A cost-effectiveness analysis of the prophylaxis versus on-demand regimens in severe hemophilia A patients under 12 years old in southern Iran.

OBJECTIVE: This study aimed to compare the cost-effectiveness of these two regimens in hemophilia A patients, under-12-years-old in southern Iran. METHODS: A cost-effectiveness study comparing prophylaxis versus on-demand was conducted on 34 hemophilia patients (24 and 10 patients were on the prophylaxis and on-demand regimens respectively) in 2017. The Markov model was used to estimate the economic and clinical outcomes. The costs were collected from the societal perspective, and the utility criterion was the 'quality adjusted life year (QALY)' indicator. The required data were collected using a researcher-made cost checklist, the EQ5D standard questionnaire and Hemophilia Joint Health Score. The probabilistic sensitivity analysis (PSA) was performed to determine the robustness of the results. RESULTS: The means of costs, joint health score and QALY in the prophylaxis regimen were $478,963.1 purchasing power parity (PPP), 96.67, and 11.98 respectively, and in the on-demand regimen were $521,797.2 PPP, 93.46 and 10.99 respectively. The PSA confirmed the robustness of the model's results. The results of the scatter plots and acceptability curves showed that the prophylaxis regimen in 97% of the simulations for the thresholds below $20950 PPP was more cost-effective than on-demand regimen. CONCLUSION: Prophylaxis regimen showed the lower costs and higher effectiveness and utility in comparison with the on-demand regimen. It is recommended that prophylaxis should be considered as the standard care for treatment of hemophilic patients.

Correlation of bleeding score with frequency and severity of bleeding symptoms in FXIII deficiency assessing by the ISTH Bleeding Assessment Tool.

OBJECTIVES: The ISTH bleeding assessment tool (ISTH-BAT) is developed for standardization of bleeding symptoms in bleeding disorders. The aim of this study is to apply this bleeding score for FXIII deficient patients and its relation to the frequency and severity of symptoms. METHODS: In this cross-sectional study, 63 patients with severe FXIII deficiency were evaluated for the assessment of bleeding score according to the standard ISTH-BAT questionnaire. All patients were registered at two major thrombosis and hemostasis centers in Iran affiliated to Zahedan University of medical sciences (50 patients) and Shiraz University of medical sciences (13 patients). RESULTS: Significant correlations between the bleeding score and number of symptoms (r = 0.668, P < 0.001) and with a number of severe symptoms (r = 0.938, P < 0.001) were detected. There was no significant relationship between the mean bleeding score and CNS bleeding (P = 0.390). CONCLUSION: The ISTH-BAT score is an acceptable bleeding assessment tool for standardization and evaluation of patients with FXIII deficiency.

Blood transfusion versus hydroxyurea in beta-thalassemia in Iran: a cost-effectiveness study.

INTRODUCTION: Thalassemia intermedia is a type of anemia which has several treatments modalities. We aimed to study the cost effectiveness of two treatments, including blood transfusion and hydroxyurea, in patients with beta-thalassemia intermedia in south of Iran referred to a referral center affiliated to Iran, Shiraz University of Medical Sciences in 2015. MATERIALS AND METHODS: This was a cost-effectiveness study which was conducted on 122 patients with beta-thalassemia intermedia. The indicator of effectiveness in this study was the reduction of growth disorder (normal BMI). Data analysis was done using SPSS 21, Excel 2010 and Treeage 2011. Finally, the one-way sensitivity analysis was performed to determine the robustness of the results. RESULTS: The average annual costs of blood transfusion and the use of hydroxyurea in 2015 were 20733.27 purchasing power parity (PPP)$ and 7040.29 PPP$, respectively. The effectiveness of blood transfusion was57.4% while in hydroxyurea group was 60.7%. CONCLUSION: The results showed that the cost effectiveness of using hydroxyurea was more than that of blood transfusion. Therefore, it is recommended that the use of hydroxyurea in the treatment of patients with beta-thalassemia intermedia would become the first priority, and more basic and supplementary insurance coverage for treating such patients using hydroxyurea should be considered.

The ICET-A Survey on Current Criteria Used by Clinicians for the Assessment of Central Adrenal Insufficiency in Thalassemia: Analysis of Results and Recommendations.

