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

Ernst, Frank R.; Barr, Peri; Elmor, Riad; Sandulli, Walter; Thevathasan, Lionel; Sterman, Arnold B.; Goldenberg, Jessica; Vora, Kevin

doi:10.1007/s40261-016-0462-3

Cited by 42 publications

(44 citation statements)

References 39 publications

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“…The consumption of individual resource events per annum was estimated using per unit resource costs from the literature [30] (Table 1). In cases where more than one direct cost was available, the higher cost was used, which allowed for a conservative estimate.…”

Section: Summary Results -Resource Unitsmentioning

confidence: 99%

“…Costs used in the model were derived from published literature [30] and government/public sources [31]. Considered principal diagnosis of hyperthyroidism (ICD-9-CM code 244.9) derived from weighted national estimates available from the US Healthcare Utilization Project (HCUP) National Inpatient Sample (NIS).…”

Section: Methodsmentioning

confidence: 99%

“…For ED visits and hospitalization, clinical considerations were drawn from studies in the literature, and only patients with hyperthyroid symptoms (tachycardia, tremors, or anxiety) with a reduction in levothyroxine dose within 3 weeks of the documented ED visit or hospitalization were included in the analysis [30]. Patients treated with levothyroxine less than 12 months were excluded based upon the assumption that dosage adjustments were likely attributable to treatment initiation rather than inadequate therapeutic effect [29].…”

Section: Emergency Department (Ed) Visitmentioning

confidence: 99%

“…Increased frequency of levothyroxine dose adjustments has been associated with higher direct and indirect resource costs [30]. In the CONTROL Switch Study, a medical chart review of 99 patients switched from levothyroxine tablets to levothyroxine gel caps, a statistically significant (P <0.0001) reduction of dose adjustments was observed among patients initiated on levothyroxine tablet formulation [29].…”

Section: Emergency Department (Ed) Visitmentioning

confidence: 99%

“…Borrowing from the estimated time and cost of a physician visit noted above (121 minutes), the cost of the laboratory visit was calculated at $18.48. [30].…”

Section: Emergency Department (Ed) Visitmentioning

confidence: 99%

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The Economic Impact of Changing Levothyroxine Formulations in Difficult-to-Treat Hypothyroid Patients: An Evidence-Based Model

Elmor¹,

Sandulli²,

Carter³

2017

Pharmacoeconomics

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Objective: To determine the budget impact of incorporating levothyroxine gel caps in the treatment plan of patients diagnosed with hypothyroidism who experience multiple levothyroxine dose or formulation changes annually due to inadequate efficacy or tolerability.Methods: Cost estimates of levothyroxine formulations were obtained. Estimated utilization patterns and costs of physician services, laboratory tests, ancillary healthcare services, and lost productivity were quantified based on published literature and government/public sources. The patient population was based on epidemiology reports and estimates from the American Association of Clinical Endocrinology and the American Thyroid Association. All calculations of economic outcomes were determined using a budget impact model constructed in a MS Excel platform.Results: The economic model demonstrated for a population of 500,000 persons, there are 23,000 (4.6%) people with hypothyroidism, of which 18,400 (80.0%) receive pharmacologic treatment, including 17,480 (95.0%) that receive levothyroxine. The proportion of patients requiring ≥ 1 dosage changes annually is 31.4%, producing 5,489 "hard-to-treat" patients. Similarly, the proportion of patients requiring ≥ 2 dosage changes annually is 8.0% or 1,398 "harder-to-treat" patients. Using evidence-based data of the tolerability and absorption characteristics of levothyroxine gel caps, changing 20.0% of the target cohort to the gel cap formulation produced annual net cost savings of $542,901 in direct medical costs and $564,650 in lost productivity for "hard-to-treat" patients and savings of $409,107 in direct medical costs and $441,926 in lost productivity for "harder-to-treat" patients. Conclusions:Consideration of switching levothyroxine product from a tablet to a gel cap formulation is justified on an economic and therapeutic basis for hypothyroid patients at risk of subadequate drug efficacy or tolerability as measured by the need for one or more annual levothyroxine dosage or formulation adjustments.

