title: Taking Personalized Medicine Seriously: Biomarker Approaches in Phase IIb/III Studies in Major Depression and Schizophrenia.
abstract: The success rate in the development of psychopharmacological compounds is insufficient. Two main reasons for failure have been frequently identified: 1) treating the wrong patients and 2) using the wrong dose. This is potentially based on the known heterogeneity among patients, both on a syndromal and a biological level. A focus on personalized medicine through better characterization with biomarkers has been successful in other therapeutic areas. Nevertheless, obstacles toward this goal that exist are 1) the perception of a lack of validation, 2) the perception of an expensive and complicated enterprise, and 3) the perception of regulatory hurdles. The authors tackle these concerns and focus on the utilization of biomarkers as predictive markers for treatment outcome. The authors primarily cover examples from the areas of major depression and schizophrenia. Methodologies covered include salivary and plasma collection of neuroendocrine, metabolic, and inflammatory markers, which identified subgroups of patients in the Netherlands Study of Depression and Anxiety. A battery of vegetative markers, including sleep-electroencephalography parameters, heart rate variability, and bedside functional tests, can be utilized to characterize the activity of a functional system that is related to treatment refractoriness in depression (e.g., the renin-angiotensin-aldosterone system). Actigraphy and skin conductance can be utilized to classify patients with schizophrenia and provide objective readouts for vegetative activation as a functional marker of target engagement. Genetic markers, related to folate metabolism, or folate itself, has prognostic value for the treatment response in patients with schizophrenia. Already, several biomarkers are routinely collected in standard clinical trials (e.g., blood pressure and plasma electrolytes), and appear to be differentiating factors for treatment outcome. Given the availability of a wide variety of markers, the further development and integration of such markers into clinical research is both required and feasible in order to meet the benefit of personalized medicine. This article is based on proceedings from the "Taking Personalized Medicine Seriously-Biomarker Approaches in Phase IIb/III Studies in Major Depression and Schizophrenia" session, which was held during the 10th Annual Scientific Meeting of the International Society for Clinical Trials Meeting (ISCTM) in Washington, DC, February 18 to 20, 2014.
authors.affiliation: Dr. Murck is with Acorda Therapeutics in Ardsley, New York, and Phillips-University Marburg, Marburg, Germany (Dr. Murck was with Covance Inc., Princeton, New Jersey, during the preparation of this manuscript); Dr. Laughren is with Laughren Consulting, Rockville, Maryland, USA; Dr. Lamers is with the Department of Psychiatry, VU University Medical Center / GGZ inGeest, Amsterdam, The Netherlands; Dr. Picard is with MIT Media Laboratory and Empatica, Inc., Boston, Massachusetts, USA; Dr. Walther is with University Hospital of Psychiatry, Bern, Switzerland; Dr. Goff is with the Department of Psychiatry, NYU Langone Medical Center, New York, New York, USA; Dr. Sainati is with FORUM Pharmaceuticals, Boston, Massachusetts, USA.
authors.forename: Harald
authors.initials: H
authors.lastname: Murck
authors.affiliation: Dr. Murck is with Acorda Therapeutics in Ardsley, New York, and Phillips-University Marburg, Marburg, Germany (Dr. Murck was with Covance Inc., Princeton, New Jersey, during the preparation of this manuscript); Dr. Laughren is with Laughren Consulting, Rockville, Maryland, USA; Dr. Lamers is with the Department of Psychiatry, VU University Medical Center / GGZ inGeest, Amsterdam, The Netherlands; Dr. Picard is with MIT Media Laboratory and Empatica, Inc., Boston, Massachusetts, USA; Dr. Walther is with University Hospital of Psychiatry, Bern, Switzerland; Dr. Goff is with the Department of Psychiatry, NYU Langone Medical Center, New York, New York, USA; Dr. Sainati is with FORUM Pharmaceuticals, Boston, Massachusetts, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Laughren
authors.affiliation: Dr. Murck is with Acorda Therapeutics in Ardsley, New York, and Phillips-University Marburg, Marburg, Germany (Dr. Murck was with Covance Inc., Princeton, New Jersey, during the preparation of this manuscript); Dr. Laughren is with Laughren Consulting, Rockville, Maryland, USA; Dr. Lamers is with the Department of Psychiatry, VU University Medical Center / GGZ inGeest, Amsterdam, The Netherlands; Dr. Picard is with MIT Media Laboratory and Empatica, Inc., Boston, Massachusetts, USA; Dr. Walther is with University Hospital of Psychiatry, Bern, Switzerland; Dr. Goff is with the Department of Psychiatry, NYU Langone Medical Center, New York, New York, USA; Dr. Sainati is with FORUM Pharmaceuticals, Boston, Massachusetts, USA.
