Project:

Quality by Design

overview icon Overview

JUST THINK | Monitoring and Quality by Design (QbD) in Clinical Trials

Avoiding errors, collecting data that is fit-for-purpose, and reducing patient burden are just a few of the many benefits of applying Quality by Design (QbD)—an approach that focuses resources on the errors that matter to decision making during a trial, such as primary endpoints and patient safety.

CTTI has built a suite of resources—including recommendations for monitoring, recommendations for QbD, a principles document and a QbD toolkit—that outline how to apply QbD principles in clinical trials. We are also working on new case studies, models, and other assets that will give sponsors and other stakeholders the tools and confidence they need to effectively implement QbD at their organization.

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Discover Additional Deliverables Generated From This Project

Press Release

New Recommendations to Improve Quality in Clinical Trials

Highlighted Presentation

Clinical Quality-by-Design (QbD): Principles to Practice by Coleen Glessner at DIA 2015

Webinar

Translating quality by design principles into practice, part 3

Webinar

Translating quality by design principles into practice, part 2

Webinar

Translating quality by design principles into practice, part 1

Expert Meeting Materials

Workshop on Quality Risk Management: Understanding What Matters - Executive Summary of Meeting held January 29-30, 2014

Expert Meeting Materials

View materials from the Workshop on Quality Risk Management: Understanding What Matters, hosted January 28-29, 2013

Publication

Clinical Trials: Rethinking How We Ensure Quality published in Drug Information Journal

Expert Meeting Materials

Materials from the Workshop on Quality Risk Management: Understanding What Matters held September 20-21, 2012

Expert Meeting Materials

Materials from the Workshop on Quality Risk Management held August 23-24, 2011

Press Release

First Report from Public-Private Partnership Shows Variability in How Clinical Trials Are Monitored

Publication

Monitoring the quality of conduct of clinical trials: a survey of current practices by Morrison BW, Cochran CJ, White JG, Harley J, Kleppinger CF, Liu A, Mitchel JT, Nickerson DF, Zacharias CR, Kramer M, Neaton JD published in Clinical Trials

Expert Meeting Materials

Materials from CTTI's Expert Meeting, Developing effective quality systems in clinical trials: an enlightened approach, hosted October 13-14, 2010

Project Report

Quality objectives of monitoring

Poster

A CTTI Survey of Current Monitoring Practices - Presented May 17, 2010 at the annual meeting of the Society for Clinical Trials in Baltimore, MD

Expert Meeting Materials

Materials from the Panel Discussion, Quality Objectives of Monitoring, held November 4, 2009

Webinar

QbD recommendations and toolkit

“CTTI’s recommendations emphasize the importance of prospectively building quality into the scientific and operational design of clinical trials, rather than relying only on retrospective monitoring, inspection or scientific review. This systematic, proactive, and focused approach is compatible with FDA guidance on risk-based monitoring.”

Robert Temple, M.D. Deputy Center Director for Clinical Science at the U.S. Food and Drug Administration

“Optimized trial designs can help us deliver important medicines to patients more quickly. In the Development Design Center, we collaborate with product teams to design and plan streamlined studies. We do this in part by posing questions to the team that challenge assumptions and stimulate creative thinking. The CTTI QbD Project Critical to Quality Factors Principles Document is a valuable reference as we plan for these group discussions.”

Julie Dietrich, Director, Development Design Center, Amgen, Inc.

“CTTI inspired and enabled us to implement QbD principles at Pfizer. None of what we’ve done would have been possible without the backing, influence, and support of CTTI. It has been amazing to watch the dialogue in the industry change.”

 

Coleen Glessner, Vice President, Clinical Trial Process and Quality, Pfizer

“QbD is a concept whose time has come. The CTTI Principles Document provided a framework that helped Seattle Genetics practice QbD concepts and identify elements that are critical to quality.”

 

Marta Fields, Senior Director, Compliance and Quality Systems, Seattle Genetics

PCORnet, the national patient-centered clinical research network, is applying CTTI’s QbD principles in its clinical trials task force work.

The Medical Device Innovation Consortium (MDIC) supports the use of CTTI’s QbD Framework. For more information on CTTI and MDIC's strategies for designing quality, efficient clinical trials, you can view this webinar recording.

The Duke Clinical Research Institute (DCRI) has restructured the organization of their quality assurance operations. They created a new role, director of Quality by Design, and cited CTTI’s work in the explanation for the evolution in their approach to the development, implementation, and administration of DCRI's quality strategy.

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Stakeholders across the clinical trial enterprise have expressed concern that the current model for conducting trials is unaffordable and unsustainable, and potentially impedes the generation of reliable evidence. Overcoming this inefficiency rests on improving protocol design, trial planning, and quality oversight.

