Why “Participant Voice and Experience” Matters in Clinical Research
Kendal K. Whitlock
Decentralized Trials & Research Alliance, Research Curriculum
Initiative 3C

uring the early months of the coronavirus pandemic, drug development was accelerated in response to the sudden increase in morbidity and mortality. However, as Emergency Use Authorizations (EUA) were issued but later revoked (e.g., hydroxychloroquine and chloroquine), public confusion grew about which therapies were effective and safe. By summer 2020, clinical research methods were under a global spotlight and trust in science has been on trial ever since.

Without the knowledge of demographic variations (e.g., between men and women, different age groups) derived from a rigorous clinical investigation, the optimal use of medicines remains unknown and is based on a limited participant pool. For future therapies to have broad generalizability, learning from the participant’s voice and experience (PVAE) in clinical research is an urgent necessity. This article highlights key strategies used in clinical research to capture the PVAE based on existing regulatory frameworks.

The Food and Drug Administration’s (FDA) thinking has evolved over several decades, and the inclusion of participants from different subgroups by gender, age, race, and ethnicity in drug development trials is now well-established. The Action Plan for the FDA Safety and Innovation Act (FDASIA), for example, ensures the completeness and quality of data submitted in support of drug approvals. One output from FDASIA was the Patient-Focused Drug Development (PFDD) Program, designed to engage the PVAE in the development of medical products and regulatory decision-making.

The modernization of medical product development and review through provisions (e.g., use of real-world evidence and patient experience data) described in the 21st Century Cures Act aims to accelerate the development of novel medicines and improve efficiencies. PVAE adds value by providing therapeutic choices more rapidly and with a greater understanding of use.

FDA is addressing PVAE issues via the four-part PFDD guidance for enhancing the incorporation of the PVAE in medical product development and regulatory decision-making. This article describes six strategies to capture the PVAE in clinical research in alignment with the existing regulatory framework. For this, it is important to understand PFDD-Guidance 2, which emphasizes the PVAE from the following perspectives: (1) PVAE as an enabler of greater access to evaluating novel medical products and sharing insights on product adequacy and usability; (2) Regulatory Affairs as it includes the PVAE in clinical research per regulatory framework, expecting accurate testing of the safety and efficacy of investigational medical products in diverse races and ethnic populations; and (3) Sponsor as it improves recruitment, enrollment, and retention, making trials more efficient and less costly.

Six Strategies for PVAE Assessment in Clinical Research

  1. The first strategy is to identify and understand what’s important to participants. It is used in early planning evaluations to take a holistic approach to understanding participant populations and enable foundational knowledge when designing clinical trials.
  2. The second strategy uses qualitative methods such as individual interviews or focus groups involving up to eight people. Both methods allow researchers to capture the in-depth meaning of clinical research-related topics discussed with prospective participants. The validity and accuracy of these methods depend on asking carefully crafted questions to control for bias, an FDA expectation. Bias can be controlled by distilling the essence of the PVAE when considering how best to frame questions. Bias can also be mitigated by having a skilled and impartial moderator for interviews or focus groups who may use prompts for participants to expand upon the initial information shared on a topic of relevance connected with a clinical trial. This is important to accurately evaluate a novel medical product. A moderator with predetermined expectations about the participants’ responses can risk the discovery (and quality) of insights by introducing bias in assessing the PVAE. A moderator’s role is not to judge responses when using qualitative PVAE assessment methods.
  3. The third strategy uses quantitative PVAE assessment methods. Self-administered or interviewer-administered surveys may be used to quantify insights for analysis and interpretation. For example, an exit survey enables screening and the collection of PVAE data following the last trial visit. An interviewer-administered survey may be more prone to bias and cost more than a self-administered survey, aspects to be considered when using these methods for specific purposes to support clinical research.
  4. The fourth strategy combines qualitative and quantitative sequential methods for PVAE data collection. For instance, a mixed strategic method could be useful to learn from participants and caregivers in a specific disease area via a series of in-person focus groups, followed by self-administered surveys. This strategy offers the major advantage of allowing researchers to build a multilayered understanding of PVAE, including participant needs, but it may also generate conflicting data, in which case, a plan to analyze and understand potentially conflicting information is strongly recommended.
  5. Clinical research sometimes presents barriers for participants to conduct self-reporting assessments. In such cases, managing barriers to self-reporting may be instrumental to gather the PVAE. This strategy incorporates methods to allow participants with different abilities (e.g., speaking, hearing, and seeing) to self-report their needs and experiences in clinical trials.
  6. Lastly, the sixth strategy involves the use of social and digital media to collect both qualitative and quantitative PVAE data from clinical research, which offers convenience to participants and researchers, but it needs to control for identity verification and privacy and confidentiality of participants as done in digital medicine.

The evolution of the PVAE is a dynamic process, embraces diversity and inclusion, is multifactorial, and leads to more accurate safety and efficacy data to evaluate novel medical products. It is growing and recognized in clinical research. It is supported by an evolving regulatory framework, and it is impacted by the explosive growth of digital medicine, in which the PVAE is a prominent feature.