Évaluation de l'impact clinique et économique du développement d'un traitement pour la schizophrénie

Aim: Pharmacological strategies for schizophrenia have received increasing attention due to the development of new therapies more effective, better tolerated but more expensive. Schizophrenia is a chronic illness with various states of illness.   Objectives: This research program aimed: 1) to evaluate the factors associated with the risk of being in a specific state of schizophrenia in order to construct the risk functions of the course of schizophrenia modeling; 2) to develop and validate a Markov model with Monte-Carlo micro-simulations in order to simulate the natural course of patients who have been newly diagnosed with schizophrenic based upon the individual risk factors profile; and 3) to estimate the direct healthcare and non-healthcare cost of schizophrenia and to simulate clinical and economic impact of developing a new treatment, in a cohort of patients newly diagnosed with schizophrenia, over the first 5 years following their diagnosis. Methods: For the first objective of this research program, a total of 14,320 newly diagnosed patients with schizophrenia were identified based on data from the RAMQ and Med-Echo databases. Six disorder states of schizophrenia were defined: first episode (FE), low dependency state (LDS), high dependency state (HDS), Stable state (Stable), Well state (Well) and Death state (Death). To evaluate factors associated to the risk of being in each disease state, we constructed 4 risk functions based on the Cox proportional hazard analysis for competing risks. For the second objective, a Markov model with Monte-Carlo microsimulations with the six specific states of schizophrenia was developed and validated. In the model, each subject had his own probabilities of transition between specific states, which were estimated based on the cumulative incidence function. For the third objected, we used the Markov model we previously developed. The model includes direct healthcare costs estimated from the Régie de l’assurance maladie du Québec and Med-Echo databases and direct non-healthcare costs estimated from the surveys and publications of Statistics Canada.  Results: A total of 14,320 individuals were identified in the study cohort as newly diagnosed patients with schizophrenia. The mean follow-up of the subjects was of 4.4 (± 2.6) years. The age, the sex, the schizophrenia treatment, and having comorbidities are factors that are associated with the schizophrenia course. After a five-year period, our results show that 41% of patients will be considered as having recovered, 13% will be in stable condition and 3.4% of patients will have died. The mean direct healthcare and non-healthcare cost of schizophrenia over the first 5 years following diagnosis was estimated $36,701 Canadian (CAN) (95% CI: 36,264 to 37,138). The direct healthcare cost accounted for 56.2% of the total cost, welfare assistance for 34.6% and long term care facilities for 9.2%. On the direct healthcare cost, hospitalisation cost accounted for 64.6%, medical cost for 11.4% and drug-related cost for 24%. In the case where a new treatment with 20% increase of effectiveness will be available, the direct healthcare and non-healthcare costs can be reduced up to 14.2%. Conclusion: We have identified factors associated with the schizophrenia’s specific states, The Markov model we have developed is the first Canadian model incorporating transition probabilities adjusted for individual risk factor profiles using real-life data. The model shows a good internal and external validity. Based on the cost estimates, our results indicate that a new treatment could possibly reduce hospitalization and long-term care facility costs while potentially enabling patients to return to active employment that would in turn contribute to the reduction of the welfare assistance cost.

Keyphrases: validation interne, schizophrenia, risk factors, specific states of schizophrenia, internal validation, external validation, Markov Model with Monte-Carlo microsimulations, costs of schizophrenia, direct healthcare cost, direct non-healthcare cost