Proposal for a European Parliament and Council Decision adopting a programme of Community action 1999-2003 on rare diseases in the context of the framework for action in the field of public health
Date: 1997-05-26
Institutions: European Commission
Subjects: EU programme, action programme, health policy, illness, public health

COMMISSION OF THE EUROPEAN COMMUNITIES 

Brussels,  26.05.1997 
COM(97)  225  final 

97/0146  (COD) 

COMMUNICATION FROM THE COMMISSION 

concerning a programme of Community action on rare diseases within the framework for 
action in the field of public health 

Proposal for a 
EUROPEAN PARLIAMENT AND COUNCIL DECISION 

adopting a programme of Community action  1999-2003 
on rare diseases in the context of the framework for action 
in the field of public health 

(presented by the  Commission) 

COMMUNICATION FROM THE COMMISSION 

concerning a programme of Community action on rare diseases within the framework for 
action in the field of public health 

CONTENTS 

I. 

INTRODUCTION 

IL 

IMPORTANT ASPECTS OF RARE DISEASES 

III.  DEFINITION OF RARE DISEASES 

8 

IV.  OVERVIEW OF PUBLIC HEALTH ACTIONS IN THE MEMBER 
STATES AND INTERNATIONALLY  CONCERNING RARE 
DISEASES 

10 

V*  OVERVIEW OF COMMUNITY ACTIONS RELEVANT TO RARE 

DISEASES 

VI.  COMMUNITY ACTION PLAN 

VII.  CONSULTATION, ASSESSMENT AND REPORTS 

11 

12 

16 

I. 

1 

2 

3 

4 

5 

INTRODUCTION 

In its Communication  of 24 November  1993 on the framework for  action in 
the field of public health1 the Commission defined  objectives  for protection of 
health  as  laid  down  in  Article  3(o)  and  129  of  the  Treaty  establishing  the 
European  Community.  The  role  of  the  Community  is  identified  as 
underpinning  the  efforts  of  the  Member  States  in  the  public  health  field, 
assisting in the  formulation  and  implementation  of  objectives  and  strategies, 
and contributing to the provision  of health protection  across  the  Community, 
setting as a target the best results already obtained in a given area anywhere in 
the Community. 

In initiating action under Article  129, the  Community has to  address  itself to 
preventing  diseases,  particularly  the  'major  health  scourges'  and  protecting 
health.  Based upon criteria laid down in the Cornmission communication, rare 
diseases have been identified as a priority for Community action. 

Public  health  is  by  definition  addressed  to  the  health  needs  of  the  entire 
population.  This  means  that  available  health  services  and  resources, 
particularly  preventive  measures,  should  be  used  for  the  benefit  of  as  many 
people  as possible.  This principle  applies just  as much to  those  affected  by 
rare  diseases  as  it  does  to  those  affected  by  the  'major  health  scourges'. 
However,  the  very  fact  of  the  rareness  of  the  low-prevalence  diseases  and 
conditions  and  the  consequent  lack  of  information  about  them  can  lead  to 
many  affected  by  these  conditions  not  receiving  the  health  resources  and 
services  they  need.  This  is  because  there  may  be  a  particular  shortage  of 
relevant information  and expertise  and a lack of consensus  about  appropriate 
intervention for a specific rare disease. 

The  Commission's  framework  communication  on  public  health  presents 
several  criteria for  deciding  on Community  priorities.  These  are:  a  disease's 
impact on morbidity and mortality, a disease's socio-economic impact, how far 
a  disease  is  amenable  to  effective  preventive  action  and  of  particular 
importance, how far there is scope for Community actions to complement and 
add value to what is being done by the Member States. 

Clearly rare diseases do not meet the criteria on a population level.  However 
at the  level  of the individual  and family  they  do  cause  significant  premature 
morbidity, mortality or loss of disability-free  life.  With regard to whether they 

COM(93) 559  final 

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are preventable, this varies between the thousands  of rare diseases; some  are 
now  so,  some may  become  so  in the  future.  But  the final criterion,  that  of 
providing  added value at  Community  level has  a particular  relevance  to  rare 
diseases. 

It is self-evident that rare or low-prevalence diseases have a limited impact on 
society  as  a  whole  and  are  responsible  for  relatively  little  morbidity  and 
mortality.  They  cannot  therefore  be  considered  as  being  major  health 
scourges.  However,  they  are  by  no  means  unimportant  economically,  for 
providing  effective  advice,  diagnosis  and  health  interventions  tends  to  cost 
disproportionately more than similar provision for more common conditions. 

In this area there is much that the Community can offer.  Work at Community 
level can confer  a number of important benefits.  In particular, because of the 
much larger population of the Community as a whole, individual cases can be 
aggregated to form a much larger group sharing the same characteristics.  This 
provides the opportunity to undertake a much wider range of interventions and 
to initiate co-ordinated  actions with patients who might otherwise  be isolated 
or incorrectly diagnosed. 

The  public  health  importance  of  rare  diseases  can  also  be  considered  in 
another way.  They can sometimes occur with greater frequency in particular 
regions and in specific population groups, such as ethnic communities, than in 
the national population  as a whole.  Thus the  consequences  at national level 
may be slight, but at regional or group level they may be very significant.  This 
is particularly true for genetic diseases. 

Moreover, one should not forget the wider issue of diseases which are rare in 
the European Community but common elsewhere in the world. We could use 
our expertise to provide assistance in the fight against tropical diseases which 
are  rare  in  our  lands  but,  can  cause  huge  suffering  and  loss  of  life  in  the 
developing world. 

In addition, some diseases with a low prevalence  at present may in the  friture 
become major  health scourges.  This is for  instance possible  if the disease is 
caused  by  an  unknown  agent  as  was  the  case  with  HIV/AIDS  or  more 
recently  with Bovine  Spongiform  Encephalopathy/Creutzfeldt-Jacob  Disease 
(BSE/CJD).  A similar effect  can be caused by a newly introduced medicinal 
product, thalidomide being an obvious example.  A co-ordinated  Community 
approach-offers  an effective  way to tackle these potentially large-scale health 
problems. 

11 

12 

13 

Some diseases  and especially communicable  diseases which were  once  very 
common,  such  as  poliomyelitis,  have  become  rare  in  the  Community  as  a 
result  of  effective  preventive  measures,  notably  paediatric  vaccinations. 
However,  such  diseases  can  and  do  re-emerge  if  for  example  population 
immunity falls.  In this connection the sudden appearance  of cases  of such a 
disease  in  one  country  can  provide  an  early  warning  to  others  that  their 
vaccinations  or  other  preventive  measures  may  be  becoming  ineffective. 
Action  at  Community  level  can help  individual  Member  States  to  recognise 
such problems at an early stage and to co-ordinate their response. 

The  aetiology  of many  diseases,  and  especially  rare  diseases,  is  unknown. 
Preventive  measures  are  dependent  upon  this  basic  knowledge.  The 
thousands of rare diseases or conditions, their low prevalence  and the limited 
means and budgets for  scientific research to unravel their aetiologies, make it 
less  likely  that  swift  progress  in  their  treatment  and  cure  will  be  made. 
Therefore  collaboration between the Member  States and work  at Community 
level  in  this  domain  can  provide  added  value  to  the  actions  of  individual 
Member States. 

The  limited  resources  within  health  systems  are  primarily,  and  necessarily, 
directed  at  major  health  scourges,  thus  there  is  likely  to  be  only  limited 
attention  given  to  low-prevalence  diseases  in  individual  Member  States.  It 
falls  within  the  scope  of  the  Community's  public  health  policy  to  help  the 
Member States achieve the most efficient  use of resources in this respect,  hi 
the  case  of  these  conditions  there  may  be  real  economies  of  scale  by 
combining limited national expertise and resources at Community level. 

14 

It is for these reasons that the Commission has decided to  ^VQ  rare  diseases 
priority within the public health framework. 

IL 

IMPORTANT ASPECTS OF RARE DISEASES 

INFORMATION 

15  An unknown number of Europeans suffer from rare diseases.  Many of these 
low-prevalence  diseases  have  no  specific  patient  support  organisation  or 
agency dedicated to research, prevention, diagnosis or treatment.  Information 
of  all  kinds  for  patients  and  their  families,  physicians,  researchers,  health 
authorities and the general public is lacking or poorly disseminated. 

