Beyond Numbers: Uses and Value of In-Trial Interview Data for Regulatory and Health Technology Assessment (HTA) Decision Making.

Key Points For Decision Makers

There is a growing interest in qualitative in-trial interviews, and their integration into the regulatory space and HTA processes is evolving. Regulators use qualitative data to gain insights into patient experiences, assess the relevant concepts, evaluate changes in core symptoms, understand treatment benefits, and interpret meaningful change. Ten products ( n = 10/406) included in-trial data in FDA regulatory reviews, and eight products in EMA EPAR public reports; only Xermelo and Yorvipath were reviewed by both agencies. While both agencies commonly use ITR data to support meaningful change or score interpretation, the EMA also use the data to support treatment benefit and risk benefit of the novel drugs. Of the eight products ( n = 8/657) that included in-trial interview data reviewed by the EMA, two included qualitative data in a subsequent HTA report (NICE, SMC), leading to funding arrangements for individual applications (Xermelo) or resulting in a positive reimbursement decision (Luxturna). This study highlights the need for early planning and alignment of qualitative in-trial research objectives with regulatory and HTA requirements to enhance the relevance and impact of qualitative evidence in drug development and healthcare decision making.

Introduction

Regulatory agencies are placing growing emphasis on integrating patient and caregiver perspectives into the drug development process and regulatory decision making—particularly regarding the meaningfulness of treatment benefits [ 1 – 3 ]. This ensures that approved therapies not only demonstrate clinical efficacy but also address outcomes that matter most to those receiving care. Since 2018, the Food and Drug Administration (FDA) has sequentially released several guidance documents over time under its Patient-Focused Drug Development (PFDD) Guidance Series including four initial draft guidance documents and three final guidance documents. These guidance documents are aimed at incorporating patient experience data (PED) and qualitative input from patients and caregivers into medical product development and regulatory decision making [ 4 , 5 ]. As defined in the 21st Century Cures Act [ 6 ], PED refers to information from patients, caregivers, or others about the impact of both disease and treatment on patients’ lives—covering symptoms, quality of life, and treatment preferences.

In December 2024, the FDA hosted a virtual public workshop focusing on PED use in the drug development process, and discussing the methodological challenges of designing and implementing in-trial qualitative interviews [ 7 , 8 ]. The workshop reinforced the FDA’s commitment to advancing the use of patient-centered evidence in regulatory decision making, and highlighted the growing role of qualitative research in clinical trials. Similarly, the European Medicines Agency (EMA) demonstrated its commitment to patient engagement by revising existing patient engagement frameworks and developing new guidelines on patient data collection [ 9 ]. At the Drug Information Association (DIA) Global Annual Meeting in June 2025, it was announced that the EMA is introducing a dedicated PED section in regulatory submissions, as part of a broader initiative to systematically incorporate patient perspectives into the evaluation and approval of new medicines [ 10 ].This was followed in September 2025 with the publication of a reflection paper to encourage stakeholders to engage early in the collection of PED in medicine development programs [ 11 ].

Building on this regulatory momentum, qualitative in-trial interviews are gaining traction in their use across a range of medical conditions [ 12 – 22 ] to contextualize and interpret clinical outcome assessment (COA) data and other trial endpoints [ 23 ]. Between 2012 and 2022, the number of peer-reviewed articles and guidelines around the use of in-trial interviews has doubled [ 24 ]. These interviews provide information on patients’ lived experiences with their condition, and offer valuable insights into patients’ (and sometimes caregivers’) perceptions [ 25 , 26 ] of treatment experiences to support the interpretation of COAs and other clinical trial efficacy and safety endpoints [ 27 ]. Additionally, they help improve understanding of participant experiences during the trial—including any burdens associated with trial participation.

The value of qualitative data extends beyond regulatory approval and can play a significant role in health technology assessment (HTA) processes. While the primary goal of the regulatory process is to ensure that a product is safe and effective for its intended use, HTA aims to inform decision making that supports an equitable, efficient, and high-quality health system. Traditionally, HTA focuses on assessing the clinical and cost effectiveness of treatments and interventions. Recently, HTA bodies have increasingly recognized the importance of incorporating patient-based insights into their assessments—including health experiences, quality-of-life considerations, and interactions with healthcare and health services [ 1 ]. This is often achieved by collecting data through standardized, validated, quantitative. patient-reported outcome (PRO) measures, such as those developed through initiatives like the Patient-Reported Outcomes Measurement Information System (PROMIS ® ) [ 28 ], European Organization for Research and Treatment of Cancer (EORTC) [ 29 ], or Functional Assessment of Chronic Illness Therapy (FACIT) [ 30 ]. Qualitative research adds layers of context and meaning, making the overall assessment more comprehensive, and enhancing the interpretation of results from quantitative studies on clinical and cost effectiveness. Despite the growing recognition of qualitative research, a review of submissions to the National Institute for Health and Care Excellence (NICE) and the Canadian Agency for Drugs and Technologies in Health (CADTH) between 2019 and 2021 revealed that less than 15% and 20% of submissions (respectively) included any qualitative research [ 31 ]. Since then, however, NICE has updated its guidelines to formally include qualitative methods in their recommendations—reflecting this shift towards a more holistic approach to healthcare assessment, and a broader recognition of the value they bring to understanding patient perspectives.

Michel and colleagues undertook a comprehensive review of PROLABELS and PRO-INSIGHT databases from January 2011 up until February 2022, with further follow-up reviews of HTA reports. The goal was to identify case studies where qualitative interviews contributed to regulatory submissions, product labeling, or market authorization for treatments, including telotristat ethyl (Xermelo), dupilumab, emicizumab, and pembrolizumab [ 24 ]. Since 2022, there has been a notable increase in regulatory requests and guidance relating to the use of qualitative research in drug development [ 32 – 35 ]. Our study aimed to assess whether this growing interest has translated into an increased inclusion of qualitative research in regulatory and HTA reviews from 2017 (when the FDA developed the PFDD working group) until 2025, and to identify cases where qualitative data were submitted to both regulatory and HTA bodies.

Methodology

We conducted a comprehensive review of multiple data sources, including recent regulatory and HTA methodological guidance documents, FDA clinical guidance documents across selected therapeutic areas, a systematic review of FDA and EMA new drug approvals between January 2017 and March 2025, and HTA reports published for a selection of EMA-approved products. The objective of this review was to assess how patient and caregiver perspectives—derived from qualitative research or in-trial data—are being considered in regulatory and HTA decision making.

Part 1: Review of Relevant Regulatory Guidance Documents

We began by reviewing the FDA’s methodological PFDD documents, including a series of four methodological guidance documents released from June 2018 to October 2025 [ 34 ]. They outline the systematic approaches for collecting, analyzing, and incorporating patient and caregiver input into medical product development and regulatory decision making. In the absence of specific EMA guidance on collecting PED, we reviewed the EMA’s Strategic Reflection Paper on Regulatory Science to 2025 [ 9 ].

