COMMISSION STAFF WORKING DOCUMENT EXECUTIVE SUMMARY OF THE IMPACT ASSESSMENT REPORT ON THE REVISION OF THE 'CLINICAL TRIALS DIRECTIVE' 2001/20/EC Accompanying the document Proposal for a Regulation of the European Parliament and of the Council on clinical trials on medicinal products for human use, and repealing Directive 2001/20/EC
Date: 2012-07-17
Institutions: European Commission
Subjects: administrative formalities, bio-ethics, experiment on humans, harmonisation of standards, market approval, medical research, medicinal product, testing

EUROPEAN COMMISSION 

Brussels, 17.7.2012  
SWD(2012) 201 final 

COMMISSION STAFF WORKING DOCUMENT 

EXECUTIVE SUMMARY OF THE IMPACT ASSESSMENT REPORT ON THE 
REVISION OF THE 'CLINICAL TRIALS DIRECTIVE' 2001/20/EC 

Accompanying the document 

Proposal for a Regulation of the European Parliament and of the Council 

on clinical trials on medicinal products for human use, and repealing Directive 
2001/20/EC 

{COM(2012) 369 final} 
{SWD(2012) 200 final} 

EN 

   EN 

 
 
 
 
  
 
COMMISSION STAFF WORKING DOCUMENT 

EXECUTIVE SUMMARY OF THE IMPACT ASSESSMENT REPORT ON THE 
REVISION OF THE 'CLINICAL TRIALS DIRECTIVE' 2001/20/EC 

Accompanying the document 

Proposal for a Regulation of the European Parliament and of the Council 

on clinical trials on medicinal products for human use, and repealing Directive 
2001/20/EC 

1. 

1. 

2. 

3. 

4. 

5. 

PROBLEM DEFINITION 

Clinical  trials  in  the  sense  of  the  Clinical  Trials  Directive  are  investigations  of 
medicines  in  humans  where  the  medicines  are  applied  outside  normal  clinical 
practice on the basis of a research protocol. Applications for marketing authorisation 
and  publications  in  medical  journals  are  based  on  data  generated  in  clinical  trials. 
Therefore,  clinical  trials  are  essential  to  develop  medicinal  products  and  improve 
medical treatment.  

Clinical trials are regulated by the Clinical Trials Directive 2001/20/EC. The key aim 
of  the  Directive  is  to  ensure  safety  and  rights  of  subject,  and  reliability  and 
robustness of data generated in a clinical trial. 

The Clinical Trials Directive is criticised by all stakeholders (ranging from patients 
to  researchers  and  industry)  for  having  caused  a  significant  decline  in  the 
attractiveness of patient-oriented research and related studies in the EU. Indeed, the 
number of clinical trials applied for in the EU has fallen from 5028 (2007) to 4400 in 
2010.  This  trend  greatly  reduces  Europe’s  competitiveness  in  the  field  of  clinical 
research and, thus, has a negative impact on the development of new and innovative 
treatments  and  medicines.  The  main  problems  identified  relate  to  the  following 
issues: 

Separate  submission  and  diverging  assessments  and  regulatory  follow-up  of 
applications  for  clinical  trials:  Clinical  trials  are  subject  to  an  authorisation 
(submission and assessment) and regulatory follow-up/supervision. The submission, 
assessment and regulatory follow-up for the same clinical trial are conducted in the 
different  Member  States  completely  separate  from  another.  Moreover,  within  each 
Member  State,  two  distinct  bodies  are  involved:  the  national  competent  authority 
(NCA)  and  one  or  more  Ethics  Committee(s)  (EC).  This  system  induces  elevated 
administrative burdens, and cumbersome hurdles to conduct research with associated 
delays of access to innovative, potentially life-saving, treatment.  

Greater difficulties with conducting clinical trials due to regulatory requirements not 
adapted to practical considerations and needs: The risk to patient safety in a clinical 
trial can vary widely, depending on in particular the extent of knowledge and prior 
experience with the medicine which is object of the clinical trial (the 'investigational 

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6. 

2. 

7. 

8. 

