Case Studies in using FACTS to design Clinical Trials: A two-arm study with adherence model driven effect size and irregular interim analyses

Author Sabrina Paganoni, MD, PhD, of Massachusetts General Hospital and Harvard Medical School, discusses results of the first 4 drug regimens from the HEALEY ALS platform trial and how this study design makes efficient use of resources.

Don Berry presents as part of a panel of Researchers on the topic of “Improving Scientific Reproducibility in an Age of International Competition and Big Data I” at the PCAST Public Meeting on January 31, 2014.

Roger J. Lewis, MD, PhD, discussed Bayesian Analysis: Using Prior Information to Interpret the Results of Clinical Trials with Melanie Quintana, PhD.

Global Coalition for Adaptive Research released a series of Spotlight short videos presented by Don Berry on the GBM AGILE Trial.

This Podcast series by JAMA provides valuable interviews about the statistical and methodological foundations of clinical research.

This Podcast series by JAMA provides valuable interviews about the statistical and methodological foundations of clinical research.

This Podcast series by JAMA provides valuable interviews about the statistical and methodological foundations of clinical research.

This Podcast series by JAMA provides valuable interviews about the statistical and methodological foundations of clinical research.

This Podcast series by JAMA provides valuable interviews about the statistical and methodological foundations of clinical research.

This Podcast series by JAMA provides valuable interviews about the statistical and methodological foundations of clinical research.

This Podcast series by JAMA provides valuable interviews about the statistical and methodological foundations of clinical research.

This Podcast series by JAMA provides valuable interviews about the statistical and methodological foundations of clinical research.

In this September 6, 2024 episode by SciPod Health and Medicine, SciPod summarizes the recent paper “Lecanemab for Patients with Early Alzheimer Disease: Bayesian Analysis of a Phase 2b Dose-Finding Randomized Clinical Trial” by Dr. Donald Berry (Founder of Berry Consultants) and Scott Berry (President of Berry Consultants).

Using FACTS to design a large 2-arm safety study, borrowing information from a previous trial, exploring alternative endpoints and using an enriched population.

A Phase 2 dose finding study using a Bayesian dose response model and response adaptive randomization across multiple doses and treatment regimens. Includes a presentation of the interim analyses from the actual trial that lead to the successful phase 3 trial of Lecanemab.

A randomized two arm study, using a utility weighted modified Rankin score and rules for adapting the enrolment criteria based on the location of the haemorrhage.

Designing a phase 1 dose escalation using Bayesian Logistic Regression Model (BLRM), with open enrolment (rather than cohort) using FACTS N-CRM.

Using FACTS to design a two-arm study where differences in adherence between the arms drive the effect size. Uncertainty in the effect size prompted spacing the interims to correspond to different sample sizes resulting in irregular interim analyses. Using a uses a finite mixture model from previous data on the analysis endpoint to justify the irregular interims.

Is this the most complex and most successful trial ever designed and run? Looking at the AWARD 5 trial for what became Eli Lilly’s Trulicity drug. The drug used response adaptive randomization, longitudinal modelling, dose response modelling and a utility function combining 4 endpoints. The trial selected a successful dose and switched early from phase 2 to a successful phase 3.

Don Berry speaks as part of the press conference for I-SPY 2, an innovative breast cancer clinical trial.

Don Berry at the 2012 International Society for Bayesian Analysis (ISBA) World Meeting in Kyoto, Japan. https://videolectures.net/videos/isba2012_berry_bayesian_ideas

Scott Berry presents at the Royal Statistical Society’s, “PSI Debate: This house believes that pharmaceutical drug development and regulation should become fully Bayesian”.

Scott Berry presents at the “Transforming Drug Development – Delivering Innovation and Efficiency through Adaptive Clinical Trials” conference that was co-sponsored by Berry Consultants.

Don Berry’s presentation at the Simons Institute for the Theory of Computing at University of California Berkeley.

https://remap-cap.org

REMAP-CAP

Scott Berry from Berry Consultants gives an overview of the current state statistical model for REMAP-CAP.

PREPARE Webinar 07/04/2021 - Why future clinical trials will be platform trials

PREPARE Webinar 07/04/2021 - Why future clinical trials will be platform trials

Learn more about this groundbreaking trial designed by Berry Consultants to accelerate the development of effective treatments for people in ALS. Weekly updates and additional videos can be found on HEALEY ALS Platform Trial Video Library of Mass General Hospital.

Dr. Ben Saville of Berry Consultants and Dr. Chris Butler of Oxford University present a Grand Rounds session on the PRINCIPLE Adaptive Platform Trial.

Bringing Bayesian Statistics into Clinical Trials - Shortened Version

What makes GBM AGILE an innovative trial?

How is GBM AGILE paving the way for more innovative research?

Global Coalition for Adaptive Research released a series of Spotlight short videos presented by Don Berry on the GBM AGILE Trial.

Roger J. Lewis, MD, PhD, lectured on REMAP-ILD at HCOR scientific meeting (Sao Paulo, Brazil).

Dr. Melanie Quintana, statistical scientist and director at Berry Consultants, discussed innovative clinical trial design in ALS research at the 2023 MDA conference.

In this video we look at the different types of MAMS designs that includes Platform Trail designs. We look at the different design issues and analysis methods available for these sorts of trials. Originally aired November 9, 2023

In this video we look at designing Phase 2 Basket Trials where a treatment is explored in a large number of sub-groups (too many to be able to suitably power the trial in each sub-group).

In this video we look at designing seamless phase 2/3 trials, where a multi-arm phase 2 transitions when it can, selecting a dose and transitioning to a confirmatory phase 3.

In this video we look at designing response adaptive randomization (RAR) and arm dropping multi-arm phase 2 trials.

In this video we look at designing Group Sequential trials for confirmatory phase 3 trials, where the trial includes interims to stop early for efficacy and futility.

In this video we look at the issues around designing Phase 1 Dose Escalation trials in oncology, where the aim is to explore increasing dose levels up to a limiting rate of toxicities.

Looking at RAR with 3 aims: 1) A surprising amount of the literature considers just the two arm setting, when arguably the most interesting setting for this technique is the multi-arm one. 2) There have been a number of papers over the years critical of RAR and I’d like to add present some results in favour of RAR. 3)

Dr. Scott Berry and Dr. Kert Viele from Berry Consultants delivered a presentation during the EU-PEARL webinar on February 24.

Berry Consultants released a video showcasing their support for the LA County Predictive Modeling for the COVID-19 Pandemic, which was recognized among the top achievements in quality and productivity by the County's Quality and Productivity Commission in 2021.

The Sean M. Healey & AMG Center for ALS at Mass General has successfully enrolled its first participants in a pioneering clinical trial aimed at advancing ALS research.

On October 2, Berry Consultants hosted a public FACTS webinar led by Dr. Kert Viele, discussing the latest protocols and safety concerns of SARS-COV-2 vaccine trials from major pharmaceutical companies, with the recording available on their YouTube channel.

On April 24, Berry Consultants hosted a public FACTS webinar on COVID-19 trials, featuring presentations from various experts, with recorded sessions and additional resources available on their YouTube channel and linked articles.

On October 29, 2018, Berry Consultants launched a video series featuring Dr. Anna McGlothlin discussing the benefits and challenges of single arm clinical trials, particularly in rare diseases, while encouraging viewers to explore additional resources on the ICTR website.

Berry Consultants has launched three new videos on adaptive designs, featuring experts discussing topics such as DSMBs, biomarkers, and the intersection of NCAA football and the Ebola pandemic, adding to their previously released videos on related subjects, all available on their YouTube channel.