Cost-utility analysis comparing radioactive iodine, anti-thyroid drugs and total thyroidectomy for primary treatment of Graves' disease.

OBJECTIVE: Little data is in existence about the most cost-effective primary treatment for Graves' disease. We performed a cost-utility analysis comparing radioactive iodine (RAI), anti-thyroid drugs (ATD) and total thyroidectomy (TT) as first-line therapy for Graves' disease in England and Australia. METHODS: We used a Markov model to compare lifetime costs and benefits (quality-adjusted life-years (QALYs)). The model included efficacy, rates of relapse and major complications associated with each treatment, and alternative second-line therapies. Model parameters were obtained from published literature. One-way sensitivity analyses were conducted. Costs were presented in 2015£ or Australian Dollars (AUD). RESULTS: RAI was the least expensive therapy in both England (£5425; QALYs 34.73) and Australia (AUD5601; 30.97 QALYs). In base case results, in both countries, ATD was a cost-effective alternative to RAI (£16 866; 35.17 QALYs; incremental cost-effectiveness ratio (ICER) £26 279 per QALY gained England; AUD8924; 31.37 QALYs; ICER AUD9687 per QALY gained Australia), while RAI dominated TT (£7115; QALYs 33.93 England; AUD15 668; 30.25 QALYs Australia). In sensitivity analysis, base case results were stable to changes in most cost, transition probabilities and health-relative quality-of-life (HRQoL) weights; however, in England, the results were sensitive to changes in the HRQoL weights of hypothyroidism and euthyroidism on ATD. CONCLUSIONS: In this analysis, RAI is the least expensive choice for first-line treatment strategy for Graves' disease. In England and Australia, ATD is likely to be a cost-effective alternative, while TT is unlikely to be cost-effective. Further research into HRQoL in Graves' disease could improve the quality of future studies.

Is subtotal thyroidectomy a cost-effective treatment for Graves disease? A cost-effectiveness analysis of the medical and surgical treatment options.

BACKGROUND: The 3 treatment options for Graves disease (GD) are antithyroid drugs (ATDs), radioactive iodine (RAI), and thyroid surgery. We hypothesized that thyroid surgery is cost-effective for Graves disease when compared to RAI or ATD. METHODS: Cost-effectiveness analysis was performed to compare operative strategies to medical treatment strategies for GD. The decision model, based on a reference case, included treatment outcomes, probabilities, and costs derived from literature review. Outcomes were weighted using quality of life utility factors, yielding quality-adjusted life years (QALYs). The uncertainty of costs, probabilities, and utility estimates in the model were examined by univariate and multivariate sensitivity analysis and Monte Carlo simulation. RESULTS: The subtotal thyroidectomy strategy produced the greatest QALYs, 25.783, with an incremental cost-effectiveness ratio of $26,602 per QALY, reflecting a gain of 0.091 QALYs at an additional cost of $2416 compared to RAI. Surgery was cost-effective when the initial postoperative euthyroid rate was greater than 49.5% and the total cost was less than $7391. Monte Carlo simulation showed the subtotal thyroidectomy strategy to be optimal in 826 of 1000 cases. CONCLUSION: This study demonstrates that subtotal thyroidectomy can be a cost-effective treatment for GD. However, a 49.5% initial postoperative euthyroid rate was a necessary condition for cost-effective surgical management of GD.

Treatment options for Graves disease: a cost-effectiveness analysis.

BACKGROUND: First-line treatment for Graves disease is frequently 18 months of antithyroid medication (ATM). Controversy exists concerning the next best line of treatment for patients who have failed to achieve euthyroidism; options include lifelong ATM, radioactive iodine (RAI), or total thyroidectomy (TT). We aim to determine the most cost-effective option. STUDY DESIGN: We performed a cost-effectiveness analysis comparing these different strategies. Treatment efficacy and complication data were derived from a literature review. Costs were examined from a health-care system perspective using actual Medicare reimbursement rates to an urban university hospital. Outcomes were measured in quality-adjusted life-years (QALY). Costs and effectiveness were converted to present values; all key variables were subjected to sensitivity analysis. RESULTS: TT was the most cost-effective strategy, resulting in a gain of 1.32 QALYs compared with RAI (at an additional cost of 9,594 US dollars) and an incremental cost-effectiveness ratio of 7,240 US dollars/QALY. RAI was the least costly option at 23,600 US dollars but also provided the least QALY (25.08 QALY). Once the cost of TT exceeds 19,300 US dollars, the incremental cost-effectiveness ratio of lifelong ATM and TT reverse and lifelong ATM becomes the more cost-effective strategy at 15,000US dollars/QALY. CONCLUSIONS: This is the first formal cost-effectiveness study in the US of the optimal treatment for patients with Graves disease who fail to achieve euthyroidism after 18 months of ATM. Our findings demonstrate that TT is more cost effective than RAI or lifelong ATM in these patients; this continues until the cost of TT becomes > 19,300 US dollars.

