Food and Drug Administration Perspective on Negative Symptoms in Schizophrenia as a Target for a Drug Treatment Claim

Food and Drug Administration, DNDP, HFD-120, 5600 Fishers Lane, Rockville, MD 20853, USA.
Schizophrenia Bulletin (Impact Factor: 8.45). 05/2006; 32(2):220-2. DOI: 10.1093/schbul/sbi039
Source: PubMed


Negative symptoms of schizophrenia are not adequately addressed by available treatments for schizophrenia. Thus, it is reasonable to consider them as a target for a drug claim. This article describes the thought process that the Food and Drug Administration (FDA) will undertake in considering negative symptoms of schizophrenia as a novel and distinct drug target. Beyond this basic question, this article identifies a number of design issues that the FDA needs to consider regarding how best to conduct studies to support claims for this target. These design issues include (1) what population to study, (2) what phase of illness to target, (3) whether to focus on the negative symptom domain overall or on some specific aspect of negative symptoms, (4) the role of functional measures in negative symptom trials, and (5) optimal designs for targeting drugs for add-on therapy or broad-spectrum agents.

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    • "In order to evaluate whether restoration of positive mood symptoms in MDD could be a " legitimate " target for a drug development program, developers might ask a series of questions (Laughren and Levin, 2005): • Are decreased positive mood states phenomenologically distinct from other symptoms of MDD, and do they have a course that is distinct from other symptoms? • Do experts in the scientific community consider decreased positive mood states a distinct aspect of MDD, and is this distinctness reflected in the diagnostic nomenclature? "
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    Journal of Psychopharmacology 05/2014; 28(6). DOI:10.1177/0269881114532857 · 3.59 Impact Factor
    • "For example, high-functioning youth with ASD with anxiety disorders have shown a positive response to CBT in several pilot trials (Reaven et al. 2012; Storch et al. 2013; White et al. 2013; Wood et al. 2009a). A drug development program built on the notion that anxiety disorders are independent from ASD and not different from anxiety disorders in typically developing children would likely encounter the regulatory issue referred to as pseudospecificity (Laughren and Levin 2006). This term reflects the FDA's concern about a drug approval built on a narrow indication. "
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    ABSTRACT: Despite the high rate of anxiety in individuals with autism spectrum disorder (ASD), measuring anxiety in ASD is fraught with uncertainty. This is due, in part, to incomplete consensus on the manifestations of anxiety in this population. Autism Speaks assembled a panel of experts to conduct a systematic review of available measures for anxiety in youth with ASD. To complete the review, the panel held monthly conference calls and two face-to-face meetings over a fourteen-month period. Thirty eight published studies were reviewed and ten assessment measures were examined: four were deemed appropriate for use in clinical trials, although with conditions; three were judged to be potentially appropriate, while three were considered not useful for clinical trials assessing anxiety. Despite recent advances, additional relevant, reliable and valid outcome measures are needed to evaluate treatments for anxiety in ASD.
    Journal of Autism and Developmental Disorders 10/2013; 44(5). DOI:10.1007/s10803-013-1974-9 · 3.06 Impact Factor
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    • "The single-minded emphasis on monotherapy for disorders that are heterogeneous (at least as currently defined) may be one factor that tends to preclude attention to neglected clinical targets (Hyman and Fenton 2003). On the other hand, inappropriately narrow clinical indications are likely to be disapproved by the FDA as ''pseudospecific'' (Laughren and Levin 2006), leading to the need to ''walk the tightrope'' in adequately addressing these targets. More generally, there is little evidence that the morbidity or mortality associated with psychiatric illness has changed in the era of modern psychopharmacology (Insel and Scolnick 2006). "
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