented through specific programmes developed within each activity; whereas each Specific Programme shall define the detailed rules for implementing it, fix its duration and provide for the means deemed necessary;

Whereas this programme is implemented mainly through shared cost, concerted actions, specific and preparatory measures as well as accompanying and support measures.

Whereas in accordance with Article 130 I (3) of the Treaty, it is appropriate to make an estimate of the means deemed necessary for the realization of this Specific Programme; whereas the final amounts shall be decided by the budgetary authorities according to the relative priority given to the domain forming the subject of this present programme within the First Action of the Fourth Framework Programme;

Whereas the Decision . . ./. . ./EC (Fourth Framework Programme) foresees that the overall maximum amount available for the Fourth Framework Programme will be reviewed no later than 30 June 1996 in view of being increased, and that as a result of this review, the amount deemed necessary to implement the present programme could be supplemented;

Whereas the research activities and technological developments in biomedicine and health should be encouraged in order to improve efficiency of political health within the Community;

Whereas the contents of the Fourth Framework Programme for Community RTD activities have been defined in conformity with the principle of subsidiarity; whereas this programme further sets out detailed contents of activities to achieve in conformity with this principle;

Whereas the Decision . . ./. . /EC (Fourth, Framework, Programme) foresees that a Community activity is required if, among other reasons, the research contributes to the economic and social cohesion of the Community and encourages the overall harmonious development of the quality of its science and technology and that the present programme is supposed to contribute to the realization of these objectives;

Whereas this programme and its implementation should contribute to improving the synergies between the RTD activities in biomedicine and health, by research centres, universities and industry, in particular small and medium enterprises (SME), established in the Member States, and between these and the corresponding Community activities;

Whereas the rules for the participation of undertakings, research centres (including the Joint Research Centre, JRC) and universities, as well as the rules governing the dissemination of research results, are laid down in the measures provided for in Article 130 J;

Whereas for the implementation of this programme, besides associating the countries which are members of the European Economic Area (EEA), other international cooperation activities might be necessary, in accordance with Article 130 M, with other third countries and international organizations;

Whereas the implementation of this programme also implies activities for the dissemination and exploitation of RTD results, in particular towards SME, as well as activities to promote mobility and training of researchers carried out within this programme and in so far as necessary for its adequate implementation;

Whereas the implementation of this programme requires to provide for measures intended to encourage participation of SME, in particular technology stimulation measures;

Whereas basic research in biomedicine must be encouraged to re-enforce the scientific and technological bases of the European health industry;

Whereas an assessment should be made of the socio-economic impact and of any technological risks, of the activities undertaken in this programme;

Whereas, on the one hand, this programme's state of implementation should be reviewed in a permanent and systematic way, in order to adapt it, where necessary, to the scientific and technological developments in this field; and on the other hand, an independent evaluation should be conducted, in due time, on the results achieved by the programme, in order to provide every appropriate information as necessary to determine the goals of the Fifth RTD Framework Programme; whereas, a final evaluation will be necessary at the end of the programme to assess the results obtained in terms of the objectives defined in this Decision;

Whereas the JRC may participate in the indirect action covered by this programme;

Whereas the Scientific and Technical Research Committee (CREST) has been consulted.

HAS ADOPTED THIS DECISION:

Article 1

A specific programme of research, technological development and demonstration in biomedicine and health, as defined in Annex I is hereby adopted for a period beginning on (date of adoption) and ending on 31 December 1998.

Article 2

1. The funds estimated as necessary for the execution of the programme amount to ECU 336 million, including 8,5 % for staff and administrative expenditure.

2. An indicative allocation of funds is set out in Annex II.

3. The funds estimated necessary as indicated above may be increased, as a result of, and in conformity with, the Decision mentioned in Article I, of paragraph 3, of the Decision . . ./. . ./EC (Fourth Framework Programme).

4. The budgetary authority shall lay down the available appropriation for each financial year in agreement with the scientific and technological priorities fixed by the Fourth Framework Programme.