In-trial interview research is especially valuable in rare disease clinical trials, where reliable and valid COAs are often lacking; in oncology, in-trial research is used to support benefit–risk assessments from the patient perspective; and also in complex trials involving emerging gene therapies. Accordingly, three additional FDA guidance documents were reviewed because, in the experience of the authors, these are growing areas of interest for ITR studies: Core Patient Reported Outcomes in Cancer Clinical Trials: Guidance for Industry (Final in October 2024) [ 36 ]; Rare Diseases: Considerations for the Development of Drugs and Biological Products (Final, December 2023) [ 37 ]; and Human Gene Therapy for Rare Diseases (January 2020) [ 38 ].

These methodological and clinical guidance documents were reviewed for content related to PED and qualitative in-trial data information.

Part 2: Regulatory Drug Approval Search: EMA and FDA

A systematic review was conducted to identify any in-trial research (ITR) that was used to support the approval or authorization of new drugs from January 1, 2017 through March 31, 2025 (Fig. 1 ). Searches were conducted using the FDA’s Center for Drug Evaluation and Research (CDER) database of novel drug approvals for US-based approvals, as well as the EMA’s database for authorized drugs for European Union (EU)-based approvals. The searches were not restricted by age, gender, indication or by country and used the following terms to identify ITR data: ‘qualitative’, ‘interview’, ‘exit’ and ‘embedded’. These databases provide access to publicly available regulatory review documents, which were analyzed to identify qualitative data references. For FDA drug approvals, this included multi-discipline reviews, integrated reviews, cross-discipline leader reviews, and other review documents or publications. For EMA drug authorizations, this review focused on initial EMA marketing authorization documents as part of the European Public Assessment Report (EPAR). If an FDA or EMA review explicitly noted that the submitted qualitative data were not reviewed, the corresponding review packages were excluded from further analysis. Fig. 1 Regulatory agency approved drugs with qualitative data in the product label (January 2017 to March 2025). FDA Food and Drug Administration, EMA European Medicines Agency

We first reviewed all publicly available FDA and EMA regulatory review documents. When qualitative data were identified in one of the review documents, the following data were extracted: qualitative data type (e.g., key opinion leader interviews, focus groups, cognitive interviews, or exit interviews), qualitative study objectives (e.g., to establish a PRO’s content validity, to evaluate treatment benefit), and FDA or EMA regulatory commentary regarding the submitted evidence or recommendations for future qualitative research.

Subsequently, we reviewed all FDA-approved labels and EMA Summaries of Product Characteristics (SmPCs) to determine whether in-trial qualitative data were specifically included in the labeling. For any labeling language related to PRO data, we further examined whether evidence from qualitative interview data was provided, and whether the agencies considered it sufficient to support the PRO’s use as a primary or key secondary endpoint.

Part 3: Reviews of Qualitative Data from HTA Documents

Review of HTA Guidance Documents

The websites of six prominent HTA bodies in Europe and the UK were searched to identify their positions on qualitative research—the Scottish Medicines Consortium (SMC) for Scotland; the NICE for the UK; the Haute Autorité de Santé (HAS) for France; the Federal Joint Committee (Gemeinsamer Bundesausschuss [G-BA] [ 39 ]) and the Institute for Quality and Efficiency in Health Care (Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen [IQWiG] 1 ) for Germany; the Italian Medicines Agency (Agenzia Italiana del Farmaco [AIFA]) for Italy; and the Spanish Agency of Medicines and Medical Devices (Agencia Española de Medicamentos y Productos Sanitarios [AEMPS]) for Spain.

Review of Qualitative Data from Health Technology Assessment (HTA) Review of EMA-Approved Drugs

The European HTA bodies (including the UK and Scotland at the time of the searches) that published guidance on the use of qualitative research were selected as candidates for further review of HTA reports. Consequently, products for new indications that received EMA approval between January 1, 2017, and March 31, 2025, and included in-trial qualitative data in their labels and/or EPAR public documents, were identified for further analysis among the selected HTA candidates. The specific aim of this review was to determine whether qualitative data were included in the HTA candidates’ reports.

