Using ePRO solutions to ensure compliance with FDA guidelines on the prospective assessment of suicidal ideation and behavior

By Michael Federico, Vice President, ePRO Solutions, ERT

Preventing, monitoring and understanding treatment-related suicidal ideation and behavior relies upon proactive assessment and identification. However, there has been a lack of clarity and standardized approaches in clinical trials when assessing suicidal tendencies. As a result, drug safety efforts have often been undermined. To ensure patients are proactively identified and treated for suicidal symptoms, the U.S Food and Drug Administration (FDA) recently released a guidance document, entitled: ‘Guidance for Industry: Suicidality Prospective Assessment of Occurrence in Clinical Trials’.

The FDA document was released September 10^th, 2010 with the intention of clarifying the need and providing direction regarding the assessment of treatment-related suicidal tendencies in clinical trials of drug and biological products. This article will explore the general principles recommended in the FDA guidance and how ePRO Solutions can successfully facilitate compliance to these recommendations.

FDA Recommendations

There is increased concern regarding suicidal ideation and behaviors in patients taking medication as part of clinical trials. Significant evidence has been produced that demonstrates medicines which were previously thought to have minimal effects on the central nervous system actually pose a potential suicidal risk. These drugs include isotretinoin and other tretinoins, beta blockers, reserpine, smoking cessation drugs and drugs for weight loss. Adding complexity to the issue is the lack of conceptual clarity and well-defined suicidal behavior terminology which means investigator variability can occur. As a result, this can lead to suicidal behavior and ideation not being consistently and accurately identified.

The FDA guidance places emphasis on the need for "the prospective assessment of suicidal ideation and behavior", which "proactively queries patients about the occurrence of suicidal thinking and behavior, rather than relying on patients to report such occurrences spontaneously, followed by retrospective classification of events into appropriate categories"(Lines 7-9).

The Columbia-Suicide Severity Rating Scale (C-SSRS) is recommended in the Guidance as a valid instrument for the assessment of suicidal ideation and behavior. The C-SSRS is highlighted by the FDA Guidance document as a recommended and validated means to prospectively and systematically assess suicidal tendencies. The C-SSRS clearly identifies risky ideation and behaviors, providing more consistent research data which, in turn, improves aggregated analyses and better informed risk analyses.

An example of the importance of compiling accurate and reproducible assessments of suicidal ideation and behavior can be found in recent trials involving nine anti-depressants and more than 4,400 pediatric patients. Throughout these trials, the FDA identified a small signal for increased 'suicidality' in children and adolescents receiving anti-depressants, compared with those receiving a placebo (4% versus 2%). Given the growing range of medications being evaluated for suicidal signals in clinical trials, it has become clear that the development of a fully-structured, reliable and replicable process for prospectively obtaining C-SSRS compliant data is needed.

Facilitating Compliance with ePRO Technology

Over recent years, ePRO technology has revolutionized data collection in clinical trials and is increasingly used to support drug development, whilst being acknowledged as a valuable technology by regulatory agencies. The increase in usage of ePRO is based primarily on the technology's capacity to facilitate the streamlined delivery of high-quality patient-reported data.

Advantages of ePRO solutions over paper-based data collection are significant. ePRO solutions ensure and document that patients report their data on time and accurately, enabling investigators to directly and consistently monitor their patients and increase overall data validity and patient safety. In addition, phone based ePRO systems are simple and accessible for all users, requiring no hardware training and performing error and validation checks to ensure that there are no transcription or scoring errors.

The Power of eC-SSRS

Developed in collaboration with scale authors and in anticipation of the FDA Guidance, the eC-SSRS,is an electronic self-rated version of the C-SSRS. It provides a cost-effective method of prospectively monitoring suicidal ideation and behavior for trial sponsors. The eC-SSRS technology utilizes a user-friendly telephone interface to collect sensitive suicidal data directly from trial subjects. The program can reliably and accurately identify changes in suicidal signals which, in turn, increase patient safety. Unlike traditional interview techniques, the eC-SSRS ensures that all relevant questions are asked in a consistent manner. C-SSRS also benefits from procedural reliability in content and delivery, scalability for delivery to thousands of patients at any one time and accurate recording, storage and documentation of patient responses.