16 

17 

For rare diseases the sources of appropriate detection, recognition and medical 
care  are  limited  or  even  non-existent.  Little  or  nothing  is  available  for 
effective  prevention and treatment; little may be known to  inform  the patient 
and  his  family  about  the  future  course  of  the  disease,  the  possibilities  of 
avoiding  risks  and the  creation  of environments  and life-styles  conducive  to 
health. 

The US National Commission on Orphan Diseases has undertaken a detailed 
study of the problems of people in the USA with these rare  conditions.  This 
found  that it took between  1 and  5 years  for  one third  of them to  receive  a 
proper  diagnosis,  and  15%  went  undiagnosed  for  six  or  more  years. 
Moreover,  the  costs  of these  conditions,  in monetary  and  human  terms,  are 
enormous.  Half the patients said their illnesses caused great financial hardship 
for themselves and their families; and that their diseases prevented them from 
working or attending school. 

PATIENT SUPPORT GROUPS 

18 

Patient help  groups  can play a key role in rare  diseases.  A number  of such 
groups  covering many  rare  diseases  have  been  created  in  the  past  decades, 
sometimes  in  response  to  a  feeling  that  the  statutory  authorities  were  not 
devoting  sufficient  attention  to  these  conditions.  Moreover,  there  is 
considerable collaboration between these groups at regional and national level 
and internationally, often related to the different  groups of diseases.  There are 
also  several  international  umbrella  organisations,  such  as  the  European 
Alliance  of  Genetic  Support  Groups  (EAGS).  These  patient  and  parent 
organisations  have  a wealth  of knowledge  based  upon their  own  experience 
with a disease.  This is particularly valuable given the facts of frequent delay in 
establishing  a diagnosis, the limited knowledge  of health  care  providers,  the 
lack of medicinal products, and health insurance problems. 

CLUSTERS 

19 

20 

In  considering  rare,  low-prevalence  diseases  and  conditions  it  is  useful  to 
address the issue of clusters.  These can be defined  as an aggregation in time 
and place of occurrences of a rare disease.  Another way to put it is that in a 
defined  area during a defined period, conspicuously more cases occurred of a 
rare disease than was predicted from the Tjase-line' or the expected number of 
this  condition.  The need  to  deal  effectively  with  clusters,  (i.e. identifying  a 
real increase, detennining causal factors, assessing  implications and assuaging 
public concern) is obvious: a specific  local factor  could have been the cause, 
or contributed to the cause, and this has to be identified. 

In dealing with clusters the actions taken should follow a particular order:  first, 
identification of a cluster by for example early warning systems; second, using 
monitoring  and  surveillance  systems  to  establish  a  comparison  with  the 
established baselines for the relevant diseases, (however for rare diseases this 
process may not be possible because the necessary epidemiological  data may 
not exist.); third there is the need to allay public concern by communicating as 
accurately  as possible  the risks involved.  Handling  clusters  effectively  has 
great benefits  for  public health.  This is not  merely  because  responding  to a 
particular problem  quickly and adequately can help avoid any possibility of a 
specific cluster developing into a wider problem, but more generally because it 
helps  create  public  confidence  in  the  ability  of  the  authorities  to  safeguard 
health. 

CLASSIFICATION OF RARE DISEASES 

21 

Improper  classification  of  low-prevalence  diseases  and  lack  of  official 
recognition  pose  problems  in  the  recognition,  detection,  treatment  and 
prevention of those diseases.  Diagnoses identified  in the WHO's International 
Classification  of  Diseases  (ICD  10)  are  grouped  into  23  major  categories 
based  on organ systems; these categories  are  subdivided  into 470  diagnosis-
In  some  instances,  there  is  little  emphasis  on  individual 
related  groups. 
diseases in these groups. 

22  Moreover,  the  validity  and  the  usefulness  of  these  classifications  for  low-
prevalence  diseases  is  limited.  There  are  many  instances  in  which  these 
diseases  are not included  in  conventional  classification  systems,  such  as the 
ICD and the British Paediatric Association classification  for birth defects.  In 
other  instances,  low-prevalence  diseases  are  inappropriately  or  inadequately 

classified:  the  ICD  classification  number  assigned  to  Marfan  syndrome,  for 
instance, is shared by more than 20 other conditions. 

23 

The  terms  rare  diseases  or  low-prevalence  diseases  relate  to  perhaps  more 
than  5,000 different  conditions  or illnesses.  There  seems  to be  no  common 
denominator  to  define  the  entity  of  a  rare  disease.  Some  are  based  upon 
syndromes  (the  combination  of  associated  symptoms  or  defects),  or  single 
defects  or  non-associated  conditions.  Obviously,  priorities  have  to  be  set 
when actions at a Community level have to be initiated. 

III.  DEFINITION OF RARE DISEASES 

PROBLEMS WITH A NUMERICAL DEFINITION 

24 

It might seem that a definition  of rare or low-prevalence  diseases based upon 
numbers  of  cases  would  be  straightforward.  However,  in  the  case  of  rare 
diseases these data either do not exist, or if they do, the figures produced  on 
the basis of routine data collections will be broad estimates which are likely to 
understate the true rate. 

25  Difficulties  in estabhshing precise prevalence and incidence rates may arise for 
several reasons: differences  in defining a disease; a lack of specific methods to 
monitor patients with these low-prevalence diseases;  low diagnostic accuracy, 
particularly for the less serious diseases; and finally, distortion  of  information 
between data collection and analysis. 

26  Well-known  diseases  may  be  classified  and  sub-classified  repeatedly.  For 
instance, cancers are often differentiated  by pathologic classifications  so that a 
number would fit numerical criteria for rare cancers.  On the other hand,  the 
classification  of less-understood  diseases is sometimes based upon symptoms 
In  this  way  specific  low-
which  in  fact  group  several  diseases  together. 
prevalence diseases may be subsumed within larger entities. 

8 

DEFINITION BY FIXED NUMBER OR LIMIT 

27  One way to  overcome the problems inherent in using a fixed number for the 
definition  of  rare  diseases  is  to  establish  limits.  The  Commission  services 
have  discussed  this  question  with  national  experts.  Several  possibilities  for 
fixing limits  were  discussed:  a mortality  rate  not  exceeding  a  given  certain 
figure  in  a  certain  number  of  Community  countries,  or  an  incidence  not 
exceeding a given certain value  or a reported prevalence  among  Community 
inhabitants  not  exceeding  a  certain  value.  Another  possibility  might  be  the 
criterion  that  the  condition  is  not  among  the  100  most  common  causes  of 
morbidity and mortality in the European Community. 

PROPOSED DEFINITION 

28 

For  the  purposes  of  this  programme  rare  diseases  will  be  defined  as  life-
threatening  or  chronically  debilitating  diseases  which  are  of  such  low 
prevalence that special combined efforts  are needed.  They are those diseases 
with  a  generally-accepted  prevalence  in  the  total  Community  population  of 
less than 5 per 10,000.  Moreover, the diseases to be specifically  addressed by 
this programme  will be  those where  special  combined  efforts  are needed  to 
ensure  that  there  is  no  significant  prenatal  and  premature  morbidity  or 
mortality,  great  loss  of  quality  of  life  or  socio-economic  potential  for  the 
individual. 

RELATED ISSUES 

29 

In considering actions on rare diseases we need also to take account of other 
related areas of Community work, such as research and the development  and 
marketing  of  orphan  products,  including  pharmaceuticals,  which  are  mainly 
indicated  for  rare  diseases.  Given that rare  diseases  involve  small numbers, 
there is a need to  establish  a population  large  enough for  research  purposes, 
regard. 
such  as  clinical  trials.  The  Community  can  take  action  in  this 
Similarly  the  commercial  interest  for  the  industrial  sector  in  developing 
medicinal products for small numbers of potential patients is limited.  There is 
therefore  a need  to  encourage  investment  within  the  context  of  Community 
industry  policy.  Actions  in  these  areas  can  complement  well  work  in  the 
public health domain. 

30  Within the field of orphan medicinal products, a considerable amount of action 
has been taken at Community level.  Recently, for  example, the  Commission 
has  supported  studies  examining  the  issue  with  a  view  to  formulating  a 

Community  policy.  An  expert  group  was  convened  in  February  1995 
consisting of Commission officials  and experts from both Member States  and 
other countries to consider the findings of the studies and arrive at conclusions. 
During  1995  further  consideration  was  given  to  this  issue,  and  a  Council 
Resolution  on  this  was  adopted  on  20  December  1995,  which  invited  the 
Commission  to undertake  further  work, particularly  on the  development  and 
marketing of orphan products. 

