CELEX: 51977PC0282
Language: en
Date: 1977-06-21
Title: FIRST PROGRAMME OF RESEARCH ACTIONS in the sector of MEDICAL AND PUBLIC HEALTH RESEARCH PROPOSAL FOR A COUNCIL DECISION adopting a concerted action in the field of Registration of Congenital Abnormalities (Medical and Public Health Research)#PROPOSAL FOR A COUNCIL DECISION a adopting a concerted action in the field of Cellular Ageing and Decreased Functional Capacity of Organs (Medical and Public Health Research)#PROPOSAL FOR A COUNCIL DECISION adopting a concerted action in the field of Extracorporeal Oxygenation (Medical and Public Health Research) (submitted to the Council by the Commission)

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COM (77) 282
Vol. 1977/0095
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 ---pagebreak---      COMMISSION OF THE EUROPEAN COMMUNITIES
                                                           COM(77)282 final.
                                                           Brussels . 21 June 1977 .
                           FIRST PROGRAMME OP RESEARCH ACTIONS
                                    in the sector of
                           MEDICAL AND PUBLIC HEALTH RESEARCH
                             PROPOSAL FOR A COUNCIL DECISION
                     adopting a concerted action in the field of
                      Registration of Congenital Abnormalities
                         (Medical and Public Health Research )
                                                                        ,             A
                                                                                 .
                                                              ■
                             PROPOSAL FOR A COUNCIL DECISION
                                                                                   i-   :
                                                                   A
                     adopting a concerted action in the field of
            Cellular Ageing and Decreased Functional Capacity of Organs /
                         /                                      \ ^ Ul ! , ■ v \
                         (Medical and Public Health Research )
                             PROPOSAL FOR A C OUÏE IL DECISION
                     adopting a concerted action in the field of
                               Extracorporeal Oxygenation
                         (Medical and Public Health Research)
                      ( submitted to the Council by the Commission)
CQK(77 ) 282 final .
 ---pagebreak---                                     - 1 -
                    FIRST PROGRAMME OF RESEARCH ACTIONS
                             in the sector of
                    MEDICAL AND PUBLIC HEALTH RESEARCH
                              TABLE OF CONTENTS
                                                                         Page
   I.       Introduction                                  ......           2
 II .       Elaboration and choice of the actions                          3
III .       Short description and charactetistics of the actions .         4
 IV .       Implementation of the first action programme                   6
  V.        Financial volume                                      ..       7
  VI .      Prospectives                                                   7
 -    Multiannual concerted action     <3 years ) in the field of
      " Registration of Congenital Abnormalities "
      including PROPOSAL FOR A COUNCIL DECISION                   A.1 - A.11
 -    Multiannual concerted action     (4 years ) in the field of
      " Cellular Ageing and Decreased Functional. Capacity of
        Organs "
      including PROPOSAL FOR A COUNCIL DECISION                   B.1 - 8.13
 -    Multiannual concerted action     (4 years ) in the field of
      " Extracorooreal Oxygenation "
      including PROPOSAL FOR A COUNCIL DECISION                   C.1 - C.12
          '  \
 ---pagebreak---                           FIRST PROGRAMME OF RESEARCH ACTIONS
                                     in the' sector of
                          MEDICAL AND PUBLIC HEALTH RESEARCH
INTRODUCTION
According to, the Council 's Resolution of January 1974 on the co-ordination of
national policies and the definition of projects of interest to the Community
in the field of science and technology , the Committee on Medical and Public
Health Research ( CRM ), set up by the PREST group on June 1972 , became
responsible to CREST in order to assist it , and in turn the Community
Institutions , in performing their tasks .
In compliance with its mandate , CRM , assisted by three Specialized and three
Ad Hoc Working Groups , executed its explorative tasks according to the time­
table appearing in the Annex of the Resolution and covering the 1974-1976
period , and reported to CREST ( Doc . CREST/ 21 and 22/ 1976 ) in particular on
the conclusions drawn from the experience gained during this first phase .
The conclusions of relevance to this proposal for a First Programme of Research
Actions are the followings :
(a)   The main objectives of European co-operation in the medical field should
      be in the prevention , in the early detection of disease and in rehabili­
      tation .
(b)   Implementation of common actions should be performed by or in association
      with the research organizations of the Member States .
(c)   Following important criteria should be applied to the choice of common
      actions and to the selection of priorities :
     -    the topic should be of importance to the Community as a whole ;
      -   the topic should have practical importance in particular from the
          social and economic point of view ;
      -   on scientific grounds : either the project should need to be implemented
          jointly or at least could be carried out much more effectively on an
          conisranity   basis than separately in each Member State ;
      -   the project should be expected to give clear and reasonably early
          results .
(d)   Co-ordination of national policies should encourage coherence of methods
     of working of the national research organizations , thus laying the
      foundations for an effective scientific community .
(e)   It is shown that in respect to co-ordination of medical and public health
      research policies within the Community there is a common pattern . of
     organization in all Member States , but within this pattern there are wide
     differences of detail . Mainly both facts , namely that the machinery within
     the national research organizations and the existing scientific policies
 ---pagebreak---                                                                         XII / 269 / 77
             of these organizations are widely differing , and that research in the
             medical field is largely carried out as small projects , put constraints
             on policy making . Variations in ways of categorizing work and defining
             priorities rr*ke the establishment of general common policy priorities
             difficult at this time . However , comparison and co-operation in respect
             of research pv.'icies is considered possible for specific fields of
              research directed to one of a few closely related practical objectives .
      CREST in turn accepted these conclusions ( Doc . CREST/ 27/ 1976 ), gave a fevourabl
      opinion on criteria for choosing topics and selecting priorities , considered
      CRM 's explorative work as an extremely valuable basis to enter immediately a
      second working phase which would consist in the elaboration , before the end
      of 1976 , of a first programme of research actions , and invited the Commission
      to submit to the Council a corresponding proposal for decisions .
II *  ELABORATION AND CHOICE OF THE ACTIONS
                                                                 « < 1
      Several preliminary studies for possible common action have been performed
      by CRM 's Working Groups after identification of specific fields of common
      interest , according to their terms of reference . The procedure applied to
      such an elaboration requires survying various fields of interest from the
      following points of view :
     -    state of knowledge and critical aspects of the field in relation to the
          present status of medical and public health problems ;
     -    identification of the most significant problems with particular reference
          to the development of prevention , early diagnosis and rehabilitation ;
     -    evaluation of the needs for the most efficient handling of the above-
          mentioned problems , from the point of view of research and / or training
          requirements .
     On the background of these studies , CRM has suggested as components of the
      First Programme of Research Actions three subjects which are related to the
     particular fields of :
     (A )   Registration of Congenital Abnormalities
     (B)    Cellular Ageing and Decreased Functional Capacity of Organs
     (C)    Extracorporeal Oxygenation
     On the basis of the opinions of CRM and CREST , the Commission then prepared
     the proposal for a Council Decision adopting three multiannual concerted
     actions in the above-mentioned fields of Medical and Public Health Research .
     The choice was performed by applying the approved criteria , by considering
     the feasibility of a gradual co -ordination ( both mentioned under I ), and by
     taking into account the relevant activities of appropriate International
     Organizations such as WHO', OECD , Council of Europe , European Medical Research -
     Councils , European Science Foundation , etc .
 ---pagebreak---                                     - 3 bis -               XII / 269/ 77
There are obviously many other research themes as important as those which
were retained now , which can be taken into consideration in the frame of
a Community programme in medical research . The preparative work carried
out by the specialized working groups of CRM led to the presentation to
CRM of 5 projects . Among them , and next to the 3 projects presented in
this document , were : thrombosis , and human factors in road traffic
accidents . During its meeting of June 30, 1976 , CRM requested further
information on these two subjects . They will be reexamined together with
a series of new projects in June 1977 . As to the 3 projects presented
hereafter , they were retained as being in conformity with the Community
objectives and interests according to the criteria described on pages 2
and 3 of this note . Chapter III ( p. 4 and 5 ) outlines for each of them the
motivation for Community approach .
Thus , the 3 above mentioned themes must be considered as the first elements
of a more comprehensive programme of which other elements are presently
being studied , and which will be the subject of future proposals .
 ---pagebreak---                                               - 4 -                   XII / 269/ 77
III .  SHORT DESCRIPTION AND CHARACTERISTICS OF THE ACTIONS
        (A )  Multiannual Concerted Action (3 years ) in the field of
              " Registratio n of Congenital Abnormalities "
       Objective : Registration of congenital malformations and of Inherited
       biochemical and chromosome abnormalities as well ss of twins and multiple
       pregnancies in selected areas of the Community in order to monitor incidence
       and prevalence of congenital abnormalities and to allow early institution
      of remedial measures .                                                                    ;
      Harmonization of existing national registers and standardization of re­
      gistration procedures .                                                                 j
      Gradual co-ordination of the research covered by the concerted action .              -J
      Motivation      :   Congenital abnormalities have become a major cause of still - j
      birth , infant death and childhood disablement . Still , the number of cases          j
      of congenital abnormalities occurring in any one area as well as in a single |
      country is insufficient for an effective study at national level alone ;
      therefore , only a Community effort can ensure statistically valid results .          !
