By the end of 2025, more than 1 million people across the world will be diagnosed with schizophrenia. The WHO estimates that more than 24 million people globally live with the severe delusions, hallucinations, and cognitive impairment caused by the disease, which significantly damages their quality of life. In fact, Quality of Life (QoL) is a crucial outcome when studying the effects of a schizophrenia treatment, as the condition profoundly affects various aspects of a person's life beyond cognitive and emotional health. Schizophrenia often disrupts social relationships, employment, and daily functioning, leading to isolation and reduced independence.
By using clinical outcome assessments (COAs) and patient-reported outcome measures (PROMs), healthcare providers and researchers can assess the broader effects of the treatment on patients’ quality of life, ensuring that the intervention not only alleviates the cognitive symptoms of schizophrenia, but also addresses the social and emotional impacts of the illness, leading to improved overall wellbeing.
Growing role of COAs in schizophrenia research
COAs are standardized instruments, such as questionnaires, assessments, and diaries, that measure, describe, or reflect how a patient feels, functions, or survives. COAs provide insights that go beyond traditional clinical measures to support the development of new patient-centered medications and treatments. The four types of COAs are Patient-Reported Outcomes (PROs), Clinician-Reported Outcomes (ClinROs), Observer-Reported Outcomes (ObsROs) and Performance Outcomes (PerfOs).
On September 26, 2024, the U.S. Food and Drug Administration approved Cobenfy (xanomeline and trospium chloride capsules), the first new treatment for schizophrenia in more than 50 years. Key to securing FDA approval was Cobenfy’s use of schizophrenia-specific ClinROs: the Positive and Negative Symptom Scale (PANSS) and the Clinical Global Impressions Scale (CGI-S). The PANSS is a widely used clinical outcome assessment designed to measure the severity of schizophrenia symptoms and evaluate the effectiveness of treatment. The CGI-S is used by clinicians to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis.
Key COAs in schizophrenia research and treatment
While PANSS and CGI-S are crucial for assessing symptom severity, several other validated COAs play an important role in understanding treatment effectiveness in patients suffering from schizophrenia. Most notable is the Schizophrenia Quality of Life Scale (SQLS), a PRO designed to measure quality of life effects of treatment on people suffering from the unique challenges of schizophrenia. The SQLS evaluates psychosocial functioning, energy levels, and motivation – aspects that significantly impact daily life but might not be captured by traditional symptom scales. Among other widely-used COAs are measures that assess specific domains such as social functioning, cognition, and treatment satisfaction. This variety of tools, when used in conjunction with other measures such as biomarkers and neuroimaging, provide a comprehensive view of schizophrenia treatment outcomes, helping researchers and clinicians understand the full impact of interventions on patients' lives.
Challenges in measuring outcomes in schizophrenia
Given the cognitive impairment associated with schizophrenia, assessing treatment outcomes for the disease presents unique challenges. Cognitive symptoms can lead to patients’ inability to self-report symptoms and experiences accurately. Furthermore, the heterogenous nature of schizophrenia means that patients may experience vastly different combinations of positive symptoms such as hallucinations and delusions, negative symptoms such as reduced emotional expression and social withdrawal, and cognitive, mood and motor symptoms. This complexity means that to capture the full spectrum of treatment effects, researchers must take a multidimensional approach to measuring outcomes and treatment efficacy. In fact, to address the unmet medical need and the lack of fit-for-purpose PerfO measures to assess cognitive function in patients with schizophrenia, researchers developed a new PerfO designed specifically for the disease: the EPICOG-SCH. This multidimensional PerfO is comprised of a battery of tests designed to measure multiple cognitive domains such as working memory, speed of information processing, verbal memory and executive functioning.
Regulatory recognition of COAs in schizophrenia label claims
The FDA and EMA's increasing emphasis on patient-focused drug development has elevated the importance of COAs in the development and regulatory approval processes. This trend is evidenced by the growing number of schizophrenia treatments that include COA-derived endpoints in their label claims. In fact, Mapi Research Trust’s PROLABELS database shows that 48 approved drugs for schizophrenia include COA data in their label claims, demonstrating regulatory bodies’ recognition of the importance of COAs in determining treatment effectiveness.
The recent regulatory approval of Cobenfy highlights how COAs can provide compelling evidence of treatment efficacy within schizophrenia. The inclusion of both PANSS and CGI-S data in Cobenfy's label claim helped demonstrate its significant impact on patient outcomes, supporting its historic approval as the first new treatment mechanism for schizophrenia in decades.
For any schizophrenia therapies currently under development, selecting and implementing COAs in their clinical trial protocols will be an important element in ultimately securing regulatory approval. Within the PROQOLID and PROLABELS databases, which provide access to more than 7,700 COAs and nearly 2,400 drugs with COA claims respectively, researchers can access 16 COAs developed specifically for schizophrenia research, including gold-standard measures like the SQLS.
The importance of patient experience in schizophrenia research
While a reduction in symptoms will likely remain a key primary endpoint for any schizophrenia therapies in development, the increasing adoption of quality-of-life focused COAs reflects a broader understanding of how treatment success can be measured. Beyond tracking improvements in positive and negative symptoms through tools like PANSS, the integration of quality-of-life focused COAs ensures that treatment effectiveness is evaluated through the lens of the patient’s lived experience. This comprehensive approach, recognized by the FDA’s CDER Patient-Focused Drug Development guidance, ensures that our understanding of true treatment success in schizophrenia, for the millions around the world suffering, extends beyond symptom management to encompass improvements in social relationships, daily functioning, and overall well-being.
To access validated COAs for schizophrenia research, or to learn more about how COAs have been used in successful schizophrenia label claims, please visit ePROVIDE.