Managing multi-site clinical trials Belinda Fazekas, Linda Devilee - PowerPoint PPT Presentation

Managing multi-site clinical trials Belinda Fazekas, Linda Devilee Flinders University receives funding for PaCCSC from the Australian Government Department of Prepared for: CPC Research Colloquium 2015 Health and Ageing under the National Palliative Care Program.

Overview  What is PaCCSC?  Phase III clinical trials conducted by PaCCSC  The clinical trial lifecycle – Pre-study – Recruitment – Completion  Recap  Supporting multi-site studies in palliative care

What is PaCCSC  The Palliative Care Clinical Studies Collaborative (PaCCSC) is a national research network that aims to: – Generate high quality research evidence to support the use of medicines and other interventions at the end of life to better manage or alleviate symptoms in patients such as: pain; confusion; breathlessness; appetite; and gastrointestinal problems including nausea; bowel obstruction; and constipation. – Build capacity within the health workforce in the conduct of high quality clinical research in patients nearing the end of life and the translation of research results into clinical practice.

Where is PaCCSC?  Members  Governance Structure – Management Advisory Board – Scientific Committee – Data and Safety Monitoring Committee – Trials Management Committee  PaCCSC Recruiting Sites across the country  Central Coordinating Office in Adelaide  Flinders University

PaCCSC Sites St Vincent’s Hospital/Centre for Palliative Care, Victoria The Royal Melbourne Hospital, Victoria The Austin Hospital, Victoria Barwon Health, Geelong, Victoria Mater Health Services, Queensland The Prince Charles Hospital, Queensland St Vincent’s Private Hospital, Queensland Nambour Hospital, Queensland Southern Adelaide Palliative Services, South Australia Lyell McEwin Hospital, South Australia Braeside Hospital, New South Wales Calvary Mater Newcastle, New South Wales Sacred Heart Hospice, New South Wales Calvary Health Care, Kogarah, New South Wales Greenwich Hospital, New South Wales Westmead Hospital, New South Wales John Hunter Hospital, New South Wales Liverpool Hospital, New South Wales Concord Hospital, New South Wales Ballarat Health Service, Victoria Hollywood Hospital/Curtin University, Western Australia St John of God Hospitals, Western Australia The Alfred Hospital, Victoria

MULTI-SITE CLINICAL TRIAL LIFECYCLE

Clinical Trial Life Cycle Year 2 Year 1 Year 3 Years 4-8 Year 9 Year 10 Trial Reach HREC final New idea SOPs Recruitment Governance sample size reporting Protocol Data Data Agreements Regulatory Clinical study development management management report Site Ethics/ Site Protocol Sponsor Finalise SAP selection governance start up amendments Disseminatio n activities Peer/ Investigation Site Undertake scientific Budget al Product payments analysis review Study closure Data Equipment/ Disseminatio Draft Funding Management licences n plan publication Pre Study Completion Recruitment

YEAR BY YEAR

Year one Year 1 New idea Protocol development Sponsor Peer Scientific review Funding Pre Study

Year 1 – The New Idea Year 1  The light bulb moment!  Where does the idea come from? New idea  How do I turn my new idea into a research reality?  Where do I start? Protocol  Who do I need to convince? development  Where do I get support to progress the idea? Sponsor  Who do I want on my team?  What expertise might I need to assist me? Peer  PaCCSC Standard Operating Procedure (SOP) to support Scientific review new idea development Funding Pre Study

Year 1 – Development of the Protocol Year 1 New idea What expertise do I need to turn this idea into a reality Protocol development Sponsor Peer Scientific review Funding Pre Study

Year 1 – Development of the Protocol  What will each individual bring to the study; impact factor; Year 1 clinical expertise; recruiting site; have they been involved before; who do they know – networks are vital to success New idea  What does a protocol look like – Templates, other examples Protocol development Sponsor Peer Scientific review Funding Pre Study

