The economic impact of switching from Synthroid for the treatment of hypothyroidism.

AIMS: To compare hypothyroidism-related costs for patients who continuously used Synthroid and patients who switched from Synthroid to alternative therapies. MATERIALS AND METHODS: Truven's Health Analytics MarketScan Commercial Claims and Encounters database from January 1, 2007 to June 30, 2014 was queried for US adults diagnosed with hypothyroidism who initiated Synthroid and adhered to such therapy for at least 6 months. Propensity score matching matched continuous users of Synthroid to patients who switched from Synthroid to alternative levothyroxine agents. Kruskal-Wallis tests assessed differences between the matched cohorts in several categories of costs, including disease-related drug costs, non-drug medical costs, and total direct medical costs. RESULTS: There were 10,159 individuals included in the study, with 7,991 continuous users of Synthroid and 2,168 switchers. After matching (n = 2,052 for each cohort), continuous use of Synthroid was associated with significantly lower hypothyroidism-related non-drug medical costs ($595 vs $1,023; p = .003) and reduced hypothyroidism-related total medical costs ($757 vs $1,132; p = .010), despite being associated with significantly higher drug costs ($161 vs $109; p < .001). Hypothyroidism-related total medical costs rose as the number of switches of hypothyroidism treatment increased, with continuous users having significantly lower hypothyroidism-related total medical costs ($757) compared with patients who switched twice ($1,179; p = .001) or three or more times ($1,268; p = .004). LIMITATIONS: The analyses focused on continuously insured patients who were adherent to Synthroid for at least 6 months and results may not be generalizable. The reliance on claims data does not allow for clinical examination of hypothyroidism or inclusion of some factors that may be associated with outcomes. The analyses assume that all prescriptions filled are taken as prescribed. CONCLUSIONS: Results indicate that there are significant direct economic healthcare costs associated with switching from Synthroid to alternative levothyroxine therapies, and that these costs increase as patients switch therapies more frequently.

Are multisource levothyroxine sodium tablets marketed in Egypt interchangeable?

A clinical study was initiated in response to patients' complaints, supported by the treating physicians, of suspected differences in efficacy among multisource levothyroxine sodium tablets marketed in Egypt. The study design was a multiple dose (100µg levothyroxine sodium tablet once daily for 6 months) and involved 50 primary hypothyroidism female patients (5 equal groups). Tablets administered included five tablet batches (two brands, three origin locations) purchased from local pharmacies in Alexandria. Assessment parameters (measured on consecutive visits) included the thyroid stimulating hormone, total and free levothyroxine. Tablet dissolution rate was determined (BP/EP 2014 & USP 2014). In vitro vs in vivovs correlations were developed. Clinical and pharmaceutical data confirmed inter-brand and inter-source differences in efficacy. Correlations examined indicated potential usefulness of in vitro dissolution test in detecting poor performing levothyroxine sodium tablets during shelf life.

Evaluation of racial and socioeconomic disparities in medication pricing and pharmacy access and services.

PURPOSE: Results of a study to determine if disparities in drug pricing, pharmacy services, and community pharmacy access exist in a Tennessee county with a predominantly minority population are reported. METHODS: A cross-sectional survey of community pharmacies in Shelby County, a jurisdiction with a total population more than 60% composed of racial and ethnic minority groups, was conducted. Data collection included "out-of-pocket" (i.e., cash purchase) prices for generic levothyroxine, methylphenidate, and hydrocodone-acetaminophen; pharmacy hours of operation; availability of selected pharmacy services; and ZIP code-level data on demographics and crime risk. Analysis of variance, chi-square testing, correlational analysis, and data mapping were performed. RESULTS: Survey data were obtained from 90 pharmacies in 25 of the county's 33 residential ZIP code areas. Areas with fewer pharmacies per 10,000 residents tended to have a higher percentage of minority residents (p = 0.031). Methylphenidate pricing was typically lower in areas with lower employment rates (p = 0.027). Availability of home medication delivery service correlated with income level (p = 0.015), employment rate (p = 0.022), and crime risk (p = 0.014). CONCLUSION: A survey of community pharmacies in Shelby County, Tennessee, found that areas with a high percentage of minority residents had lower pharmacy density than areas with a high percentage of white residents. Pharmacies located in communities with low average income levels, low employment rates, and high scores for personal crime risk were less likely to offer home medication delivery services.