Results

Part 1: Review of Relevant Regulatory Guidance Documents

Eight regulatory guidance documents were reviewed—five methodological, and three disease- or treatment-specific [ 9 , 32 – 38 ]. Extraction of relevant information on PED and qualitative ITR is presented in Table 1 . These documents reflect a growing recognition of the value of qualitative methods in the regulatory context. Although ITR is not always explicitly addressed in regulatory guidance, it is increasingly acknowledged as a valuable approach for collecting PED directly on the populations participating in clinical trials. By interviewing trial participants, we gain unique insights into meaningful experiences related to the investigational drug—insights that cannot be obtained from the general population. Qualitative in-trial interviews can support content validity and explore meaningful change in particular patient- and observer-reported outcomes, identify and prioritize symptomatic adverse events (particularly in oncology), and inform benefit–risk assessments from the patient perspective. It also offers insights into patients’ experiences with both the disease and the trial itself. ITR methods, such as interviews or surveys, are especially useful in rare disease contexts, where pre-trial data collection is limited. Despite potential operational challenges and potential biases, well-designed ITR—conducted before or after treatment, and using appropriate methodologies—can yield unique and valuable insights to support medical drug development and regulatory decision making. The FDA encourage sponsors to submit study protocols and interview guides to the agency for early review [ 40 ]. The EMA encourages Sponsors to seek scientific advice and submit protocols in relation to wider PED but does not explicitly mention ITR [ 9 ]. Table 1 Content related to PED and ITR From selected regulatory guidance documents ( N = 7) Status, year Name and link to the guidance Main purpose of document PED-related information Information related to in-trial research Finalized in June 2020 PFDD Guidance 1: Collecting Comprehensive and Representative Input [ 32 ] Provides a general overview of methods and approaches for collection of PED Provides operational considerations for collecting PED “PED data can be collected in a variety of settings, including clinical trials , observational studies, advisory boards, public meetings (such as Patient-Focused Drug Development (PFDD) meetings), and other novel settings (e.g., social media, online patient communities)” Finalized in February 2020 PFDD Guidance 2: Methods to Identify What Is Important to Patients [ 33 ] Methods for identifying what is most important to patients with respect to their experience and disease burden Provides general considerations about methods to what is important to patients Includes a specific appendix (Appendix 5 ) on screening and exit interview studies / survey studies Cites potential strengths: “Contribute cumulative evidence of the patient experience […]; Inform initial development or refinement of a COA […]: Add greater depth to data in rare diseases where stand-alone qualitative studies are less feasible […]; Obtain participant input on meaningful outcomes and meaningful change […]; Provide information on trial integrity […]” Cites potential limitations including but not limited to extra burden on site staff and trial participants, and other operational challenges Draft, June 2022 Final, October 2025 PFDD Guidance 3: Selecting, Developing, or Modifying Fit-for-Purpose Clinical Outcome Assessments [ 34 ] Describes methods for selecting, modifying, developing, and validating COAs for use in clinical trials Focuses on COAs and their appropriateness for assessing the concept of interest in a particular context of use and how qualitative data can provide evidence of fit for purpose Although in-trial research is not specifically discussed, content validity, cognitive interviews, and qualitative exploration of meaningful change for a specific COA can be conducted within the context of clinical trials to provide evidence of COAs’ fit for purpose Draft, April 2023 PFDD Guidance 4: Incorporating Clinical Outcome Assessments into Endpoints for Regulatory Decision-Making [ 35 ] Provides recommendations on selecting and justifying COA for planned endpoints Focuses on COAs, their selection, analysis and interpretation Provides recommendation on when to consider ITR design: “For situations in which it is not feasible to obtain information to inform meaningful differences or scores before a registration trial (e.g., rare disease trials), sponsors can consider using exit interviews or surveys (refer to PFDD Guidance 2).” Provide recommendations on questions to be asked “Patients or their caregivers could be asked questions such as whether the patient experienced a change in their symptoms from baseline, whether the change was an improvement or worsening, and whether they believe the change in symptoms was meaningful…” Provides recommendations on ITR design “The interviews should be conducted after the patients complete the main portion of the study to avoid any potential compromise to trial integrity. Patients and/or caregivers should be unaware of their study group assignment. Sponsors who are considering conducting exit interviews or surveys should submit a study protocol and interview guide to FDA for review as early as possible” Final, March 2020 EMA Regulatory Science to 2025 Strategic reflection [ 9 ] Outlines key strategic goals for human medicines, to keep pace with scientific and technological innovation EMA strategic goals and recommendations Expand benefit–risk assessment and communication by including patient preferences to inform the benefit–risk assessment Reinforces the relevance of patient input in evidence generation Although in-trial research is not specifically discussed, patient preferences and patient experiences of treatment including symptomatic side effects can be collected through exit interviews In-trial interview data can be used to support a meaningful treatment effect and benefit–risk assessment of a new medicine from a patient perspective Final, October 2024 Core Patient-Reported Outcomes in Cancer Clinical Trials [ 36 ] Provides recommendations to sponsors for collection of a core set of patient-reported clinical outcomes in cancer clinical trials “Sponsors should provide a rationale for the selection of symptomatic AEs that will be assessed, based on mechanism of action, early clinical data, and input from patients and healthcare providers” Although in-trial research is not specifically discussed, in-trial interviews are an accepted source of patient input. Interviews can identify any symptomatic AEs that might be missing from standard lists and provide rationale for selection Final, December 2023 Rare Diseases: Considerations for the Development of Drugs and Biological Products [ 37 ] Assists sponsors of drugs for the treatment of rare diseases “ Patient input can provide important information about patient experiences, perspectives, needs and priorities. The FDA encourages the incorporation of patient perspectives and experiences in the drug development process ” Although ITR is not specifically discussed, in-trial interviews provide unique input from patients who have directly experienced the clinical trial and treatment Interview content can address both the patient experience and the overall experience in the clinical trial itself January 2020 Human Gene Therapy for Rare Diseases [ 38 ] Provides recommendations to sponsors developing human gene therapy (GT) products intended to treat a rare disease in adult and/or pediatric patients “ Patient experience data may provide important additional information about the clinical benefit of a GT product . The FDA encourages sponsors to collect patient experience data during product development” Although ITR is not specifically discussed, in-trial interviews provide unique input from patients on perceived meaningful treatment benefits Interview content can address both the patient experience with treatment and the overall experience in the clinical trial itself AEs adverse events, COA clinical outcome assessment, EMA European Medicines Agency, FDA Food and Drug Administration, GT gene therapy, ITR in-trial research, PED patient experience data, PFDD Patient-Focused Drug Development