Does choice of therapy save costs and improve outcomes in hyperthyroid patients?

OBJECTIVE: To compare cost of treating hyperthyroidism with antithyroid medications (ATD) versus radioactive iodine (RAI). As secondary outcome we also analyzed data in terms of remission rates. METHODS: This was a retrospective comparative analysis of hyperthyroid patients treated with ATD or RAI from January 2000 to December 2005. Cost of ATD, TSH. FT4, doctors visits; thyroid technetium scan and RAI treatment were calculated for the duration of treatment and for one year of follow-up after remission. RESULTS: A total of 143 patients were included, with an average duration of follow-up of 32 months. Mean age was 41 +/- 15.5 years and M: F' ratio was 1: 2. More expenses were incurred in treating patients with ATD (Rs. 28,900 +/- 15 400 or US$ 481.67 +/- 256.67) than with RAI (Rs.18.800 +/- 15800 or US$313.33 +/- 263.33). The former cost Rs.10,100 (US$ 168.33) more, (p < 0.001; 95%). Remission rate in the RAI group were significantly higher than the ATD group (81.3% vs 49.5%, p = 0.006). CONCLUSION: Treatment of hyperthyroid patients with RAI is not only better in terms of remission of disease, but it is also a more cost effective modality, and should be considered as first line of treatment.

[Method of medical treatment for Graves' disease based on evidence based medicine].

The Japan Thyroid Association has recently published the guideline for the treatment of Graves' disease with antithyroid drugs (ATD). According this guideline, "the best method of medical treatment for Graves' disease" is described here. The topics in this article include the following: the selection of ATD (Which is better, methimazole or propylthiouracil?), the suitable starting dosage of ATD (Is methimazole 15 mg daily equally effective as 30 mg daily?), the way of decreasing ATD (Is the titlation method to decrease the dosage of ATD suitable?), the duration of the ATD treatment (How long should the ATD treatment be continued?), the relation to smoking (Should smoking be prohibited for patients with Graves' disease?) and the restriction of iodine (Should patients restrict dietary iodine intake?).

Tratamento clínico com drogas antitireoidianas ou dose terapêutica de iodo-131 no controle do hipertireoidismo na doença de graves: avaliação dos custos e benefícios / Anti-thyroid drugs or 131I therapy to control the hyperthyroidism of graves disease: a cost-effectiveness analysis / Anti-thyroid drugs or 131I therapy to control the hyperthyroidism of graves disease: a cost-effectiveness analysis

Com o objetivo de avaliar os custos e a efetividade das 2 formas de tratamento mais utilizadas em nosso meio para a Doença de Graves, iodo radioativo e tratamento clínico prolongado, analisamos pacientes submetidos a essas terapias na região de Maringá, PR. Foram estudados 23 pacientes, 7 homens e 16 mulheres, com idade média de 35,4 anos, submetidos ao tratamento clínico, e 34 pacientes, 5 homens e 29 mulheres, com idade média de 39,4 anos, submetidos à dose terapêutica com iodeto de sódio (iodo-131). Após 2 anos de tratamento clínico com tiamazol (Tapazol®), 21 pacientes atingiram o eutireoidismo e dois permaneceram hipertireóideos. No grupo da dose terapêutica com iodeto de sódio (iodo-131), 21 pacientes evoluíram para o hipotireoidismo, enquanto que 13 atingiram o eutireoidismo. Para o cálculo do custo de cada modalidade de tratamento, analisamos o número de consultas necessárias durante o seguimento, exames complementares solicitados e medicações utilizadas, como tiamazol e/ou tiroxina. O grupo submetido ao tratamento clínico necessitou de maior número de consultas e exames, sendo que o custo médio foi de R$ 1.345,81 neste período de dois anos, enquanto que no grupo com iodeto de sódio (iodo-131) o valor médio foi de R$ 622,94. Assim, os custos da dose terapêutica com iodeto de sódio (iodo-131) foram 53,7 por cento menores do que o tratamento clínico com drogas antitireoidianas. Este trabalho demonstra que o tratamento com dose terapêutica com iodeto de sódio (iodo-131) apresenta um menor custo, sendo bastante efetivo no controle do hipertireoidismo na doença de Graves.