The Economic Impact of Levothyroxine Dose Adjustments: the CONTROL HE Study.

BACKGROUND: In general, hypothyroidism can be adequately treated with a consistent daily dose of levothyroxine. However, the need for levothyroxine dose adjustments is frequent in clinical practice. The extent to which levothyroxine dose adjustments increase the utilization of healthcare resources has not previously been described in the clinical literature. OBJECTIVE: The primary objective of our study was to measure the effect of levothyroxine dose adjustments in terms of their utilization of healthcare resources including direct and indirect costs. A secondary goal was to identify any differences in patient characteristics that may be responsible for levothyroxine dose adjustments. METHODS: A retrospective medical chart review was conducted among patients of selected healthcare providers in the USA. Patients who were recently started on levothyroxine therapy (<6 months) were excluded to avoid situations that were more likely attributable to treatment initiation than inadequate therapeutic effect. Trained nurses extracted data from patient charts and electronic medical record systems for review. We analyzed the cost of resources consumed by the frequency of levothyroxine dose changes over 24 months: 0 dose changes (no dose adjustment group); one dose change, two dose changes, three or more dose changes (≥1 dose adjustment group). RESULTS: The study included 454 patients. Overall estimated resource utilization was higher per patient in the ≥1 dose adjustment group (US$5824) vs. the no dose adjustment group (US$3166) during the 24-month study period. When direct and indirect costs were combined, overall costs of care were greatest in patients requiring three or more dose adjustments (US$8220/patient). Patients in this cohort incurred 2.5-fold greater total costs compared with patients requiring no dose adjustments (US$8220 vs. US$3166). Among the 58 patients in the group requiring three or more dose adjustments, mean direct medical costs were significantly higher than in the patients requiring no dose adjustments (US$6387 vs. US$2182). Patients with at least one dose adjustment experienced a 40.3% increase in lost productivity vs. patients who had no dose adjustments (US$1381 vs. US$984). Loss of productivity was highest among patients with three or more levothyroxine dose adjustments. Among this cohort, there was an 86.4% increase in lost productivity vs. patients who had no levothyroxine dose adjustments (US$1833 vs. US$984). CONCLUSIONS: Patients experiencing multiple levothyroxine dose adjustments were shown to consume more healthcare resources, resulting in higher costs than those who required no dose adjustments. Each care episode contributed to lost time and wages with total estimated lost productivity escalating with increasing levothyroxine dose adjustments over a 24-month period.

Services provided by community pharmacies in Wayne County, Michigan: a comparison by ZIP code characteristics.

OBJECTIVE: To document the availability of selected pharmacy services and out-of-pocket cost of medication throughout a diverse county in Michigan and to assess possible associations between availability of services and price of medication and characteristics of residents of the ZIP codes in which the pharmacies were located. DESIGN: Cross-sectional telephone survey of pharmacies coupled with ZIP code-level census data. SETTING: 503 pharmacies throughout the 63 ZIP codes of Wayne County, MI. MAIN OUTCOME MEASURES: The out-of-pocket cost for a 30 days' supply of levothyroxine 50 mcg and brand-name atorvastatin (Lipitor-Pfizer) 20 mg, availability of discount generic drug programs, home delivery of medications, hours of pharmacy operation, and availability of pharmacy-based immunization services. Census data aggregated at the ZIP code level included race, annual household income, age, and number of residents per pharmacy. RESULTS: The overall results per ZIP code showed that the average cost for levothyroxine was $10.01 ± $2.29 and $140.45 + $14.70 for Lipitor. Per ZIP code, the mean (± SD) percentages of pharmacies offering discount generic drug programs was 66.9% ± 15.0%; home delivery of medications was 44.5% ± 22.7%; and immunization for influenza was 46.7% ± 24.3% of pharmacies. The mean (± SD) hours of operation per pharmacy per ZIP code was 67.0 ± 25.2. ZIP codes with higher household income as well as higher percentage of residents being white had lower levothyroxine price, greater percentage of pharmacies offering discount generic drug programs, more hours of operation per week, and more pharmacy-based immunization services. The cost of Lipitor was not associated with any ZIP code characteristic. CONCLUSION: Disparities in the cost of generic levothyroxine, the availability of services such as discount generic drug programs, hours of operation, and pharmacy-based immunization services are evident based on race and household income within this diverse metropolitan county.

