Cost-Effectiveness Analysis of Active Surveillance Compared to Early Surgery in Small Papillary Thyroid Cancer: A Systemic Review

Figures & data

Table 1 PICO (Patient, Intervention, Comparison, Outcome) Method Keywords Used to Search the Literature on Cost-Effectiveness Analysis of Active Surveillance versus Early Surgery in Papillary Thyroid Cancer

PICO	Keywords Used to Search the Literature
P	Thyroid cancer patient Thyroid cancer (papillary, follicular, medullary, anaplastic)
I	Surgical management Surgical management: Total thyroidectomy or lobectomy with or without lymph node dissection
C	Active surveillance (close observation)
O	Cost effectiveness comparison between two interventions Comparison of cost-effectiveness of surgical management to active surveillance; cost-effectiveness; including just sum of costs (cost-effectiveness analysis, cost-utility analysis)

Figure 1 Among 62 searched papers, 5 papers were selected. Papers that had irrelevant titles, were written in foreign languages, or were review articles without original results were excluded.

Figure 2 Decision tree example. Each node can represent decision options (such as whether to opt for a particular treatment) and it is connected to branches. The chance of going down one branch versus another is decided by the probabilities of events estimated with data. “P” represents the probabilities.

Notes: Adapted from: 2011 Medical Economic Evaluation Guideline. Health Insurance Review & Assessment Service (HIRA); 2016. Available from: http://www.hira.or.kr/cms/participation/05/07/__icsFiles/afieldfile/2013/04/01/3.pdf. Korean. 2016 Copyright HIRA.³¹

Figure 3 Markov model example. Each circle represents a specific medical condition. “P” represents the probability that a medical event can happen.

Notes: Adapted from: 2011 Medical Economic Evaluation Guideline. Health Insurance Review & Assessment Service (HIRA); 2016. Available from: www.hira.or.kr. Korean. 2016 Copyright HIRA.³¹

Table 2 Selected Five Key Papers About Cost-Effectiveness Analysis of Active Surveillance versus Early Surgery in Papillary Thyroid Cancer

Year	Author	Journal	Country	Cost		Decision Model*	Results						Conclusion
				Perspective	Type		AS			Surgery
							Cost	QALY	ICER	Cost	QALY	ICER
2015	Lang et al^Citation21	European J Endo	Hong-Kong	Institution	Direct medical	Y	$7204	15.23	473.1 (per Pt)	$6521	14.97	435.7 (per Pt)	AS preferred
2017	Venkatesh et al^Citation22	Surgery	USA	Third party	Direct medical	Y	$5724	20.29	NA	$13,866	22.13	$4437 (per QALY)	Undetermined
2017	Oda et al^Citation23	Endocrine Journal	Japan	NA	Direct medical	N	$1525 ~ $2052	NA	NA	$7225 (L)** Or $9873 (T)**	NA	NA	AS preferred
2020	White et al^Citation24	Annals Surg	USA	NA	Direct medical	Y	$14,752	13.09	NA	$20,126	12.43	NA	AS preferred
2020	Lin et al^Citation26	Surgery	Australia	NA	Direct medical	N	$698 (fixed) +$556 (yearly)	NA	NA	$7516 (fixed) +$173 (yearly)	NA	NA	ES preferred

Notes: *Decision tree or Markov model was used as a decision model, **L for lobectomy and T for total thyroidectomy. 

Abbreviations: USA, United States of America; AS, active surveillance; QALY, quality-adjusted life-year; ICER, incremental cost-effectiveness ratio; ES, early surgery; Pt, patient; NA, not available.

Table 3 Utility Score of the Three Key Reference Papers About Cost-Effectiveness Analysis of Active Surveillance versus Early Surgery in Papillary Thyroid Cancer

Key Reference Paper (Year), Country	Utility Score
Lang et al (2015), Hong Kong^Citation21
Alive without permanent complication	1
Alive with permanent complication	0.54
Death	0
Venkatesh et al (2017), USA^Citation22
Disease-free state after lobectomy without complication	0.99
Disease-free state after operation and RAI	0.95
Disease-free state after lobectomy with short-term complication	0.75
Lobectomy	0.74
RAI	0.64
Disease-free state after lobectomy with long-term complication	0.63
Redo LND	0.56
TTLND	0.55
TTLND with complication	0.54
Disease recurrence	0.54
Redo LND with complication	0.41
Disutility difference of AS compared to disease-free state post-lobectomy without complication	0.11
White et al (2020), USA^Citation24
Hypoparathyroidism	0.836
Hypothyroidism	0.83
Unilateral RLN injury	0.627
Cancer recurrence	0.54
Distant metastatic disease	0.25
Bilateral RLN injury	0.205
Diagnosis	−0.04^a
FNA biopsy	−0.5
Hematoma during surgery	−0.5
Airway problem during surgery	−0.5
Patient baseline utilities	Variable

Notes: ^aWhite et al²⁴ estimated disutility and summed it into the patient’s total lifetime utility score.

