Fairmont The Queen Elizabeth Montreal, Quebec
Transcription
Fairmont The Queen Elizabeth Montreal, Quebec
3 7 th A n n ua l Me e t i ng M a y 15 - 1 8 , 2 0 1 6 • • • • Program Information Registration Form Schedule of Events P re-Meeting Workshop Information • Invited Session Details • C ontributed Paper and Poster Presentations • H otel & Travel Reservation Information Fairmont The Queen Elizabeth Montreal, Quebec www.sctweb.org General Information SCT Annual Meeting May 15 - 18, 2016 Sustainable Car Travel The Fairmont properties in the Québec province have installed electric vehicle charging stations in partnership with Hydro-Québec’s Electric Circuit. Electric vehicle users can now drive worry-free, knowing that a public network of charging stations is available to meet their needs. Our charging station is located in the indoor parking. The Society for Clinical Trials, an international community of professionals from a variety of disciplines involved with the design, conduct and analysis of clinical trials, invites you to attend its 37th Annual Meeting, May 15 – 18, 2016, at Fairmont The Queen Elizabeth in Montreal, Quebec, Canada. Travel by Air The closest airport to Fairmont The Queen Elizabeth is the Montréal-Pierre Elliott-Trudeau International Airport (YUL) located 14 miles (22 km) from the hotel. Visas and Entry Requirements Visit www.travel.state.gov for information regarding visas and entry requirements for Canada. You may also contact the nearest U.S. Embassy in your region. Transportation Options Fairmont The Queen Elizabeth 900 René-Lévesque West Montréal, QC H3B 4A5, Canada +1 514-861-3511 http://www.fairmont.com/queen-elizabeth-montreal/ Taxi There is a flat rate of $40 CAD to downtown hotels. Arrangements for a limousine transfer can be arranged with the hotel concierge upon request. Subway The hotel has direct access to the Bonaventure Metro Station. There is a hotel entrance from the metro station. Follow signage. SCT has secured a rate of $229 CAD single/double at Fairmont The Queen Elizabeth. The SCT rate is available through April 13, 2016 or until the hotel block is full. After that, rooms and rates are subject to availability. Visit www. sctweb.org for hotel information and reservation links. Train The hotel is located directly above Central Station, which is the stop for VIA Rail, Amtrak and several local trains. There is a hotel entrance from Central Station. Follow the signage. Hotel Internet Access SCT has secured free internet in sleeping rooms for SCT meeting attendees at the Fairmont The Queen Elizabeth, which also offers wireless internet connectivity in all public areas such as the main lobby and lounges. Unfortunately, due to cost constraints, SCT is not able to secure Wi-Fi Internet access in the general meeting area. 747 Express Bus Featuring nine stops in each direction, the 747 service operated by the city of Montréal is provided 24 hours a day, 365 days a year, and offers transportation between downtown Montréal and Montréal-Pierre-Elliott-Trudeau International Airport. Tickets are purchased at the cost of $10 inside the terminal before boarding. When returning, a $10 bus fare is paid aboard the bus (coins only, bills are not accepted). Tickets provide travelers with a transit pass valid on the STM bus and metro network for 24 hours. For more information, visit the STM website. Parking The hotel parking areas are owned and operated by Indigo: Valet parking Entrance on North side of Belmont Street or on Cathcart Street: • $29 per night, taxes extra, departure prior to 4:00 p.m. • In and out privileges Self-parking Entrance on South side of Belmont Street Fees must be paid at the parking pay stations. Return Meeting and Membership Forms ONLY to: Society for Clinical Trials, Inc. 100 North 20th Street, Suite 400 Philadelphia, PA 19103 Tel: +1.215.320.3878 Fax: +1.215.564.2175 Email: [email protected] Website: sctweb.org 1 Annual Meeting Registration Registration Early Bird registration is available through April 1, 2016. Registrations received after this date will not qualify for the reduced registration fee. Please register online to pay by credit card (Visa, MasterCard, or American Express). SCT also accepts payments by personal or company check, which can be made payable to the Society for Clinical Trials, and mailed to: SCT, 100 N. 20th St. Suite 400, Philadelphia, PA, 19103. All fees are in U.S. Dollars. Pre-Meeting Workshop Half Day . . . . . . . . . . . $100 each Annual Meeting . . . . . . . . . . . . . . . . . . . . . . . $300 **To see the list, go to the following: http://www.sctweb.org/docs/membership/SCT 2015 list of Developing Countries.pdf Pre-registration closes May 12, 2016. After May 12, attendees can register onsite when the meeting opens at Fairmont The Queen Elizabeth on May 15. Registration Fees Early Bird registration is available through April 1, 2016. Registrations received after this date will not qualify for the reduced registration fee. All fees are in U.S. Dollars. Full Meeting Registration will include access to mid-morning and afternoon coffee breaks (Monday – Wednesday), luncheons (Monday and Tuesday) and receptions. Arrangements for special dietary meals must be made in advance by contacting SCT Headquarters at [email protected] or +1.215.599.6633. Pre-Meeting Workshop Registration For SCT Members On or Before April 1 (Early Bird Special!): Pre-Meeting Workshop Half Day . . . . . . . . . . . $200 each Annual Meeting . . . . . . . . . . . . . . . . . . . . . . . $475 Guests accompanying meeting participants to luncheons are required to pay a fee of $40 per luncheon. Please notify SCT Headquarters of any guests before the meeting by contacting [email protected] or +1.215.599.6633. After April 1: Pre-Meeting Workshop Half Day . . . . . . . . . . . $250 each Annual Meeting . . . . . . . . . . . . . . . . . . . . . . . $575 Cancellation Policy All cancellations must be written and received at the SCT office by Sunday, May 1, 2016. Annual Meeting cancellations will be refunded less a $100 administrative fee. Pre-Meeting Workshop Sessions will be refunded less a $50 administrative fee. After May 1, NO REFUNDS will be issued. Refunds will be issued 4 - 6 weeks post conference. Special requests should be directed to the SCT Office at [email protected] or +1.215.599.6633. (Reminder: SCT Annual Dues for 2016 must be paid in full in order to qualify for the Member Registration Fee.) For Non-Members On or Before April 1 (Early Bird Special!): Pre-Meeting Workshop Half Day . . . . . . . . . . . $200 each Annual Meeting . . . . . . . . . . . . . . . . . . . . . . . $675 Registration Transfers Registration transfers MUST be in writing and received by the SCT Business Office by Sunday, May 1, 2016. After this date, refunds will not be issued for unused registrations. Transfers cannot be made onsite. After April 1: Pre-Meeting Workshop Half Day . . . . . . . . . . . $250 each Annual Meeting . . . . . . . . . . . . . . . . . . . . . . . $775 *Non-Member Registration at the Non-Member price includes SCT membership for June – December 31, 2016. Onsite Registration Onsite registration is available for the Annual Meeting; however, your choice of Pre-Meeting Workshops cannot be guaranteed. After Thursday, May 12, 2016, attendees must register onsite in Montreal. For Students (Proof of Full Time Student Status must be provided with Registration) Pre-Meeting Workshop Half Day . . . . . . . . . . . $75 each Annual Meeting . . . . . . . . . . . . . . . . . . . . . . . $150 Student Non-Member Workshop Half Day . . . . . $75 each Student Non-Member Annual Meeting . . . . . . . $225 37th Annual Meeting Registration Desk Hours Sunday, May 15 7:00 AM – 7:00 PM Monday, May 16 7:00 AM – 5:30 PM Tuesday, May 17 7:00 AM – 5:30 PM Wednesday, May 18 7:00 AM – 11:00 AM Accepted proof of student status: Copy of valid student ID card, letter from institution registrar, letter from department head, copy of paid tuition bill for current semester. For Members from Developing Countries** Pre-Meeting Workshop Half Day . . . . . . . . . . . $100 each Annual Meeting . . . . . . . . . . . . . . . . . . . . . . . $200 For Non-Members from Developing Countries** 2 Schedule of Events • Workshops are a separate fee from the Meeting. Please register using the SCT meeting registration form. • Attendees may sign up for up to three workshops (AM and PM Half Day Workshops plus an Evening Workshop). * Breaks on Monday, Tuesday, Wednesday, as well as lunch on Monday and Tuesday and the Monday evening reception are included with Annual Meeting Registration. For Sunday workshops, breaks are included but lunch is not provided. For workshop descriptions and faculty listing, see page 7 All information subject to change. Sunday, May 15, 2016 7:00 AM – 7:00 PM Registration Pre-Meeting Workshops 8:00 AM – Noon Workshop P1 Essentials of Randomized Clinical Trials Part 1: Clinical Trials Design and Conduct 1:00 PM – 5:00 PM Workshop P6 Essentials of Randomized Clinical Trials Part 2: Basic Concepts in Statistical Analysis and Reporting of Results 7:00 PM – 9:00 PM Half Day Workshops - Morning Workshop P2 Clinical Trial Management in Multicenter Trails: Navigating the Complexities Workshop P3 Independent Data Monitoring Committee Reports: A Practical Guide for Reporting Statisticians Workshop P4 Platform Trials: A Vision of the Future Workshop P5 Leveraging Online Technology for Purposes of Remote Monitoring Throughout the Protocol Lifecycle Workshop P9 Overview of Non-Inferiority Studies Workshop P10 Modern Approaches to the Design and Analysis of PatientReported Outcomes (PROs) Half Day Workshops – Afternoon Workshop P7 Workshop P8 Crafting Clinical Trial Conducting Valid Data for Sharing Trials: The Critical the Reuse - Moving (and Misunderstood) from Basic Data Roles of Management to Randomization and Practicing Data Complete Follow-Up Curation Evening Workshops Workshop P11 Modern Mediation Analysis in Randomized Trials Workshop P12 Protocols in Real Life: Training Study- Site Staff the GPC Way 3 Workshop P13 Cost Effective Analysis for Clinical Trials Schedule of Events Monday, May 16, 2016 7:00 AM – 5:30 PM Registration 8:00 AM – 5:30 PM Exhibits 8:00 AM – 8:15 AM Welcome - SCT President, Wendy R. Parulekar NCIC Clinical Trials Group. Kingston, ON Canada 8:15 AM – 8:30 AM Presentation of the Class of 2016 Fellows 9:00 AM – 10:15 AM Curtis Meinert Lecture – Denis Lacombe, MD, PhD “European Organization for Research and Treatment of Cancer (EORTC): Vision, Strategic Focus and Implementation Strategy” 10:15 AM – 10:45 AM Break: Exhibits/Posters 10:45 AM – 12:15 PM Invited Sessions I Invited Session 1 Challenges and Solutions to the Coordination and Conduct of an Emergency Treatment Trial Invited Session 2 Early-Phase Designs for Contemporary DoseFinding Problems in Oncology Invited Session 3 Recommendations on the Use, Conduct, and Training of Data Monitoring Committees: The Clinical Trials Transformation Initiative’s Data Monitoring Committee Project Invited Session 4 Data and Biorepositories: Enhancing Collaborative Science Invited Session 5 Missing Data Issues in Cluster-Randomized Designs for Pragmatic Trials: A Practical Overview M, TM, E ST ST, TM IS/DM, ST, R ST 12:15 AM – 1:30 PM Lunch (included with meeting registration) 1:30 PM – 3:00 PM Contributed Paper Sessions I CPS 1 CPS 2 CPS 3 Time to Event Miscellaneous The Trials and Analyses in RCTs Statistical Issues in Tribulations of RCTs Study Coordination ST ST CPS 4 Managing Data Across the Trial Lifecycle CPS 5 The Ins and Outs of Trial Design IS/DM M, DM, ST SC 3:00 PM – 3:30 PM Break: Exhibits/Posters 3:30 PM – 5:00 PM Invited Sessions II Invited Session 6 It’s Always Too Early until Suddenly It’s Too Late: Designing Surgical RCTs Relevant to Patients, Staff, and Changing Technologies Invited Session 7 What Happens When a Trial Is Interrupted? How to Deal with Suspension of Randomization and Restart Your Trial Invited Session 8 Courage, Controversy, and Clinical Trials: Lessons from the Ebola Epidemic M, ST TM TM, ST, E 6:30 PM – 8:00 PM CPS 6 Thomas Chalmers Student Scholarship Presentations Invited Session 9 Invited Session 10 Design, Conduct Ethical Challenges in and Reporting of Pragmatic Comparative Pilot and Feasibility Effectiveness Trials Studies Carried Out in Preparation for an RCT TM, ST E, M, ST Reception *All information/scheduling subject to change. Track Key Information Systems/Data Management (IS/DM); Medical (M); Regulatory Issues (R); Ethics (E); Study Coordination (SC); Statistical (ST) Trial Management (TM) 4 Schedule of Events Tuesday, May 17, 2016 7:00 AM – 5:30 PM Registration 8:00 AM – 5:30 PM Exhibits 8:00 AM – 9:00 AM Contributed Paper Sessions II CPS 7 CPS 8 CPS 9 Statistical Issues Statistical Lessons Coordinating RCTs: in Non-Inferiority from Across the Lessons Learned Trials Trial Spectrum ST 9:00 AM – 10:30 AM Invited Session 11 Pragmatic Trials ST CPS 12 Cluster Randomized Trials/CrossProtocol Analyses IS/DM M, SC ST SC ST ST TM, IS/DM ST Invited Session 18 Collaborating with Patient Advocacy Groups at the Design State of Your Clinical Trial: Why It Is So Important Invited Session 19 Use of Mobile Health Technologies in Pragmatic Clinical Trials Invited Session 20 Innovative Trial Designs for Precision Medicine TM TM, ST, E ST 10:30 AM – 11:00 AM Break: Exhibits/Posters 11:00 AM – 12:30 PM Invited Sessions IV Invited Session 16 Invited Session 17 Improving Health by Guidance on Specifying Improving Trials: The the Target Difference UK MRC Hubs for Trial (Effect Size) for an RCT Methodology Research (HTMR), a Nationwide Network to Develop Capacity and Optimize Trial Design and Conduct IS/DM, TM M, ST Lunch/SCT Business Meeting (included with meeting registration) 1:45 PM – 2:45 PM Contributed Paper Sessions III CPS 13 CPS 14 CPS 15 Systematic Novel Statistical Improving Reviews and Meta Approaches to Participant Analysis RCTs: stratification, Involvement in global outcomes, RCTs personalized treatments and mediation ST, M CPS 11 Engaging Communities/ Topic-Specific Trial Issues Invited Sessions III Invited Session 12 Invited Session 13 Invited Session 14 Invited Session 15 Efficient Study Designs Statistical Challenges Expanding Your Clinical Trial in Clinical Research in Recent Development Reach: Innovations Simulations: The When, of Personalized and Opportunities for Where, and What Medicine -- Through Remote Participant Biomarker Subgroup Visits to Boost Identification to Retention and Companion Diagnostic Enrollment in Research Device Development Studies ST, M, R 12:30 PM – 1:45 PM CPS 10 Implementation of Electronic Data Capture Systems ST SC, DM 5 CPS 16 Electronic Data Capture and Data Visualization CPS 17 Compliance and Adherence CPS 18 Multiplicity in RCTs IS/DM, R ST ST Schedule of Events 2:45 PM – 3:15 PM Break/Exhibits/Posters 3:15 PM – 4:45 PM Invited Sessions V Invited Session 21 Challenges of Implementing an Adaptive Design in an Academic Network Setting Invited Session 22 Streamlining Clinical Trials: The Practicalities Invited Session 23 Statistical Challenges in Immuno-Oncology Invited Session 24 Building the Clinical Trials Enterprise of the Future Invited Session 25 Prospective Individual Participant Data MetaAnalysis ST, M, TM ST, TM, R ST, M IS/DM, ST, R ST, M 4:45 PM – 6:00 PM Trial of the Year - The Learning Early about Peanut Allergy (LEAP) Trial Wednesday, May 18, 2016 7:00 AM – 11:00 AM Registration 8:00 AM – 9:00 AM ounders Lecture - Richard Stephens F “Patients as Cancer Research - Walking the Walk in the UK” 9:00 AM – 9:15 AM Break 9:15 AM – 10:45 AM Invited Sessions VI