      On the other hand , co-ordination will be greatly facilitated by the limited ;
      number of existing national registers .                                               '
      Starting phase : Establishment of an appropriate network of national
      registers with the initial participation of 14 regional services from all            I
      the Member States .                                                                -j
      After the Council 's Decision non-Member States involved in European co- .           !
      operation in the field of scientific and technical research ( COST ) will be
      invited to participate .
      Continuation      :   Submission of a possible new action proposal in due time .
      Related activities       :  First centralized exercise to co-ordinate the national
      policies for research on Congenital Abnormalities by a new Ad Hoc Working
      Group of CRM .
      Actual elaboration of a research programme in the field of " Prenatal and
      Perinatal screening of inborn metabolic diseases and chromosome abnormalities
      (B)    Multiannual Concerted Action <4 years ) in the field of
             " Cellular Ageing and Decreased Functional Capacity of Organs "
      Objective     :   Oriented research on cellular ageing as the basis for decreased
      functional capacity of organs in order to understand the resulting phy-           ■'
      siological ageing processes occurring at the level of the whole individual ;
      study of the mechanisms underlying the age-related functional decline in
      particular of the liver , of the immune system and of the lens .                        ]
      Gradual co-ordination of the research covered by the concerted action .                  j
      Motivation      :   There is a clear need to enhance multidisciplinary collaboratioi
      and exchange of experience and knowledge in an increasingly important area of
      research related to the health status of elder persons , which is a major socio
      medical problem in Europe . This area has never received the attention it de­
      serves and interaction at the executive scientific level has to be regarded
       as not being sufficiently developed .
 ---pagebreak---                                        - 5 -                    XII / 269 / 77
 An attempt should be made to initiate a gradual co-ordination of a vary larga
 snd diversified research domain , where numerous small projects a r e carried
 out by relative small research te-^rns from various scientific disciplines , by
 starting from a few ,but well defined fundamental research topics .
 Starting phase     :  Collaboration between more than 70 scientists from about
 20 institutes of the Member States .
 After the Council 's Decision non-Member States involved in European co­
 operation in the field of scientific and technical research ( COST ) will be
 invited to participate .
 Continuat ion : A proposal for a largely extended programme in this field
 will very probably be necessary in a later stage in order to meet the numerous
 research and co-ordinat ion requirements , which are inherent but uncovered by
 this programme .
 (C)    Multiannual Concerted Action (4 years ) in the field of
        " Extracorporeal Oxygenation "
 Objective : Collaborative research on improvement of present extracorporeal
 oxygenator principles as well as on development of alternative ones , including
 methods for continuous monitoring and dynamic compensation of the patients
 deficiencies , in order to obtain the possibility of a clinically satisfactory
 long-term treatment ; a particular effort is directed towards technologies
 which diminish the damage to the blood and at the same time increase the
 efficiency of gas exchange .
 Co-ordination of the research covered by the concerted action .
 Mot i vat ion : Presently available oxygenators work satisfactorily for periods
 up to 5 - 10 hours . Longer working period are needed . Since individual countries
each tackle separately only some of the inherent problems and since none of
these national efforts is likely to ensure adequate and reasonably early results ,
the chances of success can be significantly improved by an integration of all
related activities ongoing in the Member States into a common action .
Starting phase      :  Collaboration between more than 100 scientists from about
20 institutes of the Member States .
After the Council 's Decision Non-Member States involved in European co­
operation in the field of scientific and technical research ( COST ) will be
invited to participate .
Continuation : A decision to continue this action will rsainly depend or.
the results obtained from research execution and co-ordination during the
first three years .
 ---pagebreak---                                         - 6 -                     XII / 269 / 77
IV .   IMPLEMENTATION OF THE FIQST ACTION PROGRAMME
      The first programme of research actions in the sector of Medical and Public
      Health Research ,, which will be implemented by carrying out its three multi-
      annual concerted actions , will be of considerable interest , because of its
      social and economic importance , to all Member States , even to those not
      involved in a particular line of research or lacking the required facilities
      to participate actively in a particular way .
     After the Council 's Decision non-Member States involved in European co­
     operation in the field of scientific and technical research ( COST ) will be
      invited to participate in each single concerted action .
     In principle , the competent national authorities are responsible for the
     execution of the national contributions to each action within the framework
     of their commitments and are prepared to integrate the research , covered by
     each concerted action , into a process of co-ordination at Community level
     over the respective periodsof time .
                                                                                     ι
     For each single action a Concerted Action Committee is established in which
     the Member States are represented by one delegate and one alternative . The
     terms of reference are laid down in the respective Annex B to the Draft
     Council Decision .
     Provision will be made for an adequate representation of the possibly
     participating ncn-iv'.ember States on each committee .                         '
     The competences of the Committee for Medical and Public Health Research
     cover also the implementation of each sinjle action ; this Committee is in
     particular duly qualified for giving to the research its proper place within
     the sectorial policy of the Eurooean Communities as well as for ensuring its
     success .                                                                      |
     The co-ordination of each singLe action will be carried out under the          !
     responsibility of the Commission , assisted by a Project Leader to be          !
     appointed by the Commission in agreement with the respective Concerted         I
     Action Committees .                                             -           '  i
                                                                                    »
                 V
 ---pagebreak---                                                                    XII / 269/ 77
 FINANCIAL VOLUME
 The estimated financial volume of the researcn to be carnea out by the
 Member States within the framework of each action are as follows           :
 Concerted action   A   : " Registration of Congenital Abnormalities "
                            0.85  m.u.a . for a 3-year period with the active
                                           participation of all the Member States .
 Concerted action   3   : " Cellular Ageing and Decreased Functional Capacity
                            of Organs "
                            4.0   m.u.a . for a 4-year period with the active
                                           participation of Belgium , Denmark ,
                                           France , Germany , Ireland , Italy ,
                                           The Netherlands and United Kingdom .
 Concerted action   C   : " Extracorporeal Oxygenation"
                            4.1   m.u.a . for a 4-year period with the active
                                           participation of Belgium , Denmark ,
                                           France , Germany , Ireland , Italy ,
                                           The Netherlands and United Kingdom .
 These figures are based on estimates as communicated by the competent
 national authorities .
 The costs of co-ordination , on charge of the Community budget , are estimated
 at   :
 Concerted action   A       330,000   u.a . for a 3-year period
 Concerted action   B       400,000   u.a . for a 4-year period
 Concerted action   C       360,000   u.a . for a 4-year period
PROSPECTIVES
The present proposal must be seen as oearmg on the first elements of the
Community Medical Research Programme . They will be gradually complemented
by other action proposals , all of which will have to meet the criteria laid
down for Community action . Sub-groups are presently carrying out preparatory
work , which will be screened by CRM at a later stage .
It is expected that a proposal for a second programme will "be ready for pre3entat
to the Council in 1978 .
 ---pagebreak---                                       - Α. 1 -                  XII / 269/ 77
                          MULTIANNUAL CONCERTED ACTION
                                 in the field of
                   "R EGISTRATION OF CONGENITAL ABNORMALITIES "
                                    (3 years )
                               TABLE OF CONTENTS
   I.    Introduction                                                       A. 2
 II .    Motivation                                                         A. 2
III .    Specific aims .                                                    A. 3
 IV .    Content                                                            A. 4
  V.     Structure                                                          A. 4
  VI .   Duration                                                           A. 5
  VII .  Implementation                                                     A. 5
  VIII . Financial volume                                                   A.ó
  ANNEX   I
  PROPOSAL FOR A COUNCIL DECISION adopting a concerted action
  in the field of " Registration of Congenital Abnormalities"
  ( Medical and Public Health Research )                                   A. 7
  Annex A to ANNEX I                                                     A. 10
  Annex B to ANNEX I                                                     A. 11
 ---pagebreak---                                       - Α. 2 ~                  XII / 269 / 77
                                   CONCERTED ACTION
                                    in the field of
                   " REGISTRATION OF CONGENITAL ABNORMALITIES "
                       ( Medical and Public Health Research )
INTRODUCTION
In compliance with its mandate , the Committee on Medical and Public Health
Research ( CRM ), assisted by its Specialized Workinq Group : Epidemiological ,
Statistics and Clinical Trials , has recommended as a project of interest to the
Community a joint action in the field of " Registration of congenital Abnor­
malities " and advised the Commission in elaborating this proposal for a multi-
annual concerted action .
In accordance with this opinion the Commission has" chosen this specific research
field :
-   on the basis of an extensive review, sponsored by CRM and the Commission ,
    recording the ongoing activities in the Member States ;
-   by considering the agreed objectives of European co-operation in the
    medical and public health domain , and                             ... . .
-   by applying the approved criteria for the selection of research priorities .
The relevant activities ongoing in non-Member States , particularly in European
countries , as well as those of appropriate International Organizations have
been taken into account .
The overall aim of the proposed action is to set up in each participating "
Member States ( where possible for the whole country , where not possible in
a region with a defined birth population ) a register of all congenital ab­
normalities observed at birth ( or during a period after birth to be defined )
in the total birth population ( including still-births ), either by making use
of existing registers of by creating new ones .
Particular attention is drawn on the fact that the information available from
such registers will also be of particular importance for the implementation
of specific topics relevant to the "Biology and Health Protection Programme"
( 1976-1980 ) and to the " Environmental Research Programme ( 1976-1980 ), both
ongoing Indirect Actions of the Commission .
As modality of research execution preference is given to a " Concerted Action".