IV.  OVERVIEW OF PUBLIC HEALTH ACTIONS IN THE 
MEMBER  STATES AND INTERNATIONALLY 
CONCERNING RARE DISEASES 

MEMBER STATES 

31  A number  of Member  States  are pursuing work with regard  to  information, 
detection, recognition, intervention and prevention  of particular rare diseases, 
including  support  for  patient  and  parent  groups.  For  example  the  United 
Kingdom has  established  a programme  on Creutzfeldt-Jakob  disease; France 
has  set  up  a  centre  of  information  on  genetic  diseases  and  has  some  well-
established  centres  for  monitoring  and  surveillance  of  birth  defects;  and 
Portugal has a special interest in and is undertaking actions on paramyloidosis. 

0 

32  On the basis of information received from the Member States it would appear 
that only a few Member  States, notably'France, Sweden and Italy, which has 
set  up  a European  School for  Rare Diseases,  are  attempting  to  address  rare 
diseases in a systematic way. 

INTERNATIONAL ACTIONS 

^ 
i 
:>:> 

The country that is very much in the lead on this is the United States. In  1983 
an Orphan Drug act was enacted to speed up the development and marketing 
of  orphan  products.  Also  in  1983  the  National  Organisation  for  Rare 
Disorders  was  set  up; this brings  together  and  assists  the  voluntary  bodies 
which support people with rare diseases.  A National Commission on Orphan 
Diseases was formed in 1985 to review national policy in this area. It reported 
in  1989.  Its main recommendations were that there should be  a central  focal 
point to foster  the development, research  and marketing of orphan products. 
Furthermore an Office  of Rare Diseases at the National Institutes of Health has 
been established. 
Within  the  context  of  co-operation  with  third  countries  and  following  the 
recent Joint EU-US Action plan, the two parties have among others pledged to 

10 

establish  a task force  to  develop  and implement  an effective  global  warning 
system  and  response  network  for  communicable  diseases,  including  rare 
diseases,  while  co-operating  on  respective  programmes  on  health-related 
matters and in the research  field. 

V.  OVERVIEW OF COMMUNITY ACTIONS RELEVANT TO 

RARE DISEASES 

COUNCIL 

34 

In  its  Resolution  of  20  December  19952  the  Council  and  the  Ministers  for 
Health,  meeting  within  the  Council,  invited  the  Commission,  in  close  co 
operation with the competent authorities of the Member States to take stock of 
the knowledge and experience available in the Member States, the Community 
and international organisations and to look into the situation of orphan drugs in 
Europe  in relation to rare diseases. 

EUROPEAN PARLIAMENT 

35 

In its Resolution A4-0311/953 on the Medium-Term Social Action Programme 
1995-1997 the Parliament asked the Commission to present, under the proper 
in  the 
procedures,  the  action  programme  for  rare  diseases  foreseen 
Commission's framework communication on public health. 

ECONOMIC AND SOCIAL COMMITTEE 

36 

In its wide-ranging  Opinion  of 6 July  1994  on the  Commission's framework 
communication  on public  health  it  urged  the  Commission  to  adopt  a  broad 
approach to the subject and emphasised the importance of rare diseases. 

OJC350 30.12.95 p.3 
OJ C 032  05.02.96, p. 15-24 

11 

VI.  COMMUNITY ACTION PLAN 

EUROPEAN COMMUNITY INFORMATION ON RARE DISEASES 

37  Accurate  information  is  essential  for  ensuring  effective  interventions  in  rare 
diseases.  The most immediate need  of anyone with  a rare  disease  is for  an 
accurate  diagnosis,  followed  closely  by  the  need  for  treatment  and  support 
services.  Once diagnosed, patients  and their families  are  anxious to find  out 
all there is to know about their disease and often become experts on it.  They 
want information  about the cause, prognosis, genetic basis (if any), and  future 
manifestations  of  the  disease,  the  availability  of  effective 
therapeutic 
interventions  or,  if  none  exists,  how  to  cope  with  the  disease,  as  well  as 
information  on current research.  Patients want also information  about  support 
groups and treatment or focal centres. 

* 

38  All these kinds of information,  where they exist at all, are widely  dispersed. 
Moreover, available information may relate to a disease in general or a group 
of  people,  but  it  may  be  specific  to  an  individual,  which  will  necessitate 
appropriate  safeguards  for  confidentiality.  A  further  problem  is  that  several 
different  groups  apart from those  directly  concerned  in  an  individual  case 
have  a  need  for  information  at  various  levels  of  detail.  These  include 
physicians and researchers, governmental agencies, patient support groups and 
the pharmaceutical industry. 

39 

40 

In the Hght of the major  advances being made in genetics  and  of the  current 
difficulties  in obtaining up to date information  on rare diseases, set out above, 
there  is  a  pressing  need  for  a  Community  information  database  on  rare 
diseases and for a system for gathering and disseminating data. 

In developing such a Community system, there must be close liaison with the 
Community's  telematics  programme.  This  might  help  define  the  technical 
requirements  for  the  database  and  system  and  determine  the  most  effective 
mechanisms for  disseminating the information  to the  different  interest  groups 
and the relevant agencies in the Member  States.  A telematic network linking 
those  working  in  the  field  would  also  provide  a  mechanism  for  the 
identification  of  relevant  research  and  researchers  and  for  the  exchange  of 
information. 

41 

The objective  of Community  action  could be to provide  a better  information 
about  rare  diseases  especially  for  patients,  health  professionals  and 
researchers. 

12 

42 

The actions to be taken to achieve this objective could include: 

encouragement  and  support  for  the  establishment  of  a  European  rare 
diseases  database, with entries listing the disease name, synonyms, a  general 
description  of  the  disorder,  symptoms,  causes,  diagnostic  tests  available, 
affected  population,  standard  treatments,  investigational  treatments  (when 
available) and a list of resources that can be contacted for further  information 
about the condition; 

promoting access to information  and co-ordinating existing  information 
systems  and  services  by  supporting  the  setting  up  and  strengthening  of 
networks at local, regional, national and community level; and 

organising  consensus meetings  among health professionals  in  order to 
improve the early detection, recognition, intervention  and  prevention  of  rare 
diseases. 

PATIENT AND FAMILY SUPPORT GROUPS 

43 

These  organisations  have  a wide-ranging  role.  They  support  the  collection, 
dissemination  and  exchange  of  knowledge  and  experiences,  foster  public 
awareness and stimulate research and raise ethical issues.  They  also provide 
counselling for individuals and ensure that patients' interests  are  safeguarded, 
for  example  in  terms  of  confidentially  and  informed  consent  to  clinical 
procedures.  There  is  a  need  to  promote  the  development  of  these  patient 
support groups so that all areas of the Commumty are properly covered and to 
encourage their co-operation at regional, national and European level.  There 
is also a need to estabhsh one or more umbrella organisations  at Community 
level which can undertake a clearinghouse, linking and support role.  There are 
already some organisations, such as the European Alliance of Genetic Support 
Groups (EAGS), that might be able to develop their activities in this way. 

44  One  of the  objectives  of Community  action could be to  estabhsh,  foster  and 
strengthen  voluntary  organisations  involved  in  supporting  people  directly  or 
indirectly  affected  by  rare  diseases,  such  as  various  neurodegenerative 
conditions. 

13 

45 

The actions to be taken to achieve this objective could include: 

promoting the establishment  of groups of those persons with the same 
rare  conditions  or those professionally  involved  in order  to  disseminate  their 
experiehce, to  facilitate  training and to  co-ordinate  their  activities  at national 
and Community level; 

promoting the groups' collaboration and networking and the  setting  up 
and fostering of umbrella bodies, focusing particularly on  efforts  to  encourage 
the continuity of work and cross-national co-operation. 

