Delayed Negative Symptom Response to Antipsychotics: An Individual Participant Data Analysis

Summary This protocol outlines an individual participant data (IPD) analysis investigating the temporal dynamics of schizophrenia symptoms during antipsychotic treatment. Using harmonized data from six antipsychotic drug trials, we aim to examine weekly trajectories of Positive and Negative Syndrome Scale (PANSS) sub-scores over a 26-week period. Our aim is to determine whether reductions in positive symptoms precede and predict improvements in negative symptoms. To this end, will conduct (i) descriptive analyses, showing the trajectories of five PANSS sub-scores over time; (ii) test potential a “delay” until response in negative symptoms (versus positive symptoms) is reached; and (iii) examine if improvements in positive symptoms predict changes in negative symptoms one week ahead. Competing Interest Statement The authors have declared no competing interest. Funding Statement This study did not receive any funding. Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The present work describes the protocol of an individual participant data meta-analysis (IPD-MA), with secondary data collected in a trial repository hosted by TU Munich (ebmpp.org/helpful-tools/warehouse/). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Footnotes stefan.leucht{at}tum.de susan.illing{at}mri.tum.de slevine{at}univ.haifa.ac.il Main changes in version 2 of this protocol and SAP reflect the specification of a path analysis, which was included as a sensitivity analysis in addition to the previous analyses of symptom reduction delays. Data Availability All data analyzed in the present study are available at the TU Munich EBMPP trial warehouse: ebmpp.org/helpful-tools/warehouse/.