Good Practice Action 6: Quality-by-design

Apply quality-by-design approaches targeting critical determinants of trial quality to strengthen design and reduce avoidable errors

A quality-by-design approach ensures that factors critical to trial quality are prospectively identified and managed. This approach will uphold trial integrity, participant safety, and the reliability of results. Potential risks to quality can be identified and mitigated during the clinical trial process. Errors that may derail the clinical trial can be avoided, and participants will be better protected from risks. Ultimately, by building in quality-by-design, the trial findings are more likely to be reliable and informative.

[link to video]

[Added comments in connection to video, e.g. highlighted quotes]

Trial teams and others should:

Research teams should plan a systematic and proactive strategy that uses risk assessment to identify potential sources of variability, and how these could impact the trial. Trial teams are encouraged to use monitoring activities to oversee aspects of the trial where there are potential risks to critical determinants.

As a requirement of Good Clinical Practice (GCP) standards issued by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), ICH GCP requires in Section 5.1, that the sponsor implements and maintains systems for quality assurance and quality control (European Medicines Agency). The ICH E6(R3) GCP Guideline update (ICH, 2025) reflects advances in trial design, technology, and data governance. There is an emphasis on clinical trials being fit-for-purpose, with improved efficiency and transparency.

The Clinical Trials Transformation Initiative (CTTI) co-founded by Duke University and the United States Food and Drug Administration has developed helpful Quality By Design (QbD) resources to increase the quality, efficiency, and patient-centredness of clinical research. This initiative aims to address clinical trials systems that are expensive, unsustainable, and that fail to generate useful evidence (uninformative trials). CTTI members offer a wide range of perspectives, including academic researchers, clinical investigators, industry leaders, patient advocates, and regulators. Broad principlesfor QbD can be applied across all clinical trials, and there is a toolkit for implementation, comprising documents, guidelines, forms and videos to help operationalise QbD. An introduction to the toolkit is given in this short video.

Error prevention by risk-based monitoring was highlighted in CTTI’s work as preferable to error remediation. Critical-to-quality (CTQ) factors are set out in the principles document, which need to be prospectively identified, and periodically reviewed, including:

  • Protocol design (see also Good Practice Actions 2 and 4)
  • Feasibility (see also Good Practice Action 8)
  • Patient safety
  • Study conduct
  • Study reporting (see also Good Practice Actions 11 and 12)
  • Stakeholder engagement (see also Good Practice Actions 1, 3 and 12)

Further recommendations are:

  • Creating a culture that values and rewards critical thinking and open dialogue about quality, beyond reliance on tools and checklists (see also Good Practice Actions 2 and9)
  • Focusing efforts on activities essential to the credibility of study outcomes (see also Good Practice Action 8)
  • Involving those with a vested interest in protocol development and discussions about study quality (see also Good Practice Action 3).

Case studies of how QbD principles were applied in trials are presented by CTTI and can be found here:

In addition to the QbD resources, the European Clinical Research Infrastructure Network (ECRIN) hosts a Risk Based Monitoring Toolbox of resources providing information on tools available for risk assessment, monitoring and study conduct, the institutions where they are used, and other relevant details such as links and user feedback.

How funders can ensure this happens

  1. Point researchers to resources that support them to apply quality-by-design approaches, and to think about their risk assessment and monitoring strategies.
  2. Ask about their quality-by-design approach.
  3. Ask about their strategy for risk assessment ahead of the trial.
  4. Ask about their strategy for monitoring risks throughout the trial.
Scroll to Top