BACKGROUND: In March 2015, the International Network of Clinicians for Endocrinopathies in Thalassemia and Adolescent Medicine (ICET-A) implemented a two-step survey on central adrenal insufficiency (CAI) assessment in TM patients and after analysis of the collected data, recommendations for the assessment of hypothalamic-pituitary- adrenal (HPA) axis in clinical practice were defined. METHODS: To ascertain the current practice for assessment of CAI in thalassemia, the Coordinator of ICET-A sent two questionnaires by email: i) The first to evaluate the current interpretation of basal serum cortisol level (first step) and ii) The second to assess the current usage of ACTH test and the variability in practice" (second step). Based on the surveys the core ICET-A group prepared the recommendations for the assessment of suspected CAI in thalassemia (third step). RESULTS: A total of 19 thalassemologists/endocrinologists have participated in the first survey and 35 specialists participated in the second step questionnaire. The study demonstrated a considerable variability in almost all aspects of relevant current criteria used for the diagnosis of CAI. An ROC analysis using peak value > 20 µg/dl (> 550 nmol/L), after ACTH stimulation test, was performed with the aim of identifying the optimal basal serum cortisol cut-off. The optimal threshold that maximizes sensitivity plus specificity for morning basal cortisol against peak post-ACTH value >20 µg/dl (>550 nmol/L) was 10 µg/dl (275 nmol/L). Furthermore, the values associated with the highest negative predictive value (NPV) and highest, positive predictive value (PPV) were 4.20 (115 nmol/L) and 18.45 µg/dl (510 nmol/L), respectively. Surprisingly, 20 specialists in thalassemia working in blood bank, thalassemia centres (day hospital), internal medicine, hematology and onco-hematology had poor knowledge and experience in testing for CAI and stopped filling the questionnaire after the second question. In contrast, 9 endocrinologists (8 pediatricians) and 6 hematologists working in collaboration with endocrinologists completed the questionnaire. CONCLUSIONS: While waiting for more extensive adequately powered and targeted studies, physicians should adopt an acceptable policy for accurate assessment of HPA in TM patients. Regular surveillance, early diagnosis, treatment and follow-up in a multi-disciplinary specialized setting are also recommended. The ICET-A recommendations are reported in order to facilitate for interested physicians the approach to a successful assessment of adrenal function in thalassemia.

The effects of economic sanctions on disease specific clinical outcomes of patients with thalassemia and hemophilia in Iran.

BACKGROUND: The sanctions applied by both the USA and the EU against Iran do not formally ban the exports of medicines; in practice, however, patients are experiencing great difficulty in securing the treatment. This article documents the impact of international sanctions on patients with thalassemia and hemophilia in southern Iran. METHODS: This survey examined the specific effects of external sanctions on the access of patients to their treatment between 2009 and 2012 from the point of view of patients with thalassemia (n=69) and congenital coagulation disorders (n=40) as well as related physicians (n=20). Also, clinical manifestation and laboratory data of patients were compared in the same period. RESULTS: Access to deferoxamine and Exjade as iron chelators in patients with thalasseamia, respectively, declined by almost 70% and half over this period. In addition, access to lyophilized coagulation factor VIII concentrate in hemophilia A dramatically dropped from 96.7% in 2009 to 3.3% in 2012. The clinical results showed a significant deterioration of arthropathy (P<0.001) in hemophiliac patients and a significant increase in serum ferritin levels in thalassemia patients (P=0.036). CONCLUSION: Sanctions had significant effect on public health on patients with thalassemia and hemophilia.

Cost-utility analysis of oral deferasirox versus infusional deferoxamine in transfusion-dependent ß-thalassemia patients.

BACKGROUND: Deferasirox (DFX) is a novel iron chelator that has been shown to have similar efficacy and safety compared with deferoxamine (DFO) in patients with ß-thalassemia. The aim of this study was to determine the cost utility of DFX versus DFO in ß-thalassemia major patients from Iran's society perspective. STUDY DESIGN AND METHODS: A Markov model has been developed to determine lifetime cost and quality-adjusted life-years (QALYs) of patients. To estimate the annual cost of each method, a cross-sectional study was conducted among two groups of patients who received DFO and DFX (n = 100 and n = 45, respectively). Also a time trade-off method was used to estimate the utility of two strategies. Finally a one-way and probabilistic sensitivity analysis was conducted to examine the strength of the results. RESULTS: Our base-case analysis showed that estimated total lifetime costs per patient for DFX and DFO were 47,029 international dollar ($Int) and $Int143,522, respectively, while the estimated total discounted QALYs per person were 12.28 and 7.76, respectively. Calculated incremental cost-effectiveness ratio showed that DSX is a dominant therapy and its estimated lifetime net monetary benefit was $Int273,528. CONCLUSION: We conclude that the use of DFX instead of DFO represents a cost-effective use of resources for treatment of iron overload in patients with ß-thalassemia from Iran's society perspective.

Cost-utility analysis of immune tolerance induction therapy versus on-demand treatment with recombinant factor VII for hemophilia A with high titer inhibitors in Iran.

