Beyond Numbers: The Value of In-Trial Interview Data for Regulatory and Health Technology Assessment (HTA) Decision-Making
Regulatory health authorities now recognize the significance and value of in-trial qualitative interviews in gaining greater insight into the patient experience. These interviews provide supplementary data that can greatly enhance clinical trial design, interpretation of findings and product value for payers while addressing the unmet needs of patients.
Speakers:
- Carla Dias Barbosa, MSc, senior research leader & in-trial research lead, patient-centered research
- Miriam Kimel, Ph.D., senior research scientist, patient-centered research
- Karen Bailey, Ph.D., research scientist, patient-centered research
- Paulina Rolska-Wójcik, Ph.D., director, value & access consulting
Key insights from this webinar include:
- Advantages of utilizing in-trial interview data in drug development
- Use of in-trial data by regulators and health technology assessment (HTA) bodies
- Methodological guidance and current trends
- Recommendations for evidence generation planning
- Opportunities for reimbursement decision-makers
Expert Insights: Webinar Q&A
Live webinar questions answered by our speakers. We would like to thank all attendees for your interest and questions.
Q1) Why do you think 2022 had a greater number of drug interviews per U.S. Food and Drug Administration (FDA) data?
Although the percentage of any interviews being reviewed by the FDA was highest for 2022 (14%), the actual number of reviews (n=5) was comparable across years (5-7 reviews in five of the eight years evaluated from 2017 to 2023). However, 2022 had the lowest number of reviews (n=37) compared to the other years (typically around n=50). The lower number of studies reviewed may have reflected the COVID-19 pandemic and its impact of clinical research leading to fewer drugs being ready for review.
Of note, the interview results reviewed in 2022, as well as the other years, were primarily to establish content validity of patient-reported outcome measures for inclusion in the label.
Q2) Are there any suggestions to increase patient participation in rare diseases?
Interviews are typically positive experiences for patients who contribute to their engagement in the study. Most patients want to be heard, and they appreciate the opportunity to discuss their perspectives and experiences with a skilled, non-judgmental and interested interviewer. It is important to convey the importance of the interviews to the patients during the consent process so that they understand why their contribution is valuable.
Of note, the participation rate in in-trial research is generally higher among patients with rare diseases because unmet needs and the need for new therapeutic options are higher.
Regarding patient recruitment in your clinical trials, you can consider working closely with patient advocacy groups as partners to reach rare disease patients. Do so in a way that is collaborative and involves them in the wider co-creation in study design (rather than just recruitment vendors).
Q3) I appreciated the distinction that Paulina made between patient engagement inputs and qualitative evidence. Can she elaborate on the differences between the two?
The distinction between patient engagement inputs and qualitative evidence is indeed important and nuanced.
Simplified definitions:
- Patient engagement input refers to the various activities that can take place to facilitate the active involvement of patients in various stages of health care, research or policymaking processes. This could involve sharing experiences, providing feedback on treatment plans or trial design, or collaborating on health care decisions. It can be done informally and in an ad hoc way or it can be done more systematically (see below).
- Qualitative evidence refers to robust and systematic collection of information to capture patient (or caregiver) perceptions collected through qualitative research methods, such as interviews, focus groups or observations. It is one but not the only way to engage patients.
Key Differences:
- Focus: Patient engagement inputs focus on directly involving patients in health care decisions, research development or policy development, whereas qualitative evidence is about the systematic gathering of detailed insights to understand patient experiences, beliefs or perspectives, which is on a par with quantitative evidence.
- Process: Patient engagement is an active process in which patients participate in shaping decisions. It can be done via various activities that don’t necessarily meet definitions of robust research (e.g. patient advisory boards). Qualitative evidence should be collected a way that meets evidence of good quality research (there are many checklists available to do this) and offers a deeper understanding of patients’ experiences and perceptions, helping to highlight issues that may not be captured by quantitative data alone, such as meaningfulness of change or unmet needs.
- Outcome: Patient engagement is aimed at influencing decisions, policies or practices, while qualitative evidence is about providing context and deeper understanding to identify for example relevant patient outcomes and align measurement strategies.
Both approaches are essential in health care but serve different purposes — one being more participatory and the other more research-oriented.
It is also worth noting that both patient engagement inputs and qualitative evidence can be used during the regulatory or health technology assessment processes to support decision-making.
Q4) Do you see exit/in-trial interviews being used for acceptability and tolerability assessment in a pediatric trial?
There are many reasons for conducting in-trial interviews, including treatment acceptability and tolerability. This information is valuable to address questions about the risks versus benefits of a new drug for both regulators and health technology appraisers. This is particularly relevant for indications or populations in which limited treatments or little information are available. For example, many drugs approved for adults are used off-label in pediatric populations and not evaluated in clinical trials. Conducting in-trial interviews within this age group would enhance the knowledge base around the acceptability and tolerability of new drugs in this population and would be of interest to regulators and health technology appraisers, as well as a valuable contribution to the literature (if that also is a goal of the research).
