2023 Webinars
Statistical Considerations for Tumor Agnostic Drug Development
Cindy Lu; Kui Shen
March 14
Recent years have witnessed a few successful drug approvals with tumor agnostic pathway. Meanwhile, the limited numbers of approvals in this pathway may indicate tremendous challenges from translational, regulatory and statistical perspectives. In this presentation, ASA BIOP Oncology Methods SWG Master Protocol Sub-team and DIA Innovative Design Scientific Working Group (IDSWG) oncology sub-team will provide a deep dive into the cases leading to successful approval and a few case studies with investigational drug yet approved and share some implications and lessons learned from the working group. Statistical considerations such as controlling type I error, addressing homogeneous efficacy in certain tumor types with small sample sizes, and defining/handling potential negative data post accelerated approval will be discussed. Regulatory challenges will also be reviewed and shared with case examples.
Diversity in Clinical Trials
Mark Rothmann
April 21
CDER has published Drug Trials Snapshots and annual reports beginning in 2015 which provide the distributions of demographic subgroups and other important subgroups that participate in
those clinical trials that lead to the initial approval of the drug/therapeutic biologic along with
subgroup analysis. In April 2022, FDA released a draft guidance on Diversity Plans to Improve
Enrollment of Participants from Underrepresented Racial and Ethnic Populations in Clinical
Trials to provide recommendations to sponsors developing medical product on the approach for
developing a Race and Ethnicity Diversity Plan. Public Law 117-328 enacted in December 2022
requires diversity action plans of phase 3 studies of drugs, biologics, and devices. FDA is working on revising related guidances and has multiple projects on assessing representation of underrepresented groups. We have held a workshop and symposium in recent years on heterogeneous treatment effects with the workshop concentrated on statistical approaches.
Statistical Translation of Extrapolation: demonstrating efficacy and safety of investigational medicines in pediatric populations
James Travis; Jingjing Ye; Margaret Gamalo
May 16
Pediatric drug development often faces substantial challenges, including economic, logistical, technical, and ethical barriers, among others. Pediatric drug development lags adult development by about 8 years and often faces infeasibility of trials, resulting in children being a large, underserved population of "therapeutic orphans," as an estimated 80% of children are treated off-label (Mulugeta et al. in Pediatr Clin 64(6):1185-1196, 2017). Among many efforts to mitigate these feasibility barriers and as an ethical approach to minimizing exposing pediatric patients to the research risks, increased attention has been given to extrapolation; that is, the leveraging of available data from adults or older age groups to draw conclusions for the pediatric population. Recent ICH E11A harmonization on a pediatric extrapolation framework provides a clearer path forward for pediatric drug development programs leveraging some degree of extrapolation despite uncertainties. In this framework, the degree to which extrapolation can be used lies along a continuum representing the uncertainties to be addressed through generation of new pediatric evidence (Gamalo et al. 2021). The webinar will cover topics including regulatory history of pediatric drug development overview, ICH guidelines, including extrapolation strategy, process, concept, and plan, the statistical methodologies in pediatric extrapolation source and target population, Bayesian framework and methodologies, and the extend of development relating to safety and assessment of safety in pediatric patients.
Scientific Evaluation of Safety Data and Aggregate Safety Assessment Planning for IND Safety Reporting
Greg Ball; Jacqueline Corrigan-Curay; Barbara Hendrickson; Brian Waterhouse
June 15
The webinar will describe the ASAP process and a procedural workflow: a blinded quantitative review process is coupled with qualitative data evaluation to decide whether to escalate major adverse cardiovascular (MACE) events for unblinded review during the conduct of a hypothetical Phase III programme. We will demonstrate this workflow in conjunction with the BDRIBS method, which has an associate R Shiny application that allows for dynamic visualisation and assessment.
ASA-DIA Safety Working Group
Hong Yang; Leo Plouffe; Lisa R. Rodriguez; Mike W. Colopy
October 2
Recently, CIOMS WG XII Benefit-Risk report was released, outlining the benefit-risk (BR) landscape and promoting the use of a structured BR framework (SBRF) from the beginning and continuously updated and applied throughout the product lifecycle, including key decision-making steps. The report also mentioned the visualization of benefit-risk assessment (BRA) and its importance in the BR process. Members from CIOMS WG XII will provide an overview of this document. Members from BRAP and BRATS will discuss the WG's deliverables and progress (such as BRAP's template that is under development), and BRATS efforts and considerations for an R-Shiny based interactive tool.
Interdisciplinary Safety Evaluation for Learning and Decision-Making: Education for Executives
Greg Ball; Jacqueline Corrigan-Curay; Barbara Hendrickson; Sheila Mahoney-Jewels
November 16
Jacqueline Corrigan-Curay (FDA) set the stage with a regulatory perspective on the IND Safety Reporting Final Rule and the new FDA Medical Queries and Standard Safety Tables and Figures. Sheila Mahoney (LifeSciHub) provided a business case to senior leaders for devoting additional resources to achieve a more proactive approach to clinical safety assessment. Greg Ball (ASAP Process) explained how meeting the spirit of the final rule requires a culture change in how we do programme-level safety assessments throughout the clinical development life cycle. And Barbara Hendrickson (University of Chicago) advocated for an aggregate safety assessment planning process to scientifically evaluate accumulating programme-level safety information, support IND reporting decisions, operationalise FDA Medical Queries (FMQs) and Standard Safety Tables and Figures, and leverage interactive safety graphics for safety data assessment and communication. Jacqueline Corrigan-Curay closed out the webinar and the series highlighting how FDA–industry partnerships have strengthened aggregate safety assessments to improve identification and characterisation of risks for a medicinal product on a programme level. Approaching safety differently as a result of the IND Safety Reporting Final Rule can positively impact the bottom line and mitigate PR risk.
Benefits of joining our community of stats in small biotech
Liang Fang; Mohamed Hamdani; Alan Hartford; Sharon C. Murray; Alan Y. Chiang
December 1
With the rapid growth of biotechnology in the last half century, new drug discovery and development have now reached an inflection point where hundreds of emerging small biotech are evolving into the clinical development stage. These companies employ a growing number of statisticians. While the majority of statisticians in the pharmaceutical industry are employed by big pharma, we are seeing an increasing number taking the leap into the small biotech world. The purpose of this panel-discussion is to connect statisticians who either work for or want to work for a small biotech company so that they can share strategies, experiences, and ideas.