CTTI first recognized the need for applying QbD methods to clinical trials while working to improve monitoring procedures. A key conclusion of the CTTI Monitoring Project was that clinical trial monitoring should be viewed as one component of an overall quality framework. Project participants, representing a broad cross-section of the clinical trials enterprise, agreed that widespread adoption of the QbD approach to trial planning, conduct, and oversight was needed to ensure trial quality and efficiency; however little information was available on how to apply QbD principles to clinical trial design.

The Monitoring Project: “Effective and Efficient Monitoring as a Component of Quality Assurance in the Conduct of Clinical Trials” (2009-2011)

Quality by Design (QbD): “Workshops on Quality by Design (QbD) and Quality Risk Management (QRM) in Clinical Trial” (2011-2015)

Quality by Design (QbD) Adoption (2018-ongoing)

  • Develop broad principles for QbD applicable across clinical trials
  • Provide hands-on opportunities for stakeholders involved in clinical trial development, implementation, and oversight to translate QbD principles into practice
  • Identify mechanisms to disseminate agreed principles and promising approaches identified during the workshops to a broad array of stakeholders
  • Using the QbD toolkit to build trial quality from the start will help minimize errors that matter and improve the overall integrity of the trial while increasing participant safety and credibility of results.
  • Focusing on critical aspects (e.g., those critical to quality factors [CQFs] defined in the Principles Document) of a trial will improve trial efficiency and also substantially reduce the burden of clinical trial conduct by relieving sponsors of a perceived obligation to mitigate every potential risk posed by a trial.
  • Literature review
  • Electronic survey
  • Expert meetings and workshops
    • CLICK HERE to view materials from the January 29-­30, 2014 Workshop on Quality Risk Management
    • CLICK HERE to view materials from the January 28-29, 2013 Workshop on Quality Risk Management
    • CLICK HERE to view materials from the September 20–21, 2012 Workshop on Quality Risk Management
    • CLICK HERE to view materials from the August 23-24, 2011 Workshop on Quality Risk Management
    • CLICK HERE to view materials from the October 13 - 14, 2010 Expert Meeting on Monitoring
    • CLICK HERE to view materials from the November 4, 2009 Expert Meeting on Monitoring
  • Qualitative Interviews

CTTI’s investigation of monitoring practices across sponsor companies found that practices vary widely and that choice of monitoring practices was often not based on empirical evidence. Experts agreed that the main objectives of monitoring practices were to ensure patient safety, represent key data accurately, comply with the protocol, and improve trial quality. Because monitoring is most effective when it can identify errors early so that corrective training can address issues, and should be tailored to the needs of a particular trial, risk-based monitoring was suggested as a more effective alternative.

During the investigation of monitoring practices and analyses of results, it became apparent that additional factors contribute to trial quality and efficiency. An expert working group suggested convening a follow-on Quality by Design (QbD) Project. QbD employs an approach to prospectively build quality into the scientific and operational design of clinical trials, such that important errors are prevented rather than remediated after the fact, and trials are feasible to conduct. Through evidence-gathering activities, CTTI described those factors that are “critical to quality” [CTQ] in CTTI’s Principles Document and include the following:

  • Protocol design
  • Feasibility
  • Patient safety
  • Study conduct
  • Study reporting
  • Third-party engagement

In addition to the factors mentioned above, the project recommended additional practices that contribute to successful application of QbD principles to clinical trials, including:

  • Creating a culture that values and rewards critical thinking and open dialogue about quality, and that goes beyond sole reliance on tools and checklists;
  • Focusing effort on activities that are essential to the credibility of the study outcomes;
  • Involving the broad range of stakeholders in protocol development and discussions around study quality; and
  • Prospectively identifying and periodically reviewing the critical to quality factors.

CTTI provided examples of successful application of these principles in the QbD Webinar Series and guidance on how to implement QbD in clinical trials in the QbD Toolkit.