Invited Session 26 The International Behavioural Trial Network (IBTN): An International Effort to Improve the Rigor and Impact of Behavioral Clinical Trials Invited Session 27 FDA IND Reporting Rule Compels a New Dialog among the DMC, Sponsor, and FDA Invited Session 28 Central IRBs: Implementation, Effectiveness, and Optimization Invited Session 29 Use of Administrative and Registry Data in Clinical Trials Invited Session 30 Crossover Trials: New Perspectives and Practical Implications for an Efficient Design TM M, ST M, ST, R, E M, R, E, ST ST, M 10:45 AM – 11:00 AM Break 11:00 AM – 12:30 PM Contributed Paper Sessions IV CPS 19 CPS 20 CPS 21 Statistical Statistical Issues Trial Management Approaches in in Cancer and & Study Stepped Wedge Adaptive Trials Coordination Designs Across the Trial Lifecycle ST ST DM, SC CPS 22 Managing Data in the 21st Century CPS 23 Pragmatic Trials/ Stepped Wedge/ Missing Data CPS 24 Regulatory and Ethical Issues in Trials IS/DM, SC ST R, E *All information/scheduling subject to change. Track Key Information Systems/Data Management (IS/DM); Medical (M); Regulatory Issues (R); Ethics (E); Study Coordination (SC); Statistical (ST) Trial Management (TM) 6 Pre-Conference Workshops May 15, 2016 Half Day Workshops – Morning Workshop P1 Essentials of Randomized Clinical Trials Part 1 - Clinical Trials Design and Conduct 8:00 AM – Noon Part 1 (AM) and Part 2 (PM) of the “Essentials of Randomized Clinical Trials” workshop are distinct and can be taken individually or together. Although Part 1 is not a prerequisite for Part 2, the two workshops are complementary. This workshop is an introduction to design and conduct of clinical trials. Statisticians and non-statisticians working in trial-related jobs wishing a more full understanding of the basic concepts used in modern clinical trials would benefit from this course. Real-world examples are used to demonstrate essential tenants of clinical trial methodology. The following specific topics are covered: • Rationale for Clinical Trials, Clinical Trial Phases, Equipoise • Most Common Trial Designs • Key issues in the design of a RCT • Ethics, Informed Consent, and Patient Safety • Choice of Endpoints • Randomization • Data Collection, Routine Monitoring and Reporting, and Quality Control Target Audience: The workshop is intended for those with little previous experience or formal training in clinical trials as well as those who have some basic clinical trial experience but desire a better fundamental understanding of the methodological principles and concepts involved in clinical trials. Goals: 1. To explain in simple English the basic concepts behind clinical trial methodology, with real-world examples to illustrate these concepts. 2. A ttendees should be able to describe the essential elements of clinical trials and use this knowledge to contribute as a researcher and collaborator in the successful conduct of a clinical trial. Faculty: Laura Lovato, Wake Forest University Michele Melia, Jaeb Center for Health Research Yves Rosenberg, National Heart, Lung, and Blood Institute, NIH Workshop Organizers: Laura Lovato, Wake Forest University Michele Melia, Jaeb Center for Health Research Yves Rosenberg, National Heart, Lung, and Blood Institute, NIH Paul Wakim, Clinical Center, NIH Workshop P2 8:00 AM – Noon Clinical Trial Management in Multicenter Trials: Navigating the Complexities There are many partners involved in the design and implementation of multicenter clinical trials. These include the sponsor, participating clinical sites, vendors, regulatory bodies, as well as contract research organizations or academic coordinating centers. In order to implement trials efficiently and achieve high quality data, there must be good harmonization of efforts among all partners. These include study start-up, ongoing trial activities, drug/device and supply management, training and certification, data collection, on-site monitoring, 7 Pre-Conference Workshops May 15, 2016 safety management, regulatory review, and performance monitoring. The first issue to be worked out is who is responsible for what? Then, are they aware of their responsibilities? Followed by, how do we all help each other achieve our responsibilities? This workshop will present different techniques and models for communication utilized in multicenter clinical trial management to promote harmonization. This workshop will also highlight the complexities of conducting international and genomically-driven trials. Scenarios will be presented such as building data systems and integrations across multiple systems, enrolling the first subject, adverse event reporting, monitoring visits, different models for education and training, and preparing a DSMB report. These will be examined from multiple partners’ perspectives. Tips and tools will be provided to promote harmonization. Target Audience: Principal Investigators, Study Coordinators, Statisticians, Information Technology Managers, Project Managers, Data Managers, and Site Monitors. Goals: To provide the audience with tools and tips to achieve better harmonization of efforts to successfully implement and conduct from start to finish multicenter clinical trials from all partner perspectives.. Faculty: Marianne Kearney Chase, Massachusetts General Hospital Leigh Ann Chamberlin, Cincinnati Children’s Hospital Michelle Mahoney, Mayo Clinic Shauna Hillman, Mayo Clinic Workshop Organizers: Dixie Ecklund, University of Iowa Sumithra Mandrekar, Mayo Clinic Workshop P3 8:00 AM – Noon Independent Data Monitoring Committee Reports: A Practical Guide for Reporting Statisticians In many clinical trials, an Independent Data Monitoring Committee (IDMC) is responsible for safeguarding participant safety and trial integrity. To discharge these responsibilities, the IDMC relies on multiple sources of information, but none is so important as the IDMC Interim Report, the comprehensive report on emerging trial data received at regular intervals from a reporting statistician or statistical group. Providing these reports to IDMCs is a daunting task, and good advice on best reporting practices is hard to find. Because of the confidential nature of IDMC operations, sponsors and CROs may have a limited understanding of how IDMCs actually use these reports, and IDMC members themselves frequently find it difficult to articulate their needs before seeing actual displays of real data. Usually, the burden falls on the reporting statistician to take an active role in providing the most effective reports to IDMCs. This workshop will deal with practical issues related to preparing IDMC Interim Reports that best meet the needs of the IDMC. We have had years of collective experience serving on and reporting to IDMCs. We will use insights we have gained – and opinions that we have – to discuss what experienced IDMC members look for in IDMC Interim Reports. We will describe general analytic techniques most applicable to reporting on interim data. We will demonstrate principles of presentation and organization that facilitate IDMC review (sample tables of content, merits of small and large reports, executive summaries, etc.). We will look specifically at techniques for presenting analyses of common types of clinical trial data (e.g., enrollment and disposition, adverse events, and laboratory measures). Recurring themes will include the essential differences between IDMC Interim Reports and final Clinical Study Reports; the relative merits of timeliness versus cleanliness in data and analysis; and the importance of flexibility and adaptability in IDMC reporting to meet IDMC needs as they evolve over the course of the trial. Target Audience: The target audience includes statisticians who report to IDMCs, sponsors and CROs who are responsible for providing data to these reporting statisticians, and members of IDMCs who want to learn what to expect (and demand!) from IDMC Interim Reports. 8 Pre-Conference Workshops May 15, 2016 Goals: To help participants understand: • how IDMCs use IDMC Interim Reports and what they expect from a well prepared report • the differences between IDMC Interim Reports and other trial reports • the challenges of analyzing interim data and the balance between timeliness and cleanliness • a typical table of contents for such a report • organizational techniques that encourage efficient IDMC review • the role of flexibility in the reporting process • how Sponsors and CROs can facilitate the reporting statistician’s job of reporting to the IDMC Faculty: Janet Wittes (Moderator), Statistics Collaborative Inc. Kevin Buhr, University of Wisconsin - Madison Janelle Rhorer, Statistics Collaborative Inc. Matt Downs, Statistics Collaborative Inc. Jean Rouleau, Montreal Heart Institute Workshop Organizer: Kevin Buhr, University of Wisconsin – Madison Workshop P4 Platform Trials: A Vision of the Future 8:00 AM – Noon Traditionally, clinical trials have been designed to evaluate a single treatment in a homogeneous group of patients. However, such trials do not provide the physician with the necessary information to make decisions regarding the best treatment for an individual patient. To overcome this disconnect between trial design and personalized patient care, we advocate the use of multi-arm platform trials. Platform trials have master protocols that evaluate multiple treatments across one or more types of patients. Such designs are especially useful for exploring heterogeneity and interactions of treatment effects, evaluating combinations of treatments, and for direct comparisons between competing treatments. The sharing of resources in platform trials possibly between multiple sponsors can greatly reduce costs and increase statistical efficiency. Adaptive platform designs offer flexible features such as dropping treatments for futility, declaring one or more treatments superior, or adding new treatments to be tested during the course of a trial. In an era of personalized medicine, platform trials provide the innovation needed to efficiently evaluate modern therapies. Target Audience: Statisticians, clinicians, and researchers involved in clinical trial design. The minimum requirement is an introductory background in clinical trial design and analysis. Goals: This workshop will 1. Present the motivation and principles underlying platform trials from a physician’s perspective; 2. Demonstrate statistical efficiencies of platform trials relative to traditional strategies; 3. D escribe real applications and innovative features of platform trials, e.g. pandemic influenza & brain cancer (GBM); 4. Show how simulations are used in the design stage to refine prospective master protocols; 5. D iscuss challenges (statistical, logistical, & regulatory interactions) associated with the implementation of platform trials. Faculty: Jason Connor, Berry Consultants Roger Lewis, Harbor-UCLA Medical Center Ben Saville, Berry Consultants Workshop Organizers: Ben Saville, Berry Consultants 9 Pre-Conference Workshops May 15, 2016 Workshop P5 8:00 AM – Noon Leveraging Online Technology for Purposes of Remote Monitoring Throughout the Protocol Lifecycle When you think of monitoring a clinical trial, do you picture a clinical research associate physically traveling to a research site to initiate or close a study, or to conduct an interim visit? New perspectives on monitoring emphasize the benefit of more efficient monitoring of data, documents and processes throughout the lifecycle of a study, and ongoing developments in information technology have expanded the standard repertoire of monitoring strategies to allow for alternative monitoring approaches. While traditional on-site monitoring is still valuable and often necessary, many other options are available as alternatives or supplements for the monitoring of clinical trials. Among these are remote site initiation, remote consent form monitoring, real-time protocol deviation and Adverse Event monitoring, periodic integrity checks of data and processes as well as monitoring status reports, and remote site close out visits. These procedures offer a convenient and affordable way to monitor, allow for more flexibility in scheduling and accessibility (e.g., in the case of remote site visits), and enhance the conduct of high-quality studies. This workshop will outline the range of remote monitoring options, provide general guidelines for designing remote site visits, and elaborate on a case study for monitoring in a multi-center clinical trial that is part of the National Institute on Drug Abuse (NIDA) Clinical Trial Network (CTN) studies. This will include hands on exercises designed to allow attendees to experience the challenges for implementing a real-world remote monitoring plan integrating a variety of available options and including considerations to participant privacy. Target Audience: Investigators and Study Coordinators, Clinical Research Associates, Clinical Trial Project Managers and Training Specialists, Data Managers, Information Technology staff, and other key staff involved in Clinical Trial implementation or specifically site monitoring in the context of clinical trials. Goals: The main objective of this workshop is for attendees to learn how to leverage remote monitoring options as convenient and affordable alternatives or supplements to on-site monitoring solutions. The workshop will incorporate theoretical principles and active group exercises to review the variety of tools and features available for use remotely as well as identify the particular sites, studies, conditions and content areas (e.g., data, processes) that may be most suited for remote monitoring. Faculty: Donna Brown, Emmes Corporation Kayla Daniels, Emmes Corporation Dikla (Dee) Blumberg, Emmes Corporation Anne Hoen, Emmes Corporation Ashley Case, Emmes Corporation Workshop Organizer: Oscar Moreno, Emmes Corporation Half Day Workshops – Afternoon Workshop P6 1:00 PM – 5:00 PM Essentials of Randomized Clinical Trials – Part 2 – Basic Concepts in Statistical Analysis and Reporting of Results Part 1 (AM) and Part 2 (PM) of the “Essentials of Randomized Clinical Trials” workshop are distinct and can be taken individually or together. Although Part 1 is not a prerequisite for Part 2, the two workshops are complementary. This workshop is not an introduction to clinical trials. In fact, it assumes some knowledge of and experience in clinical trials. Nor is it an introduction to biostatistics. It does not teach how to perform statistical tasks; there 10 Pre-Conference Workshops May 15, 2016 are no formulas and no proofs. Instead, this workshop explains why these statistical tasks are performed and what the results mean once the tasks are performed. It focuses on the statistical design and analysis aspects of a clinical trial and some of the statistical issues encountered when preparing the manuscript for publication. Statistical issues frequently discussed or requiring collaboration between non-statisticians and the biostatistician are also addressed. The following specific topics are covered: • Intention-To-Treat analysis vs. per protocol • Overview of hypothesis testing • Confidence intervals • Sample size and power • Data and safety monitoring • Subgroup analysis • Reporting results (manuscript preparation) Target Audience: Non-statisticians with some experience in clinical trials who seek a better understanding of statistical concepts encountered when conducting a clinical trial. Goals: 1. To explain in simple English the reasoning and intuition behind basic statistical concepts used in clinical trials. 