{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T02:27:35Z","timestamp":1778812055039,"version":"3.51.4"},"reference-count":33,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2016,3,25]],"date-time":"2016-03-25T00:00:00Z","timestamp":1458864000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Clinical Trials"],"published-print":{"date-parts":[[2016,6]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>The \u2018gold standard\u2019 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\u2019 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>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\u2019 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>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\u2019 preferences for specific drugs used for the respective patients were analysed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>The idea of patient-oriented randomisation can be generalised. In light of the heterogeneity and complexity of patient\u2013drug interaction, this design should prove particularly useful.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/1740774516639910","type":"journal-article","created":{"date-parts":[[2016,3,26]],"date-time":"2016-03-26T20:13:05Z","timestamp":1459023185000},"page":"251-259","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":7,"title":["Patient-oriented randomisation: A new trial design applied in the Neuroleptic Strategy Study"],"prefix":"10.1177","volume":"13","author":[{"given":"Constanze","family":"Schulz","sequence":"first","affiliation":[{"name":"Competence Center for Clinical Trials Bremen, University of Bremen, Bremen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00fcrgen","family":"Timm","sequence":"additional","affiliation":[{"name":"Competence Center for Clinical Trials Bremen, University of Bremen, Bremen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joachim","family":"Cordes","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, Medical Faculty, Heinrich-Heine-University D\u00fcsseldorf, D\u00fcsseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerhard","family":"Gr\u00fcnder","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, RWTH Aachen University, Aachen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernd","family":"M\u00fchlbauer","sequence":"additional","affiliation":[{"name":"Competence Center for Clinical Trials Bremen, University of Bremen, Bremen, Germany"},{"name":"Department of Pharmacology, Klinikum Bremen Mitte, Bremen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eckart","family":"R\u00fcther","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University of G\u00f6ttingen, G\u00f6ttingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Heinze","sequence":"additional","affiliation":[{"name":"Department for Psychiatry and Psychotherapy, Brandenburg Medical School, Immanuel Klinik R\u00fcdersdorf, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2016,3,25]]},"reference":[{"key":"bibr1-1740774516639910","unstructured":"Gabel W, Falkai P, Weinmann S, S3-Praxisleitlinien in Psychiatrie und Psychotherapie\/Bd.1 Behandlungsleitlinie Schizophrenie (ed Deutsche Gesellschaft f\u00fcr Psychiatrie, Psychotherapie and Nervenheilkunde). Darmstadt: Steinkopff, 2006, p. 82."},{"key":"bibr2-1740774516639910","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)60486-9"},{"key":"bibr3-1740774516639910","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa051688"},{"key":"bibr4-1740774516639910","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.63.10.1079"},{"key":"bibr5-1740774516639910","first-page":"649","volume":"23","author":"Naber D","year":"2009","journal-title":"CNS Drugs"},{"key":"bibr6-1740774516639910","first-page":"58","volume":"6","author":"Constantine RJ","year":"2007","journal-title":"Curr Psychiatry"},{"key":"bibr7-1740774516639910","doi-asserted-by":"publisher","DOI":"10.1093\/biostatistics\/kxr016"},{"key":"bibr8-1740774516639910","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3223(00)00946-X"},{"key":"bibr9-1740774516639910","doi-asserted-by":"publisher","DOI":"10.1002\/sim.2022"},{"key":"bibr10-1740774516639910","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-clinpsy-032511-143152"},{"key":"bibr11-1740774516639910","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.2007.164.3.415"},{"key":"bibr12-1740774516639910","first-page":"93","volume-title":"Non-random reflections on health services research","author":"Kleijnen J","year":"1997"},{"key":"bibr13-1740774516639910","doi-asserted-by":"publisher","DOI":"10.1214\/ss\/1028905885"},{"key":"bibr14-1740774516639910","volume-title":"4th European conference on schizophrenia research","author":"Heinze M"},{"key":"bibr15-1740774516639910","volume-title":"35the annual conference of the international society for clinical biostatistics","author":"Schulz C"},{"key":"bibr16-1740774516639910","volume-title":"Der SF-36 Fragebogen zum Gesundheitszustand: SF-36-Handbuch f\u00fcr die deutschsprachige Fragebogenversion","author":"Bullinger M","year":"1998"},{"key":"bibr17-1740774516639910","first-page":"218","volume-title":"ECDEU assessment for psychopharmacology","author":"National Institute of Mental Health","year":"1976"},{"key":"bibr18-1740774516639910","doi-asserted-by":"publisher","DOI":"10.1093\/schbul\/13.2.261"},{"key":"bibr19-1740774516639910","doi-asserted-by":"publisher","DOI":"10.1016\/S0920-9964(00)00166-3"},{"key":"bibr20-1740774516639910","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0447.2000.tb10933.x"},{"key":"bibr21-1740774516639910","doi-asserted-by":"publisher","DOI":"10.1016\/j.eurpsy.2005.05.009"},{"key":"bibr22-1740774516639910","doi-asserted-by":"publisher","DOI":"10.1001\/jama.290.20.2693"},{"key":"bibr23-1740774516639910","doi-asserted-by":"publisher","DOI":"10.3109\/15622970701429854"},{"key":"bibr24-1740774516639910","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.v67n1104"},{"key":"bibr25-1740774516639910","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.162.5.947"},{"key":"bibr26-1740774516639910","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2007.06.004"},{"key":"bibr27-1740774516639910","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0447.2004.00486.x"},{"key":"bibr28-1740774516639910","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa002028"},{"key":"bibr29-1740774516639910","first-page":"65","volume":"6","author":"Holm S.","year":"1979","journal-title":"Scand J Stat"},{"key":"bibr30-1740774516639910","unstructured":"Bundesministerium f\u00fcr Bildung und Forschung (BMBF). Antipsychotika im Fokus. In: Aktuelle Ergebnisse der Gesundheitsforschung (Newsletter 74). BMBF, August 2015, pp. 8\u20139, http:\/\/www.gesundheitsforschung-bmbf.de\/_media\/NL_74_barrierefrei.pdf (accessed 29 September 2015)."},{"key":"bibr31-1740774516639910","doi-asserted-by":"publisher","DOI":"10.1016\/S2215-0366(16)00085-7"},{"key":"bibr32-1740774516639910","volume-title":"61th biometric colloquium of the German regions of the international biometrical society (IBS-DR)","author":"Schulz C"},{"key":"bibr33-1740774516639910","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.312.7023.71"}],"container-title":["Clinical Trials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1740774516639910","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/1740774516639910","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1740774516639910","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T17:29:27Z","timestamp":1777397367000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/1740774516639910"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,3,25]]},"references-count":33,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2016,6]]}},"alternative-id":["10.1177\/1740774516639910"],"URL":"https:\/\/doi.org\/10.1177\/1740774516639910","relation":{},"ISSN":["1740-7745","1740-7753"],"issn-type":[{"value":"1740-7745","type":"print"},{"value":"1740-7753","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,3,25]]}}}