International Journal of Thyroidology

Table. 3.

Table. 3.

Major economic findings of the studies that dealt with the most common topics

First author (year) (Country) Type of Study Patients Intervention [I], Comparison [C] Direct cost [DC], Indirect cost [IC] Outcomes Analysis Results and conclusion Economic analysis indicator
Hemithyroidectomy (HT) versus total thyroidectomy (TT) for low- to intermediate-risk papillary thyroid carcinoma (PTC)
Shrime (2007)(Literature review from PubMed: 940 PTC papers from 1966/01/01-2007/01/01) CEA 1 million hypothetical low-risk PTC cases (AMES score <6, and AGES score <4, or adherence to the Memorial Sloan–Kettering low-risk categories) [I] HT
[C] TT
[DC] Hospital charges for inpatient operative procedure, FU cost, complication cost, and recurrence cost
[IC] Cost for death from unintentional injuries: $1,130,000 based on National Safety Council estimates of death
Cost and ICER for cause-specific mortality (CSM) or recurrence-free survival (RFS)
CSM or RFS under same cost assumption
CSM and RFS derived from literature reviews (31 studies finally selected)
- Monte Carlo microsimulation using fixed probability estimates of complications and recurrence derived from 31 eligible studies
- Sensitivity analyses using 6% annual discount and cost-to-cost ratio estimated from 31 eligible studies
- Threshold analyses: comparison of net monetary benefits obtained from TT and HT using a variable range of willingness-to-pay (WTP) values
- TT dominates HT as initial treatment for low-risk PTC
- 20-year ICER: [I] HT, $15,037.58-$15,063.75; [C] TT, $13,896.81-$14,241.24
- 20-year CSM under the same cost assumption: similar HT and TT
- 20-year RFS under the same cost assumption: higher in TT (89.9%) than HT (75.2%)
- Sensitivity analyses: HT sensitive to recurrence rates and FU costs
- Threshold analyses: robust when compared with WTP
Cost, ICER
Lang (2016)(China) CUA Hypothetical cohort of 100,000 non-pregnant women aged 40 years with a unifocal intrathyroidal 2.5-cm clinically nodal negative PTC but without family history of non-medullary thyroid cancer and neck irradiation [I] Lobectomy
[C] TT
[DC] Costs of surgery, RAI, surgically related complications, and annual thyroxine replacement based on data obtained from Medicare reimbursement data
[IC] Not included
QALY gained during 25 years.
Estimates of the quality adjustment factor for hypothyroidism needing thyroxine (0.99), uni- and bi-lateral vocal cord palsy (VCP) (0.63, and 0.21, respectively), hypoparathyroidism (0.78), and 1-year recurrence (0.54) derived from the literature
- Markov decision model with literature-based probabilities and utilities
- Sensitivity analyses: each clinical parameter varied from lowest to highest values, as suggested in the literature, while other parameters remained constant
- Threshold analyses: threshold of $50,000/QALYs
- Initial lobectomy was a more cost-effective long-term option than initial TT for 1 to 4 cm PTCs without clinically recognized high-risk features
- After 25 years, lobectomy cost $772.08 more than TT, but gained an additional 0.300 QALY (ICER, $2,577.65/QALY)
- Sensitivity analyses: lobectomy began to become cost-effective only after 3 years. Despite varying the reported prevalence of clinically unrecognized high-risk features, complication from surgical procedures, annualized recurrence rates, unit cost of surgical procedure or complication, and utility score, lobectomy remained more cost-effective than TT
- Threshold analyses: Lobectomy was regarded as cost-effective if the ICER was below the threshold of the %50,000/QALY
Al-Qurayshi (2020)(US) CUA Base-case scenario, a 40-year-old woman who presented with a 2-cm single thyroid nodule after a preoperative FNA biopsy that was suspicious for PTC [I] TT
[C] Lobectomy
[DC] Costs of surgery, complications, post-operative surveillance, and drugs retrieved from the literature
[IC] Cost of loss of productivity for 2 weeks based on the literature
20-year cost for QALY measured by ICER (Δcost/ΔQALY)
Utility scores for QALY calculation extracted from the literature; absence of complications, 1; hypothyroidism, 0.99; hypoparathyroidism, 0.778; unilateral recurrent laryngeal nerve (RLN) injury, 0.627; and bilateral RLN injury, 0.205
- Markov model with literature-based probabilities (TNM stage categories on surgical pathology, RLN injury, hypothyroidism, hypoparathyroidism)
- Sensitivity analyses: varying the risk of PTC stage III or IV, risk of hypoparathyroidism, and risk of RLN injury
- Threshold analyses: threshold of $50,000/QALY
- TT produced an incremental cost of $2,681.36 and incremental effectiveness of −0.24 QALY compared to lobectomy (−$11,188.85/QALY)
- Sensitivity analyses: TT became cost-effective if the risk of stages III and IV PTC is 82.4% among patients with suspicious PTC on preoperative FNA. Lobectomy was cost-effective and preferred over TT as long as lobectomy complications were less than 50%
- Threshold analyses: lobectomy was considered cost-effective if ICER was less than $50,000/QALY
Immediate surgery versus active surveillance (AS) for micro-PTC
Oda (2017)(Japan) CMA 2153 patients diagnosed with low-risk PTC by ultrasound-guided FNA biopsy From February 2005 to August 2013 at Kuma Hospital (a model was created using patients from a previous study) [I] Immediate surgery
[C] AS
[DC] Costs of the initial diagnosis step, costs of surgeries (including all medical costs of preoperative examinations, surgery, anesthesia, pathological examination, and admission), and costs of follow-up care (Japanese Healthcare Insurance System)
[IC] Not included
Medical cost - A model created from the actual flow of the managements of those 2153 patients with low-risk PTCs - 10-year simple cost of active surveillance: ¥7,780/patient
- Simple cost of immediate surgery: ¥794,770/patient to ¥1,086,070/patient, depending on the type of surgery and post-operative medication
- 10-year total cost of active surveillance: ¥225,695/patient when conversion surgeries and recurrence considered
- Total cost of immediate surgery: ¥928,094/patient when recurrence considered
- 10-year total cost of immediate surgery was 4.1 times expensive than active surveillance
Lang (2015)(Hong Kong) CUA Base-case scenario, a 40-year-old woman diagnosed with a unifocal intra-thyroidal 9 mm PTC [I] Non-surgical approach (NSA)
[C] Early surgery (ES)
[DC] Costs of surgery (HT+CND, TT+CND, and TT+ CND+SND) estimated based on Medicare reimbursement data in 2014
Complication and half yearly ultrasound surveillance costs derived from the literature
[IC] Not included
20-year QALY gained measured by ICER (ΔCost/ΔQALY)
Quality of life adjustment is quantified by a utility score ranging from 0 to 1. Utility scores for each health state derived from the literature using the values 1 for alive without permanent complication, 0.54 for alive with permanent complication, and 0 for death
- Markov decision tree model
- Sensitivity analyses (+): according to clinical parameters suggested in the literature
- Threshold analyses (+): threshold defined as the ICER of NSA to ES became zero or infinity
- After a 20-year period, NSA cost an extra $682.54 but gained an additional 0.260 QALY over NSA
- 20-year ICER for NSA relative to ES was $2,630
- NSA was cost saving up to 16 years from diagnosis and remained cost-effective from 17 years
- Sensitivity analyses: NSA remained cost-effective regardless of patient age, complications, rates of progression, year cycle, and discount rate
- Threshold analyses: none of the scenarios that could have changed the conclusion appeared clinically likely
Venkatesh (2017)(US) CUA Base-case scenario, a 40-year-old patient with a biopsy-proven, unifocal micro-PTC without features that would necessitate immediate HT [I] AS
[C] HT
[DC] Published Medicare reimbursement rates and Healthcare Costs and Utilization Project adjusted to 2015 US$. Cost of thyroid hormone supplementation obtained from the Redbook online database
[IC] Not included
20-year cost for QALY measured by ICER (Δcost/ΔQALY)
Health state utility inputs used to calculate QALY obtained from the literature; disutility difference of AS compared to disease-free state post-HT without complication, 0.11; disease-free state after HT without complication, 0.99; disease-free state afterHT with short-term complication, 0.75; disease-free state after HT with long-term complication, 0.63; HT, 0.74; TTLND, 0.55; TTLND with complication, 0.54; Redo LND, 0.56; Redo LND with complication, 0.41; RAI, 0.64; disease-free state after operation and RAI, 0.95; and disease recurrence, 0.54
- Markov model with literature-based probabilities (disease progression during AS, stability of disease after surgery, operative complications, locoregional recurrence)
- Sensitivity analyses: range for costs distributed uniformly from 50% to 150% of published data
- Threshold analyses: threshold of $100,000/QALY
- 20-year FU, HT was costlier at $13,866 but also afforded patients increased effectiveness of 22.13 QALYs.
