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

Effect of Myo-inositol and N-acetyl-L-cysteine on processed human spermatozoa for use in modern methods of fertility treatment

Background and aims: Today, the prevalence of structural and functional disorders of sperm and subsequently the possibility of occurrence of autism, spontaneous abortion, and infertility has increased dramatically. This study aimed to investigate the potential effects of myo-inositol and N-acetyl-L-cysteine (NAC) on the improvement of processed spermatozoa indices. Methods: In this study, 63 patients with male factor infertility were studied in Hazrat Zahra Infertility Center of Shahrekord. To do liquefaction, the semen sample was incubated at 37°C for 20 minutes. The Density Gradient Centrifugation protocol was used to process sperm. The processed sperm samples were incubated at 37°C for 20 minutes in four groups of control, myo-inositol (2 mg/mL), NAC antioxidant (10 Mm/L) and myo-inositol+NAC. All biological parameters of sperm were evaluated using Makler slide, SQA-V sperm analyzer gold version 2.48, TUNEL assay, and Toluidine blue staining. Results: In the present study, 63 men aged 22-58 years with infertility complaints were studied. The NAC group and the myo-inositol group exhibited significantly higher motility in comparison with the control group (P 0.05). Conclusion: NAC and myo-inositol were able to improve certain indices such as sperm motility and integrity; therefore, the quality of sperm could be improved by these drugs to treat infertility. Keywords: Myo-inositol, N-acetyl-L-cysteine, Infertility treatment, Biological parameters of sperm, IVF, ICS

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

In vivo biocompatibility and pacing function study of silver ion-based antimicrobial surface technology applied to cardiac pacemakers

INTRODUCTION Evidence suggests that the rate of cardiovascular implantable electronic device (CIED) infections is increasing more rapidly than the rates of CIED implantation and is associated with considerable mortality, morbidity and health economic impact. Antimicrobial surface treatments are being developed for CIEDs to reduce the risk of postimplantation infection within the subcutaneous implant pocket. METHODS AND ANALYSIS The feasibility of processing cardiac pacemakers with the Agluna antimicrobial silver ion surface technology and in vivo biocompatibility were evaluated. Antimicrobially processed (n=6) and control pacemakers (n=6) were implanted into subcutaneous pockets and connected to a part of the muscle using an ovine model for 12 weeks. Pacemaker function was monitored preimplantation and postimplantation. RESULTS Neither local infection nor systemic toxicity were detected in antimicrobial or control devices, and surrounding tissues showed no abnormal pathology or over-reactivity. Semiquantitative scores of membrane formation, cellular orientation and vascularity were applied over five regions of the pacemaker capsule and average scores compared. Results showed no significant difference between antimicrobially processed and control pacemakers. Silver analysis of whole blood at 7 days found that levels were a maximum of 10 parts per billion (ppb) for one sample, more typically ≤2 ppb, compared with <2 ppb for preimplantation levels, well below reported toxic levels. CONCLUSIONS There was no evidence of adverse or abnormal pathology in tissue surrounding antimicrobially processed pacemakers, or deleterious effect on basic pacing capabilities and parameters at 12 weeks. This proof of concept study provides evidence of basic biocompatibility and feasibility of applying this silver ion-based antimicrobial surface to a titanium pacemaker surface