authors.forename: Femke
authors.initials: F
authors.lastname: Lamers
authors.affiliation: Dr. Murck is with Acorda Therapeutics in Ardsley, New York, and Phillips-University Marburg, Marburg, Germany (Dr. Murck was with Covance Inc., Princeton, New Jersey, during the preparation of this manuscript); Dr. Laughren is with Laughren Consulting, Rockville, Maryland, USA; Dr. Lamers is with the Department of Psychiatry, VU University Medical Center / GGZ inGeest, Amsterdam, The Netherlands; Dr. Picard is with MIT Media Laboratory and Empatica, Inc., Boston, Massachusetts, USA; Dr. Walther is with University Hospital of Psychiatry, Bern, Switzerland; Dr. Goff is with the Department of Psychiatry, NYU Langone Medical Center, New York, New York, USA; Dr. Sainati is with FORUM Pharmaceuticals, Boston, Massachusetts, USA.
authors.forename: Rosalind
authors.initials: R
authors.lastname: Picard
authors.affiliation: Dr. Murck is with Acorda Therapeutics in Ardsley, New York, and Phillips-University Marburg, Marburg, Germany (Dr. Murck was with Covance Inc., Princeton, New Jersey, during the preparation of this manuscript); Dr. Laughren is with Laughren Consulting, Rockville, Maryland, USA; Dr. Lamers is with the Department of Psychiatry, VU University Medical Center / GGZ inGeest, Amsterdam, The Netherlands; Dr. Picard is with MIT Media Laboratory and Empatica, Inc., Boston, Massachusetts, USA; Dr. Walther is with University Hospital of Psychiatry, Bern, Switzerland; Dr. Goff is with the Department of Psychiatry, NYU Langone Medical Center, New York, New York, USA; Dr. Sainati is with FORUM Pharmaceuticals, Boston, Massachusetts, USA.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Walther
authors.affiliation: Dr. Murck is with Acorda Therapeutics in Ardsley, New York, and Phillips-University Marburg, Marburg, Germany (Dr. Murck was with Covance Inc., Princeton, New Jersey, during the preparation of this manuscript); Dr. Laughren is with Laughren Consulting, Rockville, Maryland, USA; Dr. Lamers is with the Department of Psychiatry, VU University Medical Center / GGZ inGeest, Amsterdam, The Netherlands; Dr. Picard is with MIT Media Laboratory and Empatica, Inc., Boston, Massachusetts, USA; Dr. Walther is with University Hospital of Psychiatry, Bern, Switzerland; Dr. Goff is with the Department of Psychiatry, NYU Langone Medical Center, New York, New York, USA; Dr. Sainati is with FORUM Pharmaceuticals, Boston, Massachusetts, USA.
authors.forename: Donald
authors.initials: D
authors.lastname: Goff
authors.affiliation: Dr. Murck is with Acorda Therapeutics in Ardsley, New York, and Phillips-University Marburg, Marburg, Germany (Dr. Murck was with Covance Inc., Princeton, New Jersey, during the preparation of this manuscript); Dr. Laughren is with Laughren Consulting, Rockville, Maryland, USA; Dr. Lamers is with the Department of Psychiatry, VU University Medical Center / GGZ inGeest, Amsterdam, The Netherlands; Dr. Picard is with MIT Media Laboratory and Empatica, Inc., Boston, Massachusetts, USA; Dr. Walther is with University Hospital of Psychiatry, Bern, Switzerland; Dr. Goff is with the Department of Psychiatry, NYU Langone Medical Center, New York, New York, USA; Dr. Sainati is with FORUM Pharmaceuticals, Boston, Massachusetts, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Sainati
keywords: Wearable devices; biomarker; predictive marker; surrogate marker; treatment outcome