- For a utility difference of 0.11, the ICER for HT was $4,437/QALY gained
- Sensitivity analyses: AS was dominant for a health utility <0.01 below that for disease-free, post HT state, or for a remaining life expectancy of <2 years
- Threshold analyses: HT was cost-effectives in 79% of the 100,000 simulations at a WTP threshold of $100,000/QALY
Lin (2020)(Australia) CMA 349 micro-PTC patients included from a prospectively collected surgical cohort of patients treated for papillary thyroid cancer between 1985 and 2017 [I] Surgical treatment
[C] AS
[DC] Blood test, consult with an endocrinologist/endocrine surgeon, FNA, medications, ultrasound, CND, LND, RAI(anonymized data provided by clinical costing team from the Royal North Shore Hospital and University of Sydney)
[IC] Not included
Complications of thyroid surgery, recurrence-free survival, overall survival, and cost of surgical treatment and active surveillance Papillary thyroid microcarcinoma patients included from a prospectively collected surgical cohort of patients treated for PTC between 1985 and 2017 - Total cost of surgical treatment: $10,226
- Hypothetical AS cost: $756/year.
- Estimated cost of surgical micro PTC treatment was equivalent to the cost of 16.2 years of AS
- If young Australian patients require more than 16.2 years of follow-up in an AS scheme, surgery may have a long-term economic advantage.
- Sensitivity analyses: AS is more cost-efficient over a longer period.
It would be less cost-efficient for patients between 20 and 30 years of age to be in an AS program
TT with prophylactic CND (pCND) versus TT for low-risk PTC
Lang (2014)(Hong Kong) CEA 100,000 hypothetical non-pregnant female patient cohort at age 50 years with low-risk PTC (1.5-cm cN0 PTC within one lobe) [I] TT with pCND until death or age 70 years
[C] TT until death or age 70 years
DC] 20-year cumulative cost, including procedural cost, RAI ablation, complication cost, hospitalization, annual routine surveillance (Hospital Authority cost published in the 2013 Government Gazette)
[IC] Not included
20-year accumulative medical cost. Surgical procedures, complications, and RAI ablation - A decision-tree model was constructed to compare the estimated long-term cost between TT alone and TT+pCND. Patients underwent one of two strategies, namely TT alone or TT+pCND, and were followed until age 70 years
- All the costs were discounted by annual rate of 3%
- Sensitivity analysis performed to explore the uncertainty on the clinical parameters of complications, RAI ablation, and annualized recurrence rates
- TT+pCND is more expensive in the medium- and long-term in low-risk PTC patients
- TT: US$ 19,888.36 in 20-year cumulative cost
- TT+pCND: US$ 22,760.86 in 20-year cumulative cost
- Incremental cost: US$ 2,872.50
- Sensitivity analyses: no change
Cost, incremental cost
Zanocco (2013)(US) CUA Base-case scenario, a 40-year-old patient with a 2-cm, non-invasive PTC that was without preoperative or intraoperative evidence of nodal involvement [I] TT with routine pCND
[C] TT alone
[DC] 2010 national Medicare charge limits for surgery, anesthesiology, and pathology services rendered in each strategy. Hospital costs and surgical costs estimated by 2009 Medicare cost-to-charge ratios and 2009 Nationwide Inpatient Samples, respectively. Thyroid hormone-replacement costs based on average US wholesale prices. Costs for complications based on previous studies
