From a Regulatory Medical Writer’s Perspective
By ‘Femi Fajimi
Clinical trial quality is often discussed in terms of compliance: whether the protocol follows Good Clinical Practice (GCP), whether the required procedures are documented, and whether the study records meet regulatory expectations. These remain essential considerations. However, compliance alone does not necessarily establish that a clinical trial has been designed to produce reliable, interpretable results while adequately protecting participants.
This is where Quality by Design (QbD) becomes important.
QbD is not a new regulatory concept introduced by ICH E6(R3). It is an established quality principle reinforced by ICH E8(R1) and further integrated into the revised Good Clinical Practice guideline. Its central premise is straightforward: consider quality during clinical trial design rather than assessing it only after problems emerge.
For regulatory medical writers, this has practical implications. The role extends beyond producing documents that satisfy prescribed requirements. It also involves communicating the scientific and operational decisions that support trial quality.
Understanding Quality by Design (QbD) and Critical-to-Quality (CTQ) Factors
ICH E6(R3), particularly Principle 6, states that quality should be built into the scientific and operational design and conduct of clinical trials. It also emphasises proactively identifying factors critical to trial quality, commonly referred to as Critical-to-Quality (CTQ) factors.
CTQ factors are trial attributes fundamental to participant protection, the reliability and interpretability of results, and the decisions made based on those results.
These factors will differ between trials. For example, in an oncology study, the validity and consistency of tumour response assessments may be critical to interpreting the primary endpoint. In a trial involving an investigational medicine with important safety considerations, appropriate eligibility criteria, safety monitoring and dose-modification rules may be particularly important.
The point is not to classify every trial activity as critical. It is to identify prospectively the elements whose failure could meaningfully affect participant protection or the credibility of the study findings.
This distinction matters because quality management should be proportionate to the risks involved and the importance of the data being collected.
What This Means for Protocol Development
The clinical study protocol is one of the clearest places where QbD principles become visible.
A protocol should do more than describe what investigators are expected to do. It should communicate the scientific rationale, operational requirements and safeguards that make the study capable of answering its research question.
Consider a trial in which the primary endpoint depends on an imaging-based assessment. If the assessment method, timing or interpretation criteria are insufficiently defined, inconsistencies may arise across study sites. These inconsistencies could affect the reliability of the endpoint and ultimately the interpretation of treatment effects.
A well-developed protocol should therefore provide sufficiently clear instructions on the assessment process, including relevant timing, procedures and criteria. The level of detail should be appropriate to the endpoint and the risks identified during trial planning.
The same principle applies to eligibility criteria, safety monitoring, randomisation, blinding and other trial processes. Their inclusion should reflect the study’s scientific and operational needs rather than simply being carried forward from previous protocols or standard templates.
This is also where unnecessary complexity can become a quality concern. Excessive procedures, avoidable data collection and requirements that are difficult to implement consistently may place additional burdens on participants and investigators without improving the reliability of the results.
QbD encourages a more considered approach: document what is necessary to protect participants and achieve the trial objectives, and ensure that the requirements are operationally feasible.
The Medical Writer’s Contribution Begins Before the First Draft
Traditionally, medical writers may become involved after key trial decisions have already been made. The clinical team develops the protocol, and the writer is then asked to organise the information, apply the appropriate structure, and ensure consistency.
That contribution remains important, but it can be limited if the writer is involved only at the document-production stage.
A QbD-oriented approach creates an opportunity for earlier involvement. During protocol development, medical writers can work alongside clinical, statistical, safety and operational colleagues to understand the trial objectives, the identified CTQ factors and the decisions made to manage relevant risks.
This does not mean that the medical writer assumes responsibility for identifying or approving CTQ factors. Those responsibilities sit within the sponsor’s trial design and quality-management processes. Rather, the writer contributes by translating agreed scientific and operational decisions into clear, consistent and usable documentation.
For example, where a particular safety risk has informed an eligibility restriction or monitoring requirement, the protocol should communicate that requirement accurately. Where an endpoint’s reliability depends on standardised assessment procedures, the relevant instructions should be sufficiently precise to support consistent implementation.
The writer should also recognise when information appears unclear, contradictory or insufficiently supported and raise it with the appropriate subject-matter experts. This is not a substitute for clinical or statistical judgement. It helps ensure the document accurately reflects the decisions the trial depends on.
Moving Beyond Template-Driven Documentation
Templates are valuable in regulatory medical writing. They support consistency, completeness and alignment with established document structures. However, a template cannot determine whether the content fits a particular trial.
A protocol can include all expected headings and still fail to clearly communicate key trial requirements. Conversely, adding more procedures and explanatory text does not automatically improve quality.
The challenge is to distinguish between necessary documentation and documentation that merely increases volume.
A risk-proportionate approach asks whether each requirement serves a clear purpose. Does it support participant safety? Does it protect the reliability of an important endpoint? Does it address a meaningful operational risk? Is it feasible for investigators and participants?
These questions help move protocol development away from a checklist mentality and toward documentation that reflects the study’s actual design and needs.
The same principle applies to other clinical trial documents. An Investigator’s Brochure, for example, should communicate relevant information about the investigational product, including its safety profile, clearly and in an appropriately structured manner. It is not a substitute for the protocol’s operational requirements or the sponsor’s wider quality-management plan.
A More Strategic Role for Regulatory Medical Writers
ICH E6(R3) reinforces the importance of considering quality throughout trial design and conduct. For medical writers, this is an opportunity to contribute more meaningfully to trial documentation.
The writer’s value is not simply producing a polished protocol or ensuring every section is populated. It is in understanding why particular requirements exist and ensuring that the document communicates them accurately.
That requires familiarity with the trial objectives, an understanding of the CTQ factors identified by the study team, effective engagement with subject-matter experts and the ability to recognise inconsistencies that could affect document clarity or implementation.
It also requires knowing the limits of the role. Medical writers do not independently determine the clinical risk profile of a study or own the sponsor’s quality-management system. Their contribution is to support accurate, coherent communication of decisions made by the responsible experts.
Conclusion: Quality Should Be Designed, Not Just Documented
Quality by Design (QbD) challenges the idea that a compliant document necessarily proves a well-designed trial. A protocol may satisfy structural and regulatory expectations while still containing unclear requirements, unnecessary complexity or insufficient detail around important trial procedures.
The principles reinforced by ICH E6(R3) encourage a more deliberate approach: identify what matters to trial quality early, manage risks proportionately and ensure that trial processes are fit for purpose.
For regulatory medical writers, this means looking beyond the final document. The opportunity is to become involved early enough to understand the decisions shaping the trial and to ensure those decisions are communicated clearly and consistently.
A protocol should not simply record how a trial will be conducted. It should make clear how the trial has been designed to protect participants and produce reliable evidence.
References and further reading
International Council for Harmonisation (ICH). E6(R3) Guideline for Good Clinical Practice. Principles and Annex 1. 2025. ICH guideline (PDF).
International Council for Harmonisation (ICH). E8(R1) General Considerations for Clinical Studies. 2021. ICH guidelines.
European Medicines Agency. ICH E6 Good Clinical Practice. Guideline status and implementation information.
US Food and Drug Administration. E6(R3) Good Clinical Practice: Guidance for Industry. September 2025. FDA guidance.
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