Quality by Design Toolkit

Quality by Design (QbD) is a principled approach to reducing errors and maximizing quality through ongoing learning and continuous improvement throughout a clinical trial’s lifecycle (Meeker-O’Connel 2016). Originally implemented in the manufacturing industry to reduce production waste, the QbD framework has more recently been applied to clinical trials, where quality is defined as the absence of errors that impact the safety of trial participants or the credibility of the trial results. A number of research organizations, including pharmaceutical companies and academic medical centers, have adopted the approach and started contributing to a community of practice. The SC CTSI has expanded the approach to include study designs beyond clinical trials.

Introduction to Quality by Design - Dr. Thomas Buchanan, SC CTSI director, and Dr. Allison Orechwa, senior director of Strategy & Innovation.
This 11-minute video previews the QbD program for researchers supported by SC CTSI, including the intended benefits and steps in the process.

Quality by Design: A Manufacturing Perspective by Dr. Satyandra K. Gupta.  
This 11-minute video introduces the framework from the manufacturing perspective. This video elaborates on how incorporating a quality mindset during the design stage can eliminate defective outcomes and lead to cost efficiencies. Watch the full-length (75 minutes) video here.

The SC CTSI QbD framework for clinical and translational research aims to provide:

1. A proactive approach to facilitate early identification of risks during study development from multiple perspectives. The cross-functional QbD advisory board proactively identifies, prioritizes, and mitigates the key risks to quality in the research project.
2. An end-to-end process for study progress and quality risk management. It helps study teams focus on critical-to-quality factors to ensure the safety of the participants and the credibility of study results. The process of QbD planning includes protocol design, operational considerations, and project management.
3. Development of mitigation strategies to minimize risks beforehand, address problems as issues occur, and periodically check in to ensure successful project execution.

This proactive approach prepares the research team to periodically review their critical-to-quality factors and evaluate their research protocol during the study conduct. Project management assistance and team science support are also provided in the SC CTSI QbD process to further increase the chances of success.

Step 1 - QbD Introduction Meeting: The QbD Specialist introduces the QbD program to the study team, while the PI finalizes the study protocol and milestones. After becoming familiar with the research project, the QbD Specialist creates a customized QbD Advisory Board for the study team and schedules a Design Studio with both the study team and the QbD Advisory Board.

Step 2 - QbD Design Studio: The studio includes a presentation of the protocol by the study Principal Investigator to the QbD Advisory Board, followed by a collaborative review of the factors in the QbD Principles Document. Advisors ask questions that are intended to spark critical evaluation of the factors driving quality in the project, such as: “Are the endpoints commensurate with the objectives of the study?” and “Are all eligibility criteria relevant to ensuring the specific subject population needed for the trial?” Click HERE to view a sample agenda. The outcome of the Studio is a set of highest priority risks and mitigation plans. (For example, in a Design Studio for a study comparing the efficacy of group vs. individual medical visits in neurology clinics, advisors identified a potential technology barrier for participants joining virtual group settings and recommended helping each patient prepare their phone or laptop for a Zoom meeting before the visit.) Any necessary protocol revisions can be made immediately following the meeting.

Step 3 - Regular Check-ins: The QbD Specialist regularly communicates with the study team to monitor the study milestones and help address any challenges.

Step 4 - Close-out Interview: Once the study has concluded, the QbD Specialist gathers information from the study team about study success--such as reaching target accrual and meeting all milestones on time--as well as actual challenges faced during study conduct. An important part of the QbD framework is sharing lessons learned with the broader research community.

Documents:
1. QbD Introduction Meeting Agenda
2. QbD Design Studio Sample Agenda
3. CTTI Quality by Design Project - Critical to Quality (CTQ) Factors Principles Document
4. Quality by Design Principles Document for Health Services Research

Having a diverse advisory board strengthens the QbD approach by bringing in multiple perspectives that are tailored to each study, which facilitates the identification of risk from different angles and leads to more comprehensive and effective risk mitigation strategies.

The advisory board at the Design Studios is customized for each specific project. Generally, it includes key members of the study team and faculty and staff from SC CTSI who contribute expertise in various areas. Below is a list of typical Advisory Board attendees

• SC CTSI Director or Co-Director
• QbD Specialist
• Study Design & Analysis Specialist
• Recruitment Specialist
• Community Engagement Specialist
• Team Science Specialist
• Informatics Specialist
• Clinical Research Coordination Specialist
• Ad Hoc members, e.g., relevant regulatory specialist or ancillary service representative
• Patient or Community Member

Our initial experience with the QbD program indicates that we are meeting our goal of optimizing projects’ scientific and operational design and conduct. Design Studios are uncovering possible issues that study teams alone did not anticipate. In addition, researchers are appreciating the support.

• Design Studios helped identify ~4 potential risks per study, on average.
• All responding PIs found the program valuable and helpful.
• "Yes, the meeting was very valuable. I appreciate that there were representatives from every domain of academic research." - KL2 Scholar
• "It seemed to help give me a 'bird’s eye view' of how to triage some concerns about potential roadblocks for my project and how to address them." - Pilot Awardee

Learn more about Quality by Design:

Quality by Design - CTTI
Overview of Quality by Design by Clinical Trial Transformation Initiative (CTTI). It provides additional resources to implement Quality by Design in research projects.

Quality by Design in Clinical Trials Program
A series of five one-hour lectures covering the concept of QbD, the QbD framework and tools for implementation, and strategies for adaptation of principles to real-life cases. The presentations were recorded in 2020 at the Spring Regulatory Science symposium hosted by SC CTSI and the USC Mann School of Pharmacy.