Article 3

Detailed rules for the implementation, besides those provided for in Article 5, are set out in Annex III.

Article 4

1. The Commission shall continually and systematically monitor, with appropriate assistance from independent, external experts, the progress within this programme in relation to the objectives set out in Annex I, and in particular whether the objectives, the priorities and the funds are still adequate to the changing situation. Where necessary, this review shall be accompanied by proposals to adapt or complete this programme, in accordance with the review's conclusions.

2. In order to contribute to the global assessment provided for in Article 4.2 of the Decision adopting the Fourth Framework Programme, an evaluation of the management and the results achieved by the activities undertaken in the field covered by this programme, during the five years preceding the evaluation, shall be conducted in due time for the Commission by independent experts.

3. At the end of this programme, the Commission shall conduct a final evaluation by independent experts of the results obtained concerning the objectives defined in Annex III of the Fourth Framework Programme and in Annex I of this Decision. It shall submit the final evaluation report to the European Parliament, the Council and the Economic and Social Committee.

Article 5

1. A work programme shall be drawn by the Commission according to the objectives set forward in Annex I which can be, if necessary, updated. It shall give in detail the scientific and technological objectives and specify the phases of implementation and the financing planned for each mode of realization.

2. The Commission shall make calls for proposals for projects on the basis of the work programme.

Article 6

1. The Commission shall be charged with the execution of the programme.

2. In the conditions laid down in Article 7, paragraph 1, the Commission shall be assisted by a committee of a consultative nature composed of representatives of the Member States and chaired by the representative of the Commission.

The representative of the Commission shall submit to the committee a draft of the measures to be taken. The committee shall deliver its opinion within a time limit which the chairman may lay down according to the urgency of the matter, taking a vote thereon should the need arise.

The opinion shall be entered in the minutes; moreover, each Member State shall have the right to request that its position be recorded in the said minutes.

The Commission shall take the greatest account of the opinion delivered by the Committee. It shall take the greatest account of the opinion delivered by the Committee. It shall inform the Committee of the way in which it took the said opinion into account.

Article 7

1. The procedure laid down in Article 6, paragraph 2 shall apply to:

- the preparation and updating of the work programme referred to in Article 5, paragraph 1,

- the assessment of the projects and concerted actions provided for in Annex III and the estimated amount of the Community's contribution to them where this amount exceeds ECU 0,1 million per year,

- the measures to be undertaken to evaluate the programme,

- any adaptation of the indicative breakdown of the amount set out in Annex II, not having being decided through the budgetary procedure.

2. The Commission shall inform the committee, for each of its meetings, of the current state of implementation of the programme as a whole.

Article 8

The Commission is authorized to negotiate, in accordance with Article 228 (1), international agreements with European third countries with a view to involving them in all or part of the programme.

Article 9

This Decision is addressed to the Member States.

ANNEX I

SCIENTIFIC AND TECHNICAL CONTENT

This specific programme fully reflects the approach embodied in the Fourth Framework Programme, applies its selection criteria and specifies its scientific and technological objectives.

Paragraph 4.B of Annex III, first activity of the abovementioned Framework Programme, is an integral part of this programme.

This programme will be implemented in synergy between other specific programmes in the field of life sciences and technologies, as well as in such fields as Telematics, Measurement and testing, and targeted socio-economic research.

CONTENT

Health is of the highest value for every European citizen. Health care is a first economic sector absorbing 7,25 % of the GDP and creating work for more than 6 million people or 7 % of the active population. There are more than one million qualified nurses, 850 000 medical doctors, 3 million hospital beds and 0,8 % of the population per day is in a hospital bed.

Research is essential to any strategy to improve health of the citizens and the competitiveness of the health industry. It is important to target the research towards projects of interest to the Community and consumers, and promote the transfer of research to clinical practice.

