Recently the FDA published the revised draft guidance on "Adaptive Designs for Clinical Trials of Drugs and Biologics". This is a quick summary of the guidance and what sample size challenges and opportunities Biostatisticians are expected to face.
Update: Jan 2020
Who is the guidance applicable to?
The purpose of the guidance is, according to FDA Commissioner Scott Gottlieb, M.D., to modernize the approach to clinical trial design in efforts to:
(1) Make clinical trials more efficient while maintaining patient safety and
(2) Increase the amount of information concerning product safety and benefits.
This makes it applicable to any sponsor involved with upcoming:
Adaptive designs have the potential to "improve ... study power and reduce the sample size and total cost" for investigational drugs, including "targeted medicines that are being put into development today”
- FDA Commissioner - Scott Gottlieb -
What is the Adaptive Designs for Clinical Trials of Drugs and Biologics Guidance for Industry?
The September 2018 release replaces the 2010 draft guidance issued by the FDA. The clinical trial landscape has changed since 2010 regards the FDA’s stance on adaptive clinical trial design.
The guidance provides examples for Biostatisticians to review where adaptive designs have been featured. Use cases include chronic heart failure, Ebola treatment, HPV vaccine, prostate cancer plus other successful cases of an adaptive design.
What is the FDA’s definition of adaptive design?
This document describes what the FDA view as the important principles for designing, conducting and reporting the results from an adaptive clinical trial. This includes Bayesian adaptive designs and complex designs relying on computer simulations.
The FDA define an adaptive design as “a clinical trial design that allows for prospectively planned modifications to one or more aspects of the design based on accumulating data from subjects in the trial.” The FDA also explains how adaptive trial designs can allow a trial to adjust to information that was not available when the trial began.
The Winter 2018 nQuery release has an module dedicated to Sample Size Determination for Adaptive Clinical Trials. You can see more about this in our What's New in nQuery page
What are the limitations of adaptive designs for clinical trials?
While there are many benefits to adaptive designs, the draft guidance recognizes that adaptive designs require careful consideration as, like any trial, a poorly planned and operated trial can result in incorrect conclusions of safety or effectiveness.
What do industry experts think of the new guidance?
An article on outsourcing-pharma.com quotes many industry experts in response to the new guidance. CRO's as well as pharmaceutical Biostatisticians are happy with the updated guidance.
“ACRO supports this benefit of adaptive design trials as a learning system, where clinical researchers can integrate new data and refine trials to be smarter and more efficient,” ...including concepts of adaptive enrichment, adaptive endpoint selection, and the use of single control arms.
- Karen Noonan, Association of Clinical Research Organizations (ACRO), VP of Global Regulatory Policy -
nQuery contains a module for sample size determination for adaptive clinical trials. The module - nQuery Adapt - provides Biostatisticians with a range of tables that spans various adaptive disciplines for sample size calculation.
How do I learn more about adaptive design clinical trials?
We recently held a webinar discussing adaptive designs. You can watch Innovative Sample Size Methods for Adaptive Clinical Trials below. Given the high failure rates and the increased costs of clinical trials, researchers need innovative design strategies to best optimize financial resources and reduce the risk to patients. Adaptive designs are emerging as a way to reduce risk and cost associated with clinical trials.
In this webinar, we demonstrate the new nQuery adaptive module focusing on Sample Size Re-Estimation & Group-Sequential Design.
In this webinar you will learn about: