Clinical Trial Infrastructure in Centres Lillian L. Siu Princess Margaret Hospital

Key elements for success  Building a research team  Engaging others in your research  Be engaged in the work of others who collaborate with your research  Know some basic accounting  Learn how to navigate the system  Publish your work  Make sure your staff are well trained

Personnel  Your research program’s success depend on the “buy-in” from your team: Other investigators:  Oncologists, laboratory scientists, pathologists, radiologists, etc. Trial nurses, clinical research associates Pharmacists Biostatisticians  Meet with them regularly and tell them what’s happening!

Resources - institutional  Grants and contracts services  Research financial services  Technology development and commercialization  Institutional review board/research ethics board/ethics committee (IRB/REB/EC)  Protocol review committee

Step-by-step guide to activating a clinical trial - 1  Concept ---  protocol development Pharmaceutical-sponsored Investigator-initiated research (IIR) Academic agency-sponsored (e.g. NCIC, NCI, RTOG, etc)  Once confidential non-disclosure is established, review the protocol in detail, and asks key individuals in your research team for input  Protocol review committee (if any)

Step-by-step guide to activating a clinical trial - 2  Key questions you need to ask before deciding to take part: Do you have enough patients to put on the trial? Do you have any competing trials? Do you have the personnel to run the trial? Do you have the resources and infrastructure to run the trial (e.g. electronic data capture; IV pumps; treatment space, etc)?

Step-by-step guide to activating a clinical trial - 3  Once you decide to participate in a study, the following processes should be activated: Grants and contracts office – existent templates would expedite contract review Budget – you (or someone familiar with the costs of procedures and tests in your institution) need to review this carefully IRB/REB/EC submission

Example of budget items – don’t forget the overhead (indirect costs)! Procedure Administrative Cost per Patient Visit (Includings Nursing) Adverse Event / Toxicity Assessment (Average) BIOCHEM-HCG (PREGNANCY) QUANT - S Biomarkers Biopsy - Procurement Biopsy - Processing Blood Sample Collection - Pharmacokinetic (PK) Blood Sample Processing - Pharmacokinetic (PK) Blood Sample Processing / Shipping Blood test-Other Concomitant Medication Assessment Coordinator Activity - Pt Visit (Unit 0.25 Hour) CT scans Documentation (Source) - Follow-Up Documentation (Source)-Eligibility/Entry (Average) Documentation (Source)-Treatment Visit (Average) Drug Administration (Oral) eCase Report Form Completion Treatment, (Average) eCase Report Form Completion, Baseline (Simple) ECG / EKG / Electrocardiogram Eligibility or Inclusion/Exclusion Assessment History (Medical) Informed Consent (ICF) - Other (See Note) NUCLEAR-MUGA SCAN NUC MED Patient Teaching / Patient Education (Average) Performance Status (ECOG) Pharmacy Activity Physical, Weight & BSA Routine Study Screening Telephone Contact Archival Tissue Sample Collection Coordination Tumour Response Assessment (RECIST) TOTAL Total Plus 30% Overhead Cumulative visit totals Total cost per patient over study (all sites): One Time Financial Events (All Sites) OCREB (Ontario REB) Initial Local Submission and Annual Renewal Document Archiving Pharmacy Fees (Start-Up) Pharmacy Fees (Annual) x 5 Study Start-Up (Average) Study Close-Out

Step-by-step guide to activating a clinical trial - 3  Health Canada submission for a Clinical Trials Application (CTA): Pharmaceutical-sponsored – done by company or by a Clinical/Contract Research Organization (CRO) Investigator-initiated research (IIR) – you may have to do this yourself! Academic agency-sponsored (e.g. NCIC, NCI, RTOG, etc) – done by the sponsor ususally the academic agency itself. Typically done prior to IRB submission

Step-by-step guide to activating a clinical trial - 4  Protocol submission: IRB/REB/EC  Format consent forms to meet your institutional format and IRB preferred language Other institutional committees that need to approve of protocol before activation

Step-by-step guide to activating a clinical trial - 5  Collecting documents prior to trial activation: PI and investigator CVs, GCP certificates Lab licenses/certificates, normal ranges Financial disclosure agreements

Regulatory binder index 1. Protocol  Study Protocol  Study Protocol Amendments  Protocol or Amendment Signature Pages  Non-Disclosure Agreement  Investigator Drug Brochure /Regulatory Forms/CV  Form FDA 1572 (If applicable)  Curricula Vitae  Medical Licenses (US only, if applicable)  Financial Disclosure Agreement 3. Approved Consent Form(s)  Informed Consent(s) 4. IRB Approvals and Correspondence  IRB/IBC/RAC Approvals for Protocol  Amendments, Advertisements, Renewals  IRB Correspondence (Progress reports, letters of submission for approval, IRB notification, responses to SAE reports, and Safety Reports, Etc. 5. Laboratory  Lab Certifications (CAP & CLIA)  CV pathologist, if applicable 6. Study Logs  Investigator Personnel Team Signature Page  Site Visit Logs  Site Signature Logs  Master Subject Logs  Screening Logs  Training Logs (Site initiation Visit attendance log & training certificates) 7. Correspondence  Study related correspondence between the site, sponsor, CRO,etc. 8. Serious Adverse Events (SAE)  Master SAE Reporting Form and Instructions  Blank SAE Forms  Safety Letters  Completed SAE Reports (or note where they are located) 9. Drug Accountability  Study Drug Receipt/packing invoices  Study Drug Accountability Form  Study Drug Supply Forms 10. Miscellaneous  Miscellaneous (CRF transmittal logs), etc.

Step-by-step guide to activating a clinical trial - 6  Site initiation visit (SIV) Personnel/signature log Drug and protocol review Investigator responsibilties Patient enrollment procedures Serious adverse event reporting Handling and shipment of biological samples Drug shipment, storage, dispense CRF completion

McJoynt, T. A. et al. J Clin Oncol; 27: Future state value stream map for the protocol development process