Clinical Trials Series: Part 2 – Design with the Patient in Mind: Building a Patient-Centric Protocol

Published on: Jul 10th, 2025

In the first part of our series, we outlined the regulatory and strategic building blocks you need to consider when launching your first EU clinical trial, such as understanding the EU Clinical Trial Regulation (EU CTR), site readiness, and submission planning. (Missed it? Read Part 1 here: First Steps into Europe: Key considerations for your first EU clinical trial). Now, let’s explore the next foundational element: designing a protocol that is truly patient-centric.

As clinical research evolves in Europe and beyond, sponsors are increasingly recognizing that the success of a clinical trial isn’t defined by regulatory approval alone, it also depends on how well the study resonates with the people it aims to serve: patients.

One of the most impactful shifts in protocol development over the past decade has been the rise of patient-centric design, a methodology that prioritizes the perspectives, needs, journey and lived experiences of the very people who will participate in your study. For sponsors planning their first European clinical trial, adopting a patient-centric protocol is not just about ethics or empathy, it’s about data quality, operational feasibility, and long-term success.

From Subject to Stakeholder: Why Patient-Centricity Matters

Historically, clinical trial protocols were primarily designed by physicians, researchers and sponsors, with limited or no involvement from patients themselves. These protocols were typically built around scientific hypotheses and regulatory requirements, with a strong focus on measurable clinical outcomes and methodological rigor. While these protocols emphasized scientific integrity and regulatory rigor, they often overlooked the day-to-day realities of patients’ lives, including the burden of participation, logistical challenges and personal preferences. As a result, many trials faced issues such as:

• Low recruitment
• High dropout rates
• Protocol deviations
• Poor generalizability of results

Today, European regulators, HTA bodies, ethics committees, and research sponsors are aligned in their demand for more relevant, inclusive, and patient-focused clinical research. The transition to patient-centered protocols represents a paradigm shift, where patients are no longer passive subjects but active contributors to study design. Designing protocols that incorporate their voices from the outset helps ensure studies are not only scientifically sound, but also more feasible, inclusive, and impactful.

Why Patient-Centric Protocols Matter in European Clinical Trials

This patient-centric approach not only improves the overall experience of participants but also enhances recruitment and retention, increases the relevance and generalizability of the findings and ultimately contributes to more successful and impactful trials.

 1. Improved Recruitment and Retention

Patient involvement directly addresses many of the reasons why individuals choose not to participate (or drop out) of trials. By minimizing logistical burdens and focusing on outcomes that matter to them, patients become more motivated to join and stay in clinical trials. This allows for a lower dropout rate, speeds up recruitment, and enhances overall study efficiency. As a result, quicker enrollment and fewer protocol amendments contribute to significant cost savings. Getting patients involved right from the start of designing the protocol builds respect and makes them feel like they really own the process, which improves their commitment

2. Regulatory Alignment

European regulators increasingly expect evidence of patient engagement in protocol development. Under the Clinical Trials Regulation (CTR) EU No. 536/2014, ethical review and competent authority approvals hinge not only on scientific merit but also on participant safety and feasibility, areas directly influenced by patient-centric design.

3. Increased Relevance of Results

Outcomes that resonate with patients and reflect their concerns, such as quality of life, daily function, or symptom relief, offer more useful data for clinical decision-making, health technology assessment, and market access. These patients reported outcomes (PRO) incorporate direct feedback from patients about their health status and treatment impact to capture their perspective. Integrating these aspects enhances the clinical relevance of the study, the reliability of the data collected and the overall impact on medical practice

Key Elements of a Patient-Centric Protocol

A patient-centric protocol is one that integrates patient input into key design decisions (from inclusion criteria to endpoints), study logistics to communication materials. It’s built not just for patients, but with them.

Creating a patient-centric trial means not only meeting compliance and scientific standards, but also addressing the real-world needs of your study population. This complements what we explored in Part 1 about optimizing trial timelines and site selection: if patients don’t join or stay, the trial can’t succeed, no matter how well the backend is structured.

Here are some key points to help you build this:

1. Active Early and Ongoing Patient Engagement

Involving patients at the concept stage sets the tone for the entire study. Sponsors should consider:

• Advisory Boards with patient experts or advocacy groups helps integrate their perspective throughout the entire process.
• Focus groups and interviews, or other burden mapping tools such as patient surveys to express patients needs and priorities
• Co-design workshops to develop visit schedules and communication materials

When designing study protocols, it is essential to invest time in understanding the lifestyle of the patient population. A crucial element of effective patient engagement involves carefully mapping the entire patient journey throughout the clinical trials, from initial study awareness through final follow-up. Approaching the trial from the patient’s perspective helps identify obstacles and barriers to recruitment and retention. For example, patients may flag that frequent hospital visits for assessments are too disruptive, suggesting alternatives like home-based visits or remote monitoring.

