D. Layton, V. Osborne, M. Davies, I. Ratcliffe, S. Clarke, S. Shakir, J. Reilly, A. Hale.
Generalisability of results from Modified Prescription-Event Monitoring (M-PEM) studies conducted in primary-care may be limited by excluding patients with complex characteristics (underlying/concurrent disease, medications) exclusively managed in hospital. Specialist Cohort Event Monitoring (SCEM) applies to secondary care. A risk management plan of quetiapine extended release (XL) had a need to describe use and monitor long-term (12+ months) and short term (12 weeks) safety in primary and secondary care, respectively. An M-PEM study monitored safety and use (all indications). A SCEM study monitored early-onset events during titration and at higher doses (>600mg) in Schizophrenia and Bipolar Disorder adults (>18 years) for whom the decision to treat was made by psychiatrists; a comparator (immediate release (IR) quetiapine) was included (ENCEPP Study 5412).
To explore the potential of bias by comparing M-PEM and SCEM patient characteristics.
Both studies used an observational cohort design. MPEM data derived from dispensed prescriptions September 2008-February 2013 and questionnaires sent to GPs 12+ months after each patient started treatment. SCEM data derived from questionnaires completed by psychiatrists 12+ weeks after each patient started treatment December 2009-December 2012. Descriptive statistics and Odds Ratios (OR) +95%CI (exact method) were calculated.
SCEM XL cohort (n=646) included 258 (39.9%) with Schizophrenia, and 345 (53.4%) with Bipolar Disorder. M-PEM cohort (n=3276) included 2362 (17.8%) adults with Schizophrenia, 3820 (28.6%) with BD. In Schizophrenia, SCEM patients were significantly more likely than M-PEM patients to be < 30 yrs old [84vs488; OR 1. (1.2,2.2)], have a history of: depression [152vs446; OR 6. (4.8, 8.1)], extrapyramidal symptoms (EPS) [46vs103; OR 4. (3.2,7.0)] and prior antipsychotic use [175vs779; OR 4.2 (3.2,5.6)]; recent (<28 days prior) IR use was less likely [18vs632; OR 0.2(0.1,0.3)]. In BD, SCEM patients were more likely than M-PEM patients to have a history of: depression [258vs1344; OR 5. (4.2,7.0)], EPS [34v66; OR 6.2(3.9,9.7)], diabetes [37vs168; OR 2.6 (1.7, 3.8)] and prior antipsychotic use [182vs772; OR 4.4(3.5,5.5)]; recent IR use was less likely [17vs985; OR 0.2(0.1,0.2)].
SCEM patients had a higher prevalence than M-PEM patients of depression, EPS, diabetes and antipsychotic use which are risk factors for some adverse events. Considerations include differences in: the data available within medical records; prescribing guidelines; method of identifying patients; and overlap of study populations. These findings suggest that selection bias may exist which may affect generalisability of primary-care based study results to all treated patients, thus there is a need for surveillance in secondary care.