Clinical Research - Suicidality in clinical trials

Suicidality in clinical trials

Michael Federico explains how ePRO technology is improving on investigator assessments in suicidality monitoring

The increased risk of suicidal behaviour and ideation in patients taking medication is of growing concern. Even medicines previously thought to have minimal effect on the central nervous system have been shown to pose a potential risk. Adding to the problem is a lack of conceptual clarity and well-defined suicidal behavior terminology, which increases the risk of investigator variability, thereby resulting in a greater chance of inconsistency in identification of suicidal behavior and ideation.

In response, the US Food and Drug Administration (FDA) now requires an increasing number of drugs in clinical trials to be monitored for causing suicidal tendencies. To help investigators, the agency commissioned researchers at Columbia University to develop the Columbia-Classification Algorithm for Suicide Assessment (C-CASA), which provides an ordered severity classification scheme for suicidal behaviours and ideation. Different classifications include preparatory actions, suicide ideation and self-injurious behaviours.

An example of the importance of compiling reliable and reproducible assessments can be found in recent trials involving nine antidepressants and more than 4,400 paediatric patients. During these trials, the FDA identified a small signal for increased suicidality in children and adolescents receiving antidepressants compared with those receiving a placebo (4% compared with 2%). This difference highlights the importance of performing consistent assessments.

The electronic solution

Electronic solutions is one answer to complying with the new requirements. A recent development in this area is the use of electronic patient reported outcomes (ePRO) using an automated telephone-based eC-SSRS program for the collection of patient data.

ePRO technology is commonly identified with patient diaries, but it is now increasingly being used in a wide range of clinical programmes, from accelerating patient recruitment, providing consistent screening, unbiased clinical assessments, improving retention, increasing compliance, real-time safety monitoring and checking, and more recently, in the area of suicidality monitoring.

The technology uses a telephone interface as a computer terminal to collect sensitive suicidality data directly from trial subjects. Subjects call a toll-free number and enter their responses using the familiar telephone keypad. The automated telephone-based eC-SSRS program identifies changes in suicidality signals. While collected data go directly into the vendor’s central database, certain patient-reported answers trigger alerts to the trial site by a pair of call centers and contact is maintained until the investigators are alerted and patient follow-up is initiated.

ePRO solutions emulate the ideal human interviewer, but unlike traditional interview techniques, the eC-SSRS programs specific algorithms to ensure all relevant questions are asked, while branching around irrelevant questions. Patients are more likely to disclose sensitive subject matter in relation to suicidality in computer interviews than to human interviewers, which allows highly sensitive questions to be asked and replies received in a non-judgmental environment.

The system also allows scalability for delivery to thousands of patients at any one time, accurate recording, storage and documentation of patient responses, and procedural reliability in content and delivery. Indeed, a recent study reported in the Journal of Clinical Psychiatry utilising the Treatment for Adolescents with Depression Study (TADS) database showed that self-rated instruments of suicidality and depression are more sensitive in detecting suicidal risk than rating scores supplied by a clinician.

As with all automated patient tests, such as clinical labs and ECGs, the eC-SSRS is not intended to replace clinical judgment but to provide clinicians with useful, unbiased information for exercising clinical discretion regarding patient safety.

By allowing clinical trial investigators to capture sensitive information directly from patients without face-to-face interviews, ePRO solutions combined with eC-SSRS are helping to reduce the time and cost associated with clinician-administered suicidality assessments. In addition, the technology provides a standard of procedural reliability that surpasses that of human investigators performing suicidality monitoring assessments, thereby helping to meet the primary objective – addressing the new regulatory concerns.

Michael Federico is Vice President – ePRO, ERT, a company that provides technology and services to the global biopharmaceutical and medical device industries

ERT is organising an educational pre-conference workshop co-hosted with Healthcare Technology Systems (HTS) at the Clinical Trials in CNS conference, entitled Assessing Suicidality in Clinical Trials and Addressing the Regulatory Directives, on 24 November 2009, in London, UK.

For details go to: www.smi-online.co.uk