MOTIVATION
In the countries of the European Community, as a result of an increasing
control of other major conditions in childhood, congenital abnormalities
have become a leading cause of still-birth , infant death and childhood
disablement . Meanwhile they represent a major birth problem because they are
common , they cause a great amount of suffering and their care creates a
considerable financial burden to the society .
 ---pagebreak---                                              - Α.3 -                  XII / 269/ 77
         Better knowledge of the factors responsible for congenital abnormalities can
         lead to the prevention of some and greatly reduce the number of others because
         these abnormalities often result from environmental factors within the uterus
         as well as from genetic factors : for example drug or toxic substances taken
        by the mother , or certain infections during pregnancy . While some of these
        factors have been identified , there is a need for an early warning system to
        recognize changing patterns of congenital abnormalities due to factors not yet
        identified .
        Various systems for recording are , as the performed review shows, existing in
        the Member States but , unfortunately , useful information regarding congenital
        abnormalities rests at present very limited for following reasons :
        -   systematic information differs in its completeness from one country to
            another due to legal and fiscal differences in setting-up records and in
            running registers ;
       -    the number of cases occurring in any one area as well as in a single country
            is insufficient for an effective study at national level alone ;
       -    the recorded data are of various types because the diagnostic criteria
            applied vary to a great extent .
        The establishment of a register and an appropriate network is therefore ne­
        cessary to m^ke on a standardized basis statistically valid studies feasible .
III .   SPECIFIC AIMS
       The proposed register and the appropriate network have the following specific
       aims :
       (1)    To monitor incidence and prevalence of congenital abnormalities ( conge­
              nital malformations and inherited abnormalities ) in different population
              groups and to follow fluctuations of trends with time .
       (2)    To assemble a sufficient number of specific abnormalities for retrospective
              studies of the effects of suspected environmental factors .
       (3)    To set up groups for prospective studies on the effectiveness of care ,
              the cost and the psychological effects of abnormalities in order to assist
              in genetic counselling .
       (4)    To identify twins with or without abnormalities and to identify them as
              far as possible into monozyqotic and dizygotic twins ; abnormalities with
              chromosomal patterns and with genetic determinants can then be studied.
       Finally , it should be stressed that an important consequence will be to raise
       the level of existing congenital abnormalities registers to a " European
       standard " mainly by :
      - the standardization of diagnostic criteria and of recording procedures
           to allow comparability ;
       -   the dissemination of information ;
                                                                       Λ
      ~    the exchange of experience and knowledge ;
      -    the exchange of personnel , and
      **   the training of skilled personnel .
 ---pagebreak---                                            - Α.4 -                     XII / 269/ 77
IV .  CONTENT
      The action involves setting up a notification system to collect data aboiit
      any congenital defect observed by the person in attendance at the birth
      ( doctor or midwife ) for every birth ( live or stillborn ) in the country ( or
      in one of its defined regions ). A report of any observed defect however
       trivial would be asked for , but initially the study data would be analysed
       for only those malformations which are immediately obvious and for which
       the data would likely be reasonably complete .
       Screening newborn children for biochemical abnormalities is carried out in
       the most European countries but the data collected are not centralised , they
       remain usually in the laboratories and hospitals where the children were
       examined . Laboratories in European countries begin to exchange information
       about these screening procedures but there is an urgent need for centra­
       lisation of information to permit much needed epidemiological studies to be
       set up .
       Methodological studies will be carried out in order to improve completeness
       arid representativeness of ascertainment , procedures and of diagnostic con­
       sistency , as well as to speed up reporting procedures for monitoring needs
       in order to allow early institution of remedial measures on the part of
       health authorities .
       Initially the programme will not try to encompass all congenital abnormalities .
       Preliminary studies suggest that the listing of abnormalities reportable to
       the registers should be restricted and include the anomalies of th :- central
       nervous system ( anencephaly , spina bifida etc ...), Down 's syndroire , gross
       anomalies of the limbs , multiple abnormalities , phenylketonuria and celiac
       disease . Twins and multiple pregnancies will also be registered . The pro­
       gramme will be expanded once the initial aims of fostering reporting systems
       and upgrading the standards of existing systems will be achieved .
V.     STRUCTURE
       The structure of the concerted action is based on an extensive review of the
       existing systems for recording births and congenital abnormalities in the
     ■ countries of the EC as well as in a number of neighbouring countries with
       similar technical problems .
       From these systems a selection of regional registers or services has been
       made with regard to their competences , facilities and willingness of collabo­
       ration .
       Thus , the proposed network of registers will initially be established on the
       collaboration between the following existing regional registers of the Member
       States   :
       BELGIUM                :      Brugge
                                     Hainaut
       DENMARK                       Odense
       FRANCE                        Paris
       GERMANY                       Hessen
       IRELAND                       Dublin
                                     Galway
 ---pagebreak---                                             - Α. 5 -                   XII / 269 / 77
        ITALY                       Mi lano
                                     Roma
       LUXEMBOURG                    Luxembourg •
       NETHERLANDS                   Leidschendam
       UNITED KINGDOM                Belfast
                                     Glasgow
                                     Liverpool
       Since certain countries outside of the EC built up    a high level of expertise
       in the running of corresponding registers end thus    con actively contribute
       to the success of this endeavour , an amendment for   the participation of non-
      Member countries involved in European co-operation     in the field of scientific
       and technical research ( COST ) in this action is foreseen after the Council 's
       Decision .
 VI .  DURATION
      A duration of 3 years is   proposed for this concerted action .
       Due to the complexity of  the problem to be tackled , this period should be
       considered as an initial  phase . Continuation is foreseen by the submission
      of a new proposal in due   time .
VII .  IMPLEMENTATION
      The concerted action is to be implemented with the participation of all Member
      States .
      After the Council 's Decision non-Member States involved in European co­
      operation in the field of scientific and technical research ( COST ) will be
      invited to participate .
      In principle , the competent national authorities are responsible for the
      execution of the national contributions to this action and are prepared to
      integrate the research , covered by this concerted action , into a process of
 v    co-ordination at Community level over a period of 3 years .
      A Concerted Action Committee is established in which the Member States are
      each represented by one delegate and one alternative who may be assisted by
      experts .
      Provision will be made for an adequate representation of the participating
      non-Member States on the Concerted Action Committee .
      The competences of the Committee on Medical and Public Health Research cover
      also the implementation of this action ; this Committee is in particular duly
      qualified for giving to this research its proper place within the sectorial
      policy of the European Communities as well as for ensuring its success .
      The Concerted Action Committee 1s the body in which the exchange of informatior
      between the Member States , CRM and the Commission is staged . The Commission anc
      the Committee will be assisted by a Project Leader .
                     V
 ---pagebreak---                                      - Α.6                     XII / 269/ 77
®.®yond this ^ the terms of reference of this Conimlttee are essentially :
-   to assist in the co-ordination of the national research projects executed
    in this field and to advise the executing laboratories ;
- to advise governments and the Commission with' regard to research needs in
    this field ;
-   to evaluate the results of research and to draw conclusions with regard
    to their applications ;
-   to promote exchange of experience between the scientists involved by
    organizing symposia , etc . ...;
-   to promote the dissemination of knowledge .
FINANCIAL VOLUME
The financial volume of the research in this field to bo executed by the
participating registers or services of all the Member States is estimated
at 0.85 m.u.a . for a 3-year period .
This figure is based on estimates , as communicated by the competent national
aut horities .
The costs of co-ordination , on charge of the Community budget , are estimated
at 330,000 u.a . for the 3-year period .
 ---pagebreak---                                                     \
                                       - Α.7 -
                                                              ANNEX   I
                     PROPOSAL FOR A COUNCIL DECISION
                 adopting a concerted action in the field of
                   Registration of Congenital Abnormalities
                     ( Medical and Public Health Research )
 THE COUNCIL OF THE EUROPEAN COMMUNITIES ,
Having regard to the Treaty estaolishing the European Economic Community /
and in particular Article 235 thereof ;
Having regard to the proposal of the Commission ;
Having regard to the opinion of the European Parliament ;
Whereas by virtue of Article 2 of the Treaty, the Community has been assigned
the task of promoting throughout the Community a harmonious development of
economic activities , a continuous and balanced expansion and an accelerated
raising of the standard of living ;
Whereas the Council stressed in its Resolution of 14 January 1974 on an
initial outline programme of the European Communities in the field of science
and technology that an appropriate approach should be adopted towards the
whole range of available ways and means , including concerted action and that
whenever it proves desirable that third countries , particularly European ones ,
should be associated in these projects , steps should be taken to make this
possible ;                         ' ■         .
Whereas on 14 January 1974, the Council entrusted the Community Institutions
aided by the Scientific and Technical Research Committee ( CREST ) with the
task of ensuring the gradual co-ordination of national policies in the field
of science and technology ;
Whereas a concerted Community research action in the field of registration
of congenital abnormalities is likely to contribute effectively to the
achievement of the above-mentioned aims;
Whereas the Member States intend , as part of the rules and procedures appli­
cable to their national programmes , to carry out the research described in
Annex A , and are prepared to integrate such research into a process of co­
ordination at Community level over a period of three years ;
Whereas the carrying out of such research as described in Annex A will require
a financial contribution of about 0.85 MUA from the Member States ;
Whereas the Treaty has not provided the necessary powers for this purpose ;
                V
 ---pagebreak---                                        Α. 8 -                XII / 269 / 77
                                                             ANNEX     I
Whereas the Scientific and Technical Research Committee ( CREST ) has given
 its opinion with regard to the Commission proposal ;
HAS DECIDED    :
                                  Article 1
        The Community shall implement for a period of 3 years a concerted
action in the field of Registration of Congenital Abnormalities .