Year 1 – Development of the Protocol Year 1 New idea Protocol development Sponsor Peer Scientific review Funding Pre Study

Year 1 – Development of the Protocol  Where can I get assistance with the writing process Year 1 – Some template sections don’t make sense  Is what I’m trying to do in this study achievable New idea – Focus – Clear limits Protocol  Keeping track of changes ( version control ) development Sponsor Peer Scientific review Funding Pre Study

Year 1 - Sponsor  What does a Sponsor do? Year 1 – Quality assurance and quality control – Medical expertise, safety reporting, New idea – Trial design – Trial management, data handling and record keeping – Investigator selection and allocation of responsibilities Protocol development – Compensation to participants and investigators – Regulatory (CTN) and confirmation by the HREC Sponsor – Investigational product, manufacturing, packaging, supply – Monitoring and audit Peer  Who is the most appropriate sponsor for my study? Scientific review – University; Hospital; Pharmaceutical companies; biotech Funding Pre Study

Year 1 Peer/Scientific Review of the Protocol  What is peer/scientific review? Year 1  How does this review benefit my study? – Expertise in study design and methodology New idea – Scientific rigour – Lessons learned Protocol – Logistically successful development – Implementation issues  If the average length of a CT is 10 years the protocol needs to Sponsor be right from the start Peer  Who can do this? Scientific review – Scientific Advisory Committee – Independent review x 2 (at least) Funding Pre Study

Year 1 - Funding Year 1 New idea Protocol development Sponsor Peer Scientific review Funding Pre Study

Year 1 - Funding  How much is this going to cost? Year 1  Where can I source funds?  Who will hold the funding – remember the Sponsor is primarily New idea responsible for funding  Develop a plan – if one grant fails where to next? Protocol development  Prepare submissions – expect rejection  Will the study be stalled until funding is secured? Sponsor  Can the study be conducted differently, piloted initially with limited funds to gain data to support a larger scale funding Peer Scientific application? review  Have I got the right team to attract funding? Funding Pre Study

Year Two Year 2 Trial Governance Agreements Site selection Investigational Product Data Management Pre Study

Year 2 – Trial Governance  Who needs to be involved in the governance of the trial Year 2  Is there a structure already in place that you can tap into Trial  What committees need to be developed for what purpose Governance  What meetings need to be held  How often should they meet Agreements  What needs to be reported  How will specialist items such as safety reporting be reported Site selection during the trial What decisions are made where  Investigational Product How does the study report to the Sponsor, to the participating  sites, to the funding bodies Data Management Pre Study

Year 2 - Agreements Year 2  What agreements/contracts are needed, who with and what for? Trial Funding agreement – which institution is best placed to be the  Governance lead for the study = SPONSOR or ???  Do we need Research Collaboration Agreements or Multi- Agreements Institutional Agreements put in place; with whom; will there be funding exchanged Site selection  Clinical Trial Research Agreements – Medicines Australia standard template Investigational – Are any changes required Product – Will these changes stall the review and signature process – Is the funding body the Sponsor Data Management Pre Study

Year 2 – Site selection Year 2 Trial Governance Agreements Site selection Investigational Product Data Management Pre Study

Year 2 – Site selection  Which sites see the patients we want to recruit to this study Year 2  What information would be helpful for decision making about Trial what sites to chose Governance  What previous success has the site had with recruitment to other trials Agreements What are any known risks at the site/s  What other infrastructure at the site is in place  Site selection Staffing – is the Site Investigator interested in the trial, do they  have a research team to support their involvement Investigational  How many sites will the study need to reach the sample size Product in a reasonable timeframe Data Management Pre Study

Year 2 – Site selection  Consider site feasibility assessments Year 2 – Patient population Trial – Likely referral numbers Governance – Current research experience – Clinical interest Agreements – Infrastructure • Office Computer • Site selection Resources • Investigational Product Data Management Pre Study