Part 2: Regulatory Drug Approvals Search: EMA and FDA

Review of FDA Labels and Other Review Documents

Between 37 and 59 novel drugs were approved by the FDA per full year between 2017 and 2024. Seven novel drugs were approved in the first quarter of 2025 (Fig. 1 ). Among the FDA approvals for novel drugs reviewed during the research period, 16% or fewer applications included reviews of any qualitative data type. Of the 406 applications assessed, the number that included reviews of in-trial interview data ranged from 0 to 2 per year, with 10 applications (<3%) incorporating such information in one of the FDA’s publicly available review documents (Fig. 3 ). The majority of applications with in-trial data ( n = 7/10 [70%]) were for treatments for rare conditions. None of these applications included in-trial interview data in the product label (Fig. 2 ). Instead, other important uses were identified for in-trial (exit) interview data by US regulators. These included the following: providing insights on the patient experience of symptoms (Xolremdi), supporting interpretation of meaningful change of PRO measures and anchors (e.g., Romvimza, Yorvipath, Aimovig), confirming relevance of the concepts measured by the PRO (Fabhalta), and documenting changes in core symptoms (Veopoz, Xermelo). However, the FDA reported some limitations on the designs of in-trial interview studies, either related to the small sample size ( n = 3 for Aimovig), study design (e.g., open label for Veopoz), and concerns surrounding data quality (Bylvay); in one circumstance, the FDA did not review the exit interview data. The sample size for the seven interview studies where data were available (surveys excluded) ranged from three (Aimovig) to 96 (Romvimza) participants, which was 0.3% ( n = 3/955) to 78% ( n = 96/123) of the trial population. All ten trial participants for Veopoz for CHAPEL disease (a rare condition) participated in the exit interviews (Table 2 ). Fig. 2 Review of characteristics for submissions to regulatory agencies with in-trial interview data. Note: Some ITR studies addressed more than one evaluation objective. ClinRO clinician-reported outcome, EMA European Medicines Agency, FDA Food and Drug Administration, PRO patient-reported outcome Table 2 FDA review characteristics for submissions with in-trial interview data ( N = 10) Year Drug name Condition and review type In-trial research interview characteristics a FDA comments on in-trial research interviews PRO included in label ITR mentioned in label 2025 Romvimza (vimseltinib) Condition: tenosynovial giant cell tumor Rare disease: yes Review type: Multi-Discipline & Other Type: exit interviews Sample size: n = 96/123 Objectives: assessment of meaningful change of a PRO PRO supported: PROMIS-PF Distribution- and anchor-based methods triangulated with patient exit interviews were used to calculate potential thresholds [meaningful change] FDA recommends the use of anchor-based methods to establish meaningful within-patient change (MWPC) in COA-based endpoint scores, although other methods (e.g., qualitative evidence ) can be used Based on the submitted qualitative data , FDA agrees that the active ROM assessment (as measured by a goniometer) and the 15-item PROMIS-PF assesses relevant and important aspects of tenosynovial giant cell tumor (i.e., active ROM and physical function, respectively) “The final proposed threshold was triangulated using the potential distribution and anchor based thresholds and informed by the results of the qualitative interviews of the participants conducted within 28 days before the End of Part 1 study visit. ... The responder definitions that were determined using this method is robust and contributes to interpretation of clinically meaningful difference in patient-reported outcome (PRO) scores between the treatment arms.” “The Applicant did not propose a target anchor change category based on the PGIS-Physical Function item. The Applicant provided insufficient evidence to support the target anchor change category on the PGIC-Physical Function based on the approach used in their exit interview study.” Yes No 2024 Xolremdi (mavorixafor) Condition: WHIM syndrome (warts, hypogamma-globulinemia, infections and myelopathies) Rare disease: yes Review type: Integrated & Other Type: exit interviews Sample size: not reported Objectives: understanding symptom experience PRO supported: not applicable Almost all patients with WHIM syndrome experience infections in their life with variable severity and frequency, based on a study of the natural history of WHIM syndrome, and as reported in the medical history of the Patient Exit Interview report No No 2024 Yorvipath (palopegteriparatide) Condition: hypoparathyroidism Rare disease: yes Review type: Multi-Discipline & Other Type: embedded interviews Sample size: n = 9/84 Objectives: assessment of meaningful change of a PRO PRO supported: HPES FDA made recommendations on external anchors for the HPES measures and provided comments regarding SF-36 v2.0 and requested a protocol for the planned exit interviews (previously recommended exit interviews) To assess participants’ changes in physical and cognitive symptoms and functional impacts over the course of the trial period, participants were asked to respond to the PGI-S scales, PGI-C scales and the HPES items within the Physical domain, Cognitive domain, Physical Functioning domain and Daily Life domain and then share their thoughts on what constituted a meaningful change for the corresponding measure (using actual reported changes from the clinical trial and hypothetical changes) The results concluded the most participants reported that a ≥1 category change (improvement) on the PGI-S scales represents a meaningful within-patient change No No 2023 Fabhalta (iptacopan) Condition: paroxysmal nocturnal hemoglobinuria (PNH) Rare disease: yes Review type: Integrated & Other Type: exit interviews Sample size: n = 39/37 Objectives: Confirmation of PRO relevance in the context of use PRO supported: FACIT-Fatigue Exit interviews with participants were scheduled within 14 days of their Week 24 study visit for both trials. All interviews were conducted by telephone and lasted approximately 60 minutes A total of 17 patients in the APPLY-PNH trial participated in the qualitative interviews . The results suggest that the FACIT-Fatigue measures relevant and important aspects of the fatigue experience in patients with PNH A total of 22 patients in the APPOINT-PNH trial participated in the qualitative interviews . Consistent with what is reported above from APPLY-PNH, the results also suggest that the FACIT-Fatigue measures relevant and important aspects of the fatigue experience in patients with PNH No No 2023 Veopoz (pozelimab-bbfg) Condition: CHAPLE disease Rare disease: yes Review type: Multi-Discipline & Other Type: exit interviews Sample size: n = 10/10 Objectives: assessment of meaningful change in key symptoms PRO supported: not applicable Exit interviews with subjects and caregivers (although limited by the open-label nature of the trial) consistently indicated that subjects felt better in their core signs/symptoms including abdominal pain, which was reported in all subjects at baseline After 24 weeks of pozelimab treatment, the Applicant stated that all subjects experienced a complete resolution in their most bothersome symptom based on the exit interviews However, the qualitative exit interview data should be interpreted with caution given the open-label study design No No 2021 Bylvay (odevixibat) Condition: pruritus in progressive familial intrahepatic cholestasis Rare disease: yes Review type: Multi-Discipline & Other Type: exit surveys Sample size: n = 42/62 Objectives: assessment of meaningful change of a PRO PRO supported: worst daily scatching score FDA recommendation to conduct interviews to assess meaningful change Interpretation of the exit survey results is limited by (a) the focus of the survey questions on change, which may be either improvement or worsening, and (b) the misalignment of response collection timeframe with timing of Caregiver Global Impression of Symptoms administration and evaluation of efficacy endpoint “change in Worst Weekly Scratching Score from baseline to Weeks 21– 24 ” proposed by the Agency to facilitate interpretation of MWPC in pruritus Further, interpretation is precluded by concerns surrounding response data quality. Although examination of patient and caregiver responses to exit survey question suggests patients and caregivers interpreted meaningful ‘change’ in Questions 1–3 as meaningful improvement, it is unclear in many cases who is actually providing the responses. As such, exit interview results cannot yield trustworthy information and cannot be used to help inform evaluation of either meaningful improvement or meaningful decline Yes No 2020 Blenrep (belantamab mafodotin-blmf) Condition: multiple myeloma Rare disease: yes Review type: Multi-Discipline & Other Type: embedded interviews Sample size: not reported Objectives: not reported PRO supported: not reported FDA did not review the questions from the trial-embedded interview sub-study, therefore cannot comment on the satisfaction results No No 2019 Vyleesi (bremelanotide) Condition: hypoactive sexual desire disorder Rare disease: no Review type: Multi-Discipline Type: exit surveys and interviews Sample size: n = 242/1267 survey; n = 80/1267 interviews Objectives: assessment of meaningful change of a PRO PROs supported: FSFI FSDS-DAO The applicant defined a clinically meaningful score change in the FSFI Desire Domain and FSDS-DAO Question 13 scores as 0.6 points and 1 point, respectively, based on anchor-based methods using phase III clinical trial data While we agree with the applicant’s proposed threshold for the within-patient meaningful score change in the FSDS-DAO Question 13 (i.e., one-point change), we disagree with the proposed threshold for the FSFI Desire Domain as the data from the anchor-based methods and combined with patient input from exit surveys and interviews indicated ≥1.2 score points change is a more appropriate threshold in FSFI Desire Domain Integrating patient input from an exit survey as an anchor may also be helpful to supplement patient-reported global anchors scales to inform the threshold of improvement Yes No 2018 Aimovig (erenumab-aooe) Condition: migraine Rare disease: no Review type: Other Type: exit interviews Sample size: n = 3/955 Objectives: assessment of meaningful change of a PRO PRO supported: MPFID During the IND phase, this reviewer recommended that the applicant consider having trained interviewers conduct patient interviews at study exit in both of the phase III clinical trials to assess their perception of what constitutes a clinically meaningful change from baseline in MPFID domain items and scores, as well as in reduction in mean monthly migraine days. And ensure that the patient population for the exit interviews includes patients with a range of migraine severity and other relevant demographics to provide robust data to help supplement the anchor-based and cumulative distribution function methods to determine a clinically meaningful threshold and generate a responder definition. Optimally, patients would be interviewed at the beginning, middle and end of the trial The applicant conducted some exit interviews at the end of the double-blind treatment phase of Trial 20120296 We [the Agency] do not believe that there were enough subjects in the exit interview study to draw concrete conclusions regarding the clinical meaningfulness of changes in MPFID domain scores; however, the data obtained from the three subjects appears to be consistent with the rest of the applicant’s MPFID content validity and psychometric evaluation data Yes No 2017 Xermelo (telotristat ethyl) Condition: carcinoid syndrome diarrhea Rare disease: no Review type: Other Type: exit interviews Sample size: n = 35/135 Objectives: assessment of meaningful change in key symptoms PRO supported: Bowel Movement Question in diary PRO Reduction of two BMs or 30% from baseline per day is considered meaningful by the patients interviewed in the patient-reported outcome sub-study (patient exit interviews conducted in study LX1606.301). However, this responder definition was not proposed as a study endpoint ‘Durable response’ defined as “reduction of at least 30% in BM frequency from Baseline for at least 50% of the days of participation in the double-blinded trial period” was not appraised by the patients during the exit interviews No No BM bowel movement, COA clinical outcome assessments, FACIT-Fatigue Functional Assessment of Chronic Illness Therapy–Fatigue Scale, FDA Food and Drug Administration, FSDS-DAO Female Sexual Distress Scale-Desire/ Arousal/Orgasm (FSDS-DAO) instrument, FSFI Female Sexual Function Index–Desire Domain, HPES Hypoparathyroidism Patient Experience Scale, ITR in-trial research, MPFID Migraine Physical Function Impact Diary, PGI-C Patient Global Impression of Change, PGI-S Patient Global Impression of Severity, PNH paroxysmal nocturnal hemoglobinuria, PRO patient-reported outcomes, PROMIS-PF PROMIS Physical Function, ROM range of motion, SF-36 36-Item Short Form, WHIM warts, hypogamma-globulinemia, infections and myelopathies a Sample size is reported as the number of interviews or surveys out of the entire sample