9. 

medicinal product' - IMP). It is critical to take into account whether or not the IMP is 
already  authorised  in  the  EU  or  elsewhere.  However,  the  Clinical  Trials  Directive 
does  not  sufficiently  address  these  differences  in  risk  and  take  them  into  account. 
Instead,  the  obligations  and  restrictions  laid  down  in  the  Directive  apply  largely 
irrespectively  of  the  risk  to  subject  safety  and  without  matching  practical 
considerations and requirements. 

Reliability of clinical trial data in a globalised research environment: There is a trend 
towards globalisation of clinical research, in particular towards emerging economies. 
Clinical research on a global scale is of benefit to the countries participating, to their 
populations  and  to  global  public  health.  However,  the  globalisation  of  clinical 
research  poses  a  challenge  when  it  comes  to  supervision  of  compliance  with  good 
clinical practice (GCP).  

ANALYSIS OF SUBSIDIARITY 

Union  legislation  on  clinical  trials  is  based  on  Article  114  of  the  Treaty  on  the 
Functioning of the European Union (TFEU). Based on Article 114 of the TFEU, the 
EU exercises a shared competence.  

Harmonised  rules  open  up  the  possibility  of  referring  to  the  results  and  findings  of 
clinical trials in applications for an authorisation for placing a medicinal product on 
the  Union  market.  This  is  critically  important  as  practically  all  larger  clinical  trials 
are  often  performed  in  more  than  one  Member  State.  To  address  this  issue,  the 
Clinical  Trials  Directive  lays  down,  at  Union  level,  the  exhaustive  rules  to  be 
complied with for clinical trials. 

While  regulation  of  clinical  trials  is  compatible  with  the  principle  of  subsidiarity, 
there are limits set by the Treaties which have to be considered when formulating the 
policy options: The Treaty sets limits concerning the harmonisation of ethical aspects 
(i.e. in particular the need to obtain ‘informed consent’ from the subject). Moreover, 
there are several  aspects which are of an intrinsically national nature, such as rules 
for establishing who is a ‘legal representative’ of a subject and rules on the liability 
for damages suffered by a subject.  

3. 

OBJECTIVES 

•  Objective No 1: A modern regulatory framework for submission, assessment and 
regulatory  follow-up  of  applications  for  clinical  trials,  taking  into  account  the 
multinational  research  environment.  This  means  the  operational  objectives  of 
reducing administrative burdens and operational costs, and reducing delays for the 
launch of the clinical trial, as far as they are caused by regulation. 

•  Objective  No  2:  Regulatory  requirements  which  are  adapted  to  practical 
considerations,  constraints  and  needs,  without  compromising  the  safety,  well-
being  and  rights  of  participants  in  clinical  trials  and  without  compromising  data 
robustness.  This  means  the  operational  objectives  of  reducing  administrative 
burdens  and  operational  costs  as  regards  two  key  regulatory  requirements:  the 
annual safety report and the obligatory insurance/indemnification. 

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•  Objective No 3: Addressing the global dimension of clinical trials when ensuring 
compliance  with  GCP.  This  means  the  operational  objective  of  ensuring 
compliance with GCP of clinical trials conducted in non-EU countries. 

4. 

POLICY OPTIONS 

4.1. 

Objective No 1 — A modern regulatory framework for submission, assessment 
and regulatory follow-up of applications for clinical trials 

4.1.1.  Policy  option  No  1/1  —  No  action  at  Union  level  and  reliance  on  voluntary 

cooperation of Member States (baseline option) 

4.1.2.  Policy option No 1/2 — Single submission with separate assessment 

10. 

This policy option would consist of central submission, via an IT gateway located at 
EU-level, and subsequent separate assessment in each Member State concerned. 

4.1.3.  Policy option No 1/3 — Single submission with joint assessment by Member States of 

issues not related to ethical aspects 

11. 

This  policy  option  would  consist  of  central  submission  and  subsequent  joint 
assessment  by  the  Member  States  where  the  clinical  trial  takes  place.  Under  this 
policy  option  the  involvement  of  the  Commission  or  the  Agency  (apart  from  the 
single submission point, see above) would be limited to technical support of the joint 
assessment, and to acting as 'facilitator' in the joint assessment.  