The challenge for health research is to combat the great scourges such as cancer, AIDS, cardio-vascular diseases, neuro-mental diseases and problems linked with age and handicaps. Rising health care costs have become a concern for all EC countries, while the European citizen is demanding more and more high-quality health care. New health technologies and health care systems are expected to face these common problems. The development of new medicines has become more and more expensive in both time and money, mainly due to the need to satisfy increasingly complex regulatory requirements which need to be streamlined with an international context.

Certain fundamental health problems the health industry of which the competitivity must be safeguarded and improved. Rather than adding a supplementary tone to substantial investments already made by the Member States and European industry, the Community research will bring added value by an integration action, by synergy of national efforts and by interaction of all disciplines from basic to clinical research towards problem-solving activities.

Measures intended to encourage participation of SMEs will be implemented, in particular technology stimulation measures and interactions between science parks and biomedical and health SMEs, as recommended by the White Paper on Growth, Competitiveness, and Employment.

With the launching of the Biomedical and Health Research Programme Biomed 1 within the Third Framework Programme, more than 6 000 research teams are collaborating within 400 networks designed to encourage cooperation between teams from all EC and EEA countries and between complementary disciplines, with a view to tackling health-related problems not readily solved in a narrower context.

Within the Fourth Framework Programme it is intended to go beyond concertation only and to participate in cost-sharing research where indicated only for specific task-oriented research. There are numerous priorities to establish taking into account the large variations in national health systems, research structures, health industries, clinical practices and therapeutic procedures. Only those proposals with a sound scientific concept, a high likelihood of success, a clear Community added value and contributing to the health and wealth of the European citizen will be selected.

RTD ACTIVITIES PROPOSED

The objectives on AIDS, tuberculosis and other infectious diseases; cancer; pharmaceutical research; brain research and research on the human genome will be realized by concentration of means whereas other objectives will mainly be dealt with concertation.

Research on AIDS, tuberculosis and other infectious diseases

Important progress in the battle against AIDS has been made through concertation of AIDS research at European Community level. Nevertheless the number of seropositives is growing. The immuno-suppression caused by HIV in infected people provides an opportunity for the occurrence of old diseases, already drug resistant in some areas, and for opportunistic cancers.

In a continuously changing industrial society which is characterized by a new permeability of borders, mobility of persons, immigration and a change of social behaviours, AIDS, tuberculosis and other infectious diseases will have an impact on the health welfare and quality of life in the European Union.

Focus will be placed on the integration of basic and clinical research in the following areas:

- Viro-immunological research, the genetics, molecular and structural biology of HIV and its variability.

- Contribution to the development of a safe and effective vaccine against AIDS and the establishment of markers to evaluate vaccine efficiency and to follow up the evolution of disease.

- The identification, synthesis and evaluation of antiviral compounds and drugs against AIDS.

- Clinical research, mainly focused on clinical trials, treatment of AIDS and opportunistic diseases, prognostic and progression of these diseases and the impact of therapeutic practices.

- Studies on the host response, pathogenesis, experimental models and new pathologies such as prions, and resistance mechanisms to conventional therapy, including the problem of hospital infections.

- Disease prevention, including the development of new specific monitoring systems to determine the distribution patterns of old and new infectious diseases, analysis of risk factors for the development of AIDS, opportunistic diseases and novel infectious agents.

- Socio-economic and health services research: requirements for caring and prevention, analysis of socio-economic consequences and forecasts in cooperation with public health research.

Cancer research

Improvements in cancer diagnosis, therapy and prevention require integrated fundamental and clinical approaches to research. It is particularly important to bring new advances in cellular, molecular and developmental genetics into contact with oncology and epidemiology, in order that new biological insights into the underlying causes of cancer allow for the development of novel approaches. The study of host-tumour interaction in the context of immune response and of somatic gene therapy targeted at cancer cells are fundamental together with epidemiological studies for investigating possible causative factors in carcinogenesis.

Subjects to be pursued in the field of cancer research

- Molecular mechanisms of tumorigenesis and metastasis, including characterization of the genes and proteins responsible. Together with human genome research, genetic factors of cancer predisposition.

