Purpose: To estimate the willingness and ability of private plans to manage costs during the generic drug procurement reform era that began in 2006 in Canada. Two cost management aspects were assessed; the prices paid for generic drugs and the extent to which private plans have enacted measures to increase generic substitution. Methods: IMS-Brogan Pharmastat data was used to estimate the price of commonly prescribed generic drugs and generic share of prescriptions, by plan type, province and quarter from 2003 to 2012. Results: Prices did not decline unless the provincial governments mandated the reductions. Savings from this mandate was approximately $264 million in Ontario. Rates of generic substitution were unaffected by the price reductions, possibly because the rates were high beforehand. Conclusion: Private plans did not independently obtain lower generic prices. Due to already high substitution rates, there may have been limited potential for additional savings from mandatory substitution controls.

Purpose: To estimate the willingness and ability of private plans to manage costs during the generic drug procurement reform era that began in 2006 in Canada. Two cost management aspects were assessed; the prices paid for generic drugs and the extent to which private plans have enacted measures to increase generic substitution. Methods: IMS-Brogan Pharmastat data was used to estimate the price of commonly prescribed generic drugs and generic share of prescriptions, by plan type, province and quarter from 2003 to 2012. Results: Prices did not decline unless the provincial governments mandated the reductions. Savings from this mandate was approximately $264 million in Ontario. Rates of generic substitution were unaffected by the price reductions, possibly because the rates were high beforehand. Conclusion: Private plans did not independently obtain lower generic prices. Due to already high substitution rates, there may have been limited potential for additional savings from mandatory substitution controls.

Clinical practice guidelines (CPGs) are statements that include recommendations intended to optimize patient care that are informed by a systematic review of evidence and an assessment of the benefits and harms of alternative care options. CPGs’ recommendations have traditionally focused on informing clinicians and patients on the best options, i.e., supporting decisions that occur at the clinical encounter level. Considering all their advantages (a systematic and comprehensive review of the evidence, a multidisciplinary team assessing the evidence and balancing benefits and harms, and the additional considerations such as patients’ preferences, implementability and feasibility of interventions and their costs) CPGs have also become powerful tools to inform decisions and activities outside the clinical encounter. This, because the clinical encounter cannot be completely separated from other decisions that indirectly affect that level, such as those related to quality improvement activities and economic decisions in healthcare. Moreover, activities that are not directly related to the clinical encounter can benefit from CPGs, like education and licensing activities and research prioritization processes, or judicial decisions. The role of CPGs in all these activities has been neglected in the literature. In this study, I performed a critical interpretive synthesis of the literature to summarize the different roles CPGs play outside the clinical encounter and to understand how, and under what conditions CPGs are used in these roles. I also conducted an international survey to describe how frequent these roles exist, from the CPGs developers' perspectives. Lastly, I conducted a multiple case study to understand how and under what conditions CPGs play one of the main roles outside the clinical encounter (drug funding decisions), in two different settings (Colombia and Canada/Ontario). Based on the results, I developed a framework to describe and categorize the roles of CPGs outside the clinical encounter and to determine how and under what conditions CPGs are used in these roles. I highlighted the key areas that require additional methodological research and categorize the roles in main, secondary and unanticipated roles. I also described how international developers reported that CPGs play these roles and how these roles are part of their CPGs final aims in the second study. Lastly, in the case study, I revealed that CPGs were instrumentally used to inform one of the main roles, drug funding decisions, in the Colombian case, and they had a minor conceptual use in the case of Canada/Ontario. / Thesis / Doctor of Philosophy (PhD)

