Are patients enrolled in first episode psychosis drug trials representative of patients treated in routine clinical practice?
Section snippets
Background
Evidence on the efficacy of pharmacotherapies in treating psychotic disorders comes primarily from randomized controlled drug trials. Since these trials carefully select eligible patients who consent to participate in regimented treatment programs they offer a high degree of internal validity but have unknown external validity or generalizability (Pocock, 1983), which needs to be established Dans et al., 1998, Olschewski et al., 1992.
The evidence from such drug trials suggests that
Samples
The data for this paper were drawn from two sources, a countywide epidemiological study of first episode psychosis, the Suffolk County Mental Health Project, and a multi-country randomized controlled trial of risperidone versus haloperidol in first episode psychosis. Both studies were conducted according to the relevant IRB and good clinical practice rules.
Results
One-third (n=59 out of 179) of the Suffolk County patients would not have been eligible for the drug trial. The most common reason was current treatment with antidepressant medication (n=26, 34%), substance abuse during current month (n=15, 25.4%), current alcohol abuse (n=2, 3.3%), suicide attempt (n=9, 15.2%), current alcohol and drug abuse (n=1, 1.7%), antidepressant use and suicide attempt (n=1, 1.7%), substance abuse and antidepressant use (n=1, 1.7%), substance abuse and suicide attempt (n
Discussion
The results of this study suggest that, while some of the patients from the epidemiological cohort would have not met criteria for the drug trial, primarily because they were taking antidepressants, the patients in the two studies were similar. Perhaps the most direct test of the effect of the exclusion criteria and artifice of the drug trial is the comparison of the Suffolk County drug trial patients to the Suffolk county epidemiological cohort that consisted of different patients from the
Acknowledgements
The randomized controlled drug trial presented in this paper was conducted by Janssen Research Foundation. The study included the following investigators and locations: Australia—P. McGorry (Melbourne); T. Lambert (Bentley); J. Kulkarni (Dandenong); Austria—W. Fleischhacker (Innsbruck); Canada—D. Addington (Calgary); L. Kopala (Halifax); R. Williams (Calgary); G. Chouinard (Montreal); A. Labelle (Ottawa); A. Malla (London); S. Purdon (Edmonton); M. Saxena (Hamilton); V. Nair (Montreal); R.
References (14)
- et al.
Epidemiology and natural history of schizophrenia
Biol. Psychiatry
(1999) - et al.
Analysis of randomized and nonrandomized patients in clinical trials using the comprehensive cohort follow up study design
Controlled Clinical Trials
(1992) Methodological and design issues in clinical trials of new neuroleptics: an overview
Br. J. Psychiatry
(1993)- et al.
The epidemiology of psychosis: the Suffolk County Mental Health Project
Schizophr. Bull.
(1992) - et al.
Measurement of premorbid adjustment in chronic schizophrenia
Schizophr. Bull.
(1982) - et al.
Users' guides to the medical literature: XIV. How to decide on the applicability of clinical trial results to your patient. Evidence Based Medicine Working Group
JAMA, J. Am. Med. Assoc.
(1998) - Emsley, R.A., Rabinowitz, J., Torreman, M., Emsley, R., Rabinowitz J., Torreman, M., RIS-INT-35 Early Psychosis Global...
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Biomarkers of treatment outcome in schizophrenia: Defining a benchmark for clinical significance
2015, European NeuropsychopharmacologyCitation Excerpt :Against a backdrop of this, the extent to which it is possible to extrapolate from a clinical trial (i.e., efficacy settings) to the real world (i.e., effectiveness settings) is debatable. To date, only one study (Rabinowitz et al., 2003) has compared clinical trial and epidemiological samples of first-episode patients to address this issue empirically. Results showed that compared to the epidemiological cohort, the clinical trial missed 33% of patients but that the data samples did not significantly differ on age of onset, age, gender and premorbid functioning; but drug trial patients had higher BPRS, slightly lower CGI scores, and less formal education than those in the epidemiological study.
One-year, randomized, open trial comparing olanzapine, quetiapine, risperidone and ziprasidone effectiveness in antipsychotic-naive patients with a first-episode psychosis
2012, Psychiatry ResearchCitation Excerpt :Studies specifically exploring predictors of antipsychotic discontinuation in FEP patients have identified several risk factors, such as severity of suspiciousness and delusions, low baseline occupational status, alcohol use, lack of insight, extrapyramidal side effects, male gender and younger age (Miller, 2008). Recent evidence has shown that results yielded from randomized controlled trials of antipsychotic efficacy may not apply to usual clinical practice (Rabinowitz et al., 2003; March et al., 2005). In comparison to efficacy studies, pragmatic and naturalistic studies do not imply overly restrictive inclusion criteria, have longer follow-up periods, and use clinically meaningful outcome measures in order to enhance the generalizability of findings for usual clinical practice (Fleischhacker et al., 2005; Stroup et al., 2006).
Eligibility of schizophrenia inpatients to participate in clinical trials
2012, Revista de Psiquiatria y Salud MentalElaboration on the Early-Onset Hypothesis of Antipsychotic Drug Action: Treatment Response Trajectories
2010, Biological PsychiatryCitation Excerpt :The sample was selected according to criteria for a RCT and might not accurately represent routine clinical practice. Previous research, however, has suggested that a sample from a recent-onset clinical trial (7) resembled in many key ways a large first-episode epidemiological cohort (32). That study also had five symptom severity trajectories over 4 weeks and 6 months that resembled the ones found here (7).