Many Tools and Methods can help to visualize the study from the patient’s point of view, identifying pain points that may not be obvious to researchers or clinicians, such as:

• Burden mapping surveys
• Journey mapping exercises
• Persona-based protocol walkthroughs

2. Protocol Flexibility and Accessibility

In multi-country European clinical trials, logistical and cultural flexibility is vital. By involving patients in the protocol design process, sponsors can streamline procedures and offer adaptable options that accommodate patients’ lifestyles and clinical needs through a patient-centred approach. These flexible approach may include:

• Decentralized trial models, such as home visits or local lab use
• Telehealth and remote monitoring
• eConsent platforms 
• Flexible visit windows to accommodate working patients or caregivers

A study designed around these flexible elements often improves participant satisfaction, and ultimately enhances data quality and study outcomes by making trials both scientifically rigorous and patient-centered, while reducing missing data caused by dropout.

Tip: Consider implementing a “Protocol Feasibility Assessment” with patient partners before finalizing your study design.

3. Real-World Endpoints: Aligning Clinical and Patient Value

A well-designed clinical trial should measure what truly matters to patients. This means going beyond traditional biomarkers and incorporating Patient-Reported Outcomes (PROs), including:

• Quality of life (e.g., EQ-5D, SF-36)
• Symptom scales (e.g., pain severity, breathlessness)
• Daily functioning and social participation
• Treatment satisfaction and convenience

A Regulatory Note:

Endpoints important to patients are not always aligned with regulatory gold standards. Striking the right balance is key.

As an example, in a gene therapy trial targeting a rare neuromuscular disorder, patients identified breathing difficulties, especially during sleep, as a major concern. The sponsor proposed Forced Vital Capacity (FVC) as the primary endpoint to reflect this fear. While meaningful to patients, regulators did not consider FVC alone a gold-standard outcome.

To address this issue the final design used a combined endpoint, merging FVC with the North Star Assessment for Neuromuscular Disorders (NSAD), a validated functional tool. This dual approach satisfied both patient expectations and regulatory requirements, an ideal compromise for any EU clinical trial.

4. Participant-Friendly Study Materials and Communication

Patient-centricity doesn’t stop at study design, it extends into how you communicate with participants. Patients can play an active role in developing communication materials like brochures, flyers, and explanatory videos, and leverage their networks to share recruitment messages authentically and accessibly. They can also participate in reviewing questionnaires and enhancing informed consent documents. Effective strategies include:

• Plain-language informed consent forms
• FAQ documents co-written with patient representatives
• Multilingual recruitment materials adapted for local audiences
• Visual storytelling via patient testimonials and video explainers

Patients are also powerful ambassadors for the trial. In one European study, a rare disease organization co-created a video message to encourage enrolment, reaching thousands of patients through social media.

5.  Transparent Dissemination of Study Results

European regulators, ethics committees, and patients all expect that trial results, positive or negative, be made public. Involving patients in:

• Drafting lay summaries of trial results
• Co-hosting webinars for participants and caregivers
• Advising on appropriate dissemination channels

can significantly improve the transparency and trustworthiness of your research.

Benefits of a Patient-Centric Approach

• Faster enrolment:  Integrating patient perspectives and flexible options like teleconsultations and home-based monitoring makes trials more accessible and convenient.
• Lower dropout:  Early patient involvement and clear communication foster trust and ownership, increasing engagement.
• Fewer amendments:  Patient input improves protocol feasibility, reducing the need for costly and time-consuming amendments.
• Improved data quality:  Reducing participant burden and using digital tools like eConsent and telemedicine improves follow-up and data completeness, leading to higher data quality.
• Cost savings:  Improved recruitment, retention, and trial efficiency lead to significant cost savings and shorter study timelines.

Above all, a patient-centric protocol creates a sense of partnership, patients are not just “subjects,” but co-creators of medical progress.

Challenges and Considerations

Designing patient-centric protocols isn’t without hurdles:

• Balancing scientific rigor with participant comfort
• Reaching consensus between patients and regulators
• Managing cross-country differences in expectations, language, and access

That’s why it’s critical to approach patient involvement as a continuous process, not a one-time checkbox.

Integrating Patient Perspectives: Practical Steps for Sponsors

If you’re new to designing a European clinical trial with patient-centric principles, here’s a simple roadmap to get started:

• Map the Patient Journey: Identify touchpoints from pre-screening to final follow-up.
• Engage with Advocacy Groups: They offer fast access to patient panels, insights, and dissemination networks.
• Conduct a Patient Impact Assessment: Assess burdens, expectations, and motivators before finalizing your protocol.
• Validate Materials: Use cognitive debriefing or patient expert to ensure consent forms and study brochures are understandable.
• Collaborate on Endpoints: Discuss proposed outcome measures early with both patients and regulators to ensure alignment.
• Use Technology Thoughtfully: ePRO, wearable tech, and telehealth tools should enhance, not complicate, the patient experience.

Conclusion: The Future is Patient-First

Whether you’re navigating startup strategy (as outlined in Part 1: First Steps into Europe: Key considerations for your first EU clinical trial) or refining the patient experience, a patient-centric mindset is crucial at every step of your first EU clinical trial.

Incorporating patient perspective into trial design is no longer a “nice-to-have”, it’s a strategic imperative. Especially in the European regulatory environment, where authorities increasingly value real-world relevance and patient experience, a patient-centric protocol can provide a critical competitive advantage for your trial.

By putting patients at the heart of protocol design, you don’t just boost recruitment and retention, you also improve outcomes, efficiency, and long-term impact.

Stay tuned for our next post in the series, where we’ll explore the data integrity in Europe.