In this study, we set out to evaluate the costs and effectiveness of the 2 most used therapies in our region, ATD or RAI. 23 patients, 6 men and 16 women, with a mean age of 35.4 years, treated with ATD, and 35 patients, 5 men and 30 women, mean age of 39.4 years, treated with RAI, were studied. After 2 years receiving ATD, 21 patients achieved euthyroidism and 2 remained hyperthyroid. In the RAI group, 21 patients presented hypothyroidism and 13 became euthyroid. To calculate the costs of each therapy, we analyzed the number of visits during this period, the laboratory data and the drugs needed, such as tiamazol and/or thyroxine. The group treated only with ATD needed a higher number of visits and laboratory measurements, with the mean total cost of R$ 1,345.81, while the RAI group spent a mean amount of R$ 622.94. Therefore, the costs of the RAI treatment were 53.5 percent lower than clinical therapy with ATD. The present study demonstrates that RAI treatment has a lower cost than ATD, being very effective in controlling the hyperthyroidism of Graves disease.

[Clinical treatment with anti-thyroid drugs or iodine-131 therapy to control the hyperthyroidism of graves disease: a cost-effectiveness analysis]. / Tratamento clínico com drogas antitireoidianas ou dose terapêutica de iodo-131 no controle do hipertireoidismo na doença de graves: avaliação dos custos e benefícios.

In this study, we set out to evaluate the costs and effectiveness of the 2 most used therapies in our region, ATD or RAI. 23 patients, 6 men and 16 women, with a mean age of 35.4 years, treated with ATD, and 35 patients, 5 men and 30 women, mean age of 39.4 years, treated with RAI, were studied. After 2 years receiving ATD, 21 patients achieved euthyroidism and 2 remained hyperthyroid. In the RAI group, 21 patients presented hypothyroidism and 13 became euthyroid. To calculate the costs of each therapy, we analyzed the number of visits during this period, the laboratory data and the drugs needed, such as tiamazol and/or thyroxine. The group treated only with ATD needed a higher number of visits and laboratory measurements, with the mean total cost of R dollars 1,345.81, while the RAI group spent a mean amount of R dollars 622.94. Therefore, the costs of the RAI treatment were 53.5% lower than clinical therapy with ATD. The present study demonstrates that RAI treatment has a lower cost than ATD, being very effective in controlling the hyperthyroidism of Graves disease.

[Cost-effectiveness of the clinical treatment of Grave's disease in a public University Hospital: a retrospective analysis and prospective projection for a therapeutic approach]. / Impacto médico-social do tratamento medicamentoso da moléstia de Graves-Basedow em Hospital Público Universitário: avaliação retrospectiva e projeção prospectiva de conduta terapêutica.

The aim of the present study was to evaluate a new proposal for increasing compliance to the clinical management of patients with Graves' disease (GD) in a large and public University Hospital. The patients were carefully selected (no previous GD treatment, goiter volume less than 6 mL must be living in the metro area of São Paulo), received medication at no cost, were contacted frequently by the social worker and alerted for the date of consultation and only referred to a single endocrinologist during all phases of treatment. We recruited 229 patients with GD that were initially treated with methimazole (MMI--60 mg q.d) in a single daily dose followed by a combination of MMI (20 mg) plus L-T4 (100 microg) daily for 24 months. Only 83 patients (36.2%) completed the protocol and were subdivided in: Group 1 (n= 34) that were in remission for 3 years after discontinuation of the MMI and Group 2 (n= 49) that presented recurrence of GD between 2 and 36 months without MMI. Predictive factors associated with remission were: decrease of the glandular volume, serum TG< 40 ng/mL and normal TRAb values. We concluded that in spite of a careful protocol planned to increase compliance, more than 60% of patients with GD did not complete the therapeutic trial and were referred for radioiodine treatment. The solution for this low therapeutic success for GD should be the possible identification of factors that would indicate patients that are not inclined to follow a long period of clinical therapy.

