A systematic review on thalassaemia screening and birth reduction initiatives: cost to success.

INTRODUCTION: Thalassaemia has been prevalent with high morbidity and mortality rates since 1925. Although there is a lack of systematic review on the costs of prevention that has yielded reductions in thalassaemia prevalence, this review will show a widespread presence of complex but effective strategies in reducing national thalassaemia prevalence. MATERIALS AND METHODS: A systematic search was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020). Designated keywords were combined with search functions and Boolean operators in databases like Scopus, Web of Science and several other search databases. RESULTS: The search identifed 5425 potential articles. Most countries reported a decline in thalassaemia prevalence after implementing intervention programmes for several decades. The screening methods, however, varies, and the speed of reductions depends on the type of screening approach that involves blood screening of adolescence and antenatal mothers and, in some countries, includes termination of pregnancy. In addition, the cost of these initiatives varies as it was challenging to find a common denominator. However, the endpoint concedes that the cost of screening, although substantial, would be offset by the cost of reduction of cases. In some countries, cost-effectiveness analyses have been reported to support the initiatives of thalassaemia screening and prevention in the long run. CONCLUSION: The results showed significant variations in success rates with a significant reduction in the prevalence of Thalassaemia. Most successful are countries with comprehensive and aggressive prevention and control programmes that engaged with lab screening, counselling, and termination of pregnancy as a package.

Estimating the Cost of Thalassemia Care across the World: A Thalassemia International Federation Model.

Estimating the cost of thalassemia care is important for the optimization of care planning, resource allocation and the empowerment of patient advocacy. However, available evidence is heterogeneous, reflecting diverse healthcare systems and cost estimation methods. We sought to build a globally applicable cost model for thalassemia care. We followed a three-step approach, including (i) a targeted literature review to identify previous cost-of-illness studies on thalassemia; (ii) a generic model development based on the main determinants of cost in different countries emerged from a literature review and validated by a team of medical experts; (iii) a piloting of the model using data from two diverse countries. The literature review revealed studies focusing on the total costs of thalassemia care or the cost or cost-effectiveness of specific treatment or prevention modalities in high- and low-prevalence countries across the world. The resulting evidence was used to build a model that calculates total annual therapy cost based on entry of country-level and patient-level data, and data on healthcare modalities, indirect costs and prevention. Testing the model using published data from the UK, Iran, India and Malaysia, revealed an annual cost per patient of £81,796.00 for the UK, Iranian rial (IRR) 13,757.00 for Iran, Indian rupee (INR) 166,750.00 for India and Malyasian ringgit (or dollar) (MYR) 111,372.00 for Malaysia. A globally applicable model that calculates total annual cost of thalassemia care was built based on existing evidence. The model successfully predicted the annual cost of thalassemia care in the UK, Iran, India and Malaysia.

Socio-demographic Profile and Economic Burden of Treatment of Transfusion Dependent Thalassemia.

OBJECTIVE: To compile the socio-demographic profile and estimate the economic burden of transfusion dependent thalassemia. METHODS: This cross-sectional descriptive study was conducted at a tertiary care hospital in north India. Transfusion dependent thalassemia patients on regular blood transfusion for at least a year were selected. Thalassemia diagnosis was based on HPLC and/or mutation analysis results. Clinical and laboratory parameters were collected from electronic health records. Information regarding socio-economic profile and costs incurred, including indirect costs were collected by interviewing patients' guardians. The data was analyzed as a whole cohort and also in subgroups based on age. RESULTS: The data of 261 patients with a median age of 127 mo was collected. The median age at diagnosis was 9.8 mo. The total treatment expenses of a patient per year ranged from US$ 629 (INR 41,514) to US$ 2300 (INR 151,800), in the different age groups, at an average of US$ 1135 (INR 74,948). More than half (53%) of this was spent on medications. On an average, 38.8% of the family income was spent on the treatment of a thalassemia patient annually. Only 19 of 262 cases had an average pre-BT Hb ≥ 9 g/dl and serum ferritin ≤1500 ng/dl. CONCLUSIONS: The treatment for transfusion dependent thalassemia is costly and mostly borne by the families in India. This study provides a realistic magnitude of this burden and will be useful in planning a thalassemia management program at the state or national level.

A national registry of haemoglobinopathies in Greece: deducted demographics, trends in mortality and affected births.

