Production and regulatory issues for theranostics.

Theranostics has become a major area of innovation and progress in cancer care over the last decade. In view of the introduction of approved therapeutics in neuroendocrine tumours and prostate cancer in the last 10 years, the ability to provide access to these treatments has emerged as a key factor in ensuring global benefits from this cancer therapy approach. In this Series paper we explore the issues that affect access to and availability of theranostic radiopharmaceuticals, including supply and regulatory issues that might affect the availability of theranostic treatments for patients with cancer.

Trends in nuclear medicine and the radiopharmaceutical sciences in oncology: workforce challenges and training in the age of theranostics.

Although the promise of radionuclides for the diagnosis and treatment of disease was recognised soon after the discovery of radioactivity in the late 19th century, the systematic use of radionuclides in medicine only gradually increased over the subsequent hundred years. The past two decades, however, has seen a remarkable surge in the clinical application of diagnostic and therapeutic radiopharmaceuticals, particularly in oncology. This development is an exciting time for the use of theranostics in oncology, but the rapid growth of this area of nuclear medicine has created challenges as well. In particular, the infrastructure for the manufacturing and distribution of radiopharmaceuticals remains in development, and regulatory bodies are still optimising guidelines for this new class of drug. One issue of paramount importance for achieving equitable access to theranostics is building a sufficiently trained workforce in high-income, middle-income, and low-income countries. Here, we discuss the key challenges and opportunities that face the field as it seeks to build its workforce for the 21st century.

Cost-Effectiveness Comparison between Ticagrelor and Clopidogrel in Acute Coronary Syndrome in Iran.

Background: The present study aimed to determine the cost-effectiveness of ticagrelor compared with clopidogrel in Iranian patients with acute coronary syndrome (ACS). Methods: A 1-year decision tree model combined with a 20-year Markov transition model was used to simulate the long-term cost and effectiveness of both ticagrelor and clopidogrel in Iran based on an Iranian payer's perspective. Clinical efficacy data were extracted from the PLATO trial and other published studies. Costs were estimated based on local prices in public sectors. Deterministic and probabilistic sensitivity analyses were used to test the robustness of base-case results over the uncertainties of model inputs. All calculations, analyses, and modeling were done in TreeAge 2011 and Microsoft Excel 2013. Results: Compared with clopidogrel, the treatment of Iranian ACS patients with ticagrelor for 20 years resulted in an additional cost of US$ 2.39 in a hypothetical cohort of 1000 patients. However, ticagrelor led to 7.2 quality-adjusted life-years (QALYs) gained per 1000 hypothetical patients. Accordingly, the estimated incremental cost-effectiveness ratio for this analysis was US$ 332.032 per 1 QALY gained. Conclusion: Ticagrelor was a cost-effective antiplatelet medicine compared with clopidogrel in Iranian patients with ACS. This could help Iran's policymakers to allocate resources more efficiently to ACS.

Cladribine tablets are a cost-effective strategy in high-disease activity relapsing multiple sclerosis patients in Iran.

Background: Cladribine tablets are the foremost oral immune-reconstitution therapy for high disease activity relapsing multiple sclerosis (HDA-RMS). We aimed to assess the cost-effectiveness of cladribine tablets compared to natalizumab in patients with HDA-RMS in Iran. Methods: A 5-year cohort-based Markov model was developed with 11 expanded disability status score (EDSS) health states, including patients with HDA-RMS as on and off-treatment. All costs were identified from the literature and expert opinion and were measured in Iranian Rial rates, changed to the 2020 USD rate and were discounted by 7.2%. Quality adjusted life years (QALY), discounted by 3.5%, and life years gained (LYG) were adopted to measure efficacy. The final results were presented as incremental cost-effectiveness ratio that was compared to a national willingness to pay (WTP) threshold of 1 to 3 gross domestic product (GDP) per capita. Deterministic and probabilistic sensitivity analyses (D/PSA) were employed to evaluate uncertainty. Results: Cladribine tablets dominated natalizumab and yielded 6,607 USD cost-saving and 0.003 additional QALYs per patient. LYG was comparable. The main cost component was drug acquisition cost in both arms. DSA indicated the sensitivity of the results to the cost discount rates and also the patients' body weight; while they were less sensitive to the main clinical variables. PSA indicated that cladribine tablets were cost-effective in Iran, with a probability of 57.5% and 58.6% at lower and higher limits of threshold, respectively. Conclusion: Cladribine tablets yielded higher QALYs and lower costs compared to natalizumab, in patients with HDA-RMS in Iran.

