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Long-acting injectable versus daily oral antipsychotic treatment trials in schizophrenia: pragmatic versus explanatory study designs.

Bossie CA, Alphs LD, Correll CU - Int Clin Psychopharmacol (2015)

Bottom Line: Each study's design was rated using the six-domain ASPECT-R (A Study Pragmatic : Explanatory Characterization Tool-Rating).Nonparametric Wilcoxon rank-sum tests compared ratings of studies supporting (n=7) and not supporting (n=4) a LAI advantage.ASPECT-R total and domain scores were significantly higher (more pragmatic) in studies finding a LAI versus oral AP treatment advantage than those that did not.

View Article: PubMed Central - PubMed

Affiliation: aJanssen Scientific Affairs, LLC, Titusville, New Jersey bDepartment of Psychiatry, The Zucker Hillside Hospital, Glen Oaks cHofstra-North Shore LIJ School of Medicine, Hempstead, New York, USA.

ABSTRACT
Trial design characteristics related to the explanatory : pragmatic spectrum may contribute toward the inconsistent results reported in studies comparing long-acting injectable (LAI) versus daily oral antipsychotic (AP) treatments in schizophrenia. A novel approach examined the hypothesis that a more pragmatic design is important to show the advantages of LAI versus oral APs. A literature search identified comparative studies assessing the clinical efficacy/effectiveness of LAI versus oral APs in more than 100 schizophrenia patients, with 6-month or more duration/follow-up, and published between January 1993 and December 2013 (n=11). Each study's design was rated using the six-domain ASPECT-R (A Study Pragmatic : Explanatory Characterization Tool-Rating). Nonparametric Wilcoxon rank-sum tests compared ratings of studies supporting (n=7) and not supporting (n=4) a LAI advantage. ASPECT-R total and domain scores were significantly higher (more pragmatic) in studies finding a LAI versus oral AP treatment advantage than those that did not. The rank order of this significance among domains was as follows: 'participant compliance assessment' (P=0.005), 'medical practice setting/practitioner expertise' (P=0.006), 'intervention flexibility' (P=0.007), 'follow-up intensity/duration' (P=0.009), 'primary trial outcomes' (P=0.012), and 'participant eligibility' (P=0.015). Findings support that more pragmatic, less explanatory design features are important to show advantages for LAI treatment. Explanatory studies may introduce features that obscure advantages related to adherence.

No MeSH data available.


Related in: MedlinePlus

Flow chart of identification, screening and eligibility, and inclusion of clinical trials. AP, antipsychotic; LAI, long-acting injectable.
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Figure 1: Flow chart of identification, screening and eligibility, and inclusion of clinical trials. AP, antipsychotic; LAI, long-acting injectable.

Mentions: This literature review consisted of three components: (i) a search engine-based literature review; (ii) an examination of relevant review articles; and (iii) any other published studies known to the authors (Fig. 1). The literature search was performed using MEDLINE/PubMed. Search terms and criteria were as follows: (((Antipsychotic) AND schizophrenia) AND ((depot OR injection OR long-acting))) AND oral. Filters included clinical trial, human, English language, and publication dates of 1 January 1993 to 31 December 2013. The manual review of citations identified by MEDLINE/PubMed removed those that: (i) did not include both a LAI and an oral AP treatment arm; (ii) did not include a measure of clinical efficacy or effectiveness; (iii) represented findings from a pooled analysis (vs. a single study); (iv) had a duration of less than 6 months; (v) enrolled less than 100 participants; (vi) were not in English; and (vii) were a secondary publication of a previously included study (i.e. post-hoc subpopulation data). This literature search was then supplemented by an examination of references cited in relevant review articles and any other published studies known to the authors through December 2013.


Long-acting injectable versus daily oral antipsychotic treatment trials in schizophrenia: pragmatic versus explanatory study designs.

Bossie CA, Alphs LD, Correll CU - Int Clin Psychopharmacol (2015)

Flow chart of identification, screening and eligibility, and inclusion of clinical trials. AP, antipsychotic; LAI, long-acting injectable.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4525810&req=5

Figure 1: Flow chart of identification, screening and eligibility, and inclusion of clinical trials. AP, antipsychotic; LAI, long-acting injectable.
Mentions: This literature review consisted of three components: (i) a search engine-based literature review; (ii) an examination of relevant review articles; and (iii) any other published studies known to the authors (Fig. 1). The literature search was performed using MEDLINE/PubMed. Search terms and criteria were as follows: (((Antipsychotic) AND schizophrenia) AND ((depot OR injection OR long-acting))) AND oral. Filters included clinical trial, human, English language, and publication dates of 1 January 1993 to 31 December 2013. The manual review of citations identified by MEDLINE/PubMed removed those that: (i) did not include both a LAI and an oral AP treatment arm; (ii) did not include a measure of clinical efficacy or effectiveness; (iii) represented findings from a pooled analysis (vs. a single study); (iv) had a duration of less than 6 months; (v) enrolled less than 100 participants; (vi) were not in English; and (vii) were a secondary publication of a previously included study (i.e. post-hoc subpopulation data). This literature search was then supplemented by an examination of references cited in relevant review articles and any other published studies known to the authors through December 2013.

Bottom Line: Each study's design was rated using the six-domain ASPECT-R (A Study Pragmatic : Explanatory Characterization Tool-Rating).Nonparametric Wilcoxon rank-sum tests compared ratings of studies supporting (n=7) and not supporting (n=4) a LAI advantage.ASPECT-R total and domain scores were significantly higher (more pragmatic) in studies finding a LAI versus oral AP treatment advantage than those that did not.

View Article: PubMed Central - PubMed

Affiliation: aJanssen Scientific Affairs, LLC, Titusville, New Jersey bDepartment of Psychiatry, The Zucker Hillside Hospital, Glen Oaks cHofstra-North Shore LIJ School of Medicine, Hempstead, New York, USA.

ABSTRACT
Trial design characteristics related to the explanatory : pragmatic spectrum may contribute toward the inconsistent results reported in studies comparing long-acting injectable (LAI) versus daily oral antipsychotic (AP) treatments in schizophrenia. A novel approach examined the hypothesis that a more pragmatic design is important to show the advantages of LAI versus oral APs. A literature search identified comparative studies assessing the clinical efficacy/effectiveness of LAI versus oral APs in more than 100 schizophrenia patients, with 6-month or more duration/follow-up, and published between January 1993 and December 2013 (n=11). Each study's design was rated using the six-domain ASPECT-R (A Study Pragmatic : Explanatory Characterization Tool-Rating). Nonparametric Wilcoxon rank-sum tests compared ratings of studies supporting (n=7) and not supporting (n=4) a LAI advantage. ASPECT-R total and domain scores were significantly higher (more pragmatic) in studies finding a LAI versus oral AP treatment advantage than those that did not. The rank order of this significance among domains was as follows: 'participant compliance assessment' (P=0.005), 'medical practice setting/practitioner expertise' (P=0.006), 'intervention flexibility' (P=0.007), 'follow-up intensity/duration' (P=0.009), 'primary trial outcomes' (P=0.012), and 'participant eligibility' (P=0.015). Findings support that more pragmatic, less explanatory design features are important to show advantages for LAI treatment. Explanatory studies may introduce features that obscure advantages related to adherence.

No MeSH data available.


Related in: MedlinePlus