Screening for autoimmune thyroid disorders after spontaneous abortion is cost-saving and it improves the subsequent pregnancy rate.

BACKGROUND: Hypothyroidism and/or autoimmune thyroid disorders (AITD) may contribute to spontaneous abortions (SpA). Cost-effectiveness analyses of thyroid screening in women after SpA are lacking. Our aim was to evaluate the cost-effectiveness of screening for AITD and/or hypothyroidism and their treatment in women after SpA with regard to their reproductive health. METHODS: We performed a cross-sectional non-randomized study with follow-up in 2008-2011 in the settings of Departments of Endocrinology and Obstetrics/Gynecology of a university hospital. We enrolled 258 women after SpA before the 12th gestational week and followed them for a median of 3 years. At enrollment, serum concentrations of thyroid stimulatory hormone (TSH), antibodies to thyroid peroxidase (TPOAb) and free thyroxine (FT4) were measured and thyroid ultrasound performed. Women with overt hypothyroidism were treated with levothyroxine (n = 45; 61.6%) and women with subclinical hypothyroidism or euthyroid AITD were treated (n = 28; 38.4%) or left untreated (n = 38; 14.7%). Euthyroid women without signs of AITD served as controls (n = 147; 57.0%). RESULTS: Of the 38 untreated women with AITD and/or subclinical hypothyroidism, 8 (21.1%) reported secondary infertility as compared to 16/147 (10.9%) controls and 3/73 (4.1%) treated women (p = 0.021). Treatment was associated with an increased rate of successfully completed subsequent pregnancies (increment of 6 newborns/100 women) and a savings of €19,539/100 women. Total costs per successfully completed pregnancy were €1,189 in controls, €1,564 in the treated, and €2,488 in the untreated women. CONCLUSIONS: Screening for thyroid disorders in women after SpA and treatment with levothyroxine is cost-saving and it improves the subsequent pregnancy rate.

Levothyroxine and lung cancer in females: the importance of oxidative stress.

BACKGROUND: Levothyroxine (LT4) treatment can lead to iatrogenic hyperthyroidism and oxidative stress that can cause patient discomfort. Oxidative stress is also recognized as one of the causes of chronic diseases and cancer. METHODS: The prevalence of breast, colorectal, gastric and lung cancer in 18 Italian Regions during 2010 was correlated with the sales of LT4 in 2009. The cancer prevalence was analyzed in women aged 30-84. This age range corresponds to more than 80% of the consumers of the drug and to about 99% of all malignant cancers. The correlation between sales of LT4 and cancers was determined with the technique of Density Ellipses. The age and smoking contribution for lung cancer was determined with the Sequential test. RESULTS: No significant correlation was seen between LT4 sales and breast, colorectal and gastric cancers. A significant correlation was instead found for lung cancer (p<0.05) corrected for smoking and age. CONCLUSIONS: LT4 consumption in Italy is about 0.7 boxes/women/year. There is a correlation between lung cancer and LT4 treatment and oxidative stress caused by LT4 supplementation can be one of the causes. Although we cannot exclude that dysthyroidism needing LT4 supplementation might be the ground for lung cancer itself and measuring oxidative stress could be helpful in avoiding excessive use of the drug.

Generic drug discount programs: are prescriptions being submitted for pharmacy benefit adjudication?

