Improving decision-making for drug reimbursement in Iran

Reimbursement decision making in any healthcare system is an important process to ensure patient access to various healthcare services in an affordable manner. A proper reimbursement decision making happens when it can concurrently pursue three main goals including quality of care, population of health, and affordability. However, achieving the goals requires enough knowledge and proper healthcare governance. In middle-income countries (MICs) improving the three main goals is likely to be difficult due to weakness in the knowledge production infrastructure and healthcare governance. To investigate possible solutions for improving the drug reimbursement decision-making system in MICs, this thesis focuses on the drug reimbursement decision-making system in Iran. Subsequently, we focus on use of a monoclonal antibody in breast cancer. Trastuzumab (Herceptin) is widely used in the treatment of overexpressed human epidermal growth factor receptor 2 (HER2-positive) breast cancer. Trastuzumab, as an expensive drug, has continued to be a topic of conversation in many healthcare systems since its launch into the pharmaceutical markets. The overall aim of this thesis is to investigate how an MIC (in this case, focusing on Iran) can improve its drug reimbursement decision-making system. Therefore, this thesis provided important information on how an MIC can improve the drug reimbursement decision-making system in three parts. Firstly, we discussed the current situation and subsequent consequences of the drug reimbursement decision-making system in Iran. Secondly, we provided some solutions to improve limited health economics-related evidence in Iran. And finally, some recommendations are provided to improve the system. This thesis includes three parts and each of these provides an answer to one or more research questions. In the first part (chapters 2 and 3), the current situation and subsequent consequences of the drug reimbursement decision-making system in Iran are discussed. The second part focuses on knowledge production in MICs. As already mentioned, obtaining information is not an easy task in MICs and researchers have to find solutions to overcome this shortage of information. Therefore, this part provides some solutions for this problem. In addition, it describes some economic evaluations and a scenario analysis for efficient and affordable treatment. This part has three chapters (4−6). The third part provides recommendations to improve the system. It describes how MICs can benefit from HTA studies and knowledge production in order to achieve the overall goals of a reimbursement decision-making system. This part has two chapters, which are chapter 7 and 8

Energy loss rates of two-dimensional hole gases in inverted Si/Si0.8Ge0.2 heterostructures

We have investigated the energy loss rate of hot holes as a function of carrier temperature TC in p-type inverted modulation-doped (MD) Si/SiGe heterostructures over the carrier sheet density range (3.5–13)×1011 cm–2, at lattice temperatures of 0.34 and 1.8 K. It is found that the energy loss rate (ELR) depends significantly upon the carrier sheet density, n2D. Such an n2D dependence of ELR has not been observed previously in p-type SiGe MD structures. The extracted effective mass decreases as n2D increases, which is in agreement with recent measurements on a gated inverted sample. It is shown that the energy relaxation of the two-dimensional hole gases is dominated by unscreened acoustic phonon scattering and a deformation potential of 3.0±0.4 eV is deduced

Learning Provably Stabilizing Neural Controllers for Discrete-Time Stochastic Systems

We consider the problem of learning control policies in discrete-time stochastic systems which guarantee that the system stabilizes within some specified stabilization region with probability~$1$. Our approach is based on the novel notion of stabilizing ranking supermartingales (sRSMs) that we introduce in this work. Our sRSMs overcome the limitation of methods proposed in previous works whose applicability is restricted to systems in which the stabilizing region cannot be left once entered under any control policy. We present a learning procedure that learns a control policy together with an sRSM that formally certifies probability~$1$ stability, both learned as neural networks. We show that this procedure can also be adapted to formally verifying that, under a given Lipschitz continuous control policy, the stochastic system stabilizes within some stabilizing region with probability~$1$. Our experimental evaluation shows that our learning procedure can successfully learn provably stabilizing policies in practice.Comment: Accepted at ATVA 2023. Follow-up work of arXiv:2112.0949

Adjuvant Trastuzumab Therapy for Early HER2-Positive Breast Cancer in Iran: A Cost-Effectiveness and Scenario Analysis for an Optimal Treatment Strategy

Introduction: Clinical guidelines have recommended a 1-year trastuzumab regimen as standard care for early human epidermal growth factor receptor 2 (HER2)-positive breast cancer; however, th