        This action shall consist in the co-ordination at Community level of
research which is described in Annex A and which forms part of the research
programme of the Member States .
                                  Article 2
       The Commission shall bo responsible for such co-ordination .
                                  Article 3
       The maximum financial contribution by the Community to such co-ordination
action is estimated at 330,000 UA , the unit of account being defined according to
nancial regulation in force .
                                  Article 4
       To facilitate the carrying out of the action , a concerted action Committee
on the " Registration of Congenital Abnormalities ", hereinafter referred to as
" the Committee", is hereby established .
A project leader : shall be appointed by the Commission witn the Committee , s
agreement . He assists in particular the Commission in its co-ordinating action .
       The terms of reference and the composition of this Committee are defined
in Annex B.
        The Committee shall draw up its rules of procedure . Its secretariat will
be provided by the Commission .
                                  Article 5
(a)         In accordance with a procedure to be adopted by the Commission in
     agreement with the Committee , the participating States shall exchange re­
     gularly all useful information concerning the execution of the research
     covered by the concerted action and forward to the Commission all infor­
     mation useful for co-ordination . They shall also endeavour to provide the
     Commission with information in similar research planned or carried out by
     bodies for which they are not responsible . This information shall be
     treated as confidential if requested by the Member State which provides it .
(b)         The Commission shall prepare yearly progress reports on the basis of
     the information supplied , and shall forward them to the Member States .
(c)         At the end of the co-ordination period , the Commission in agreement
     with the Committee shall forward to the Member States and to the European
     Parliament a general report on the execution and results of the co­
     ordination action . The Commission shall publish this report six months
     after it has been forwarded , unless a Member State objects . In this case
 ---pagebreak---                                  - Α.9 -                XII / 269 / 77
                                                        ANNEX     I
the report shall be distributed , at their request , solely to the institu­
tions and undertakings of which the research or production activities are
justifying access to the knowledge resulting from the performance of the
research covered by the Community concerted action . The Commission mr.y
make provision tha > the report remains confidential and is not passed to
third parties .
                               Article 6
       In accordance with the provisions laid down in Article 228 of the
Treaty establishing the EEC , the Community may conclude agreements with
other States involved in European Co-operation in the field of Scientific
and Technical Research ( COST ) with a view to extending the co-ordination
which is the subject of this Decision to research undertaken in these
States .
       The Commission is hereby authorized to open negotiations for the
conclusion of agreements of the type referred in the preceding paragraph .
                               Article 7
       This Decision shall come into force on the 1st January , 1978 .
                                   Done at              on
                                             For the Council
                                              The President
                                                    }
 ---pagebreak---                                                 Α . 10                  XII / 269 / 77
                                                                        Annex A to ANNEX I
                          ANNEX A TO THE PROPOSED COUNCIL DECISION
                         adopting a concerted action in the field of
                           Reqistration of ConqenitnL Abnormalities
                             ( Hedical and Public Health Research )
      The research will be carried out with the purpose of acquiring scientific and
      technical knowledge in this field , selected for its importance at Community
      level .
      The research is expected to cover the following topics        :
      (1)   Registration of congenital malformations as well as of inherited bio­
    •       chemical and chromosome abnormalities in selected regions of the
            Community . Initially , the recorded abnormalities will include the
            anomalies of the nervous system ( anencephaly , spina bifida , etc .
          . Down 's syndrome , gross anomalies of the limbs , multiple abnormalities ,
   '        phenylketonuria and celiac disease .
i?.
      (2)   Registration of twins and multiple pregnancies in selected regions of
            the Community .
      (3)   Relevant methodological studies in order to obtain an optimal co-ordination
            of both existing national registers and registration procedures .
i     The co-ordination will include the following regional registers of the Member
      States
      BELGIUM                       Brugge and Hairiaut
      DENMARK                       Odense
      FRANCE                        Paris
      GERMANY                       Hessen
      IRELAND                       Dublin end Galway
      ITALY                         Milano and Roma
      LUXEMBOURG                    Luxembourg
      NETHERLANDS                   Leidschendam
      United Kingdom                Belfast , Glasgow and Liverpool
      These countries will contribute research under alt three tooics mentioned
      above .
                                                                      ι
 ---pagebreak---                                              Α . 11               XII / 269 / 77
                                                                 Annex B to ANNEX I
                      ANNEX B TO THE PROPOSED COUNCIL DECISION
                     adopting a concerted action in the field of
                       Registration of Congenital Abnormalities
                          ( Medical and Public Health Research )
 l£H2S-2Í-££Í£C®Q£§_2Q^_£2!!!!22£Í£Í2Q_2Í_Í.Di.£2D£££££íí.§£ÍÍ2Q_£2!!3'3ÍÍS£I
 "I§2Í§£ü¿£Í2Q_2Í_£2GíI£n i * a ^ Abno rma l i t i es "
 1.         The Committee shall     :
     1.1 .  Contribute to the optimum execution of the programme by giving its
            opinion on all of its aspects ;
     1.2 .  Evaluate the results and draw conclusions as regards to their
            application ;
    1.3 .  Ensure the exchange of information referred tp in Article 5(a );
    1.4 .  Keep abreast of national research being done in the fields covered
           by the concerted action., and more especially of scientific and
           technical developments likely to affect the carrying out of the
           action ;
    1.5 .  Indicate the orientations to the project leader .
2.         The Committee 's reports and opinions shall be transmitted to the
    Commission and to the participating States . The Commission shall forward
    these opinions to the CREST .
3.         The Committee shall be composed of on£ representative and one
    alternative responsible for co-ordinating the national contributions
    to the programme / and the project leader . Each member may be accompanied
    by experts .
                  \
 ---pagebreak---                                                              XII / 269/ 77
                        MULTIANNUAL CONCERTED ACTION
                                in the field of
        " CELLULAR AGEING AND DECREASED FUNCTIONAL CAPACITY OF 03G<U 'S "
                                   (4 years )
                              TABLE OF CONTENTS
                                                                          Pane
  I.       Introduction                                                   8.2
 II .      Motivation .......                   .........                 B.2
III .      Content and topics                                             B.3
 IV .      Structure                                                      D.5
  V.       Durât icn                                    .....             B.6
  VI .     Implementation                                                 B.6
  VII .    Financial volume                                               B.7
  ANNEX     I
  PROPOSAL FOR A COUNCIL DECISION adopting a concerted action
  in the field of " Cellular Ageing and Decreased Functional
  Capacity of Organs
  < Mc-dical and Public Health Research )                                 B.8
  Annex A to ANNEX I                                                    B.11
  Annex B to ANNEX I                                                    B.13
 ---pagebreak---                                             - Β. 2 -                XII / 269/ 77
                                        CONCERTED ACTION
                                         in the field of
                 " CELLULAR AGEING AND DECREASED FUNCTIONAL CAPACITY OF ORGA'.'S "
                           ( Medical and Public Health Research )
 I.  INTRODUCTION
     In compliance with its mandate , the Committee on Medical and Public Health
     Research ( CRM ), assisted by its Specialized Working Group : Research in the
     field of Medical Biology , has recommended as a project of interest to the . Commun
     the joint implementation of research in the field of " Cellular ageing and
     decreased functional capacity of organs " and advised the Commission in elabo­
     rating a corresponding proposal for a multiannual concerted action .
     In accordance with this opinion the Commission has chosen this specific research
     field :
     -  on the basis of the exploratory work carried out by the Specialized
        Working Group ;
     -  by considering the agreed objectives of European co-operation in the
        medical and public health domain ;
     -  by applying the approved criteria for the selection of research
        priorities , and
     -  having regard to the conclusions elaborated by the European experts
        in this specific field during a workshop , held on 12-14 February 1976
        under the sponsorship of CRM and the Commission ,, where according to the
        present state of the art the most significant research problems were
        identified , and where the needs for the most efficient handling of the
        problem , from the point of view cf research and training requirements ,
        were evaluated .
     The relevant activities ongoing in non-Member States , particularly in European
     countries , as well as those of appropriate International Organizations have
     been taken into account .
     As modality of research execution preference is given to a " Conc®rted Action".
II . MOTIVATION
     The health status of elder persons and problems connected to it are of major       \
     socio-medi ca I concern since at least 11% of the population in the European       j
     Community is older than 65 years of age . Social and medical advances will         j
     continue to change the age-structure of the population and increase the pro-        .
     portion of elder persons in it . Also birth rate may play an additional role       j
     in future ; thus it can be expected that these changes in size and structure       j
     of the population will have a great impact of health , health care and . health
     research in the EC .                                                               j
 ---pagebreak---                                        Β. 3 -                   XII / 269/ 77
Biological ageing processes are the cause for the gradual change of a young
 individual into an old one and they contribute to the development of many
diseases in the elderly population . In the 11% quoted above , between 80 and
90 % suffer from one or more chronic disease . Thus , increasing sums have to
be yearly allocated by the single Member States for the health care of elderly
persons .
Nevertheless , research in the domain of GERONTOLOGY , covering the biological ,
psychological and social aspects of ageing , has never received all the atten­
tion it deserves . Although research is carrying out in the Member States on
the various aspects of this complex problem and several scientific centres
have reached a high level of special knowledge and expertise , the scientific
developments in this area have not kept up neither with the needs of our
society nor the requi rements . of our scientific community .
