A research study has indicated that researchers should better consider time differences between individual symptom improvement during schizophrenia clinical trials.
A paper, published in Lancet Psychiatry, looked at individual participant data (IPD) from six antipsychotic drug trials.
Discover B2B Marketing That Performs
Combine business intelligence and editorial excellence to reach engaged professionals across 36 leading media platforms.
It found that while all five symptom domains on the Positive and Negative Syndrome Scale (PANNS) showed substantial improvements during the first weeks of treatment, plateauing from week 15 onwards, some improved quicker than others.
Within the first six months, hostility and excitability symptoms decreased by 76% from baseline, positive symptoms by 64%, anxiety and depression symptoms by 57%, cognitive and disorganisation symptoms by 61%, and negative symptoms by 50%.
This equated to a three-week time to response for hostility and excitement, and four weeks for positive symptoms and anxiety and depression, compared with eight weeks for negative symptoms and cognitive and disorganisation symptoms.
The regulatory standard for schizophrenia endpoint selection has long favoured the total PANSS score or BPRS total score as the primary endpoint, with domain scores playing a supporting role.
The European Medicines Agency’s (EMA) guideline on schizophrenia trial standards, tracked by RAPS, confirms that short-term efficacy assessments should centre on total-scale instruments such as PANSS or BPRS.
The US Food and Drug Administration (FDA) published a benefit-risk framework, which was finalised in 2023, evaluating a drug’s overall clinical profile without mandating domain-level temporal disaggregation as a protocol design requirement.
This research paper has found that while both agencies are evaluating the correct endpoints, the time scales could be improved upon.
Currently, when a patient did not see improvement in negative symptoms, it would be determined they were a non-responder. This paper suggests, however, that the patient may not have had enough time to respond.
According to the researchers, both psychiatrists and patients should allow more time to observe substantial therapeutic effects of antipsychotic treatment on negative symptoms and in cognitive and disorganisation symptoms compared to other measures.
As a result, treatment changes or patient discharge in trials should therefore not be made prematurely when positive symptoms have responded but negative and cognitive and disorganisation symptoms have not yet improved.
The authors used individual participant data (IPD) of 2079 patients undergoing acute antipsychotic treatment from six antipsychotic drug trials to explore the temporal patterns of symptom change during the first six to 12 months of treatment.
According to GlobalData research in December 2024, the schizophrenia market size across the seven major markets (7MM: US, France, Germany, Italy, Spain, UK, and Japan) was $8.4bn in 2021 and is forecast to reach $17bn by 2031.
The “Schizophrenia: Seven-Market Drug Forecast and Market Analysis – Update” reveals that the late-stage pipeline products are expected to capture a significant portion of the schizophrenia market, accounting for 33.4% of global sales in 2031, despite the atypical antipsychotics retaining the largest portion of patient shares.
GlobalData is the parent company of Clinical Trials Arena.