HANDLING OF RARE DISEASES CLUSTERS 

46  Handling  clusters  of  cases  effectively  involves  analysing,  assessing  and 
managing the problem and communicating clearly to the public.  Such action is 
both  necessary  and  difficult.  The  necessity  is  clear  since  any  local  factor 
which might have been the causative or contributing agent has to be identified. 
But  it  is  also  difficult  because  there  are  many  reasons  for  a  cluster  to  be 
identified,  and all possibilities need to be considered and investigated before a 
particular causal association is proposed.  However, clusters occur only rarely 
in any particular region.  This means that there is little  opportunity  for  those 
involved in an individual case to gain the necessary experience. 

47 

48 

In this  situation  there  would  be  value  in  estabhshing  within  the  Community 
'Rare  Disease  Cluster  Response  Teams',  involving  those  with  appropriate 
expertise which would be available to  give assistance  to the local  authorities 
concerned.  The  experience  gained  recently  with  Creutzfeldt  Jacob  disease 
indicates the need for  such an approach  enabling the best use to be made of 
scarce expertise in risk assessment and management. 

In  the  case  of  clusters  of  rare  diseases  there  is  a  need  for  the  creation  of 
networks  of  focal  points  for  particular  rare  diseases  or  groups  of  related 
diseases, which would help in providing early warnings of potential problems, 
co-ordinating the investigation of clusters and provide relevant information,  for 
example  on expected  prevalence  levels, to  the response  teams.  These  focal 
points will need  a high level of expertise  in  epidemiology  and  statistics,  and 
the  epidemiological  information  that  is  available  on  low-prevalence  diseases 
from  monitoring and surveillance programmes, both those at Community level 
and those undertaken nationally and regionally. 

14 

49  As mentioned above, epidemiological data for rare diseases  are not  currently 
comprehensive.  Such  data  depend  on  effective  monitoring  and  surveillance 
programmes.  The majority  of rare  diseases  are  congenital  disorders,  and in 
this  area  a  monitoring  and  surveillance  programme  has  been  set  up: 
EUROCAT  (European  Registration  of  Congenital  Anomalies).  This  is  a 
concerted action with mainly participants from the Member States who locally 
and sometimes regionally study a population and investigate the number, type 
and  possible  causes  of  birth  defects  in  order  to  pre^nt  these  congenital 
malformations.  The  Commission  contributes  financially  to  EUROCAT. 
Other birth defects  monitoring programmes  exist  in the  Member  States,  and 
collaboration with these programmes and with programmes that monitor other 
(groups of rare diseases) is necessary to permit an optimal use and analysis of 
the available data. 

50 

The objective of Community action would be to ensure an efficient  handling of 
the problem of clusters, which is of key importance for rare diseases. 

51 

The actions to be taken to achieve this objective could include: 

supporting  the  monitoring  (sentinel)  of  rare  diseases,  including  birth 
defects,  genetic  disorders  or  diseases  of  different  organ  systems  and  the 
appropriate  techniques  for  low-prevalence  diseases,  in  order to  meet  on the 
one hand  the demands  of detection, treatment  and research  and on the  other 
hand the demands of relevant statistical monitoring ; 

promoting  the  creation  of  rare  diseases  response  teams  and  of 

specialised training courses for those investigating clusters ; 

estabhshing surveillance systems and detecting timely possible clusters; 

and 

encouraging  the  exchange  of  expertise  in  the  evaluation,  assessment, 
communication  and  management  of  clusters  of  rare  diseases  that  are 
associated with exogenic causes. 

ORPHAN PRODUCTS 

52 

In the  context  of the  Community's  work  on the  control  and  authorisation  of 
pharmaceutical products, a legislative proposal is being prepared which has the 
aim of providing a legal framework for 'orphan medicinal products'.  This will 
cover the following  areas: designation of orphan medicinal products;  support 
of research; market access; and monitoring, including pharmacovigilance. 

15 

As part  of this proposal,  the  Commission  intends  to propose  a  definition  for 
such  products,  along  the  following  lines:  any  substance  or  combination  of 
substances presented as proprietary medicinal product which is: 

used  for  the treatment, prevention  or diagnosis  of a life-threatening  or 

chronically debilitating disease in human beings, 

where that disease indication affects not more than 5 per  10,000 people 

in the European Community, and 

where the commercial return is  insufficient. 

16 

EUROPEAN  COMMUNITY  RESEARCH  ON  RARE  DISEASES  AND 
ORPHAN PRODUCTS 

53 

The  Fourth  Framework  Programme  (1994  -  1998)  for  Research  and 
Technological Development4 namely the Biomedecine and Health programme 
(Biomed2), area  1 "Pharmaceutical research" and area 4.6  "Research  on rare 
diseases" covers the research  activities  on the  development  of  orphan  drugs 
and supports the basic and clinical research on rare diseases 

54  Under the area of "Rare Diseases" the research tasks include the definition of 
diagnostic  criteria,  causes,  genetic  aspects,  and methods  of prevention,  with 
emphasis  on  the  establishment  of  European  epidemiological  observatories, 
information  networks, and registries of patients with rare diseases in order to 
increase information available on rare diseases. 

55  Under the area of "Pharmaceutical research" the aim is to support research on 
the treatment of rare diseases, including methodologies for fast-track  schemes 
in the development of orphan drugs and repositories of available orphan drugs 
in Europe. 

VII.  CONSULTATION, ASSESSMENT AND REPORTS 

CONSULTATION 

56 

The actions of this programme will be implemented in close collaboration with 
the Member  States, particularly as regards  co-ordination  of their policies  and 
programmes.  To facilitate  this, the  Commission proposes  the  creation  of an 
Advisory  Committee  of representatives  of  the  Member  States.  Appropriate 
links  will  also  be  maintained  with  the  WHO,  other  relevant  international 
organisations  and third  countries  in accordance  with the requirements  of the 
programme's actions. 

EVALUATION REPORTS 

5 7  Assessment of the programme will be provided in two reports : 

a  mid-term  report  to  the  Council,  the  European  Parliament,  the 
Economic  and  Social  Committee,  and  the  Committee  of  the  Regions.  The 

4 

Decision 94/1110/EC of 26..04.1994, OJL126,  18.05.94, p.l, as amended by Decision 96/616/EC of 
25.03.1996, OJL86, 04.04.96, p.69 

17 

purpose  of the mid-term report  is to  ensure  that  the  Commumty  Institutions 
and,  through them,  all the parties  concerned, are kept  fully  informed  on the 
progress of the actions undertaken.  It will include information  on the projects 
supported under the different actions. 

a  final  report  on  the  implementation  of  the  programme,  which  will 
include  an  evaluation  of  the  actions  undertaken,  will  be  submitted  to  the 
above-mentioned  institutions  by the  Commission  after  the  completion  of the 
programme. 

GENERAL INFORMATION ACTIVITIES 

58 

59 

The Commission will ensure that reports on the activities undertaken are made 
available to concerned parties and the general pubhc. 

Future Community pubhc health action on rare diseases must take account of 
the existing large body of  work, in particular that undertaken under Articles 
129 and  130f of the EC Treaty.  In accordance with Article  129 of the Treaty, 
the Community shall contribute towards ensuring a high level of human health 
protection  by  encouraging  co-operation  between  Member  States,  lending 
support  to  their  actions  and  promoting,  in  close  contact  with  them,  co 
ordination  of their policies  and programmes,  and fostering  co-operation  with 
third  countries  and  international  orgamsations  competent  in  the  sphere  of 
pubhc health. 

18 

Proposal for a 
EUROPEAN PARLIAMENT AND COUNCIL DECISION 

adopting a programme of Community action 1999-2003 on rare diseases 
in the context of the framework for action in the field of public health 

H 

EXPLANATORY  MEMORANDUM 

1 

2 

3 

4 

5 

6 

7 

In  its  Communication  COM(93)  559  final  of  24  November  1993  on  the 
framework  for action in the field of pubhc health, the Commission outlined the 
principles  and  strategy  to  be  followed  in  undertaking  Community  activities 
directed  towards  the  attainment  of  the  objectives  on  health  protection  laid 
down  in  Articles  3(o)  and  129  of  the  Treaty  estabhshing  the  European 
Community. 

The  role  of  the  Community  is  identified  as  underpinning  the  efforts  of  the 
Member  States  in  the  pubhc  health  field,  assisting  in  the  formulation  and 
implementation  of objectives  and strategies, and contributing to the provision 
of health protection across the Community, setting as the target the best results 
already obtained in a given area anywhere in the Commumty. 

