Health Technology Assessment on Point of Care Testing for the Management of Clozaril in Individuals with Treatment-Resistant Schizophrenia

Condition Description – Schizophrenia is a serious, chronic psychiatric disorder that affects how a person thinks, perceives reality, and behaves. Individuals with schizophrenia experience a decreased overall quality of life, depression, treatment side effects, cognitive, social, and occupational impairment, morbidity, homelessness, stigmatization, violence, and abuse. The estimated life expectancy of individuals with schizophrenia is 15-20 years shorter than the general population; for unnatural causes of death, suicide is the largest risk factor for premature mortality among individuals with schizophrenia.

Approximately 10-30% of individuals with schizophrenia are resistant to treatment. Individuals with treatment-resistant schizophrenia (TRS) retain positive symptoms of the illness after two or more trials of antipsychotic medication.

Current treatment options – There is no cure for schizophrenia, and treatments, usually psychotherapy and medication, are centered around symptom management. Clozapine is the recommended pharmacotherapy for TRS. Clozapine use is associated with serious side effects including agranulocytosis, cardiomyopathy, diabetes mellitus, pneumonia, and seizures. Agranulocytosis is the most well-known side effect of clozapine and occurs in 0.4 to 0.8% of clozapine users. As a result, diligent monitoring throughout the treatment course is essential.

Description of the Assessed Technology(ies) – Point of Care (POC) testing can identify low white blood cell counts (WCB) and absolute neutrophil counts (ANC). CSAN Pronto and similar POC devices may potentially reduce the monitoring burden for patients, by providing quick results at the physician’s clinic without the inconvenience or delayed results associated with a laboratory visit. In addition, the finger prick sampling may be less painful than venous blood draws and the use of POC devices may improve patient adherence to clozapine therapy.

However, CSAN Pronto only monitors WCB and ANC so venous blood draws are still required for clozapine levels and any other tests such as blood glucose and liver functioning.

Health Technology Assessment Committee’s Findings: 

After reviewing the available evidence, the Health Technology Assessment Committee found:

1. The available evidence for the use of CSAN Pronto to support monitoring for one of the serious potential side-effects of Clozaril in people with treatment-resistant schizophrenia (TRS) is extremely limited.
2. It is paired with a specific brand-name drug (Clozaril) and according to the manufacturer, not available for patients taking therapeutically equivalent and lower cost generic versions of clozapine.
3. The device links with a private, industry-owned registry of patient data.

Given the limited available evidence and other equity and ethical concerns, review of the other available point-of-care testing devices for the assessment of white blood cell counts (which do not require concurrent use of any specific pharmaceutical products) would be beneficial if considering implementation of a POC device for TRS. Such a review would ideally:

• Identify other devices that may be eligible to aid in the monitoring of side effects in individuals taking clozapine as patients with TRS may realize the most benefit from POC testing given:
  • POC may significantly reduce barriers of accessing care for TRS patients.
  • Considerably decrease caregiver workload and burnout associating with frequent mandatory blood draws for laboratory testing.
• Be conducted within an Assertive Community Treatment team setting to assess the associated harms and benefits.

Upon examination of the above, HTAC suggests further evidence is required such as an implementation study using a point-of care device not restricted to a specific drug. This would ideally include consideration of the CSAN Pronto device upon any changes to the company’s stance for compatibility with Clozapine as well as Clozaril. Such a study should be conducted within an Assertive Community Treatment team setting to assess the associated harms and benefits.