4.1.4.  Policy option No 1/4 — Single submission with central assessment by the Agency of 

issues not related to ethical aspects 

12. 

13. 

This  policy  option  would  consist  of  central  submission  and  subsequent  central 
assessment by a scientific committee located and administered within the European 
Medicines Agency ('Agency'). 

In addition, each Member State concerned would issue a national decision covering 
the ethical aspects of the clinical trial. 

4.1.5.  Policy option No 1/5 – Choice of legal form: adopting the text of the Clinical Trials 

Directive in the form of a Regulation 

4.1.6.  Policy option No 1/6 – Combination of policy option No 1/3 (joint assessment) and 

No 1/5 (legal form of a Regulation) 

4.2. 

Objective No 2 — Regulatory requirements adapted to practical considerations 
and needs  

4.2.1.  Policy option No 2/1 — No action at Union level (baseline option) 

4.2.2.  Policy option No 2/2 — Enlarging the scope of non-interventional trials 

14. 

The Clinical Trials Directive applies only to ‘interventional trials’, but not to ‘non-
interventional’  trials.  Non-interventional  trials  are  trials  with  authorised  medicines, 
where  subjects  are  not  assigned  in  advance  and  where  no  additional  intervention 

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takes place. This policy option would broaden the scope of non-interventional trials 
by removing the last requirement (additional intervention). Consequently, the scope 
of the Clinical Trials Directive would be narrowed. 

4.2.3.  Policy option No 2/3 — Excluding ‘non-commercial sponsors’ 

15. 

The requirements laid down by the Clinical Trials Directive are particularly onerous 
for sponsors who do not always have the means and resources to comply with them. 
This  mainly  applies  to  ‘non-commercial  sponsors’.  ‘Non-commercial  sponsors’  are 
usually  universities  or  academic  institutes,  foundations  or  charities.  This  policy 
option  would  follow  the  example  of  the  U.S.  and  Japan  by  excluding  ‘non-
commercial sponsors’ from the scope of the regulation of clinical trials. 

4.2.4.  Policy  option  No  2/4  —  Removing  regulatory  requirements  on  the  basis  of  the 

knowledge of the IMP 

16. 

This  policy  option  would  remove  certain  regulatory  requirements  (for  example  the 
compulsory insurance/indemnity and the obligatory annual safety report) for clinical 
trials  with  authorised  medicinal  products  used  for  the  authorised  indication  or  with 
IMPs used in a well-known use. 

4.2.5.  Policy option No 2/5 — Insurance/Optional ‘national indemnification mechanism’ 

17. 

is 

relevant  only 

the  obligatory 
This  policy  option 
insurance/indemnity. It would put Member States under an obligation to provide for 
an indemnification mechanism for clinical trials performed on their territory, taking 
account of the national legal system for liability. It would be optional for sponsors to 
join this national indemnification mechanism. 

issue  of 

the 

for 

4.2.6.  Policy option No 2/6 – Combination of policy option No 2/4 and No 2/5 

18. 

This policy option is only relevant as far as the obligatory insurance/indemnification 
is  concerned:  Low-risk  clinical  trials  would  be  excluded  from  the  obligatory 
insurance/indemnification  (policy  option  No  2/4).  Other  clinical  trials  would  be 
covered by the obligatory indemnification mechanism (policy option No 2/5). 

4.3. 

Objective  No  3  —  Addressing  the  global  dimension  of  clinical  trials  when 
ensuring compliance with GCP 

4.3.1.  Policy option No 3/1: Leaving the situation as it is (baseline option) 

19. 

The  ‘self-regulation’  option  would  mean  continuing 
to  rely  on  voluntary 
commitment on the part of sponsors to ensure that clinical trials in non-EU countries 
are  performed  in  accordance  with  GCP,  regulatory  supervision  and  inspections  by 
non-EU  countries  in  their  jurisdictions,  and  some  inspections  by  the  inspectors  of 
Member States in the framework of applications for marketing authorisation. 