[IC] Missed patient work due to surgery assigned an hourly cost based on 2010 annual US hourly earnings
Quality-adjusted life expectancy (values based on the literature) for undergoing reoperation for recurrence and complications measured by ICER (Δcost/ΔQALY) - Markov transition-state model with literature-based outcome probabilities and utilities(risk of recurrence, risk of endocrine complications)
- Sensitivity analyses for all variables, including lifetime recurrence after TT alone, recurrence risk reduction with additional pCND, and risk of recurrent laryngeal nerve (RLN) injury and permanent hypoparathyroidism with pCND were performed using 1,000 Monte Carlo iterations
- Threshold analyses: threshold of $100,000/QALY
- pCND cost $10,315 and produced an effectiveness of 23,785 QALYs. The addition of routine pCND resulted in an expected incremental cost of $166 and a loss of 0.006 QALYs
- Sensitivity analyses: pCND became cost-effective when the probability of recurrence increased from 6% to 10.3%, the cost of reoperation for recurrence increased from $8,900 to $26,120, or added probabilities of RLN injury and hypoparathyroidism due to pCND were less than 0.20% and 0.18%, respectively.
- Threshold analyses: pCND was not cost-effective in 97.3% of iterations
Wong (2014)(Hong Kong) CUA 100,000 hypothetical non-pregnant female patient cohort at age 50 years with low-risk PTC (1.5-cm cN0 PTC within one lobe) [I] TT+pCND
[C] TT
[DC] operation and reoperation costs, RAI, hospitalization cost, complication cost, and follow-up cost, based on a literature review (Medicare reimbursement data in 2005)
[IC] Not included
Disease-free survival, recurrence-free survival, and overall death derived from a literature review (31 eligible studies) - Markov decision tree model based on literature review of outcome probabilities, utilities, and costs
- Sensitivity analyses based on uncertainty model with discount rate of 3% per year
- Threshold analyses based on uncertainty model: $50,000/QALY
- Monte Carlo microsimulation using the fixed probability estimates of complications and recurrence derived from 31 eligible studies
- Sensitivity analyses using 6% annual discount and cost-to-cost ratio estimated from 31 eligible studies
- TT+pCND is more cost-effective than TT along for low-risk PTC in the long-term. It began to become cost-effective after 9 years from the initial operation.
- 20-year ICER: TT+pCND, $105.97 relative to TT at threshold of $50,000/QALY
- TT+pCND: extra cost of $34.25 but scored 0.323 QALYs) more than TT
- Sensitivity analyses: positive ICERs of TT+pCND based on difference parameters. TT+pCND became cost-saving at 20 years if associated permanent vocal cord palsy was ≤1.37%, permanent hypoparathyroidism was ≤1.20%, and/or postoperative RAI ablation use was ≤73.64%.
- Threshold analyses: robust when compared with WTP
Garcia (2014)(US) CEA Base-case scenario, a 40-year-old non-pregnant healthy woman with a biopsy-confirmed 2-cm PTC without clinically or radiologically involved neck lymph nodes (Stage II: T1bN0M0) [I] TT with routine CND
[C] TT alone
[DC] Medicare reimbursement data in 2010
[IC] Opportunity loss based on published US government data. Cost of living determined from the Bureau of Labor Statistics
Lifetime cost-utility measured by ICER (ΔCost/ΔQALY).
