Channeling of New Neuropsychiatric Drugs—Impact on Safety and Effectiveness Studies

This study aimed to examine differential prescribing due to channeling and propensity score non-overlap over time in new versus established treatments for common neurological conditions. We conducted cross-sectional analyses on a national sample of US commercially insured adults using 2005–2019 data. We compared new users of recently approved versus established medications for management of diabetic peripheral neuropathy (pregabalin versus gabapentin), Parkinson disease psychosis (pimavanserin versus quetiapine), and epilepsy (brivaracetam versus levetiracetam). Within these drug pairs, we compared demographic, clinical, and healthcare utilization characteristics of recipients of each drug. In addition, we fit yearly propensity score models for each condition and assessed propensity score non-overlap over time. For all three drug pairs, users of the more recently approved medications more frequently had prior treatment (pregabalin = 73.9%, gabapentin = 38.7%; pimavanserin = 41.1%, quetiapine = 14.0%; brivaracetam = 93.4%, levetiracetam = 32.1%). Propensity score non-overlap and its resulting sample loss after trimming were the greatest in the first year that the more recently approved medication was available (diabetic peripheral neuropathy, 12.4% non-overlap; Parkinson disease psychosis, 6.1%; epilepsy, 43.2%) and subsequently improved. Newer neuropsychiatric therapies appear to be channeled to individuals with refractory disease or intolerance to other treatments, leading to potential confounding and biased comparative effectiveness and safety study findings when compared to established treatments. Propensity score non-overlap should be reported in comparative studies that include newer medications. When studies comparing newer and established treatments are critically needed as soon as new treatments enter the market, investigators should recognize the potential for channeling bias and implement methodological approaches like those demonstrated in this study to understand and improve this issue in such studies.