4.3.2.  Policy option No 3/2: Facilitating GCP inspections by increasing transparency 

20. 

This  option  would  put  sponsors  under  an  obligation  to  register  publicly  all  clinical 
trials  whose  results  are  used  subsequently  in  an  application  for  authorisation  of  a 
clinical trial or for marketing authorisation for a medicinal product. This would allow 

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enforcement  authorities  to  intervene  and  police  these  clinical  trials.  It  would  also 
build up pressure for sponsors to comply with GCP. 

4.3.3.  Policy  option  No  3/3:  Inspections  of  non-EU  countries'  regulatory  systems  for 

clinical trial 

21. 

This option introduces the possibility for the Commission or the Agency to conduct 
'system inspections' in non-EU countries, in order to assess whether their regulatory 
and enforcement system for clinical trials is equivalent to that in the EU. 

4.3.4.  Policy option No 3/4: GCP inspections by the Agency in non-EU countries 

22. 

Under  this  option  the  Agency  or  Commission  would  be  empowered  to  performing 
inspections in clinical trial sites in non-EU countries without drawing on inspection 
capacity provided voluntarily by Member States.  

4.3.5.  Policy option No 3/5: Combination of policy option No 3/2 and No 3/3 

5. 

ASSESSMENT OF IMPACTS 

5.1. 

Objective No 1 — A modern regulatory framework for submission, assessment 
and regulatory follow-up of applications for clinical trials 

5.1.1.  Policy  option  No  1/1:  No  action  at  Union  level  and  reliance  on  voluntary 

cooperation of Member States (baseline option) 

23. 

In  terms  of  social/health  impacts,  the  current  ‘patchwork’  of  separate  assessment 
procedures  for  clinical  trials  by  each  Member  State  concerned  does  not  necessarily 
ensure  the  highest  possible  standard  of  assessment  in  the  EU.  Moreover,  the  same 
clinical trial may be subject to different changes and adjustments in the authorisation 
procedure. These divergences can have an impact on data generated in the trial. If the 
conduct  and  design  of  the  trial  diverge  too  much,  sponsors  decide  to  withdraw  the 
clinical  trial  from  one  or  more  Member  States.  This  means  that  patients  in  those 
Member States are deprived of the potential benefits of clinical research, which leads 
to inequalities in public health. 

24. 

In terms of economic impact the Clinical Trials Directive creates administrative costs 
of  approximately  306 m  EUR  per  year  and  operational  non-administrative  costs  of 
approximately 2 200 m EUR per year. 

5.1.2.  Policy option No 1/2 — Single submission with separate assessment 

25. 

26. 

As regards the impact on terms of health and patient safety there would be no change 
compared with the present situation.  

In terms of economic impact this policy option would reduce administrative costs to 
45.5m EUR. In terms of operational costs, however, the situation would be identical 
to  policy  option  No  1/1,  as  this  policy  option  is  limited  to  an  IT-tool  to  submit 
information. In terms of implementation costs, the one-off costs for IT and to running 
costs  vary  depending  on  the  technical  solution  and  range  between  1.62m  EUR  and 
6.3m  EUR  one-off  costs,  plus  running  costs  between  0.34m EUR  (plus  0.25  FTE) 

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and 1.26m EUR (plus 19 FTEs). The choice as to which technical solution is to be 
pursued is intrinsically linked to the decision as to where the single submission point 
is located at the Agency or at the Commission. This is a political decision to be taken 
at a later stage, to which the impact assessment serves as aid. 

5.1.3.  Policy option No 1/3 — Single submission with joint assessment by Member States of 

issues not related to ethical aspects 

27. 

28. 

29. 

In  terms  of  social/health  impact,  the  protection  and  the  safety  and  rights  of 
participants  would  improve  as  compared  with  the  baseline  option,  as  expertise  of 
different  Member  States  would  be  brought  together.  A  uniform  response  to  the 
request for conducting a clinical trial would allow quicker start of a clinical trial on 
the  basis  of  an  identical  protocol,  thus  removingthe  inequalities  identified  in  the 
baseline option. 