Utility scores based on the literature. Health states summed as per the Markov model over all 42 cycles to obtain QALYs. Patients reaching the death state before the 42nd cycle retained in the model to calculate opportunity loss (Patients who developed non-neck recurrence of cancer given a median utility of 0.6 based on the literature)
- Markov model with utilities and outcome probabilities obtained from the literature
- Sensitivity analyses: one-way and two-way and Monte Carlo simulation performed
- Threshold analyses: not performed
- TT with CND was not a cost-effective strategy in low-risk PTC
- TT alone: cost savings of $5,763 per patient with slightly higher effectiveness per patient (0.03 QALY) for a cost savings of $285/QALY
- Sensitivity analyses: TT alone offered no advantagewhen RAI became more detrimental to a patient’s state of health, when the incidence of non-neck recurrence increased above 5% in patients undergoing TT alone, decreased below 3.9% in patients undergoing TT with CND, or the rate of permanent hypocalcemia rose above 4%
Molecular test versus no molecular test (standard management or diagnostic lobectomy) for indeterminate thyroid nodules
Najafzadeh (2012)(US, Canada) CUA 10,000 patients with an initial indeterminate FNA cytological diagnosis [I] Molecular diagnostic (DX) test
[C] No molecular diagnostic (NoDX) test
[DC] Costs for TT or HT based on results from a previous study
[IC] Calculated based on average lengths of hospitalizations subsequent to those surgeries and assuming an average income of $99 per day; calculated average annual income based on US census data and assuming 12% of the patients were men
Simulated outcomes for 10 years: initial and final cytology, occurrence of cancer, type of cancer, HT, TT, completion thyroidectomy, complications, and mortality
Health outcomes: QALYs and costs for each patient.
A health state utility value derived from short form 36 (SF-36) assigned to each of 10 health states to facilitate the calculation of QALYs
- Patient-level simulation model with literature-based probabilities
- Sensitivity analyses conducted by varying the value of model parameters over a viable range on the overall outcomes of the model, and by varying the annual discount rate from 3% to 0%
- Threshold analyses: threshold of $50,000/QALY
- DX test strategy appears to be the dominant diagnostic strategy if shown to have a high sensitivity and specificity with a reasonable cost per test
- DX test resulted in a gain of 0.046 QALYs and saving of $1,087 in direct cost per patient
- Sensitivity analyses: sensitivity of the DX test had a larger influence on the overall outcomes than specificity did. Assuming the DX test could maintain a sensitivity and specificity of 95%, 0.025 QALYs gained at a cost of $291, which is less than that in the NoDX strategy
- Threshold analyses: robust when compared with WTP
Cost, QALY gained
Lee (2014)(US, Canada) CUA Low-risk patients with AUS thyroid nodules [I] Molecular test with
i) routine GEC,
ii) routine GEC+ selective GMP,
iii) routine GMP, or
iv) routine GMP+ selective GEC
[C] Standard management without molecular test
[DC] Cost of the GEC and GMP obtained from the respective manufacturers
US costs obtained from the Medicare reimbursement data in 2011 and 2013
Canadian costs obtained from Canadian Institute for Health Information case-mix groups and Quebec provincial cost manuals
Drug costs based on US and Quebec provincial wholesale costs
[IC] Not included
Lifetime costs and QALY.
