clinical trials an industry perspectivecrdi.ie/uploads/presentation 2- rebecca cramp- clinical...
TRANSCRIPT
Clinical Trials
An Industry Perspective
Rebecca Cramp PhD
Scientific & Regulatory Affairs Manager, IPHA
January 2012
Benefits of Clinical Research
Patients: Early access to new medicines, improved diagnosis, improved treatment, Best Practice
Investigators: Training (incl how to effectively manage drug toxicities), publications, funding, prestige & partnership in new medicine development
Hospitals: Income, training, funding, prestige, employment, equipment, better patient outcomes due to patients receiving cutting edge treatments
Company: Data for regulatory approval, employment, reputation within their global company, further studies
Ireland: Experience & data on Irish patients & clinicians with knowledge of new medicines, treatments, investment, innovation agenda, jobs, economy etc
Industry Contribution
Clinical research is a core activity for our member companies
13 of the top 15 pharma companies are in Ireland
Recent investments ranged from €100,000 to €4 million per
company per study
Also invests in equipment, research nurses, training, facilities etc
Research grants €5,000-€100,000/annum/company, bursaries for
research etc
Good Clinical Practice (GCP) procedures & general regulatory
expertise
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 (IMB Annual report data: 162
in 2004; 117 in 2008; 108 in 2009 and decreasing further in recent
years... )
• Experience and consequence
• International reputation in relation to clinical research
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
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?
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?
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’.
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
Choice of location for a clinical trial
Concerns
• Non adherence to legislation
• Administrative barriers
• Delays, random additional costs
• Lack of predictability
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
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’
Legislation Requirements ctd.
• Timelines, irrespective of quorum or meeting dates etc
− Protocol review within 60 days of application receipt (Reg 13.9)
− Amendments within 35 days of application receipt (Reg 21.4)
• Fees
− Protocol review = €1,000 basic + €150/additional site (Reg 52).
− Substantial amendment = €200
− No fee for annual report, SSA or other activities envisaged or set
down in law (the existing fees cover all activities of a clinical trial)
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
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
Check list for Clinical Trial Agreement
Sign off; Interventional Clinical Trial
Document Required? Issue
State Claims Agency Standard
Clinical Trials Indemnity Form
(CTIF)
√ Standard template no changes permitted for HSE
owned hospitals
For non-HSE hospitals should MMI hold the list that
advises the correct term instead of ‘Authority’
Clinical Trial Agreement √ Standardise data protection paragraph of the CTA?
No additional indemnity, just refer to the SCA CTIF?
Insurance cert √ Some hospitals do not sign CTA until insurance cert
reviewed by commercial insurance company. Why
(acceptable insurance limits)? State Claims Agency set
the standard? Additional unnecessary step adds cost,
delay, confusion and is bureaucratic.
Standardise limits of liability?
Insurance policy √ Provides details
Protocol √ No review, no authority to change
Informed Consent x No review, no authority to change
Patient Instructions/ GP letter
/Patient ID card
x Not required, no authority to change
Financial Controllers letter x Not required, no authority to change
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?
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
Limit of liability per occurrence set too high
What would work?
Adherence to legislation & DoH guidance
− No multiple opinion – one review
− SSA form and indemnity only as per the requirements – no added criteria
− Transparent and clear sign off route
MMI hold the list of who is the ‘Authority’ for non HSE owned hospitals
Electronic submission of applications (EudraCT) (IMB and rest of
Europe already doing this)
Predictability
Administrative collaboration - meeting dates published for whole year,
once a year, on website
Standardise limit of liability
Standardise limit of liability?
Advantages
Removal of expensive re-review that could result in less robust conditions
Reduce time delays – faster patient access to trials
Ensures best possible indemnity is in place
Remove another unnecessary, costly administrative burden
First time in Ireland but common in other countries
Confidence building for patients, hospitals, industry
Steps
Developed by State Claims Agency (Clinical Indemnity Scheme)?
Used for ALL trials, a ‘standard terms and conditions’
Limits of Liability
European Norms per occurrence
Belgium, Croatia, Czech Republic, Demark, Finland, Norway, Switzerland,
Greece etc €1.2 million
Austria, Spain €2.9 million
Netherlands €4.1 million
Ireland €6.5 million
Innovation 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
