Trial exclusion criteria and their impact on the estimation of antipsychotic drugs effect: A case study using the SOHO database

Nordon, Clémentine; Bovagnet, Thomas; Belger, Mark; Jiménez, Javier González; Olivares, Robert; Chevrou‐Séverac, Hélène; Verdoux, Hélène; Haro, Josep María; Abenhaim, Lucien; Karcher, Hélène

doi:10.1016/j.schres.2017.07.031

Cited by 8 publications

(6 citation statements)

References 53 publications

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“…frequent clinical assessments and by excluding patients who have somatic co-morbidity, psychiatric comorbidity like substance misuse or are otherwise unstable (Alphs et al, 2014). These characteristics were all linked to relapse in the current study and they are most likely also linked to a reduced adherence to treatment (Alphs et al, 2014;Nordon et al, 2017). Furthermore, in contrast to RCTs, observational studies like mirror-image studies, in which LAI is chosen by the clinician on the basis of patient´s behavior like non-adherence, have shown a significant reduction in relapse (Kishimoto et al, 2013).…”

Section: Discussionmentioning

confidence: 72%

Second-generation LAI are associated to favorable outcome in a cohort of incident patients diagnosed with schizophrenia

Nielsen

Hessellund

Valentin

et al. 2018

Schizophrenia Research

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Section: Discussionmentioning

confidence: 72%

Second-generation LAI are associated to favorable outcome in a cohort of incident patients diagnosed with schizophrenia

Nielsen

Hessellund

Valentin

et al. 2018

Schizophrenia Research

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“…Contrary to numerous RCTs, 30 the expected level of adherence to treatment is not an exclusion criterion in PCTs. Participants' level of adherence will be reflecting that of routine clinical practice.…”

Section: Resultsmentioning

confidence: 99%

A first step towards best practice recommendations for the design and statistical analyses of pragmatic clinical trials: A modified Delphi approach

Palin

Staa

Steels

et al. 2022

Brit J Clinical Pharma

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Aim Pragmatic clinical trials (PCTs) are randomized trials implemented through routine clinical practice, where design parameters of traditional randomized controlled trials are modified to increase generalizability. However, this may introduce statistical challenges. We aimed to identify these challenges and discuss possible solutions leading to best practice recommendations for the design and analysis of PCTs. Methods A modified Delphi method was used to reach consensus among a panel of 11 experts in clinical trials and statistics. Statistical issues were identified in a focused literature review and aggregated with insights and possible solutions from experts collected through a series of survey iterations. Issues were ranked according to their importance. Results Twenty‐seven articles were included and combined with experts' insight to generate a list of issues categorized into participants, recruiting sites, randomization, blinding and intervention, outcome (selection and measurement) and data analysis. Consensus was reached about the most important issues: risk of participants' attrition, heterogeneity of “usual care” across sites, absence of blinding, use of a subjective endpoint and data analysis aligned with the trial estimand. Potential issues should be anticipated and preferably be addressed in the trial protocol. The experts provided solutions regarding data collection and data analysis, which were considered of equal importance. Discussion A set of important statistical issues in PCTs was identified and approaches were suggested to anticipate and/or minimize these through data analysis. Any impact of choosing a pragmatic design feature should be gauged in the light of the trial estimand.

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“…This likely stems from the fact that most guidelines are based on RCTs, which have limited possibilities for long-term follow-up and exploring maintenance treatments, and are often more focused on acute-phase treatment. Randomized controlled trials also often have very stringent inclusion criteria, which have become more stringent over the years, leading to the exclusion of many patient groups, including those with schizophrenia that is resistant to APM treatment [38][39][40][41]. This review focuses on the more recent data based on large studies emphasizing real-world data and high-quality meta-analyses.…”

Section: Antipsychotic Polypharmacy (App) and Treatment Guidelinesmentioning

confidence: 99%

Antipsychotic Polypharmacy for the Management of Schizophrenia: Evidence and Recommendations

Lähteenvuo

Tiihonen

2021

Drugs

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Schizophrenia is a debilitating illness with a lifetime prevalence estimate of 0.6% and consists of symptoms from the positive, negative, and cognitive domains. Social support, therapy, psychoeducation, and overall case management are very important aspects of the treatment of schizophrenia. However, as abnormalities in neurotransmission are one of the key findings of schizophrenia pathology, pharmacotherapies are cornerstones of the management of schizophrenia. Antipsychotics have been used as the primary pharmacological treatment of schizophrenia. These agents often have a good effect on reducing positive symptoms, but may not markedly improve negative symptoms or cognitive defects. However, at least 20% of individuals with schizophrenia do not experience a substantial response from monotherapy with antipsychotics. Further, despite evolving treatment protocols and advances in early recognition of the disorder, 70% of patients with schizophrenia require long-term, even lifetime, medication to control their symptoms and do not achieve complete recovery. To address these shortcomings, clinicians and research scientists have explored different combinations of treatments, polypharmacy, to improve the treatment of patients. Antipsychotic polypharmacy has been shown to cause more side effects than monotherapy, which is the main reason why most treatment guidelines caution against it. Antipsychotic monotherapy should be strived for and clozapine should be tried at the latest if two monotherapy trials with other antipsychotics have failed and no absolute contraindications exist. If residual symptoms exist despite trials of adequate dose and duration, other reasons that may reduce treatment effect should be ruled out. Long-acting injectables or blood concentration measurements should be considered to affirm compliance and proper serum levels. Antipsychotic polypharmacy should be considered and discussed with patients from whom the aforementioned procedures do not produce a satisfactory treatment result. In some cases, antipsychotic polypharmacy may produce better results than other forms of treatment augmentation, such as benzodiazepines. In particular, combining aripiprazole with clozapine may be effective in reducing treatment side effects or residual symptoms, and this is likely to hold true for combining other partial dopamine D 2 agonists with clozapine as well, although currently scant data exist. More research is needed, both in controlled but also real-world settings, to define optimal antipsychotic polypharmacy and/or other psychotropic treatment augmentation strategies for specific patient groups and situations.

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Trial exclusion criteria and their impact on the estimation of antipsychotic drugs effect: A case study using the SOHO database

Cited by 8 publications

References 53 publications

Second-generation LAI are associated to favorable outcome in a cohort of incident patients diagnosed with schizophrenia

Second-generation LAI are associated to favorable outcome in a cohort of incident patients diagnosed with schizophrenia

A first step towards best practice recommendations for the design and statistical analyses of pragmatic clinical trials: A modified Delphi approach

Antipsychotic Polypharmacy for the Management of Schizophrenia: Evidence and Recommendations

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