The objective of this study was to predict the health and economic impact of employing technologies that improve medication compliance by extending drug delivery and decreasing frequency of administration. The study was based on the hypothesis that improving medication compliance will lead to a reduction in illness relapse and the costs associated with treating the relapses. Modeled and clinical support for this hypothesis exists in the published literature
[6, 9, 15, 16, 21, 23, 28]. The model used for the presented analysis implements information for risperidone available in the public domain as a basis for forward-thinking analysis. The results estimate the value of seeking opportunities to reduce illness relapse in this patient population.
Most published data support the hypothesis that prolonging the duration of action of an antipsychotic medication (with a resultant reduction in dosing frequency) is associated with a reduction in schizophrenia symptom exacerbation compared to standard oral therapy
[15, 16, 21]. Over one year of treatment, the bi-weekly injectable formulation of risperidone reduced the number of relapses per person by 0.2 while, at five years, 0.56 relapses were avoided. The one year reduction in the present analysis is somewhat less than the prediction of 0.6 relapses avoided in a model published by Edwards, et al.
 and the precise explanation for the difference is unknown. However, the Edwards model predicted a greater number of relapses for both the standard oral therapy and long-acting injectable groups which may have been a contributing factor. Conversely, the five year projection in our model of 0.56 relapses avoided is consistent with data presented by multiple models
At present, there are no long-acting formulations of antipsychotic therapy for schizophrenia with dosing frequencies that extend beyond one month. Moreover, there are no long-acting formulations of risperidone that have dosing frequencies of greater than two weeks. Nonetheless, given the application of existing technologies for prolonging the duration of action of pharmaceutical agents for up to one year in other therapeutic areas, it was of interest to estimate the potentially beneficial effects of applying these technologies to the treatment of schizophrenia. Extending the duration of action to three months was associated with further reductions in the number of relapses compared with both standard, daily risperidone therapy (RIS-SOT) as well as the currently available risperidone long-acting injection (RIS-LAI). Further improvements were seen when the duration of action was extended to six and nine months. Quantified estimates of reductions in relapse produced in this study represent the value of the study methodology and provide evidence supporting the potential therapeutic benefit of extending the duration of action of antipsychotic medications beyond that which is currently available.
Because relapse is a primary cost driver in the management of schizophrenia, it is anticipated that a reduction in relapses would be associated with corresponding reductions in the cost of treatment. This association has been reported in the literature
[8, 28] and is confirmed in the current model. At one year, total direct medical costs were greatest for daily, standard therapy and decreased with increasing duration of action.
In our analysis, improving medication compliance by prolonging duration of action and reducing administration frequency from daily to once every two weeks resulted in a reduction in direct medical costs of almost $1300/patient at the end of one year. The cost reduction seen when comparing the Less Frequent Administration (LFA) options (> 3 months) to RIS-SOT was even more substantial, resulting in cost reductions ranging from $4600 to $5300 per patient. The LFA options also demonstrated cost reductions versus the bi-weekly risperidone injection with the 3-, 6-, and 9-month alternatives reducing costs by $3300/patient, $3700/patient, and $4000/patient, respectively. Importantly, most of the reduction in direct medical costs was produced via a reduction in the costs associated with inpatient care. A sensitivity analysis confirmed the central contribution of relapses requiring inpatient hospitalization to direct medical costs associated with managing schizophrenia.
Additional calculations (data not shown) estimating the societal burden of disease from the base case model were performed using US population data from the 2010 census
 and the prevalence of schizophrenia data from the National Institute of Mental Health
. The incremental difference between RIS-SOT and RIS-LAI was estimated to be a savings of $4.3 billion; extending the frequency of administration to nine months resulted in estimated savings of $17.8 billion compared to RIS-SOT. Base case total burden was found to be consistent with previously published estimates
In this study, we were limited by the fact that risperidone-based therapeutic options with dosing frequencies of greater than two weeks do not exist. While this limitation may have impacted our assumptions concerning the persistence of therapy with the LFA options, it should not have influenced the adherence levels. Assuming that less frequent dosing will be accomplished via utilization of a long-acting injection or implantation of a drug or drug-device combination, once administered, adherence will be 100% for the identified dosing period. The fact that these longer duration alternatives do not exist in schizophrenia also impacts the total absolute costs and cost differentials as we were not able to include “cost of therapy” in our total direct medical cost calculations.
This study is also limited in its applicability to compare the potential benefits of utilizing one antipsychotic agent versus another as we assumed the use of risperidone in all dosing scenarios. However, we believe that restricting our model to one molecule eliminates the potential confounding that might occur as a result of differences in safety/tolerability and efficacy that might be seen when two different molecules are compared.
There are many potentially fertile areas for future research including an opportunity to further evaluate both the clinical and economic consequences of improved medication adherence and persistence in patients with schizophrenia. More data is required to determine the most effective combination of drug delivery mechanism and dosing frequency for optimal disease management. From an economic perspective, the societal costs associated with schizophrenia are well-documented. However, it will be of great interest to predict the potential impact of a new treatment option not only on direct medical costs but also on the larger societal burden.