In terms economic impact, this policy option would have largely the same impact as 
No  1/2.  It  would  reduce  administrative  costs  to  34.3 m  EUR,  a  saving  of  271.7 m 
EUR per year compared with the baseline option. In terms of operational costs, this 
policy  option  would  lower  the  costs  for  performing  clinical  trials  in  the  EU 
considerably (savings would be in the range of 440 m EUR).  

Depending on the extent of the support structure resource needs are between 1.5 and 
7 FTEs. The choice as to the scale of the support structure is linked to the decision 
who  provides  the  support  structure:  the  Agency  or  at  the  Commission.  This  is  a 
political decision to be taken at a later stage, to which the impact assessment serves 
as aid. 

5.1.4.  Policy  option  No  1/4:  Single  submission  with  central  assessment  by  the  Agency  of 

issues not related to ethics 

30. 

31. 

In  terms  of  social/health  impact,  this  policy  option  has  the  benefit  of  involving  all 
Member States, thus assembling the best expertise of regulators available. However, 
this option might lead to additional delays in the start of a clinical trial because the 
dual  approval  system  (national  and  EU  level)  is  likely  to  lead  to  contradictions, 
hence  creating  additional  delays  in  solving  these.  Moreover,  the  involvement  of 
every Member State, including Member States not necessarily concerned, would add 
to the  complexity  of the discussions and  of finding a compromise. In addition, this 
policy  option  would  lead  to  an  ‘institutional  continuum’  between  the  authorisation 
procedure for clinical trials throughout development of a medicinal product and the 
marketing authorisation of the resultant product. This carries the risk of removing a 
'fresh pair of eyes' that assesses the data at the end of the development process during 
the marketing authorisation application. 

In  terms  of  economic  impact/costs,  this  policy  option  would  lead  to  savings  of 
264.2 m EUR in administrative costs. In terms of operational costs, the impact would 
be  similar  to  policy  option  No  1/3,  i.e. savings  of  approximately  440 m EUR.  In 
terms of implementation costs, these would relate largely to an additional role of the 
Agency. It can be estimated that the additional staff needs would be in the range of 
4 000 FTEs. 

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5.1.5.  Policy  option  No  1/5  —  Choice  of  legal  form  —  Adopting  the  text  of  the  Clinical 

Trials Directive in the form of a Regulation 

32. 

This policy option would ensure that the Member States would base their assessment 
of an application for authorisation of a clinical trial on an identical text, rather than 
on various, inevitably diverging, national transposition measures. 

5.1.6.  Policy option No 1/6 – Combination of policy option No 1/3 (joint assessment) and 

No 1/5 (legal form of a Regulation) 

33. 

In this policy option the joint assessment (pol. opt. No 1/3) would be strengthened by 
a legal text in the form of a Regulation (No 1/5). This would facilitate cooperation 
between Member States in the assessment of a clinical trial application. 

5.2. 

Objective No 2 — Regulatory requirements adapted to practical considerations 
and needs 

5.2.1.  Policy option No 2/1: No action at Union level (baseline option) 

34. 

35. 

The  obligatory  insurance/indemnity  ensures  that,  in  case  of  damages  caused  by  a 
clinical trial, the subject receives compensation — irrespective of the financial means 
of the sponsor or investigator. The annual safety report can be a useful tool for NCAs 
or  ECs  to  supervise  and  follow  up  the  safety  profile  of  an  IMP,  particularly  if  the 
compound is still largely unknown and not yet authorised. 

The  yearly  costs  for  the  obligatory  insurance/indemnity  and  the  safety  report  are 
approximately  222.8 m EUR,  plus  administrative  costs  of  7.2 m EUR.  On  the  other 
hand,  approximately  0.025 %  of  all  subjects  successfully  claim  compensation  for 
damages  suffered  in  a  clinical  trial.  Each  damages  claim  is  worth,  on  average, 
between 3 000 and 6 000 EUR. 

5.2.2.  Policy option No 2/2 — Enlarging the scope of non-interventional studies 

36. 