Abbreviations: RLN, recurrent laryngeal nerve; FNA, fine needle aspiration; RAI, radioactive iodine; LND, lymph node dissection; TT, total thyroidectomy.

Table 4 Method of Modeling, Cost Sources, Utility Source, and Validation Level of Selected Papers

	Lang et al (2015, HK)^Citation21	Venkatesh et al (2017, USA)^Citation22	Oda et al (2017, Japan)^Citation23	White et al (2020, USA)^Citation24	Lin et al (2020, Australia)^Citation26
Method of modeling	Decision tree	Decision tree	None	Markov decision model	None
Cost sources	Public access file from Centers for Medicare and Medicaid Services	Publications of Medicare reimbursement rates and the Healthcare Costs	Japanese Health Care Insurance System	The fee schedule at a major academic hospital, and Centers for Medicare and Medicaid Services’ National Inpatient Sample database	Royal North Shore Hospital and the University of Sydney
Utility source	From authors’ own assumption	Publications for asymptomatic prostate cancer	None	Based on more than 20 studies of the QOL of patients with PTC	None
Validation level*	13	14	6	12	5

Notes: *The validation level was scored according to the criteria suggested by Chiou et al²⁰ [Chiou et al. Development and validation of a grading system for the quality of cost-effectiveness studies. Med Care. 2003;41(1):32–44]. The higher number indicates a more validated model with high reliability. See more details in Supplementary Table 1.

Abbreviations: USA, United States of America; QoL, quality of life; PTC, papillary thyroid cancer.

Table 5 Costs Mentioned in the Five Key Reference Papers on Cost-Effectiveness Analysis of Active Surveillance versus Early Surgery in Papillary Thyroid Cancer

	Lin et al (2020, Australia)^Citation26	White et al (2020, USA)^Citation24	Oda et al (2017, Japan)^Citation23	Venkatesh et al (2017, USA)^Citation22	Lang et al (2015, HK)^Citation21
Initial diagnosis & follow-up costs
AS				$226 (AS) $283 (surveillance post-lobectomy) $431 (surveillance after post-operation RAI)
Visit to physician	$117 (visit to endocrinologist)	$96.96 (primary care physician visit) $145.72 (specialist visit)	$20
Blood test	$50	$23.1 (serum TSH test)	$81
US	$102	$124.86	$32
FNA	$406	$497.78	$55
CT scan		$287.11
Medication	$19 (L-thyroxine) $14 (Ca & vit. D)	$111.83 (annual)	$34 (L-thyroxine) $99 (L-thyroxine & vit. D)
Procedural costs
Thyroid surgery	$6428	$12.178 (neck dissection) $9175 (lobectomy) $11,352 (TT)	$2198 (lobectomy with PD) $2801 (TT with CND) $3165 (CT with MND)	$7967 (lobectomy) $6482 (Redo LND) $9134 (TTLND)	$4513 (lobectomy + CND) $6013 (TT+CND) $12,495 (TT+CND + selective neck dissection)
RAI		$6097.09 (RAI) $2103.80 (thyrotropin injection)		$451
Complication costs
Complications		$5790.24 (airway problem) $5790.24 (hematoma) $1651.18 (hypoparathyroidism, annual) $158.03 (hypothyroidism, annual) $55,983.11 (Surgical mortality)		$17,692 (complication post-TTLND) $17,692 (complication post-redo LND)	$5754 (hematoma requiring neck re-exploration) $15,404 (chyle leak)
Short-term		$2224.24 (Unilateral temporary RLN injury) $867.77 (temporary hypoparathyroidism)		$6318 (short-term complication post lobectomy)	$564 (temporary vocal cord palsy including consultation, laryngoscopy and speech therapy) $863 (temporary hypoparathyroidism including follow-up visits, blood tests and medications)
Long-term		$27,874.28 (Bilateral permanent RLN injury) $6623.08 (Unilateral permanent RLN injury)		$16,121 (long-term complication post lobectomy)	$10,367 (permanent vocal cord palsy including consultations, laryngoscopy, speech and medialization)
Distant metastasis
Treatment		$60,196 (initial) $35,189 (ongoing)

Notes: All costs are costs mentioned in the original papers. Inflation has not been applied.

Abbreviations: USA, United States of America; AS, active surveillance; RAI, radioactive iodine; TSH, thyroid stimulating hormone; US, ultrasonography; FNA, fine needle aspiration; CT, computed tomography; L-thyroxine, levothyroxine; Ca, calcium; vit. D, vitamin D; PD, paratracheal dissection; TT, total thyroidectomy; CND, central neck dissection; CT, complete total thyroidectomy; MND, modified radical neck dissection; LND, lymph node dissection.

Health Insurance Review & Assessment Service (HIRA). 2011 Medical Economic Evaluation Guideline; 2016. Available from: http://www.hira.or.kr/cms/participation/05/07/__icsFiles/afieldfile/2013/04/01/3.pdf. Korean.

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