The 2024 Graybill Conference will be held jointly with the 2024 WNAR/IMS Annual Meeting (https://www.wnar.org/wnar2024). The theme of the Graybill Conference is “Rare Disease Drug Development”. For the WNAR/IMS Annual Meeting all topics are welcome.

“Rare diseases are rare, but rare disease patients are numerous.” – Orphanet.

Finding cures for pediatric and rare disease is now a global health priority. According to Orphanet (https://www.orpha.net/consor/cgi-bin/index.php), a 37-country network, reported 6172 unique rare diseases, affecting 300 million people worldwide, about 72% of which are genetic and about 70% of which are exclusively pediatric onset. More than 90% of rare diseases are without an FDA-approved treatment.

Rare diseases are numerous, heterogenous in nature, and geographically disparate. Developing a treatment for pediatric and rare diseases presents unique challenges. Various public policy, regulatory initiatives have been implemented in US and rest of the world to help reduce the barriers. Given its limited patient pool, the success of advancing patient care and treatment options hinges on multi-stakeholders and interdisciplinary collaboration. The conference is organized to dive deep in each of those areas with the goal to bring more effective and safe treatments to patients diagnosed with rare diseases worldwide.

From the Graybill Program Committee

It is with deep sorrow to learn of the passing of our esteemed colleague and friend, Dr. Dionne Price, Deputy Director for the Office of Biostatistics in the Center for Drug Evaluation and Research at the US Food and Drug Administration (FDA). During her 20+ years at the FDA, Dionne made significant contributions to the Office of Biostatistics, including work as Deputy Director during the COVID-19 pandemic response, oversight of rare disease drug development, and being a key stakeholder in the FDA’s Accelerating Rare disease Cures Program. In addition to her work at the FDA, Dionne also had a broad impact on the statistical community, including most recently serving as the 118th President of the American Statistical Association in 2023. Her dedication to outstanding work, coupled with her kindness and modesty, has profoundly influenced countless individuals and will continue to resonate in the lives she impacted. As we mourn the passing of our beloved colleague and friend, we find comfort in the privilege of having known her and having been enriched by her guidance, insight, and leadership. Let us strive to continue her commitment to curing rare diseases and promoting statistical practice.

Travel Information

Rental Car

If traveling by rental car, we recommend using a Maps App, such as Google Maps, Apple Maps, etc. The venue address is 1101 Center Ave Mall, Fort Collins, CO 80521. The drive to Fort Collins from Denver takes approximately 1 hour, but depends on traffic. This drive may have tolls, depending on the route you choose in your maps app.

Taxis

Taxi cabs and mobile taxi services (Uber/Lyft) are also available, but are fairly expensive ($120-350).

Airport Shuttle (Recommended)

Groome Transportation offers an airport shuttle that will take you from the airport directly to Colorado State University’s Lory Student Center. The ride, which takes about 1 hour, 20 minutes will cost $30-40. You must purchase this option in advance by visiting the Groome Transportation website.

When booking online, choose “FC – CSU Transit Center” and “Denver International Airport” as your destinations.

Train / Bus

For the Train / Bus option, you will follow signs in Denver International Airport to the A-line. Once you purchase your ticket ($5-10), get on the A-line headed toward Union Station and depart the train at Union Station.

From Union Station, you will exit the train terminal onto Wewatta Street, which is where the bus picks up. Purchase your ticket ($10) and board the NORTH line toward Fort Collins and depart at Downtown Transit Center in Fort Collins.

From the transit center, you will purchase your ticket (free at this time) and board the MAX line bus to Laurel Street Station and depart at the Colorado State University Campus. From here, follow signs for the Lory Student Center.

Registration

Registration is now open. Please register at: https://conferencereg.colostate.edu/WNAR-IMS-Graybill-2024

• Registration deadline is May 6, 2024.
• After registering, you’ll get a confirmation email detailing how to book discounted hotel rooms. Availability is limited, so register early to secure your spot.
• Limited on-campus lodging is available on a first-come, first-served basis. Complimentary parking permits and a free shuttle from Denver International Airport to Fort Collins on June 9 and 12 are available in limited quantities. Register soon to reserve yours.
• Upon the approval of the organizing committee, cancellation requests must be received by the Office of Conference Services at (970) 491-7501, Fax (970) 491-7747, or e-mail conferences@colostate.edu no later than 11:59pm MST, May 10, 2024. A $60 processing fee will be charged for each cancellation. No cancellation requests will be honored after this time, though substitutions will be allowed.
• For other important dates, refer to the WNAR/IMS/Graybill website.

