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