Impacto médico-social do tratamento medicamentoso da moléstia de Graves-Basedow em Hospital Público Universitário: avaliação retrospectiva e projeção prospectiva de conduta terapêutica / Cost-effectiveness of the clinical treatment of GraveÆs disease in a public University Hospital: a retrospective analysis and prospective projection for a therapeutic approach

O objetivo do presente estudo foi avaliar esquema terapêutico medicamentoso para aumentar a aderência ao tratamento da moléstia de Graves-Basedow (MGB) em Hospital Público Universitário. Os pacientes foram selecionados segundo critérios rigorosos, que incluíam volume glandular inferior a 60cm³, origem da área urbana de São Paulo e não submetidos a terapia prévia da MGB. Receberam gratuitamente a medicação, eram avisados antecipadamente da data da consulta e acompanhados por um único médico durante todo o tratamento. Foram incluídos 229 pacientes, tratados inicialmente com metimazol (MMI - 60mg/dia) em dose única diária, seguindo-se com combinação de MMI (20mg) com LT4 (100æg) em dose única diária por 24 meses. Apenas 83 pacientes (36,2 por cento) completaram o protocolo quando foram subdivididos em 2 grupos, após a suspensão do MMI+LT4: Grupo 1 (n= 34), que permaneceram em remissão por 3 anos, e Grupo 2 (n= 49), que apresentaram recidiva da doença entre 2 e 36 meses. Os fatores preditivos associados à remissão foram: decréscimo do volume glandular, tireoglobulina sérica < 40ng/ml e valores séricos normais de anticorpos anti-receptor de TSH. Constatamos que apesar do planejamento cuidadoso, mais de 60 por cento dos portadores de MGB não completaram o protocolo e foram encaminhados a tratamento com radioiodo. Admitimos que esse baixo êxito terapêutico poderia ser melhorado mediante identificação dos fatores capazes de indicar quais pacientes estariam propensos a seguir um tratamento de longa duração.

[Cost-utility analysis of antithyroid drug therapy versus 131I therapy for Graves' disease].

There is no comparative cost-utility study between 131I therapy and antithyroid drugs (ATD) therapy for Graves' disease, though 131I therapy has higher remission rate and less side effects. The objective of the study was to analyze the cost-utility of ATD therapy versus 131I therapy by calculating life-long medical costs and utility, based on the responses of Graves' disease patients to questionnaires. To determine the expected cost and expected utility, a decision tree analysis was designed on the basis of the 2 competing strategies of ATD therapy versus 131I therapy. A simulation of 1000 female patients weighing > or =50 kg who assumed to experience the onset of Graves' disease at the age of 30, to first complain of thyrotoxic symptoms and moderate goiter 2-3 mo. previously, and to undergo a 40-years-long cohort study, was created for each strategy using a decision tree and baselines of other relevant variables. The variables and costs were based on the literature and hospital bills. The maximum and minimum values of utility were defined as 1.0 and 0.0, respectively. Future costs and utilities were discounted 5%. The medical costs and utilities were 85,739-88,650 yen/patient/40 years and 16.47-16.56/patient/40 years, respectively, for the ATD therapy strategy, and 81,842 yen/patient/40 years and 17.41/patient/40 years, respectively, for the 131I therapy strategy. These results quantitatively demonstrated that the 131I therapy strategy was superior to the ATD therapy strategy in terms of both cost and utility. 131I therapy should be used more widely in Japan because of its greater utility and lower cost.

Risk assessment for benefits analysis: framework for analysis of a thyroid-disrupting chemical.