Electronic recording of research assessments allows for timely identification of potential risks with prompt feedback and reporting to study sites for follow-up and evaluation. Certain patient-reported answers trigger alert calls to the trial site so patient follow up can be initiated. Another benefit is that patients are more likely to disclose sensitive subject matter in computer interviews than they will to human interviewers. Highly sensitive questions can be asked and replies received in a non-judgmental environment. ePRO solutions emulate the ideal human interviewer, comprehensively and consistently asking questions covering relevant topics The risk of false negatives is reduced and signal sensitivity is maximized to efficiently evaluate the true effects of new compounds and drugs. A recent study utilizing the Treatment for Adolescents with Depression Study (TADS) database highlighted the fact that self-rated instruments of suicidal ideation and behavior and depression are more sensitive in detecting suicidal risk than rating scores supplied solely by a clinician. The ePRO solutions provide objective and accurate data which work to inform a clinician's overall judgement, enabling an accurate and efficient assessment of risk.  

In a recent survey of more than 250 clinicians and study manager, 99% of respondents agreed that the eC-SSRS can serve as an effective approach to meeting the regulatory requirements recommended in the FDA guidance. An impressive 97% of respondents stated that using the coordinated self-rated solution versus a clinician-only administered approach could reduce their costs. Confirming the positive move towards the use of eC-SSRS, ERT, a global provider of technology and services, has processed over 21,000 eC-SSRS assessments since it became available to customers.

Conclusion

The recently released FDA Guidance document on Suicidal Monitoring highlights the importance of suicidal ideation and behavior assessment in psychiatric and non-psychiatric drug trials and provides general principles for how best to achieve effective assessment throughout the drug development process. In addition, the document highlights the Columbia Suicide Severity Rating Scale (C-SSRS) as an approved assessment instrument.

The eC-SSRS solution is an electronic version of the C-SSRS, which utilizes interactive voice-response technology validated against the C-SSRS. 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.

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. Combining eC-SSRS interviews and immediate, automated, standardized reports of the patient's responses with clinician judgment will facilitate accurate, efficient, and thorough assessment of suicidal risk.

For further information on ERT and its technology and services please email info@ERT.com, call +1 215 972 0420 or visit www.ERT.com.

For further press information please contact Fiona Robinson, The Scott Partnership, 1 Whiteside, Station Road, Holmes Chapel, Cheshire CW4 8AA, United Kingdom. Phone +44 1477 539539, Fax +44 1477 539540, Email ert@scottpr.co.uk

About ERT

Based in Philadelphia, PA, eResearchTechnology, Inc. (www.ert.com) is a global technology-based service and medical device provider to the pharmaceutical and biotechnology industries specializing in customization of the devices used to collect and process clinical data.  The Company is a market leader in providing centralized core-diagnostic electrocardiographic (ECG) technology and services to evaluate cardiac safety in clinical development. It is also a leading provider of centralized respiratory technology and services to evaluate pulmonary function efficacy and safety in clinical development.  Sponsors can further use the Company's solutions to streamline the clinical trials process by automating the collection, analysis, and distribution of ePRO clinical data using multi-mode technology in all phases of clinical development as well as customized medical devices for the clinical trials and healthcare industries.

Statements included in this release may constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Such statements, including, but not limited to, 2009 financial guidance, involve a number of risks and uncertainties such as the Company's ability to obtain new contracts and accurately estimate net revenues due to uncertain regulatory guidance, variability in size, scope and duration of projects, and internal issues at the sponsoring client, integration of acquisitions, competitive factors, technological development, and market demand. As a result, actual results may differ materially from any financial outlooks stated herein. Further information on potential factors that could affect the Company's financial results can be found in the Company's Reports on Form 10-K and 10-Q filed with the Securities and Exchange Commission. The Company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise.