IPHA's Industry Perspective

1. Clinical TrialsClinical Trials
IPHA’s IndustryIPHA’s Industry
PerspectivePerspective
Oliver O’ConnorOliver O’Connor
CEO, IPHACEO, IPHA
October 2015October 2015

2. Benefits of Clinical Research
Patients: Early access to new meds, improved diagnosis &
treatment
Investigators: Training (manage drug toxicities), publications, funding,
prestige & partnership in new medicine development
Hospitals: Income, training, funding, prestige, employment,
equipment, better patient outcomes from newest treatments
Company: Data for regulatory approval, employment, reputation within their
global company, further studies
Ireland: Experience & data on Irish patients, clinicians with knowledge of

3. IndustryIndustry Contribution
 Clinical research is a core activity for our member companies
 13 of the top 15 pharma companies are in Ireland
 Recent investments from €100,000 to €4 million per company /study
 Also invest in equipment, research nurses, training, facilities etc
 Research grants €5-100K /annum/company, bursaries for research etc
 Good Clinical Practice (GCP) procedures & general regulatory expertise

4. Choice of location for a clinical trial
Fundamentals
• Adherence to legislation (critical)
• Meet timelines (essential)
• Predictability in all areas
• Transparency
• Recruitment targets met (better to promise 5 and deliver 8 than
promise 15 and deliver 14 – will be categorised as not delivering)
• Population
Advantage/deciding factor
• Speed, efficiency
• Research hub
• Data quality

5. Level of Clinical Research
Background
•Should be increasing & equal to investment of companies in Ireland
•Given pharma footprint expect 400 industry sponsored trials/annum
Concern
•Fewer trials being conducted in Ireland year on year
•Experience and consequence
•International reputation in relation to clinical research

6. EFPIA report on
clinical trials
EFPIA report on
clinical trials

8. Roadblock to Investment
‘It is an absolute fact that every hour we are losing out on clinical trials.
This is a game that you’re either in or you’re not’
Frank Giles, Medical Independent, 20.10.11
Ireland removed from ‘core country list’ for some research-based
pharmaceutical companies
− Lack of compliance
− Lack of predictability
− Cost issues
− System too person dependent
− Research infrastructure fragmented
Pfizer, Medical Independent, 20.10.11

9. Roadblock to Investment - details
a)Absence of a positive view to research leading to failure to address
resolvable issues e.g. delays in signing standard but key documents
b)Unjustified charges for clinical trials
c)Lack of adherence to legislation, by Hospital Recognised ECs
d)Absence of a standard Clinical Trial Agreement
e)No ring fencing of funding
f)Absence of dedicated and protected research time for staff
g)Costly and ineffective disease-specific research networks

10. Sep 2014 to Sep 2015 – sign off times

11. Choice of location for a clinical trial
Concerns
• Non adherence to legislation
• Administrative barriers
• Delays, random additional costs
• Lack of predictability (recruitment targets, timelines, processes etc)
Overview
• Losing millions of euro/yr to other nations delighted to receive trials
• Claiming delays are due to time for questions does not stand up
(internationally 35/60 days sufficient for full review of trials so Ireland,
with our competencies, should be the same or better)
• Pharma industry highly regulated – random payments not permitted

12. What would work?
The commitment that we would like to see from the CEOs is;
a)Positive Attitude to, and Engagement on, research. One designated
signatory for clinical trials per hospital together with
a) an agreed process for reviewing sign-off requests
b) Agreed timeline for signature and response (7 + 2 days)
b)Hospitals only to levy the statutory charges
c)CEOs ensure that Hospital RECs adhere to legislation, timelines etc.
d)CEO endorsement of a standard Clinical Trial Agreement for hospitals
e)Ring fencing of funding for clinical trials
f)Dedicated and protected research time for staff
In addition to basics of recruitment targets met, predictability, data quality

