Legal & Regulatory
Documents
Angela Henjak, Alfred Health
Documents
• Clinical Trial Notification (CTN) Form • Insurance certificate • Indemnity • Research Agreement • Information can be found on our Legal & Regulatory Requirements
page: http://www.alfredresearch.org/ethics/legal.htm
CTN Form
• Notifies TGA of trials conducted at each Site • Allows for access to unapproved medicines and devices
• Unapproved medicines or devices:
– Medicines or devices which do not appear in the Australian Register of Therapeutic Goods (ARTG)
– ARTG goods used outside of the marketing approval, eg different indication, dose, formulation, route of administration
CTN Form
• Need to nominate the Sponsor of the trial
• The Sponsor is the company, organisation, institution, body or individual (enterprise) that initiates, organises and supports a clinical study of an investigational product on human subjects.
– Commercially sponsored studies: the Local Sponsor – Collaborative group studies: the Collaborative Group – Investigator-initiated studies: the Institution which is the
custodian of the Protocol, eg Alfred Health, Monash University, Baker Heart & Diabetes Institute,
• The Sponsor has to be an Australian entity
CTN Form
• The CTN submission process is now online • It is the responsibility of the Sponsor of the Study to do the online
submission • Alfred Health will submit and send an invoice to researchers • A CTN Form which captures the information will need to be
completed • An excerpt or draft CTN form is required for all submissions • Remember to include placebo • Complete Devices section
– Includes devices which are TGA-approved but are imported directly from overseas, eg ECG machines, point of care devices, blood collection tubes
– ECG machines and point of care devices require statement in the PICF
Insurance Certificate
• An insurance certificate is required from the custodian of each Protocol, eg commercial sponsor, collaborative group, research institution, hospital etc.
• Commercially sponsored studies: Needs to nominate the Local Sponsor (full legal name) listed on the CTN form as an “Insured” or an “Additional Insured”. “Certificate Holder” is not acceptable
• Limit of Liability: – The class of insurance should be for Public and Product
Liability or equivalent such as General Liability or Clinical Trial – In Victoria: $10 million per occurrence and in the annual
aggregate – In NSW: $20 million per occurrence and in the annual
aggregate
Insurance Certificate
• Deductible (excess) is not to exceed $25,000 for each and every claim or series of claims arising from a single cause.
• If the certificate lists the Study title and Protocol Number, these
details must be correct. • The certificate should be current throughout the trial period. • Need to check details on renewed insurance certificates have not
been altered.
Indemnity
• Required for commercially sponsored studies • Some collaborative groups provide an indemnity but not required • Not required for investigator initiated studies
Indemnity
• There are two kinds of indemnities: – Standard indemnity:
> Covers the conduct of study at the site as well as the HREC review
> Always required
– HREC Review Only indemnity: > Necessary if HREC is reviewing for other sites > Required for streamlined applications (SERP & NMA)
Indemnity
• There are separate indemnities for drug and device trials – Drugs: Medicines Australia (MA) – Devices: Medical Technology Association of Australia (MTAA)
• The name of the Compensation Guidelines for drugs and devices differs slightly:
– Drugs: Guidelines for Compensation for Injury Resulting from Participation in a Company-Sponsored Clinical Trial
– Devices: Guidelines for Compensation for Injury Resulting from Participation in a Company-Sponsored Clinical Investigation
• Compensation wording in the PICF should reflect the correct: – Peak body: MA or MTAA – Compensation Guidelines – Full legal name of the Local Sponsor
Indemnity
• Please use the CTRA & Indemnity Checklist to check details are correct:
– “To” clause which defines “the Indemnified Party” – “From” clause which defines “the Sponsor” – “Re” clause: Study title and Protocol Number – Paragraph Number 1 – Standard indemnity:
> Correct participant group selected: “patients of the Indemnified Party” or “non-patient volunteers”
> Correct name of Principal Investigator
Indemnity
• Please use the CTRA & Indemnity Checklist to check details are
correct: – Paragraph Number 1 – HREC Review Only indemnity:
> Correct participant group selected: “patients of the Indemnified Party” or “non-patient volunteers”
> Correct, legal name of each Site > Correct name of each Site Principal Investigator
Research Agreements
• The Australian Code requires that an Agreement be signed for each trial, even investigator-initiated studies
• Agreements cover issues such as – Obligations and responsibilities of each Party – Indemnity and insurance requirements – Payment – Publication restrictions – Authorship – Intellectual property
• Contact the Ethics or Research Governance Office if unsure • If there are intellectual property issues, please seek legal advice from your
Institution
Research Agreements
• Commercially Sponsored and Collaborative Group Studies:
– Drug Trials: > Medicines Australia Standard Form > Medicines Australia Contract Research
Organisations (CROs) acting as the Local Sponsor
> Medicines Australia Collaborative or Co-operative Research Group (CRG) Studies
> Medicines Australia Phase IV Clinical Trials
Clinical Trial Research Agreements
• Commercially Sponsored and Collaborative Group Studies:
– Device Trials: > Medical Technology Association of Australia
Standard Clinical Investigation Research Agreement (CIRA)
Research Agreements
• Investigator-initiated, Company Supported Studies: – Alfred Health template
• Investigator-initiated Studies:
– Clinical Trials: > VMIA investigator-initiated: Accepted in Victoria
and some interstate sites > Medicines Australia Collaborative or Co-operative
Group (CRG): Accepted by interstate sites
Research Agreements
• Investigator-initiated Studies: – Non-Clinical Trials:
> Alfred Health Research Collaboration Agreement
• Material Transfer Agreements (MTAs): – Governs the exchange of materials between two
organisations, usually for research purposes and should be used for the transfer of tissue and other material
– Two types of MTAs: incoming and outgoing
Research Agreements
• There are templates for Research Agreements and indemnities • Please use the CTRA & Indemnity / Research Agreement Checklists to
correctly complete and check the CTRAs. • The body of the indemnity or Agreement template should not be altered
• For Agreements, changes should be detailed in:
– Schedule 7 for commercially sponsored template – Schedule 4 for collaborative group and VMIA investigator-initiated
template – Schedule 3 for Research Collaboration Agreement and investigator-
initiated, company supported template
Legal Documents
• Please submit the signed CTRA & Indemnity / Research Agreement checklist
• Need to be submitted for review • Should only be signed by authorised representatives • Principal Investigator:
– Should NOT sign as a Party, eg “agree to be bound by the terms”
– Should sign as “read and acknowledged the terms”
Confidential Disclosure Agreements (CDA)
• Many are currently signed by the Principal Investigator • Some institutional CDAs have been signed • Medicines Australia is working on a CDA template
Changes to Legal & Regulatory Documents
• CTN Form: – Changes which require an amended CTN form:
> Drug details: dosage, route of administration, strength
> Device details > Sponsor > Study Title > Principal Investigator > Addition of Sites
Changes to Legal & Regulatory Documents
• Insurance Certificate: – Changes which require an amended insurance
certificate: > International Sponsor > Local Sponsor > Study title and Protocol Number if listed
Changes to Legal & Regulatory Documents
• Indemnity – Standard and HREC Review Only: – Changes which require an amended indemnity:
> Local Sponsor > Study Title > Principal Investigator(s)
Changes to Legal & Regulatory Documents
• Research Agreements: – Any revisions are to submitted as an Amendment or
Addendum to the Agreement rather than an entire new Agreement
– There are templates on our website