EMA Regulatory Drug Approval Search

Between 54 and 95 drugs were authorized by the EMA per full year between 2017 and 2024. Twenty-eight drugs were authorized in the first quarter of 2025 (Fig. 1 ). Except for 2025 (which was 11%), < 5% of drug applications included reviews for any qualitative data type. Of the 657 applications assessed, the number that included reviews of in-trial interview data ranged from 0 to 2 per year, with a total of eight applications (approximately 1%) incorporating such information in EPAR public assessment reports (Fig. 3 ). Approximately one-third of applications with in-trial data ( n = 3/8 [38%]) were for treatments of rare conditions. One of these applications included in-trial interview data in the SmPC (Xermelo) (Fig. 2 ). Fig. 3 Drugs reviewed by regulatory agencies with in-trial interview data. EMA European Medicines Agency, FDA Food and Drug Administration. ^ FDA-reviewed drugs and indications with in-trial interview data: Aimovig (migraine), Blenrep (multiple myeloma), Bylvay (pruritus in progressive familial intrahepatic cholestasis), Fabhalta (paroxysmal nocturnal hemoglobinuria), Romvimza (tenosynovial giant cell tumor), Veopoz (CHAPLE disease), Vyleesi (hypoactive sexual desire disorder), Xermelo (carcinoid syndrome diarrhea), Xolremdi (WHIM syndrome), and Yorvipath (hypoparathyroidism). ^^ EMA-reviewed drugs and indications with in-trial interview data: Kayfanda (cholestatic pruritus in Alagille Syndrome adenocarcinoma), Luxturna (Leber congenital amaurosis, retinitis pigmentosa), Opzelura (vitiligo), Paxneury (attention deficit disorder with hyperactivity), Ryeqo (leiomyoma), Vyloy (gastric or gastroesophageal junction adenocarcinoma), Xermelo (carcinoid tumor, neuroendocrine tumors), Yorvipath (hypoparathyroidism)

EU regulators used in-trial (exit) interview data to describe treatment benefit (Paxneury, Yorvipath, Kayfanda), provide insights into patients’ experiences with symptoms (Xermelo, Luxturna), support the interpretation of meaningful change of PRO or clinician-reported outcome measures (Vyloy, Ryeqo, Opzelura), or support risk–benefit assessment of the novel drug (Xermelo).

