IACRN Meeting Role of a CRO in Rare Disease Trials Jane Ahlrichs - PowerPoint PPT Presentation

IACRN Meeting – Role of a CRO in Rare Disease Trials Jane Ahlrichs RN, BSN, M.Ed. Executive Director, Study Management CTI Clinical Trial and Consulting Services IACRN Regional Meeting 15-Feb-2017 1

Introduction IACRN Regional Meeting 15-Feb-2017 2

Objectives 1. Role of a Clinical Research Organization (CRO) vs. Industry Sponsor in the conduct of clinical trials 2. Role of a CRO in managing trials in rare disease populations 3. Importance of collaboration and partnership between the Sponsor, CRO and site staff in the successful conduct of rare disease trials 3 IACRN Regional Meeting 15-Feb-2017

Activities to Meet the Objectives 1. Overview of the role and responsibilities of Industry sponsor and CRO 2. Overview of a CRO organizational structure and roles of the CRO team 3. Overview of Rare Disease Designation 4. Specific aspects of trial management in rare disease trials 5. Enrollment and retention, and strategies to enable patients to be able to participate in clinical trials 6. Present a case study – Managing a trial in a rare disease population 7. Importance of collaboration between the Sponsor, CRO and site staff 4 IACRN Regional Meeting 15-Feb-2017

What is a Clinical Research Organization (CRO) IACRN Regional Meeting 15-Feb-2017 5

Clinical Research Organization CROs • Provides support to the pharmaceutical, biotechnology, and medical device industries • Services outsourced on a contracted basis • Grew when Pharma companies needed to decrease overhead • Opted for outsourcing solutions – transfer of services to outside vendors (Monitoring, Safety, Data, Regulatory) • Range from large, international full-service organizations to small, niche specialty CROs 6 IACRN Regional Meeting 15-Feb-2017

Responsibilities of Sponsors, CROs and Investigators and Keys to Success IACRN Regional Meeting 15-Feb-2017 7

Responsibilities in Clinical Trials The Ultimate Goal Regulatory Authority Sponsor CRO Improvement in Subject Safety Patient Care Efficacy Quality/Integrity IRB/IEC Site 8 IACRN Regional Meeting 15-Feb-2017

Who is Who…and What Do They Do? Sponsors Regulatory Authorities IRB/IEC Pharmaceutical Companies FDA Central • Biotech Companies EMEA WIRB • Individual Investigators HealthCanada Shulman Local: Per institution  Develop products to  Ensure the safety and effectively and safely treat efficacy of any drug  Ensure the safety of patients patients utilized to treat patients in using IP in their institutions their country Sites Vendors CROs Academic Center Central Labs CTI Clinical Trial and Consulting • Hospitals Drug Depots PPD • Clinics IWRS Quintiles Research Centers Home Health MedPace Practioners  Perform required patient  Perform all contracted services Phase 1 Units research services that to secure quality, integrity and protect integrity of safety of patients and data  Secure best tx options, specimens, assessments, care and safety of their and data patients IACRN Regional Meeting 15-Feb-2017 9

General Responsibilities: Sponsor Sponsor Responsibilities  Protocol and IB: Develop, maintain and distribute  IND: Submit and maintain the IND (Investigational New Drug Application)  Investigators: Select and ensure they are qualified and provide essential information  Financial Disclosure: Ensure no investigator bias from financial gain  Compliance: Ensure investigation is conducted according to the protocol  Monitoring: Ensure compliance through proper monitoring  Safety: Ensure Regulatory Authorities and investigators are informed of significant adverse events and risks associated with drug – stop study if needed  Drug Accountability: Control of the Investigational Product  Records: Maintain adequate records (Medical Records, ISF, TMF, trial documents)  Access: Allow Regulatory Authority inspection of records and reports  Annual Reports: Keep Regulatory Authorities apprised of study progress IACRN Regional Meeting 15-Feb-2017 10

General Responsibilities: Investigator Investigator Responsibilities  Protect the rights, safety and welfare of subjects  Ensure subjects provide informed consent prior to participation  Conduct and provide oversight of the investigational plan  Ensure compliance with all requirements of the protocol  Ensure all colleagues are informed and trained in their study responsibilities  Control drug under investigation  Maintain adequate records (Drug, Medical Records, ICF)  Ensure IRB/EC review and approval IACRN Regional Meeting 15-Feb-2017 11