Cost-effectiveness of ocrelizumab for treatment of Iranian patients with relapsing multiple sclerosis.

Background: The current study desired to conduct an economic analysis on ocrelizumab (OCR), a new relapsing multiple sclerosis (RMS) treatment strategy, in comparison to natalizumab (NTL), as one of the mostly-used disease-modifying therapies (DMTs) in Iran. Methods: A 31-health-state Markov model, based on Expanded Disability Status Scale (EDSS), containing patients on- and off-treatment with annual cycles was developed. Baseline demographics and utility scores were extracted from OPERA 1 and 2 trials. Confirmed disability progression (CDP) and annualized relapse rates (ARR) were extracted from the literature. Mortality was calculated based on age, sex, and disease state. Quality-adjusted life years (QALYs) and life years gained (LYG) were measurements of efficacy. Direct and indirect costs were identified and calculated based on the national book of tariffs in Iranian Rial (IRR) rates, then converted to the 2020 United States Dollar (USD). Final results were reported in terms of incremental cost-effectiveness ratio (ICER), which showed extra costs required for one additional QALY. Robustness of the model was analyzed through deterministic sensitivity analysis (DSA) and probabilistic sensitivity analysis (PSA). Results: OCR dominated NTL and was associated with cost-savings of 6971 USD, longer LYG (0.004), and higher QALYs (0.27). Although OCR had higher acquisition costs, which was the main component in both comparator arms, it was associated with lower total costs, due to lower disability progression and productivity loss. Results remained robust in DSA and PSA (93.5% cost-effectiveness in Iran's pharmacoeconomic threshold, 2709 USD). Conclusion: Results suggested that OCR was a more cost-effective option than NTL for the treatment of patients with RMS in Iran.

Pharmacogenomics Implementation and Hurdles to Overcome; In the Context of a Developing Country.

Having multiple dimensions, uncertainties and several stakeholders, the costly pharmacogenomics (PGx) is associated with dynamic implementation complexities. Identification of these challenges is critical to harness its full potential, especially in developing countries with fragile healthcare systems and scarce resources. This is the first study aimed to identify most salient challenges related to PGx implementation, with respect to the experiences of early-adopters and local experts' prospects, in the context of a developing country in the Middle East. To perform a comprehensive reconnaissance on PGx adoption challenges a scoping literature review was conducted based on national drug policy components: efficacy/safety, access, affordability and rational use of medicine (RUM). Strategic option development and analysis workshop method with cognitive mapping as the technique was used to evaluate challenges in the context of Iran. The cognitive maps were face-validated and analyzed via Decision Explorer XML. The findings indicated a complex network of issues relative to PGx adoption, categorized in national drug policy indicators. In the rational use of medicine category, ethics, education, bench -to- bedside strategies, guidelines, compliance, and health system issues were found. Clinical trial issues, test's utility, and biomarker validation were identified in the efficacy group. Affordability included pricing, reimbursement, and value assessment issues. Finally, access category included regulation, availability, and stakeholder management challenges. The current study identified the most significant challenges ahead of clinical implementation of PGx in a developing country. This could be the basis of a policy-note development in future work, which may consolidate vital communication among stakeholders and accelerate the efficient implementation in developing new-comer countries.

Short and long term impacts of COVID-19 on the pharmaceutical sector.

