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Redefining affective disorders: relevance for drug development

Steven D Targum1, Mark H Pollack, Maurizio Fava

  • 1Department of Psychiatry, Clinical Trials Network and Institute, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. sdtargum@yahoo.com

CNS Neuroscience & Therapeutics
|May 17, 2008
PubMed

Insights

Rigid diagnostic systems hinder drug development. This study proposes symptom-specific patient selection criteria for more effective central nervous system (CNS) clinical trials.

Area of Science:

  • Neuroscience
  • Clinical Pharmacology
  • Psychiatry

Background:

  • Current diagnostic systems (e.g., DSM-IV) may not adequately capture patient heterogeneity in central nervous system (CNS) clinical trials.
  • Patient selection based on broad diagnoses can lead to enrollment of individuals not representative of the target illness, potentially compromising drug efficacy evaluation.
  • Existing classification systems may not align with the specific mechanisms of action of novel drug entities.

Purpose of the Study:

  • To propose operational criteria for a more symptom-specific and ecologically valid approach to patient identification in clinical trials.
  • To address limitations in current diagnostic and patient selection processes that impede the evaluation of new drug entities.
  • To enhance the precision of patient selection in CNS drug development by focusing on primary nosological entities.

Main Methods:

  • Review and critique of current diagnostic classification systems and patient selection methodologies in CNS clinical trials.
  • Development of proposed operational criteria for identifying patients based on symptom-specific and outcome-oriented approaches.
  • Emphasis on aligning patient characteristics with the intended mode of action of novel therapeutic agents.

Main Results:

  • Identification of limitations in rigid diagnostic systems for evaluating drugs with specific mechanisms of action.
  • Proposal of a framework for selecting patients based on the primary nosological entity and acute symptoms targeted by a drug.
  • Advocacy for a more symptom-specific and ecologically valid approach to patient identification.

Conclusions:

  • A shift towards symptom-specific patient selection is crucial for effective clinical drug development in CNS disorders.
  • Operationalizing criteria for identifying the 'valid patient' based on targeted symptoms will improve trial outcomes.
  • This approach aims to enhance the reliability and validity of clinical trial results for novel CNS therapies.

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