In  accordance  with  Article  129, the  Commission  presents  proposals  for  the 
adoption  by the European  Parliament  and  the  Council  of incentive  measures 
intended  to  contribute  towards  ensuring  a  high-level  of  human  health 
protection. 

The aforementioned  Commission communication sets out criteria on which to 
determine  priority  areas  for  Community, action  programmes.  In  accordance 
with these criteria, rare diseases were identified as such a priority area. 

The  present  Commission  proposal,  based  on  Article  129  and  already 
announced in the Commission programme of work for  1996, comes under the 
principle  of  shared  competence  between  the  Community  and  the  Member 
States, and seeks to improve information  on rare diseases, support for patient 
groups  and  risk  analysis  and  risk  management  in  case  of  clusters  of  rare 
diseases.  This Community action will follow the principles of subsidiarity and 
proportionality. 

According  to  the  principle  of  subsidiarity,  action  on  matters  not  under  the 
exclusive competence of the Community, such as action on rare diseases, must 
be undertaken by the Community only if and in so far as, by reason of its scale 
or effects,  it may be better achieved at Community level. 

Rare diseases  are those  diseases  with  a generally-accepted  prevalence  in the 
total  Community  population  of  less  than  5 per  10,000.  The  diseases  to  be 

2C 

specifically  addressed  by  this  programme  will  be  those  where  special 
combined efforts  are needed to ensure that there is no significant  prenatal and 
premature  morbidity  or  mortality,  great  loss  of  quality  of  life  or  socio 
economic potential for the individual. 

8 

The proposed 5-year action programme seeks to complement ongoing work in 
the  Member  States  by  actions  addressed  to  the pubhc,  health  professionals, 
and the authorities. 

9  With the limited resources available it would be impractical for  a Community 
pubhc health programme to address all the approximately  5,000 rare  diseases 
and all aspects of rare diseases. 

10 

11 

12 

In selecting objectives and defining  actions to be included in the programme, 
account has been taken of the situation currently existing in the Member States 
and  at  Community  level  in  the  field  covered  by  the  programme.  The 
programme  aims  at  bringing  about  an  accelerated  and  effective  sharing  of 
information,  support  for  patient  groups  and  umbrella  orgamsations,  and  the 
efficient  establishment  of cluster response  teams, and  increased  co-operation 
of Member States.  This will avoid unnecessary duplication of work and speed 
up the adoption of the best  solution to problems  common to  all the Member 
States concerning such diseases. 

Finally,  the  criterion  of  providing  added  value  at  Community  level  has  a 
particular relevance to rare diseases, all of the activities involved being of such 
unique scale and effect  as to provide added value to all Member States. 

This  programme  is  undertaken  on  the  basis  of  a European  Parhament  and 
Council  decision  pursuant  to  Article  129. 
It  does  not  come  under  the 
exclusive  competence  of  the  Community,  and  does  not  require  the 
harmonisation of national provisions in the field covered. 

13  An  evaluation  of  the  actions  implemented  under  the  programme  will  be 
provided  in two  reports:  a mid-term  report  reviewing progress  and  a  final 
report  on  the  implementation  of  the  programme.  These  reports  will 
incorporate  information  on  Community  financing  in  the  various  fields  of 
action as well as the results of evaluations.  They will be transmitted  to the 
Council  and  the  European  Parliament,  as  well  as  to  the  Economic  and 
Social Committee and the Committee of the Regions. 

a\ 

Proposal for a 
EUROPEAN PARLIAMENT AND COUNCIL  DECISION 

adopting a programme of Community action 1999-2003 on rare diseases 
in the context of the framework for action in the field of public health 

THE EUROPEAN PARLIAMENT  AND THE COUNCIL  OF THE  EUROPEAN 
UNION 

Having regard to the Treaty estabhshing the European  Community, and in particular 
Article 129 thereof, 

Having regard to the proposal from the Commission,1 

Having regard to the opinion of the Economic and Social Committee,2 

Having regard to the opinion of the Committee of the Regions,3 

Acting in accordance with the procedure referred to in Article 189b of the Treaty, 

1.  Whereas,  the  very  fact  of  the  rareness  of  the  low-prevalence  diseases  and 
conditions  and  the  consequent  lack  of  information  about  them  can  lead  to 
people  affected  by  these  conditions  not  receiving  the  health  resources  and 
services they need; 

2.  Whereas, for the purposes of this programme rare diseases will be defined  as 
life-threatening  or  chronically  debilitating  diseases  which  are  of  such  low 
prevalence that special combined efforts  are needed to address them;. 

3.  Whereas, in accordance with point (o) of Article 3 of the Treaty, Community 
action  shall  include  contribution  towards  the  attainment  of  a  high  level  of 
health protection; 

4.  Whereas  Article  129  expressly  provides  for  Community  competence  in  this 
field  in so far as the Community contributes to it by encouraging co-operation 

1 
2 
3 

OJ -n° 
OJ  n° 
OJ  n° 

11 

between the Member States and, if necessary, lending support to their action; 
promoting  co-ordination  of their policies  and programmes,  and  fostering  co 
operation with third countries and international orgamsations competent in the 
sphere  of  pubhc  health;  whereas  Community  action  should  be  directed 
towards the prevention of diseases, and the promotion of health education and 
information; 

5.  Whereas rare diseases have been identified  as a priority area for  Community 

action within the framework for action in the field of pubhc health4; 

6.  Whereas in its Resolution  (A4-0311/95) on the Medium-Term  Social Action 
Programme  1995-19975  the  Parhament  asked  the  Commission  to  present, 
under the proper procedures, the action programme for rare diseases  foreseen 
in the Commission's framework communication on pubhc health; 

7.  Whereas, in accordance  with the principle  of  subsidiarity,  action  on matters 
not under the exclusive competence of the Community, such as action on  rare 
diseases, must be undertaken by the Community  only if and in  so far  as, by 
reason of its scale or effects, it may be better  achieved at Community level; 

8.  Whereas, the Commumty can provide added value to the actions of Member 
States  concerning  rare  diseases,  through  the  co-ordination  of  national 
measures,  the  dissemination  of  information  and  experiences,  the  joint 
establishment  of priorities, the  development  of networking  as  appropriate, 
selection  of  European  Community-wide  projects  and  the  motivation  and 
mobilisation of all involved; 

9.  Whereas  co-operation  with  the  international  organisations  competent  in  the 

field  of pubhc health and with third countries should be fostered; 

10.  Whereas,  by  providing  support  for  acquiring  better  knowledge  and 
understanding of,  and wider dissemination  of information  about rare  diseases 
and by developing actions complementary to existing Community programmes 
and  actions,  while  avoiding  unnecessary  duplication,  the  programme  will 
contribute to the achievement of the Community  objectives  set out in Article 
129; 

11.  Whereas,  in  order  to  increase  the  value  and  impact  of  the  programme,  a 
continuous  assessment  of the  actions undertaken  should  be  carried  out, with 

COM (93) 559  final 
OJN°C32  05.02.96, p. 15-24 

/3> 

particular regard to their effectiveness  and the  achievement  of the  objectives 
set and, with a view where appropriate, to making the necessary adjustments; 

12.  Whereas  this  programme  should  be  of five-year duration  in  order  to  allow 
sufficient  time for actions to be implemented to achieve the objectives set; 

13.  Whereas  the  introduction  of  specific  Community  arrangements  will  help  to 
ensure  that  all  Member  States  are  swiftly  informed  in  the  event  of  an 
emergency situation, so that the protection of the population can be ensured; 

14.  Whereas 

these  Community  arrangements  for 

the  rapid  exchange  of 
information  do  not  affect  the  Member  States'  rights  and  obligations  under 
Treaties or bilateral and multilateral conventions; 

15.  Whereas an agreement on a modus vivendi  between the European Parhament, 
the Council and the Commission concerning measures for  the implementation 
of acts  adopted under the procedure laid  down in Article  189b of the Treaty 
was reached on 20 December 1994. 

16.  Whereas  this  decision  lays  down,  a  financial  framework  constituting  the 
principal point of reference, within the meaning of point  1 of  the Declaration 
of  the  European  Parhament,  the  Council  and  the  Commission  of  6  March 
1995, for the budgetary authority during the annual budgetary procedure; 

17.  Whereas the Community's financial perspective is valid up until  1999 and 

will have to be revised for the period beyond that date; 

18.  Whereas  the financial framework for  the  last  four  years  of  the  programme 
(2000-2003) shall be determined after the establishment of the future financial 
perspectives; 

^ 

HAVE DECIDED AS FOLLOWS: 

Article 1 

Establishment of the programme 

1. 

