adaptive trial design

November 20, 2020: Drug Development in Kidney Disease: Proceedings from a Multi-Stakeholder Panel (Daniel Edmonston, MD)

Posted on by Gina Uhlenbrauck

Speaker

Daniel Edmonston, MD
Medical Instructor
Duke University School of Medicine

Topic

Drug Development in Kidney Disease: Proceedings from a Multi-Stakeholder Panel

Keywords

Chronic kidney disease (CKD); Dialysis; Evidence-based medicine; Electronic health records; Think Tank

Key Points

  • Only 5 percent of treatment recommendations for kidney disease reach a Grade A level of evidence.
  • In 2019, the DCRI convened a panel to address the urgent need for evidence-based treatments for kidney disease. “Accelerating Drug Development for Chronic Kidney Disease and End-Stage Renal Disease” included stakeholders from regulatory agencies, kidney societies, patient advocacy organizations, academia, and industry.
  • Key discussions explored the uses of interconnected data and site research networks, pragmatic and adaptive trial designs, robust surrogate endpoints, real-world data, and methods to improve the generalizability of trial results and uptake of approved drugs for kidney-related diseases.

Discussion Themes

Since there is more than one therapeutic agent showing promise for CKD, how should evidence be generated to understand the right combination of agents?

Could the principles laid out in the FDA Patient Focused Drug Development guidance be applied in these trials to ensure the patient perspective is included?

What are your thoughts on whether to focus on enrolling early CKD patients—some of whom will not progress—or patients later in the course of disease, when disease modification may be more challenging?

Read more about the Think Tank in a special report in the American Journal of Kidney Disease.

Tags

#pctGR, @Collaboratory1

September 11, 2020: Launching CONNECTS: Collaborating Network of Networks for Evaluating COVID-19 and Therapeutic Strategies (Gordon Bernard, MD; Sonia Thomas, DrPH)

Posted on by Gina Uhlenbrauck

Speakers

Gordon R. Bernard, MD
CONNECTS ACC Science Unit P
Professor of Medicine
Executive Vice President for Research
Senior Associate Dean for Clinical Science
Vanderbilt University Medical Center

Sonia Thomas, DrPH
CONNECTS ACC Principal Investigator
Senior Research Statistician
RTI International

Topic

Launching CONNECTS: Collaborating Network of Networks for Evaluating COVID-19 and Therapeutic Strategies

Keywords

COVID-19; CONNECTS; NHLBI; Collaborative research; Data sharing; Adaptive trials; Data standardization; ACTIV; Therapeutic agent prioritization

Key Points

  • The Collaborating Network of Networks for Evaluating COVID-19 and Therapeutic Strategies (CONNECTS) is a research partnership coordinated by the Research Triangle Institute, Vanderbilt University Medical Center, and the National Heart, Lung, and Blood Institute (NHLBI) of the NIH.
  • CONNECTS aims to build on existing clinical research networks to better understand the risk of severe illness from COVID-19 and to identify therapies that will slow or halt the disease progression and speed recovery. Studies will enroll participants with health conditions that are known to increase their risk for severe complications from COVID-19.
  • The immediate goal is to design and implement master protocol-driven adaptive clinical trials, including outpatient, inpatient, and recovering master protocols.
  • CONNECTS is part of a larger ecosystem in the Department of Health and Human Services that includes the FDA, CDC, BARDA, Operation Warp Speed, and NIH. More than 34 trial networks and 1,000 sites are participating in CONNECTS.

Discussion Themes

Are the CONNECTS resources, such as the common data elements manual, draft protocols, and case report forms, publicly available?

In your effort to reach underrepresented communities, have you considered collaborating with Historically Black Colleges and Universities (HBCUs), particularly those that conduct health research?

While COVID-19 is providing you with plenty to focus on, do you see the potential for sustainability of CONNECTS beyond this pandemic?

Read more about CONNECTS.

