Dr. Michael McKelvey, CEO of ERT , a leading provider of centralized ECG and eClinical technology, ePRO, and other services to the biopharmaceutical, medical device, and related industries, discusses the benefits of electronic patient reported outcomes (ePRO) tools for assessing and monitoring suicidality in clinical drug trials.
Over the years, there has been increasing concern regarding suicidal ideation and behaviors in patients taking medications. Pharmaceutical drugs can influence chemicals that enter the brain and affect emotions, thoughts and behaviors. It has been shown that even medicines used to treat diverse indications, such as acne, asthma and insomnia, may affect or even cause suicidal tendencies.
In recent trials involving nine antidepressants and more than 4,400 pediatric patients, the U.S. Food and Drug Administration (FDA) identified a small signal for increased “suicidality” in children and adolescents receiving antidepressants compared with those receiving a placebo (4% verses 2%). This highlighted the importance of reliable and accurate assessments.
The need for prospective monitoring of suicidality in clinical trials of medications seeking regulatory approval is increasing, including non-psychiatric patients and medications. In response to the possible psychiatric side effects of such medicines, the FDA has issued guidelines regarding the assessment of suicidality during clinical trials.
Suicide ratings scales
The Columbia-Suicide Severity Rating Scale (C-SSRS) is a semi-structured clinical interview developed by researchers at Columbia University. While the C-SSRS has been used in sponsored clinical trials for over four years, data regarding reliability has not been published. However, clinician-administered assessments are known to be plagued by rater variability, which can be even greater when clinicians have minimal mental health training. Even after extensive training, rater skills deteriorate over time. Such variability decreases the reliability and accuracy of these assessments and ultimately their value in detecting suicidality signals.
Given the growing range of medications being evaluated for suicidality signals in clinical trials, development of a fully-structured, procedurally-reliable and replicable process for prospectively obtaining SSRS data is needed. Studies have demonstrated that patients tend to disclose more suicidal thoughts and behaviors to non-human computer interviews than to clinicians during an interview.
ePRO driving automated safety alerts
ePRO tools have distinct advantages in suicidality monitoring over both face-to-face and paper-based data collection methods. For example, ePRO offers confidentiality since information is collected directly from patients without the involvement of another human being. Direct patient-computer interviews can be conducted by text-based assessments or by interactive voice response (IVR) technology using telephones as a ubiquitous and low-tech alternative to PC-based technology.
Automated IVR-SSRS programs reliably and accurately identify changes in suicidality signals, which in turn increase patient safety. Incorporating comprehensive suicide assessments into clinical trials that are backed by a response system assures swift reaction to suicide concerns. In ERT clinical trials, certain patient-reported answers trigger alerts to the trial site by a pair of call centers that maintain contact until the investigators are alerted and the patient is successfully contacted. This quick response system ensures that the responsible investigator is notified and the patient is reached.
In clinical trials, patient responses are obtained, checked for validity and the data stored in an electronic database. IVRS provides the opportunity to ask highly sensitive questions and receive replies in a non-judgmental environment. Using computers and phones to automate suicidality assessments reduces the risk of false negatives and maximizes signal sensitivity to evaluate the true effects of new compounds and drugs.
IVRS is not intended to replace clinical judgment but to provide clinicians with useful, unbiased information for exercising clinical judgments regarding patient safety. The reliability and validity of the assessment process is a primary determinant of data quality. Combining computer-automated IVR interviews alongside clinician judgment can facilitate accurate, efficient, thorough assessment of suicide risk and provide clinicians with valuable information for evaluating and managing patient safety.