2. To improve communication between non-statisticians involved in clinical trials and their biostatisticians. Faculty: Paul Wakim, Clinical Center, NIH Workshop Organizers: Laura Lovato, Wake Forest University Michele Melia, Jaeb Center for Health Research Yves Rosenberg, National Heart, Lung, and Blood Institute, NIH Paul Wakim, Clinical Center, NIH Workshop P7 1:00 PM – 5:00 PM Crafting Clinical Trial Data for Sharing and Re-use: Moving from Basic Data Management to Practicing Data Curation Government agencies, journals, and evolving scientific norms have come to expect and/or require access to data underlying research activity. Data curation is an ongoing process that can be implemented at points across the data life cycle. Studies have shown that earlier curation work leads to better documented data and improved use and re-use. Bringing together experts from the US Inter-university Consortium for Political and Social Research (ICPSR), a social science data archive, and the NIH-National Heart Lung and Blood Institute (NHLBI) data repository, accumulated knowledge about data curation and data sharing will be passed along to workshop attendees. ICPSR is a social and behavioral science data repository established over 50 years ago and makes data accessible from thousands of research studies including in recent years a number of clinical trial studies. The NHLBI data repository, established in 2000, shares data collected from approximately 130 studies, more than 90 of which are clinical trials. These kinds of infrastructure developments reflect growing interest in the sharing of clinical trial data making this workshop a timely, practical activity for many involved in data collection and data management. There are clear actions that clinical trial teams can take prior to submitting data to a repository to ensure the usability and safekeeping of valuable data resources. The workshop will cover four main topics: (1) crafting metadata and data for better use and sharing, (2) evaluating and selecting a repository for your data, and (3) preparation for and data deposit to a repository and (4) understanding what typically happens after clinical 11 Pre-Conference Workshops May 15, 2016 trial data are shared (type of investigator who requests data, number of secondary publications produced). This workshop will also cover the curation of confidential (and/or sensitive) data that cannot by fully DE-identified. Target Audience: Clinical research investigators, sponsors of clinical research, biostatisticians, data managers, as well as early career investigators who want to gain hands-on experience with data curation tools. Goals: Participants in this workshop will learn a variety of data curation steps from a professional data archive staff that can be implemented into data management workflows as clinical trial data are collected and organized. Participants should bring a laptop computer to participate fully in this session. Participants will leave with knowledge and experience of how to review, assess, curate, and promote data collections for long-term access. Faculty: Amy Pienta, Inter-university Consortium for Political and Social Research (ICPSR), University of Michigan Justin Noble, ICPSR, University of Michigan Sean Cody, National Heart, Lung, and Blood Institute, NIH Jared Lyle, ICPSR, University of Michigan Workshop Organizer: Amy Pienta, University of Michigan Workshop P8 1:00 PM – 5:00 PM Conducting Valid Trials: The Critical (and Misunderstood) Roles of Randomization and Complete Follow-Up The purpose of a randomized clinical trial is to assess whether there is a causal relationship between an intervention and outcome of interest. While it is commonly believed that the purpose of randomization is to remove bias in treatment assignments or balance baseline characteristics, we will demonstrate that, in reality, randomization is the critical design feature that enables us to conclude that observed statistical associations between interventions and patient responses are causal relationships. Using easily understood examples, interactive activities and minimal mathematics, we will demonstrate how randomization is essential to objective assessments of causality, and we will discuss the implications this has for study design, conduct and analysis. For example, we will explain why the Intention to Treat (ITT) principle is essential to inference based on randomization and not merely a means to conservatively estimate the “realworld” treatment effect (another popular misconception). We will address how missing data or incomplete follow-up compromise our ability to draw causal conclusions and explain why there cannot be a statistical solution to the problem of missing data; the only remedy is to minimize missingness to the greatest extent possible and to employ sensitivity analyses to try to contain the problem. As a result, it is critical that clinical coordinators and investigators understand the importance of ensuring that data are as complete as possible, and it is imperative that studies be designed to ensure that collection of efficacy, laboratory, adverse event, or other assessments be continued until the planned end of follow-up even after participants discontinue their treatment. We will address the impact of non-adherence to assigned treatment on the study results and the conclusions that may be drawn. Even when subjects are non-adherent to their assigned treatment, the intention-to-treat analysis still provides valid causal inference regarding the effect of assignment to treatment. While clinical investigators may have a strong desire to assess the effect of receipt of treatment under conditions of full adherence, we will show that unless we force subjects to adhere, it is not possible to conduct a trial to measure this effect directly, and no statistical procedure can recover this effect from a trial without full adherence. In particular, alternatives to ITT such as “per-protocol” and “as-treated” analyses do not measure this effect. Instead, they merely subvert the randomization and therefore cannot yield valid causal conclusions. We will also discuss the role of imbalances in baseline risk factors and why observed (or unobserved) imbalances do not invalidate trial results. We will consider the role of baseline adjustment in the analysis of trial data and 12 Pre-Conference Workshops May 15, 2016 the desirability of allocation procedures, such as “minimization” that seek to ensure balance. Additional topics include: the impact of errors in randomization and other protocol violations; assessments of safety including the analysis of adverse events; analysis of post randomization subgroups such as survivors or responders; and implications for the conduct and analysis of non-inferiority trials. Target audience: Anyone involved in the design or implementation of randomized clinical trials with an interest in ensuring the quality and integrity of those trials. This includes clinicians, clinic coordinators, statisticians, data managers, and others. No formal statistical background is required, and both statisticians and clinicians can expect to benefit. Goals: To help participants develop a deeper understanding of: • The rationale and importance of randomization, • What randomization provides, and what it doesn’t provide, • The effect missing data has on analysis and the importance of minimizing missingness to the greatest extent possible, • The rationale and importance of the ITT analysis and the perils of using non-ITT approaches, • The implications of randomization for proper study design, conduct, and analysis in a wide range of settings. Faculty: Thomas Cook, University of Wisconsin, Madison Kevin Buhr, University of Wisconsin, Madison T. Charles Casper, University of Utah School of Medicine Workshop Organizer: Thomas Cook, University of Wisconsin, Madison Workshop P9 Overview of Non-Inferiority Studies 1:00 PM – 5:00 PM This workshop gives an overview of many of the issues faced by those designing, running, analysing, presenting and interpreting studies aimed at showing that a new therapy is ‘no worse than’ (from a practical point of view) an existing therapy. Such trials are becoming increasingly common and often misused. In March 2010, the FDA published Draft Guidance in regards to Non-Inferiority Studies; the EMA published guidance in 2006. Frequent cross-reference to these guidances will be given. The course will include scientific and regulatory issues, with examples taken from the US and Europe. Examples of proper implementation and improper application will be given. The presentations will be at a non-technical level (statistically) but require, as a pre-requisite, a basic level of understanding of the fundamental principles of clinical trials. Target Audience: The course is relevant both to statisticians and non-statisticians because the issues to be covered are more at a conceptual level than a detailed analysis level. It is relevant to those in the pharmaceutical sector as well as those from government and academia. Goals: Attendees should understand the purpose and potential benefits of non-inferiority studies and how they differ from equivalence and superiority studies. Attendees should also understand the extra difficulties associated with these types of studies, over and above those of superiority studies, including such points as assay sensitivity, choice of control group, choice of population to study/analyse, choice of endpoint and choice of non-inferiority margin. Faculty: Simon Day PhD, Clinical Trials Consulting & Training Limited. Nicole C. Close PhD, EmpiriStat Inc. Workshop Organizer: Simon Day PhD, Clinical Trials Consulting & Training Limited. Nicole C. Close PhD, EmpiriStat Inc. 13 Pre-Conference Workshops May 15, 2016 Workshop P10 1:00 PM – 5:00 PM Modern Approaches to the Design and Analysis of Patient-Reported Outcomes (PROs) This pre-conference workshop provides an introduction to the use and analysis of patient-reported outcomes (PROs) in clinical trials, integrating up-to-date approaches and examples throughout. Presentations and discussion will cover approaches for designing and analyzing high-quality studies with PRO endpoints. A PRO is any report of the patient’s health that comes directly from the patient and may measure a wide range of outcomes such as symptoms (e.g., pain, fatigue, nausea, etc.), well-being (e.g., physical, mental, social), quality of life, or treatment satisfaction. PROs are inherently important in this era of patient-centered healthcare. Specific topics to be addressed include: • Selection of appropriate tools with introduction of new tools, • Cross-sectional and longitudinal statistical analysis strategies, • Considerations for the use of PROs in personalized medicine trials, and • Current regulatory perspectives on PROs in the drug approval process. Target Audience: Any clinical trial researcher, statistician, or other staff member who is interested in learning about PROs in clinical trials. No prior knowledge of PROs is needed. However, this workshop will incorporate contemporary methods and examples so will be of interest to those with existing intermediate knowledge of PROs as well. Goals: Attendees should be able to describe the key elements of designing and analyzing PROs in clinical trials. Attendees will be given examples and references to assist in integrating modern approaches to PROs in their own clinical trials. Faculty: Amylou Dueck, Mayo Clinic Stephanie Pugh, American College of Radiology Joseph Unger, Fred Hutchinson Cancer Research Center Paul Kluetz, US Food and Drug Administration Workshop Organizer: Amylou Dueck, Mayo Clinic Evening Workshops Workshop P11 7:00 PM – 9:00 PM Mediation Analysis in Randomised Trials In randomised clinical trials, investigators often aim to assess both whether a particular intervention works (“Does it work?”), but also what is the underlying treatment mechanism (“How does it work?”). Clinical trial investigators have a long tradition of designing RCTs to answer the first of these two questions but very little knowledge or experience of the use of trials to answer the second. Answering the second question, and providing an efficacy and mechanisms evaluation, requires the use of statistical methods for mediation analysis. This workshop gives an introduction to these modern mediation analysis methods, specifically in the context of randomised trials. To begin, we will introduce the terminology of causal inference and mediation analysis. We will explain standard methods for constructing inferences for mediation parameters in the single mediator model, and discuss the assumptions made by such analyses. These assumptions include restrictions to linear models, no treatment by mediator interaction, no measurement error in the mediator and no unmeasured confounding between the mediator and the outcome. We will then extend the concepts to relax these assumptions. Specifically, we will introduce estimation 14 Pre-Conference Workshops May 15, 2016 approaches for the non-linear case and to allow for a treatment × mediator interactions. We will briefly describe methods that can deal with measured post-randomisation confounders and unmeasured confounders. The statistical methods touched on in this course will include structural equation modelling and conducting mediation analysis by fitting parametric regression models. We will illustrate these using trials of complex interventions in mental health, and highlight where participants can find out further information. We will discuss how these methods are currently implemented in statistical software including Stata, R, SPSS and SAS. Target Audience: Practitioners (clinical trial statisticians and trial clinicians) interested in learning more about mediation analysis. The course is not aimed at the specialist causal inference audience. Technical details will be kept to a minimum, and only a basic knowledge of statistics (equivalent to linear regression) is required. No prior knowledge of any statistical software package is assumed. Goals: 1. P rovide an introduction to the terminology of causal inference and mediation analysis, describing both its potential and outlining the major difficulties. 2. Provide an introduction to contemporary statistical methods for mediation analysis. 3. Illustrate mediation analysis on real examples of trials of complex interventions. 