Utilities valued from a scale of 0 (death) to 1 (perfect health). Utilities for each health state taken from three different studies: unilateral RLN palsy, 0.63; bilateral RLN palsy, 0.21; hypoparathyroidism, 0.78; disease-free after HT, 0.99; disease-free after TT and RAI, 0.95; recurrence, 0.54 pre-RAI (post-surgery), 0.55; postRAI 0-4 wk, 0.64; and post-RAI 4-8 wk, 0.82
- Microsimulation model (1 million patients; 1-year cycle length) with literature-based probabilities (risk of mortality, recurrence, and malignancy, complications, and sensitivity and specificity of diagnostic tests) and utilities
- Sensitivity analyses: varying one or more variables at a time across a specified range of values
- Threshold analyses: cost-effectiveness acceptability curves, representing the proportion of times (out of the total number of simulated patients) that each option is optimal for a given cost/QALY threshold
- From the US perspective, routine GEC+ selective GMP was the dominant strategy
- From the Canadian perspective, standard management was most likely to be cost-effective
- Sensitivity analyses: the decisions from both perspectives were sensitive to variations in the probability of malignancy in the nodule and the costs of the GEC and GMP
- From the US perspective, the routine GEC+selective GMP strategy would be the least costly only if the cost of a thyroid lobectomy exceeded $6,686
- Threshold analyses: none of the strategies had a probability of cost-effectiveness higher than 35% at any cost/QALY threshold
Nicholson (2019)(US) CEA Base-case scenario, a 40-year-old euthyroid woman with a solitary 2-cm Bethesda III or IV thyroid nodule [I] Molecular testing using, i) Afirma GSCii) ThyroSeq ver.3 (TSv3)
[C] Diagnostic lobectomy (DL)
[DC] Costs related to management strategy and related surveillance derived from Medicare reimbursement data in 2018 and the literature
[IC] Not included
Cost per correct diagnosis (defined as malignant histology after DL or 20 years of nodule stability after negative molecular test) - Decision tree model with literature-based probabilities (cancer prevalence, molecular test failure, sensitivity and specificity of each test, post-operative complication, and surveillance of molecular test-negative nodule)
- Sensitivity analyses performed for costs, pretest probability of malignancy, and performance parameters
- Threshold analyses: Not done
- Either of the major molecular test was considerably more cost-effective than DL, although TSv3 was more likely to be cost-effective than GSC
- Cost per correct diagnosis: $14,277 for TSv3, $17,873 for GSC, and $38,408 for DL
- TSv3 was preferred over both GSC and DL
- Sensitivity analyses: One-way sensitivity analysis between TSv3 and GSC demonstrated that the results were robust to variations in cost,cancer prevalence, and length of surveillance. In the two-way sensitivity analysis, TSv3 was preferred over GSC at all considered test costs, and in probabilistic sensitivity analysis, TSv3 was the preferred management strategy in 68.5% of cases
Cost, ICER
Balentine (2018)(US) CUA Base-case scenario, a 40-year-old woman with a 1-cm indeterminate (Bethesda III-IV) nodule [I] Genetic testing (Afirma)
[C] DL
[DC] Medicare reimbursement data in 2016 with a 3% discount rate
[IC] Not included
5-year cost forQALYs (ΔCost/ΔQALY), unnecessary operative procedures, cases requiring long-term hormone replacement, and permanent operative complications.
Estimates of utilities drawn from previously published values: post-lobectomy, no hormone replacement required, 0.990; post-lobectomy, hormone replacement required or thyroidectomy, 0.950; distant cancer, 0.700; detected local cancer, 0.950; permanent complications of lobectomy, 0.700; permanent complications of thyroidectomy, 0.650; 6 months before death from distantcancer, 0.350; routine surveillance, 0.980; temporary complications of lobectomy or thyroidectomy, 0.950; surveillance with Afirma, 0.980; and temporary decrease in utility due to lobectomy/thyroidectomy, 0.013.
- Markov decision model with literature-based probabilities and utilities
- Sensitivity analyses: Monte Carlo probabilistic sensitivity analysis with 10,000 replications to derive 95% uncertainty intervals for primary and secondary outcomes and ICERs
- Threshold analyses: threshold of $100,000/QALYs
- DL dominates genetic testing as a strategy for ruling out malignancy of indeterminate thyroid nodules
- During a 5-year, lobectomy was less costly and more effective than AfirmaⓇ (lobectomy: $6,100; 4.50 QALYs vs. AfirmaⓇ: $9,400; 4.47 QALYs)
- Sensitivity analyses using the 2015 guidelines found that an AfirmaⓇ-based strategy is slightly more effective than operative thyroidectomy (+0.0017 QALYs) but at considerably greater cost (+$3,130) for an ICER of $1,843,000
- Threshold analyses: in 253 of 10,000 simulations (2.5%), AfirmaⓇ showed a net benefit at a cost-effectiveness threshold of $100,000/QALY
RAI using rhTSH versus RAI after thyroid hormone withdrawal (THW)
Borget (2015)(France) CUA ESTIMABL trial: 752 patients with thyroid cancer who underwent TT were randomly assigned to one of four strategies, with each strategy combining one TSH stimulation method (rhTSH or THW) and one I-131 activity (1.1 or 3.7 GBq) [I] TSH stimulation using rhTSH
[C] TSH stimulation using THW
[I] 1.1 GBq of I-131 activity
[C] 3.7 GBq of I-131 activity
[DC] Fixed and variable costs extracted from the French National Cost Survey, using the diagnosis-related group code, for I-131 administration. Cost of rhTSH was obtained from the French drug database. Transportation costs were estimated using the French health insurance reimbursement tariffs according to the home-hospital distance and the type of transportation used
[IC] The value of lost productivity was based on the national added value estimated at €198 per day
8-month total costs, QALY.