Haemoglobinopathies are the most common hereditary disorders in Greece. Although there is a successful national prevention program, established 35 years ago, there is lack of an official registry and collection of epidemiological data for haemoglobinopathies. This paper reports the results of the first National Registry for Haemoglobinopathies in Greece (NRHG), recently organized by the Greek Society of Haematology. NRHG records all patients affected by thalassaemia major (TM), thalassaemia intermedia (TI), "H" Haemoglobinopathy (HH) and sickle cell disease (SCD). Moreover, data about the annual rate of new affected births along with deaths, between 2000 and 2010, are reported. A total of 4,506 patients are registered all over the country while the number of affected newborns was significantly decreased during the last 3 years. Main causes for still having affected births are: (1) lack of medical care due to financial reasons or low educational level; (2) unawareness of time limitations for prenatal diagnosis (PD); due either to obstetricians' malpractice or to delayed demand of medical care of couples at risk; and (3) religious, social or bioethical reasons. Cardiac and liver disorders consist main causes for deaths while life expectancy of patients lengthened after 2005 (p < 0.01). The NRHG of patients affected by haemoglobinopathies in Greece provides useful data about the haemoglobinopathies in the Greek population and confirms the efficacy of the National Thalassaemia Prevention Program on impressively decreasing the incidence of TM and sickle cell syndromes.

Screening for sickle cell and thalassaemia in primary care: a cost-effectiveness study.

BACKGROUND: Haemoglobinopathies, including sickle cell disease and thalassaemia (SCT), are inherited disorders of haemoglobin. Antenatal screening for SCT rarely occurs before 10 weeks of pregnancy. AIM: To explore the cost-effectiveness of offering SCT screening in a primary care setting, during the pregnancy confirmation visit. DESIGN AND SETTING: A model-based cost-effectiveness analysis of inner-city areas with a high proportion of residents from ethnic minority groups. METHOD: Comparison was made of three SCT screening approaches: 'primary care parallel' (primary care screening with test offered to mother and father together); 'primary care sequential (primary care screening with test offered to the mother and then the father only if the mother is a carrier); and 'midwife care' (sequential screening at the first midwife consultation). The model was populated with data from the SHIFT (Screening for Haemoglobinopathies In First Trimester) trial and other sources. RESULTS: Compared to midwife care, primary care sequential had a higher NHS cost of £34,000 per 10,000 pregnancies (95% confidence interval [CI] = £15,000 to £51,000) and an increase of 2623 women screened (95% CI: 1359 to 4495), giving a cost per additional woman screened by 10 weeks of £13. Primary care parallel was dominated by primary care sequential, with both higher costs and fewer women screened. CONCLUSION: The policy judgement is whether an earlier opportunity for informed reproductive choice has a value of at least £13. Further work is required to understand the value attached to earlier informed reproductive choices.

Update on iron chelators in thalassemia.

Over the past four decades, there have been dramatic improvements in survival for patients with thalassemia major due in large measure to improved iron chelators. Two chelators are approved for use in the United States and Canada, parenteral deferoxamine and oral deferasirox. Three are available in much of the rest of the world, where oral deferiprone is also approved (in the United States, deferiprone is only available in studies, for emergency use, or on a "compassionate-use" basis). Many trials and worldwide clinical experience demonstrate that each of the three drugs can chelate and remove iron, and thereby prevent or improve transfusional hemosiderosis in thalassemia patients. However, the chelators differ strikingly in side-effect profile, cost, tolerability and ease of adherence, and (to some degree) efficacy for any specific patient. The entire field of chelator clinical trials suffers from the fact that each drug (as monotherapy or in combination) has not been tested directly against all of the other possibilities. Acknowledging the challenges of assessing chelators with diverse properties and imperfect comparative data, the purpose of this review is to summarize the last 4 years of studies that have improved our understanding of the applications and limitations of iron chelators in various settings for thalassemia patients, and to point out areas for much-needed future research.

Hematopoietic stem cell transplantation in thalassemia.

Almost 30 years have passed since the first successful hematopoietic stem cell transplantation in thalassemia and that first patient is now a healthy young adult with a completely normal life. Since that time, more than 3000 such transplants have been performed worldwide. This review provides a brief history of hematopoietic stem cell transplantation in thalassemia and reassesses current clinical results with the objective to provide outcome predictions based on modern transplant technologies. The role of hematopoietic stem cell transplantation in the oral chelation era and implications for possible closure in the approach to future gene therapy will also be discussed.

Choosing offspring: prenatal genetic testing for thalassaemia and the production of a 'saviour sibling' in China.