In  terms  of  social/health  impact  the  immediate  impact  would  be  that  these  studies 
would be regulated at national level by Member States. Depending on the measures 
taken by each Member State, this would mean tighter, looser or no regulation of this 
type of study. In terms of economic impact/costs this policy option would generate 
savings of 16.98m EUR operational costs, plus 219 000 EUR administrative costs. 

5.2.3.  Policy option No 2/3 — Excluding ‘non-commercial sponsors’ 

37. 

In terms of social/health impact, subjects enrolled in a clinical trial run by an ‘non-
commercial  sponsor’  would  not  be  protected  at  EU  level.  Nor  would  the  EU  rules 
ensuring  the  robustness  and  reliability  of  data  apply.  This  would  be  a  major 
drawback in terms of a creating a level playing field for conducting clinical trials in 
the EU without compromising on protection of rights and safety of patients in the EU 
and data robustness in the EU. This policy option would also have a negative impact 
on  public  health  in  general.  Clinical  trials  run  by  ‘non-commercial  sponsors’  can 
have  a  crucial  impact  on  public  health  as  the  results  may  be  published  and,  thus, 
impact to the choice of treatment options and treatment in general.  

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38. 

In  terms  of  economic  impact/costs  this  policy  option  would  generate  savings  of 
73.9m EUR operational costs, plus 926 000 EUR administrative costs. 

5.2.4.  Policy  option  No  2/4:  Removing  regulatory  requirements  on  the  basis  of  the 

knowledge of the IMP 

39. 

Clinical trials with authorised medicinal products pose a risk to public health which 
is  typically  only  minimally  higher  to  that  posed  by  standard  care,  if  at  all.  Thus, 
removing the obligatory insurance/indemnity and the obligation to submit an annual 
safety  reporting  would  have  no  discernible  impact  on  subject  protection.  In 
particular,  regarding  insurance,  if  an  (unlikely)  damage  occurs,  there  would  be  a 
number  of  additional  types  of  insurance  such  as  product  liability  insurance  of  the 
marketing  authorisation  holder  for  the  authorised  medicine,  and  professional 
negligence insurance by the treating physician. 

40. 

In  terms  of  economic  impact/costs  this  policy  option  would  generate  savings  of 
34m EUR (operational costs) and 438 000 EUR administrative costs. 

5.2.5.  Policy option No 2/5 —Insurance/optional ‘national indemnification mechanism’ 

41. 

42. 

A  national  indemnification  mechanism  would  give  the  same  assurance  of 
compensation 
obligatory 
the 
insurance/indemnity currently required by the Clinical Trials Directive.  

suffering 

damages 

subject 

any 

for 

as 

Administrative  and  operational  costs  for  sponsors  would  be  limited  and  produce 
important savings compared to the baseline option. In terms of implementation costs, 
as  the  number  of  damage  claims  granted  is  very  limited,  costs  for  Member  States 
would be limited to approximately 0.817m EUR per year. 

5.2.6.  Policy option No 2/6 – Combination of policy option No 2/4 and No 2/5 

43. 

The  impact  in  terms  of  public  health  and  patient  safety  would  be  the  sum  of  the 
policy options No 2/4 and No 2/5: Low-risk trials would be covered by other liability 
schemes (product  liability  etc.). Other than low-risk trials would be covered by the 
national indemnification scheme. In terms of economic impact/costs, the savings in 
this policy option would be 0.03m EUR higher than in policy option No 2/5. 

5.3. 

Objective No 3: Addressing the global dimension of clinical trials when ensuring 
compliance with GCP 

5.3.1.  Policy option No 3/1: Leaving the situation as it is (baseline option) 

44. 

This policy option would not address the questions raised in the problem definition. 

5.3.2.  Policy option No 3/2: Facilitating GCP inspections by increasing transparency 

45. 

This policy option would contribute to securing compliance with GCP with the aid of 
a  stronger  degree  of  transparency.  The  economic  impact/costs  for  sponsors  will 
mainly  be  felt  in  the  administrative  costs  (approximately  6.72m EUR  per  year)  for 
submitting information on clinical trials in non-EU countries to a public register. 