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Section: Summary Results -Resource Unitsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Emergency Department (Ed) Visitmentioning

confidence: 99%

Section: Emergency Department (Ed) Visitmentioning

confidence: 99%

“…Borrowing from the estimated time and cost of a physician visit noted above (121 minutes), the cost of the laboratory visit was calculated at $18.48. [30].…”

Section: Emergency Department (Ed) Visitmentioning

confidence: 99%

See 3 more Smart Citations

The Economic Impact of Changing Levothyroxine Formulations in Difficult-to-Treat Hypothyroid Patients: An Evidence-Based Model

Elmor¹,

Sandulli²,

Carter³

2017

Pharmacoeconomics

Self Cite

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Model‐Informed Precision Dosing Using Machine Learning for Levothyroxine in General Practice: Development, Validation and Clinical Simulation Trial

Janssen Daalen,

Doesburg,

Hunik

et al. 2024

Clin Pharma and Therapeutics

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Levothyroxine is one of the most prescribed drugs in the western world. Dosing is challenging due to high‐interindividual differences in effective dosage and the narrow therapeutic window. Model‐informed precision dosing (MIPD) using machine learning could assist general practitioners (GPs), but no such models exist for primary care. Furthermore, introduction of decision‐support algorithms in healthcare is limited due to the substantial gap between developers and clinicians' perspectives. We report the development, validation, and a clinical simulation trial of the first MIPD application for primary care. Stable maintenance dosage of levothyroxine was the model target. The multiclass model generates predictions for individual patients, for different dosing classes. Random forest was trained and tested on a national primary care database (n = 19,004) with a final weighted AUC across dosing options of 0.71, even in subclinical hypothyroidism. TSH, fT4, weight, and age were most predictive. To assess the safety, feasibility, and clinical impact of MIPD for levothyroxine, we performed clinical simulation studies in GPs and compared MIPD to traditional prescription. Fifty‐one GPs selected starting dosages for 20 primary hypothyroidism cases without and then with MIPD 2 weeks later. Overdosage and underdosage were defined as higher and lower than 12.5 μg relative to stable maintenance dosage. MIPD decreased overdosage in number (30.5 to 23.9%, P < 0.01) and magnitude (median 50 to 37.5 μg, P < 0.01) and increased optimal starting dosages (18.3 to 30.2%, P < 0.01). GPs considered lab results more often with MIPD and most would use the model frequently. This study demonstrates the clinical relevance, safety, and effectiveness of MIPD for levothyroxine in primary care.

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Levothyroxine treatment and gastric juice pH in humans: the proof of concept

Virili

Bruno

Santaguida³

et al. 2022

Endocrine

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Purpose Despite the absorption of oral thyroxine (T4) occurs in the small bowel, several patients with gastric disorders show an increased need for T4. In vitro evidence suggested that medium pH variations interfere with T4 dissolution. This study was aimed at finding the proof of concept of a direct relationship between the minimal effective dose of T4 and the actual gastric juice pH. Patients and methods Among 311 consecutively thyroxine-treated patients, 61 bearing Hashimoto’s thyroiditis (52 F/9 M; median age = 51 years) who complained persistent dyspepsia and/or upper abdominal symptoms following a noninvasive workup for gastrointestinal disorders, underwent EGDS with multiple biopsies and gastric juice pH measurement. All patients accepted to take thyroxine in fasting conditions, abstaining from eating or drinking for one hour. Results Thyroxine requirement increased along with the rising gastric pH (ρ = 0.4229; p = 0.0007). A multivariate analysis revealed that gastric pH was, beside body mass index, the far more important independent variable in determining the effective dose of T4 (p = 0.001). The ROC curve revealed that the pH threshold for an increased thyroxine requirement was at 2.28, being the AUC by 78%. Subdividing patients by the histologic findings, it appeared a significant increase (p = 0.0025) along with the progressive damage of gastric mucosa. Conclusion The in vivo measurement of gastric pH highlighted its key role in determining the minimal effective dose of oral T4 and may explain the interference of food, of some drugs and gut disorders on levothyroxine treatment

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

Cited by 42 publications

References 39 publications

The Economic Impact of Changing Levothyroxine Formulations in Difficult-to-Treat Hypothyroid Patients: An Evidence-Based Model

The Economic Impact of Changing Levothyroxine Formulations in Difficult-to-Treat Hypothyroid Patients: An Evidence-Based Model

Model‐Informed Precision Dosing Using Machine Learning for Levothyroxine in General Practice: Development, Validation and Clinical Simulation Trial

Levothyroxine treatment and gastric juice pH in humans: the proof of concept

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