title: Patient-oriented randomisation: A new trial design applied in the Neuroleptic Strategy Study.
abstract: The 'gold standard' for clinical studies is a randomised controlled trial usually comparing specific treatments. If the scientific study expands to strategy comparison with each strategy including various treatments, the research problems are increasingly complicated. The strategy debate in the psychiatric community is the starting point for the development of our new design. It is widely accepted that second-generation antipsychotics are the therapy of choice in the treatment of schizophrenia. However, their general superiority over first-generation antipsychotics could not be demonstrated in recent randomised controlled trials. Furthermore, we are becoming increasingly aware that the experimental conditions of randomised controlled trials, as in the European First Episode Schizophrenia Trial and Clinical Antipsychotic Trials of Intervention Effectiveness Phase 1 studies, may be inappropriate for psychiatric treatments. The high heterogeneity in the patient population produces discrepancies between daily clinical perception and randomised controlled trials results. The patient-oriented approach in the Cost Utility of the Latest Antipsychotic drugs in Schizophrenia Study reflects everyday clinical practice. The results, however, are highly dependent on the physicians' preferences. The goal of the design described here is to take an intermediate path between randomised controlled trials and clinical studies such as Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study, combining the advantages of both study types.
  
  
  
  The idea is to randomise two treatment pairs each consisting of one first-generation antipsychotic and one second-generation antipsychotic in a first step and subsequently, to involve the investigators in deciding for a pair most appropriate to the patients' needs and then to randomise the allocation to one drug (first-generation antipsychotic or second-generation antipsychotic) of that chosen pair. This idea was first implemented in the clinical trial, the Neuroleptic Strategy Study, with a randomised design comparing efficacy and safety of two different strategies: either to use first-generation antipsychotics (haloperidol and flupentixol) or second-generation antipsychotics (olanzapine, aripiprazole and quetiapine) in patients suffering from schizophrenia.
  
  
  
  In the course of the Neuroleptic Strategy Study, feasibility of this design was demonstrated. All aspects of the new design were implemented: randomisation process, documentation of responses from investigators as well as patients and drug logistic experience. In implementing the design, furthermore, we could investigate its theoretical properties. The physicians' preferences for specific drugs used for the respective patients were analysed.
  
  
  
  The idea of patient-oriented randomisation can be generalised. In light of the heterogeneity and complexity of patient-drug interaction, this design should prove particularly useful.
authors.affiliation: Competence Center for Clinical Trials Bremen, University of Bremen, Bremen, Germany conschul@math.uni-bremen.de.
authors.forename: Constanze
authors.initials: C
authors.lastname: Schulz
authors.affiliation: Competence Center for Clinical Trials Bremen, University of Bremen, Bremen, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Timm
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Cordes
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, RWTH Aachen University, Aachen, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Gründer
authors.affiliation: Competence Center for Clinical Trials Bremen, University of Bremen, Bremen, Germany Department of Pharmacology, Klinikum Bremen Mitte, Bremen, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Mühlbauer
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Göttingen, Göttingen, Germany.
authors.forename: Eckart
authors.initials: E
authors.lastname: Rüther
authors.affiliation: Department for Psychiatry and Psychotherapy, Brandenburg Medical School, Immanuel Klinik Rüdersdorf, Berlin, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Heinze
mesh_terms: D014150:Antipsychotic Agents / Q000627:therapeutic use*; D000068180:Aripiprazole / Q000627:therapeutic use; D001569:Benzodiazepines / Q000627:therapeutic use; D000068456:Clinical Studies as Topic; D005475:Flupenthixol / Q000627:therapeutic use; D006220:Haloperidol / Q000627:therapeutic use; D006801:Humans; D000077152:Olanzapine; D018802:Patient-Centered Care; D000069348:Quetiapine Fumarate / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D012559:Schizophrenia / Q000188:drug therapy*
chemical_list: D014150:Antipsychotic Agents; D001569:Benzodiazepines; D000069348:Quetiapine Fumarate; D000068180:Aripiprazole; D005475:Flupenthixol; D006220:Haloperidol; D000077152:Olanzapine
keywords: Neuroleptic Strategy Study; ethics; first-generation antipsychotics; patient-oriented randomisation; schizophrenia; second-generation antipsychotics; strategy comparison