With the FDA striving to avoid post-market reactions to drugs with worrisome side-effect profiles, preventive measures that screen for obvious risks such as suicidal behavior and abuse potential are making their way into the lexicon of regulators and drug developers alike, in tandem with its mandate that stresses safety first and efficacy a close second.
In the specific effort to mitigate the risk of what it now labels as suicidal ideation and/or behavior (SIB), the FDA issued its second draft guidance last year on how to effectively assess patients for SIB in clinical trials, mainly for drugs that affect the central nervous system. The FDA maintains within the guidance that while an assessment of SIB is not required of every drug, it’s better to ask the agency if they think it’s a good idea or not, in other words, better safe than sorry.
ERT, one organization focused on addressing this issue, recently unveiled its AVERT system, an electronic self-report mechanism that allows patients in clinical trials to complete the assessment in privacy and send results directly to the clinician. The AVERT assessment tool is done at regular intervals during the trial, initially for pre-screening purposes and throughout the trial to assess the drug’s ability to increase frequency of SIB among patients. AVERT uses FDA’s preferred rubric, the Columbia Suicide Severity Rating Scale (CSSRS) to determine if the patient is at-risk or not.
The FDA’s updated guidance also states that while any drug developed for a psychiatric disorder should require the assessment; non-psychiatric drugs for the treatment of patients with no history of psychiatric disorders are not necessarily exempt. The new guidance specifically references antiepileptics, neurologic drugs with CNS activity, drugs that are pharmacologically similar to isotretinoin and other tretinoins, beta blockers (especially those entering the brain), reserpine, drugs for smoking cessation, and drugs for weight loss as drugs that require assessment. But as far as unmentioned drugs are concerned, “the only way to find out if a drug requires the assessment or not is to ask the FDA,” said Dr. Jean Paty, Chief of Science and Regulatory Affairs at ERT. He added, “No organization wants to be the one that didn’t at least attend to this procedure and experience the consequences.”
It remains unclear as to when the draft guidance will be finalized, especially with the recent departure of the measure’s greatest champion Dr. Thomas Laughren, former director of the Division of Psychiatry Products in the Office of New Drugs in the Center for Drug Evaluation and Research at FDA.