Program

Short Courses

N-of-1 Trials for Personalized Healthcare

Sunday, June 9, 8:30 AM – 11:00 AM

Instructor: Christopher Schmid, Brown University

The DOOR is Open: A Patient-Centric, Pragmatic Approach to Clinical Trials based on Benefit: risk

Sunday, June 9, 8:30 AM – 11:00 AM

Instructors: Scott Evans and Toshimitsu Hamasaki, George Washington University

Small Sample, Sequential, Multiple Assignment, Randomized Trial (snSMART) Designs and Methods for Chronic, Rare Disease Drug Development

Sunday, June 9, 1:30 PM – 4:00 PM

Instructor: Kelley Kidwell, University of Michigan

Bayesian Borrowing Techniques for Rare Disease Clinical Research

Sunday, June 9, 1:30 PM – 4:00 PM

Instructors: Joseph Koopmeiners and Steffen Ventz, University of Minnesota

Invited Sessions

Keynote: The Order of Operations is Important: It is Time to Correct the Clinical Trial Arithmetic

Tuesday, June 11, 8:30 AM – 10:30 AM
Scott Evans, George Washington University

Statistical Methods for Environmental Epidemiology

Monday, June 10, 10:30 AM – 12:15 PM
Chair & Organizer: Tianjian Zhou, Colorado State University

• Kayleigh Keller, Colorado State University. Mitigating measurement error and confounding in cohort studies of air pollution and cognitive aging
• Ander Wilson, Colorado State University. Heterogeneous distributed lag models to estimate personalized effects of maternal exposures to air pollution

• Glen McGee, University of Waterloo. Testing for non-additive interaction in flexible Bayesian models for multi-pollutant mixtures
• Shanshan Zhao, National Institute of Environmental Health Sciences. Accommodating limit of detection of multiple exposures in environmental mixture analyses: an overview of statistical approaches

Subgroup and Small Sample Analysis Issues

Monday, June 10, 10:30 AM – 12:15 PM
Chair & Organizer: Brian Wiens, ACELYRIN

• Yao Chen, Novartis. Workflow to assess treatment effect heterogeneity in clinical drug development
• Peter Thall, MD Anderson Cancer Center. Bayesian treatment screening and selection using subgroup-specific utilities of response and toxicity

• David Shera. Employing mixed models for longitudinal data and small sample sizes: evaluating gene therapy for Canavan’s disease

Utilizing External Data to Inform Drug Development in Pediatric Oncology

Monday, June 10, 1:45 PM – 3:30 PM
Chair & Organizer: Pallavi Mishra-Kalyani, FDA

• Lindsay Renfro, Children’s Oncology Group. Considerations for external controls in pediatric oncology
• Arup Sinha, FDA. Regulatory considerations for and examples of external controls in pediatric oncology drug development

• Haitao Pan, St. Jude’s Hospital. Evaluating the type I/II error rates in trials incorporating external control data
• Satrajit Roychoudhury, Pfizer. Discussion

Statistical Models for Rare Disease Studies

Monday, June 10, 3:45 PM – 5:30 PM
Chair & Organizer: Yuan Ji, University of Chicago

• Joseph Ibrahim, University of North Carolina at Chapel Hill. The scale transformed power prior for time-to-event data
• Tianjian Zhou, Colorado State University. RoBoT: a robust Bayesian hypothesis testing method for basket trials

• Alexander Kaizer, University of Colorado Anschutz Medical Campus. Increasing the statistical efficiency of rare disease research studies through master protocol designs
• Yuan Ji, University of Chicago. Discussion

Panel Discussion: Regulatory Innovations and Collaborations to Promote Rare Disease Development

Tuesday, June 11, 10:30 AM – 12:15 PM
Chair & Organizer: Erik Bloomquist, Merck
Moderator: Brian Wiens, ACELYRIN

• Gregory Levin, FDA
• Guei-Feng (Cindy) Tsai, Taiwan CDE

• Andrew Thompson, EMA
• Frank Pitavy, EMA

Graybill Career Lunch Roundtable

Tuesday, June 11, 12:15 PM – 1:45 PM

• Lei Wang, The Lotus Group
• Toshimitsu Hamasaki, George Washington University

• Naitee Ting, Boehringer Ingelheim
• Gregory Levin, FDA

Design and Analysis in Clinical Trials

Tuesday, June 11, 1:45 PM – 3:30 PM
Chair & Organizer: Zhezhen Jin, Columbia University

