Given financial constraints, drug manufacturers are required to provide pharmacoeconomic evaluations to demonstrate the value for money of their drug compared to current treatment when requesting reimbursement by publicly funded health care systems. This thesis is a retrospective examination of pharmacoeconomic evaluations submitted for review to the Common Drug Review process. Its purpose was to determine the pattern of adherence to guidelines, trends in methodological quality, and transparency, changes in the adoption and practice of sensitivity analysis and probabilistic methods, use of indirect treatment comparison, and identify methodological factors−determinants of recommendations. Using an instrument that was developed and tested, information from 201 pharmacoeconomic evaluations was collected and analysed. Pharmacoeconomic evaluations may have improved over time in terms of adherence, methodological quality, transparency, use of probabilistic sensitivity analysis and indirect treatment comparison. However, such improvements have been minimal and further efforts are needed to better improve pharmacoeconomic evaluations in the future.

Magister Scientiae - MSc (Pharmacy Administration and Policy Regulation) / Aim: The purpose of this research was to assess the validity of pharmacoeconomic evaluation in Egypt three years after the guideline was issued and analyse challenges and opportunities for improvement. Objectives: To conduct a literature review of pricing, medicine reimbursement, and pharmacoeconomic evaluation. Examine, in conjunction with relevant stakeholders, the progress of the pharmacoeconomic evaluation. To present examples of pharmacoeconomic evaluation deployment. To propose recommendations on how to optimize the pharmacoeconomic implementation. Methods: A literature review and a qualitative research method that was conducted using a semi-structured interview with stakeholders of the reimbursement process in Egypt. In addition, examples were analysed to determine the impact of pharmacoeconomic methods on medicine reimbursement in Egypt. Results: The Egyptian Pharmacoeconomic Evaluation Unit was established in 2013, it supports various reimbursement decisions, especially for new technologies. The unit evaluations depended mainly on the available international data. However, fragmentation of the health care system in Egypt is a major obstacle to progress. The guidelines are still non-compulsory for implementation, and accordingly some reimbursement committees do not consider its evaluation in its decision making. Conclusion and Recommendations: The pharmacoeconomic evaluation has demonstrated a good start in Egypt. To gain the full benefit of pharmacoeconomic evaluation, authorities need to consider reducing the complexity of health care system, setting clear strategies, building capabilities to improve pharmacoeconomic awareness; endorsing risk sharing strategy and building a proper health related information system along with creation of full Health Technology Assessment program. The above-mentioned recommendations could be associated together under the Universal Health Coverage road map that Egypt committed to achieve by 2030.

Les maladies cardiovasculaires (MCV) ont une prévalence élevée dans le monde et sont considérées comme la deuxième cause de mortalité chez la population canadienne. Les statines sont reconnues comme le traitement par excellence dans la prévention des MCV. Toutefois, les statines ne conviennent pas à tous les patients, potentiellement, en raison de la survenue d’effets secondaires et du manque d’efficacité. Avec l’avancement de la science, de nouvelles thérapies voient le jour dans le milieu cardiovasculaire. Les inhibiteurs de la proprotéine convertase subtilisine-kexine de type 9 PCSK9 (iPCSK9) constituent un traitement efficace pour réduire les évènements cardiovasculaires. Cependant, ces thérapies sont dispendieuses pour le système de santé. Cette thèse a pour but d’explorer la pharmacoéconomie des thérapies dispendieuses ayant démontrées une efficacité clinique importante dans le traitement préventif des MCV. La pharmacoéconomie est un outil d’évaluation destiné aux décideurs ayant comme objectif d’optimiser l’utilisation des ressources humaines et financières. Tout d’abord, dans un premier article, nous avons évalué l’efficacité maximale d’une thérapie hypolipémiante à partir des grilles de risque cardiovasculaires. Selon les résultats obtenus, l’efficacité maximale qu’il est raisonnable d’espérer a correspondu à une diminution du risque relatif variant entre 0,46 et 0,66. Ensuite, dans un deuxième article, nous avons estimé l’efficacité d’une thérapie dispendieuse dans un contexte différent puisque les études cliniques étaient en cours. Avec l’aide d’un modèle de Markov, la propension à payer a été fixée à deux seuils distincts, alors que le coût d’acquisition de la thérapie est demeuré fixe. Nos résultats ont estimé que pour atteindre les seuils de propension à payer de 50 000 $ et 100 000 $ par année de vie ajustée pour la qualité, l’efficacité devrait être de 0,58 et 0,78 respectivement. Finalement, l’étude randomisée contrôlée établissant l’efficacité clinique des iPCSK9 a été publiée. Nous avons donc pu évaluer le coût-utilité réel des iPCSK9 avec une nouvelle méthode de simulation, nommée Conditions et évènements discrètement intégrés. Cette étude est l’objet 2 de mon troisième article. Les résultats de cet article ont estimé que l’iPCSK9 n’est pas coût-efficace selon l’efficacité obtenue dans les études cliniques. En conclusion, suite aux résultats présentés dans cette thèse rédigée par articles, il serait envisageable d’intégrer dans le modèle pharmacoéconomique l’option d’un test génétique afin d’individualiser le traitement de chaque patient. / Cardiovascular diseases (CVD) have a high prevalence worldwide and are considered the second leading cause of death in the Canadian population. Statins are recognized to be the gold standard treatment in the prevention of CVD. However, statins are not suitable for all patients, potentially because of side effects and lack of efficacy. With the advancement of science, new therapies are emerging in the cardiovascular field. Inhibitors of proprotein convertase subtilisin-kexin type 9 (iPCSK9) have been shown to be effective in reducing cardiovascular events. However, these therapies are expensive. This article-based thesis aims to explore the pharmacoeconomics of expensive therapies that have demonstrated significant clinical efficacy in the preventive treatment of CVD. Pharmacoeconomics is an evaluation tool for decision-makers with the objective of optimizing the use of human and financial resources. In the first publication, we evaluated the maximum effectiveness of lipid-lowering therapy from cardiovascular risk grids. According to our results, this maximum expected benefit fluctuates between 0.46 and 0.66. In the second publication, we estimated the effectiveness of an expensive therapy. At the time of our second publication, the results of the randomized controlled trial evaluating the clinical efficacy of iPCSK9 had not been published yet. Therefore, we used a Markov model to estimate the necessary clinical efficacy of PCSK9 inhibitors to reach two arbitrarily selected willingness-to-pay (WTP) thresholds. Our results showed that an efficacy of 0.58 and 0.78 were necessary to reach WTP thresholds of $50,000 and $100,000 per quality-adjusted life years respectively. Once the clinical efficacy of iPCSK9 was published, we evaluated their cost-utility. This was the object of our third article and a new simulation method named Discretely Integrated Condition was used. Our results suggested that at the current price, the PCSK9 inhibitors were not cost-effective. Following the results presented in this article-based thesis, it would be of interest to integrate the option of a hypothetical genetic test into the pharmacoeconomic model. This genetic test would be able to identify good responders in order to optimize the treatment of each individual patient.