It should be noted that in pediatric populations, researchers should pay particular attention to the development of the interview guides and consider using creative activities1 such as drawing to help children provide useful information during the interviews. Additionally, interviews should be performed without parents whenever possible to capture the perspective of the children. For young children (younger than 5 years old) or young patients not able to self-report, you can consider collecting the perspective of family members or caregivers to report on patients’ treatment experience.
1 Matza LS, Patrick DL, Riley AW, Alexander JJ, Rajmil L, Pleil AM, Bullinger M. Pediatric patient-reported outcome instruments for research to support medical product labeling: report of the ISPOR PRO good research practices for the assessment of children and adolescents task force. Value Health. 2013 Jun;16(4):461-79. doi: 10.1016/j.jval.2013.04.004. PMID: 23796280.
Q5) Are physician/trial PI interviews to validate ClinROs considered exit/in-trial interviews?
The short answer is, “it depends.”
If the study objective cannot be addressed with physicians outside the trial and if the physician/trial PI perspective on the ClinRO is based on their experience using this instrument with patients involved in the clinical trial, the answer is yes, this is considered as in-trial research. The research can be conducted following an embedded design (under the auspices of the clinical trial) or associated using an independent protocol.
Q6) With embedded design with the same ICF, is the interview portion optional or mandatory? Are exit interviews usually conducted to reach saturation, therefore a small sub-sample of the trial population?
The short answer is, “it depends.” Either approach (i.e., optional interviews or more mandatory) can be used and is dependent on multiple factors that are specific to the trial, including the research objectives, the countries where the interviews are being conducted, or the trial population.
For example, in a study with a rare disease population, the interviews may be more mandatory to obtain a relatively larger sample size or optional for concern that these participants may be overburdened and may not participate in the trial at all if too much is asked. However, the interviews cannot be strictly mandatory. As with any study activity the patients are consenting to participate in, they have the right to withdraw from the interviews at any time without any negative consequences.
Regarding saturation, we typically assess saturation to ensure that the sample size is sufficient to address in-trial research objectives. However, depending on the study objectives (e.g., unexpected effect of treatment), saturation of concepts may not be applicable.
Q7) Is there a role for qualitative research with non-patients in clinical trials? Perhaps spending time with the providers or other staff providing the treatment to understand what impact adding this treatment would have on their workloads or other aspects of practice?
We have seen an increased interest in conducting in-trial interviews with caregivers of participants in the trial, not only when they are needed to give a proxy view (e.g., pediatrics and people with memory issues), but also to capture the burden of caregiving so it can be considered under cost-effectiveness (this was the case with the NICE example for Luxturna that we shared on the webinar).
Additionally, principal investigators/study coordinators and/or study nurses who are in direct contact with patients can provide valuable information about the drug (e.g., its use, convenience, perceived effectiveness, barriers to implementation in practice). as well as information about patients’ experiences using it in a clinical trial (tolerability, acceptability). Interviews with principal investigators/staff may be listed as an optional study activity within the trial.
Q8) Do you think that the lack of use of qualitative data in HTA is hampered by the lack of adequate tools translating patient comments?
Possibly. For example, in the case of NICE, patient insights and views can be submitted in different ways and could include comments from 1-2 patients through to the systematic collection from a suitable sample. Until recently we did not have the HTA guidance on conducting qualitative research or literature reviews — now we do. It may also be because sponsors are not aware that data collected more systematically and meeting the standards of scientific evidence is of value to HTA bodies. Qualitative data collected by methods that meets regulatory standards will be suitable for HTA, so there are missed opportunities if sponsors are not thinking about using such data for the purposes of reimbursement and commercialization later down the pipeline.
Q9) Are these qualitative/quantitative data exit studies related to patient preference studies?
In-trial research can address many objectives including eliciting patient preference information (PPI) (e.g., assessments of the desirability or acceptability to patients of treatment attributes). Qualitative PPI collected in the context of a clinical trial can provide valuable insights into which outcomes, endpoints or other attributes are most valued by patients and which factors affect patients’ perspectives. Qualitative PPI can complement quantitative PPI that can be collected outside or alongside of the clinical trial.
Q10) Do you recommend in trial interviews for ANDA drugs?
Yes, it can add value. For ANDA, generic applicants must scientifically demonstrate that their product performs in the same manner as the innovator drug. If this is extended into patient reported outcomes, then harnessing the voice of patients in non-inferiority trials can help support this evidence. Where applicable, in-trial interviews can also help identify additional benefits related to the delivery of the products such as treatment convenience, reduced administration burden, etc.
Learn more about conducting qualitative interviews within clinical trials