In an earlier blog, we discussed why and when clinical trial sponsors and CROs should include Suicidal Ideation and Behavior (SIB) monitoring in clinical studies to keep patients safe and meet regulatory requirements. We mentioned that the Columbia-Suicide Severity Rating Scale (C-SSRS) is the only risk assessment tools specifically identified by the FDA as acceptable for use in clinical trials.
Here we review the different approaches sponsors can take to implementing this important assessment in their clinical trials and the pros / cons of each.
What are the options for capturing SIB assessments via the C-SSRS during clinical trials?
During clinical trials, SIB assessments were traditionally collected by a clinician interviewing the patient using a paper-and-pencil version of the C-SSRS. These Clinician Reported Outcome (ClinRO) assessments proved burdensome to clinicians who had to sort through paper forms for historical data and to site staff who had to copy paper forms for monitors and sponsors.
Sponsors now have the option of providing digital tablets for clinicians to use when administering the C-SSRS. Although this solution overcomes some of the burden associated with the paper-and-pencil approach (i.e., branching logic and device error checks eliminate missing / invalid data), the data it collects is still subject to inter-rater bias and is less accurate than when patients complete the assessments themselves.
Is there a patient (self-report) version of the C-SSRS?
Yes. The eC-SSRS is a unique, electronic monitoring solution which enables patients to complete self-reports of the SIB assessment. This computer-automated version of the C-SSRS is also identified by the FDA as acceptable for use in clinical trials.
With the eC-SSRS, patients complete the SIB assessment on their own, and are automatically sent to the appropriate follow-up questions (if any) based on their responses. The eC-SSRS provides significant benefits over clinician-administered assessment options (Figure 1).
Figure 1: Comparison of C-SSRS Implementation Options
What are the benefits of patient self-rated SIB assessment?
Improved Patient Candor = More Accurate Data
Self-reported assessments are better at detecting suicide signals than clinician-rated assessments, because when patients self-report, they are more comfortable, honest and open with their answers. The self-rated eC-SSRS eliminates the inter-rater bias that occurs during traditional clinician-patient interviews and enables patients to complete assessments confidentially and with more candor1, which leads to more accurate data.
Real-Time Alerts Keep Patients Safe
By enabling patients to self-report SIB assessments using the eC-SSRS, site staff, caregivers and supervisors receive real-time alerts any time a positive response is recorded, enabling them to intervene to ensure patients’ safety. This real-time data enables trial sponsors to quickly and accurately identify treatment-emergent SIB, which enables faster, better-informed ‘go / no-go’ decisions regarding the safety of the drug in development.
Reduces Patient and Clinician Burden
Another important consideration is that, because the eC-SSRS is relatively brief, most patients without SIB can complete it quickly and with less burden than clinician-rated assessments. In fact, in one study conducted by a global biotechnology company, patients completed the self-rated eC-SSRS in four minutes or less.2
The eC-SSRS enables clinical trial sponsors and CROs to gain greater visibility into patient safety and increased confidence in meeting regulatory guidance on SIB during clinical development. The resulting reliable and high-quality data allows sponsors and regulators to document the drug’s true effect on suicidal ideation and behaviors.
Rinah Yamamoto, PhD is a Senior Science Advisor at ERT.
1 Yamamoto, et. al. “Patients with psychiatric diagnoses indicate willingness to report suicidal ideation and behavior more honestly by self-report than in face-to-face interviews,” 2016 CNS Summit