BACKGROUND: In developing countries, the treatment of hemophilia patients with inhibitors is presently the most challenging and serious issue in hemophilia management, direct costs of clotting factor concentrates accounting for >98% of the highest economic burden absorbed for the health care of patients in this setting. In the setting of chronic diseases, cost-utility analysis, which takes into account the beneficial effects of a given treatment/health care intervention in terms of health-related quality of life, is likely to be the most appropriate approach. OBJECTIVE: The aim of this study was to assess the incremental cost-effectiveness ratios of immune tolerance induction (ITI) therapy with plasma-derived factor VIII concentrates versus on-demand treatment with recombinant-activated FVIIa (rFVIIa) in hemophilia A with high titer inhibitors from an Iranian Ministry of Health perspective. METHODS: This study was based on the study of Knight et al, which evaluated the cost- effectiveness ratios of different treatments for hemophilia A with high-responding inhibitors. To adapt Knight et al's results to the Iranian context, a few clinical parameters were varied, and cost data were replaced with the corresponding Iranian estimates of resource use. The time horizon of the analysis was 10 years. One-way sensitivity analyses were performed, varying the cost of the clotting factor, the drug dose, and the administration frequency, to test the robustness of the analysis. RESULTS: Comparison of the incremental cost-effectiveness ratios between the three ITI protocols and the on-demand regimen with rFVIIa shows that all three ITI protocols dominate the on-demand regimen with rFVIIa. Between the ITI protocols the low-dose ITI protocol dominates both the Bonn ITI protocol and the Malmö ITI protocol and would be the preferred ITI protocol. All of the three ITI protocols dominate the on-demand strategy, as they have both a lower average lifetime cost and higher quality-adjusted life-years (QALYs) gained. The cost per QALY gained for the Bonn ITI protocol compared with the Malmö ITI protocol was $249,391.84. The cost per QALY gained for the Bonn ITI protocol compared with the low-dose ITI protocol was $842,307.69. CONCLUSION: The results of data derived from our study suggest that the low-dose ITI protocol may be a less expensive and/or more cost-effective option compared with on-demand first-line treatment with rFVIIa.

Ultrasonographic assessment of the prevalence of cholelithiasis and biliary sludge in beta-thalassemia patients in Iran.

BACKGROUND: Thalassemia is a hereditary disease related to hemoglobin synthesis. The aim of this study was to determine the prevalence of gallbladder sludge and stones in beta-thalassemic children. MATERIAL/METHODS: One hundred fifty-three beta-thalassemia patients on a long-term transfusion/chelation program were selected by a cluster randomized method and were evaluated ultrasonographically for the presence of sludge and biliary lithiasis. Relationships between the prevalence of gallbladder sludge and stones with age, sex, age at the start and the frequency of transfusion, mean pretransfusion Hb and ferritin levels, age at start of deferoxamine injection, splenectomy, and degree of splenomegaly were evaluated statistically. RESULTS: Gallstones and biliary sludge were detected in 12.4% and 13.1% of the patients, respectively. There was a significant increase in the prevalence of gallstones with increasing age, transfusion periods of <21 days, severe splenomegaly, splenectomy, and deferoxamine injection started after 5 years of age. Such a relationship was not detected for hemoglobin and ferritin levels. Multiple logistic regression analysis revealed that the frequency of transfusions and age at the start of deferoxamine injections were the only positive factors that predicted the subsequent development of gallstones. CONCLUSIONS: Longer survival of beta-thalassemic patients leads to a higher prevalence gallbladder sludge and stones. Therefore a proper follow-up of patients with abdominal ultrasonography and improving the transfusion/chelation program should be mandatory.

Assessment of the prevalence of iron deficiency anemia, by serum ferritin, in pregnant women of Southern Iran.

BACKGROUND: Iron-deficiency anemia (IDA) is a public health problem in the developing and even industrialized countries. Pregnant women and children under 5 years of age are among the high-risk population. Our main objectives in this study were to obtain the prevalence of IDA in pregnant women by routine methods and by serum ferritin. MATERIAL/METHODS: We analysed the blood of 270 healthy pregnant mothers, 16 weeks of gestational age. A series of determinations were conducted to determine haemoglobin concentration (Hb); red blood cells count (RBC); serum ferritin and other indexes. Then a questionnaire for epidemiological data, type of diet, level of education, laboratory data, etc. was filled. RESULTS: The mean values (SD) of haematological indexes were as follows: Hb 12.07I1.5 g/dl; serum ferritin 24.87I19.32 ng/ml; mean corpuscular haemoglobin concentration (MCHC) 31.9I1.4 g/dl; mean corpuscular volume (MCV) 82.2I9 fl and mean corpuscular haemoglobin (MCH) 26.4I3.2 pg. 28.5 % of the subjects were anaemic at the time of the study according to serum ferritin (SF < 12 ng/ml) and 16.7% of the mothers had low serum Haemoglobin (Hb<11 g/dl) (P=0.005). There was a positive correlation (r=0.76; P=0.01) between Hb concentration and serum ferritin levels. CONCLUSIONS: The prevalence of IDA was 28.5%, which is the same as the prevalence found in other developing countries (25-35%). This shows that in southern Iran we are still far behind the health status in the industrialized countries (5-8%).