Benefit-cost analysis is of growing importance in developing policies to reduce exposures to environmental contaminants. To quantify health benefits of reduced exposures, economists generally rely on dose-response relationships estimated by risk assessors. Further, to be useful for benefits analysis, the endpoints that are quantified must be expressed as changes in incidence of illnesses or symptoms that are readily understood by and perceptible to the layperson. For most noncancer health effects and for nonlinear carcinogens, risk assessments generally do not provide the dose-response functions necessary for economic benefits analysis. This article presents the framework for a case study that addresses these issues through a combination of toxicology, epidemiology, statistics, and economics. The case study assesses a chemical that disrupts proper functioning of the thyroid gland, and considers the benefits of reducing exposures in terms of both noncancer health effects (hypothyroidism) and thyroid cancers. The effects are presumed to be due to a mode of action involving interference with thyroid-pituitary functioning that would lead to nonlinear dose response. The framework integrates data from animal testing, statistical modeling, human data from the medical and epidemiological literature, and economic methodologies and valuation studies. This interdisciplinary collaboration differs from the more typical approach in which risk assessments and economic analyses are prepared independently of one another. This framework illustrates particular approaches that may be useful for expanded quantification of adverse health effects, and demonstrates the potential of such interdisciplinary approaches. Detailed implementation of the case study framework will be presented in future publications.

Radioiodine or surgery for toxic thyroid adenoma: dissecting an important decision. A cost-effectiveness analysis.

OBJECTIVE: To examine the cost effectiveness of therapeutic strategies for toxic thyroid adenoma. DESIGN: Markov state transition decision analytic model. SETTING: Ambulatory and inpatient. PATIENTS: Hypothetical cohort of 40- year-old women with toxic thyroid adenomas. Patient age was varied in sensitivity analyses. Data on the prevalence of coincident thyroid cancer, complications, and treatment efficacies were derived from a systematic review of the literature. INTERVENTIONS: Thyroid lobectomy after a 3 month-course of antithyroid drugs (ATDs), high-dose (<555 MBq) radioactive iodine (RAI), low-dose (>555 MBq) RAI, and lifelong ATDs. MEASUREMENTS AND MAIN RESULTS: Outcomes were measured in quality-adjusted life years (QALYs). Costs were estimated from the health care system perspective. Future costs and effectiveness were discounted at 3% per year. For a 40- year-old woman, surgery was the most effective, while low-dose RAI was the least costly. The marginal cost-effectiveness of surgery versus low-dose RAI was $13,183 per QALY. Surgery was less costly and more effective than lifelong ATDs. RAI was more effective than surgery if surgical mortality exceeded 0.90% (base-case 0.001%). Surgery provided relatively inexpensive gains (<$50,000 per QALY) in quality-adjusted life expectancy in patients less than 74 years of age. CONCLUSIONS: For most patients less than 60 years of age, surgery is an effective strategy with a reasonable cost. However, for any given patient, surgical mortality, therapeutic costs and preference must be considered in choosing an appropriate therapy.

[Hypothyroidism: clinical and economical implications in a health area]. / Hipotiroidismo: implicaciones clínicas y económicas en un área de salud.

OBJECTIVE: To analyze the clinical, biochemical and epidemiological characteristics in patients with hypothyroidism, substitutive dose and annual direct costs, in a health area. MATERIAL AND METHODS: Seventy five patients attended in a health area were included in the review. Data was divided in epidemiological, biochemical, clinics and economics. RESULTS: A 94.7% were females and 5.3% males, with an average age of 52.07 + 16.5 years. The most frequent disease was Thyroiditis of Hashimoto 48% and atrophic thyroiditis 46.6%. Average value of TSH was 17.57 + 40.8 mUI/ml and TPO 629.3 + 1049 UI/ml and Ac TG 532.1 + 1028 UI/ml. A 58.7% of patients had goiter, only evident 2.6%. The average dose of T4 was 81 + 53.5 mg/day. The average number of visits was 2.67 + 1.08. The highest cost was due to specialists visit 160 + 65 euros with a total average cost of 212.9 + 81.5 euros. Levels of TPO was higher in T. Hashimoto, with a higher number of visits and costs. CONCLUSIONS: The most prevalent disease was autoimmune (T Hashimoto and atrophic thyroiditis) with higher levels of TPO in Hashimoto. Total cost is higher in T. Hashimoto.

Determination of propylthiouracil using 1,3-dibromo-5,5-dimethylhydantoin (DBH): analytical methods of pharmacopeias with DBH in respect to environmental and economical concern: part 9.