• Shikun Wang, Columbia University. A general backward joint model of longitudinal and survival data with application to dynamic prediction
• Toshimitsu Hamasaki, George Washington University. Risk assessment in clinical trials

• Ying Lu, Stanford University. The trade-off between bias and efficiency in borrowing RWD in hybrid designed trials
• Shangwu Samuel Wu, University of Florida. Pick-the-winner sequential parallel comparison designs

Bridging the Knowledge Gap: Advances in Pediatric Extrapolation

Tuesday, June 11, 1:45 PM – 3:30 PM
Chair & Organizer: Vickie (Yuanye) Zhang, Servier BioInnovation

• Hengrui Sun, FDA. Regulator’s view on pediatric extrapolation, ICH E11A and other guidelines
• Vickie (Yuanye) Zhang, Servier BioInnovation. Mechanism of action-based Bayesian extrapolation strategy to accelerate pediatric drug development

• Mayadah Shabbout, GSK. Extrapolation analysis plan for an integrated pharmacokinetic, safety, and efficacy open-label trial for the treatment of anemia associated with chronic kidney disease in male and female children and adolescents aged 3 months to under 18 years requiring dialysis
• Antara Majumdar, GSK. Discussion

Opportunities, Gaps and Promises Brought by Digital Health Technology

Tuesday, June 11, 3:45 PM – 5:30 PM
Chair & Organizer: Yaohua Zhang, Vertex Pharmaceuticals

• Vincent Tan, Vertex Pharmaceuticals. New kids on the block: analyzing data from state-of-the-art diabetes devices
• Darrian Rice, Regeneron. Characterizing hemodynamic response during postural transitions with ambulatory ECG and accelerometry

• Vadim Zipunnikov, Johns Hopkins University. Developing more sensitive endpoints by leveraging novel statistical methods for Digital Health Technologies (DHTs) data
• Nishit Agarwal, Medidata. Redefining patient assessment in clinical trials with digital technologies

Endpoint Development and Analysis Considerations for Rare Disease Clinical Trials

Wednesday, June 12, 8:30AM – 10:15 AM
Chair & Organizer: Rebecca Chiu, FDA

• Monica Morrell, FDA. Applications of patient-focused drug development in rare disease programs
• Mitch Thomann, Boehringer Ingelheim. Developing a clinical endpoint model for hidradenitis supperativa

• Satrajit Roychoudhury, Pfizer. Dynamic enrichment of Bayesian small sample, sequential, multiple assignment randomized trial (snSMART) design using natural history data: a case study from Duchenne muscular dystrophy
• Yared Gurmu, FDA. Global tests for multiple endpoints in rare disease trials

Innovative Methods for Incorporating Real-World and Historical Data into Clinical Trials

Wednesday, June 12, 8:30AM – 10:15 AM
Chair & Organizer: Tianjian Zhou, Colorado State University

• Dehua Bi, University of Chicago. PAM-HC: a Bayesian nonparametric construction of hybrid control for randomized clinical trials using external data
• Meizi Liu, Takeda. Propensity-score based meta-analytic predictive prior for incorporating real world data

• Noirrit K. Chandra, University of Texas at Dallas. Bayesian nonparametric common atoms regression for generating synthetic controls in clinical trials
• Hongfei Li, Incyte. An informative prior for borrowing historical data under the mixture cure rate model

Bayesian Methods in Clinical Drug Development

Wednesday, June 12, 10:30AM – 12:15 PM
Chair & Organizer: Antara Majumdar, GSK

• Ming-Hui Chen, University of Connecticut. Bayesian re-design of a new pediatric trial via borrowing information from concurrent adult trials and historical pediatric and adult trials with similar mechanism of action
• James Rogers, Metrum Research Group. Evaluating conditional exchangeability assumptions for Bayesian borrowing, with application to pediatric extrapolation

• Illana Trumble, GSK. Building a hybrid external control arm using a fusion of Bayesian borrowing and causal inference
• Hengrui Sun, FDA. Discussion

Local Organizing Committee

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History

The Graybill Conference has been hosted annually by the Department of Statistics at Colorado State University. Dr. Franklin A. Graybill came to Colorado in 1960 and was involved in the development of the statistics program, first as part of mathematics and then in its own department. He founded the Graybill Statistical Laboratory in 1961, which recently celebrated its 50th year in operation.

Read more about the history here.