2. 

A programme of Commumty action on rare diseases hereinafter  referred  to as 
"this  programme",  is  hereby  adopted  for  the  period  1 January  1999  to  31 
December  2003  in  the  context  of  the framework for  action  in  the  field  of 
pubhc health. 

The aim of this programme  is to  contribute towards  ensuring  a high  level  of 
health  protection  in relation  to  rare  diseases  by  providing  knowledge  about 
these diseases by promoting and strengthening patient  support  groups  and by 
fostering the setting up of cluster response teams. 

3. 

The  actions  to  be  implemented  under  this  programme  and  their  specific 
objectives are set out in the Annex under the headings: 

1) 
2) 
3) 

Actions on Community information on rare diseases-
Actions in support of patient and family support groups 
Actions on handling rare diseases clusters 

Article 2 

Implementation 

1.  The  Commission  shall  ensure  implementation,  in  close  co-operation  vvitli  the 

Member States, of the actions set out in the Annex. 

2.  The Commission shall  co-operate with institutions and organisations  active in 

the field of rare diseases. 

2s 

Article 3 

Budget 

1. 

The financial  framework  for  the  implementation  of the  programme  for  the 
year  1999  shall  be  ECU  1,3  Million,  in  keeping  with  current  financial 
perspectives.The  financial  framework  for  the  final  four  years  of  the 
programme 
the 
establishment of the future  financial  perspectives. 

(2000-2003)  shall  be  determined 

in  detail  after 

2. 

The annual appropriations  shall be  established  by the Budgetary Authority in 
accordance with the financial perspectives. 

Article 4 

Consistency and  complementarity 

The Commission shall ensure that there is consistency and complementarity  between 
the  Community  actions  to  be  implemented  under  this  programme  and  those 
implemented under other relevant Community programmes and actions. 

Article 5 

Committee 

1. 

In implementing this action plan, the Commission shall be assisted by an advisory committee, 
hereinafter  referred  to  as  "the  Committee",  consisting  of  two  representatives  from  each 
Member State, and chaired by  the Commission representative. 

The representative of the Commission shall submit to the Committee a draft  of 
the measures to be taken concerning, in particular: 
(a) 

the criteria, and procedures for selecting and financing projects 
under this programme; 
the evaluation procedure. 

(b) 

The Committee shall deliver its opinion on the draft, within a time limit which 
the  chairperson  may  lay  down  according  to  the  urgency  of  the  matter,  if 
necessary by taking a vote. 

2U 

The opinion shall be recorded in the minutes; in addition, each Member  State 
shall have the right to ask to have its position recorded in the minutes. 

The Commission shall take the utmost account of the opinion delivered by the 
Committee.  It shall inform the Committee on the manner in which its opinion 
has been taken into account. 
The  representative  of  the  Commission  shall  keep  the  Committee  regularly 
informed  about  Commission  proposals  or  Community  initiatives  and  the 
implementation of programmes in other pohcy areas which are relevant to the 
achievement of the objectives of this programme. 

Article 6 

International  co-operation 

1. 

2. 

In  the  course  of  implementing  this  programme,  co-operation  with  third 
countries and with international organisations  competent in the field of pubhc 
health shall be fostered. 

This programme  shall be  open to participation by the associated  countries  of 
Central  Europe  (CEC),  in  accordance  with  the  conditions  laid  down  in  the 
Association  Agreements  or  Additional  Protocols  related  thereto  concerning 
participation  in  Community  programmes.  This  programme  shall  be  open  to 
participation by Cyprus and Malta on the basis of additional appropriations in 
accordance  with  the  same  rules  as  those  apphed  to  the  EFTA  countries,  in 
accordance with procedures to be agreed with those countries. 

Article 7 

Monitoring and evaluation 

1 

In  the  implementation  of  this  Decision,  the  Commission  shall  take 
the  necessary  measures  to  ensure  the  monitoring  and  continuous 
evaluation  of  the  programme  taking  account  of  the  general  and 
specific  objectives referred  to in Article  1 and in the Annex. 

2> 

During  the  third  year  of  this  programme,  the  Commission  shall 
present to the European Parliament and to the Council an evaluation 
report 

The  Commission  shall  submit  to  the  European  Parliament  and  the 
Council a final report on completion of this programme. 

The Commission shall incorporate into these two reports information 
on  Community  financing  in  the  various  fields  of  action  and  on 
complementarity  with the  other  actions  referred  to  in  Article 4,  as 
well as the results of the evaluations. It  shall also  send them to the 
Economic and Social Committee and the Committee of the Regions. 

Done at Brussels, 

For the European Parhament 
The President 

For the Council 
The President. 

«=) S 

ANNEX 

SPECIFIC OBJECTIVES AND ACTIONS 

I. 

ACTIONS ON COMMUNITY INFORMATION ON RARE 
DISEASES 

Objective: 
professionals  and researchers. 

to provide knowledge about rare diseases especially for patients, health 

1. 

2. 

3. 

Encouragement and support for the establishment  of a European rare  diseases 
database,  with  entries  listing  the  disease  name,  synonyms,  a  general 
description  of  the  disorder,  symptoms,  causes,  affected  population,  standard 
treatments, investigational treatments  (when available)  and  a list  of resources 
that can be contacted for further information about the condition. 

Promoting  access  to  information  and  co-ordinating  existing  information 
systems  and  services  by  supporting  the  setting  up  and  strengthening  of 
networks at local, regional, national and community level. 

Organising consensus meetings among health professionals in order to improve 
the early detection, recognition, intervention and prevention of rare diseases. 

II.  ACTIONS IN SUPPORT OF PATIENT AND FAMILY 

SUPPORT GROUPS 

Objective: 
supporting people directly or indirectly affected  by rare diseases. 

to  estabhsh,  foster  and  strengthen  voluntary  organisations  involved 

in 

4. 

Promoting  the  establishment  of  groups  of  persons  with  the  same  rare 
conditions  or  those  professionally  involved  in  order  to  disseminate  their 
experience, to facilitate  training  and to  co-ordinate  their  activities  at  national 
and Community level. 

n 

Promoting  the  groups'  collaboration  and  networking  and  the  setting  up  and 
fostering  of umbrella bodies, focusing particularly on efforts  to encourage the 
continuity of work and cross-national co-operation. 

III.  ACTIONS ON HANDLING RARE DISEASES CLUSTERS 

Objective: 
key importance for rare diseases. 

to ensure an efficient  handling of the problem of clusters, which is of 

6. 

7. 

8. 

9. 

Supporting the monitoring (sentinel)  of rare  diseases, including birth  defects, 
genetic  disorders  or  diseases  of  different  organ  systems  and  the  appropriate 
techniques for low-prevalence  diseases, in order to meet on the one hand the 
demands  of  detection,  treatment  and  research  and  on  the  other  hand  the 
demands of relevant statistical monitoring. 

Promoting  the  creation  of  rare  diseases  response  teams  and  of  specialised 
training courses for those investigating clusters. 

Supporting surveillance and early warning systems for clusters. 

Encouraging  the  exchange  of  expertise  in  the  evaluation,  assessment, 
communication and management of clusters of rare diseases that are associated 
with exogenic causes. 

FINANCIAL STATEMENT 

1 

TITLE OF OPERATION 

Proposal for a European Parhament and Council Decision adopting a programme of 
Community action on rare diseases in the context of the framework for action in the 
field  of pubhc health 

2 

BUDGET HEADING INVOLVED 

.  B3-..... 

3 

LEGAL  BASIS 

Article 3(o) and Article 129 of the Treaty estabhshing the European Community. 

4 

DESCRIPTION OF OPERATION 

4.1  General objective 

To contribute to achieving the objectives laid down by the Treaty: 

under Article 3 (o), the Commumty is required to make a contribution to the 

attainment of a high level of health protection; 

Article  129 requires  the  Community  to  contribute  towards  ensuring  a high-
level of human health protection, in particular by encouraging co-operation  between 
the Member  States, and if necessary lending support to their action,  promoting  co 
ordination  of their pohcies  and  programmes,  and  fostering  co-operation  with  third 
countries and the competent international organisations in the sphere of public health. 
Community action is directed towards the prevention of diseases, in particular major 
health  scourges, by promoting research  into their  causes  and their  transmission,  as 
well as health information and education. 