Therefore , as a realistic approach in order to tackle a basic part of the
problem connected with the physiology of ageing in a more efficient way , and
to achieve clear and reasonably early results , a joint European research
effort was deemed necessary .
Since changes at the cellular level are probably responsible for most of the
physiological ageing processes occurring at the organ Level and at the level
of the whole individual , the emphasis was placed on cellular ageing as the
basis for decreased functional capacity of organs .
Three representative topics , each with its own specific approach to the
problem of the cellular basis of ageing , all closely related to the physiology
of elderly people , were selected for initial action . These were :
A.   Cellular basis of liver ageing
B.   The immune response during ageing
C.   Ageing of the lens
CONTENT AND TOPICS
A.   Cellular basis of liver ageing
     Many mammalian organs , including the liver , show a decrease in functional
     capacity with age . Due to the complex manner in which organs function , it
     is very difficult to differentiate between cellular and extracellular
     causes for the impairment in function . Furthermore , it is impossible to
     make a detailed interpretation of the ageing of an organ in the absence
     of quantitative information on the properties of the various cell classes
     within the organ in question .
     The cellular basis of the ageing process has been studied in organs ,
     tissues and cell organelles , in particular in the liver / the functions of
     which decline with age . A better understanding of the mechanism under­
     lying this functional decline will be achieved by improving the methods
     of analyzing separately the different cell types of the liver and by re­
     constituting in vitro the relationships which exist between parenchymal
     cells and Kupffer and endothelial cells , in order to determine their
     respective importance . The analysis of the various cell types will include
     the comparison of alterations in bioenergetic and other biochemical cha­
     racteristics of mithochondria and in the regulation of lysosomal enzyme
     activities .
 ---pagebreak---                                     Β.4 -                     XII / 269 / 77
  Tho immune response during ageing
  The disciplines of immunology and gerontology impinge upon each other in
  several ways .
 The immune systerr provides a convenient model for the investigation of
 ageing processes - "J an immense a-nount of background information is
 available . The system can be studied by a wide variety of well-established
 quantitative techniques arid is known to undergo progressive age-associated
 changes . Longitudinal studies are practicable in both animals and , to a
 more limited extent , in man .
 The existing patterns of , and immediate potential for , collaboration in
 immunogerontology are perhaps less highly evolved partly due to the
 broadness of the subject and the diversity of topics currently understudy .
 Such diversity is a source of strength , provided that good contact can be
 maintained and developed among the interested laboratories . In the immediate
 future, exchanges of techniques and material among several laboratories are
planned . In a slightly longer term , it is envisaged that more extensive
 collaboration will develop in certain areas , particularly in the application
to man of investigational systems developed in animals .
Ageing of the lens
The lens grows during the whole lifespan , increasing in weight and volume .
 It is the organ with the highest protein content ; about 35% of its wet
weight consists almost completely of organ specific proteins which , through
a special arrangement , are responsible for its transparency .
Ageing leads to 2 different effects representing a decreased functional
capacity , which have been well-known to ophthalmologists for centuries :
a ) around the 4th decade , the human lens looses the ability of accomodation ,
which means that the capacity for changing the lens shape to enable lens
focusing at different distances becomes weaker ,
and
b ) each ageing person develops morphological lens changes . However , it is
remarkable that only in some patients do these circumscribed opacities
progress to mature cataracts , the time of occurrence warying widely .
The proposed co-operative research on ageing of the lens should provide
more complete information on the different age-induced mechanisms loading
to well-differentiates types of senile cataracts . From experimental
cataract research , there is evidence that certain models provide transpa­
rency changes which are similar to those observed in the ageing human .
This study has to be perfected in order to perform future investigations
with suitable animal models . It is necessary to gain better knowledge on
the age-related disturbances and modifications which could influence the
process of cell division and differentiation for the synthesis of crystallin
and capsular material .
In epithelial and terminally differentiated lens cells , the machinery for
protein synthesis has to be maintained . This implies a stabilization of
mRNA , the molecular mechanisms of which have not yet been completely elu­
cidated . Proteins once synthesized undergo age-induced changes by aggrega­
tion , insolubi lisation and posttranslational modifications of primary
structure . The underlying mechanisms of such changes must be further in­
vestigated in order to better understand how they effect the functional
capacity of the lens . Discoveries in the mechanisms of ageing in the lens
will probably be applicable to the mechanisms in most of the other tissues
not readily available for research purposes .
 ---pagebreak---                                       - Β.5 -                     XII / 269 / 77
 Finally in addition to these research topics , the concerted action has tp
 include the following possibilities and technical facilities , respectively :
-   short term exchange of research workers between collaborating laboratori' >
    in order to train in special methods or to perform special investigations
    on the spot using available experimental material ;
-   an information centre to advice on availability of material ( animals , organs
    and tissues ) which is scarce and expensive . This would not only lead to con­
    siderable savings by avoiding waste , but also permit an optimal utilization
    of old animals , which are difficult to obtain ;
- . a one year plenary meeting at which an interdisciplinary view of the related
    research and results as well as future trends and plans may be obtained by
    all participants . This general meeting would also permit the establishment
    of standardization in materials and methods used ;
-   twice yearly inter laboratory exchange of ideas , methods and results by visits
    of scientists within each sub-group . These in-depth discussions should be
    done by rotation of the meeting places to allow a better knowledge of the
    facilities , methods and research of each team, and
-   a project leader .
STRUCTURE
Since the national authorities are responsible for the execution of their
respective contributions to this concerted action , several Member States have
designated their competent medical research organizations as active partici­
pants , while other Member States designated directly the participating insti­
tutes , which were chosen with regard Lo their competences , facilities and
willingness for collaboration .
BELGIUM
        - F.N.R.M.    Fonds National de la Recherche Médicale , Bruxelles
DENMARK   .
        - Danish Medical Research Council , Copenhagen
                             t
FRANCE­
        - INSERM    Institut National de la Santé et de la Recherche Médicale ,
                    Paris
GERMANY
D1      - Institut für Experimentelle Ophthalmologie der Universität Bonn
            Abteilung Biochemie des Auges , Bonn-Venusberg
D2      - Max -Planck - Institut für Immunbiologie , Freiburg-Zähringen
IRELAND
        - Medical Research Council of Ireland , Dublin
ITALY                                                 '                      '
        - C.N.R.    Consiglio Nazionale della Ricerca , Roma ■
 ---pagebreak---                                              - 3.6 -                      XII / 269/ 77
     NETHERLANDS
     NL1          - Laboratorium voor Biochemie Universiteir van Nijmegen , Nijmegen
     NL2          - Institute for Experimental GërontoLcgy TNO , Rijswijk
     NL3          - Centraal Laboratorium Bloed Transfus-iedienst , Amsterdam
     unII§2_!<ING£0M
                  - M.R.C.  Medical Research Council , London
V.   DURATI0N
     A duration of 4 years is proposed for this concerted action .
VI . IMPLEMENTATION
     The concerted action is to be implemented with the agreement of all Member
     States .
     After the Council 's Decision non-Member States involved in European co­
     operation in the field of scientific and technical research ( COST ) will be
     invited to participate .
     In principle , the competent national authorities are responsible for the
     execution of the national contributions to this action and are prepared to
     integrate the research , covered by this concerted action , into a process of
     co-ordination at Community level over a period of 4 years .
     A Concerted Action Committee is established in which the Member States are
     each represented by one delegate and one alternative , who may be assisted by
     experts .
     Provision will be made for an adequate representation of the participating
     non-Member States on the Concerted Action Committee .
     The competences . of the Committee on Medical and Public Health Research cover
      also the implementation of this action ; this Committee is in particular duly
     qualified for giving to this research its proper place within the sectorial
     policy of the European Communities as well as for ensuring its success .
     The Concerted Metier; Committee is the body in which the exchange of information
      i- wt -.,een the Member States , CRM and the Commission is staged . The Commission and
      the Committee will be assisted by a Project Leader .
     Beyond this , the terms of reference of this Committee are essentially             :
       -     to assist in the co-ordination of the national research projects executed
             in this field and to advise the executing laboratories ;
       - to advise governments and the Commission with regard to research needs in
             this field ;
      -     to evaluate the results of research and to draw conclusions with regard
            to their applications ;
      - to promote exchange of experience between the scientists involved by
           organizing symposia , etc . ...;
     ~ to promote the dissemination of knowledge .
 ---pagebreak---                                                                      XII / 269 / 77
VII .  FINANCIAL VOLUME
       The financial volume of the research in this field to be executed by the
       Member States is estimated at 4,0 m.u.a . for a 4-year period .
      This figure is based on estimates , as communicated by the competent national
      authorities .
      The inventory of the research projects indicates that Belgium , Denmark , France ,
      Germany , Ireland , Italy , The Netherlands and United Kingdom would contribute
      research under the three topics of this concerted research action .
      The cost of co-ordination , on charge of the Community budget , is estimated
      at 400,000 u.a . for the 4-year period .
 ---pagebreak---                                     - Β.8 -
                                                                ANNEX  I
                     PROPOSAL FOR A COUNCIL DECISION
                adopting 3 concerted action in the field cf
        Cellular Ageing and Decreased Functional Capacity of Organs
                   ( Medical and Public Health Research )
THE COUNCIL OF THE EUROPEAN COMMUNITIES ,
Having regard to the Treaty establishing the European Economic Community ,
and in particular Article 235 thereof ;
Having regard to the proposal of the Commission ;
Having regard to the opinion of the European Parliament ;
Whereas by virtue of Article 2 of the Treaty , the Community has been assigned
the task of promoting throughout the-' Community a harmonious development of
economic activities , a continuous and balanced expansion and an accelerated
reising of the standard of living ;
Whereas the Council stressed in its Resolution of 14 January 1974 on an
initial outline programme of the European Communities in the field of science
and technology that an appropriate approach should be adopted towards the
whole range of available ways and means , including concerted action and that
whenever it proves , desirable that third countries , particularly European ones ,
should be associated in these projects , steps should be taken to make this
possible ;
Whereas on 14 January 1974 , the Council entrusted the Community Institutions
aided by the Scientific and Technical Research Committee ( CREST ) with the
task of ensuring the gradual co-ordination of national policies in the field
of science and technology ;
Whereas a concerted Community research action in the field of cellular ageing
and decreased functional capacity of organs is likely to contribute effectively
to the achievement of the above-mentioned aims ;
Whereas the Member States intend , as part of the rules and procedures appli­
cable to their national programmes * to carry out the research described in
Annex A , and are prepared to integrate such research into a process of co­
ordination at Community level over a period of four years ;
Whereas the carrying out of such research as described in Annex A will require
a financial contribution of about 4,0 MUA from the Member States ;
Whereas the Treaty has not provided the necessary powers for this purpose ;
 ---pagebreak---                                      - Β. 9                 XII / 269 / 77
                                                            Annex     I
Whereas the Scientific and Technical Research Committee ( CREST ) has given
 its opinion with regard to the Commission proposal ;
                                                                                    ••
HAS DECIDED :
                                   Article 1
        The Community shall implement for a period of 4 years a concerted
action in the field of Cellular Ageing and Decreased Functional Capacity of
Organs .
        This action shall consist in the co-ordination at Community level of
research which is described in Annex A and which forms part of the research
programmes of the Member States .
                                   Article 2
       The Commission shall be responsible for such co-ordination .
                                   Article 3
       The maximum financial contribution by the Community to such co-ordination
action is estimated at 400,000 UA , the unit of account being defined according to thi
financial regulation in force .
                                   Article 4
       To facilitate the carrying out of the action , a concerted action Committee
on the " Cellular Ageing " hereinafter referred to as " the Committee", is
hereby established . A project leader shall be appointed by the Commission with
the Committee 's agreement . He assists in particular the Commission in its co­
ordinating action .
       The terms of reference and the conposition of this Committee are defined
in Annex B.
       The Committee shall draw up its rules of procedure . Its secretariat will
be provided by the Commission .
                                   Article 5
<a)         In accordance with a procedure to be adopted by the Commission in
     agreement with the Committee , the participating States shall exchange re­
     gularly all useful information concerning the execution of the research
     covered by the concerted action and forward to the Commission all infor­
     mation useful for co-ordi nation . They shall also endeavour to provide the
     Commission with information on similar research planned or carried out by
     bodies for which they are not responsible ., This information shall be
     treated as confidential if requested by the Member State which provides it .
(b)         The Commission shall prepare yearly progress reports on the basis of
     the information supplied , and shall forward them to the Member States .
<c)         At the end of the co-ordination period , the Commission in agreement
     with the Committe;e shall forward to the Member States and to the European
     Parliament a general report on tho execution and results of the co­
     ordination action . The Commission shall publish this report six months
     after it has been forwarded , unless a Member State objects . In this case
 ---pagebreak---                                 - Β . 10 -               XII / 269 / 77
                                                         Annex     I
                                                   -»   –––.
   the report shall be distributed , at their request , solely to the institu­
   tions and undertakings of which the research or production activities are
   justifying access to the knowledge resulting from the performance of the
   research covered by the Community concerted action . The Commission mry
   mak ? provision that the report remains confidential and is not passed to
   third parties .
                              Article 6
1.      In accordance with the provision laid down in Article 228 of the
   Treaty establishing the EEC , the Community may conclude agreements with
   other States involved in European Cc-operation in the field of Scientific
   and Technical Research ( COST ) with a view to extending the co-ordination
   which is the subject of this Decision to research undertaken in these
   States .
2.      The Commission is hereby authorized to open negotiations for the
    conclusion of agreements of the type referred in the oreceding paragraph .
                              Article 7
        This Decision shall come into force on the 1st January , 1978.
                                         Done at                 on
                                                  For the Council
                                                  The President
 ---pagebreak---                                           - Β . 11 -                XII / 269 / 77
                                                                    Annex A to ANNEX I
                       AN NEX A TO THE P80P0SED COUNCIL DECISION
                      adopting a concerted action in th ? field of
          Cellular Ageing and Decreased Functional Capacity of Organs
                           ( Medical and Public Health Research )
The research will be carried out wich the purpose of acquiring scientific and
technical knowledge in this field , selected for its importance at Community
level .
The research is expected to cover the following topics            :
(1)     Cellular basis of liver ageing : biophysical and biochemical studies
        at organ , cellular and subcellular level of the progressive , cge-
        associated functional alterations , including comparative studies in
       other cell types .
( 2)    The immune response during ageing : oriented studies in both animals
        and , to a limited extent , in man of the age-induced changes in the
        immune system with emphasis on immunodeficiencies and possibilities
       of therapy .
(3)     Ageing of the Ions : physiological ,- morphological and biochemical
        studies in human and animal tissues of the age-related functional
        alterations leading to senile cataracts .
 The co-ordination will include the following competent medical research
 organizations respectively participating institutes of the Member States :
 BELGIUM
           - F.N.M.R.      Fonds National de la Recherche Médicale , Bruxelles
  DENMARK
           - Danish Medical Research Council , Copenhagen
  FRANCE
           - INSERM     Institut National de la Santé et de la Recherche Médicale ,
                        Paris
  GERMANY
            - Institut für Experimentelle Ophtalmologie der Universität Bonn
               Abteilung Biochemie des Auges , Bonn- Venusberg
            - Max - Planck- Institut für Immunbiologie , Freiburg-Zähringen
   IRELAND
             - Medical Research Council of Ireland , Dublin
    ITALY
             - C.N.R.    Consiglio Nazionale della Ricerca , Roma
 ---pagebreak---                                      - 8.12 -                  XII / 269 / 77
                                                               Annex A to ANNEX I
NETHERLANDS
       - Laboratorium "voor Biochemie - Universiteit van Nijmegen , Nijmegen
        - Institute for Experimental Gerontology TNO , Rijswik
        - Centraal Laboratorium Bloed Transfusiedienst , Amsterdam
        - M.R.C.  Medical Research Council , London
These countries will contribute research under the three topics mentioned
above .
;
 ---pagebreak---                                          - B.13 -                XII / 269/ 77
                                                                 Annex B to ANNEX I
                     AMNEX 'd TO THE -ROPOSED COUNCIL DECISION
                    adontin :-) a crncerted action in the field of
            Cellular Ageing and Decreased Functional Capacity of Organs
                         ( Medical and Public Health Research )
Terffis_£f_reíerençG_ind_çori£2£ÍÍÍ2Q_2Í_Ab2_£2Q£e£ted_açtÍ2Q-.Çommitte2
" Cellular_Ageinn
1.         The Committee shall     :
   1.1 .   Contribute to the optimum execution of the programme by giving
           its opinion on all of its aspects ;
   1.2 .   Evaluate the results and draw conclusions as regards to their
           application ;
   1.3 .   Ensure the exchange of information referred to in Article 5(a );
   1.4 .   Keep abreast of national research being done in the fields covered
           by the concerted action , and more es ecially of scientific and
           technical developments likely to affect the carrying out of the
           action .
   1.5 .   Indicate the orientations to the project leader .
2.         The Committee 's reports and opinions shall be transmitted to the
   Commission and to the participating States . The Commission shall forward
   these opinions to the CREST .
3.         The Committee shall be composed of one representative and one alter­
   native responsible for co-ordination the national contributions to the
   programme , and the project leaser , Each member may be accompanied •
   by experts .
 ---pagebreak---                                    - C.1 -                 XII / 269 / 77
                     MULTIAMNUAL CONCERTED ACTION
                              in the field of
                     " EXTRACORPOREAL OXYGENATION "
                                 (4 years )
                           TABLE OF CONTENTS
                                                                       Paqe
  I.      Introduction                                                 C.2
 II .     Motivation                                                   C.2
III .     Objectives                                                   C.4
 IV .     Structure                                                    C.4
  V.      Duraticn                                                     C.5
  VI .    Implementation              ......                           C.5
  VII .   Financial volume                                             C.6
  ANNEX   I
  PROPOSAL FOS A COUNCIL DECISION' adonting a concerted action
  in the field of " Extracorporeal Oxygenation"
  ( Medical and Public Health Research )                               C.7
  Annex A to ANNEX I                                                C.10
  Annex B to ANNEX I                                              . C.12
          V
 ---pagebreak---                                              - C.2 -                   XII / 269/ 77
                                       CONCERTED ACTION
                                         in the field of
                                 " EXTRACORPOREAL OXYGENATION"
                          ( Medical end Public Health Research )
INTRODUCTION
In compliance with its mandate, the Committee on Medical and Public Health
Research ( CRM ), assisted by its Specialized Working Group : Research in the
field of Biomedical Engineering , has recommended as a project of interest to the
Community the joint implementation of research in the field of " Extracorporeal
Oxygenation" and advised the Commission in elaborating a corresponding pro­
posal for a multiannual concerted action .
