Suicide Risk Assessment

Prospective suicide risk assessment is used to measure lifetime suicidal ideation and behavior to provide a baseline and insight into the prospective risk for future suicidal behavior, as well as a means for ongoing monitoring. Here you will find a complete guide to suicide risk assessment in trials and other clinical settings.

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ABOUT THE FDA GUIDANCE

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Why collect suicide risk assessment data prospectively? Suicide - A growing concern in clinical development.

Guidance for Industry - Suicidal Ideation and Behavior: Prospective Assessment of Occurrence in Clinical Trials

When developing certain medical products, there is a risk of treatment-emergent suicidal ideation and behavior (SIB) in clinical trial patients. Appropriate prospective suicide risk assessment adheres to the FDA's recommendations and helps increase patient safety during the trial.

After two years of review, comment and redrafting, the FDA released it's second draft of the Guidance on August 6, 2012. Over all there were no fundamental policy shifts and it is a reinforcement and clarification of their original objectives – patient safety and quality data.  Click 'More' to view these clarifications. 


Revised FDA Draft Guidance: 
Guidance for Industry: Suicidal Ideation and Behavior - Prospective Assessment of Occurrence in Clinical Trials

These clarifications can be summarized and referenced [ ] as follows: 
  • “Suicidality” becomes “Suicidal Ideation and Behavior” [Title]
  • Expands the C-CASA classification categories to 11 [Apdx A]
  • Revises advice on particular trials and patients that need assessment and timing of assessments [272]
  • Addresses concerns about assessment time burden, citing eC-SSRS data [188-198]
  • Recognizes the value of the lifetime assessments in providing protection for patients, citing eC-SSRS data [Footnote 8]
  • Specifically cites “The eC-SSRS … is an alternative approach to obtaining data on suicidal ideation and behavior.” [196-198]
While the FDA has received comments on this draft and discussion continues, this approach, and the application of solutions designed and currently implemented to meet this guidance, should move forward with confidence. 

ERT's Commentary on the FDA Guidance for Industry

Original FDA Draft Guidance:
Guidance for Industry Suicidality: Prospective Assessment of Occurrence in Clinical Trials - Draft September 2010 – The Division of Psychiatric Products of the FDA identified the shortcomings of the legacy ad-hoc approach used in clinical trials and outlined the need for a more thorough, consistent, prospective assessment.  They recommended prospective assessment application in every development phase, every clinical trial, and at every study visit.   This is outlined in the draft guidance document, below: 
  1. Overview – Thomas Laughren, MD,  Director, Division of Psychiatry Products, Food and Drug Administration, NCDEU 2010
    a. Presentation -  ERT Summary
    b. Thomas Laughren, MD Presenation
  2. Guidance For Industry: Suicidality: Prospective Assessment of Occurrence in Clinical Trials
    a. Introduction – (see lines 18-43)
    b. Background – (see lines 46-79)
    c. General recommendations 
    i.   Instruments – (see lines  85-188)
    ii.  Data Management – (see lines 189-24)
    iii. Trial considerations – (see lines 246-311)
    d. Indications – (see lines 314-352)

AVERT™

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Intelligent Suicide Risk Assessment in Clinical Research

AVERT, ERT’s electronic patient reported suicide risk assessment system provides you with simple audio (phone) or visual (web or tablet) solutions that are efficiently and effectively implemented in any study. 

Investigative sites can count on systematic, comprehensive, consistent assessments with reduced staff burden (compared to traditional paper methods). AVERT presents electronic administration of scientifically proven suicide risk assessments. This includes the application of an electronic, patient self-rated version of the Columbia Suicide Severity Rating Scale (eC-SSRS), which is cited in the draft FDA SIB guidance as an acceptable instrument for assessing suicide risk.

By utilizing AVERT, clinical trial patients can comfortably and privately respond to a brief, SIB-related assessment during investigative site visits. If AVERT identifies an at-risk patient, the clinician is alerted immediately, enabling them to take swift and appropriate action per the trial protocol. The site also has access to an online report for all subjects, including those that are identified as at-risk.

By utilizing AVERT sponsors benefits from:
  • Electronic self-assessment via phone, web, or tablet increases patient candor, resulting in greater clarity on the patient’s risk
  • Patient self-rating eliminates clinician variability across sites and between studies
  • Reliable, low burden assessment reduces time and effort for site staff, allowing them to better focus their resources 
  • Evaluates both lifetime and recent patient experience so you can better identify the risk potentially associated with your product
  • Complete and immediate data capture, reporting, and alerting improves efficiency and provides a timely response

SUICIDE RISK ASSESSMENT BACKGROUND

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About the Columbia – Suicide Severity Rating Scale (C-SSRS)

The C-SSRS is a questionnaire used for the assessment of suicide risk. Deployed widely in both clinical practice and clinical research, the C-SSRS is a powerful screening and monitoring tool that assesses the full range of evidence-based ideation and behavior items, and provides criteria for next steps. This valuable tool is recommended by numerous international agencies and is available in 100+ languages. 

Prior to the use of the C-SSRS, suicide risk assessment was measured with ad-hoc reporting by patients and/or clinical teams. At most, this important data was “evaluated” by a question in another assessment. The shortcomings of this approach and value of accurate assessment of suicide severity are reviewed in the following resources.


Origin of the C-SSRS:
C-CASA Project:
While the C-SSRS existed previously, one of the original assessment research projects was commissioned by the FDA in 1999. A team at Columbia, headed by Dr. Kelly Posner, was contracted to review and categorize the Suicidal Ideation and Behavior in trial subjects by retrospectively reviewing CRFs. To accomplish this, the C-CASA classification scale was used. This scale and its limitations are reviewed in:
Prospective Assessment in Clinical Trials - the C-SSRS:
The C-SSRS is currently the only approved scale for meeting the FDA Guidance for Prospective Assessment of Suicidal Ideation and Behavior outlined below. C-SSRS is a semi-structured assessment intended for administration by clinicians or study staff during scheduled study visits. It explores suicidal ideation and intensity, as well as behaviors and lethality. The domains, application, benefits and training for this scale are outlined in: 

ABOUT THE eC-SSRS BY AVERT

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The Electronic Columbia – A Self-Rated Assessment Tool

The electronic C-SSRS (eC-SSRS) is a fully-structured clinical interview, designed for computer-administration directly by patients using interactive voice response (IVR), tablet or web technology. AVERT‘s application of the eC-SSRS probes patients to provide insight into their suicidal ideations and behaviors through a systematic structure of questions that logically branch to appropriate follow-up questions based on their previous answers. This self-rated approach enables patient candor and the systematic process ensures consistency across all patients, at all sites, in the clinical trial.
   
The findings of the assessment are registered and scored, and a report is immediately sent to the site. Report content is reviewed with the patient as needed and followed up per the protocol. This approach provides consistent assessment, documentation, and reduces site burden.

eC-SSRS Resources:
  1. Overview Presentation
  2. The Benefits of the self-rated, pre-screen approach – By John Greist, MD
  3. Request a copy: The eC-SSRS Self-Rated Interview Script
  4. The eC-SSRS Findings Report - Sample
  5. Demonstration – contact ERT for a demo with our phone, web, or tablet version of the eC-SSRS on AVERT.
Development and Validation
The eC-SSRS was developed in close collaboration with the C-SSRS scale authors and Drs. Greist, Mundt, and Gelenberg of Healthcare Technology System (HTS), who possess over 30 years of experience in developing computerized patient assessments and suicide ideation and behavior assessment.  These scripts, flow algorithms, and user interface rules were configured in the ERT EXPERT system.  After completing system testing and documentation, the scale was clinically validated against the clinician rated C-SSRS standard. 
Proven in Practice
  1. After almost 15,000 administrations in clinical trials an analysis of the findings showed that the eC-SSRS was a valid and effective means for prospectively assessing suicidal ideation and behaviors in diverse patient populations over long intervals. 
    • ISCTM Experience Poster - 15,000 Applications

  2. The eC-SSRS has been used in over 
    • 100,000 assessments 
    • 62 studies
    • 20 indications 

  3. In the first 75,000 assessments, the eC-SSRS has exhibited
    • A 99% completion rate
    • Negatives (98.3%) average 3.0 minutes
    • Positives (1.7%)  average 6.5 minutes

  4. Greater sensitivity, which has been confirmed in a study by the Epilepsy Study Consortium.  This is consistent with a variety of clinician vs. self rated findings over the past 40 years. The Benefits of the Self-Rated, pre-screen approach – John Greist, MD

  5. Full linguistic validation has been performed to develop a library of over 60 country/language applications
    a. Linguistic Validation Process

    b. Language and Country Listing
Benefits
  1. Reliability in content and delivery
  2. Accurate documentation and reporting
  3. Increased patient candor
  4. Reduced assessor variability
    • Fewer inconsistencies
    • Fewer queries
    • More accurate referrals
    • Less staff and referral burden
  5. Reduced site burden 
  6. Immediate suicide risk notification
  7. Combines with Clinician knowledge, experience, intuition
  8. Scalability 
  9. Cost neutral
Predictive Properties
We are only beginning to be able to mine these eC-SSRS data.  In review of the first 75,000 applications, this predictive finding was identified: 
  1. Subjects reporting prior suicidal ideation with intent, behavior or both in their lifetime are 4 to 9 times more likely to report suicidal behavior during the trial (presentation on this subject by John Greist).
  2. ISCTM Predictive Properties Poster
  3. A manuscript is soon to be published - check back soon

IMPLEMENTATION / OPERATION OF AVERT

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A Guide to Policy and Protocols, Data collection and Data Management

Using AVERT in your trial is like any other clinical test in your protocol.  Very little training for the site and almost no training for the patient is required.  


