Transcript Document

Using Australian Clinical Sites
– Challenges for International
Sponsors
Prof A J (Tony) Webber
Clinical Network Services Pty Ltd
Brisbane, Australia
General Considerations
Australian Health Care System
• public and private sector providers
• supported by a federal Medicare system
• both sectors considered to provide quality
health care
• major hospitals in both sectors exhibit a
strong commitment to medical research
• many are experienced clinical trial sites
• access to trained study/site coordinators
Australian Regulatory System
Two major Australian Government Bodies
• Therapeutics Goods Administration (TGA)
• The National Health and Medical
Research Council (NH&MRC)
Therapeutic Goods Administration
• TGA – acts as Australia’s regulatory
authority in relation to the registration
and/or listing of pharmaceuticals,
neutraceuticals, and medical devices
• Has adopted ICH GCP in principal – minor
amendments concerning membership of
Institutional Review Boards and comments
concerning informed consent, retention of
records and adverse drug reporting
National Health & Medical Research Council
• Allocates funds for health and medical
research
• Provides health advice
• Considers ethical issues
• Regulates sensitive medical research
activities
Other Organizations
• Office of the Gene Technology Regulator (ORTG)
• An additional level of approval for genetically modified
products
• Gene and Related Therapies Research Advisory
Panel (GTRAP)
• GTRAP is a subcommittee of the Research Committee,
a principal committee of the NHMRC.
• Provides advice to Council on scientific, medical and
technical issues related to gene and related therapies,
xenotransplantation and human stem cell research;
• Medicines Australia
• Represents Australian pharmaceutical manufactures
• Gives guidance on issues such as the form of indemnity
governing clinical trials and patient compensation
Approval for the Conduct of a Clinical
Trial – The Sponsor
• The Sponsor of a clinical trial to be
undertaken in Australia MUST be an
Australian legal entity
• Contract Research Organizations holding a
TGA “Enterprise Number” can perform the
role of Australian Sponsor when an overseas
company does not have Australian office or
agent
Regulatory Approval to Conduct a
Clinical Trial – Two Routes
Clinical Trial Notification (CTN)
• 95% of all trials approved by the CTN route
• Onus on Human Research Ethics
Committees (HREC) for
• ethical considerations
• scientific merit/safety of the study.
• TGA will provide written acknowledgement
within 10 days of receiving notification via a
CTN form and appropriate payment.
• A separate CTN form for each site
Regulatory Approval to Conduct a
Clinical Trial – Two Routes
Clinical Trial Exemption (CTX)
• Sponsor submits an application to the
TGA for its evaluation and comment.
• Review of clinical and pre clinical data is
required to be completed within 50 days.
• This clock may be stopped for questions
• Once approved, the study can then be
considered by HRECs and conducted at
any number of sites
• If a HREC is concerned with scientific/
safety issues of a study submitted to it for
CTN approval it can require that the
study go through the CTX process
Clinical Trials in Australia
- CTN Applications
2500
2235
2378
1989
1908
2000
2374
1710
1597
1500
1109
1000
650
727
1247
794
500
0
1992-93
1993-94
1994-95
1995-96
1996-97
1997-98
1998-99
1999-00
2000-01
2001-02
2002-03
2003-04
Clinical Trials in Australia
- CTX Applications
40
35
30
25
33
37
23
20
15
10
5
0
9
8
9
3
3
4
5
2
1993-94 1994-95 1995-96 1996-97 1997-98 1998-99 1999-00 2000-01 2001-02 2002-03 2003-04
Summary of Australian Regulatory
Process
Process
CTN
(Clinical Trial
Notification)
CTX
(Clinical Trial
Exemption)
TGA Review
Not required

HREC
Approval


Agency
Timelines
7-14 days
30 days or 50 days
Fees
$A240
($US188)
$A15,300
($US11,964)
99
1
% per year
CTX similar to IND
Ethics Approval
• Irrespective of route, CTN or CTX, all
clinical trials must be submitted to an
Australian Independent Ethics Committee,
termed HRECs in Australia
• HRECs must comply with the requirements
laid down by the NH&MRC who has a
responsibility to oversee their operation
Approval Times
• Most HRECs and their Research
Committees meet monthly
• Some will not meet December/January
• Submission dates range from 2-6 weeks
before scheduled meetings
• Approval between 5 weeks to 8 weeks from
submission to approval
• Typically, overall process takes 8 13 weeks
Informed Consent Forms (ICF)
• Must conform with the particular HREC’s
requirements (template) and ICH GCP
• Likely to require major changes from the
sample ICF often provided by overseas
sponsors
• Australian details on data protection,
patient compensation and reimbursement
must be included
Patient Recruitment Issues
• Payments
• reimbursement all out of pocket expenses
associated with attending clinical trial
visits – Must be approved by the HREC
and detailed in the patient information
sheets
• Advertising
• Advertising and accelerated recruitment
strategies require HREC approval
Indemnity and Insurance
• The majority of HRECs have standardised
on, and require sponsors to use, the “Form
of Indemnity for Clinical Trials” published by
Medicines Australia
www.medicinesaustralia.com.au
• While clinical trial insurance may be held by
the overseas sponsor, some Australian
states require clinical trial insurance to be
held by an Australian legal entity
Labelling Requirements
Major points
• Name of the Sponsor – must be the
sponsor listed on the CTN form
• Pharmaceutical dosage form,
administration route etc
• Batch and/or code number
• Trial subject identification – where
appropriate
• Directions for use
• “for clinical trial use only”
www.tga.gov.au/docs/pdf/unapproved/un
app.pdf
Study Close-out and Archiving
• Australian regulations stipulate records be
retained for 15 years following completion
of a clinical trial, or
• As per ICH GCP requirements, whichever
is longer
• Investigational sites often request
additional financial support from the
sponsor for off site archiving by a third
party or that the sponsor supports this
process directly.
Thank you!