The Drug Reimbursement Decision-Making System in Iran

Background:  Previous studies of health policies in Iran have not focused exclusively on the drug reimbursement process. Objective: The aim of this study was to describe the entire drug reimbursement process and the stakeholders, and discuss issues faced by policymakers. Methods: Review of documents describing the administrative rules and directives of stakeholders, supplemented by published statistics and interviews with experts and policymakers. Results: Iran has a systematic process for the assessment, appraisal, and judgment of drug reimbursements. The two most important organizations in this process are the Food and Drug Organization, which considers clinical effectiveness, safety, and economic issues, and the Supreme Council of Health Insurance, which considers various criteria, including budget impact and cost-effectiveness. Ultimately, the Iranian Cabinet approves a drug and recommends its use to all health insurance organizations. Reimbursed drugs account for about 53.5% of all available drugs and 77.3% of drug expenditures. Despite its strengths, the system faces various issues, including conflicting stakeholder aims, lengthy decision-making duration, limited access to decision-making details, and rigidity in the assessment process. Conclusions: The Iranian drug reimbursement system uses decision-making criteria and a structured approach similar to those in other countries. Important shortcomings in the system include out-of-pocket contributions due to lengthy decision making, lack of transparency, and conflicting interests among stakeholders. Iranian policymakers should consider a number of ways to remedy these problems, such as case studies of individual drugs and closer examination of experiences in other countries

Circulating levels of Meteorin-like protein in polycystic ovary syndrome: A case-control study

Patients diagnosed with polycystic ovary syndrome (PCOS) are at high risk of developing a myriad of endocrinologic and metabolic derailments. Moreover, PCOS is a leading cause of habitual abortion, also known as recurrent pregnancy loss (RPL). Meteorin-like protein (Metrnl) is a newly discovered adipokine with the potential to counteract the metaflammation. This study aimed at determining the associations of serum Metrnl levels with homocysteine, hs-CRP, and some components of metabolic syndrome in PCOS-RPL and infertile PCOS patients.This case-control study was conducted in 120 PCOS patients (60 PCOSRPL and 60 infertile) and 60 control. Serum hs-CRP and homocysteine were assessed using commercial kits, while adiponectin, Metrnl, FSH, LH, free testosterone and insulin levels were analyzed using ELISA technique. Serum Metrnl levels were found to be lower in PCOS patients when compared to controls (67.98 ± 26.66 vs. 96.47 ± 28.72 pg/mL, P 0.001)). Furthermore, serum adiponectin levels were lower, while free testosterone, fasting insulin, HOMA-IR, homocysteine, and hs-CRP were significantly higher in PCOS group compared to controls. Moreover, serum Metrnl correlated with BMI, adiponectin, and homocysteine in controls, and inversely correlated with FBG, fasting insulin, and HOMA-IR in PCOS group and subgroups. Besides, it inversely correlated with hs-CRP in control, and PCOS group and subgroups. These findings revealed a possible role of Metrnl in the pathogenesis of PCOS and RPL. Nevertheless, there is a necessity for future studies to prove this concept. © 2020 Public Library of Science. All rights reserved

Severity-Adjusted Probability of Being Cost Effective

Background In the context of priority setting, a diferential cost-efectiveness threshold can be used to refect a higher societal willingness to pay for quality-adjusted life-year gains in the worse of. However, uncertainty in the estimate of severity can lead to problems when evaluating the outcomes of cost-efectiveness analyses. Objectives This study standardizes the assessment of severity, integrates its uncertainty with the uncertainty in cost-efectiveness results and provides decision makers with a new estimate: the severity-adjusted probability of being cost efective. Methods Severity is expressed in proportional and absolute shortfall and estimated using life tables and country-specifc EQ-5D values. We use the three severity-based cost-efectiveness thresholds (€20.000, €50.000 and €80.000, per QALY) adopted in The Netherlands. We exemplify procedures of integrating uncertainty with a stylized example of a hypothetical oncology treatment. Results Applying our methods, taking into account the uncertainty in the cost-efectiveness results and in the estimation of severity identifes the likelihood of an intervention being cost efective when there is uncertainty about the appropriate severity-based cost-efectiveness threshold. Conclusions Higher willingness-to-pay thresholds for severe diseases are implemented in countries to refect societal concerns for an equitable distribution of resources. However, the estimates of severity are uncertain, patient populations are heterogeneous, and this can be accounted for with the severity-adjusted probability of being cost efective proposed in this study. The application to the Netherlands suggests that not adopting the new method could result in incorrect decisions in the reimbursement of new health technologies

Use of data-mining to support real-world cost analyses: An example using HER2-positive breast cancer in Iran

INTRODUCTION: Patient registries play an important role in obtaining real-world evidence of the cost-effectiveness of treatments. However, their implementation is costly and sometimes infeasible in many middle-income countries (MICs). We explored the combination of data-mining and a large claims database to estimate the direct healthcare costs of HER2-positive breast cancer (BC) treatment in Iran and the fraction of total costs from trastuzumab use.METHOD: We performed a retrospective analysis of claims data from the Iran Social Security Organization, a health insurer which covers approximately 50%(~40 million) of the Iranian population, in the period of 21/03/2011-20/03/2014. A data-mining algorithm using R software and validated using patient dossiers in the Cancer Research Center identified 1295 patients and divided them into the three main HER2-positive breast cancer stages (early, loco-regional and advanced). A payer perspective was used to calculate the absolute and relative direc