UNLABELLED:   BACKGROUND: In 2006, pharmacies began offering select generic prescription drugs at discount prices (e.g., $4 for a 30-day supply) through nonmembership and membership programs. As part of the contract in membership generic drug discount programs, the member agrees to forgo submission of the claim to the insurance company. Claims not submitted for insurance adjudication may result in incomplete pharmacy benefit manager (PBM) and health plan data, which could negatively influence adherence reporting and clinical programs. To address potentially missing claims data, the Centers for Medicare Medicaid Services (CMS) encourages Medicare Part D sponsors to incentivize network pharmacies to submit claims directly to the plan for drugs dispensed outside of a member's Part D benefit, unless a member refuses. The extent of PBM and health plan claims capture loss due to generic drug discount programs is unknown. OBJECTIVE: To identify changes in levothyroxine utilizers' prescription claims capture rate following the advent of generic drug discount membership and nonmembership programs. METHODS: This retrospective concurrent cohort study used claims data from 3.5 million commercially insured members enrolled in health plans located in the central and southern United States with Prime Therapeutics pharmacy benefit coverage. Members were required to be 18 years or older and younger than 60 years as of January 1, 2006, and continuously enrolled from January 1, 2006, through December 31, 2010. Members utilizing generic levothyroxine for at least 120 days during January 1, 2006, through June 30, 2006 (baseline period) from the same pharmacy group with supply on July 1, 2006, were placed into 1 of 3 pharmacy groups: (1) nonmembership (Walmart, Sam's Club, Target, Kroger, City Market, and King Soopers pharmacies), (2) membership (Walgreens, CVS, Albertsons, and Savon pharmacies), or (3) the reference group of all other pharmacies. The index date was defined as July 1, 2006. The levothyroxine claim providing supply on July 1, 2006, was the index claim. Members with a Kmart pharmacy index claim were excluded, since the Kmart membership drug discount program began prior to July 1, 2006. Levothyroxine claims capture nonpersistency, defined as the occurrence of a claim supply end date prior to a 180-day gap, was the primary outcome variable and was assessed from July 1, 2006, through June 30, 2010 (follow-up period). The odds of levothyroxine claims capture nonpersistency by pharmacy group were assessed using a logistic regression analysis adjusted for the following covariates: age, gender, median income in the ZIP code of residence (binomial for ≤ $50,000 vs. greater than $50,000), switch to a brand levothyroxine product during the follow-up period, index levothyroxine claim supply of 90 days or more, and index levothyroxine claim member cost share per 30-day supply in tertiles (≤ $5.00, $5.01-$7.99, ≥ $8.00). RESULTS: Of 2,632,855 eligible members aged 18 years or older, 13,427 met all study eligibility criteria. The baseline pharmacy groups were membership with 3,595 (26.8%), nonmembership with 1,919 (14.3%), and all other pharmacies with 7,913 (58.9%) members. The rates of levothyroxine claims capture persistency throughout the 4-year follow-up period were 85.4% for nonmembership (P = 0.593 vs. all other pharmacies), 77.7% for the membership group (P less than 0.001 vs. all other pharmacies), and 85.9% for all other pharmacies. The Kaplan-Meier comparison of claims capture persistency found nearly identical claims capture loss for the nonmembership compared with all other pharmacies group, and when compared in a multivariate logistic regression model, there was no difference in the odds of levothyroxine claims capture over 4 years follow-up (OR = 1.01, 95% CI = 0.88-1.16, P = 0.900). The membership generic drug discount programs (Walgreens, CVS, Alberstons, and Savon pharmacies) had a statistically significant 61% higher odds (OR = 1.61, 95% CI = 1.45-1.79, P less than 0.001) of levothyroxine claims capture nonpersistency. The onset of the difference between the membership group and the all other pharmacies group was temporally associated with the launch of the membership programs. In comparison to index levothyroxine member cost of ≤ $5.00 per 30-day supply, higher cost shares were associated with higher levothyroxine claims capture nonpersistency ($5.01 to $7.99 OR 1.34, 95% CI 1.19-1.52 and ≥ $8.00 OR 1.60, 95% CI 1.40-1.82). CONCLUSIONS: Among levothyroxine utilizers in 2006 (prior to the advent of drug discount programs), those with claims from a pharmacy that subsequently implemented a nonmembership generic drug discount program did not appear to have a different rate of levothyroxine claims capture than members from the reference group when followed through June 2010. Utilizers with claims from a pharmacy that subsequently implemented a membership program had a significantly lower levothyroxine claims capture rate. Increasing index levothyroxine member cost was associated with higher levothyroxine claims capture loss. Because the analysis could not directly measure claims capture loss associated with members who switched to a new pharmacy group without presenting their insurance information (e.g., membership discount programs), further research is needed to confirm these findings.

