What is the importance of the FDA guidance document ‘Suicidality: Prospective Assessment of Occurrence in Clinical Trials’ and how can I comply?

Michael Federico, Vice President, ePRO Solutions, ERT

What is the importance of assessing suicidal ideations and behaviors in drug trials? How can we best accomplish this assessment during drug development? Is this an area of concern in therapeutic areas previously considered to have minimal psychiatric side effects, such as asthma, acne and insomnia? These are the questions that this FDA Guidance seeks to clarify. In addition, there is also a lack of conceptual clarity and well-defined suicidal behavior terminology that means investigator variability can occur when assessing suicidal tendencies in clinical trial participants. This can then lead to suicidal behaviour and ideation not being consistently or accurately identified.

The need for the monitoring of suicidal ideation and behavior in clinical trials is increasingly recognized as a vital safety requirement. To ensure patients are proactively identified and treated for suicidal systems, the US Food and Drug Administration (FDA) has recently released a guidance document entitled: 'Guidance for Industry Suicidality: Prospective Assessment of Occurrence in Clinical Trials'.

Guidance

The FDA guidance document is intended to assist sponsors in assessing the occurrence of treatment-related suicidal ideation and behavior in clinical trials or drug and biological products. The guidance highlights the increasingly recognized importance of suicidal assessment in psychiatric and non-psychiatric drug trials and provides general principles for how best to achieve effective assessment during the drug development process. In addition, the document highlights the Columbia Suicide Severity Rating Scale (C-SSRS), which comprises a detailed interview as an approved assessment instrument

The 'prospective assessment of suicidal ideation and behavior' recommended by the FDA Guidance involves proactively querying patients about the occurrence of suicidal thinking and behavior, instead of relying on patients to report such occurrences of their own will and the subsequent retrospective classification of these events into appropriate categories. Traditionally, it has been the investigator sites who take the responsibility of producing reliable assessments in clinical trials when new safety requirements have been introduced. Therefore, it is important pharmaceutical companies identify a reproducible suicidal monitoring method to relieve the burden on investigators and facilitate compliance.

eC-SSRS

ERT's eC-SSRS is an electronic self-rated version of the C-SSRS, which was developed in collaboration with the scale authors and provides a cost-effective method of proactively monitoring suicidal ideation and behavior for trial sponsors. The solution was designed in anticipation of the FDA recommendations. Using interactive voice-response technology validated against the C-SSRS, the eC-SSRS is a fully structured interview providing standardized questions, relevant follow-up questions, error-handling routines using Interactive Voice Responsive (IVR) and scoring conventions. Helping to facilitate the FDA requirements, the eC-SSRS solution enables timely identification of possible risks and supplies rapid feedback to study sites for evaluation and follow-up.

Industry

The industry can benefit from using this approach in several ways. Following the C-SSRS algorithm ensures all questions are asked in a consistent manner, resulting in reduced clinical variability. Suicidal risks are identified with prompt feedback to study sites for timely follow up, and the investigator site burden is reduced and sponsors can save as much as 25 percent.

The unique advantages of this new solution were demonstrated in a validation study sponsored by a major pharmaceutical company. The eC-SSRS was used by psychiatric inpatients and healthy control volunteers. The results demonstrated the feasibility, reliability and validity of the eC-SSRS for assessing suicidal ideation and behavior prospectively. A survey of more than 250 clinicians and study managers resulted in 99 percent of respondents agreeing that the eC-SSRS can serve as an effective approach to meeting the FDA regulatory requirements.

Summary

This reliability in scalability for delivery to thousands of patients with accurate recording, storage and documentation of patient responses will allow for easy unproblematic compliance with the FDA guidance document. Using this monitoring method enables pharmaceutical companies to produce high quality research, relieve site burden, reduce costs as well as adhering to the guidelines provided by the FDA and fulfilling the ultimate aim of saving lives.

About

Michael Federico, Vice President, ePRO Solutions, ERT is responsible for managing all aspects of the ePRO Solutions suite at ERT, including product development, operations and sales. Before his current position, Michael was VP for Business Development at ERT. He has over 20 years experience in the healthcare field and holds both Bachelors and Masters Degrees in Engineering from Rensselaer Polytechnic Institute in Troy, New York.