4. Demonstrate how these statistical methods can be implemented within standard statistical software. Faculty: Richard Emsley, Senior Lecturer in Biostatistics, Centre for Biostatistics, Institute of Population Health, The University of Manchester, UK Sabine Landau, Professor of Biostatistics, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, UK Workshop Organizer: Richard Emsley, Institute of Population Health, The University of Manchester, UK Workshop P12 7:00 PM – 9:00 PM Protocols in Real Life: Training Study-Site Staff the GCP Way This pre-conference workshop will explore the challenge of qualifying, and training, study-site staff for the operation of a multisite clinical trial. Presentations and discussions will cover issues related to the vetting, qualifying, and training of study-site staff both before, and during, a clinical trial and provide examples used by the Coordinating Centers for an NIH-funded Network (NeuroNEXT). Specific topics to be addressed will include: • GCP guidelines related to training • Standard Operating Procedures (SOPs) related to training • Tools used to vet the qualifications of both site and staff • Curriculum and tools used for Investigator Meetings and ongoing training which are applicable to networks and individuals. We will briefly discuss: - Template agendas - The major elements of training; e.g., protocol training, outcomes training, electronic data capture training, interactive web response system training, drug accountability training -M ethods and tools used to train varied personnel with varying time constraints; e.g., clinical study site PIs and coordinators, outcomes evaluators, pharmacists, lab personnel, ancillary site staff, and dedicated data entry personnel - When to re-train? - Documentation of training 15 Pre-Conference Workshops May 15, 2016 - The role of existing certifications for compliance and outcome measures - Training sites to prepare for monitoring Target Audience: Principal investigators, study coordinators, pharmacists, data managers, and information technology personnel. Goals: To explore the full range of study operations-related training methods one can employ for study initiation, and as-needed. Materials and tools will be presented as the methods used over the lifetime of a study. Faculty: Trevis Huff, Data Manager, Clinical Trials Statistical and Data Management Center (CTSDMC), University of Iowa Richard Peters, Information Technology Manager, CTSDMC, University of Iowa Michael Bosch, Lead Data Coordination Center Coordinator for NeuroNEXT, CTSDMC, University of Iowa Brenda Thornell, Senior Project Manager, Clinical Coordination Center for NeuroNEXT, Massachusetts General Hospital Workshop Organizer: Michael Bosch, University of Iowa Brenda Thornell, Massachusetts General Hospital Workshop P13 7:00 PM – 9:00 PM Cost Effective Analysis for Clinical Trials Cost-effectiveness analysis is of growing importance internationally and nationally. A number of countries make national formulary coverage decisions by use of such analyses. Nationally, value-based insurance plans use it to identify what’s of value; some government departments, such as the US Department of Veterans Affairs, consider it in formulary decisions. When appropriately designed and analyzed, one source of clinical and economic data for estimating costeffectiveness is randomized controlled trials. This course will review issues in the design of such evaluations (e.g., what data should be collected? what is the appropriate sample size? how naturalistic should the study design be?). The workshop will address the applicability of various statistical models (for example, Ordinary Least Square Models, Generalized Linear Models, Generalized Estimating Equations, etc.,) that are commonly used for the analysis of cost (and preference score) data. The workshop will also address the analysis and reporting of sampling uncertainty for cost-effectiveness analysis (acceptability curves, confidence intervals for cost-effectiveness ratios and net benefits, and value of information). Target Audience: Individuals interested in designing and analyzing economic evaluations in clinical trials. Goals: After attending the workshop the participants will be able to • identify the economic outcomes data that should be collected during the trial, • determine the sample size required for/power of the cost-effectiveness analysis, • understand the strengths and weaknesses of alternative methods for analyzing data on costs and qualityadjusted life years, and • understand methods for reporting sampling uncertainty for cost-effectiveness analysis (acceptability curves, confidence intervals for cost-effectiveness ratios and net monetary benefit, and value of information). Faculty: Jalpa Doshi, Department of Medicine, University of Pennsylvania Henry Glick, Departments of Medicine and Health Care Management, University of Pennsylvania Workshop Organizer: Kousick Biswas, Cooperative Studies Program, US Department of Veterans Affairs Track Key Information Systems/Data Management (IS/DM); Medical (M); Regulatory Issues (R); Ethics (E); Study Coordination (SC); Statistical (ST) Trial Management (TM) 16 Monday, May 16, 2016 All information subject to change 7:00 AM – 5:30 PM Registration 8:00 AM – 5:30 PM Exhibits 8:30 AM – 9:00 AM Welcome - SCT President, Wendy Parulekar NCIC Clinical Trials Group, Kingston, Ontario, Canada Presentation of the Class of 2016 Fellows 9:00 AM – 10:15 AM urtis Meinert Lecture – Denis Lacombe C “European Organization for research and Treatment of Cancer (ROC); Vision, Strategic Focus and Implementation Strategy” 10:15 AM – 10:45 AM Break: Exhibits/Posters 10:45 AM – 12:15 PM Invited Sessions Time Slot I 10:45 AM – 12:15 PM Invited Session 1: Challenges and Solutions to the Coordination and Conduct of an Emergency Treatment Trial M, ST The Established Status Epilepticus Treatment Trial (ESETT) is a randomized, adaptive, comparative effectiveness trial of three second-line therapies for the treatment of benzodiazepine-refractory status epilepticus in children and adults. This trial is conducted in an emergency setting with a short therapeutic window and meets the criteria for exception from informed consent. These operational challenges have created special requirements for the coordination and conduct of the trial including management of exception from informed consent activities, management of study drug inventory, and randomization, treatment, and data collection in the emergency room setting. This session starts with an overview of the ESETT study design by Jordan Elm, including details on the challenges encountered with the response-adaptive randomization and age stratification requirements of the study. Next, Catherine Dillion will review the challenges associated with the coordination of study drug distribution and tracking, as well as implementation of emergency unblinding procedures. Deneil Harney will address exception from informed consent requirements and the management and results of community consultation and public disclosure activities for ESETT. Finally, Robert Silbergleit will discuss the challenges associated with implementation of a large emergency trial involving large numbers of treating emergency department physicians and study team members across the trial network. He will provide specific solutions to implementation challenges including protocol assist devices, use next boxes, and training. Speakers: Chair/Organizer: Jordan Elm, Medical University of South Carolina Catherine Dillon, Medical University of South Carolina Deneil Harney, University of Michigan Robert Silbergleit, University of Michigan Catherine Dillon, Medical University of South Carolina 10:45 AM – 12:15 PM Invited Session 2: Early-Phase Designs for Contemporary Dose-Finding Problems in Oncology ST The current explosion of new targeted and immunotherapeutic agents for cancer treatment has challenged statisticians to reconsider early-phase designs developed for cytotoxic agents. The goal of determining the maximum tolerated dose (MTD) is no longer desirable because novel agents are characterized by a reduced toxicity profile, to the point of being essentially safe within the therapeutic dose range. Moreover, for targeted agents, the relationship between target effect and toxicity might not be linear, implying that the most efficacious dose might be below the MTD. Under these circumstances, dose selection should not be based solely on toxicity but also examine both toxicity and activity. Recent Phase I trials for single-agent or combination therapy have focused on detecting signals of antitumor activity, pharmacokinetic/pharmacodynamics (PK/PD) relationships, or on assessing the feasibility and utility of 17 Monday, May 16, 2016 biological correlative assays. Progress has been made, yet there is still much confusion about which biological endpoints to incorporate, and how, to determine the optimal dose and/or schedule of new drugs for Phase II trials. Cody Chiuzan will discuss the challenges of early-phase development for targeted- immunotherapy agents and review the most recent designs proposed for testing these novel therapies. Nolan Wages will describe the implementation of an adaptive early-phase method for identifying the optimal combination of two oral targeted inhibitors in an ongoing study. Results of simulation studies demonstrate this method’s ability to effectively recommend optimal combinations in a high percentage of trials with manageable sample sizes. Arzu Onar-Thomas will focus on special considerations for pediatric populations, particularly regarding dosing issues and adaptations to the CRM used effectively in a series of multi-institutional Phase I trials conducted by the Pediatric Brain Tumor Consortium over the past fifteen years. Emily Dressler will conclude with strategies for identifying the next dose to treat, given the need to balance toxicity and efficacy considerations, in addition to changing paradigms regarding monotonic dose-toxicity assumptions. Speakers: Chair/Organizer: Cody Chiuzan, Columbia University Nolan Wages, University of Virginia Arzu Onar-Thomas, St. Jude Children’s Research Hospital Emily Dressler, University of Kentucky Emily Dressler, University of Kentucky 10:45 AM – 12:15 PM Invited Session 3: Recommendations on the Use, Conduct, and Training of Data Monitoring Committees: The Clinical Trials Transformation Initiative’s Data Monitoring Committee Project ST, TM The Clinical Trials Transformation Initiative Data Monitoring Committees Project aims to (1) describe the current landscape of DMC use and conduct, (2) clarify the purpose of and rationale for using a DMC, (3) identify best practices for independent DMC conduct, (4) describe effective communication practices between independent DMCs and trial stakeholders during all phases of DMC activity, and (5) identify strategies for preparing a robust pool of DMC members. As part of this effort, the project team conducted a survey to assess current use and conduct of DMCs and training practices for DMC members and then convened focus groups to gain in-depth understanding of needs and best practices related to DMC use. Survey and focus group findings were presented at the 2015 SCT Annual Meeting. Subsequently, findings from these activities were presented to and discussed among a multi-stakeholder group of experts in DMC issues at an expert meeting. Based on data gathered via these evidence-gathering activities and feedback from discussion at the expert meeting, the project team has developed recommendations intended to improve the quality and efficiency of DMCs. Presenters will introduce the issue, provide a brief project overview, briefly review project findings, and present— for the first time publicly—new recommendations covering: 1. Role of the DMC, including issues related to DMC access to blinded data and independence. 2. DMC composition, including issues related to conflict of interest and use of patient advocates in DMCs. 3. C ommunication related to the DMC, including communication between the DMC, trial sponsor, statistical analysis center, IRBs, and regulatory bodies. 4. DMC charter, including a sample table of contents and points for consideration. 5. T raining of DMC members and statistical analysis center statisticians, including suggested training formats and apprenticeship opportunities. Additional tools will also be presented related to specific responsibilities of the DMC. Track Key Information Systems/Data Management (IS/DM); Medical (M); Regulatory Issues (R); Ethics (E); Study Coordination (SC); Statistical (ST) Trial Management (TM) 18 Monday, May 16, 2016 Speakers: Chair: Organizer: Karim Calis, FDA/CDR, NIH/NICHD Raymond Bain, Merck Research Laboratories Jane Perlmutter, Patient Advocate Dave DeMets, University of Wisconsin Annemarie Forrest, Clinical Trials Transformation Initiative 10:45 AM – 12:15 PM Invited Session 4: Data and Biorepositories: Enhancing Collaborative Science IS/DM, ST, R Responsibilities for submission to repositories are often held by the data coordinating center in a multicenter study. Those responsibilities are increasingly complex and resource intense. The utility of the clinical data, biological samples, genetic sequences, and other information is a function of the rigor with which the submissions are collected, curated, de-identified, stored, and disseminated. Speakers in this session discuss their experiences with repositories. The first presentation considers the NIH perspective, describing BioLINCC, NHLBI’s biospecimen and data repository. The next four speakers will share examples of challenges and possible solutions encountered during the archive process. A discussant will summarize the presentations with thoughts for meeting repository requirements in the future. Speakers: Discussant: Chair: Organizer: Elizabeth Wagner, NIH/NHLBI Valerie L Durkalski-Mauldin, Medical University of South Carolina Suzanne Firrell, George Washington University Katherine Kirkwood, Mount Sinai Hospital Sharon Lawlor, University of Pittsburgh Mei Lu, Henry Ford Health Systems Shaun Treweek, University of Aberdeen, UK Kathleen Jablonski and Mary Foulkes, George Washington University 10:45 AM – 12:15 PM Invited Session 5: Missing Data Issues in Cluster-Randomized Designs for Pragmatic Trials: A Practical Overview M, IS, DM, R An ever-increasing number of clinical trials are being implemented in a pragmatic setting, at times employing multilevel interventions randomized to natural clusters or groups of individuals, with outcomes measured at each level. As with all clinical studies, missing data are an unavoidable feature. Handling this is further complicated within cluster-randomized designs, to the extent that missing data methods developed for individually randomized trials require customized adaptations. While research methodologists have proposed ways to mitigate the impact of missing data for over a decade, the use of these designs still lags behind this literature, as evidenced by recent systematic reviews. It is not clear whether investigators involved in recent studies appreciate that their estimates often would only be unbiased under the rather restrictive assumption that data are missing completely at random. Investigators’ lag in adopting the most appropriate methods for their data may simply reflect convenience: default implementations and options accessible in commercial software often entail more restrictive assumptions. This session provides a practical overview of these issues and offers approaches to navigate their potential pitfalls. Topics to be covered include: • Comparison of population-averaged and cluster-specific models for the analysis of cluster randomized trials with missing binary outcomes. • Analysis of cluster-randomized trials with missing dichotomous outcomes: empirical and simulation results. • Bayesian methods for modeling non-ignorably missing data in cluster-randomized trials with binary outcomes. • Inverse-probability-weighted semi-parametric estimation of treatment effect in cluster randomized trials with missing data. 19 Monday, May 16, 2016 • A pattern-mixture model approach for handling missing outcome data in cluster-randomized trials. David Murray will comment on the presentations and direct discussion with an eye to highlighting implementable solutions for those engaged in cluster-randomized designs of pragmatic trials that require multilevel modeling. Speakers: Chair/Discussant: Organizer: Lehana Thabane, McMaster University, Canada Jinhui Ma, University of Ottawa, Canada Catherine Crespi, University of California at Los Angeles Mélanie Prague, Harvard University Mallorie Fiero, University of Arizona David Murray, NIH/Office of Disease Prevention Kenneth Wilkins, NIH/NIDDK 12:15 PM – 1:30 PM Lunch 1:30 PM – 3:00 PM Contributed Paper Session Time Slot I CPS 