Project Team Members

Rolesort descending Name Affiliation Project
EC Champion John Alexander Duke University QbD Adoption
EC Champion Donna Cryer Global Liver Institute QbD Adoption
Project Manager Annemarie Forrest Clinical Trials Transformative Initiative QbD
Project Manager Zach Hallinan Clinical Trials Transformation Initiative QbD Adoption
Team Leader Mark Behm AstraZeneca Pharmaceuticals LP QbD
Team Leader Coleen Glessner Alexion QbD
Team Leader Martin Landray University of Oxford, CTSU QbD
Team Leader Briggs Morrison Development Syndax QbD
Team Leader Jean Mulinde Food and Drug Administration QbD
Team Leader Stephanie Shapley Food and Drug Administration QbD
Team Leader Louise Bowman University of Oxford QbD Adoption
Team Leader Karlin Schroeder Parkinson's Foundation QbD Adoption
Team Member Ryan Fischer Parent Project Muscular Dystrophy QbD Adoption
Team Member Danica Marinac-Dabic Food and Drug Administration QbD
Team Member Annie Fors University of Kansas Medical Center QbD Adoption
Team Member Ann Meeker-O'Connell Johnson and Johnson Pharmaceutical Research Development QbD
Team Member Coleen Glessner Alexion Pharmaceuticals, Inc QbD Adoption
Team Member Roxana Mehran Mt. Sinai Medical Center QbD
Team Member Dagmar R Görtz Janssen QbD Adoption
Team Member Jules Mitchel Target Health Inc. QbD
Team Member Martin Hamilton Food and Drug Administration/CDRH QbD Adoption
Team Member David Nickerson Pfizer Inc. QbD
Team Member Richard Ohye University of Michigan QbD
Team Member Jan Hewett Food and Drug Administration/CDER QbD Adoption
Team Member Ileana Pina Montefiore Medical Center QbD
Team Member Helen Howitt Syneos Health QbD Adoption
Team Member Ellen Pinnow Food and Drug Administration QbD
Team Member Irfan Khan Food and Drug Administration/CDRH QbD Adoption
Team Member Tejashri Purohit-Sheth Food and Drug Administration QbD
Team Member Kerstin Koenig EMD Serono QbD Adoption
Team Member Eric Richardson Food and Drug Administration QbD
Team Member Stacey Lallier Johnson & Johnson/Janssen QbD Adoption
Team Member John Alexander Duke University QbD
Team Member David Rodin Pfizer Inc. QbD
Team Member Martin Landray University of Oxford, CTSU QbD Adoption
Team Member Patrick Archdeacon Food and Drug Adminstration QbD
Team Member Daniel Rose Pulmonary Fibrosis Foundation QbD
Team Member Marion Mafham University of Oxford QbD Adoption
Team Member Tim Baldwin National Institutes of Health QbD
Team Member Peter Scheimann Widler & Schiemann AG QbD
Team Member Ann Meeker-O'Connell Vertex Pharmaceuticals Inc QbD Adoption
Team Member Leslie Ball Food and Drug Administration QbD
Team Member Tamara Shipman St. Jude Medical QbD
Team Member Jules Mitchel Target Health, Inc QbD Adoption
Team Member David Breiter Covidien Vascular Therapies QbD
Team Member Ken Sprenger Pfizer Inc QbD
Team Member Hamid Moradi University of California, Irvine QbD Adoption
Team Member Oana Brosteanu Universitaet Leipzig QbD
Team Member Fergus Sweeney European Medicines Agency QbD
Team Member Jamie Phalp University of Kansas Medical Center QbD Adoption
Team Member Robert Campbell Children's Hospital of Philadelphia QbD
Team Member James Tcheng Duke University QbD
Team Member Petra Rathje Amgen Inc QbD Adoption
Team Member Lynda Chick Bristol-Myers Squibb QbD
Team Member Robert Temple Food and Drug Administration QbD
Team Member Craig Reist Duke University QbD Adoption
Team Member Theodora Cohen Harvard Clinical Research Institute QbD
Team Member Jean Toth-Allen Food and Drug Administration QbD
Team Member David Rodin Amici Clinical Research QbD Adoption
Team Member Sabrina Comic-Savic The Medicines Company QbD
Team Member Spiros Vamvakas European Medicines Agency QbD
Team Member Margaret Schneider University of California, Irvine QbD Adoption
Team Member Jason Connor Berry Consultants QbD
Team Member Roseann White Abbott Vascular QbD
Team Member Ansalan Stewart Food and Drug Administration/CDER QbD Adoption
Team Member Xiangchen (Bob) Cui Vertex Pharmaceuticals QbD
Team Member Beat Widler Widler & Schiemann AG QbD
Team Member Fergus Sweeney European Medicines Agency QbD Adoption
Team Member Dan Delaney CR Bard, Inc QbD
Team Member Mary Taylor Becton, Dickinson and Company QbD Adoption
Team Member Jaques Demotes ECRIN QbD
Team Member Dianne Dorman National Organization for Rare Diseases QbD
Team Member John Farley Food and Drug Administration QbD
Team Member Angeles Alonso Garcia European Medicines Agency QbD
Team Member Cyrus Guidry Johnson & Johnson Devices QbD
Team Member Liz Adams Quorum Review IRB QbD Adoption
Team Member Allen Heller Pharma Study Design QbD
Team Member Keith Barber Syneos Health QbD Adoption
Team Member Janet Hietshetter Dystonia Medical Research Foundation QbD
Team Member Kousick Biswas Department of Veterans Affairs QbD Adoption
Team Member Heather Jorajuria Genentech - a Member of the Roche Group QbD
Team Member Sabrina Comic-Savic The Medicines Company QbD Adoption
Team Member Michael Lincoff Cleveland Clinic Coordinating Center for Clinical Research QbD
Team Member Dan Cooper University of California, Irvine QbD Adoption
Team Member Ted Lystig Medtronic QbD