Adaptive Platform Trials

Adaptive Platform Trials

Adaptive Platform Trial for PTSD - Cohen Veterans Bioscience

The Challenge:

ZERO: The number of diagnostic tests and treatments for Post-Traumatic Stress Disorder approved by the FDA in the past 18 years.

Our military warfighters and veterans and all people with PTSD deserve better.

People with PTSD can experience very different physical and emotional symptoms. Certain psychotherapies are recommended by the Veterans Affairs and Department of Defense PTSD Treatment Guidelines, but they are often not preferred by or accessible to the majority of those suffering with PTSD. There are only two FDA-approved medications for the treatment of PTSD. Likewise, these medications do not work well for a lot of people, particularly when the presentation of PTSD is complex as is often the case in active-duty and veteran military service members.

At this time, there are a few potential new treatments in development. However, several of those treatments already failed in PTSD patients. The VA’s 2017 Consensus Statement of the PTSD Psychopharmacology Working Group and other sources confirm that there is a deficient pipeline of new PTSD medications. The clinical, social and financial burden of ineffectively treated PTSD is enormous.

We need to find better ways to select and test new treatments.

The challenge is that not all forms of PTSD are the same – we need biomarkers to subtype individuals (as we currently do in different forms of heart disease and cancer) – to individualize therapy.

To select better candidate therapies to test, we need better targets based on an understanding of biological pathways and circuits – so we can develop precision therapeutics.

With this combination, clinicians would be able to recommend a specific treatment for a person with a specific subtype of PTSD, a practice known as personalized or precision medicine.

Our Goal:

Build a new precision medicine pipeline by:

  1. Establishing a national network of centers that incorporate innovative and streamlined design approaches to test multiple therapeutics in parallel under highly rigorous and standardized methods.
  2. Identifying a pipeline of candidate therapeutics to test based on available evidence.
  3. Accelerating the validation of biomarkers for subtypes of PTSD.
  4. Creating a learning system where data from these studies is used to foster a better understanding of biological mechanisms that cause PTSD to find the next generation of targets and biomarkers.
  5. Advancing successful treatments and biomarkers to the next stage of development and ultimately to the clinic.
Our Flagship Project:

CVB spearheaded the conception and design of an innovative, well-powered, adaptive platform trial (APT) protocol to both identify safe and effective PTSD treatments and future discovery of PTSD biomarkers through an award from the U.S. Army Medical Research and Materiel Command (MRMC).

In a Team Science approach, CVB’s internal experts brainstormed with experts from industry and academia to refine the design of the APT.  In addition, this study design had the benefit of input from a Joint Scientific Committee, including experts from the VA, National Institute of Mental Health, National Institute of Alcohol Abuse and Alcoholism, FDA, Defense Health Agency’s Psychological Health Center of Excellence, and Department of Defense’s PTSD Integrated Product Team.

This protocol is designed to initiate the clinical trial with participation from active duty military and veterans. The information learned in this clinical trial will be used to advance treatments through the drug approval process required for FDA approval and/or inform Clinical Practice Guidelines for the treatment of PTSD.

Next Steps:

CVB will expand upon their efforts and begin designing an evidence-driven adaptive platform trial that will more broadly address military personnel and other people diagnosed with PTSD. This APT will offer significant benefits to the millions of people diagnosed with PTSD by testing patients who do not respond to one treatment with another treatment and by analyzing biomarker data in real time, allowing early identification of patient populations who might respond better to one treatment versus another.

What is an Adaptive Platform Trial? Why is it more efficient than a traditionally designed clinical trial?

Traditionally designed clinical trials that usually test one medication at a time are generally time-consuming and expensive and have been associated with high failure rates.

Adaptive platform trials (APTs) are a newer alternative to traditionally designed clinical trials. APTs allow researchers to test multiple treatments for a medical condition at the same time. By testing these treatments at the same time and in the same way, information can be borrowed from one treatment to the next resulting in fewer patients needed to volunteer for the study. In addition, as treatments complete testing, new treatments can be added to the platform for testing so there is less time spent in closing down a trial and starting up the next one, saving valuable time and money.

APTs also serve as a learning system in which researchers can use data collected from an ongoing trial to make fast, smart, and timely adaptations to that trial that can improve its efficiency and shorten the time to achieve trial results.


How are biomarkers used in an APT to improve treatment effectiveness?

Biomarkers can be used to confirm a diagnosis, identify subtypes of a medical condition, and predict response to treatment. In an APT, biomarkers may be used to assign patients with that biomarker to specific test treatments that are predicted to target that PTSD subtype. In PTSD where there are no confirmed biomarkers, an APT can generate evidence to discover and confirm biomarkers. Once confirmed, the APT can use these biomarkers to support a precision medicine approach for PTSD and with enough evidence support the biomarkers use into everyday medical practice.