In accordance with this opinion the Commission has chosen this specific research
field :
-    on the basis of the explorative work carried out by the Specialized
     Working Group ;
-    by considering the agreed objectives of European co-operation in the
      medical and public health domain ;
-     by applying the approved criteria for the selection of research
      priorities , and
 -    having regard to. the conclusions elaborated by the European exports
       in this specific "»■»•» Id during a workshop , held on 15-20 June 1975 in
       Copenhagen under tht sponsorship of CRM and the Commission , where
       according to the preset state of the art the most significant problems
       related to this field o :- research were identified .
  The relevant activities ongoing             non-Member States , particularly in European
  countries , have been taken into «- '- 'f>unt.
   Execution in the form of a " Concerted ; **. ion" was deemed important if the-
   research problems were to be carried on - ;-■£ e i ciently . Because none of the
   national efforts alone is likely to ensure v .--.quate and reasonably early
   results , the chances of success can be sign ^ e v...ntly improved by their in­
   tegration into a concerted acti-on .
                                          r
   MOTIVATION
    Treatment with oxygenators has in the past two decades >\>-iiy been focused
    on short term use to provide cardiopulmonary support durv\ surgical cor­
    rections and replacements .
    For this purpose the presently available oxygenator types havt pr->ve clinically
    satisfactory for periods up to 5-10 hours .
     The categories of illnesses treated by such surgery are valvular functional
     defects and congenital malformations . However , these diseases constitute
     only a part of the cardio-pulmonary disorders which could potentially be
     treated better if long term extracorporeal oxygenation were possible .
 ---pagebreak---                                       - C.3 •                   XÏI / 269/ 77
For example , cardiac failure due to acute myocardial infarction is today the
most frequent cause of physical disability in the productive age groups , from
which relatively high direct and indirect costs to our society are arising .
Recent advances ir> coronary surgery provide a possibility of recovering the
full function of tht ; schaemic myocardial tissue . Here , the remarkable ca­
 pability of rapid revac.'xMlarisation of the myocardium can be utilized by
 attempting a relief of x - .-. heart through cardiopulmonary support during this
 period . Also the treatment t; reversible reduction or loss of lung function
 will require the use of extracorporeal oxygenation but for periods longer
 than a week .
  With its demand for long term use \f oxygenators what seemed earlier appa­
  rently negligible problems have grown •-> become limiting factors for the
  success of the treatment . Furthermore , v patients in question are invariably
  very ill and undergo a poor functioning o ? their regulatory systems which are
  out of control . Cardiopulmonary failure is .vsquently associated with anuria ,
   coagulopathies and often further complicated r.y infections . The victims are
   thus unable to withstand further shifts in their ohysiologi cal parameters .
   Consequently , success of treatment depends on a cloie dynamic adjustment of
   the performance according to the needs of the patient . In clinical terms this
   implies attempts not only to control the conventional blood gas and electrolyte
   parameters as well as the oxygen consumption , but also to maintain a sufficiem
   blood flow through at least the vital organs and to sustain the nutrition of
   the organism .
    From a survey of the present state of the art concerning oxygenator research
    the following main conclusions can be drawn :
    – Substitution of membrane oxygenators for those simply using direct gas-to-
        blood interface , e.g. in form of gas bubbles , may improve possibilities
        for extracorporeal clinical oxygenation from hours to weeks duration .
        The first generation of such membrane oxygenators confirms this view.
        Though improvement of flow geometry already has lead to art increase in
        the gas transfer rate , the presently available oxygenators as well as
        those of the near future will represent only a temporary solution due to
        the serious physical and biological limitations inherent in present membran
        materials .
    – Available systems are designed and used at their peak capacity and the
        problem of controlled adaptation of gas exchange capacity to the needs of
        the patient remains unsolved .
    – The currently available membrane materials are at best biologically inert,
        and these are not able to prevent blood trauma and thrombotic deposits
        which in turn leads to progressive deterioration of oxygenation efficiency
        and to an enhancement of bleeding tendency in the treated patient .
     In view of the multitude of problems to be solved , at different levels , a
     joint multidisciplinary research effort will" be more likely to overcome the
    difficulties involved .
     Furthermore, since individual countries each tackle separately only some of
    these problems and since none of these national research efforts alone is
     likely to ensure a concerted attack on the overall problem, an integration of
     all related activities , ongoing in the Member countries, into a Concerted
    Action" is likely to increase the chances of solving the problem .
 ---pagebreak---                                                 C.4 -                  XII / 269/ 77
III .  OBJECTIVES
       The following three representative objectives , all of thorn feasible and
       offering good prospects of success , were chosen for this joint European
       research effort :
       1 ) Continuous improvement in performance of present oxygenator principles
              with respect to the limitations sot by diffusion resistance and blood
              trauma .
              a ) Clinical -applicability of introduction of a controlled secondary
                   flow ( blood nixing ) into present oxygenator principles .
              b ) Studies of the effects of blood flow and shear stress on the aggre­
                   gation and adhesion of platelets , of the interaction of^red cells
                   and platelets , and of pharmacologic methods of intervention .
       2 ) Continuous development of alternative oxygenation principles and testing
              for their clinical applicability .                                     _ _
            • Here , research is aiming in particular at further development and joint
              evaluation of the principles of      :
              a)   Hyperbaric oxygenation .
              b) Physico-chemical release of oxygen ( from 2® 2 ' trough membranes
                    containing catalatic activity .
               C ) Liquid oxygenation by using inert liquids < f luorocarhons ) for direct
                   gas transfer to the blood .
        3) Development of methods for continuous control and dynamic _ compensation
               of the patient respiratory, circulatory and metabolic deficiencies .
               a ) Dynamic control systems , based on oxygen consumption and carbon
                    dioxide production in the patient , for the regulation of the gas
                    transfer rate in oxygenators .
               b) Regulation of blood electrolytes and pH in the perfused patient .
        In addition to these research objectives ,, the programme should foresee :
        - a one yearly plenary meeting at which an interdisciplinary view of the
             related research and results as well as future trends and plans may be
             obtained by all participants ,
        - inter laboratory meetings and exchange of personnel for short periods to
             familiarize with methods and equipment or actually carry out experiments
             on the spot in close collaboration with the host scientists ,
        -     a project leader .
  £V .   STRUCTURE
         Since the national authorities are responsible for the execution of their
         respective contributions to this concerted action , several Member States
         have dssionated their competent snedical research organizations as active
         participants , while other Member States designated directly the participating
          institutes , which were chosen with regard to their competences , faculties
         and willingness for collaboration .
 ---pagebreak---                                           - c.s                        XII / 269/ 77
     BELGIUM
              - F.N.R.M.   Fonds National de la Recherche Médicale / Bruxelles
     DENHARK
              - Danish Medical Research Council , Copenhagen
     FRANCE
              - INSERM   Institut National de la Santé et de la Recherche Médicale ,
                         Paris
     GERMANY
     01       - German Hearth Centre , Munich
     D2       - Dept . of Physiology , Technical University, Aachen
     D3       - MPI , System-Physiologie , Dortmund
     D4       - Dept . of Physiology , University of Mainz
     IRELAND
              - Medical Research Council of Ireland , Dublin
     ITALY
              - C.N.R.   Consiglio Nazionale della Ricerca , Roma
     NETHERLANDS
     NL1      - University of Groningen
     NL2      - Eindhoven University of Technology
     NL3      - Dept . pf Physiology , University of Nijmegen
     NL4      - Dept . of appl . Physiology and CryobioLogy , Central Red Cross Blood
                Transfusion Service , Amsterdam
     y^II£!L!<INGD0M
              - M.R.C.   Medical Research Council , London
V.   DURATI0N
     A duration of 4 years is proposed for this concerted action .
VI . IMPLEMENTATION
     The concerted action is to be implemented with the agreement of all Member
     States .
     After the Council 's Decision non-Member States involved in European co­
     operation in the field of scientific and technical research ( COST ) will be
     invited to participate .                                        v
     In principle , the competent national authorities are responsible for the
     execution of the national contributions to this action and are prepared to
     integrate the research, covered by this concerted action , into a process of
     co-ordination at Community level over a period of 4 years .
                       V
 ---pagebreak---                                         C.6 -                    XII / 269/ 77
 A Concerted Action Committee is established in which the Member States are
 each represented by one delegate and one alternative who may be assisted by
 experts .                  ....          ...
 Provision will be made for an adequate representation of the participating
non-Member States on the Concerted Action Committee .
The competences of the Committee on Medical and Public Health Research cover
also the implementation of this action ; this Committee is in particular duly
qualified for giving to this research its proper place within the sectorial
policy of the European Communities as well as for ensuring its success .
The Concerted Action Committee is the body in which the exchange of information
between the Member States , CRM and the Commission is staged . The Commission and
the Committee will be assisted by a Project Leader .
Beyond this , the terms of reference of this Committee are essentially         :
-   to assist in the co-ordination of the national research projects executed
 '  in this field and to advise the executing laboratories ;
-   to advise governments and the Commission with regard to research needs in
    this field ;
-   to evaluate the results of research and to draw conclusions with regard
    to their applications ;
-   to promote exchange of experience between the scientists involved by
    organizing symposia , etc . ...;
-   to promote the dissemination of knowledge .