Trends in thyroid hormone prescribing and consumption in the UK.

BACKGROUND: Thyroid hormone replacement is one of the most commonly prescribed and cost effective treatments for a chronic disease. There have been recent changes in community prescribing policies in many areas of the UK that have changed patient access to necessary medications. This study aimed to provide a picture of thyroid hormone usage in the UK and to survey patient opinion about current community prescribing policies for levothyroxine. METHODS: Data on community prescriptions for thyroid hormones in England between 1998 and 2007, provided by the Department of Health, were collated and analysed. A survey of UK members of a patient support organisation (the British Thyroid Foundation) who were taking levothyroxine was carried out. RESULTS: The amount of prescribed thyroid hormones used in England has more than doubled, from 7 to almost 19 million prescriptions, over the last 10 years. The duration of prescriptions has reduced from 60 to 45 days, on average over the same time. Two thousand five hundred and fifty one responses to the patient survey were received. Thirty eight percent of levothyroxine users reported receiving prescriptions of 28 days' duration. 59% of respondents reported being dissatisfied with 28-day prescribing. CONCLUSION: Amongst users of levothyroxine, there is widespread patient dissatisfaction with 28-day prescription duration. Analysis of the full costs of 28-day dispensing balanced against the potential savings of reduced wastage of thyroid medications, suggests that this is unlikely to be an economically effective public health policy.

Hypothyroidism among pediatric cancer patients: a nationwide, registry-based study.

The aim of the study was to determine the incidence and prevalence of hypothyroidism (HT) among childhood cancer survivors by means of register linkage. Patients extracted from the Finnish Cancer Registry data base (5,180 patients with cancer diagnosis at the age of 0-15 years, and born after 1970) were linked with thyroxin reimbursement data (Drug Reimbursement Register) and with thyroxin purchase data (prescription database) maintained by the Social Insurance Institution. At the end of follow-up, the prevalence of HT (10,509/100,000) was found to exceed that in the general population (240/100,000) for those aged <35 years. Diagnostic group (p < 0.0001) and gender (p < 0.0025) had significant effect on the risk of developing HT. Males were less prone to the development of HT. Cumulative incidence rate of HT was highest in patients with thyroid cancer (TC), Hodgkin lymphoma, central nervous system (CNS) tumors and neuroblastoma. Except in patients with TC (4.5 months) and CNS tumors (19 months), the median time for the appearance of HT was quite long, varying between 2 and 4.5 years. We consider our results valuable in providing new data for the planning of thyroid function follow-up in different diagnostic groups of childhood cancer survivors.

[Will the thyroglobulin assay with lower functional sensitivity whilst the patients are on L-T4 treatment replace the TSH-stimulated thyroglobulin assay in the follow-up of patients with differentiated thyroid cancer?]. / O ensaio de tiroglobulina com melhor sensibilidade funcional enquanto os pacientes tomam L-T4 substituirá a tiroglobulina estimulada pelo TSH no seguimento dos pacientes com câncer diferenciado da tiróide?

The author reviews the literature on the new assays for serum thyroglobulin (sTg) presenting lower functional sensitivity and demonstrates that its use, whilst the patients are taking L-T4, presents better results than sTg following TSH stimulation in the follow-up of patients with differentiated thyroid carcinoma. Therefore, he suggests a revision on the guidelines for the follow-up of these patients (developed when the available assays present a sensitivity of 1 ng/mL), proposing the use of sTg assays with functional sensitivity of 0.1-0.2 ng/mL with the patients on L-T4 treatment instead of sTg stimulated by TSH.

O ensaio de tiroglobulina com melhor sensibilidade funcional enquanto os pacientes tomam L-T4 substituirá a tiroglobulina estimulada pelo TSH no seguimento dos pacientes com câncer diferenciado da tiróide? / Will the thyroglobulin assay with lower functional sensitivity whilst the patients are on L-T4 treatment replace the TSH-stimulated thyroglobulin assay in the follow-up of patients with differentiated thyroid cancer?