1: Time to Event Analyses in RCTs ST CPS 2: Miscellaneous Statistical Issues in RCTs ST CPS 3: The Trials and Tribulations of Study Coordination SC CPS 4: Managing Data Across the Trial Lifecycle IS/DM CPS 5: The Ins and Outs of Trial Design M, DM, ST CPS 6: Thomas Chalmers Student Scholarship Presentations 3:00 PM – 3:30 PM Break: Exhibits/Posters 3:30 PM – 5:00 PM Invited Sessions Time Slot II 3:30 PM – 5:00 PM Invited Session 6: It’s Always Too Early Until Suddenly It’s Too Late: Designing Surgical RCTs Relevant to Patients, Staff, and Changing Technologies M, ST Multicenter randomized controlled trials (RCTs) in surgery require enormous investment and effort. Challenges specifically relate to the inclusion of evolving and novel innovations and surgeon skill and expertise. There also is a need to ensure that interventions are acceptable to patients, surgeons, and other clinical staff. These issues have hampered the progress of RCTs in surgery, with some never starting and others requiring expensive extensions. Completed and reported trials have been received with disbelief and failed to change practice because of claims that results would have been different if the interventions had been done by experts using novel techniques or tools. To increase the validity and impact of RCTs in surgery, there is a need to consider these issues and to develop methods to allow changing technologies and skills to be included in trial design. In the UK, several initiatives are under way to address these issues. Multidisciplinary collaborations between trialists, methodologists, and surgeons have been developed to optimize pretrial work and full trials. This session will provide an overview of these initiatives and consider key issues with illustrated examples. The first part will consider how surgical innovations may be included in ongoing trials and pilot work to ensure that the research question is up-to-date and relevant. This will be illustrated by two examples: recent modification of a two-group trial to a three-group trial in bariatric surgery (the By-Band-Sleeve Study) and use of mixed-methods pilot work to inform the design of an RCT (the Bluebelle Study). The second part will focus on how to design RCTs to incorporate innovation, surgeon preference, and expertise. Examples include an optional expertise paired design that allows surgeons with and without preferences to participate (the Topkat Trial) and a definitive RCT with a nested IDEAL Phase IIB study (the ROMIO Trial). The IDEAL framework described how novel surgical interventions may be evaluated, and this example is one of the first of its kind. Track Key Information Systems/Data Management (IS/DM); Medical (M); Regulatory Issues (R); Ethics (E); Study Coordination (SC); Statistical (ST) Trial Management (TM) 20 Monday, May 16, 2016 Speakers: Discussant: Chair: 3:30 PM – 5:00 PM David Beard, University of Oxford, UK Natalie Blencowe, University of Bristol, UK Jane Blazeby, University of Bristol, UK Jenny Donovan, University of Bristol, UK Leila Rooshenas, University of Bristol, UK Barney Reeves, University of Bristol, UK Jane Blazeby, University of Bristol, UK Invited Session 7: What Happens When a Trial Is Interrupted? How to Deal with Suspension of Randomization and Restart Your Trial TM There is now a fairly mature literature on early termination of studies for planned reasons. However, a study may also be put on hold while a specific issue or issues are investigated, with the prospect that the trial can resume if the problem is satisfactorily resolved. Several factors can cause a clinical trial to be suspended, the most common being a safety concern, a perceived shift in the risk/benefit balance (or other ethical concerns), or external factors such as the continued availability of funding or consumables. The catalyst for the trial suspension may even be from a changing interpretation and advice on national treatment guidelines, which may have political dimensions and involve intense media scrutiny. Such considerations triggered the temporary suspension in 2014-15 of two surgical trials that looked at surgical interventions for urinary incontinence and prolapse and were publicly funded by the UK NIHR Health Technology Assessment Programme. This session will discuss the challenges and solutions related to suspending and restarting a study, based on the experiences in these and other trials. Rather than a statistical view, this session is about the practicalities of how to manage such an unscheduled major interruption and maximize the chance of a successful restart. The first talk will describe how a trial team identifies the issue, assesses the risks and necessary actions, and then moves to create an initial action plan, communicating with all relevant stakeholders and establishing likely resource needs and timelines. The second talk will be about implementing such an action plan and the need for flexibility in adapting to what can be challenging and rapidly evolving circumstances and demands. The third talk will focus on restarting the trial, with emphasis on speed and accuracy, and also reassurance and any retraining or education needed, for example, on protocol changes. The fourth talk will be a summary reflection on what has been learned and offer suggestions on how trialists can be more prepared in advance for such events. Speakers: Alison McDonald, University of Aberdeen, UK Lynda Constable, University of Aberdeen, UK Tracey Davidson, University of Aberdeen, UK Mary Foulkes, George Washington University Chair: John Norrie, University of Aberdeen, UK Organizer: Lynda Constable, University of Aberdeen, UK 3:30 PM – 5:00 PM Invited Session 8: Courage, Controversy, and Clinical Trials: Lessons from the Ebola Epidemic TM, ST, E As West Africa begins to recover from the devastating Ebola epidemic of 2014-2015, this session offers a look back at the major studies conducted during the epidemic and discusses the lessons that can be learned about improving the scientific research community’s response to emerging infectious diseases. The three main talks will focus on the ethical, methodological, and humanitarian issues of conducting research during the Ebola epidemic: • James Neaton will give an overview of PREVAIL I, a double-blind, placebo-controlled, Phase II/III trial that compared two Ebola vaccines and was conducted in Liberia. He will highlight the difficulties in running such a trial and the lessons learned, including that simple procedures for randomization and blinding can be implemented in difficult field conditions. As the only double-blind, placebo-controlled RCT for Ebola vaccines conducted in West Africa, PREVAIL I provided valuable evidence about vaccine safety and immunogenicity. 21 Monday, May 16, 2016 (The waning epidemic resulted in too few events to assess clinical efficacy.) • Adam Levine will focus on the disconnect and the interplay between the humanitarian mission and the clinical research agenda that occur during an emerging disease epidemic. Much of this disconnect is potentially due to cultural differences between academic institutions and humanitarian organizations. However, with few high-quality research studies to guide humanitarian healthcare practice, the differences in culture need to be overcome to improve both clinical research and humanitarian care, particularly during epidemics. • Ross Upshur will outline the ethical questions raised about the value and feasibility of clinical research in the midst of a serious public health emergency. Differences between humanitarian and regulatory worldviews opened up a discussion on study design. Now that most of the trials have been closed, we can review how this discussion has changed and what we have learned. Lori Dodd will summarize the three presentations and facilitate a group discussion between the presenters and the audience. Speakers: Discussant: Chair: Organizer: James Neaton, University of Minnesota Adam Levine, Brown University Ross Upshur, University of Toronto, Canada Lori Dodd, NIH/NIAID Julian Wolfson, University of Minnesota Erin Gabriel, NIH/NIAID 3:30 PM – 5:00 PMInvited Session 9: Design, Conduct, and Reporting of Pilot and Feasibility Studies Carried Out in Preparation for a RCT TM, ST Trials carried out in a health-care setting typically involve complex interventions that require considerable planning if they are to be implemented successfully. Complex interventions are conventionally made up of several interacting components and present special problems related to their sensitivity to the local context and the logistics of applying experimental methods in a health-care setting. The UK Medical Research Council’s guidance document on complex interventions emphasizes the importance of thorough groundwork in designing and evaluating complex interventions and stresses the importance of contextualizing and conceptualizing the problem at the development stage. Pilot and feasibility studies can be an essential part of trial preparation. Recent papers have shown a dearth of pilot studies in the literature that state they are specifically in preparation for a randomized controlled trial, and that give a clear list of key objectives relating to the pilot phase. Feasibility and pilot studies are conducted to assess the feasibility and integrity of the study protocol, but the differences between the two are not clear-cut. This session will provide an overview of the objectives of feasibility and pilot studies, considering issues of study design and analysis, with useful examples and references. The rationale for the development of CONSORT extension guidelines for pilot trials will be outlined, and Pilot and Feasibility Studies, a new BioMed central journal arising from this work, will be introduced. Speakers: Discussant: Chair/Organizer: Gillian Lancaster, Lancaster University, UK Mike Campbell, University of Sheffield, UK Sandra Eldridge, Queen Mary University of London, UK Lehana Thabane, McMasters University, Canada Gillian Lancaster, Lancaster University, UK Track Key Information Systems/Data Management (IS/DM); Medical (M); Regulatory Issues (R); Ethics (E); Study Coordination (SC); Statistical (ST) Trial Management (TM) 22 Monday, May 16, 2016 3:30 PM – 5:00 PMInvited Session 10: Ethical Challenges in Pragmatic Comparative Effectiveness Trials E, ST, M Standard-of-care randomized controlled trials (RCTs) test the comparative effectiveness of two or more interventions used routinely in medical practice and provide information critical to health-care delivery. However, these trials raise ethical issues that challenge researchers, research ethics committees, regulators, and sponsors as they seek to responsibly fulfill their respective roles. In this session, we will address the importance of comparative effectiveness trials as a tool to help patients and practitioners identify more effective treatments and improve quality, while recognizing the need to control the costs of care. We will introduce FLUID as a case study of a cluster crossover trial that seeks to compare the impact of two resuscitation fluids routinely used in emergency departments and intensive care units on patient mortality and hospital readmissions. We will address the interplay between ethics and statistical design by reviewing alternative design choices and their implications for feasibility, generalizability, and validity. We also will address a dominant claim in the literature, namely that research entails additional risks compared to clinical practice. We will argue that this claim pushes the current literature and discourse of the ethics of standard-of-care RCTs in the wrong direction. If important research is to proceed, a novel ethical framework for standard-of-care RCTs is required. Working toward this goal, we will appeal to relevant foundational documents in research ethics, national and international regulations, and relevant literature to identify gaps and areas where further ethical analysis is required. Speakers: Chair: Organizer: Dean Fergusson, Ottawa Hospital Research Institute, Canada Lauralyn McIntyre, Ottawa Hospital Research Institute, Canada Monica Taljaard, Ottawa Hospital Research Institute, Canada Austin Horn, Western University, Canada Charles Weijer, Western University, Canada Dean Fergusson, Ottawa Hospital Research Institute Monica Taljaard, Ottawa Hospital Research Institute 23 Tuesday, May 17, 2016 7:00 AM – 5:30 PM Registration 8:00 AM – 5:30 PM Exhibits 8:00 AM – 9:00 AM Contributed Paper Session Time Slot II CPS 7: Statistical Issues in Non-Inferiority Trials ST CPS 8: Statistical Lessons from Across the Trial Spectrum ST CPS 9: Coordinating RCTs: Lessons Learned SC CPS 10: Implementation of Electronic Data Capture Systems IS/DM CPS 11: Engaging Communities/Topic-Specific Trial Issues M, SC CPS 12: Cluster Randomized Trials/Cross-Protocol Analyses ST 9:00 AM – 10:30 AM Invited Session Time Slot III 9:00 AM – 10:30 AM Invited Session 11: Pragmatic Trials ST, M, R Most clinical trials fail to provide the evidence that clinicians need to optimally treat patients. Pragmatic clinical trials are designed to address this limitation, seeking to inform medical decision-making. Many leaders are thus urging more pragmatism in clinical trials. Each of the session’s speakers will focus on an issue related to conducting these trials: • Merrick Zwarenstein will discuss an ongoing project on empirical studies of pragmatic trials. Using the RCTs in a large systematic review, he is exploring whether the degree of pragmatism, as measured by the PRECIS2 score, is associated with the effect size and separately with the risk of bias using the Cochrane ROB tool. These findings will evaluate whether pragmatic trials have a smaller effect size than more explanatory trials, and whether their improved external validity is at the expense of reduced internal validity. • Matt Roe will review lessons learned from recently completed pragmatic clinical trials, delineate the key attributes of pragmatic vs. traditional clinical trials, and discuss strategies for overcoming barriers for the widespread implementation of pragmatic clinical trials. • Laura Dember will focus on the advantages and challenges of conducting trials in large numbers of health-care facilities while relying on highly centralized implementation approaches and data acquired through routine clinical care. In doing so, she will draw on her experience implementing the Time to Reduce Mortality in Endstage Renal Disease Trial, a large, cluster-randomized pragmatic trial evaluating the effect of hemodialysis session duration on mortality, hospitalization rate, and quality of life. The trial is being conducted in partnership with the two largest U.S. dialysis provider companies as one of the demonstration projects of the NIH Health Care Systems Research Collaboratory. Discussants Dave Demets and Rob Califf will summarize the talks and lead active discussion with attendees. Speakers: Discussant: Chair/Organizer: Merrick Zwarenstein, Western University, Canada Matt Roe, Duke University Laura Dember, University of Pennsylvania Dave Demets, University of Wisconsin Rob Califf, FDA Scott Evans, Harvard University Track Key Information Systems/Data Management (IS/DM); Medical (M); Regulatory Issues (R); Ethics (E); Study Coordination (SC); Statistical (ST) Trial Management (TM) 24 Tuesday, May 17, 2016 9:00 AM – 10:30 AM Invited Session 12: Efficient Study Designs in Clinical Research ST Efficient designs can be defined as statistically robust designs that enable quicker and/or lower cost decisions compared to conventional designs. Efficient