Overview:
  1. The site registers the patient ID in the system 
  2. The patient contacts the system, enters their patient ID and creates a personal PIN
  3. The patient responds to each question and the system branches and probes as  appropriate, conducting a “perfect” interview, and capturing all of the responses
  4. ERT immediately delivers a findings report for site review 
  5. The site follows up with the patient per the protocol 
  6. ERT calls the site directly if there is a positive finding for suicidal ideation or behavior 
  7. Implementation / Operations Overview Presentation
  8. The eC-SSRS Findings Report
Policy and Protocols
Adding the Columbia scale to your clinical development programs is straightforward.  ERT's scientific consultants as well as Drs. Greist, Jefferson, and Posner are available to work with your medical staff and clinical teams to help create a standard policy for Prospective Assessment of Suicidal Ideation and Behaviors for your compound, therapeutic area, or company. This policy can outline the where – in which compounds, when – to be scheduled in the trial, and how – to implement this assessment.  

The C-SSRS can be added to your protocols as part of your schedule of assessments.  It is generally performed at every visit per standard FDA Guidance.  In addition, an appendix outlining how to perform the eC-SSRS is added to your protocol.   A sample is included here.

Versions - There are two versions of the eC-SSRS
Lifetime –This is the version used for all patients for their first interview.  The time frame is in their lifetime and all questions are poised as “have you ever”.   The Recency portion of the scale confirms if these thoughts or behaviors occurred in the past x months.  This section is programmable for ideation and behavior time periods separately or can be shut off completely.  This is generally used to assess protocol screening / exclusion criteria. 

Since Last Interview – This version is used for all subsequent calls. The system recalls the date of the last interview – even if it was a clinician interview – and poses the questions as “since your last interview, month xx, XX days ago, have you”.  This enables us to collect a continuum of experience for each patient.  

Using the C-SSRS and eC-SSRS – Following the publication of the validation study noted above, the FDA has said that it will accept “mixing” the C-SSRS and eC-SSRS applications in the same trial, if it would facilitate patient monitoring. The data management aspects of this approach are reviewed below.   Some examples of this might be:
  • Implementing the eC-SSRS mid trial 
  • Using the clinician interview (C-SSRS) to follow up on a positive eC-SSRS 
  • Reporting non-interview information, i.e. from a spouse or in case of hospitalization or death 
  • Using the C-SSRS in some countries and eC-SSRS in others
C-SSRS and eC-SSRS Versions - As outlined on the Columbia website, there are numerous C-SSRS versions tailored to fit unique circumstances.  The table below outlines the eC-SSRS application for each C-SSRS version. [eC-SSRS and C-SSRS website]



Project Management
ERT’s standard Project Assurance process, used in over 1,100 active studies around the world, will be used to manage the EXPERT application of the eC-SSRS for your trial.  A project manager will be involved from project kickoff through data close out.  This process is outlined in this presentation; The Study Requirement Specification (PRS) will outline the study specifications including reporting and alerting.  Much more detail is available through your ERT contact and our Project Assurance team.

Training
Everyone using the Columbia scale must be licensed and have been oriented to its content and use.  This training is provided via DVD and live Q/A during the investigator meeting and scheduled by the Center for Suicide Risk Assessment – Dr. Kelly Posner. When the eC-SSRS is used, the license and training are included in the program fees.  

In addition, training for ERT’s EXPERT ePRO system – registering the patient, receiving reports and using the study portal is provided by ERT’s Academy staff at the investigator meeting. Both the Columbia and ePRO training can be completed in an hour.

Data Management

Assessment of Suicidal Ideation and Behavior - Although not yet outlined by the FDA, nor in the Guidance, the industry anticipates the result of this data collection will be the summary tables and listings needed to write this component of the summary of safety for the compound. The attached is the recommended Data Analysis Guide for the C-SSRS developed by an industry workgroup and reviewed by the FDA.  

C-CASA / C-SSRS / eC-SSRS Data - As noted, the C-CASA is in retrospective reviews and results in the most basic findings classifications. The C-SSRS prospectively collects these assessments, enabling the next, more detailed level of findings. Similarly, using the eC-SSRS we capture even more data including all the responses to the probing questions.  Therefore the eC-SSRS database is the most comprehensive, and inclusive of the data items from the C-SSRS and C-CASA.  In this way, the database ERT delivers from the eC-SSRS self-rated interviews can easily be coordinated with any other C-SSRS data collected, or even legacy C-CASA analyses.  

As part of this assessment and data collection effort we will need the ability to gather assessment data from a variety of sources including previous trials and even the current trial due to:
  • Implementing the eC-SSRS mid trial  
  • Using the clinician interview (C-SSRS) to follow up an eC-SSRS  
  • Reporting non-interview information, i.e. from a spouse or in case of hospitalization or death 
  • Using the C-SSRS in some countries and eC-SSRS in others 
While almost all data will be collected through the eC-SSRS system, you still need to have your legacy C-SSRS data collection available for these ad-hoc items.  

Data Specification - ERT’s standard eC-SSRS data specifications. Our project management team will work with you and our data team to modify this specifications document to meet your needs, including coordination with your legacy C-SSRS data collection.

For additional information see our brief FAQ page.