EuroQoL-5D (EQ-5D) questionnaire used to assess utility and QALYs. Questionnaires collected seven times (at random assignment; immediately before 131I administration; 2, 4, and 6 weeks after radioiodine administration; and at the 3- and 8-month visits) to measure the evolution of utility scores over that period
- Net monetary benefit approach and computed cost-effectiveness acceptability curves used for both TSH stimulation methods and I-131 activities
- Sensitivity analyses: reducing the price of rhTSH by 10% and 30%
- Threshold analyses: threshold of €50,000/QALY
- rhTSH was more effective than THW in terms of QALYs but more expensive (€474/patient)
- The use of 1.1 GBq of I-131 instead of 3.7 GBq reduced per-patient costs by €955 but with slightly decreased efficacy (-0.007 QALY/patient)
- Sensitivity analyses: when the rhTSH price was lowered by 30%, the extra cost incurred with rhTSH was reduced and the probability that rhTSH would be cost-effective for a threshold of €50,000/QALY increased to 70%
- Threshold analyses: with the threshold of €50,000/QALY, the probability that rhTSH would be cost-effective was 47% and 59% when direct and total costs were considered, respectively. The probability that the lower I-131 activity would be cost-effective was 65% and 77% when direct and total costs were considered
Cost, QALY per patient
Mernagh (2010)(Canada) CUA Hypothetical patients with low-risk thyroid cancer without RAI and exogenous stimulation (i.e., rhTSH), against those prepared with endogenous stimulation (with hypothyroidism resulting from the THW) [I] RAI using rhTSH
[C] RAI after THW
[DC] Canadian resource use and unit costs sourced with a societal perspective. The most up-to-date costs sourced in all instances, with all costs as published in either 2007 or 2008.
[IC] Canadian wage rate as a proxy for productivity loss (Statistics Canada 2007)
Incremental cost and benefit for 17 weeks measured by ICER (ΔCost/ΔQALY).
QALYs derived from SF-36 data
- Markov model using the probabilities derived from a pivotal multicenter, randomized, controlled trial
- Sensitivity analyses: deterministic one-way and two-way sensitivity analysis
- Threshold analyses: considered to be fundable if the cost/QALY is between $20,000 and $100,000
- rhTSH use represents a reasonable allocation of costs, with the benefits to patients, hospitals, and society as a whole, obtained at modest cost.
- The additional benefits of rhTSH (0.0576 QALY) were obtained with an incremental cost of CDN$87, generating an incremental cost of CDN$1,520/QALY
- Sensitivity analyses: the results were demonstrated to be robust
- Threshold analyses: the results were robust when compared with WTP
Mernagh (2006)(Germany) CEA Hypothetical patients with well-DTC who had undergone thyroidectomy, but had no metastases [I] RAI using rhTSH
[C] RAI after THW
[DC] German setting; takes a societal perspective
[IC] Productivity loss using friction-cost method. Lifetime cost of secondary cancer assumed as €48,966
Pre-and post-ablation health states, secondary cancer, recurrence, death, and QALY.