L’objectif de ce travail était d’analyser de manière conjointe différents indicateurs d’abus, de dépendance et de détournement de médicaments psychoactifs en conditions réelles d’utilisation issus de sources de données hétérogènes afin d’en présenter une vision synthétique. Les sources de données utilisées dans ce travail sont issues des outils et programmes des Centres d’Evaluation et d’Information sur la Pharmacodépendance – Addictovigilance (CEIP-A). Elles permettent de mesurer directement l’abus auprès de populations spécifiques de patients dépendants ou sous traitement de substitution par l’enquête OPPIDUM (Observation des Produits Psychotropes Illicites ou Détournés de leur Utilisation Médicamenteuse). Ces outils permettent aussi de mesurer le détournement via la mesure du nombre d’ordonnances falsifiées par l’enquête OSIAP (Ordonnances Suspectes, Indicateur d’Abus Possible) ainsi que la mesure du phénomène de « Doctor Shopping » (chevauchement d’ordonnances) et la mesure du nombre de patients présentant des comportements déviants (issu d’une analyse de classification) à partir de bases de données de remboursement de l’assurance maladie. Cette approche multi-sources a d’abord été appliquée à l’analyse de l’importance du détournement d’usage du clonazépam (Publication n°1). Ce travail a permis de mettre en évidence le détournement émergent du clonazépam et a surtout permis d’illustrer les difficultés à faire émerger cette information de manière cohérente et standardisée au travers des différentes sources de données. Ensuite, l’un des pré-requis d’un système de surveillance de l’abus et du détournement de médicaments étant de permettre d’étudier des tendances évolutives, nous avons proposé la méthode de classification visant à établir des profils de sujets déviants de manière à analyser l’évolution de détournement d’usage de méthyphénidate sur quatre années (Publication n°2). Cette méthode de classification a par la suite, été appliquée de manière conjointe à une méthode de mesure du « Doctor Shopping » pour étudier le détournement d’usage de la Buprenorphine Haut Dosage (BHD) dans la région PACA-Corse (Publication n°3). Cette étude nous a non seulement permis de mettre en évidence un problème important de détournement d’usage de la BHD mais elle nous a permis aussi de montrer la concordance entre ces deux méthodes (mesure du « Doctor Shopping » et méthode de classification) et d’évaluer leurs apports respectifs pour la surveillance de l’abus des médicaments. Ces deux méthodes ont par la suite été analysées de manière conjointe aux données issues des enquêtes OPPPIDUM et OSIAP pour permettre d’étudier et de comparer le détournement d’usage des médicaments de la famille des benzodiazépines (Publication n°4) et des opioïdes (Publication n°5). Cette approche multi-sources permet de limiter les biais inhérents à chaque méthode ou source prise isolément. L’ensemble de nos travaux met en exergue la pertinence d’un tel système pour évaluer l’abus d’un médicament mais aussi pour le comparer à d’autres substances. Néanmoins, le développement d’un tel système appliqué au domaine de la pharmacodépendance est relativement nouveau, et nécessite des améliorations tant dans l’intégration d’autres sources de données, que dans la méthodologie employée pour intégrer et synthétiser l’information ainsi obtenue. Finalement, cette thèse a montré que les CEIP-A avaient le potentiel pour mettre en œuvre un système multi-sources pouvant apporter une réelle contribution à l’étude de la pharmacodépendance en France. / The objective of this work was to analyze abuse, dependence and diversion of psychoactive medicines in real settings using jointly different indicators issued from mixed datasources in order to present a synthetic vision. The datasources used in this work are issued from the tools developed by the Centres for Evaluation and Information on Pharmacodependency (CEIP). They allow to measure directly drug abuse with specific populations of dependent patients or under opiate treatment (OPPIDUM (Observation of the Illicit Psychotropic Products or Diverted from their Medicinal Use) survey)). These tools also allow to measure the diversion via the measure of the phenomenon of “doctor shopping” (overlapping of prescriptions) and the measure of the number of patients presenting a deviant behaviour from general health insurance databases; then they measure diversion through falsified prescriptions presented at pharmacies (the OSIAP (Forged prescriptions indicating potential abuse) survey).This multisources approach has been firstly applied to analyse abuse and diversion of clonazepam (1st publication). This study has highlighted the emerging problem of diversion of clonazepam, after flunitrazepam and has also illustrated the difficulty of analysing with consistency the information gathered by these different datasources. A good system for controlling drug diversion and abuse has to allow analysing trends. We have so proposed a classification method aiming at revealing profile of subjects with deviant behaviour to use it on an evolutive manner so as to study diversion of methylphenidate on a four year period (2nd publication). This classification method has then been applied jointly with a method measuring the “doctor shopping” to analyse diversion of High Dosage Buprenorphine (HDB) (3rd publication). This study has revealed an important problem of diversion of HDB, has also demonstrated that the two methods were globally concordant and has allowed to evaluate their advantages for the controlling of the abuse and diversion of prescription drugs. These two last methods have then been analysed jointly with data from the OPPIDUM and OSIAP surveys to allow to study and compare diversion of benzodiazepine drugs (4th publication) and opioids drugs (5th publication). This multisource approach allows to limit biases linked to each method seen individually. Our work points out the relevance of such a multisources system to estimate the abuse of a prescription drug and to compare it with the other substances. Nevertheless, the development of such a system applied to the domain of the drug dependency is relatively new, and requires improvements concerning the integration of the other sources of data and the methodology used to join and synthetize the information obtained. Finally, such a system "multi-sources” has the potential to exist and to make a real contribution to the domain of the drug dependency in France.