13. Innovation EconomyInnovation Economy
 The future competitive advantage of the Irish
economy depends on Ireland having a
reputation as a world class centre for
innovation and R&D in areas such as new
medicines development.
 Keys to ensuring clinical trials stay in Ireland
- Adherence to legislation
- Adherence to DoH guidance
- Absolute timeline predictability
- Focus on innovation and improving processes

14. THANK-YOU!
olilveroconnor@ipha.ie
www.ipha.ie
www.medicines.ie

15. ADDITIONAL SLIDES

16. Requirements of the legislation
Single Ethics Committee opinion
Applicable to all countries in Europe.
The European legislation specifically clarifies that the single review
is in the best interest of the patient and states that
'A single opinion for each Member State concerned reduces
delay in the commencement of a trial without jeopardising the
well-being of the people participating in the trial'.
The above applies to interventional trials – for the future apply
to non-interventional trials?

17. Principal Investigator’s legal
requirement
‘A chief investigator for a trial shall make only one
application for an ethics committee opinion in relation to that
trial regardless of the number of trial sites at which the trial
is to be conducted’.

18. Site Specific Assessment
Sites that do not perform the ethical review but are involved in the trial
perform the Site Specific Assessment (SSA) to ascertain if sufficient
– resources,
– personnel or
– facilities
at the site to conduct the trial.
"It is obligatory under the Directive (and the Regulations) that,
in the case of multi-centre clinical trials, a single ethics
committee opinion be given for each Member State. This
means that once an ethics committee opinion is given by a
recognised ethics committee for a clinical trial in this
country, that opinion must prevail at all centres where the
trial is to be conducted’’
Legally and ethically, no second ethical (committee) review of a
multi centre trial should be performed.
Any need for hospital non legislative committees?

19. Site Specific Assessment (SSA) Form
• Required
DoH Site Specific Assessment Form (contains a requirement to
include a copy of the Indemnity)
The DoH is the legal supervisory body and the DoH states that
It is the view of the Supervisory Body that the SSA form contains
all the necessary information required by the CEO or person
acting on his/her behalf to decide whether to give permission for
the clinical trial to be conducted at the site.
Some applicants provide the Schedule of Events (in the Protocol) but
not required
• Not legal
Requests for changes to the protocol, informed consent etc.
Note: company or hospital liable if changes to the trial are
made outside or study is conducted the legal framework

21. Initiation Costs
 Can be €30,000 per site
− For at least one company Ireland has the
highest non recruiting site metric out of all the
countries in Europe
− Some studies as high as 50%
− Main contributor is ‘speed to start up’

22. Hospital Sign-off / Approval
Issue Implication
 Delays of 2 days - 4 months for
CEO/risk manager/ financial
approval (set standard of max
10 days?)
 Anomalous sign off costs
 No transparency on who
responsible /who signs (CEO?)
 Process not clear / defined
 Pharma industry highly
regulated – random payments
or non adherence to
legislation is not permitted
 Move down list of preferred
sites
 If no Phase II then unlikely to
get Phase III
 Ireland no longer a site for the
conduct of trials
 Competition from and
investment to other countries

23. Pharmacy Fees
 No fee for annual report, SSA or other activities
envisaged or set down in law (the existing fees set in
the legislation cover all activities of a clinical trial)
 Admin, set up, dispensing, storage, close out. . .
 Wide variation in costs set by pharmacies €500 – 2,000
 2011, four fold dispensing fee increase in one hospital
 Prohibitive to future studies
National standard pharmacy fees?

24. Industry Concerns
 For multi-center trials multiple ethical (CEO committee)
reviews not single opinion (some call it a committee review on
behalf of CEO, but is still a second review)
 Lack of adherence to the legislation & guidance – multiple
review, SSA (additional docs & review), burdensome
requirements for sign off etc
 Use of local EC forms not approved DoH forms
 Lack of adherence to the 35/60 day timelines – no justification
 Attempts to introduce anomalous fees