Innovations in Gastrointestinal Disease Clinical Trials and DCTs

Without training only 24% of GI patients understand what rescue medication is and that number improves three-fold with even a small amount of patient training.

Digital Patient Training is Essential

While the endpoints in gastrointestinal clinical trials typically require the report of common patient symptoms and assessments at the clinic, studies show that many commonly used terms are not uniformly or well understood by patients. Our studies have shown that many of the concepts associated with primary endpoints in GI studies present as nebulous to patients. For example, at SPRIM Health, we have learned that without training only 24% of GI patients understand what rescue medication is and that number improves three-fold with even a small amount of patient training. Further, reports on abdominal pain can be difficult for patients to do accurately as approximately half do not consider the upper 3rd of the abdomen as their abdomen in the absence of training. Similarly, stool counts can be very difficult to report without training as the definition is open to interpretation as to what counts as a single episode. Terms such as bloating and distended mean the same thing to about half of patients and different things to the other half. Lastly, minimization of the placebo effect through training is also a necessary component in improving the signal to noise ratio. As such, there is a critical need for digitally training patients in GI clinical trials and hybrid studies.

eClinRO and Training of Site Staff

Digitally programming of ClinROs is critical to ease burden on site staff, remove errors induced by manual scoring and enable integration of lab values with patient and clinician reported outcomes. Digital training of site staff minimizes rater variability and improves the signal acquired from such methodologies.

Development and Validation of Novel ePRO

In GI trials, the primary endpoints are frequently a combination of ePRO in conjunction with eClinRO using tools such as the MAYO or CDAI, which are notoriously known for their poor sensitivity. Thus, it is essential to develop and validate the content for GI symptoms eDiaries using cognitive debriefing and usability testing patient interviews. Diary design needs to be simple, the content clear and engaging with minimal burden on patients and observers for pediatric studies. Given the routine and frequent nature of GI events, it is critical to utilize ePRO technology to facilitate compliance by using notifications, reminders and alarms. Further, the technology can enable both algorithms and central monitors to respond to potential AEs/SAEs in real and near real time.

Next Generation of ePRO

In recognizing some of the pain points in GI trials, pediatric trials especially, are limited by a caregiver’s ability to observe and neutrally provide eObsRO information. At SPRIM Health, we conducted studies that compared stool consistency ratings from caregivers using the Bristol Stool Scale to pediatric GI clinician ratings. We found that caregivers over-reported complete watery stool compared to clinical experts and under-reported intermediate and hard stool consistencies versus clinical experts. As such, we developed a novel methodology to improve the signal to noise ratio and optimize outcomes. Using technology, caregivers collect and upload stool images using their personal smartphones and central raters provide ratings. Using images helps eliminate bias while providing a better, more accurate and complete data set. Our technology enables removal of personal identifying information, resolution/sizing of images and ensures proper lighting and angles for image capture. There is a reconciliation of primary and secondary raters scoring and consensus and data monitoring and remediation.