USP 2000 [The United States Pharmacopeia, Rockville USA, 24th ed., 2000, pp. 1436] and PH. EUR. 1997 [European Pharmacopoeia, third ed., Council of Europe, Strasbourg, 1997, p. 1401] determine propylthiouracil using neutralization titration, whereby 0.1 M silver nitrate and twice boiling is necessary. With the application of 1,3-dibromo-5,5-dimethylhydantoin (DBH), the assay of propylthiouracil can be performed easily, faster and friendlier to environment. A mean deviation of 0.03% and a relative standard deviation of 0.3% are obtained. 5-Bromo-6-propyluracil is formed, when propylthiouracil is determined with DBH.

Outcome of thyrotoxicosis treatment with 3 different modalities.

OBJECTIVE: To assess the efficacy of 3 different treatment modalities for thyrotoxicosis and a comparison of their cost effectiveness. METHODS: The case records of 100 patients treated for thyrotoxicosis at King Khalid National Guard Hospital in Jeddah were reviewed, during the period January 1992 through to January 2000. Their various treatments and responses were recorded as well as their thyriometabolic status, one year following the last treatment. The treatment consisted of an average of 9 months of antithyroid medication, thyroidectomy or treatment with radioactive iodide. Cure was defined as a patient being euthyroid or hypothyroid for a minimum period of at least one year. Cost-effectiveness was calculated as the total cost of treating the patient in a specific treatment modality, divided by those who were considered to be cured. RESULTS: For the remainder, the cost could not be definitively determined. The mean age was 41+/- 15.7 years, with female to male ratio of 6:1. Grave's disease was the underlying cause in 76% of cases, toxic multinodular goiter in 13% and toxic nodule in 1%. Ninety-one patients, who were treated with anti-thyroid medication for an average of 9 months, had a success rate of 11%. The success rate with surgery was 54.5%, while of 68 patients treated with radioactive iodide 65 (96%) were cured. Radioactive iodide was the most cost effective modality of treatment costing 1700 Saudi Riyals, followed by surgery at 40,000 Saudi Riyals. Medical treatment was the most expensive at 135,000 Saudi Riyals per cure. CONCLUSION: A treatment of thyrotoxicosis with radioactive iodine is much more efficacious than medical or surgical modalities. Furthermore, it is by far the most cost effective and has no harmful effects.

[Cost-effectiveness analysis: radioiodine or antithyroid medication in primary treatment of immune hyperthyroidism]. / Kosten-Effektivitäts-Analyse: Radioiod oder thyreostatische Medikation bei der Primärbehandlung der Immunhyperthyreose.

AIM: As first-line therapy of hyperthyroidism caused by Graves' disease antithyroid drugs are favoured in Europe, while radioiodine therapy is favoured in the USA. Radioiodine therapy has become more economic in Germany since the new recommendations by the Federal German Radiation Protection Committee (SSK) for patient discharge guidelines. METHOD: Sensitivity analyses took into account the long-term relapse rate of conservative or radioiodine therapy, use of diagnostic tests, level of health insurance, drops in productivity and a discount factor. Costing models included the costs of follow-up care over 30 years. The costs of the hospitalisation for radioiodine therapy were calculated for 300 patients, discharged with 250 MBq 1-131 residual activity. RESULT: Antithyroid drugs were considered cost-effective when they achieved relapse rate of 50% or less, a cut in the number of tests needed and reduced working hours. Failure to meet any one of these conditions makes primary radioiodine therapy more cost-effective in 1593 of 1944 calculated costing models. Repeated conservative therapies will increase clearly the overall costs. CONCLUSION: Radioiodine is a cost-effective, first-line therapy in patients with a special risk of relapse after primary conservative therapy (goitre, younger patient, persistent elevated TSH-receptor-antibodies or Tc-uptake).

Surgery of toxic goitre in non-euthyroid patients: a preliminary report.

In recent years, the cost of medical care has skyrocketed and since medical treatment is not free, some drugs are now beyond the reach of some patients. One of such drugs is the antithyroid drug, carbimazole, which has been priced beyond the reach of our thyrotoxic patients. We have therefore been forced to operate on these patients whenever they present, even while thyrotoxic. The principle of our management is to anticipate the development of thyroid crises and to prevent its occurrence post-operatively by using saturated solution of potassium iodide (SSKI) or Lugol's iodine, propranolol, diazepam, and hydrocortisone. This is a preliminary report of the first twelve consecutive patients so treated.