CRO: Clinical Trial Operations and Project Execution IACRN Regional Meeting 15-Feb-2017 12

General Responsibilities: CRO • CROs are contracted to assume any responsibilities or obligations that are transferred from the sponsor • Should be described in writing (contract) and in Transfer of Responsibility (TORO) • CROs are responsible and held to the same standards as the sponsor making the CRO subject to the same regulatory actions • Assist sites with meeting their obligations as well 13 IACRN Regional Meeting 15-Feb-2017

Typical Clinical Trial Services Provided by a CRO Data Trial Management Management Clinical Regulatory Monitoring Affairs Clinical Trial Medical Services Biostatistics Monitoring Contracting Quality Assurance & Budget Audits Negotiation Global Drug Safety 14 14 IACRN Regional Meeting 15-Feb-2017

Typical CRO Contracted Services Sponsor CRO Other Third Party Vendors • • • Oversight of Trial Day to Day Operations Central Lab • Drug Depot • • Investigational Product Site ID and Qualification • Home Health Care • • IND Management Development of Study • IWRS Materials • Regulatory Authority • Submissions (FDA, EMEA) Clinical Monitoring • • Investigational Brochure Medical Monitoring • • Protocol Development Regulatory - Sites • • ICF Development Site Contracting/Budget • Data Management • Biostatistics • Safety • Trial Master File • Vendor Management • 15 Site Payments IACRN Regional Meeting 15-Feb-2017

Typical US Study Team Sponsor CRO Study Director Quality CRO Study Manager Assurance CRO Study Coordinator Safety Medical Monitor Lead CRA Biostatistics Data Management Regulatory Legal CRAs Study Site IACRN Regional Meeting 15-Feb-2017 16

Study Management Some would say that a Study Manager is…. A person with responsibility for doing something that has never been done before for people who don’t always know exactly what they want, who is often placed in a position of predicting the unknown, making a plan for the unforeseen and executing the plan with resources that they cannot always control but who is usually completely help responsible for the results! 17 IACRN Regional Meeting 15-Feb-2017

Study Management Seriously Though….What is a Study Manager? • Strategically they set direction, provide support, anticipate and remove obstacles. • They are a liaison between the various members of the study team, the sponsor and vendors. • They provide leadership and are champions and advocates for their study. • They carry all responsibilities associated with the study and its deliverables Active Collaboration and Problem Solving throughout the Trial Remove the Obstacles! Enable others success! 18 IACRN Regional Meeting 15-Feb-2017

CRO: Roles of Various Departments Monitoring Data Management Safety o o o Partnering with Sites and CRF and Instructions (w/ SAE reporting procedures Sponsor Study Management) o SAE review and o o Site Visits (PSV, SIV, IMV, Database development, development of patient COV) testing and maintenance narratives o o o Problem ID and resolution Data cleaning Collaborates with Med Mon and Sponsor to assess for o o Informed Consent Query management safety trends o o Subject safety, well-being Database lock o Report to Reg Authorities o Integrity of the trial data o Protocol compliance Medical Monitor Regulatory Biostatistics o o o Protocol expertise and Collection and maintenance Develop and manage support of required site regulatory randomization scheme documents o o I/E criteria questions Develop Statistical Analysis o Development/review of ICF Plan o Safety Assessments o Data analyses/CSR o DMC IACRN Regional Meeting 15-Feb-2017 19

So What is Involved in Trial Execution? IACRN Regional Meeting 15-Feb-2017 20

Begin with the End in Mind…. Sponsor CRO Site Trial Documents Patient Data Patient Records and Trial Master File Analysis of Safety and Efficacy (Compliance and Reproducibility) IACRN Regional Meeting 15-Feb-2017 21

Key to Success in all Phases • Site Success = Study Success • We cannot do this without you! • Open Collaboration with our Sites • Enrollment • Protocol and GCP Compliance • Integrity of the Data • Work to understand the needs and challenges • Collaborate to find solutions: Sites + CRO + Sponsor 22 IACRN Regional Meeting 15-Feb-2017

Trial Phases Study Start – up Enrollment Maintenance and Study Closure 23 IACRN Regional Meeting 15-Feb-2017