Tags

#pctGR, @Collaboratory1

Grand Rounds August 21: Adaptive Platform Trials: Scalable from Breast Cancer to COVID

Speaker:

Laura Esserman, MD, MBA
Director, UCSF Carol Franc Buck Breast Care Center
Alfred A. de Lorimier Endowed Chair in General Surgery
Professor of Surgery and Radiology, UCSF

Topic: Adaptive Platform Trials: Scalable from Breast Cancer to COVID
Date: Friday, August 21, 2020, 1:00-2:00 p.m. ET

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May 15, 2020: Optimized Learning While Doing: The REMAP-CAP Adaptive Platform Trial (Derek Angus, MD, MPH)

Posted on by Gina Uhlenbrauck

Speaker

Derek C. Angus, MD, MPH, FRCP
Distinguished Professor and Mitchell P. Fink Endowed Chair
Department of Critical Care Medicine
University of Pittsburgh and UPMC Health System

Topic

Optimized Learning While Doing: The REMAP-CAP Adaptive Platform Trial

Keywords

Adaptive study design; REMAP-CAP; Community-acquired pneumonia; Embedded research; Learning health system; Pandemic; Response-adaptive randomization; Global adaptive platform; COVID-19

Key Points

  • The Randomised, Embedded, Multifactorial, Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) aims to determine and continuously update the optimal set of treatments for community-acquired pneumonia.
  • An important aspect of adaptive trial designs is that already accrued data are used to increase the likelihood that patients within the trial are randomized to treatments that are beneficial.
  • With the onset of the COVID-19 pandemic, the REMAP study made use of an adaptive sub-platform called REMAP-COVID, which is studying multiple questions around COVID treatment simultaneously.

Discussion Themes

The COVID-19 pandemic requires us to do two things at once: learn and do. An integrated approach finds the optimal balance to treat patients as well as possible and learn as fast as possible.

Adaptive randomization is potentially more comfortable for physicians, where patients are preferentially assigned to the best therapy over time.

Read more about REMAP-CAP and Dr. Angus’ research in Optimizing the Trade-off Between Learning and Doing in a Pandemic (JAMA, March 2020).

Tags

#pctGR, @Collaboratory1, @remap_cap

Study Design Improvements Have Positive Effects on Trial Performance

Posted on by Gina Uhlenbrauck

A recent impact report from the Tufts Center for the Study of Drug Development details how efforts to streamline clinical trial design appear to be yielding results [1]. Industry trial sponsors are using mechanisms such as facilitated review processes and adaptive trial designs to identify and address study feasibility issues, thereby reducing trial costs and administrative burden.

The center reviewed more than 20,000 procedures from recent phase 2 and 3 trials sponsored by 8 major pharmaceutical or biotechnology companies and conducted a survey with 83 industry executive respondents on experience with facilitated review processes.

Highlights from the analyses include the following:

  • 21% of procedures in phase 2 trials and 31% in phase 3 trials were for “non-core” data that did not support primary or key secondary outcomes
  • Non-core procedures accounted for, on average, one-quarter of a study budget
  • >90% of non-core data collected were included in clinical study reports and regulatory submissions
  • 21% of companies reported using simple adaptive trial designs to reduce costs and improve chances of study success; <10% reported using sophisticated adaptive designs
  • 76% of surveyed companies reported using facilitated review processes within the past 5 years
  • Many companies reported modest to major improvements in various measures of trial performance since implementing facilitated review processes (figure)
Percentage of companies reporting modest to major improvement in trial performance measures since implementing facilitated review processes

A discussion of social media perceptions with 20 pharmaceutical and biotechnology companies, as detailed in the report, further revealed that companies see potential value in soliciting stakeholder (e.g., investigators, patients) input on study design via social media. However, serious concerns regarding lack of regulatory guidance and potential for bias have kept companies from implementing this type of engagement to date.

Reference

1. Tufts Center for the Study of Drug Development. Protocol design optimization starting to improve study performance. Tufts CSDD Impact Report. 2014;16(5).