design is in fact an umbrella term that encompasses all aspects of clinical trial conduct and analysis, as well as the design. Hence, an efficient design is a smarter way of running a trial and can save resources and time in the assessment of new health technologies. The first talk of this session uses case studies and examples of efficient study design to highlight the benefits of a range of efficient study designs. It will be highlighted how both using routinely collected data for data collection and even simple adaptive methods can have an impact on the efficiency of a study. Some of the challenges of this type of study design will also be discussed. The next speaker will focus on available methods of analysis following an adaptive design, highlighting issues of bias and accuracy, and exploring the use of such methods in current trials. The third talk will consider adaptive study designs and their impact on the economic evaluation of health-care technologies. It will highlight how by neglecting cost-effectiveness in our adaptive designs, we potentially compromise on the quality of this evidence and miss an opportunity to make our study designs more efficient by using cost-effectiveness information in interim decision-making. The final talk will examine a case study that used early time points to inform clinical trial decisions. The speaker will describe how individual patient data from a previous study and meta-analysis of mean responses can be used to provide rationale for using an early time point to predict the treatment response at a later time point. In the case study, use of an early time point improved trial efficiency by potentially reducing study time by 294 days. Speakers: Organizer: 9:00 AM – 10:30 AM Steven Julious, University of Sheffield, UK Sue Todd, University of Reading, UK Laura Flight, University of Sheffield, UK Feng Liu, GlaxoSmithKline, US Steven Julious, University of Sheffield, UK Invited Session 13: Statistical Challenges in Personalized Medicine: Through Biomarker Subgroup Identification to Companion Diagnostic Device Development ST The future of personalized medicine is highly promising. A number of recently FDA-approved companion diagnostics products are strong evidence of a successful first step. However, there are still considerable statistical challenges in areas such as exploratory biomarker identification; incorporation of each patient’s clinical characteristic and genomic signature to derive the most accurate diagnosis; and application of prespecified biomarker or companion diagnostic devices to clinical trials to streamline the development process and maximize efficacy. How to appropriately identify biomarker subgroups and efficiently move forward to companion diagnostic devices also remain challenging. A comprehensive and successful solution could only be possible when regulatory agencies, academic researchers, and industry pioneers work together to address issues in the aforementioned areas. This session serves as a good example how such collaboration and cross-agency thinking could be achieved. The session focuses on the statistical issues surrounding the development of personalized medicine, spanning the workflow from early-phase exploratory biomarker subgroup identification to validated biomarker-based companion diagnostic development. Liang Fang will discuss the practical challenges and considerations of searching a predictive biomarker in the era of personalized medicine and the increasingly fast pace of drug development. Practical and statistical issues around stratification, cutoff selection for continuous biomarker, co-primary endpoints, and clinical trial designs will be discussed. Options to overcome these issues will also be presented. Yi Huang will present various statistical challenges in enriched randomized clinical trials, in particular in the areas of subgroup identification using biomarker information from early phases or prior studies and how to synthesize results from multiple enriched randomized clinical trials. Ruixiao Lu will show the power of using genomic information to derive composite biomarker measures that maxi25 Tuesday, May 17, 2016 mize therapeutic efficacy using patient-specific molecular signatures. She will also make the important distinction between prognostic and predictive biomarkers and illustrate the appropriate ways to assess clinical impact and relevance with real-life examples. Laura Yee will provide an overview of companion diagnostics from the regulator’s perspective with the focus on prescreening with a local test. She will also discuss how to address the bias incurred in such populations. Speakers: Discussant: Chair/ Organizer: Liang Fang, Gilead Yi Huang, University of Maryland (UMBC and UMB) Ruixiao Lu, Genomic Health Laura Yee, FDA Jing Huang, Veracyte Rui (Sammi) Tang, Vertex 9:00 AM – 10:30 AM Invited Session 14: Expanding Your Reach: Innovations and Opportunities for Remote Participant Visits to Boost Retention and Enrollment in Research Studies TM, IS/DM This session will show how five different studies have expanded their reach by conducting more than 60,000 remote study visits to where participants live or work. The rationale, logistics, challenges, and successes will be discussed for each study. The pragmatic approaches to the design and conduct of these studies exemplify costeffective innovations used to bolster recruitment and retention while simultaneously minimizing subject burden. Strategies used in these five studies are applicable in domestic and international projects to promote retention and recruitment in otherwise hard-to-reach populations. JoAnn Manson will describe design features to optimize cost-efficiency in the large-scale VITamin D and OmegA3 TriaL (VITAL). Susie Day will explain how the Fuel 2 Fight Study achieved a nationally representative sample of firefighters by going directly to the subjects’ workplaces. Virginia Howard will show how in-home baseline visits for enrollment in a U.S. national cohort study of stroke risk factors in blacks and whites were achieved in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study. Matthew Curry will report on a home-visit staffing model used in the Gulf Long-Term Follow-up Study (GuLF STUDY), a prospective cohort study designed to examine the health effects associated with the cleanup effort surrounding the 2010 Deepwater Horizon oil spill disaster. Marinella Temprosa will illustrate the use of external examination services to supplement clinical visits for maintaining retention and adherence in the Diabetes Prevention Program Outcomes Study (DPPOS), a multi-center clinical trial that has been ongoing for twenty years. Speakers: Organizers: JoAnn Manson, Brigham and Women’s Hospital, Harvard Medical School R. Susie Day, University of Texas School of Public Health, Houston Virginia Howard, University of Alabama at Birmingham Matthew Curry, Social Scientific Systems Marinella Temprosa, George Washington University Marinella Temprosa, George Washington University Valerie Donohue, George Washington University Track Key Information Systems/Data Management (IS/DM); Medical (M); Regulatory Issues (R); Ethics (E); Study Coordination (SC); Statistical (ST) Trial Management (TM) 26 Tuesday, May 17, 2016 9:00 AM – 10:30 AM Invited Session 15: Clinical Trial Simulations: The When, Where, and What ST Clinical trial costs have increased almost exponentially since the 1990s, with failed clinical trials a major cost driver. Clinical trial simulations can help to improve efficiency and reduce costs by optimizing various aspects of clinical trials, including number of patients, effect size, primary outcomes, variance of endpoint measurements, design choices (for example, parallel vs. crossover, individual-based vs. community-based, adaptive trial design), inclusion-exclusion criteria, and costs. The focus of this session is on how clinical trial simulations can produce novel insights to complement traditional statistical methods for clinical trial planning, conduct, analysis, and interpretation of trial results. The session will introduce examples of clinical trial simulations for three different disease types: acute viral infections such as influenza; chronic viral infections such as HIV; and chronic noninfectious diseases such as Alzheimer’s disease, cardiovascular disease, and chronic obstructive pulmonary disease. Researchers working on different diseases may apply different methods and paradigms in clinical trial simulations. The talks will also show how simulations can help in different stages of the drug development process (PK/PD models in drug design to Phase I/II/III/IV trials). To encourage the exchange of experiences and ideas, and identify areas of agreement and disagreement about the use of clinical trial simulations, the talks will be followed by a round-table discussion. Discussion points include: Should all clinical trials be simulated? What makes a trial simulator valid? When are clinical trial simulations most appropriate (for example, contexts in which independence of individuals is unclear or interim analyses)? Do we need to develop guidelines for using models to simulate clinical trials? If yes, how stringent should these guidelines be? Do simulators have to be standardized or approved? How can guidelines for clinical trial simulators be assembled? Speakers: Chair: Organizer: Benoit Masse, University of Montreal, Canada Victor De Gruttola, Harvard University Klaus Romero, Critical Path Institute Hugo Geerts, In Silico Biology Carolin Vegvari, Imperial College London, UK Marie-Claude Boily, Imperial College London, UK Carolin Vegvari, Imperial College London 10:30 AM – 11:00 AM Break: Exhibits/Posters 11:00 AM – 12:30 PM Invited Session Time Slot IV 11:00 AM – 12:30 PMInvited Session 16: Improving Health by Improving Trials: The UK MRC Hubs for Trials Methodology Research, a Nationwide Network to Develop Capacity and Optimize Trial Design and Conduct IS/DM, TM The development and implementation of novel methods for trial design, conduct, and analysis are often slowed by lack of awareness, access to tools, and concerns about added complexity. As a result, clinical trials may not include improved methods to deliver high-quality data in a timely and cost-effective way. In 2009, the Medical Research Council (MRC) established the Hubs for Trials Methodology Research (HTMR) to create a UK-wide regionally distributed research resource to improve the design, conduct, analysis, interpretation, and reporting of clinical trials. The MRC HTMR Network adds value by supporting investment, collaboration and leadership on a nationwide scale. The network also promotes and encourages collaborative methodological research relevant to trials to accelerate implementation of the most effective and appropriate methods to improve the quality of trials and, ultimately, patient care. This session, presented by members of the Executive Committee of the MRC HTMR Network (and Hub Directors), will describe the strategy and structure of the network, and highlight and illustrate its success with some of the novel methodological innovations arising from this unique collaboration. The network’s success with capacity building and engagement with clinicians and trialists will be described, as well as the benefits and challenges of working in the trials community in the UK. Speakers will demonstrate how this knowledge can be adapted to support 27 Tuesday, May 17, 2016 improving trials on a global scale. Specific speakers and their topics include: • Jane Blazeby – Strategic investment of a network and hubs in the UK • Matthew Sydes – Guidance for working on trials: How small projects make big changes • Paula Williamson – Outcome measures in trials: Adding value through a network approach • Adrian Mander – Implementing novel trial designs • Louise Bowman – Supporting capacity building: The future of trials methodology The MRC HTMR Network is highly committed to capacity building in trials methodology, both nationally and internationally, and is successfully supporting the future of this important area of trials research. http://www.methodologyhubs.mrc.ac.uk/ Speakers: Chair: Organizer: Jane Blazeby, University of Bristol, UK Matthew Sydes, MRC Clinical Trials Unit, UK Paula Williamson, University of Liverpool, UK Adrian Mander, MRC Biostatistics Unit, UK Louise Bowman, University of Oxford, UK Paula Williamson, University of Liverpool Jane Blazeby, University of Bristol, UK 11:00 AM – 12:30 PMInvited Session 17: Guidance on Specifying the Target Difference (Effect Size) for a RCT M, ST Calculation of the number of participants needed (the sample size) is central to the validity of an RCT. This provides reassurance that the trial will identify a difference of a particular magnitude (target difference or “effect size”) if such a difference exists. From both a scientific and ethical standpoint, selecting an appropriate target difference is of crucial importance. However, determination of the size of difference that is “important” has been neglected until relatively recently. A variety of approaches have been proposed and addressed by a large recent review. However, there is a need for greater guidance to aid researchers and funders. This session’s first speaker will consider sample sizes and target difference for clinical trials. The sample size calculation is typically most sensitive to assumptions related to the target difference (effect size). In this practical talk, case studies and examples from clinical trials will be used to illustrate how an effect size may be quantified when designing a trial. The second speaker will consider the challenge of defining an important difference in a patient-reported outcome. Target effect sizes for patient-reported outcomes should ideally be the smallest that will make a difference to patients or clinical practice, the so-called minimum important difference (MID). This talk will discuss the MID, including how to estimate and use it. Following this, the third speaker will present findings from a review of target differences used in trials and consider the effect sizes used in trials for different settings as well as how these effect sizes were quantified. The final speaker will present a personal view of developing trials as a chief investigator and co-investigator and applying for funding to Canadian and U.S. funders. Attendees will be encouraged to express their views on existing research in this area and what is needed to further improve trial design. Speakers: Chair/Organizer: Steven Julious, University of Sheffield, UK Melanie Bell, University of Arizona Joanne Rothwell, University of Sheffield, UK Dean Fergusson, Ottawa Hospital Research Institute, Canada Jonathan Cook, University of Oxford, UK Track Key Information Systems/Data Management (IS/DM); Medical (M); Regulatory Issues (R); Ethics (E); Study Coordination (SC); Statistical (ST) Trial Management (TM) 28 Tuesday, May 17, 2016 11:00 AM – 12:30 PMInvited Session 18: Collaborating with Patient Advocacy Groups at the Design Stage of Your Clinical Trial: Why It Is So Important TM Engaging patient advocacy groups in the early stages of study design often appears daunting for the investigator. There are perceived challenges related to identifying the right representatives that can share the patients’ perspectives and provide the necessary contributions to protocol development. Although challenging, this involvement can be successfully achieved. This session will highlight successful collaborations between advocacy groups and clinical investigators and provide guidance on