However, the EMA also reported some limitations. For instance, they noted that some results were immature to derive thresholds to support meaningful change (Vyloy), and the number of participants involved was limited ( n = 36/674 for Opzelura and n = 30/582 in the US for Ryeqo). Sample sizes between 30 and 36 participants were noted for the three exit interview studies where data were available, comprising 4%, 6%, and 26% of the trial population for Ryeqo, Opzelura, and Xermelo, respectively (Table 3 ). Table 3 EMA review characteristics for submissions with in-trial interview data ( N = 8) Year Drug name Condition & review type In-trial research interview characteristics a EMA comments on in-trial research interviews PRO included in label ITR mentioned in the label 2025 Paxneury (guanfacine) Condition: attention deficit disorder with hyperactivity Rare disease: no Review type: EPAR – Public Assessment Report Type: embedded interviews (not explicitly stated and based on description provided) Sample size: not reported Objectives: perception of treatment effect PRO supported: not applicable Patients were interviewed by the investigational team regarding their well-being state after each dose reduction (evenings of Days 41, 44, 47) Yes No 2024 Vyloy (zolbetuximab) Condition: gastric or gastroesophageal junction adenocarcinoma Rare disease: no Review type: EPAR – Public Assessment Report Type: exit surveys Sample size: not reported Objectives: assessment of meaningful change of a PRO PRO supported: EORTC QLQ-C30 TTCD of physical function, abdominal pain/discomfort (OG25-Pain), and Global Health Status/Quality of Life (key secondary endpoint based on EORTC-QLQ-C30) was evaluated based on a threshold obtained from existing literature because the results of exit survey are pending As the exit survey started after the initiation of the clinical trial, the results are immature to derive the threshold for clinically meaningful deterioration . The clinical study report will be amended to include analysis of TTCD based on exit survey study results after sufficient data have been accrued No No 2024 Kayfanda (odevixibat sesquihydrate) Condition: cholestatic pruritus in Alagille Syndrome adenocarcinoma Rare disease: yes (Alagille Syndrome adenocarcinoma) Review type: EPAR – Public Assessment Report Type: exit interviews Sample size: not reported Objectives: perception of treatment effect PRO supported: not applicable Patient impression of treatment effect as recorded during exit interviews at Week 24 Yes No 2023 Opzelura (ruxolitinib) Condition: vitiligo Rare disease: no Review type: EPAR – Public Assessment Report Type: exit interviews Sample size: n = 36/582 in the US Objectives: assessment of meaningful change of a PRO and of a ClinRO ClinROs supported: T-VASI VNS Exit interviews were performed in participants who finished the pivotal studies The previously set threshold for meaningful improvement at the F-VASI at 75% was supported by the results of the interviews. Similarly, the threshold for meaningful improvement at the T-VASI was 50% and for the VNS this was 3–5 However, number of patients involved was limited No No 2023 Yorvipath (palopegteriparatide) Condition: hypoparathyroidism Rare disease: yes Review type: EPAR – Public Assessment Report Type: exit interviews Sample size: not reported Objectives: perception of treatment effect PRO supported: HPES SF-36 There is supportive testimony of palopegteriparatide-treated patients of feeling better at the study exit interview However, based on the comparison to a potentially suboptimal standard of care treatment in the placebo arm, the Committee for Medicinal Products for Human Use decided that results on PROs are not to be mentioned in section 5.1 of the Summary of Product Characteristics No No 2021 Ryeqo (Relugolix, estradiol, norethisterone acetate) Condition: leiomyoma Rare disease: no Review type: EPAR – Public Assessment Report Type: exit interviews Sample size: n = 30/770 Objectives: perspective on PROs assessment of meaningful change of a PRO PRO supported: UFS-QoL BPD Exit interview substudy (MVT-601-037), providing the patient’s perspective on the PROs used in the pivotal studies MVT-601-3001 and MVT-601-3002 MVT-601 037, a substudy to MVT601-3001 and MVT-601-3002, was conducted to obtain patient input via qualitative interviews of English-speaking patients who completed the pivotal phase III studies of 24 weeks on what constitutes a meaningful or relevant improvement on PROs Pain among subjects was among other, measured with the UFS QoL BPD scale to assess three symptoms associated with uterine fibroids that are common to most patients (i.e., heavy bleeding during the menstrual period, passing blood clots during the menstrual period, and feeling tightness or pressure in the pelvic area) The study results suggest that these women could distinguish a clinically meaningful change in their symptomatology A limitation of the study was that the population ( N = 30 from the US) was very small compared with the total number of subjects from MVT 601 3001 + MVT 601 3002 (total sample N = 770, total US sample N = 582) The sub-study was referred to as an exit questionnaire and exit interviews in the document Yes No 2018 Luxturna (voretigene neparvovec) Condition: Leber congenital amaurosis; retinitis pigmentosa Rare disease: yes Review type: EPAR – Public Assessment Report Type: exit interviews Sample size: not reported Objectives: understanding symptom experience PRO supported: not applicable Outcomes of the primary endpoint for subjects also appear to be confirmed by post-test interviews conducted with subjects regarding ability to function in a home setting We have interpreted the ‘post-test interviews’ to be exit interviews in this context No No 2017 Xermelo (telotristat ethyl) Condition: carcinoid tumor, neuroendocrine tumors Rare disease: no Review type: EPAR – Public Assessment Report Type: exit interviews Sample size: n = 35/135 total sample Objectives: understanding symptom experience assessment of meaningful change in key symptoms PRO supported: diary for bowel movements The purpose of the exit interview will be to gain insight and understanding of patients’ experiences with symptoms of carcinoid syndrome and to assess relevance and clinical meaningfulness of symptom improvements (e.g., reduction in bowel movement frequency) In the exit interview substudy, the patient’s view on the benefit of treatment on CS symptoms participating patients described a high BM frequency as the most important symptom of CS; about one-third of patients in the substudy noted a reduction in BM frequency and the majority of these patients described it as meaningful. However, only a subset of patients has been included in this exit interview substudy where out of 73 eligible patients 39 consented to participate; of these only 35 patients have been interviewed. Therefore, the data is of limited value and can only be considered generally supportive. Considered under section on Benefit Risk Assessment and Discussion: In exit interviews study participants described a high BM frequency as the most important symptom of CS which impacted their daily life Yes Yes ClinRO clinician-reported outcome, COA clinical outcome assessment, EMA European Medicines Agency, EORTC QLQ-C30 European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30, EPAR European Public Assessment Report, HPES Hypoparathyroidism Patient Experience Scale, IND investigational new drug, ITR in-trial research, PRO patient-reported outcome, SF-36 36-Item Short Form, T-VASI Total Body Vitiligo Area Scoring Index, TTCD time to first confirmed deterioration, UFS-QOL BPS Uterine Fibroid Symptom and Quality of Life Questionnaire Bleeding and Pelvic Discomfort Scale, VNS Vitiligo Noticeable Scale a Sample size is reported as the number of interviews or surveys out of the entire sample

In summary, Xermelo and Yorvipath were the only two products incorporating in-trial data in both FDA and EMA reviews/labels. While the EMA used in-trial data to describe the treatment effect of Yorvipath (specifically noting that participants felt better), the FDA used it to support the interpretation of meaningful change. Conversely, both agencies used in-trial data to support the interpretation of meaningful change in symptoms (e.g., reduction in bowel movement frequency) for Xermelo. However, the EMA also used the data to support the discussion of its risk–benefit assessment. In addition, both agencies reported limitations regarding the sample size of in-trial interview studies.

Part 3: Reviews of Qualitative Data from HTA Documents

Review of HTA Guidance Documents

Only three HTA bodies—SMC, NICE, and IQWiG [ 39 ]—have published guidance on the use of qualitative research. The SMC [ 41 ] emphasizes the importance of capturing patients’ perspectives through qualitative research. However, due to resource constraints, it recommends integrating individual qualitative studies within a qualitative evidence synthesis (QES). The NICE guidelines acknowledge that qualitative data can be collected through formal qualitative research studies or systematic reviews. NICE will include qualitative studies alongside randomized control trials (RCTs) to consider clinical effectiveness. They also recognize that, in some cases, qualitative empirical evidence may be useful to demonstrate the lack of content validity in measures, such as the EQ-5D. Only Germany’s IQWiG guidelines explicitly reference in-trial data, stating that qualitative research (such as focus groups) can be conducted with RCT participants. Qualitative methods can be used independently (or as a supplement to quantitative studies) to help bridge the gap between evidence and practice. In contrast, France’s HAS [ 42 ] makes only limited reference to qualitative research, focusing primarily on assessing the content validity of PRO measures in real-world evidence contexts. Italy’s HTA guidelines [ 43 ] prioritize the use of validated quantitative instruments for reporting quality of life, and do not explicitly mention qualitative methods. Finally, the Spanish HTA guidelines [ 44 ] do not incorporate qualitative research or QES in their recommended methodology for evaluating medicines.