- The control of normal cellular growth, differentiation and death, and abnormalities which can alter this to predispose to cancer, including the development of accurate cellular and transgenic models suitable for cancer research.

- Specific anti-tumour immune responses and possibilities for early detection and curative intervention.

- Research to support the effectiveness of systemic treatment modalities including cytotoxic agents as well as biological response modifiers.

- Research to improve the therapeutic ratio of radiotherapy as well in the domain of ballistic selectivity, as in the manipulation of radiation response in tumours and normal tissues.

- Quality of life as a parameter for treatment assessment including terminal care and rehabilitation.

Pharmaceuticals research

The general objective is the development of the scientific and technical bases required for the evaluation of new drugs, notably for the treatment of neurological, mental, immunological and viral diseases.

These actions should also underpin the activities of the European Medicines Evaluation Agency and provide it, at the international level, with the research-based background necessary to achieve harmonization of technical requirements for drug development. Research will be conducted through collaboration between industry, research centres, hospitals, universities, and the authorities responsible for verifying the efficacy, safety and quality of new drugs.

Research will be conducted mainly in the following areas:

- Pharmacotoxicology: Prevalidation research of in vitro alternative methods, possibly using human cells and tissues, and where unavoidable animal models, in the general aim of reducing, refining and replacing animal experimentation. Preference will be given to those tests which have reached the most advanced stages towards validation as those developed within the Biotechnology Programme. Prevalidation research on these tests should ideally provide the European Centre for the Validation of Alternative Methods with the best candidates for proper validation studies. The contribution of functional imaging to neuropharmacology research will also be explored.

- Pharmacovigilance: Development of systems for high performance surveillance networks for early detection of possible undesired effects of new drugs, in accord with the existing regulatory framework and with particular attention to the international harmonization efforts. It will include research on the exposure of patients to drugs, into harmonization of diagnostic terms and criteria, approaches to assess adverse drug reactions signals, analysis of vital statistics, transnational case-control studies, transnational registers and cohort studies.

- Clinical trials: To support intra-European collaboration in large, randomized clinical trials of high scientific quality, in order to stimulate better opportunities for improved diagnostic procedures, for therapies treatments as well as for their pharmacoeconomic aspects. The development of European clinical trials networks of high scientific standard would help an objective evaluation of new diagnostics of therapeutics in a shorter time while preserving its scientific value.

Research in this field will be mainly directed towards the establishment of clinical trials registries, research into meta-analysis methodologies and randomized clinical trials for rare diseases, including a depository of orphan drugs available for clinical research at European level.

Brain research

The high prevalence of mental illnesses and the increasing incidence of neurodegenerative diseases represent an immense economic and social burden in the EU Member States, absorbing more than 20 % of all health care costs.

The new opportunities created by molecular biology and genetics, novel instrumentation and information technology will contribute to major advances in neurosciences and improvement in prevention and treatment. Research which integrates fundamental aspects with clinical applications and industrial development will be encouraged.

In the field of brain research mainly the following areas will be promoted:

- Research on the physiopathology and basic mechanisms leading to nervous system diseases which should integrate molecular, cellular and clinical approaches.

- Research on central nervous system damage, regeneration and plasticity, development of therapeutic strategies for damage limitation, re-growth promotion and repair.

- Transdisciplinary research on the understanding of the genetic and immunological basis of nervous system diseases, in close cooperation with activities under human genome analysis and biotechnology programmes. Establishment of cell cultures and where necessary animal models of the human diseases of the brain for pathogenicity and development of therapeutic agents.

- Contribute to the development of better methods of brain imaging which combined with computer science will allow a better understanding of brain structures, functions and metabolisms, to map the distribution of proteins and other structures throughout the brain and to characterize the anatomical structures and psychological mechanisms interacting with cognitive function and dysfunction.

This approach will integrate the contribution of several disciplines, together with biomedical engineering, and bring together the most advanced technologies and infrastructures scattered over Europe.

- Research into the mechanisms of pain including the development of new therapies and the conduction of clinical trials to evaluate the effectiveness of currently available therapies.

- Research on addiction behaviour which should integrate basic and clinical approaches, with the general aim of reducing drug demand.

- Development of combined epidemiologic and long-term prevention programmes to evaluate the impact of neurological and psychiatric diseases and the benefits of their treatment also in minorities and high risk groups.

- Research on cognitive sciences including development of models of neuronal behaviour, learning, memory and psycholinguistics.

Human genome research

The achievements, activities and infra-structure established in preceding programmes have to be consolidated and - where appropriate - to be modified, to serve future needs. Fundamental research, with its emphasis on functional studies in order to ensure that advances in genetics are used to enhance human health, will be supported. Development of appropriate technologies and applications which contribute to the well-being of patients will be stimulated. In particular, attempts will be made to develop somatic gene therapy where the conditions/acceptance in Europe justify a targeted effort, e.g. cystic fibrosis.

Sharing and harmonization of genetic databanks comprising European Community participation in the management of the international database of the human genome (GDB) will be promoted. Links will be maintained with appropriate international organizations or forums (e.g. the Human Genome Organization, HUGO).

The confidentiality of any personal information collected in the course of the research must conform to the best data protection practice. No research modifying, or seeking to modify, the genetic constitution of human beings by alteration of germ cells or of any stage of embryo development which may make these alterations hereditary, will be carried out under this programme.

Subjects to be studied in the field of human genome research

- Gene mapping and genome analysis, including construction of integrated transcriptional maps; sequencing of specific chromosomal regions; exploitation of comparative approaches.

- Analysis of gene function, including the improvement of techniques for gene targeting and the development of animal models, e.g. the mouse.

- Analysis of gene regulation, including identification of regulatory sequences; analysis of mechanisms of regulation of expression of specific genes, notably those involved in disease.

- Diagnosis of genetic disease, including non-genetic factors and development of protocols for risk estimation and for genetic counselling, with an emphasis on possible prevention.

- Somatic gene therapy, including development of vectors to transfer genetic material into cells in vitro; development of methods to deliver corrected genes in vivo effectively and safely; coordination of clinical trials on somatic gene therapy.

- Databases, including experimental data collection, storage, analysis and development of an integrated genome database.

- Technology development, including promotion of research aiming at the development of methods suitable for the achievement of any one of the abovementioned objectives.

Research on occupational and environmental health

The objectives are to improve the scientific knowledge needed to increase the safety and health protection of the workers in order to avoid accidents at the workplace and prevent work-related diseases and to reduce the environmental risks for the population.

The matters to be considered will be:

- identification and control of risk factors at the workplace and quantification of the exposure with an emphasis on biological and chemical hazards in short and long-term effects

- development of techniques of safety management, including the definition of good safety practice and the evaluation of its effectiveness in reducing morbidity

- health education and preventive measures to reduce accidents at work and exposure to risk factors

- the interaction between risk factors at the workplace and in the environment and the aetiology of occupation and environment related diseases.

Research on other diseases with major socio-economic impact

From all horizontal activities such as molecular biology, physiology, genetics, statistics, epidemiology and generic technologies, the ultimate measure stick for the European citizen is the benefit for him as an individual. The population expects basic answers by integration of basic and clinical research to improve the prevention, diagnosis and treatment of these illnesses with major socio-economic impact and the around 5 000 'orphan' illnesses which can be tackled optimally at an international level.

Cardiovascular research

In order to accelerate the pace of unravelling the physiopathological mechanisms leading to cardiovascular disease development and translate these findings into prevention and treatments, multidisciplinary research will be stimulated by combining the expertise of physicians and scientists with different backgrounds in basic and clinical cardiovascular research and in molecular genetics.

In the field of cardiovascular research mainly the following subjects will be addressed:

- Analysis of the cellular and molecular mechanisms leading to diseases of the heart and blood vessels, including research on cardiac and vascular cell growth, injury and repair; cardiovascular-associated inflammation.

