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. More recently, we created additional resources—a metrics framework, maturity model, implementation guide, and documentation tool—to help organizations and individual trial teams effectively implement a QbD approach for their trials.
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)
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:
In addition to the factors mentioned above, the project recommended additional practices that contribute to successful application of QbD principles to clinical trials, including:
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.
Role![]() |
Name | Affiliation | Project |
---|---|---|---|
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 | Coleen Glessner | Alexion Pharmaceuticals, Inc | QbD Adoption |
Team Member | Roxana Mehran | Mt. Sinai Medical Center | QbD |
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 | Jan Hewett | Food and Drug Administration/CDER | QbD Adoption |
Team Member | Richard Ohye | University of Michigan | QbD |
Team Member | Helen Howitt | Syneos Health | QbD Adoption |
Team Member | Ileana Pina | Montefiore Medical Center | QbD |
Team Member | Irfan Khan | Food and Drug Administration/CDRH | QbD Adoption |
Team Member | Ellen Pinnow | Food and Drug Administration | QbD |
Team Member | Kerstin Koenig | Bristol Myers Squibb | QbD Adoption |
Team Member | Tejashri Purohit-Sheth | Food and Drug Administration | QbD |
Team Member | Martin Landray | University of Oxford, CTSU | QbD Adoption |
Team Member | John Alexander | Duke University | QbD |
Team Member | Eric Richardson | Food and Drug Administration | QbD |
Team Member | Marion Mafham | University of Oxford | QbD Adoption |
Team Member | Patrick Archdeacon | Food and Drug Adminstration | QbD |
Team Member | David Rodin | Pfizer Inc. | QbD |
Team Member | Ann Meeker-O'Connell | Vertex Pharmaceuticals Inc | QbD Adoption |
Team Member | Tim Baldwin | National Institutes of Health | QbD |
Team Member | Daniel Rose | Pulmonary Fibrosis Foundation | QbD |
Team Member | Jules Mitchel | Target Health, Inc | QbD Adoption |
Team Member | Leslie Ball | Food and Drug Administration | QbD |
Team Member | Peter Scheimann | Widler & Schiemann AG | QbD |
Team Member | Hamid Moradi | University of California, Irvine | QbD Adoption |
Team Member | David Breiter | Covidien Vascular Therapies | QbD |
Team Member | Tamara Shipman | St. Jude Medical | QbD |
Team Member | Jamie Phalp | University of Kansas Medical Center | QbD Adoption |
Team Member | Oana Brosteanu | Universitaet Leipzig | QbD |
Team Member | Ken Sprenger | Pfizer Inc | QbD |
Team Member | Petra Rathje* | Amgen Inc | QbD Adoption |
Team Member | Robert Campbell | Children's Hospital of Philadelphia | QbD |
Team Member | Fergus Sweeney | European Medicines Agency | QbD |
Team Member | Craig Reist* | Duke University | QbD Adoption |
Team Member | Lynda Chick | Bristol-Myers Squibb | QbD |
Team Member | James Tcheng | Duke University | QbD |
Team Member | David Rodin | Amici Clinical Research | QbD Adoption |
Team Member | Theodora Cohen | Harvard Clinical Research Institute | QbD |
Team Member | Robert Temple | Food and Drug Administration | QbD |
Team Member | Margaret Schneider | University of California, Irvine | QbD Adoption |
Team Member | Sabrina Comic-Savic | The Medicines Company | QbD |
Team Member | Jean Toth-Allen | Food and Drug Administration | QbD |
Team Member | Jason Connor | Berry Consultants | QbD |
Team Member | Spiros Vamvakas | European Medicines Agency | QbD |
Team Member | Fergus Sweeney | European Medicines Agency | QbD Adoption |
Team Member | Xiangchen (Bob) Cui | Vertex Pharmaceuticals | QbD |
Team Member | Roseann White | Abbott Vascular | QbD |
Team Member | Mary Taylor | Becton, Dickinson and Company | QbD Adoption |
Team Member | Dan Delaney | CR Bard, Inc | QbD |
Team Member | Beat Widler | Widler & Schiemann AG | QbD |
Team Member | Austin Allan | Kura Oncology, Inc. | QbD Adoption |
Team Member | Jaques Demotes | ECRIN | QbD |
Team Member | Prajna Kumar | Alexion | QbD Adoption |
Team Member | Dianne Dorman | National Organization for Rare Diseases | QbD |
Team Member | Bob Moroz | Individual Consultant | QbD Adoption |
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 | Allen Heller | Pharma Study Design | QbD |
Team Member | Liz Adams | Quorum Review IRB | QbD Adoption |
Team Member | Janet Hietshetter | Dystonia Medical Research Foundation | QbD |
Team Member | Keith Barber | Syneos Health | QbD Adoption |
Team Member | Heather Jorajuria | Genentech - a Member of the Roche Group | QbD |
Team Member | Kousick Biswas | Department of Veterans Affairs | QbD Adoption |
Team Member | Michael Lincoff | Cleveland Clinic Coordinating Center for Clinical Research | QbD |
Team Member | Sabrina Comic-Savic | Novartis | QbD Adoption |
Team Member | Ted Lystig | Medtronic | QbD |
Team Member | Dan Cooper | University of California, Irvine | QbD Adoption |
Team Leader | Ann Meeker-O'Connell | Johnson and Johnson Pharmaceutical Research Development | QbD |
Team Leader | Dagmar R Görtz | Janssen | 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 | Ansalan Stewart | Food and Drug Administration/CDER | QbD Adoption |
Team Leader | Louise Bowman | University of Oxford | QbD Adoption |
Team Leader | Karlin Schroeder | Parkinson's Foundation | QbD Adoption |
Project Manager | Annemarie Forrest | Clinical Trials Transformative Initiative | QbD |
Project Manager | Zach Hallinan | Clinical Trials Transformation Initiative | QbD Adoption |
EC Champion | John Alexander | Duke University | QbD Adoption |
EC Champion | Donna Cryer | Global Liver Institute | QbD Adoption |