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) was characterized as a global pandemic by the WHO on March 11th, 2020. This pandemic had major effects on the health market, the pharmaceutical sector, and was associated with considerable impacts; which may appear in short and long-term time-horizon and need identification and appropriate planning to reduce their socio-economic burden. OBJECTIVES: Current short communication study assessed pharmaceutical market crisis during the COVID-19 era; discussing short- and long-term impacts of the pandemic on the pharmaceutical sector. RESULTS: Short-term impacts of COVID-19 pandemic includes demand changes, regulation revisions, research and development process changes and the shift towards tele-communication and tele-medicine. In addition, industry growth slow-down, approval delays, moving towards self-sufficiency in pharm-production supply chain and trend changes in consumption of health-market products along with ethical dilemma could be anticipated as long-term impacts of COVID-19 pandemic on pharmaceutical sector in both global and local levels. CONCLUSION: The pandemic of COVID-19 poses considerable crisis on the health markets, including the pharmaceutical sector; and identification of these effects, may guide policy-makers towards more evidence-informed planning to overcome accompanying challenges. Graphical abstract .

Comparison of Treatment Response Achieved by Tablet Splitting Versus Whole Tablet Administration of Levothyroxine in Patients with Thyroid Cancer.

OBJECTIVES: TSH suppression by Levothyroxine consumption is a mainstay of thyroid cancer treatment. Tablet-splitting is a worldwide approach in dose adjustment in patients. However, it is highly recommended to evaluate the validity of tablet splitting for each distinctive drug by clinical trials before routinely using tablet halves in clinical practice. In this study we compared the effect of 150 µg dose of Levothyroxine by use of a100 and a 50 µg tablets or one and half 100 µg tablets in Differentiated thyroid cancer (DTC) patients. METHODS: One hundred DTC patients treated with one and half 100 µg Levothyroxine tablets were randomly divided into two groups. The first group continued taking medication as before and the second group received the same daily dose by taking one 100 and one 50 microgram Levothyroxine tablets. The mean changes in TSH and T3 levels and patients weight were compared between the groups. RESULTS: 91 patients completed the study. Levothyroxine consumption pattern, age, gender distribution, weight and TSH levels were comparable between groups at the beginning of the study. The mean change of body weights, serum levels of T3 and TSH showed no significant difference between groups in different time points during the study (P>0.05). CONCLUSION: This study showed similar efficacy of tablet splitting and two tablets administration for Levothyroxine; however, patients preferred two tablets at the end of the study. It can be concluded that tablet splitting can be used as an alternative way when the 50 µg tablet is not available.

Evaluation of serum Asymmetric Dimethyl Arginine concentrations in coronary artery disease patients without traditional cardiovascular risk factors.

BACKGROUND: Previous studies have shown that Asymmetric Dimethyl Arginine (ADMA) is increased significantly during coronary artery diseases (CAD). However it is not clear either this increase is due to cardiovascular disease (CVD) risk factors or ADMA is increased independently in CAD. The aim of this study is to evaluate ADMA's plasma level as an independent biomarker in CADs. PATIENTS AND METHODS: In current study a total of 165 subjects with no traditional CVD's RFs, who fulfilled the inclusion and exclusion criteria, were recruited; 55 CAD+ patients which had more than 50% stenosis (CAD+); 55 CAD- patients which had less than 50% stenosis in their coronary arteries (CAD-), based on their angiography record and 55 healthy individuals as controls. CAD+ patients were divided into three groups: single (SVD), double (2VD), and triple vessel (3VD) disease. Plasma level of soluble ADMA was measured with an enzyme-linked immono sorbent assay (ELISA) kit. RESULTS: No significant difference between ADMA's plasma levels was found between CAD+, CAD- and healthy groups. In addition ADMA's plasma levels was not significantly different between CAD+'s subgroups. CONCLUSIONS: The result of this study indicates no significant relation between ADMA's plasma levels and either presence or severity of coronary artery stenosis. Therefore, it is presumed that ADMA may not be an independent biomarker for CADs.