Challenges, unmet needs and future directions – a critical evaluation of the clinical trial landscape in schizophrenia research

ABSTRACT

Introduction

Developing novel antipsychotic mechanisms of action and repurposing established compounds for the treatment of schizophrenia is of utmost importance to improve relevant symptom domains and to improve the risk/benefit ratio of antipsychotic compounds. Novel trial design concepts, pathophysiology-based targeted treatment approaches, or even the return to old values may improve schizophrenia outcomes in the future.

Areas covered

In this review of the clinical trial landscape in schizophrenia, we present an overview of the challenges and gaps in current clinical trials and elaborate on potential solutions to improve the outcomes of people with schizophrenia.

Expert opinion

The classic parallel group design may limit substantial advantages in drug approval or repurposing. Collaborative approaches between regulatory authorities, industry, academia, and funding agencies are needed to overcome barriers in clinical schizophrenia research to allow for meaningful outcome improvements for the patients.

KEYWORDS:

• Schizophrenia
• clinical trial
• methodology
• novel compounds
• evidence-based medicine
• antipsychotics
• guidelines

Article highlights

• In schizophrenia clinical trials, placebo responses are increasing, leading to a relative loss of efficacy of novel antipsychotic compounds in the respective analyses.

• Non-inferiority, adaptive trial, basket, and umbrella designs as already frequently used in other medical fields, such as oncology, may help to simply and accelerate the approval of novel and the repurposing of available compounds.

• Stratified clinical trials using prognostic markers or biomarkers will help to reduce the disease-associated heterogeneity in the recruited samples, resulting in smaller but focused clinical trials.

• The importance of patient reported outcome measures and the involvement of experienced experts must be more pronounced in future schizophrenia trials.

• To develop more relevant evidence-based recommendations for clinical practice in the future, results from registry studies should be enhanced especially for clinical questions where no controlled trials are available or expected.

Declaration of interest

E Wagner was a member of the advisory boards of Recordati and Boehringer-Ingelheim. W Strube has received a speaker’s honorarium from Mag&More GmbH and Neurocare and was a member of the advisory board of Recordati. A Hasan was a member of the advisory boards of Boehringer-Ingelheim, Lundbeck, Janssen, Otsuka, Rovi, and Recordati and received paid speakership by these companies as well as by AbbVie and Advanz. He is editor of the German schizophrenia guideline. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

A reviewer on this manuscript has disclosed that they are/was an investigator for a number of the companies mentioned in this manuscript. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

The project was carried out using the clinical trials infrastructure of the DZPG (German Center for Mental Health) [FKZ: 01EE2303C].