The general  objective  of the action programme  is  to  contribute  towards  ensuring a 
high level of health protection on rare diseases. 

The method for achieving this objective consists of undertaking actions which: 

31 

provide the opportunity to undertake a much wider range of interventions and 
to  initiate  co-ordinated  actions  with  patients  who  might  otherwise  be  isolated  or 
incorrectly diagnosed. 

provide information on rare diseases 
strengthen the organisation and setting up of patient and family support groups 
enforce the setting up of response teams involved in handling clusters of rare 

diseases. 

4.2  Period covered and arrangements for renewal or extension 

5 years: 01.01.1999 to 31.12.2003 
Report  on  implementation  to  be  transmitted  to  the  Council  and  European 

Parliament during the third year of the programme 

Report  to  the  Council  and  European  Parhament  after  completion  of  the 

programme together with the results of evaluations. 

5 

CLASSIFICATION OF EXPENDITURE OR REVENUE 

Non-compulsory expenditure 
Differentiated  appropriations 

6  TYPE OF EXPENDITURE OR REVENUE 

Subsidy for joint financing with other sources in the pubhc and/or private sector (not 
exceeding a certain percentage of the total cost of the proposed projects). 
The level of funding granted depends on the scope of the measure to be financed and 
on  the  extent  to  which  the  action  programme  is  reflected  in  the  various  activities 
planned.  Such funding  will not  exceed  70% of the total budget  earmarked  for  the 
proposed projects except in the case of networks and work ordered and of direct use 
to the Commission, where the subsidy may amount to 100% . 

32 

7 

FINANCIAL IMPACT 

7.1  Method of calculating the total cost of operation (definition of unit cost) 

The  method  of  calculation  is  the  result  of  experience  acquired  in  previous  activities  related  to 
environmental health. This encompasses the various types of Community action listed in Table 4 
of Commission  Communication  COM(93)  559 final  of 24 November  1993, and  represents  10 
years  of  know-how  in  financing  cooperative  efforts  with  the  Member  States  and  NGO's  of 
collection,  analysis  and  dissemination  of  information,  setting  up  of  networks,  survey  of  the 
quality of campaigns such as European weeks, establishment  of mechanisms and procedures  of 
consultation  and  cooperation  for  setting  common  objectives  and  for  policy  coordination  and 
for  the  formulation  and  development  of  strategies  at  the  Community  level.  The specific  cost 
estimates  are  based  on  the  assumption  that  half  of  the  activities  to  be  undertaken  under  this 
programme will require 100 percent funding while the other half will require 50 percent funding and 
that the activities to be undertaken will involve most  or all of the Member  States. An  amount  of 
ECU  1.3  million  is  deemed  necessary  for  the  implementation  of  these  activities  for  the  year 
1999. The new budget  framework  for  the final  four  years will be established  in the year  2000 
taking into  account  the future  Community's  financial  perspectives.  The annual allocations will 
be decided in accordance with the normal budgetary procedures. 

7.1.1  Data base about rare disease for patients, health professionnals and researchers 

Establishment  of  european  rare  diseases.data base, with  entries  listing  the  disease  name, 
synonyms,  a  general  description  of  the  disorder,  symptoms,  causes,  affected  population, 
standard treatments, investigational treatments (when available) and a list of resources that 
can be  contacted  for  further  information  about  the  condition.  The  setting  up  of this  data 
base in 1999 is calculated as 600.000 Ecus. 
Organising  consensus  meetings  on  rare  diseases  among  health  professionals  in  1999 will 
cost  100.000 Ecus. 

7.1.2  Establishment of voluntary organisations on rare diseases 

Meetings  in  order  to  promote  the  establishment  of  voluntary  organisations  involved  in 
supporting people affected  by rare diseases in 1999 : 200.000 Ecus. 

7.1t3  Efficient  handling of clusters of rare diseases 

Setting up monitoring facilities of (sentinel) rare diseases will cost 300.000 Ecus in 1999. 

The creation of rare diseases "response teams" and setting up training courses to investigate 
clusters will cost 100.000 Ecus in 1999. 

3i |  H 

7.2 

Itemised breakdown of cost (in ECU  million) - indicative programming 

OBJECTIVE 

ACTION AREA 

YEARS 

1999 

2000 

2001 

2002 

2003 

TOTAL 

To provide knowledge 
about rare diseases 
especially for patients, 
health professionals and 
researchers 

0.6 

Encouragement and support for the establishment 
of a European rare diseases database, with entries 
listing the disease name, synonyms, a general 
description of the disorder, symptoms, causes, 
affected population, standard treatments, 
investigational treatments (when available) and a 
list of resources that can be contacted for further 
information about the condition. 

Promoting access to information and co-ordinating 
existing information systems and services by 
supporting the setting up and strengthening of 
networks at local, regional, national and 
community level. 

-

Organising consensus meetings among health 
professionals in order to improve the early 
detection, recognition, intervention and prevention 
of rare diseases. 

01 

-

-

-

-

0.6 

-

-

-

-

-

-

-

-

0.1 

35 

OBJECTIVE 

ACTION AREA 

YEARS 

1999 

2000 

2001 

2002 

2003 

TOTAL 

To establish, foster and 
strengthen voluntary 
organisations involved in 
supporting people 
directly and indirectly 
affected  by rare diseases. 

| 

Promoting the establishment of groups of those 
persons with the same rare conditions or those 
professionally involved in order to disseminate 
their experience, to facilitate training and to co 
ordinate their activities at national and Community 
level. 

-

Promoting the groups' collaboration and 
networking and the setting up and fostering of 
umbrella bodies, focusing particularly on efforts to 
promote the continuity of work and cross-national. 
co-operation. 

0.2 

-

-

-

-

-

-

-

-

-

0.2 

:s6 

i! 

OBJECTIVE 

ACTION AREA 

YEARS 

To ensure an  efficient 
handling of the problem 
of clusters, which is of 
key importance for  rare 
diseases. 

Supporting the monitoring (sentinel) of rare 
diseases, including birth defects, genetic disorders 
or diseases of different organ systems and the 
appropriate techniques for low-prevalence diseases, 
in order to meet on the one hand the demands of 
detection, treatment and research and on the other 
hand the demands of relevant statistical monitoring 

1999 

2000 

2001 

2002 

2003 

TOTAL 

0.3 

-

-

-

-

0.3 

Promoting the creation of rare diseases response 
teams and of specialised training courses for those 
investigating clusters. 

0.1 

Supporting surveillance and early warning systems 
for clusters. 

Encouraging the exchange of expertise in the 
evaluation, assessment, communication and 
management of clusters of rare diseases that are 
associated with exogenic causes. 

T O T AL 

_ 

_ 

_ 

_ 

0.1 

-

-

-

-

-

1.3 

p.m. 

p.m. 

p.m. 

p.m. 

1.3 

37 

TOTAL 

1.3 

0.78 

0.52 

7.3 

Indicative schedule of appropriations (in ECU million) 

1999 

2000 

2001 

2002 

2003 

1.3 

0.78 

0.52 

Commitment 
appropriations 

Payment 
appropriations 

1999 

2000 

2001 

2002 

2003 

Subsequent 
years 

TOTAL 

1.3 

p.m. 

p.m. 

p.m. 

p.m. 

1.3 

8  FRAUD PREVENTION MEASURES; RESULTS OF MEASURES 

TAKEN 

The grant application forms will require information  on the identity and nature of 
potential beneficiaries so that their reliability can be assessed in advance. 

38 

Fraud  prevention  measures  (checks,  intermediate  reports,  final  report)  are 
included  in  the  agreements  or  contracts  between  the  Commission  and 
beneficiaries.  The Commission will check reports and ensure that work has been 
properly carried out before intermediate and final payments are made. 

In addition, spot checks are carried out by the Commission to verify  how  funds 
have  been  used.  Checks have  already  been  carried  out  in  other  public  health 
budget lines in relation to the financial years  1991 to  1995 and have shown their 
effectiveness. 

