Quality by Design – It’s Not an Accident!

Quality by Design (QbD) defines quality as freedom from errors that matter. In the context of an EDC-based clinical trial, this could mean interruptions in study conduct, issues with data integrity, concerns with regulatory compliance, and protocol deviations.

Sponsors will also be concerned about overall study performance in terms of time and money saved, fewer patients lost to follow up, and workflow automation.

Experienced quality professionals understand the benefits of QbD and provide value to their Sponsors by guiding them down a practical path towards QbD implementation.

Reduce Regulatory Worries and Ensure Adherence with ALCOA Principles

Regulatory compliance worries fade into the background when using an EDC with a fully 21 CFR Part 11 compliant audit trail. An electronic audit trail increases attributability and assists in confirming contemporaneous data entry. Data entered directly into an EDC is considered as original, source data without requiring transcription and review. It is also clearer and more legible than hand-entered data and electronic error checks allow data to be cleaned as it is entered – increasing accuracy and reducing monitoring requirements. Selecting an EDC that provides this peace of mind is the first step towards QbD.

Design for Ease of Use

When the user experience is thought out up-front, site and study personnel spend less time wondering how to proceed and more time focusing on productive, clinical work. Elements to consider before beginning clinical trial EDC implementation include:

• Can electronic forms be laid out to look just like the forms in the protocol? When this is done, participants find data entry more intuitive and natural.
• Are there areas where automation can be used? Or is there information entered on one form that would be useful to include for reference on a different form? Identify these early and provide clear guidance to the implementation team.
• What user roles will be required for the study, and what information will they have access to? Which of these will be masked to treatment? Think about how to configure form view, edit, and review permissions in advance and make sure users have access to all the information they need (and not information they don’t!).

Automate Error Prone and Time-Consuming Activities

There are many ways to take advantage of the automation available with EDC, all of which increase quality by eliminating or reducing human error and save staff time by automating cumbersome workflows and paperwork. Some obvious examples include:

• Automatically compute weight and measure conversions, dosing, and expected visit date/times instead of requiring humans to perform these manually.
• Make use of electronic lab interfaces and mobile patient-reported outcome (ePRO) capabilities when available. These reduce the need for data transcription, provide more timely data for analysis, and increase data integrity.
• EDCs that automate busy-work such as site invoicing and inventory management save time and money by eliminating paperwork and streamlining workflows.
• Provide mechanisms for users to easily indicate when data was not collected (e.g., “No AEs”). This eliminates confusion for monitors and statisticians alike (“were there really no AEs or did the investigator just forget to enter them?”).

Increase Subject Retention

Losing subjects due to lack of follow-up is one of the most expensive overhead costs in any clinical trial – and doesn’t have to be. Use some of these techniques to increase subject retention.

• Implement a mechanism for site and study personnel to easily see scheduled study visits and other study-related events. When such activities are anticipated in advance, planning and coordination can be done pro-actively.
• Use automatic email notifications to alert staff when action is required. Some examples of this include upcoming visits, the arrival of lab data, query questions and responses, adverse event occurrence, and low inventory alerts.
• Make use of eConsent and ePRO capabilities to reduce the requirements for physical site visits. Making participation easier for subjects makes them more likely to complete the study.

Capitalize on Lessons Learned

Savvy Quality Assurance personnel add value by using past experience to introduce quality into future studies. Prelude Dynamics has studied patterns in mid-study updates and identified four major areas where such changes were required. Avoiding mid-study updates can reduce interruptions in the study workflow and make it easier for site and study personnel to complete their work.

• Form permissions. If a user can’t access or edit a form, their workflow is interrupted until access is granted. Plan ahead and ensure that each study role has access to the appropriate forms and functionality before the trial begins.
• Calculations and error checks. During study conduct monitors may recognize patterns in erroneous or incomplete data. These can be rectified, but it would be better to prevent them from the beginning. Leverage your trend analysis for past deviations and findings, identify problem areas, and institute edit checks and calculations to reduce human error.
• Database fields. Common updates include adding/deleting fields and changing options or data types. Consult Data Managers and Statisticians during study design to ensure that the database considers their needs.
• Logic and workflow. Sometimes, the right information isn’t available at the right time. Tracking these issues will help eliminate them in the future.

Conclusion

Quality by Design can save Sponsors time and money by streamlining workflows, increasing usability, and avoiding roadblocks. While requiring additional thought and effort, the benefits derived by applying these methods are substantial!

Come visit us at the 2022 Annual SQA Conference.

Find out how Prelude Dynamics can help institute Quality by Design in your clinical trials.