National mutual acceptance of
Ethical and Scientific review
of multicentre clinical trials
Andrew Thornton, Chairman, RAH HREC
Bernadette Swart, Manager, Research Governance
The MOU
The memorandum of understanding (MOU) for the
national approach to ethical review of clinical trials
has been signed and applies to public health
organisations in the following jurisdictions as at
1 November 2013:
• QLD
• NSW
• Victoria, and
• SA
There will not be retrospective acceptance of
clinical trials in to national mutual acceptance.
Working Documents
The MOU sets out the arrangements between the Parties
to achieve single ethical review of multi-centre Clinical
Trials being conducted at their Public Health
Organisations.
•
A list will be provided online
The MOU applies only to the ethical and scientific review
of multi-centre Clinical Trials. All other research will be
ethically and scientifically reviewed as per individual
jurisdictional processes.
•
With some exceptions
Standard Principles for Operations - National Approach
to Single Ethical and Scientific Review of Multi-centre
Clinical Trials (Draft)
Definitions
What is a Multi-centre Clinical Trial?
• Conduct of research at more than one
organisation;
• Research conducted jointly by investigators
affiliated with different organisations.
What is Mutual recognition
• Acceptance of ethical and scientific review of a
multi-centre Clinical Trial undertaken by one of the
Certified HRECs on the proviso that the certified
HREC is associated with the Public Health
Organisation at which the clinical trial is occurring.
•
A list will be provided online
Scope of Research Covered
Interventional research involving a drug and/or a device,
radiation therapy, surgery, treatment or diagnostic
procedure and studies associated with ongoing activities
relating to trials that have been conducted. This may
include observational research and evaluation of a trial,
developing a registry and other post-marketing surveillance
activities.
In South Australia this does not include:
o Phase 0 (first time in human) and Phase 1 clinical trials
Approval must be sought by a South Australian HREC
o Studies involving SA Aboriginal and Torres Strait
Islanders
Approval must be sought by the Aboriginal Health Research Ethics
Committee (AHREC),
(Other state exceptions and conditions will be available online)
Scope of Research Covered
The National Approach includes the above research
involving adults and/or children conducted by:
o Commercial sponsors;
o Collaborative groups/Consortiums, either
supported (in part) or not supported by a
commercial company;
o Investigator initiated groups, either supported (in
part) or not supported by a commercial company.
Private health organisations may also accept the
review of a NHMRC certified Reviewing HREC.
However, some jurisdictions may have certain
requirements to provide ethical approval for private
health organisations.
How to choose Reviewing
HREC
A Reviewing HREC is required to be a NHMRC certified
HREC in Clinical Trials.
The selection of the Reviewing HREC to undertake the
single ethical and scientific review of a given multicentre Clinical Trial is either:
•
In Victoria - through a Central Allocation System for HRECs;
•
In QLD -through the Central Co-ordinating System for HRECs;
•
In NSW - at the discretion of the Applicant for HRECs;
•
In South Australia, to the Certified HREC associated with the
site at which the Applicant is conducting the research and if
this is not applicable, the selection of the Certified HREC is at
the discretion of the Applicant;
NEAF
The National Ethics Application Form (NEAF) is to be
used for an ethics submission to a Reviewing HREC
and is submitted by the Coordinating Principal
Investigator (CPI).
The CPI must sign the declaration section of the
NEAF. PIs are not required to sign as they will make
a declaration in the SSA form
The Reviewing HREC may request changes to the
NEAF and a revised document must be submitted.
Use of the NEAF does not eliminate the need for a
research protocol or compliance with the local
requirements of the reviewing HREC.
Master participant information
and consent form
• The NHMRC templates are the recommended Master
Participant Information and Consent Forms (PICF)
• Other Master PICFs may be acceptable, providing they
adhere to the conventions of the NHMRC templates.
• A Master PICF is to be submitted on the letterhead of
the Coordinating Principal Investigator’s (CPI)
organisation.