This paper focuses on the pre-natal genetic testing and reproductive decision-making around thalassaemia in China. Findings are based on fieldwork conducted in hospitals and research institutions, interviews with families with thalassaemia-affected children, interviews with geneticists and genetic researchers and a literature review conducted between September and November 2007. The paper aims to provide insight into the ways in which those who carry thalassaemia decide to have a test for the condition and the choices available to prospective parents. The paper also analyses factors affecting reproductive choices and the decision to produce a 'saviour sibling', including financial implications, state family planning policy, images and information conveyed through the media and propaganda, advice and counselling from doctors, psychological pressure from the community and social discrimination. The paper concludes with a discussion on the issues involved in the creation of saviour siblings, some of which are particular to China.

Iron chelation therapy in the management of thalassemia: the Asian perspectives.

Worldwide, thalassemia is the most commonly inherited hemolytic anemia, and it is most prevalent in Asia and the Middle East. Iron overload represents a significant problem in patients with transfusion-dependent beta-thalassemia. Chelation therapy with deferoxamine has traditionally been the standard therapeutic option but its usage is tempered by suboptimal patient compliance due to the discomfort and demands associated with the administration regimen. Therefore, a great deal of attention has been focused on the development of oral chelating agents. Deferiprone, even though available for nearly two decades in Asia with recent encouraging data on cardiac iron removal and long-term efficacy, has serious adverse effects including agranulocytosis and neutropenia which has impeded it from routine clinical practice. A novel oral chelator; deferasirox is effective throughout a 24 h dosing period and both preclinical and clinical data indicate that it successfully removes both hepatic and cardiac iron. In Asia, optimal management of severe thalassemia patients and the availability and access to oral iron chelators still presents a major challenge in many countries. In this regard, the development and implementation of consensus guidelines for management of Asian patients with transfusion-dependent thalassemia will be a major step towards improving and maintaining the continuity of patient care.

Low cost combination of DCIP and MCV was better than that of DCIP and OF in the screening for hemoglobin E.

OBJECTIVE: To evaluate hemoglobin E screening tests in a large scale of cases. MATERIAL AND METHOD: A cross-sectional descriptive study was conducted Whole blood obtained from subjects was evaluated for CBC, OF, DCIP, and hemoglobin typing. RESULTS: Five hundred twenty seven hemoglobin E and 280 reference subjects participated. DCIP's sensitivity, specificity, positive predictive value, and negative predictive value were 97.16%, 98.93%, 99.42%, and 95.19%, respectively. These values of OF were 69.12%, 80.00%, 86.67%, and 57.88%, respectively. In the combination of DCIP and OF gave rise to these values of 99.43%, 79.29%, 90.03%, and 96.67%, respectively. Finally the combination of DCIP and MCV < 80 fL resulted in these values to be 99.43%, 98.93%, 99.43%, and 98.93%, respectively. False positive and false negative rate were 1.07% and 0.57%, respectively. CONCLUSION: Combination of DCIP and MCVwas better than that of DCIP and OF in hemoglobin E screening.

Consequences and costs of noncompliance with iron chelation therapy in patients with transfusion-dependent thalassemia: a literature review.

BACKGROUND: Patients with thalassemia major require iron chelation therapy (ICT) to prevent complications from transfusional iron overload. Deferoxamine is effective, but requires administration as a slow continuous subcutaneous or intravenous infusion five to seven times per week. Deferiprone is a three-times-daily oral iron chelator, but has limited availability in the United States. Deferasirox is a once-daily oral iron chelator that was approved in the United States in 2005 for patients older than 2 years of age with transfusional iron overload. STUDY DESIGN AND METHODS: Published evidence on rates of compliance with ICT and the association between compliance, and the incidence and costs of complications of iron overload, in patients with thalassemia major was reviewed. RESULTS: A total of 18 studies were identified reporting data on compliance with ICT, including 7 that examined deferoxamine only, 6 that examined deferiprone only, and 5 that compared deferoxamine and deferiprone; no studies reporting compliance with deferasirox were identified. In studies of deferoxamine only, estimated mean compliance ranged from 59 to 78 percent. Studies of deferiprone generally reported better compliance, ranging from 79 to 98 percent. Results of comparative studies of deferoxamine and deferiprone suggest that compliance may be better with oral therapy. Numerous studies demonstrate that that poor compliance with ICT results in increased risk of cardiac disease and endocrinopathies, as well as lower survival. Although data on the costs of noncompliance are limited, a recent model-based study estimated the lifetime costs of inadequate compliance with deferoxamine to be $33,142. CONCLUSIONS: Inadequate compliance with ICT in thalassemia major is common and results in substantial morbidity and mortality, as well as increased costs.