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5.3.3.  Policy  option  No  3/3:  Inspections  of  non-EU  countries'  regulatory  systems  for 

clinical trial 

46. 

This policy option would contribute to ensuring that clinical trial data referred to in 
EU marketing applications is reliable and robust. It would strengthen the general rule 
that clinical data from third countries has to stem from clinical trials which are based 
on principles equivalent to those in the EU. 

47. 

In terms of economic impact/costs, the implementation costs are most relevant: they 
are at approximately 5 FTEs per year, plus costs of approximately 76 000 EUR. 

5.3.4.  Policy option No 3/4: GCP inspections by the Agency in non-EU countries 

48. 

This  policy  option  would  contribute  to  securing  compliance  with  GCP  in  clinical 
trials  performed  in  a  non-EU  country.  However,  it  would  remain  impossible  to 
inspect  all  sites  regularly  and  systematically.  Moreover,  inspections  are  usually 
conducted  in  the  context  of  the  marketing  authorisation  procedure,  i.e.  many  years 
after the clinical trial has ended. 

49. 

Resource needs at EU level would be approximately 1 300 FTEs. 

5.3.5.  Policy option No 3/5: Combination of policy option No 3/2 and No 3/3 

50. 

This combination of policy options would further strengthen the impact of the policy 
options  taken  individually:  the  transparency  (policy  option  no  3/2)  allows  better 
targeting inspections of non-EU countries' regulatory systems. 

6. 

COMPARISON OF OPTIONS 

6.1. 

51. 

52. 

53. 

Objective No 1 — A modern regulatory framework for submission, assessment 
and regulatory follow-up of applications for clinical trials 

The baseline situation is insufficient to address the problem. While policy options No 
1/2 (separate assessment), No 1/3 (joint MS assessment) and No 1/4 (assessment by 
the  Agency)  have  one  common  element  (the  single  submission  point),  they  are 
mutually exclusive.  

The  common  element  which  is  part  of  policy  options  No  1/2,  No  1/3  and  No  1/4 
greatly reduces administrative costs and thus contributes to addressing the problem. 

Policy  option  No  1/2,  however  does  insufficiently  address  issues  of  separate 
assessments  of  identical  issues  in  relation  to  the  same  clinical  trial.  In  this  respect, 
policy  options  No  1/3  and  1/4,  which  address  not  only  the  submission  process,  but 
also the assessment process of a clinical trial application, are to be favoured. When 
comparing policy options No 1/3 and No 1/4, it results that policy option No 1/4 sets 
up a very heavy system which is prone for delays. It involves every Member State, 
which is not necessary in view of the roll-out of clinical trials. Only approximately 
6 % of all clinical trials are rolled out in eight Member States or more. Considering 
this  it  seems  disproportionate  to  involve  every  Member  State  in  the  assessment  of 
clinical trial application. Added to this the dual approval (EU and national) stemming 
from policy option No 1/4 adds new complexities which would be avoided in No 1/3. 

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54. 

55. 

56. 

6.2. 

57. 

58. 

59. 

60. 

6.3. 

61. 

Policy option No 1/3 provides a ‘slimmer’ procedure than policy option No 1/4. For 
the initial authorisation it involves only the Member States where the clinical trial is 
to be performed (a mechanism would have to be set up to allow roll-out to additional 
Member States subsequently). Under policy option No 1/3 approval is also likely to 
be  cheaper  and  faster  than  in  No  1/4.  This  is  in  particular  of  interest  for  academic 
research and SMEs. 

Policy option No 1/5 (Regulation vs. Directive) is not an alternative but an add-on. It 
would  ensure  an  approach  in  assessment  of  a  clinical  trial  and  follow-up  action, 
based on identical criteria.  

Policy  option  No  1/6  is  a  combination  of  policy  options  No  1/3  and  1/5.  It 
contributes  further  to  achieving  the  objective  No  1  by  providing  an  identical  legal 
framework  for  authorisation  of  clinical  trials,  thus  facilitating  cooperation  between 
Member  States  as  foreseen  under  policy  option  No  1/3.  this  helps  to  achieve  the 
operational objectives of reducing in particular administrative burdens and delays. 