• Site Master PICF may be submitted by a participating
site and must be based on the Master PICF with
addition of specific site requirements or policies relating
to the conduct of the research. The Site Master PICF
should be on the letterhead of the site with an
appropriate footer, referencing the Master PICF and
version.
Coordinating Principal
Investigator (CPI)
• is the individual who takes overall responsibility
for the research project and submits the project for
ethical review
• responsible for ongoing communication with the
reviewing HREC and passing on information from
the HREC to the sponsor and the Principal
Investigator (PI) and trial coordinator at each site
conducting the research
• is the PI at their own site and is therefore
responsible for passing on information from the
HREC to their own site’s Research Governance
Office (RGO)
• must sign the declaration section of the NEAF. PIs
are not required to sign the declaration as they will
make a declaration in the site specific assessment
form.
Principal Investigator (PI)
• is the individual who takes responsibility at their
own site for the conduct, management,
monitoring and reporting of research via the
Coordinating Principal Investigator (CPI) to the
reviewing HREC
• submits site specific assessment documents for
site authorisation and liaises with the site
Research Governance Office (RGO) throughout
the life of the research project
Ethics approval letters
• Will list all organisations (or sites) that have been
approved through single ethical review;
• State the anniversary date on which all approved sites
should submit an annual progress report to the
Reviewing HREC and stipulate if reporting should be
more frequent in accordance with the risk of the
research;
• List documents, with version identification, associated
with the clinical trial that was reviewed and approved
by the Reviewing HREC; and
• Indicate that the research cannot commence until
research governance/site specific assessment
authorisation has been completed by the participating
organisation/site.
Duration of ethics approval
• Ethical approval for interventional clinical trials will be
for a five year period or rolling approval for the life of
the study.
• An exception to a five year period may occur in cases
where a shorter time is requested for the research.
• Extension of the ethical approval period may be
requested.
• In some jurisdictions a new ethics submission, review
and ethical approval is required. The process to be
followed will depend on the decision of the Reviewing
HREC.
Annual reports
Ethical approval will be contingent upon receipt of an
annual (or more frequent) report to the Reviewing
HREC from the CPI. The due date is one year from
the date of the Reviewing HREC approval date.
In addition:
• PIs must complete a HREC Progress Report for their
Site in the format as specified by the Reviewing HREC
• PIs will complete the final HREC report for their site
• The PI will submit 1 copy of a report to the CPI and 1
copy to their site’s RGO
• The CPI submits all reports to the Reviewing HREC
AE, SAE and SUSARs
• The PI will complete the appropriate Safety Report
and submit to the CPI and the site RGO as soon as
possible (within 24 hours where required)
• If the CPI is not contactable in the urgent reporting
timeframe, the PI may submit the Safety Report to
the Reviewing HREC directly, and notify the CPI that
they have done so.
• The CPI will send a copy of the HREC review
outcome to the sponsor, PI and trial coordinator at
each site, and own site’s RGO
• PI will send a copy to their RGO
• The PI will send a copy of the RGO
acknowledgement to the sponsor
Amendments
• Must be submitted by the CPI to the Reviewing
HREC.
• The CPI is responsible for notifying all site PIs of the
amendment, in order for them to discuss it with their
RGO.
• An amendment must not be implemented at a site
until the HREC amendment has been approved by
the Reviewing HREC and (if applicable) Site
Specific Assessment (SSA) amendment has been
authorised at the site.
• If an SSA / CTRA amendment is not required, the
RGO will acknowledge receipt of the HREC
amendment
Monitoring guidelines
Safety reporting is the responsibility of CPI and PIs
and should be guided by the:
“NHMRC Australian Health Ethics Committee
(AHEC) Position Statement: Monitoring and
reporting of safety for clinical trials involving
therapeutic products”.
The Monitoring and Reporting Tables for the
National Approach should be referred to (see
http://hrep.nhmrc.gov.au/_uploads/files/Framework_f
or_Monitoring.pdf )