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In recent years, regulatory authorities like the FDA and EMA have increasingly emphasized the importance of qualitative assessment of patient-reported outcomes (PROs) namely though in-trial interviews (ITIs). This shift reflects a broader commitment to patient-centric drug development and a deeper understanding of the lived experiences of patients. Yet, despite this growing demand, there remains a critical gap: the absence of clear, standardized guidelines on how to conduct ITIs and regulations on including ITIs into the standard procedure of patient reported outcome assessment.
The Role of In-Trial Interviews
In-trial interviews are a powerful tool for capturing qualitative patient-reported data. ITIs are typically semi-structured, conducted at key timepoints—often at baseline and end-of-treatment (EOT)— and provide rich insights into symptom burden, health-related quality of life (HRQoL), and individual benefit-risk assessments. When implemented longitudinally, they allow a rigorous assessment of meaningful changes in patient experience over time—data that is invaluable for health technology assessments (HTAs) and regulatory submissions.
These interviews complement quantitative measures of clinical trials by:
- Enhancing understanding of disease and treatment experiences.
- Validating and supporting the interpretation of questionnaire-based outcome assessments.
- Supporting interpretation of scores and meaningful changes.
- Informing trial design and operational feasibility.
As Michel et al. (2023) and Williamson et al. (2025) highlight, ITIs are especially valuable in phase II and III trials, where understanding the meaningfulness of treatment effects from the patient perspective is critical.
The Regulatory Gap
In 2017, the FDA published guidelines for Patient Focused Drug Development (PFDD) to recognize the importance of patient experience data, providing recommendations and best practices for when and how interviews and surveys may be used to collect patient experience data.
Specifically, the FDA encourages the use of baseline and exit interviews within clinical studies to gather insights on symptoms, treatment expectations, and trial participation. It recommends that interviews should be conducted by a trained, neutral third party either before (screening) or after (exit) the main part (i.e. treatment phase) of the study to avoid compromising study integrity. And the FDA notes that these methods can be particularly valuable in rare diseases or conditions with limited patient input, where stand-alone quantitative studies may be less feasible. This is supported by Contesse et al. (2019) who stress that ITIs in rare disease clinical trials are indispensable because they allow for a rigorous capture of patient experiences and especially of change assessment.
While being recommended, ITIs are not formally recognized within clinical trial regulations. They are not a required data collection method for HTA dossiers or regulatory submissions. And no clear guidelines on procedure and content are provided by regulatory authorities. The article by Williamson et al. (2025) highlights this gap and offers a comprehensive overview:
Key challenges include:
- Lack of standardization: There is no consensus on how to design, conduct, or analyze ITIs, leading to variability in quality and relevance.
- Unclear regulatory expectations: Sponsors often don’t know what regulators want to learn from ITIs or how the data will be used in decision-making.
- Operational complexity: Embedding interviews into trial protocols or conducting them as standalone studies involves logistical hurdles, including site selection, training, and data management.
The Case for (Mandatory) Regulations
This lack of inclusion into clinical trial regulations creates ambiguity for sponsors and researchers: When are ITIs necessary? What exactly do regulatory authorities want to learn from these interviews? How should they be conducted and analyzed to meet regulatory expectations?
As long as ITIs are not included into clinical trial regulations, the risk is twofold: Valuable qualitative data may be collected but not accepted or utilized effectively in regulatory decision-making. And sponsors may hesitate to invest ITIs due to uncertainty about their impact on approval and reimbursement outcomes. To fully realize the potential of ITIs, we need two things:
1. In-trial interviews should be part of clinical trial regulations
ITIs should not be optional add-ons—they should be embedded as a standard practice in phase II and III trials and therefore part of clinical trial regulations.
This integration would:
- Ensure systematic capture of patient experience data.
- Improve the relevance and interpretability of trial outcomes.
- Enhance patient-centricity in drug development.
- Provide regulators and HTAs with richer, more contextualized evidence.
As Michel et al. (2023) argue, embedding ITIs into trial protocols from the outset avoids costly amendments and ensures alignment with trial objectives. Williamson et al. (2025) further emphasize that ITIs can be conducted efficiently and remotely, minimizing burden while maximizing data quality.
2. Clear guidelines on how to conduct in-trial interviews
Regulators and HTA bodies must provide detailed, harmonized guidance on:
- Methodological standards
- Timing and frequency of interviews.
- Sample size and saturation principles.
- Data analysis and reporting formats.
- Integration with COAs and trial endpoints.
Such guidelines would empower sponsors to design ITIs that meet regulatory expectations and generate data that can meaningfully inform benefit-risk assessments and reimbursement decisions.
Conclusion
ITIs offer a unique window into the patient experience—one that quantitative measures alone cannot fully capture. As their use expands, the absence of clear regulations becomes increasingly problematic.
Sponsors need clarity on how to design and conduct ITIs, what data to collect, and how to present findings in submissions. Only then can we truly capture the patient voice, understand the real-world impact of treatments, and make informed decisions that reflect what matters most: the lived experiences of those we aim to help.
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