Objective No 2 — Regulatory requirements adapted to practical considerations 
and needs 

The baseline does not address the problem identified. Options No 2/2 (enlargement 
of the scope of non-interventional trials) and No 2/3 (exclusion of "non-commercial 
sponsors")  have  the  effect  of  ‘shifting  back’  regulation  to  Member  States.  In 
addition, regarding policy option No 2/3 it is difficult to see why rules designed to 
protect the safety and rights of participants and the reliability and robustness of data 
should apply to some types of sponsors but not to others.  

Policy option No 2/4 (removing requirements on the basis of the knowledge on the 
IMP) brings about less savings for sponsors than policy option No 2/3. However, in 
terms of public health and patient safety it is superior to policy option No 2/3 as it 
leaves aside any differentiation between ‘non-commercial’ and industry sponsors and 
focuses on an objective criterion: the authorisation status of the IMP.  

Policy  option  No  2/5  (national  indemnification  mechanism)  can  be  a  useful,  cost-
effective tool to address the specific issue of obligatory insurance/indemnity. 

Policy  option  No  2/6  is  a  combination  of  policy  option  No  2/4  and  2/5.  The 
combination  reduces  administrative  burdens  beyond  policy  option  No  2/5  without 
compromising on patient safety. 

Objective No 3: Addressing the global dimension of clinical trials when ensuring 
compliance with GCP 

The baseline option is not satisfactory. Policy options No 3/3 (Inspections of non-EU 
countries' regulatory systems for clinical trial) and No 3/4 (GCP inspections by the 
Agency in non-EU countries) have relatively similar effects in terms of achieving the 
objective, even though the approach is different. Their impact diverges considerably 
as regards the impact on resources at EU level. Regarding policy option No 3/4, the 
budgetary  constraints  do  not  allow,  at  present,  an  increase  in  inspection  activity  in 
line with policy option No 3/4. The assessment of the impact of policy option No 3/3 

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62. 

63. 

7. 

64. 

8. 

65. 

shows  that  much  can  be  achieved  with  far  fewer  resources  than  specified  in  policy 
option No 3/4. 

Policy  option  No  3/2  (obligation  of  registration  of  all  clinical  trials)  can  make  a 
useful  contribution  to  effective  control  over  clinical  trials  performed  in  non-EU 
countries.  The  burden  for  the  sponsor,  which  is  limited  to  administrative  costs,  is 
acceptable in view of the benefits created by this policy option. 

Policy  option  No  3/5  is  a  combination  of  policy  option  No  3/2  and  No  3/4:  This 
combination  strengthens  further  the  tools  to  verify  and  ensure  compliance,  as  it 
allows more targeted system inspections. 

PREFERRED CHOICE OF OPTIONS 

Regarding  objective  No  1,  the  preferred  choice  of  policy  option  is  No  1/6,  which 
allows for a fast approval without setting up a new, central bureaucracy. In addition, 
in  this  policy  option  the  legal  form  of  a  Regulation  facilitates  cooperation  between 
Member  States.  Regarding  objective  No  2,  the  preferred  policy  option  is  No  2/6, 
which  reduces  costs  (administrative  burdens  and  operational  costs)  considerably 
without  compromising  on  patient  safety.  Regarding  objective  No  3,  the  preferred 
policy option is no 3/5, which combines a resource-effective inspection of regulatory 
systems  with  a  higher  degree  of  transparency,  in  order  to  be  able  to  target 
inspections. 

MONITORING AND EVALUATION 

A  key  indicator  for  achievements  of  the  objectives  is  the  number  of  clinical  trials 
applied  for  in  the  EU,  the  number  of  multi-national  clinical  trials  performed  in  the 
EU,  the  costs  for  clinical  trials  generated  by  legislation,  and  delays  in  launch  of  a 
clinical trial. This will be assessed by the Commission through regular reports from 
the  EU-database  on  clinical  trials,  a  public  consultation  and  organisation  and 
participation of fora where the legislation is evaluated by stakeholders. 

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