- Development of clinically useful agents for injury or excessive growth prevention, damage limitation and repair.

- Research on the understanding of the genetic basis of cardiovascular diseases, including identification and decoding of genes, research on expression pattern, gene function and modification; where unavoidable development of animal models and therapeutic strategies.

- Clinical research including assessment, verification and definition of the exact contribution of current basic knowledge in order to understand the onset and development of clinical pathologies; validation of preclinical screening programmes as well as multi-center clinical trials for testing devices and therapeutic procedures.

- Research on imaging and non-interventional techniques that will enable studies of the structure, metabolism, and function of the heart and blood vessels.

- Research on combined epidemiologic and long-term prevention programmes including evaluation of possible differences in risks factors, impact of psychosocial factors on incidence and prevalence of cardiovascular diseases and the benefits of their treatment in high risks groups.

Research on chronic diseases and age-related problems

In view of the social and economic importance of the management of chronic diseases specific research will be focused on auto-immune diseases and immuno-genetics, T-cell disorders and priorities to transdisciplinary, integrative research in the specific domains of chronic arthritis, diabetes mellitus, asthma and respiratory problems.

Orphan illnesses research

'Orphan' illnesses are these rare diseases (some 5 000) where the subsidiarity principle is obvious. No country in itself can afford to spend the necessary resources and case mix to implement basic and clinical research at the low number of cases occurring at national level. Nevertheless at an EC level as well as at a general scientific level these 'exceptional' cases turn out to be quite similar and to offer exceptional experiments by nature to do in-depth research on the basic mechanisms of diseases and handicaps and to offer opportunities to link genetic research with biochemical and physical expression of disease. Examples are thallassemia; inborn metabolic diseases due to defective peroxisomes, etc. Actions will include an inventory of rare disorders and together with the section on pharmaceutical research a depository of orphan drugs for clinical research.

Public health research, including health services research

More than 110 000 deaths under age 65 from 21 common diseases would be avoided annually, if only each European region could attain the optimal death rates reported nationally for each of those diseases.

Traditions, practices and the legal and administrative organization of public health services and systems are so varied in Member States as to render impractical any harmonization of services in this domain. However, objectives of research should be to assist Member States in strengthening their coverage of public health issues, assist in the formulation and implementation of objectives, policies and strategies, and contribute to continuity of health protection provision across the European Union.

Subjects to be pursued in the field of public health research

- Research on health education and prevention, primary care, asessment of health needs, including the needs of emerging dependency groups, performance measurements of health policy initiatives and the evaluation of health technologies.

- Coordination and comparison of European health data.

- The impact of the Internal Market on supply of health care across internal frontiers; regulations and de-regulations as well as the balance between health systems financed by the private and public sectors.

- Health economics and organizational aspects of health systems.

- Defining a European approach for the introduction of new technologies in health systems.

Research on biomedical technology and engineering

Health technology assessment and prenormative research become more important in a European-wide market with its directives concerning medical devices and accompanying standardization activities. For industry as well as for decision-makers at all levels, to safety, it is essential to have an addition to needs for safety, timely access to objective information on efficacy and efficiency of medical devices, before introducing these on the health market.

Research and development will be promoted mainly in the following areas:

- Minimal intervention techniques and robotics: robotics, three-dimensional imaging, micro structure technology and 'nanotechnology' to support surgical therapy, and widen the range of clinical indications for minimal medical interventions; new ergonomic approaches of the operating theatre for minimally invasive surgery.

- Imaging techniques: magnetic resonance, ultrasound, biomagnetism, positron emission tomography, etc., as well as microwave imaging and near infrared spectroscopy and imaging; comparative and integrated evaluation of different biomedical imaging technologies.

- Research on biosensors, especially with regard to their clinical value, as among others is the case of glucose monitoring for diabetes, oxygen monitoring and ion sensing for critical care.