how to initiate the collaboration during the clinical trial planning process: • Bray Patrick-Lake, director of stakeholder engagement for the Clinical Trials Transformation Initiative, will discuss effective engagement with patient groups around clinical trials. • Charles Mohan Jr., CEO and executive director of the United Mitochondrial Disease Foundation, will explain how to identify and partner with the right advocacy group. • David Schubert, vice president of Stealth Biotherapeutics, will provide industry’s perspective on conducting clinical research in collaboration with patient advocacy groups. Discussant Erika Augustine will reflect on the three presentations and share her experience working with patient advocacy groups of the NINDS-funded Parkinson’s Disease Network (NET-PD, NIH Exploratory Trials in Parkinson’s Disease) and the Batten Disease Support and Research Association. Speakers: Discussant: Chair: Organizer: Bray Patrick-Lake, Clinical Trials Transformation Initiative, Duke University Charles Mohan Jr., United Mitochondrial Disease Foundation David Schubert, Stealth Biotherapeutics Erika Augustine, University of Rochester Medical Center Valerie Durkalski, Medical University of South Carolina Valerie Durkalski, Medical University of South Carolina Charles Mohan Jr., United Mitochondrial Disease Foundation 11:00 AM – 12:30 PMInvited Session 19: Use of Mobile Health Technologies in Pragmatic Clinical Trials TM, ST, E Mobile devices have radically transformed many sectors of our society—including finance, business, retail, and social communications—and offer considerable promise for similarly transforming health-care delivery models. More than 90 percent of individuals worldwide have access to mobile devices, and mobile health interventions have frequently been shown to produce outcomes comparable to or better than care delivered by clinicians. Further, mobile health tools can be widely accessible, personalizable, and cost-effective. This session brings together leaders in fields directly relevant to the use of mobile health technologies in pragmatic clinical trials. Specifically, Lisa Marsch will review the state of the science of applying mobile health technologies to a wide array of health behavior change interventions and the role that clinical trials research has played in this field of scientific inquiry. Amar Das will then discuss the application of novel knowledge-driven computational methods to support clinical research and pragmatic clinical trials. This overview will include a discussion of big data efforts to extract information from electronic medical records and longitudinal data collected via mobile devices to support trial recruitment and monitoring. Tiffany Cvrkel will speak about ethics in the mobile era, such as obtaining consent, IRB review, and privacy-confidentiality issues. Carmen Rosa will moderate a discussion with the audience on opportunities, challenges, and future directions in the use of mobile health technologies in pragmatic clinical trials. Speakers: Discussant: Chair: Organizer: Lisa Marsch, Dartmouth College Amar Das, Dartmouth College Tiffany Cvrkel, UCLA Carmen Rosa, NIDA Lisa Marsch, Dartmouth College Lisa Marsch, Dartmouth College Carmen Rosa, NIDA 29 Tuesday, May 17, 2016 11:00 AM – 12:30 PMInvited Session 20: Innovative Trial Designs for Precision Medicine ST Recently, adaptive trial designs have drawn tremendous attention and interest in academia, industry, and government because of their potential to treat patients more ethically, improve the success rate of clinical trials, and reduce the cost of drug development. Adaptive trial designs are indispensable for precision medicine because they take into account individual variability in genes, environment, and lifestyle. Adaptive designs allow researchers to make flexible clinical decisions based on patients’ characteristics and responses during clinical trials. This session will cover innovative designs for Phase I, II, and III clinical trials in precision medicine. Specifically, Alexia Iasonos will discuss the design and analysis of Phase I trials in the presence of patient heterogeneity; Ying Yuan will present an innovative Phase II clinical trial with biomarker subgroups; Sumithra Mandrekar will review several important designs, including basket, umbrella, and adaptive enrichment strategies, which are suitable for Phase III trials; and Yu Shyr will discuss the statistical tasks for designing a clinical trial in the precision medicine era. Speakers: Chair: Organizer: Alexia Iasonos, Memorial Sloan Kettering Cancer Center Ying Yuan, MD Anderson Cancer Center Sumithra Mandrekar, Mayo Clinic Yu Shyr, Vanderbilt University Haitao Pan, MD Anderson Cancer Center Ying Yuan, MD Anderson Cancer Center 12:30 PM – 1:45 PM Lunch/SCT Business Meeting 1:45 PM – 2:45 PM Contributed Paper Session Time Slot III CPS 13: Systematic Reviews and Meta Analysis ST, M CPS 14: Novel Statistical Approaches to RCTs: Stratification, Global Outcomes, Personalized Treatments and Mediation ST CPS 15: Improving Participant Involvement in RCTs SC, DM CPS 16: Electronic Data Capture and Data Visualization IS/DM, R CPS 17: Compliance and Adherence ST CPS 18: Multiplicity in RCTs ST 2:45 PM – 3:15 PM Break: Exhibits/Posters 3:15 PM – 4:45 PM Invited Session Time Slot V 3:15 PM – 4:45 PM Invited Session 21: Challenges of Implementing an Adaptive Design in an Academic Network Setting ST, M, TM Adaptive designs have initiated a paradigm shift in the world of clinical trials. Previously, investigators were restricted to a fixed design, which left trials vulnerable to failure from ineffective treatments and incorrect assumptions regarding treatment effect or variability as well as dose, duration, and/or population of interest. Now funding agencies are requesting trials that are innovative, efficient, and able to answer more questions than ever before. Designs abound in the literature that promise to deliver on these concerns, but implementation is still a nascent undertaking with little available guidance. This session highlights several lessons learned in the design and implementation of large-scale network-based adaptive clinical trials. To ground the discussion, speakers will provide insight from a currently funded study (ESETT) and several future studies implemented within the Neurological Emergency Treatment Trials (NETT) and StrokeNet networks. The first talk will discuss how statistical modeling can be used to assist with planning decisions beyond sample size including how to optimize drug supply and distribution, number of recruiting sites, allocation ratios and imbalance methods to improve efficiency. Track Key Information Systems/Data Management (IS/DM); Medical (M); Regulatory Issues (R); Ethics (E); Study Coordination (SC); Statistical (ST) Trial Management (TM) 30 Tuesday, May 17, 2016 The second talk will focus on the clinical aspects of adaptive trials including maintaining the blind while providing necessary information for continued care; striking a balance between answering multiple clinical questions and design limitations arising from the clinical setting; and working with a clinical team unfamiliar with adaptive designs. The third talk will discuss challenges of operationalizing both the statistical and clinical features of an adaptive design, specifically considerations for developing a budget, selecting sites, operationalizing the protocol, and developing a meaningful informed consent document. A discussant will summarize the points and share how the various stakeholders are collaborating to successfully build a portfolio of innovative adaptive designs in an academic network. Speakers: Discussant: Chair/Organizer: Caitlyn Ellerbe, Medical University of South Carolina Will Meurer, University of Michigan Judith Spilker, University of Cincinnati Renee Martin, Medical University of South Carolina Caitlyn Ellerbe, Medical University of South Carolina 3:15 PM – 4:45 PM Invited Session 22: Streamlining Clinical Trials: The Practicalities ST, TM, R Randomized controlled trials are the cornerstone for reliably evaluating the safety and efficacy of therapeutic strategies. For chronic conditions, where many treatments are expected to have only moderate effects, trials need to be large in size and long in duration to achieve sufficient statistical power and ensure a robust result. The regulations surrounding clinical trials are becoming increasingly burdensome and, as a result, the cost and complexity of a standard approach to evaluating therapies is prohibitive (typically at least US$4-500M for large clinical outcome trials). The development of potentially effective drugs is often stopped prematurely on financial rather than scientific grounds, and academic trials of important scientific questions have become more difficult to perform, resulting in a distortion of the scientific agenda. It is widely recognized that the current system is unsustainable. Multi-stakeholder organizations such as the Clinical Trials Transformation Initiative (CTTI, an FDA-Duke private partnership) are working hard to tackle key obstacles, particularly in the area of regulation. In spite of these efforts, the uptake of streamlined approaches to clinical trials remains limited. This may in part be due to ignorance of appropriate methodologies for streamlining, but perhaps is also a result of anxieties about acceptability from a regulatory viewpoint. There is a need for clear illustrations of what is possible within the current regulatory framework. This session will provide practical descriptions of approaches to streamlining clinical trials, using specific examples of strategies that have been successfully adopted in a variety of settings. A series of presentations will tackle each step of the clinical trials process, concluding with an account of how these methods have been successfully applied within a U.S. context. Given the current enthusiasm of the FDA and other regulatory agencies for promoting streamlined clinical trials, it is anticipated that these illustrations will provide timely and sought-after guidance for trialists in a wide range of disciplines. Speakers: Chair: Organizer: Trudie Lang, University of Oxford, UK Louise Bowman, University of Oxford, UK Martin Landray, University of Oxford, UK Stephen Wiviott, Harvard University John Alexander, Duke Clinical Research Institute Louise Bowman, University of Oxford, UK 31 Tuesday, May 17, 2016 3:15 PM – 4:45 PM Invited Session 23: Statistical Challenges in Immuno-Oncology ST, M The past several years have witnessed a resurgence of interest in cancer immunotherapy, owing to the clinical success and regulatory approvals of several immune-targeted therapies and leading to the selection of “Cancer Immunotherapy” as the 2013 Breakthrough of the Year by the journal Science. But statistical challenges exist at all phases of clinical development. In Phase I immunotherapy trials, which assess safety and immunogenecity, there is no standardized metric to define whether a patient has achieved an immune response. In Phase II immunotherapy trials, which assess efficacy, the proportion of patients who exhibit tumor shrinkage (termed the objective response rate) and progression-free survival are commonly measured although these efficacy signals are known to not be well-suited to immunotherapy. In Phase III immunotherapy trials, which typically assess patient survival, the survival kinetics of treated patients are different from those seen in chemotherapy trials. Delayed treatment effects of three to four months are often observed. When comparing survival between treatments, this delayed separation in survival curves suggests that the proportional hazards assumption has been violated. Moreover, group sequential designs for early termination are problematic and futility testing is risky. In addition, a fraction of patients exhibit long-term survival and may be cured, which impacts power. Given a mixture of patients, those who are cured and those who are not cured, alternative analysis approaches such as mixture cure models should be considered. These are a few of the statistical challenges that we face as the pace of cancer immunotherapy research accelerates across a wide spectrum of cancers. This session will include presentations on issues arising across all phases of immuno-oncology clinical development. Katherine Panageas will describe her experience in early-phase immunotherapy trials. Tai-Tsang Chen will focus on design and analysis issues in late-stage immunotherapy trials. Michael LeBlanc will provide an overview of mixture cure models and discuss how such models may be exploited for immunotherapy trials. Keavan Anderson will summarize the presentations and share his insights. Clinical examples drawn from the oncology literature will be highlighted. Speakers: Discussant: Chair/Organizer: Katherine Panageas, Memorial Sloan Kettering Tai-Tsang Chen, Bristol-Myers Squibb Michael LeBlanc, Fred Hutchinson Cancer Research Center Keaven Anderson, Merck Rosemarie Mick, University of Pennsylvania 3:15 PM – 4:45 PM Invited Session 24: Building the Clinical Trials Enterprise of the Future IS/DM, ST, R Health-care decisions regarding when and how to use medical products are best made when high-quality evidence is available so the patient and clinician can weigh the benefits and risks of treatment. The most valid evidence of a product’s effects is obtained from well-designed randomized, controlled trials (RCTs). Nevertheless, it is not always clear that the populations studied in RCTs represent all those treated in clinical practice, nor is it feasible to answer every question regarding the clinical uses of a product with an RCT. Until recently, many experts felt there was an inevitable trade-off between internal validity and generalizability. Recent deployment of electronic health records (EHR)—with the concomitant focus on common data standards and terminology, the development of disease-specific and product-specific registries with high-quality data collection, and the proliferation of smartphones and mobile health apps—has created opportunities that could overcome this perceived trade-off. We are approaching a tipping point at which a systematic approach can be developed to integrate the clinical research enterprise with clinical practice through which observational data may be leveraged to further enhance and streamline the conduct of RCTs. This new environment could be enabled by the broader availability of real-world evidence derived from interactions within the health-care system, personal data, and environmental data that exist in electronic form. This session will focus on the use of real-world evidence to complement the data available from RCTs and to Track Key Information Systems/Data Management (IS/DM); Medical (M); Regulatory Issues (R); Ethics (E); Study Coordination (SC); Statistical (ST) Trial Management (TM) 32 Tuesday, May 17, 2016 enhance the conduct of these trials. It will provide an overview of the clinical trial enterprise as it exists today, highlighting its successes and limitations. It will also feature a discussion of efforts to create a national resource for evidence generation, including considerations such as interoperability of electronic health data management systems and development of strategies to encourage efforts to build infrastructures to facilitate higher-quality data collection and curation, including the use of data standards. Finally, it will offer a discussion of the experience of using real-world evidence for drug and device regulation. Speakers: Chair: Organizer: Robert Califf, FDA Jonathan Jarow, FDA Jeffrey Shuren, FDA Robert Califf, FDA Melissa Robb, FDA/CDER 3:15 PM – 4:45 PM Invited Session 25: Prospective Individual Participant Data Meta-Analysis ST, M Prospective Individual Participant Data Meta-Analysis (PMA) is becoming more common across all areas of healthrelated research. The Cochrane Handbook for Systematic Reviews of Interventions calls a PMA the “gold standard” of systematic reviews. A prospective meta-analysis could arise spontaneously when a rapidly emerging question with a high level of interest has multiple independent groups, possibly in different countries, considering similar trials, or it could be planned in advance as a consortium of single center trials that are similar, but not identical. This session aims to describe the advantages and disadvantages of a PMA compared with a multi-center RCT, and the principles, methodology, and logistical issues in the design, conduct, and analysis of a PMA. Examples of PMAs and lessons learned from the fields of family planning, obstetrics, and pediatrics will be presented. Lisa Askie will explain why and how to use a prospectively planned meta-analysis. Elizabeth Thom will use the example of starting an international collaborative effort in obstetrics to discuss the concept, planning, and initiation of a PMA. David Turok will talk about taking the leap to a new paradigm by providing notes on conducting a first prospective meta-analysis. Finally, Lisa Askie will share lessons learned from a PMA collaboration of more than thirteen years. Speakers: Chair: Organizer: Lisa Askie, University of Sydney, Australia Elizabeth Thom, George Washington University David Turok, University of Utah Lynda Ugwu, George Washington University Elizabeth Thom, George Washington University Lynda Ugwu, George Washington University 4:45 PM – 6:00 PMPlenary Session: Trial of the Year: The Learning Early about Peanut Allergy (LEAP) Trial 33 Wednesday, May 18, 2016 7:00 AM – 11:00 AM Registration 8:00 AM – 9:00 AM ounders Lecture - Richard Stephens F “Patients as Cancer Research - Walking the Walk in the UK” 9:00 AM – 9:15 AM Break 9:15 AM – 10:45 AM Invited Session Time Slot VI 9:15 AM – 10:45 AM Invited Session 26: The International Behavioural Trials Network (IBTN): An International Effort to Improve the Rigor and Impact of Behavioral Clinical Trials TM A rapidly growing, robust literature demonstrates that good health behaviors are associated with a reduction in mortality and the prevalance of chronic noncommunicable disease. However, despite the great potential benefits of health behavior interventions, the uptake and impact of existing behavioral interventions and the creation of promising new interventions has generally been limited by methodological challenges specific to the design and conduct of behavioral clinical trials. The International Behavioural Trials Network was created to address methodological issues unique to these trials and provide guidance on current best practices in the development and implementation of behavioral trials. This session will highlight some of the key issues unique to behavioral trials, detail novel approaches to resolve these issues, and discuss some areas where further work is needed. Simon Bacon will review some of the key work that has been done in the field of behavioral trials, such as the MRC’s complex intervention guidelines, the theoretical domains framework, and the behavior change theory taxonomy. He will also identify some of the key challenges in the delivery of behavioral trials, such as treatment fidelity and selection of the appropriate comparison group, and provide information on the structure and function of the International Behavioural Trials Network. Susan Czajkowski will describe a framework—the ORBIT model—intended to accelerate the translation of findings from basic behavioral and social sciences research to the development of new behavioral treatments to improve unhealthy behaviors. Features of the model will be described, as well as methods useful at each phase and several examples of studies that are using the model. Paul Montgomery will address the developmental process of the CONSORT Extension for Social and Psychological Interventions, highlighting key additions to the main CONSORT statement for publishing trial data. In addition, the development of behavioral trial specific GRADE guidelines and SPIRIT statements will be discussed. Kenneth Freedland will describe appropriate frameworks to develop high-quality international behavioral trial networks and systematic processes by which global research targets can be identified and agreed upon. Examples of how this has worked and failed in practice will also be discussed. Speakers: Organizer/Chair: Simon Bacon, Concordia University, Canada Susan Czajkowski, NIH/NHLBI Paul Montgomery, University of Oxford, UK Kenneth Freedland, Washington University, St. Louis Simon Bacon, Concordia University, Canada 9:15 AM – 10:45 AM Invited Session 27: FDA IND Reporting Final Rule Compels a New Dialog among the DMC, Sponsor, and FDA ST, M, R Concerns over product safety have resulted in late-stage program failures and market withdrawals. This has focused more interest on aggregate safety analyses during clinical development. The FDA IND Reporting Final Rule requires an expedited safety report whenever aggregate analysis indicates a clinically meaningful imbalance with an event occurring more frequently in the drug treatment group than in a concurrent or historic control group. The FDA guidance on Safety Reporting Requirements for INDs and BA/BE Studies amplifies the Final Rule in asserting that a systematic approach for safety surveillance “should include a process for reviewing, evaluatTrack Key Information Systems/Data Management (IS/DM); Medical (M); Regulatory Issues (R); Ethics (E); Study Coordination (SC); Statistical (ST) Trial Management (TM) 34 Wednesday, May 18, 2016 ing, and managing accumulating safety data from the entire clinical trial database at appropriate intervals.” All of the available data, including data from outside of clinical trials, should be used to assess the safety of the developing product. Any suspected adverse reactions should be evaluated relative to other events in ongoing studies as well as previous studies. DMCs evaluate accumulating unblinded data and make recommendations about the continuing safe conduct of trials. Trial sponsors must decide how best to implement these recommendations to comply with IND reporting and make the final decision on whether or not to stop a trial. However, while DMC recommendations are based on differences observed between treatment arms, sponsors are generally blinded to these differences, adding considerable uncertainty to the decision-making process. While DMCs should have unblinded access to all of the available information, sponsors must conscientiously maintain their blind, so that together these two groups can fully protect patients from unsafe treatments without compromising trial integrity or otherwise interfering with the planned analyses. Our goal is to formalize and improve conversations about safety signal monitoring and IND reporting among all stakeholders in the conduct of randomized clinical trials. In particular, we will discuss blinded analyses of accumulating safety data for the Final Rule; DMCs and the Final Rule for safety reporting; and the role of the industry sponsor and of external DMCs in aggregate safety analyses from pre-approval clinical trials. Speakers: Discussant: Chair: Organizer: Greg Ball, Merck Janet Wittes, Statistics Collaborative José Vega, Merck Dave DeMets, University of Wisconsin Amy Xia, Amgen Greg Ball, Merck Invited Session 28: Central IRBs: Implementation, Effectiveness, and Optimization IS/DM, E The regulatory requirement of Institutional Review Boards (IRBs) is to provide oversight of clinical trial research to protect human subjects and ensure ethical research conduct. Local IRBs review research performed just at their own site, while Central Institutional Review Boards (CIRBs) review research being conducted at multiple sites. The Food and Drug Administration (FDA) and the Office of Human Research Protections (OHRP) support the use of CIRBs for multicenter trials with the goal of increasing efficiency, quality, and the speed of clinical trial protocol approval. In addition, proposed changes to the Common Rule will require any U.S. institution engaged in a cooperative study to rely upon a single IRB for that study, with some exceptions. This session will focus on how CIRBs can be optimized and used effectively. Using the example of the NINDS-funded Stroke Trial Network, Michael Linke will discuss the advantages and disadvantages of using a CIRB; the resources required for establishing and administering one; the responsibilities, accountabilities, and liabilities between the local institution and the CIRB; and collaboration across multiple CIRBs. Robert Silbergleit will describe a project conducted by the Neurological Emergencies Treatment Trials (NETT) network and the Pediatric Emergency Care Applied Research Network (PECARN) to explore, revise, test, and compare measures of local context review of community consultation activities for exception from informed consent research by both local and central IRBs. Catherine Dillon will focus on how clinical trial management systems can optimize CIRB operations by eliminating redundant or multiple software infrastructures, streamlining the reporting of safety events and unanticipated problems, improving regulatory compliance, and acting as a central repository for all study-related information. 9:15 AM – 10:45 AM Speakers: Chair/Organizer: Michael Linke, University of Cincinnati/Cincinnati VA Medical Center Robert Silbergleit, University of Michigan Catherine Dillon, Medical University of South Carolina Catherine Dillon 35 Wednesday, May 18, 2016 Invited Session 29: Use of Administrative and Registry Data in Clinical Trials TM, IS/DM, E Clinical trials, the gold standard by which health interventions are tested, are worth the investment. However, in times of fiscal constraint, researchers may find greater efficiency by optimizing collaborations between traditional epidemiological and clinical trial methodology. Such harmonized processes have been established in several countries with a view to expediting advances in health-care delivery. Are randomized registry trials the next disruptive technology in clinical research? In this session, Marc Jolicoeur will describe the Canadian Randomized Registry Trial Initiative in Cardiology. Dean Fergusson will discuss pragmatic trials, comparing standards of care with simple protocols, consent, and data collection. Annette Hay will outline opportunities and challenges associated with linkage of clinical trial and administrative data, including cancer patients’ preferences. Don Willison will offer a bioethical perspective, considering ethical issues in registry-based pragmatic trials and data privacy. After these short presentations, Wendy Parulekar will facilitate an open discussion. 9:15 AM – 10:45 AM Speakers: Discussant: Chair/Organizer: Marc Jolicoeur, Université de Montréal, Canada Dean Fergusson, Ottawa Hospital Research Institute, Canada Annette Hay, Queen’s University, Canada Don Willison, Ontario Agency for Health Protection and Promotion, Canada Wendy Parukelar, Canadian Cancer Trials Group, Canada Annette Hay, Queen’s University, Canada Invited Session 30: Crossover Trials: New Perspectives and Practical Implications for an Efficient Design ST, M, E For the assessment of a rapidly acting treatment whose benefit disappears quickly after discontinuation, the crossover is an excellent trial design. Because each patient serves as his or her own control, crossover designs typically yield efficient estimates of interventional effects. The last three years have yielded important methodologic findings regarding the design and analysis of crossover designs. This session will showcase research in the areas of survival endpoints, the effective use of baseline measurements to increase efficiency, and adaptive designs. Mary Putt will briefly review the crossover design, and then our speakers will illustrate how these new statistical methodologies can be translated into more effective clinical trials. Dean Follmann will first question the conventional wisdom that crossover designs are inappropriate for absorbing binary endpoints, such as death or HIV infection. He will then explore the use of crossover designs in the context of non-repeatable binary endpoints and show that, when there is heterogeneity in individual risk, the crossover design can be more efficient than the more commonly used parallel group design Next, Yuanyuan Liang will argue that ethical considerations compel us to balance the needs of patients with the quest for balanced data and statistically efficient comparisons of treatment effects. She will propose a new allocation rule for constructing response-adaptive crossover designs, one that is aimed at balancing estimation precision and treatment benefit. She will illustrate how this new adaptive design can successfully allocate more patients to better treatment sequences while sacrificing little in estimation precision. Lastly, for the two-period, two-treatment (2×2) crossover trial, Devan Mehrotra will explore ways of incorporating pretreatment baseline measurements (PTBMs) into estimation of the treatment effect. Here, the power to detect a treatment effect reflects both the form of the variance-covariance matrix of the vector of responses, and the approach to incorporating PTBMs into the analysis. His work illustrates significant problems with the change from baseline analysis. Importantly, power gains are generally largest for an analysis of covariance approach that uses the within-subject difference in treatment response as the dependent variable and the difference in PTMBs as the covariate. 9:15 AM – 10:45 AM Track Key Information Systems/Data Management (IS/DM); Medical (M); Regulatory Issues (R); Ethics (E); Study Coordination (SC); Statistical (ST) Trial Management (TM) 36 Wednesday, May 18, 2016 Speakers: Discussant: Chair/Organizer: Mary Putt, University of Pennsylvania Dean Follmann, NIH/NIAID Yuanyuan Liang, University of Texas Health Science Center at San Antonio Devan Mehrotra, Merck Susan Ellenberg, University of Pennsylvania Mary Putt, University of Pennsylvania 10:45 AM – 11:00 AM Break 11:00 AM – 12:30 PM Contributed Paper Session Time Slot IV CPS 19: Statistical Approaches in Stepped Wedge Designs ST CPS 20: Statistical Issues in Cancer and Adaptive Trials ST CPS 21: Trial Management & Study Coordination Across the Trial Lifecycle SC, DM CPS 22: Managing Data in the 21st Century IS/DM, SC CPS 23: Pragmatic Trials/Stepped Wedge/Missing Data ST CPS 24: Regulatory and Ethical Issues in Trials R, E 2016 Program Committee 2016 Education Committee Kaleab Abebe Marianne Kearney Chase Emily Van Meter Dressler Caitlyn Ellerbe Gustavo Jimenez-Maggiora Ken Kobayashi Beverly Koski Todd MacKenzie Graeme MacLennan Sumithra J. Mandrekar Kristine M. Nelson Letitia H. Perdue Rema Raman Yves D. Rosenberg Abigail Shoben Rui Tang Marc Walton Amy Watson Kevin Wilson Wendy R. Parulekar Domenic J. Reda Kousick Biswas Lynda Constable Thomas Cook Emily Van Meter Dressler Dixie Ecklund Suzanne Firrell Virginia J. Howard Qian Li Leslie Ain McClure Oscar Moreno Yves D. Rosenberg Wendy R. Parulekar Domenic J. Reda Chair: Li Chen Co-Chair: Sumithra J. Mandrekar Chair: Leslie Ain McClure Co-Chair: William J. Meurer 37