Prenatal prevention for severe thalassemia disease at Srinagarind Hospital.

OBJECTIVE: To evaluate the results and cost-effectiveness of prenatal prevention measurement in severe thalassemia diseases at Srinagarind Hospital. STUDY DESIGN: Descriptive study. SETTING: Antenatal care (ANC) Clinic, Srinagarind Hospital, Faculty of Medicine, Khon Kaen University. SUBJECTS: 1,498 thalassemic screened pregnant women first presenting at ANC Clinic at gestational age less than 17 weeks. MATERIAL AND METHOD: Medical records of thalassemic screened pregnant women between February 2002 and February 2005 were analyzed. Those with a value of mean corpuscular volume (MCV) less than 80 fl, or positive dichlorophenol indophenol precipitation test (KKU-DCIP Clear Reagent Kit) underwent hemoglobin (Hb) typing by high performance liquid chromatography (HPLC) together with thalassemia investigation (complete blood count, MCV and Hb typing) of their husbands and to identify couples at risk of 3 severe thalassemia diseases; Hb Bart's hydrops fetalis, homozygous, -thalassemia and, -thalassemia/ Hb E disease. Then they were advised to undergo DNA analysis and, if they had fetal risk, appropriate prenatal diagnosis was offered. MAIN OUTCOME MEASURE: Number of affected fetuses detected by prenatal diagnosis. RESULTS: Nine hundred and ninety six pregnant women (66.49%) were positive on screening. Of these, 642 (64.46%) had thalassemia investigation done with their spouses. There were 19 couples at risk (1.27% of total screened pregnant women) for having fetal severe thalassemia disease from initial laboratory results. Most of them were, -thalassemia/ Hb E diseases. We found only 10 pregnant women (52.63%) that had undergone prenatal diagnosis. The consequent results were two affected fetuses (20%), one was Hb Bart's hydrops fetalis, and the other was, o-thalassemia/ Hb E disease. In these cases, their parents decided to discontinue the pregnancy. Our prevention program could save 1.14 million bahts for the cost of treatment in two prevented severe thalassemia cases. CONCLUSION: The prenatal prevention program of severe thalassemia disease at Srinagarind Hospital can effectively detect affected fetuses and reduce severe thalassemia disease, which is a major health problem in Thailand.

Keynote address: The challenge of thalassemia for the developing countries.

The thalassemias occur at some of their highest frequencies in the developing countries, particularly those of Asia. In many countries, facilities for the control of these conditions are extremely limited. Although a great deal can be done to help the situation by developing further North-South and South-South partnerships for disseminating better practice, the major problem for the future lies in the unwillingness of governments and international health agencies to accept that the thalassemias present a health burden comparable to that of other major diseases in the developing countries. However, preliminary analyses suggest that, at least in the case of Asia, this is not true. Further work of this nature, together with more detailed frequency and economic data, are required to provide solid evidence for the health burden posed by thalassemia in the developing world. Unless this is done, the large populations of patients with thalassemia in these countries will continue to be neglected.

Cost-benefit analysis of a national thalassaemia prevention programme in Israel.

OBJECTIVE: In Israel (population 5.7 million) there are around 200 known living subjects with thalassaemia major, of whom around 80% are from the northern district. This study aims at examining the costs and benefits of a national screening programme to prevent thalassaemia in Israel. MEASUREMENTS AND MAIN RESULTS: The lifetime healthcare costs of caring for a person born with thalassaemia major are $284,154. The costs of the home infusion service (33.1%) actually exceed the costs of the chelating agent itself (22.1%). The remaining 44.8% of costs are due to stay in hospital, operations, outpatient visits, laboratory tests, therapists, etc. Lost earnings and premature mortality costs account for a further $51,843 and $141,944 respectively for each case. A national screening programme would cost $900,197 and prevent around 13.4 homozygotes being born, at a cost of $67,369 for each birth prevented. The benefit-cost ratio of the programme to the health services is 4.22:1, which increases to 6.01:1 when a societal perspective is taken. However, around 13.0 homozygote births are still expected to occur, the majority owing to lack of compliance of patients at various stages in the screening process. The addition of a national health education programme for the higher risk non-Jewish population either nationally or in selected regions will incur extra costs, which may be covered by increased benefits as a result of better compliance with the screening programme. CONCLUSION: Israel should start to provide a nationwide thalassaemia screening programme as the monetary benefits to society (and even to the health services alone) will exceed the screening programmes costs.