Review of Qualitative Data from HTA Review of EMA-Approved Drugs

Given that only Scotland, the UK, and Germany have HTA guidelines that incorporate qualitative research, the HTA review focused on EMA-approved products previously identified within these specific markets.

Therefore, we conducted an analysis of the eight EMA-approved products that included ITR data in EPAR public reports and/or EMA labels (Table 3 ), reviewing the corresponding information provided in HTA reports to understand how frequently—and in what context—in-trial qualitative data were reported and utilized. Given the anticipated rarity of in-trial qualitative data inclusion in HTA reports, our review was expanded to include all qualitative data types. We also noted when quantitative PED data were utilized, in order to compare it with the frequency of qualitative data use.

Results of the review are outlined in Fig. 4 . Two EMA-approved products were not assessed by any of the three HTA bodies at the time of our review (Kayfanda and Paxneury), and three products had been reviewed by all three HTA bodies (Xermelo, Luxturna, Ryeqo). Qualitative data were included in the reviews of two products—exit interviews for Xermelo, and a focus group for Luxturna. In contrast, quantitative PED (such as surveys, utility values, and PROs) were more frequently utilized; they were used in five of the six products reviewed by the three HTA bodies. Fig. 4 The use of qualitative data in the HTA reports of the eight EMA-approved products reviewed. G-BA the Federal Joint Committee (Gemeinsamer Bundesausschuss), HTA health technology assessment, NICE National Institute for Health and Care Excellence, SMC Scottish Medicines Consortium, RWE real-world evidence, PED patient experience data, PRO patient-reported outcomes, NHS National Health Service. ^ The focus group was not in-trial, but standalone RWE. ^^ The document discussed PED. However, these evaluations cannot be considered in the benefit assessment

For Xermelo, two exit interview publications based on Phase II and III trial data were considered as part of the Clinical Evidence Review Report assessed by NICE for NHS England in 2018 [ 12 , 17 ]. The data were used to identify outcomes of most importance to patients, particularly patient-reported symptoms associated with carcinoid syndrome. The outcome of the review was that Xermelo was not routinely commissioned by NHS England. However, it remains available to patients through individual funding requests submitted to local health authorities in the UK.

For Luxturna, qualitative focus group data from real-word populations (rather than clinical trial participants) were considered in NICE’s 2019 Supporting Evidence Evaluation Report. A patient focus group was conducted to identify the ‘hidden’ costs of blindness, many of which fall outside the scope of the NHS and personal social services. This evidence was used to illustrate the lifelong burden of inherited retinal disease. These hidden financial costs were considered in the Final Evaluation document [ 45 ]. Luxturna was the first gene therapy for inherited retinal dystrophies to be funded by the NHS.

Cases of Qualitative Data Used in Both Regulatory and HTA Reviews

In the case of Xermelo (for treating carcinoid syndrome), both regulatory agencies used qualitative in-trial interview data (phase III trial) to support the interpretation of meaningful change in symptoms (e.g., reduction in bowel movement frequency); the EMA also considered the data as part of a benefit–risk assessment. These data were also included in the SmPC (EMA label). Publications from the same trial, alongside another publication of phase II in-trial data, were reviewed in a NICE evidence review for NHS England, which resulted in a funding arrangement for individual applications only.

In the case of Luxturna, a gene therapy for treating inherited retinal disease, the EMA used in-trial interview data to confirm the PRO’s relevance in the context of use (i.e., the relevance of ambulatory vision in the context of functioning at home). However, in-trial interview data were either not submitted or reviewed as part of the HTAs we reviewed. Instead, NICE used different qualitative data collected in the real-word population (i.e., focus group) to illustrate the disease’s hidden costs, which resulted in a positive reimbursement decision.

Discussion

Use of In-Trial Interview Data in Regulatory Context

There is still limited use of in-trial interview data in product labels or public regulatory reports. Xermelo is currently the only product that includes in-trial interview data in its EMA label. Ten products include this data in FDA regulatory reviews, and eight products include it in EMA EPAR public reports. This represents <3% of FDA drug approvals, and approximately 1% of EMA drug approvals, incorporating in-trial data in the review of new drug applications. However, when utilized, these data make a significant contribution by supporting the appropriateness of a PRO for product labeling (FDA), confirming relevance of the concepts measured by the PRO (EMA), offering insights on patient experience of symptoms (FDA and EMA), describing the treatment benefits and/or changes in symptoms (EMA and FDA, respectively), and supporting interpretation of meaningful change of PRO measures and anchors (FDA and EMA). Both agencies reported some limitations on the design of in-trial interview studies, either related to the small sample sizes [ 12 , 46 ], study design (e.g., open label), concerns surrounding data quality, and in one circumstance, no review of the sponsor-submitted exit interview data (FDA). Regarding small sample sizes, the authors note that this is standard in qualitative research, where the primary goal is to reflect the diversity of the trial population. Typically, a sample of 20–40 participants across multi-country sites is often sufficient to ensure adequate input from patients about important concepts [ 12 , 46 – 49 ]. However, in the case of rare indications and small clinical studies, even smaller samples are included due to the critical value of patient feedback.

Since the release of regulatory guidance documents from 2018 to 2023, largely produced by the FDA, there has been a notable increase in requests for ITR data by US and EU regulators. However, during the early drug development phases, in-trial interview studies primarily inform the selection and/or validation of clinical trial endpoints, and support internal sponsor decision making. These studies are often not published, which can underestimate the value and actual use of such data. Additionally, we also anticipate a time lag between regulatory requests and the appearance of such data in drug labels and assessment reports. An increase in the reporting of in-trial interview data is expected within a 5-year timeframe after regulatory interest/guidance—reflecting growing regulatory interest in this type of qualitative evidence. Following the EMA’s announcement in 2025 to introduce a dedicated PED section in regulatory submissions, it is anticipated that more in-trial interview data will be integrated into EU regulatory reviews and used to inform regulatory decision making.

Another important consideration is the length of qualitative reports, which can pose challenges for regulators who may not have the time or resources to fully digest extensive qualitative data. As previously mentioned, we noted one circumstance where the FDA did not review the sponsor-submitted exit interview data. In the FDA’s 2024 workshop focusing on PED and in-trial research in drug development, the FDA requested sponsors to clearly indicate in their submissions how the appended qualitative research should be used; specifically, what it was intended to support, and where in the document that could be located [ 7 ]. To address this, sponsors should explore more effective ways to identify, package, and present in-trial interview data in their submissions. This includes summarizing key insights, using visuals, and clearly linking findings to regulatory decision-making criteria. By doing so, qualitative data can be made more accessible and actionable—ultimately enhancing its utility in regulatory evaluations.