- Meeting the needs of the increasing population of elderly and handicapped persons calls for more research on rehabilitation technology in coordination with the relevant parts in the Telematics Programme. The powerful trend towards replacement in medicine requires more research in biomaterials, especially towards improved mechanical properties and biocompatibility of polymers, as well as on artificial organs, such as on artificial heart and artificial pancreas. Research aiming at the modelling of human functions, as well as in biomechanics, haemodynamics and bio-rheology, is also required in that respect.

- Cellular engineering: synergistic benefits would accrue by combining cell and molecular biology with chemical, mechanical and electrical engineering, opening new possibilities for clinical applications.

Research on biomedical ethics

Research on biomedical ethics, being of a horizontal nature, will address general standards for the respect of human dignity and the protection of the individual in the context of biomedical research and its clinical applications. The social impact and the public awareness of the problems associated with biomedical progress will be addressed.

Topics to be considered more specifically are:

- Medically assisted procreation, including gender selection, preimplantation- and prenatal diagnosis, research on embryo, use of foetal ovarian tissue, post-menopausal pregnancy, sperm and egg donation.

- Human genome analysis and its clinical applications, including testing, screening and somatotherapy.

- End of life, including palliative care, euthanasia, artificial prolongation of life by advanced medical techniques, resuscitation.

- Research allocation: ethical and social dimensions of the choices to be made in health budgets and resource allocation.

- Organ and tissue transplantation including the use of human organs and tissues, as well as the functioning of tissue and organ banks.

- Patient's consent: informed consent of the individual for diagnosis, therapy, prevention or research, including the consent of vulnerable populations like e.g. prisoners and cognitively impaired patients.

- Confidentiality and privacy considering medical data, genetic and non-genetic, with an emphasis on the specific problem raised by modern information systems such as computerization with automatic data transfer.

Objectives dealt with horizontal activities

Research activities on biomedical ethics carried out within biomedical and health research and the activities on the ethical, legal and social aspects carried out by the horizontal unit 'legal and ethical aspects' will be performed jointly in order to benefit from interdisciplinary competences.

In order to improve dialogue and mutual understanding between the main national, sociopolitical and bioethical positions, whilst recognizing the cultural differences which exist in Member States, working groups will be organized to prepare reports and surveys of interest also to the European Parliament and the Council. Targeted workshops to identify and debate areas of national and international divergences and, where appropriate, research activities with multidisciplinary approaches to such topics will be carried out. Public awareness activities on new biomedical technologies will also be funded. This horizontal activity takes into account the European Bio-ethics Convention and its draft Protocols.

Wherever possible, experimentation and testing on animals should be replaced by in vitro or other methods. No research modifying, or seeking to modify, the genetic constitution of human beings by alteration of germ cells or of any stage of embryo development which may make these alterations hereditary, nor research seeking to replace a nucleus of a cell of an embryo with a nucleus taken from a cell of any person, embryo or subsequent development of an embryo, known as cloning, will be carried out under any of these three Specific Programmes.

Demonstration activities within biomedical and health research will facilitate comparative European multi-centre trials of new drugs, new therapeutic approaches, and ready-for-testing prototypes of new medical devices. Special attention will be given to demonstration of the latest technologies in clinical diagnostics and imaging technologies, implantable sensors for the monitoring or rehabilitation of pathological conditions, artificial organs, biocompatible materials, new cancer therapies and irradiation technologies. A bottom-up approach will be used, in cooperation with other life sciences programmes, to identify the best opportunities for pre-competitive demonstration, in order to prove the technical viability of these new technologies, together with, as appropriate, their economic advantage at a pre-competitive level. The early involvement of hospitals and clinicians in these demonstrations will allow for an efficient dissemination of knowledge and a quick realization of the benefits to be derived from the adoption into practice of such innovative approaches, drugs and devices. While keeping as a first priority the benefits for patients, demonstrations in these areas will take into account the specific needs of the biomedical engineering and pharmaceutical industries and health care delivery organizations, and will be implemented by partnerships involving these manufacturing industries, the health profession, the health-care providers and health authorities.