9 

ELEMENTS OF COST-EFFECTIVENESS ANALYSIS 

9.1  Specific and quantifiable objectives 

The Community measures  aim at  contributing towards  ensuring  a high level  of 
health protection  on rare  diseases  by providing knowledge  about  rare  diseases 
especially  for  patients,  health  professionals  and  researchers,  and  to  establish, 
foster  and  strengthen  voluntary  organisations  involved  in  supporting  people 
directly  and  indirectly  affected  by  rare  diseases,  and  by  ensuring  an  efficient 
handling of the problem of clusters, which is of key importance for rare diseases . 
by the accomplishment of the following specific objectives: 

The indicators showing whether or not these objectives are achieved will include 
measures of the following kinds: 

dissemination of information on rare diseases to patients, health 
professionals and researchers; 
establishment of a European rare diseases data base; 
availability of consensus documents about the detection, recognition, 
intervention and prevention of rare diseases; 
presence and functioning of local, regional, national and Commumty 
patient organisations active in the field of rare diseases; 
presence of umbrella bodies at Community level for the promotion of 
collaboration on different rare diseases; 
existence of rare diseases response teams and of specialised trading, 
surveillance, early warning systems related to clusters of  rare diseases. 

Target Population 

39 

1. 

2. 

3. 

Competent  health  authorities  of the Member  States,  at  national,  regional 
and local level and competent international  organisations  in the sphere of 
public health; 
Patient  support  groups,  health  professionals,  health  and  medical 
associations, academic institutions etc.; 
NGO's  and  other  bodies  interested  in  health  matters,  and  the  public  in 
general. 

9.2  Grounds for the operation 

In  initiating  action  under  Article  129, the  Commumty  has  to  address  itself  to 
preventing diseases and protecting health.  The Commission's communication on 
the framework  for action in the field for public health1 sets out criteria  on which 
to determine priority areas for Community programmes.  In accordance with these 
criteria 
the  framework  Communication  evaluated  the  different  options  for 
addressing diseases, in particular major  scourges and their underlying causes, by 
various types of community actions and retained on the basis of criteria listed in 
that communication, eight priority areas of which rare diseases was one. 

For the purposes of this programme rare diseases  are defined  as  life-threatening 
or chronically debilitating diseases which are of such low prevalence that special 
combined efforts  are needed as shown on the basis of an ex-ante evaluation . 

The programme  aims  at  bringing  about  an  accelerated  and  effective  sharing  of 
information  and  experience,  Community  wide  understanding  of  key  issues  and 
questions on tackling rare diseases, and increased co-operation of Member States 
so as to avoid unnecessary duplication of work and speed up the adoption of best 
solution to problems  common to Member  States  concerning such diseases. This 
input  envisaged  for  the  Community  and  the  Commission  by  Article  129  of the 
Treaty provides a clear common framework of rules. 

As  regards  the  intervention  methods  and  the  allocation  of  funds,  the  following 
will apply: 

specific application of the principle of subsidiarity when identifying 
measures to be undertaken and co-financed; 
identification and selection of projects for co-financing in the fields of rare 
diseases 

COM(93) 559 final of 23.11.93 

40 

the concept of added Commumty value, which will continue to be realised 
in particular through the co-ordination of national measures, the 
dissemination of information and experiences, the establishment of 
priorities, the development of networking as appropriate, selection of 
European projects and the motivation and mobilisation of all involved. 

Two methods will be employed to implement the programme.  One is to support 
projects carried out in Member States and at the Community level.  The selection 
of priority projects  is based  largely  on general and intermediate  objectives,  and 
implementation  of  the  measures  themselves  depends  on  the  quality  and 
effectiveness  of projects submitted to the competent department during the course 
of the year.  The other is to undertake specific  activities necessary to achieve the 
objectives of the programme, which will be fully financed by the programme. 

The selection criteria for projects are as follows: 

Compatibility with the objectives and conformity with at least one of the 
established objectives; 
Examination of the "added Community value" of the projects (transnational 
participation, development of a model applicable in other Member States, 
information usable in other Member States, etc.); 
Presumed effectiveness  and profitability; 
Clarity and justification of requirements; 
Relevance of selected methodology; 
Organisational competence and experience; 
Suitability of budget for objectives; 
Support for projects from national partners; 
Objective assessment; 
Opinion of the advisory committee involved. 

The budget proposed of  1.3 MECU for the first year of this programme matches 
that proposed  at the same time for  the Community action programmes  on  injury 
prevention and pollution-related diseases. This reflects the equal priority attached 
to these fields for  action  determined  by the  Commission  communication  on the 
framework  for  action  in the field of public  health  (1993),  an  evaluation  which 
remains valid today. The amount proposed represents the bare minimum required 
to start the programme. 

9.3  Monitoring and evaluation of the operation 

41 

9.3.1  Monitoring of the operation 

Monitoring at the Community level is to be carried out by the Commission, which 
will submit a report half-way through the implementation of the programme, and a 
final report  after  its  completion  to  the  Council,  the  European  Parliament,  the 
Economic  and  Social  Committee,  and  the  Committee  of  the  Regions,  drawing 
from  national reports as well as evaluations of the actions under the programme 
and of individuals projects. 

9.3.2  Evaluation 

Evaluation will be by means of: 

An evaluation of the main measures and of subsidised projects involving, 
where necessary, the participation of independent experts; 
An evaluation report during the third year; 
An overall report on the quality and effectiveness  of projects implemented 
under the action plan, to be submitted by the Commission to the other 
Commumty institutions after completion of the programme. 

Performance indicators selected for this evaluation: 

Evaluation of projects by Commission officials  and/or those co-operating 
with them; 
Analysis of intermediate reports on measures scheduled and financed, 
allowing a shifting of emphasis where possible; 
Impact studies by external bodies 
Relevance of the methodology used by organisers; 
Suitability of the budget for the objectives; 
Skills and experience of bodies; 
Dissemination of results; 

Evaluation procedures and intervals: 

Drawing up of intermediate and final reports on the various measures 
undertaken in the  field; 
Development of a "standard" evaluation form for the measure, to be 
forwarded by the beneficiaries with their final reports, and checking of 
these documents by officials  either at the Commission or in the  field. 

42 

10 

ADMINISTRATIVE EXPENDITURE (PART A OF THE BUDGET) 

Actual  mobilisation  of  the  necessary  administrative  resources  will  be  conditioned  by  the 
Commission's  annual  decision  on  the  allocation  of  resources,  having  regard  in  particular  to 
additional staff and funds provided by the budgetary authority. 

10.1 

Impact on the number of employees 

Types of employees 

staff carrying out action 

source of em 

Dloyee 

duration 

permanent 
employees 

temporary 
employees 

from within DG 
or service 

Officials  or 
temporary 
agents 

A 
B 
C 

Other resources 

Total 

1 
1 
1 

3 

0 
0 
0 

0 

1 
1 
1 

3 

10.2  Financial impact of supplementary  staff 

10.3 

Increase in other running costs arising from the action 

supplem 
entary 
staff 

0 
0 
0 

0 

Budget line 

Amounts 

Method  of calculation 

Meetings 
A2510 

104,250 ECU's 

2 meetings of advisory committee/year,  ' 
1  representative/Member  State = 
2 meetings/year x  15 representatives x 695 
ECU/representatives  x 5 years =  104,250 
ECU'S 

4-3 

The resources necessary to cover the expenditure below for the 5-year period will be obtained by re 
deployment  of  existing  financial  resources  and  the  use  of  supplementary  resources  will  not  be 
required. 

a) 

b) 

Personnel Expenses (Title Al,  A2 and A5) 
3 x  100,000 ECU'S x 5 years =  1,500,000 ECU's 

Operational Expenses 
Expenses for meetings (A-250) 

2 meetings/year x  15 experts x 825 ECU's/expert  x 5 years =  123,750 ECU's 

Expenses for travel (A-130) 

24 missions/year Brussels-Luxembourg x 200 ECU's/mission x 5 years = 

24,000 ECU'S 

60 missions/year to Member States x  1000 ECU's/mission x 5 years = 

300,000 ECU's 

c) 

Total: 

1,947,750 ECU's 

44-

ISSN 0254-1475 

COM(97) 225 final 

DOCUMENTS 

EN 

05 

Catalogue number  : CB-CO-97-217-EN-C 

ISBN  92-78-19712-2 

Office  for Official  Publications of the European Communities 

L-2985 Luxembourg 

4-S~