Suchergebnisse

<b><i>Background:</i></b> Natural history (NH) studies, using observational methods, are common in rare and orphan diseases (80% of which have a genetic component). There is profound interest in identifying genetic mutations driving these diseases in these studies to support the formulation of targeted precision medicines. The global regulatory classification of NH studies with novel molecular biomarker collection has not been clearly delineated, presenting researchers with the challenge of determining how these studies are classified and regulated across multiple geographies. <b><i>Objective:</i></b> The aim of this investigation was to conduct a review of regulations related to NH studies and genetic testing to elucidate regulatory pathways to inform clinical researchers in the field. <b><i>Methods:</i></b> Regulatory provisions for NH studies and genetic testing were obtained from Pharmaceutical Product Development (PPD)'s propriety regulatory intelligence database and by surveying the company's country-specific regulatory experts. A literature search was conducted in the Google Scholar search engine and PubMed for supplementary information. <b><i>Results:</i></b> Nineteen countries were evaluated; 37% classified NH studies with biomarker collection as noninterventional and 26% required regulatory approval (increasing to 47% when molecular biomarker testing was introduced). No regulatory provisions for genetic testing could be identified in 32% of countries, and 58% did not have binding requirements for genetic counseling. <b><i>Conclusion:</i></b> Lack of harmonization of regulations governing NH studies with molecular biomarker collection contributes to the operational complexity of conducting multinational studies in orphan and rare diseases. A set of harmonized international guidelines for these studies would improve efficiency, and this may be on the horizon with the recent adaption of International Conference on Harmonisation (ICH) guideline E18.

Delphine Saragoussi,1 Maëlys Touya,2 Josep Maria Haro,3 Bengt Jönsson,4 Martin Knapp,5 Bastien Botrel,6 Ioana Florea,7 Henrik Loft,8 Benoît Rive9 1Real-World Evidence and Epidemiology, Lundbeck SAS, Issy-les-Moulineaux, France; 2Health Economics and Outcomes Research, Lundbeck, Deerfield, IL, US; 3Research and Teaching Unit, Parc Sanitari Sant Joan de Deu, CIBERSAM, University of Barcelona, Sant Boi de Llobregat, Barcelona, Spain; 4Department of Economics, Stockholm School of Economics, Stockholm, Sweden; 5Department of Health Policy, London School of Economics and Political Science, London, UK; 6Biostatistics, Inferential, Paris, France; 7Clinical Research Paediatrics, H. Lundbeck A/S, Valby, Denmark; 8Biometrics, H. Lundbeck A/S, Valby, Denmark; 9Global Analytics, Lundbeck SAS, Issy-les-Moulineaux, France Background: The Prospective Epidemiological Research on Functioning Outcomes Related to Major Depressive Disorder (PERFORM) study has been initiated to better understand the course of a depressive episode and its impact on patient functioning. This analysis aimed to identify sociodemographic and clinical factors associated with failure to achieve remission at month 2 after initiating or switching antidepressant monotherapy and with subsequent relapse at month 6 for patients in remission at month 2. Materials and methods: This was a 2-year observational cohort study in 1,159 outpatients aged 18–65 years with major depressive disorder initiating or undergoing the first switch of antidepressant monotherapy. Factors with P8 weeks (OR 0.51), being in psychotherapy (OR 0.51), sexual dysfunction (OR 0.62), and severity of depression (OR 0.87). Factors significantly associated with relapse at month 6 were male sex (OR 2.47), being married or living as a couple (OR 2.73), residual patient-reported cognitive symptoms at 2 months (OR 1.12 per additional unit of Perceived Deficit Questionnaire-5 score) and residual depressive symptoms at 2 months (OR 1.27 per additional unit of Patient Health Questionnaire-9 score). Conclusion: Different factors appear to be associated with failure to achieve remission in patients with major depressive disorder and with subsequent relapse in patients who do achieve remission. Patient-reported cognitive dysfunction is an easily measurable and treatable characteristic that may be associated with an increased likelihood of relapse at 6 months in patients who have achieved remission. Keywords: major depressive disorder, remission, relapse, patient-reported cognitive dysfunction