Use of In-Trial Interview Data in the HTA Context

Of the eight products that included in-trial interview data reviewed by the EMA, only one also included the in-trial interview data in a subsequent HTA report. We identified a second product that included qualitative data; however, this was from a real-word evidence study, and not in-trial interviews. Both of the HTA reviews were from England and Wales. In contrast, other agencies—particularly Germany and Scotland—have remained cautious in integrating qualitative data into HTA assessments. Instead, they have focused primarily on quantitative patient evidence data, such as PRO measures and utility values, despite available guidance. One possible explanation for the limited use of in-trial interview data in HTA submissions is that the objectives or research questions underpinning the research do not currently meet the needs of HTA bodies. While regulatory bodies value patient or caregiver input on meaningful changes in patient outcomes, perceived meaningful treatment benefit, and risk–benefit assessment of medications, HTA bodies seek broader insights—like unmet need and disease burden. HTA bodies tend to be interested in treatment burden, expectations, satisfaction, and preferences of patients and/or caregivers, as well as factors that can reveal barriers or facilitators to real-world use—all of which can inform HTA recommendations [ 41 , 50 ]. Such data can easily be incorporated into in-trial interview studies [ 24 , 51 ], but this requires early planning during clinical development to align in-trial research objectives with evidence generation strategies that address market access and HTA needs. Moreover, in order not to overburden participants in one interview session, Sponsors may need to consider implementing multiple interviews or a prioritization of research objectives.

The EMA has identified an opportunity to bridge clinical evaluation and market access, thereby contributing to HTA preparedness and downstream decision making for drug reimbursement. They aim to “ensure the evidence needed by HTAs and payers is incorporated early in drug development plans, including requirements for post-licensing evidence generation” [ 52 ]. This approach may also reduce the need for study sponsors to collect some of the additional real-world evidence research that is often required to supplement clinical trial data.

Once data are collected, qualitative reports and publications should focus on demonstrating how the in-trial interview data addresses the specific questions and evidence needs of HTA bodies. Furthermore, qualitative in-trial interview publications may be identified in rapid evidence reviews and qualitative syntheses of individual qualitative studies; these are of particular interest to HTA bodies [ 53 , 54 ]. In the UK, the NICE requires sponsors to supply the EQ-5D [ 55 ] with patient data to determine the cost effectiveness of new treatments. When sponsors and patients have concerns about the appropriateness of the EQ-5D to holistically capture the quality-of-life impact of a particular disease or illness [ 56 , 57 ], conducting qualitative research may be beneficial. NICE guidance acknowledges how “In some circumstances, the EQ-5D may not be the most appropriate measure. To make a case that the EQ-5D is inappropriate, provide qualitative empirical evidence on the lack of content validity for the EQ-5D, showing that key dimensions of health are missing” [ 54 ]. Qualitative data collected at trial entry, with trial participants outlining the quality of life before administration of the treatment drug or technology, could provide data to help support such arguments.

In summary, while there is a growing interest in patient-based qualitative evidence, its systematic use in HTA submissions is still limited. By using ITR to proactively meet the data evidence requirements of HTA bodies, we can enhance the integration of qualitative insights into HTA processes—ultimately leading to more patient-centered healthcare decisions.

Challenges and Limitations

A multisource approach represents a key strength of our research, as it incorporates reviews of methodological and regulatory guidance documents, product labels, and both regulatory and HTA public reports. However, we acknowledge certain caveats and limitations. The scope of our analysis was restricted to newly approved products and did not extend to products approved for additional indications. Consequently, our findings may not fully capture the broader application of in-trial research in extended indications. Moreover, regulatory documents from other regions (i.e. China and Japan) were not included in this review. As the use of ITR in these regions is increasing, these documents should be considered in future research. For HTA reviews, we relied on access to the publicly available HTA reports rather than the full HTA dossier. As a result, it is not possible to verify whether the sponsors submitted in-trial or other qualitative data. This presents the limitation that if the data are not included in the publicly available HTA report, it may be assumed that they were not considered by the HTA body. However, this does not necessarily mean that the data were not submitted. Additionally, the review of HTA reports was limited to a select number of HTA bodies that had included reference to qualitative research in their guidance. Therefore, the results may not represent all HTA bodies.

Conclusion

This research explores the increasing importance of qualitative in-trial interview data in regulatory and HTA processes to drug development. Despite currently limited use in product labels, recent regulatory developments (such as the release of US and EU guidance documents, and the announcement of a dedicated PED section in EMA submissions) show a regulatory commitment to incorporating patient qualitative evidence in drug approvals.

However, some challenges nevertheless remain. These include the underreporting of early-phase in-trial interview studies in scientific disseminations, lengthy qualitative reports that may limit their use by regulators, and misalignment between in-trial interview objectives and HTA evidence needs. Addressing these requires early evidence generation planning, incorporation of regulatory and HTA needs in the design of in-trial interview research, and strategic communication of findings to regulatory and HTA bodies. By doing so, sponsors can enhance the relevance and impact of qualitative in-trial interviews, ultimately supporting more patient-centric regulatory and HTA decisions.

In Germany, IQWiG (Institute for Quality and Efficiency in Health Care) is the scientific HTA body responsible for conducting independent benefit assessments of health technologies; particularly pharmaceuticals. They prepare these reports using predefined methods, and submit them to the G-BA (Federal Joint Committee), which is the decision-making authority. While IQWiG presents the HTA (benefit assessment) reports, the G-BA publishes the official reimbursement decisions. Moreover, the G-BA issues the methodological guidelines (e.g., dossier templates, evidence requirements, subgroup definitions) that manufacturers must follow when submitting reimbursement dossiers under the AMNOG framework. The IQWiG General Methods (version 7.0, September 2023) form the scientific methodological framework used by IQWiG when conducting early benefit assessments—including dossier assessments commissioned by the G‑BA. These methods detail how IQWiG systematically evaluates clinical evidence, incorporates external expert and patient input, and performs cost‑effectiveness analyses.

Acknowledgements

We want to thank Phil Leventhal for his time peer reviewing the manuscript.

Funding

This study was funded by PPD™ Evidera™ Patient-Centered Research.

Declarations

Conflicts of Interest

All authors are employees of PPD™ Evidera™ Patient-Centered Research.

Availability of Data and Material

Not applicable.

Ethics Approval

Not applicable.

Consent to Participate

Not applicable.

Consent for Publication

Not applicable.

Code Availability

Not applicable.

Author Contributions

CD, MK, PWR, MM were involved in the conception of the study. All authors were involved in the analysis, interpretation and manuscript writing.

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