Clinical Trials Development Resource for Hematologic Disorders (U24)

Transcription

1 Clinical Trials Development Resource for Hematologic Disorders (U24) Diane Catellier, DrPH RTI International RTI International is a trade name of Research Triangle Institute.

2 What is the U24 Resource? Funded by NHLBI in 2012 to provide a Clinical Trials Development Resource to assist investigators supported by NHLBI Clinical Trials Planning Studies for Rare Thrombotic and Hemostatic Disorders (U34) NHLBI Clinical Trial Pilot Studies (R34) for studies in area of hematology Goals Provide advice on trial design and implementation Offer training opportunities for clinical investigators so that they are better positioned to design trials in hematology in the future.

3 Goals of the collaboration between U34/R34 and U24 Resource To have more comprehensive planning done before an submission of an application for the full-scale trial (greater chance of success) and if awarded to start up faster U34 affords time and funding for investigators to complete planning steps saves precious time in initiating clinical trial when trial is ultimately funded (critical when only have 5 years to complete recruitment/follow-up in trial of rare diseases) U24 provides expert scientific and statistical advice, review of protocols and study materials, and support in planning the design and implementation of clinical trial

4 The U24 Team: Biostatisticians/Consultants Donald Brambilla, PhD Marie Gantz, PhD Diane Catellier, DrPH Sreelatha Meleth, PhD Nigel Key, MB ChB, FRCP Joe Ibrahim, PhD

5 Other RTI Staff Clinical study managers recruitment of study sites, recruitment of subjects, and development of brochures, manuals of operations and other study materials; Programmers Design of data entry systems, development of system security plans to satisfy FDA requirements Specialists in regulatory affairs Assist with interacting with the FDA

6 Provide advice on trial design and implementation Work with investigators to assess feasibility of the proposed trial the number of eligible patients at planned study sites likely willingness of eligible patients to enroll in the trial and to comply with assigned treatment, barriers to adherence to assigned treatment and study procedures Appropriateness of the proposed sample size and justification for the hypothesized treatment effect

7 Provide advice on trial design and implementation Advise investigators on study design issues including formulation of clearly specified and testable hypotheses, trial design alternatives (Bayesian or adaptive trial designs, biomarkers as surrogate endpoints) identification of clinically meaningful endpoints and associated measurement requirements measurement schedule randomization schemes drug and placebo suppliers if required study monitoring (safety, protocol adherence) statistical analysis plans

8 Provide advice on trial design and implementation Advise investigators on the practical aspects of trial implementation, enrollment plan regulatory affairs (informed consent documents, INDs, IRB approvals) oversight issues (interim analyses, adverse event reporting, reports to the DSMB) data capture and data management systems Quality assurance/quality control case report forms, manual of operations. We offer review and critique of proposals or sections thereof

9 Provide training to better position investigators to develop future clinical trials Develop guidance documents that will cover topics that are frequently encountered in trial design Recruitment and retention NHLBI grant funding application process for the Multi-Site Clinical Trials (Collaborative R01) FOA, particularly for applications that request > $500K in direct costs in any year Site selection Human subject protection, informed consent & regulatory considerations adverse event reporting, statistical analysis plans, data monitoring plans, trial coordination, and regulatory affairs.

10 Visit the Website accthd.rti.org

11 U34/R34 Studies Using the Resource Margaret Ragni INHIBIT STUDY: Phase III Randomized, Controlled Trial of Preemptive vs. Standard Prophylaxis with Recombinant Factor VIII to Prevent Inhibitor Formation in Children with Severe Hemophilia A (U34) Hemophilia Adult Prophylaxis Study (R34) Marilyn Manco-Johnson Pediatric High-Risk Deep Venous Thrombosis Lytic Outcomes (PHLO) Trial (U34) James Bussel Treatment Trial for Immune Thrombocytopenia (ITP) in Adults (U34)

12 U34/R34 Studies Using the Resource Margaret Ragni The Von Willebrand s Disease Minimize Study (U34) Keith McCrae Efficacy of Pomalidomide in Hereditary Hemorrhagic Telangiectasia (HHT)-related bleeding (U34) Thomas Ortel Anticoagulation Withdrawal in Antiphospholipid Syndrome - WAR-APS (U34) Suresh Vedantham Chronic Venous Thrombosis: Relief with Adjunctive Catheter- Based Therapy - C-TRACT (U34)

13 How do we know we are succeeding? Funding the full-scale clinical trial is critical sign of success successful implementation of the trial Critiques of applications in terms of design and feasibility will suggest quality, and identify strengths/weaknesses Greater number of R34 applicants