Utility weights for the pre- and post-ablation health states that differ between arms obtained from the pivotal controlled clinical trial. SF-36 trial data transformed into utility weights using the SF-6D method. Other utility weights, not different between arms, sourced from the literature, assumptions, and convention
- Lifetime Markov model with inputs derived from a multicenter, randomized controlled trial supplemented with additional information from the literature
- Monte Carlo simulation of 100,000 patients used to simulate patients progressing through the various health states at the individual level
- Sensitivity analyses: a discount rate of 5% per annual applied to costs and outcomes
- Threshold analyses: not undertaken
- rhTSH use prior to RAI represents good value-for-money with the benefits to patient and society obtained at modest net cost
- The additional benefits of rhTSH (0.0495 QALY) were obtained with an incremental societal cost of €47, equating to an incremental cost of €958/QALY.
- Sensitivity analyses had only a modest impact on cost-effectiveness, with all one-way sensitivity results remaining under €15,000/QALY
- Threshold analyses: not undertaken
Vallejo (2017)(Spain) CEA Hypothetical patients newly diagnosed with well-DTC undergoing total or almost TT, comparing rhTSH with THW [I] RAI using rhTSH
[C] RAI after THW
[DC] Costs estimated from hospital charge in Spain, a survey, and the price of commercialized I-131
[IC] Costs of productivity loss: the model assumes that, on average, patients in the THW arm miss 11 working days owing to hypothyroid symptoms while those in the rhTSH arm miss 5.5 days. These costs were analyzed only in the sensitivity test, 17-week cost-utility measured by ICER (ΔCost/ΔQALY)
Utility weights applied in the economic model based on data of SF-36 collected during a pivotal randomized controlled trial
Cost and cost per QALY gained measured by ICER (ΔCost/ΔQALY).
Utility weights applied in the economic model based on data of the SF-36 collected during the pivotal randomized controlled trial
- Markov model with two analysis arms (rhTSHand THW), stratified into high (100mCi/3700 MBq) and low (30mCi/1110 MBq) RAI doses, and using clinical inputs based on published studies and in a treatment survey conducted in Spain
- Sensitivity analyses
- Threshold analyses: not undertaken
- The use of rhTSH previous to RAI in Spain had cost savings, as well as a series of health benefits for the patient, making it highly cost-effective
- RAI preparation with rhTSH was superior to THW, showing additional benefits (0.048 AVAC), as well as cost savings (−€614.16), with an ICER of −€12,795/QALY
- Sensitivity analyses showed the result to be robust
Wang (2010)(US) CUA Hypothetical population of adult patients with low-risk DTC prepared for ablation by either rhTSH or thyroid hormone withdrawal [I] Ablation by rhTSH
[C] Ablation by thyroid hormone withdrawal
[DC] Physician office visits, imaging studies (ultrasound and 131I), surgery, thyroid hormone, rhTSH, and laboratory tests (2009 Medicare reimbursement schedule)
[IC] Lost work days (US Bureau of Labor Statistics 2009)
Cost-utility, measured in US$ per quality-adjusted life-year ($/QALY
PubMed database, (SF-36/Short Form 6D scoring protocol to yield utility weights)
- A Markov decision model constructed to determine the incremental cost-utility
- Sensitivity analyses tested the impact of clinical uncertainty around model inputs in the base-case analysis
- Threshold analyses based on uncertainty model: $50,000/QALY
- A discount rate of 3% per year applied to all costs and outcomes
- Use of rhTSH yielded an incremental cost-utility of $52,554/QALY.
- The majority of cost and benefit occurs during the pre-ablation, ablation, and post-ablation period
- Differences in cost are due to the cost of rhTSH and differences in productivity loss (days off work).
- Sensitivity analyses: the model was most sensitive to changes in time off work, cost of rhTSH, and differences in utilities of health states.
- Threshold analyses: robust when compared with WTP
Cost, utility, QALY, ICER

CEA: cost-effectiveness analysis, CMA: cost-minimization analysis, CND: central neck dissection, CUA: cost-utility analysis, FNA: fine needle aspiration, GEC: gene expression classifier, GMP: gene mutation panel, GSC: gene sequence classifier, ICER: incremental cost-effectiveness ratio, LND: lateral neck dissection, QALY: quality-adjusted life year, RAI: radioactive iodine, SND: selective neck dissection

Int J Thyroidol 2022;15:74-104
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