O autor apresenta evidências recentes da literatura que mostram que ensaios de tiroglobulina sérica (sTg) com maior sensibilidade funcional apresentam a mesma qualidade que a obtenção da sTg estimulada por rhTSH ou hipotiroidismo, no seguimento de pacientes com câncer diferenciado de tiróide (CDT). Desta forma, propõe modificar a prática recomendada pelas diretrizes de sociedades internacionais para o seguimento desses pacientes (desenvolvidas enquanto os ensaios disponíveis apresentavam sensibilidade de 1 ng/mL), substituindo-se a obtenção da sTg estimulada por rhTSH ou hipotiroidismo pelo acompanhamento dos pacientes na vigência da terapia com L-T4 com a medida da sTg desde que se empreguem técnicas com sensibilidade funcional da ordem de 0,1-0,2 ng/mL.

The author reviews the literature on the new assays for serum thyroglobulin (sTg) presenting lower functional sensitivity and demonstrates that its use, whilst the patients are taking L-T4, presents better results than sTg following TSH stimulation in the follow-up of patients with differentiated thyroid carcinoma. Therefore, he suggests a revision on the guidelines for the follow-up of these patients (developed when the available assays present a sensitivity of 1 ng/mL), proposing the use of sTg assays with functional sensitivity of 0.1-0.2 ng/mL with the patients on L-T4 treatment instead of sTg stimulated by TSH.

Effects of restricting levothyroxine dosage strength availability.

We conducted a prospective, randomized, controlled trial to assess whether hospital formulary restrictions involving limiting dosage strengths of levothyroxine affect physicians' ability to manage patients effectively and provide pharmacy cost savings in a tertiary care federal government research hospital. Thirty-three endocrinologists were randomly assigned to prescribe levothyroxine from a restrictive (dosage strengths of 25, 50, 100, 125, and 150 micrograms) or a nonrestrictive (dosage strengths of 25, 50, 75, 100, 112, 125, 150, 175, 200, and 300 micrograms) formulary through a central computer system. Their 241 respective outpatients' laboratory results and drug compliance were outcome measures. Achievement of treatment objectives was measured by thyroid function tests (free and total thyroxine, total triiodothyronine, thyrotropin), number of clinic visits, and compliance (survey method). Additional measures were drug distribution patterns, drug costs, and pharmacy inventory costs. Restriction of levothyroxine's dosage strength did not significantly alter therapeutic outcomes. However, the restricted formulary was associated with more complex dosing regimens, and resulted in no significant cost savings. It is not known whether such restriction would adversely affect the care of patients of nonspecialists. Prospective studies are required to verify presumed cost-containment measures before such measures are adopted for widespread application.

Screening for mild thyroid failure at the periodic health examination: a decision and cost-effectiveness analysis.

OBJECTIVE: To estimate the cost-effectiveness of periodic screening for mild thyroid failure by measurement of serum thyroid stimulating hormone (TSH) concentration. DESIGN: Cost-utility analysis using a state-transition computer decision model that accounted for case finding, medical consequences of mild thyroid failure, and costs of care during 40 years of simulated follow-up. SETTING: Periodic health examinations in offices of primary care physicians. PATIENTS: Hypothetical cohorts of women and men screened every 5 years during the recommended periodic examination, beginning at age 35 years. INTERVENTIONS: Adding the serum TSH assay to total serum cholesterol screening was compared to cholesterol screening alone. MAIN OUTCOME MEASURES: Discounted quality-adjusted life years (QALYs) and direct medical costs from a societal perspective. RESULTS: The cost-effectiveness of screening 35-year-old patients with a serum TSH assay every 5 years was $9223 per QALY for women and $22595 per QALY for men. The cost-effectiveness became more favorable when age at first screening was increased for both sexes and was always more favorable for women than men. Reduced progression to overt hypothyroidism and relief of symptoms increased QALYs, but did not substantially reduce direct medical costs. Finding hypercholesterolemia induced by mild thyroid failure reduced direct medical costs, but did not substantially increase QALYs. The cost of a TSH assay and the importance to patients of symptoms associated with thyroid failure were the most influential factors in sensitivity analyses. CONCLUSIONS: The cost-effectiveness of screening for mild thyroid failure compares favorably with other generally accepted preventive medical practices. Physicians should consider measuring serum TSH concentration in patients aged 35 years and older undergoing routine periodic health examinations. The cost-effectiveness of screening is most favorable in elderly women.