ANNEX II

>TABLE>

ANNEX III

RULES FOR IMPLEMENTING THE PROGRAMME

1. The detailed rules for the Community's financial contribution are laid down in Annex IV to the Decision on the Fourth Framework Programme.

The detailed rules for the participation of undertakings, research centres and universities, and for the dissemination of results, will be laid down in the measures provided for by Article 130 j of the Treaty.

However, for the purpose of implementing this programme, the following exceptions shall apply:

Participation in this programme is open, with financial support from the Community:

(a) to all legal entities, established and regularly carrying out RTD activities

- in the Community, or

- in a third country associated, wholly or in part, with the implementation of the relevant programme through an agreement concluded between the Community and the said third country

(b) to the Joint Research Centre

1.1. Participation in this programme is open, without financial support from the Community, and on condition that their participation is in the interests of Community policies:

(a) to legal entities established in a country which has concluded a scientific and technical cooperation agreement with the Community relating to activities covered by the programme, provided the participation accords with the terms of the agreement,

(b) to legal entities established in a European country,

(c) to international research organizations

1.2. Participation in the area of 'Human genome analysis' is open, without Community financial support, to any legal entity, on condition that its participation is in the interests of Community policies.

1.3. The participation of European international organizations may be financed on the same basis as that for Community organizations in duly specified cases.

2. This programme will be implemented through indirect actions, i.e. Community funding of RTD activities carried out by third parties or by JRC institutes associated with third parties.

2.1. Shared cost actions including the following types:

- industrial RTD projects carried out by undertakings, research centres and universities, including consortia for integrated projects which work on a common subject;

- the basic research projects within the thematic networks to be created around genetic technologies of a strategic importance for the European industry, involving enterprises, research centers and universities;

- technology stimulation which should encourage and faciltiate the participation of SMEs by supporting the exploratory stage (including the search for partners) of RTD actions and by cooperative research. This award will be granted after selection of outline proposals which may be submitted at any time;

- support of financing infrastructures or facilities necessary for the performance of a coordination action (reinforced coordination activity)

- demonstration activities, as defined in Annex III of the Framework Programme, intended to overcome the obstacles hindering the utilization of new technologies and to build the bridge between technology producers and users. Feasibility awards and direct assistance to those who get involved in these technologies may also be included;

2.2. Concerted actions, which coordinate, in particular through concertation networks, RTD and demonstration projects already funded by public authorities or private organisms. The concerted actions may also perform the coordination needed for thematic networks which, through RTD shared cost actions (cf. 2.1. (a), first indent), bring together, focusing on the same technological or industrial goal, producers, users, universities and research centres.

2.3. Specific measures, such as those encouraging standardization, and those measures intended to set up general service tools for research centres, universities and enterprises. Community contribution will be up to 100 % of the costs of these measures.

2.4. Preparatory, accompanying and support measures, including the following types:

- studies in support of this programme and in preparation of possible future actions;

- conferences, seminars, workshops or other scientific or technical meetings, including intersectorial or multidisciplinary coordination meetings;

- use of external expertise, including access to scientific data bases;

- scientific publications, including dissemination, promotion and exploitation of results (in coordination with the activities carried out in the Third Action);

- assessment studies of socio-economic implications and also of possible technological risks associated with all projects of this programme and in coordination with the programme targeted socio-economic research;

- training activities linked to the research carried out under this programme;

- independent evaluation (including studies) of management and results of programme activities;

- measures of support to the operation of networks for increasing awareness and for decentralized assistance in favour of SMEs, in coordination with the Euromanagement RTD audits actions.

The diffusion and valorization of results obtained in this programme will be complementary to those carried out by the Third Action and will be implemented in close coordination with it. The networks of partners of RTD projects are the principal mechanisms of dissemination and valorization of results. They will be reinforced with publications, conferences, promotion of results, studies of the techno-economic potential, etc. In order to ensure optimal exploitation all those factors which may facilitate the utilization of results will be considered at the start of the projects and whilst they are in progress.