title: Challenges in the design and conduct of controlled clinical effectiveness trials in schizophrenia.
abstract: BACKGROUND
  The introduction of antipsychotic medication has been a major advance in the treatment of schizophrenia and allows millions of people to live outside of institutions. It is generally believed that long-acting intramuscular antipsychotic medication is the most effective approach to increasing medication adherence and thereby reduce relapse in high-risk patients with schizophrenia, but the data are scant.
  
  
  OBJECTIVE
  To report the design of a study to assess the effect of long-acting injectable risperidone in unstable patients and under more realistic conditions than previously studied and to evaluate the effect of this medication on psychiatric inpatient hospitalization, schizophrenia symptoms, quality of life, medication adherence, side effects, and health care costs.
  
  
  METHODS
  The trial was an open randomized clinical comparative effectiveness trial in patients with schizophrenia or schizo-affective disorders in which parenteral risperidone was compared to an oral antipsychotic regimen selected by each control patient's psychiatrist. Participants had unstable psychiatric disease defined by recent hospitalization or exhibition of unusual need for psychiatric services. The primary endpoint was hospitalization for psychiatric indications; the secondary endpoint was psychiatric symptoms.
  
  
  RESULTS
  Overall, 382 patients were randomized. Determination of a persons' competency to understand the elements of informed consent was addressed. The use of a closed-circuit TV interview for psychosocial measures provided an economical, high quality, reliable means of collecting data. A unique method for insuring that usual care was optimal was incorporated in the follow-up of all subjects.
  
  
  CONCLUSIONS
  Patients with schizophrenia or schizo-affective disorders and with the common co-morbid illnesses seen in the VA are a challenging group of subjects to study in long-term trials. Some techniques unique in the VA and found useful may not be generalizable or applicable in other research or treatment settings.
  
  
  CONCLUSIONS
  The trial tested a new antipsychotic medication early in its adoption in the Veterans Health Administration. The VA has a unique electronic medical record and database which can be used to identify the endpoint, that is, first hospitalization due to a psychiatric problem, with complete ascertainment. Several methodologic solutions addressed competency to understand elements of consent, the costs and reliability of collecting interview data gathering, and insuring usual care.
authors.affiliation: Veterans Affairs (VA) Connecticut Healthcare System, West Haven, CT, USA. Robert.Rosenheck@va.gov
authors.forename: Robert A
authors.initials: RA
authors.lastname: Rosenheck
authors.forename: John H
authors.initials: JH
authors.lastname: Krystal
authors.forename: Robert
authors.initials: R
authors.lastname: Lew
authors.forename: Paul G
authors.initials: PG
authors.lastname: Barnett
authors.forename: Soe Soe
authors.initials: SS
authors.lastname: Thwin
authors.forename: Louis
authors.initials: L
authors.lastname: Fiore
authors.forename: Danielle
authors.initials: D
authors.lastname: Valley
authors.forename: Grant D
authors.initials: GD
authors.lastname: Huang
authors.forename: Carla
authors.initials: C
authors.lastname: Neal
authors.forename: Julia E
authors.initials: JE
authors.lastname: Vertrees
authors.forename: Matthew H
authors.initials: MH
authors.lastname: Liang
mesh_terms: D000284:Administration, Oral; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000191:economics / Q000627:therapeutic use; D057186:Comparative Effectiveness Research; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000191:economics / Q000627:therapeutic use; D006801:Humans; D007273:Injections, Intramuscular; D007407:Interviews as Topic; D055118:Medication Adherence; D010359:Patient Readmission / Q000191:economics; D011788:Quality of Life; D018967:Risperidone / Q000008:administration & dosage* / Q000191:economics / Q000627:therapeutic use; D012559:Schizophrenia / Q000188:drug therapy*
chemical_list: D014150:Antipsychotic Agents; D003692:Delayed-Action Preparations; D018967:Risperidone