HP&M Attorney Pens the Case for Use of Patient and Caregiver Perception of Change Assessments in Rare Disease Clinical Trials

On March 16, 2019, Advances in Therapy published a commentary authored by HP&M Attorney James E. Valentine along with co-authors Marielle Contesse, Tracy Wall, and Mindy Leffler.  The paper sets forth the case, and provides a methodologic overview, for incorporating qualitative patient and caregiver video interviews into clinical trials as one method for rigorously capturing patient experiences and caregiver observations (referred to as PPC and CPC Assessments).  This paper comes on the heels of a recent National Academies of Sciences workshop report on the Science of Patient Input that cited James Valentine’s recommendation for this type of methodology as a novel way to solicit patient experiences in clinical trials (see previous coverage here).

James Valentine and his co-authors propose the novel PPC and CPC Assessments to help overcome the many methodological challenges to measuring treatment effect in rare diseases.  Because of the small number of patients and the nature of rare diseases, study design often involves a tension between properly powering a study and minimizing heterogeneity of the study population.   Broadening the inclusion criteria to power the study can result in increased heterogeneity, which then makes it difficult to select outcome measures with sensitivity across the study population.  This diversity, combined with the novelty of the drug being assessed, may mean that it is not always possible to predict the different ways treatment benefit might manifest across patients, further complicating the selection of outcome measures.  Lastly, there is often a lack of validated, disease-specific outcome measures, which leads to borrowing outcome measures that were used in other diseases, which lack sensitivity.  These methodological challenges in rare disease clinical trials can lead to uncertainty about whether some trials fail as a result of failed measurement of the drug effect rather than failed treatment.

In an effort to:

(1) create a bulwark against type 2 errors as a result of these challenges to assessing treatment effect in rare diseases,

(2) maximize the contribution to the scientific data by each and every rare disease patient volunteering to participate in studies, and

(3) embrace the principle of “patient-focused drug development” to ensure that the breadth and depth of patient insight into their experience is considered in FDA approval decisions,

the PPC and CPC Assessments can be employed to capture patients’ and caregivers’ perceptions of change using semi-structured video interviews that can be implemented before, during, and after a clinical trial.  Furthermore, these qualitative interviews can be done in the clinic, over the phone (via a mobile application), or with a web conferencing system.  The paper provides an in-depth discussion of how to design and implement the PPC and CPC Assessment methodology based on the experiences of each of the authors who come to this as regulatory experts, patient advocates, clinical researchers, and/or drug developers.

The paper concludes that seeing the patients and caregivers on video and hearing directly from them about their experiences can be important information for regulators, payers, and prescribers.  Among other things, this kind of patient experience report may provide context to the meaningfulness of clinical trial endpoints, where patients and their caregivers voice how changes experienced during a trial impacted how they felt or functioned in daily life.  Or it may encourage regulators and payers to consider an impact on patient quality of life that may not have been documented in the study’s more conventional outcome measures.  Finally, the 21st Century Cures Act requests FDA to include a description of how patient experience data was obtained and reviewed by FDA, and this new methodology would provide a means tailor-made to this purpose.