FINANCIAL VOLUME
The financial volume of the research in this field to be executed by the
Member States is estimated at 4,1 m.u.a . for a 4-year period .
This figure is based on estimates , as communicated by the competent national
authorities .
The inventory of the research projects indicates that Belgium , Denmark , France ,
Germany , Ireland , Italy , The Netherlands and United Kingdom would contribute
research under the three topics of this concerted research action .
The cost of co-ordination , on charge of , the Community budget , is estimated
at 360,000 u.a . for the 4-year period .
 ---pagebreak---                                                               ANNEX   I
                     PROFOS.AL FOR A COUNCIL DECISION
                adopting a concerted action in the field of
                        Extracorporeal Oxygenation
                   ( Medical and Public Health Research )
THE COUNCIL OF THE EUROPEAN COMMUNITIES ,
Having regard to the Treaty establishing the European Economic Community ,
and in particular Article 235 thereof ;
Having regard to the proposal of the Commission ;
Having regard to the opinion of the European Parliament ;
Whereas by virtue of Article 2 of the Treaty , the Community has been assigned
the task of promoting throughout the Community a harmonious development of
economic activities , a continuous and balanced expansion and an accelerated
raising of the standard of living ;
Whereas the Council stressed in its Resolution of 14 January 1974 on an
initial outline programme of the European Communities in the field of science
and technology that an appropriate approach should be adopted towards the
whole range of available ways and means , including concerted action and that .
whenever it proves desirable that third countries , particularly European ones ,
should be associated in these projects , steps should be taken to make this'
possible ;
Whereas on 14 January 1974, the Council entrusted the Community Institutions
aided by the Scientific and Technical Research Committee ( CREST ) with the
task of ensuring the gradual co-ordination of national policies in the field
of science and technology ;
Whereas a concerted Community research action in the field of extracorporeal
oxygenation is likely to contribute effectively to the achievement of the
above-mentioned aims ;
Whereas the Member States intend, as part of the rules and procedures appli­
cable to their national programmes , to carry out the research described in
Annex A , and are prepared to integrate such research into a process of co­
ordination at Community level over a period of four years ;
Whereas the carrying out of such research as described in Annex A will require
a financial contribution of about 4,1 MUA from the Member States ;
Whereas the Treaty has not provided the necessary powers for this purpose ;
 ---pagebreak---                                      - C.8
                                                             ANNEX  I
 Whereas the Scientifc and Technical Research Committee ( CREST ) has given its
 opinion with regard to the Commission proposal.;
 HAS DECIDED   :
                                  Article 1
        The Community shall implement for a period of 4 years a concerted action
 in the field of Extracorporeal Oxygenation .
       This action shall consist in the co-ordination at Community level of
research which is described in Annex A and which forms part of the research
programmes of the Member States .
                                  Article 2
       The Commission shall be responsible for such co-ordination .
                                  Article 3
       The maximum financial contribution by the Community tosuch cc-ordination
action is estimated at 360,000 UA , the unit of account being defined according to th
financial regulation in force .
                                  Article 4
       To facilitate the carrying out of the action , a concerted action Committee
on the " Extracorporeal Oxygenation", hereinafter referred to as " the Committee",
is hereby established . A project leader shall bd appointed by the Commission with
the Committee 's agreement . He assists in particular the Commission in its co­
ordinating action .
       The terms of reference and the composition of this Committee are defined
in Annex B.
       The Committee shall draw up its rules of procedure . Its secretariat will
be provided by the Commission .
                                  Article 5
(a)         In accordance with a procedure to be adopted by the Commission in
     agreement with the Committee , the participating States shall exchange re­
     gularly all useful information concerning the execution of the research
     covered by the concerted action and forward to the Commission all information
     useful for co-ordination . They shall also endeavour to provide the Commission
     with information on similar research planned or carried out by bodies for which
     they are not responsible . This information shall be treated as confidential
     if requested by the Member State which provides it .
(b)         The Commission shall prepare yearly progress reports on the basis
     of the information supplied , and shall forward them to the Member States .
(c)         At the end of the co-ordination period , the Commission in agreement
     with the Committee shall forward to the Member States and to the European
     Parliament a general report on the execution and results of the co-ordination
     action . The Commission shall publish this report six months after it has been
     forwarded , unless a Member State objects . In this case the report shall be
 ---pagebreak---                                - C. 9 -                XII / 269/ 77
                                                       ANNEX     I
distributed , at their request ,, solely to the institutions and undertakings
cf which the research or production activities are justifying access to
knowledge resulting from the performance of the research covered by the
Community concerted action . The Commission may make provision that the
reoort remains confidential and is not passed to third parties .
                            Article 6
      In accordance with the provisions laid down in Article 228 of the
Treaty establishing the EEC , the Community may conclude agreements with
other States involved in European Co-operation in the field . of Scientific
and Technical Research ( COST ) with a view to extending the co-ordination
which is the subject of this Decision to research undertaken in those
States .
     The Commission is hereby authorized to open negotiations for the
conclusion of agreements of the type referred to in preceding paragraph .
                            Arti ele. 7
     This Decision shall come into force on the 1st January - 1978.
                                 Done at                      on
                                                       * • f•
                                            For the Council "
                                            The President
 ---pagebreak---                                         - C - 10 -                XII / 269/ 77
                                                                  Annex A to ANNEX I
                      ANNEX A TO THE PROPOSED COUNCIL DECISION
                     adopting a concerted action in the field of
                             Extracorporeal Oxygenation
                         ( Medical and Public Health Research )
The research will be carried out with the purpose of acquiring scientific and
technical knowledge in this field , selected for its importance at Community
level .
The research is expected to cover the following topics :
(1)   Continuous improvemeht in performance of present oxygenator principles
      with respect to the limitations set by diffusion resistance and blood
      trauma   :
      a)   Clinical applicability of introduction of a controlled secondary
           flow ( blood mixing ) into present oxygenator principles .
      b)   Studies of the effects of blood flow shear stress on the aggre­
           gation and adhesion of platelets , of the interaction of red cells
           and platelets , and of pharmacologic methods of intervention .
( 2)  Continuous development of alternative oxygenation principles and testing
      for their clinical applicability .
     Here , research is aiming in particular at further development and joint
      evaluation of the principle of :
      a)   Hyperbaric oxygenation .
      b) Physico-chemical release of oxygen ( from H^O -) through membranes
           containing catalatic activity .
      c)   Liquid oxygenation by using inert liquids (f luorocarbons ) for direct
           gas transfer to the blood .
(3)   Development of methods for continuous control and dynamic compensation
     of the patients respiratory , circulatory and metabolic deficiencies .
      a)   Dynamic control system, based on oxygen consumption and carbon
           dioxide production in the patient , for the regulation of the gas
           transfer rate in oxygenators .
      b)   Regulation of blood electrolytes and pH in the perfused patient .
The co-ordination will include the following competent medical research
organizations respectively participating institutes of the Member States :
BELGIUM
         - F.N.M.R.    Fonds National de la Recherche Médicale , Bruxelles
DENMARK
         - Danish Medical Research Council , Copenhagen
 ---pagebreak---                                        - C.11 -                   XII / 269/ 77
                                                                  Annex A to ANNEX I
 FRANCE
         - INSERM   Institut National de la Santé et de la Recherche Médicale ,
                    Paris
GERMANY                                         ...
         - German Heart Center , Munich                                   ■
         - Dept . of Physiology , Technical University, Aachen
         - MPI , System-Physiology , Dortmund
         - Dept . of Physiology , University of Mainz
IRELAND
         - Medical Research Council of Ireland , Dublin
ITALY
         - C.N.R.   Consiglio Nazionale della Ricerca , Roma
NETHERLANDS                                         /               '
         - Umversity of Groningen
         - Eindhoven University of Technology
         - Dept . of Physiology , University of Nijmegen
         - Dept . of Appl . Physiology and Cryobiology , Central Red Cross
           Blood Transfusion Services , Amsterdam                 !     ?
yNIIED_KINGDOM
         - M.R.C.   Medical Research Council , London
These - countries will contribute research under the three topics mentioned
above .
 ---pagebreak---                                      - C. 12                    XII / 269 / 77
                                                                Annex B to ANNEX I
                   ANNEX B TO THE PROPOSED COUNCIL DECISION
                  adopting a concerted action in the field of
                            Extrscorneal Oxygenation
                       ( Medical and Public Health Research )
Terms of ref erence and composit ion o f the.concerted _ action^Committeg
1.       The Committee shall
   1.1 . Contribute to the optimum execution of the programme by giving
         its opinion on all of its aspects ;
   1.2 . Evaluate the results and draw conclusions as regards to their
         application ;
   1.3 . Ensure the exchange of information referred to in Article 5(a );
   1.4 . Keep abreast of national research being done in the fields
         covered by the concerted action , and more especially of
         scientific and technical developments likely to affect the
         carrying out of the action .
   1.5 . Indicate the orientations to the project leader .
         The Committee 's reports and opinions shall be transmitted to the
   Commission and to the participating States . The Commission shall forward
   these opinions to the CREST .
3.       The Committee shall be composed of one representative and one
   alternative responsible for co-ordinating the national contributions
   to the programme , and the project leader . Each member may be
   accompanied by experts .