Accurately assessing suicidal ideation and behavior (SIB) is a critical and often required element in many clinical trials. In this first installment to a series, ERT’s Millie Gerzon provides background and answers to some common questions about why and when clinical trial sponsors and CROs should include SIB monitoring in their clinical studies to both keep patients safe and meet regulatory requirements.
Why should Suicidal Ideation and Behavior be assessed during the development of new medical products?
During clinical development, sponsors and CROs need the ability to detect possible suicidal ideation and behavior (SIB) related to their drug in the screening, baseline, treatment and follow up phases of the study. Suicidal ideation and behaviors are a threat to patient safety and as such, need to be assessed accurately and in a timely manner.
Because we cannot know the potential risk for new drugs or treatments to induce suicidal ideation and or behavior, assessment of SIB throughout the clinical development process is critical. Even drugs used to treat non-psychiatric related ailments have unexpectedly been found to alter mood and increase or induce SIB in patients.
What impact could SIB monitoring have on a development program?
If reliable SIB data is collected during clinical trials, it will appropriately screen in/out patients, detect true positive and negative events and be able to demonstrate whether a drug has an impact on suicide risk, so the sponsor can continue the development program with confidence that patient safety is maintained and that they are meeting regulatory expectations. SIB monitoring can detect if a drug increases the risk of suicide, giving sponsors solid evidence to terminate the development program early, thereby potentially saving patient lives and reducing costs by making no-go decisions sooner in development.
Do all new drug trials require SIB testing?
No. But, global regulators are recommending and often requiring SIB assessments for trials with therapies that cross the blood-brain barrier.
According to the FDA, prospective suicidal ideation and behavior assessments should be carried out in almost all clinical trials that involve the development of a drug for any type of psychiatric indication. The FDA specifically recommends including SIB monitoring when assessing the following indications and drug trials:
- Isotretinoins / tretinoins
- Beta blockers that cross the blood-brain barrier
- Reserpine (for smoking cessation)
- Weight loss drugs
- Anti-epileptic drugs or other neurologic drugs with central nervous system activity
- Any pharmacologically-similar drug
When should SIB assessment be conducted?
The FDA recommends assessing SIB in every trial for which it has been determined that the drug or indication (as noted above) is appropriate including short-term multi-dose phase 1 trials through phase 4 trials. SIB monitoring must happen at every scheduled/unscheduled clinical visit to ensure that positive signals are recognized and addressed – while also collecting evidence to clarify any association or lack thereof between treatment and self-injurious patient behavior.
What is the most effective way to assess for SIB during clinical development?
The Columbia-Suicide Severity Rating Scale (C-SSRS) and patient-reported electronic C-SSRS are the only risk assessment tools specifically identified by the FDA as acceptable for use in clinical trials. When the C-SSRS is used in pharmaceutical research, investigative site personnel ask a series of simple, plain-language questions to identify whether clinical trial participants are at risk of suicide, assess the severity and immediacy of that risk, and gauge the level of support the patient needs.
Based on an unprecedented amount of research that validates the relevance and effectiveness of its questions, the C-SSRS is often referred to as the gold standard and has been used effectively in clinical trials around the world. When implemented electronically, investigative site personnel are trained to use a tablet device, which guides them through the assessment questions and helps to reduce missing data.
The electronic C-SSRS includes branching logic that guides the user to the follow-up questions for the intensity of ideations or lethality of behaviors based on responses to the primary questions. Also, inconsistencies and errors are flagged and can be corrected immediately.
Millie Gerzon is a Senior Science Advisor at ERT.