Introduction
Material and methods
Trial design, patients and treatment
FDG-PET/CT driven management | diagnostic surgery | ||
---|---|---|---|
n = 91 | n = 41 | p | |
Female sex — n (%) | 73 (80%) | 34 (83%) | 0.71a |
Age at baseline (years) (mean ± SD) | 54.3 ± 14.6 | 54.5 ± 11.6 | 0.95b |
General medical history — n (%) | 81 (89%) | 33 (81%) | 0.19a |
Cardiovascular disease (including stroke) | 29 (32%) | 12 (29%) | 0.77a |
Non-thyroid solid malignancy | 8 (9%) | 5 (12%) | 0.54c |
Haematological disease or malignancy | 8 (9%) | 4 (10%) | 1c |
Neurological disease (excluding stroke) | 19 (21%) | 9 (22%) | 0.89a |
Otolaryngological disease | 17 (19%) | 9 (22%) | 0.66a |
Lung disease | 13 (14%) | 7 (17%) | 0.68a |
Gastro-intestinal disease | 26 (29%) | 9 (22%) | 0.43a |
Urological or gynaecological disease | 29 (32%) | 16 (39%) | 0.42a |
Endocrine disease (excluding thyroid) | 17 (19%) | 6 (15%) | 0.57 a |
Musculoskeletal disorder | 33 (36%) | 17 (41%) | 0.57 a |
Psychiatric disorder | 5 (6%) | 2 (5%) | 1c |
[18F]FDG-PET/CT — n (%) | |||
[18F]FDG-positive nodule | 65 (71%) | 26 (63%)d | 0.36a |
Incidental findings on [18F]FDG-PET/CT | 25 (27%) | 16 (39%)d | 0.23a |
[18F]FDG-positive incidentaloma | 10 (11%) | 9 (22%)d | 0.10a |
Diagnosis — n (%)e | |||
Malignant | 24 (26%) | 5 (12%) | 0.07a,e |
Borderline | 5 (5%) | 3 (7%) | |
Benign on histopathology | 37 (41%) | 32 (78%) | |
Benign on ultrasound follow-up | 25 (27%) | 1 (2%) | |
Treatment — n (%) | |||
Diagnostic surgery | 66 (73%) | 40 (98%) | 0.001a |
Watchful waiting | 25 (27%) | 1 (2%) | |
Completion thyroidectomy | 13 (14%) | 4 (10%) | 0.58c |
RAI | 12 (13%) | 4 (10%) | 0.78c |
Productivity (n = 121) — n (%)f | |||
Full-time job | 15 (17%) | 10 (29%) | 0.39a |
Part-time job | 41 (48%) | 14 (40%) | |
Unemployed | 30 (35%) | 11 (31%) | |
Average contractual work hours (hours/week) — median (IQR) | 20 (0–30) | 24 (0–36) | 0.29d |
First year costs and utilities
Modelled lifelong costs and utilities
Model structure
Model parameters
Base-case value | Source | Uncertaintya | |
---|---|---|---|
Discount rates | |||
Yearly discount rates for costs | 0.040 | Fixed | |
Yearly discount rates for utilities | 0.015 | Fixed | |
Follow-up of [18F]FDG-negative nodules | |||
Yearly probability that active surveillance of [18F]FDG-negative nodule ends | 0.33 (based on mean 3-year f/u) | 0.2–1.0 | |
Yearly probability to re-enter active surveillance for [18F]FDG-negative nodule | 0.01 | Expert opinion | − 50% to + 100% |
Yearly probability of surgery for benign lesion after continued surveillance for [18F]FDG-negative nodule | 0.02 | − 50% to + 100% | |
Probability of (surgery for) a missed malignancy after initial surveillance for [18F]FDG-negative nodule | 0.049 (1-NPV) | 0.0–0.1 | |
Maximum timespan for missed malignancy to be detected | 5 years | Expert opinion | 2–15 years |
Fraction HT of all surgery | 0.95 | [14], expert opinion | 0.90–0.98 |
Fraction of cTT following HT if malignant | 0.607 | EfFECTS | 0.5–0.7 |
Recurrence of malignancy | |||
Yearly probability of recurrent disease following HT | Year 1–5: 0.015 Year 6–10: 0.010 Year 11 onwards: 0.005 | 0.0075–0.03 0.005–0.02 0.0025–0.01 | |
Probability of (c)TT following recurrence after HT for malignancy | 0.917 | [14] | SD = 0.013 |
Yearly probability of recurrent or persistent malignant disease following (c)TT | Year 1–2: 0.070 Year 3–5: 0.040 Year 6–10: 0.010 Year 11 onwards: 0.005 | − 50% to + 100% | |
Mortality | |||
Yearly probability of death of any cause (not thyroid cancer related) | Life tables | [25] | Fixed |
Yearly probability of death due to thyroid cancer | Year 1–10: 0.005 Year 11–20: 0.003 Year 21 onwards: 0.002 | − 50% to + 100% | |
Perioperative mortality HT/(c)TT | 0.0011 | − 50% to + 100% | |
Complications of thyroid surgery | |||
Transient complication due to HT | 0.0977 | − 50% to + 100% | |
Permanent complication due to HT (excluding hypothyroidism) | 0.0056 | − 50% to + 100% | |
Medication-dependent hypothyroidism due to HT | 0.22 | SD = 0.020 | |
Transient complication due to (c)TT | 0.185 | − 50% to + 100% | |
Permanent complication due to (c)TT | 0.046 | − 50% to + 100% |
Cost parameters
Costs, Base-case value | Source | Uncertaintya | Disutility, Base-case valueb | Source | Uncertaintya | |
---|---|---|---|---|---|---|
Procedures | ||||||
FDG-PET/CT | €754 | [22] | n.a | |||
Hemithyroidectomy | €4315 | [22] | ± 25% | |||
Total / completion thyroidectomy | €6115 | [22] | ± 25% | |||
Radioiodine ablation | €5765 | [22] | ± 25% | |||
Health states, yearly costs | ||||||
Active surveillance after negative [18F]FDG-PET/CTc | €236 | ± 25% | 0.02 | 0.00–0.05 | ||
End of follow-up | €0 | Expert opinion | €0 | 0.01 | Expert opinion | 0.00–0.04 |
Observation after HT for benign nodule | ||||||
1st year | €277 | ± 25% | 0.01 | 0.00–0.04 | ||
2nd year onwards | €0 | ± 25% | 0.01 | 0.00–0.04 | ||
Observation after HT for malignancy | ||||||
1st year | €529 | ± 25% | 0.03 | 0.01–0.06 | ||
2nd–5th year | €252 | ± 25% | 0.02 | 0.00–0.05 | ||
6th year onwards | €0 | ± 25% | 0.01 | [74] | 0.00–0.04 | |
Transient complication due to HT | €1272 | ± 25% | 0.06 | 0.02–0.11 | ||
Permanent complication due to HT | ||||||
1st year | €5338 | ± 25% | 0.30 | [14] | 0.21–0.39 | |
2nd year onwards | €825 | ± 25% | 0.30 | [14] | 0.21–0.39 | |
Hypothyroidism due to HT | ||||||
1st year | €566 | ± 25% | 0.03 | 0.01–0.06 | ||
2nd year onwards | €283 | ± 25% | 0.02 | 0.00–0.05 | ||
Recurrence of malignancy after HT | €1756 | ± 25% | 0.40 | [14] | 0.31–0.50 | |
Observation after TT for benign nodule | ||||||
1st year | €843 | ± 25% | 0.06 | 0.02–0.11 | ||
2nd year onwards | €283 | ± 25% | 0.02 | 0.00–0.05 | ||
Observation after (c)TT for malignancy | ||||||
1st year | €1949 | ± 25% | 0.07 | 0.03–0.12 | ||
2nd–15th year | €753 | ± 25% | 0.04 | 0.02–0.07 | ||
16th year onwards | €0 | [12] | ± 25% | 0.02 | Expert opinion | 0.00–0.05 |
Transient complication due to (c)TT | €1106 | ± 25% | 0.06 | 0.02–0.11 | ||
Permanent complication due to (c)TT | ||||||
1st year | €3462 | ± 25% | 0.35 | 0.26–0.45 | ||
2nd year onwards | €722 | ± 25% | 0.35 | 0.26–0.45 | ||
Recurrence after (c)TT | €1452 | ± 25% | 0.40 | 0.31–0.50 | ||
Death | €0 | Convention | 0 | Convention | Fixed | |
Other health-care related costs, yearly costs | ||||||
Other health care consumptiond | €2511 | EfFECTS | ||||
Travel expenses for thyroid-related health caree | €12–€105 | EfFECTS | ± 25% | |||
Travel expenses for other health care consumptiond | € 99 | EfFECTS | ||||
Informal cared | € 604 | EfFECTS | ||||
Productivity losses, yearly | ||||||
Productivity losses due to HT | ||||||
HT for benign nodule | €3065 | EfFECTS | € 620 (SD) | |||
HT for malignant nodule | €3925 | EfFECTS | € 1,238 (SD) | |||
Productivity losses due to total / completion thyroidectomy | €4686 | € 1,028 (SD) | ||||
Productivity losses due to RAI | €1188 | € 292 (SD) | ||||
Yearly productivity losses for recurrent/ progressive malignant disease | €2493 | ± 25% | ||||
Yearly other paid productivity lossesd | € 2267 | EfFECTS | ||||
Yearly unpaid productivity lossesd | € 1153 | EfFECTS |
Utility parameters
Other parameters
Lifelong extrapolation
Statistical analysis
Cost-utility analysis
Range | References | |
---|---|---|
Probabilities | ||
Yearly probability that active surveillance of [18F]FDG-negative nodule ends | 0.05–1.00 | |
Yearly probability of surgery for benign nodule after continued surveillance for [18F]FDG-negative nodule | 0.001–0.10 | |
Yearly probability of (surgery for) a missed malignancy after initial surveillance for [18F]FDG-negative nodule | 0.00–0.05 | |
Any surgical complication (transient, permanent, and hypothyroidism) | − 100% to + 100% | |
Costs | ||
Price of [18F]FDG-PET/CT | €400–€5000 | |
Price of HT | €2500–€20,000 | |
Annual costs of observation after negative [18F]FDG-PET/CT | €0–€1000 | |
Costs of [18F]FDG-PET/CT incidental findings | €0–€1000 | |
Disutility | ||
Observation after negative [18F]FDG-PET/CT | 0.00–0.10 | |
Observation after HT for benign nodule | 0.00–0.10 |
Results
First year utilities and costs
[18F]FDG-PET/CT- driven group | Diagnostic surgery group | |||
---|---|---|---|---|
(n = 91) | (n = 41) | Mean difference | p | |
First year | ||||
Mean EQ-5D-5L domain scores: | ||||
Baseline | 0.852 | 0.791 | 0.061 | 0.14a |
3 months | 0.832 | 0.762 | 0.070 | 0.11a |
6 months | 0.749 | 0.674 | 0.075 | 0.23a |
12 months | 0.788 | 0.739 | 0.049 | 0.33a |
Mean QALYs (95% CI) | 0.778 (0.744–0.812) | 0.759 (0.706–0.812) | 0.019 (− 0.045– + 0.083) | 0.57b |
Lifelong | ||||
Mean QALYs (95% CI) | 19.273 (18.920–19.627) | 18.871 (17.937–19.805) | 0.402 (− 0.581– + 1.386) | 0.42b |
[18F]FDG-PET/CT-driven group (n = 91) | Diagnostic surgery group (n = 41) | |||
---|---|---|---|---|
Mean costs per patient (95% CI) | Mean costs per patient (95% CI) | Mean difference (95% CI) | pa | |
First year societal costs | ||||
Medical costs | ||||
Thyroid nodule-related care | ||||
Regular care | €6100 (€5400–€6800) | €7400 (€6600–€8100) | − €1300 (− €2,300– − €300) | 0.01 |
Care related to [18F]FDG-PET incidental findings | €200 (€50–€350) | − €50 (− €100– + €0) | €200 (− €50– + €400) | 0.01 |
Care related to surgical complications | €250 (€50–€400) | €200 (€0–€400) | €0 (− €250– + €250) | 0.94 |
Subtotal Thyroid nodule-related care | €6500 (€5700–€7300) | €7600 (€6800–€8300) | − €1000 (− €2100–€0) | 0.06 |
Other health care consumption | €2200 (€1500–€3000) | €3200 (€1100–€5200) | − €1000 (− €3000– + €1100) | 0.36 |
SUBTOTAL Medical costs | €8700 (€7600–€9800) | €10,700 (€8500–€13,000) | − €2000 (− €4400– + €400) | 0.10 |
Patient costs | ||||
Travel expenses | €150 (€150–€200) | €200 (€100–€300) | − €50 (− €150– + €50) | 0.31 |
Informal care | €450 (€100–€850) | €900 (€150–€1700) | − €450 (− €1300– + €350) | 0.27 |
SUBTOTAL Patient costs | €650 (€250–€1000) | €1100 (€350–€1900) | − €500 (− €1300– + €300) | 0.23 |
Productivity losses | ||||
Paid productivity losses | €5200 (€3800–€6500) | €6800 (€4300–€9300) | − €1600 (− €4400– + €1200) | 0.25 |
Unpaid productivity loss | €1000 (€600–€1400) | €1400 (€700–€2200) | − €400 (− €1200– + €450) | 0.35 |
SUBTOTAL Productivity losses | €6200 (€4750–€7650) | €8200 (€5500–€10,950) | − €2050 (− €5100– + €1050) | 0.19 |
TOTAL First year societal costs | €15,500 (€13,400–€17,700) | €20,100 (€15,800–€24,300) | − €4500 (− €9200– + €150) | 0.06 |
Lifelong societal costs | ||||
Medical costs | ||||
Thyroid nodule-related care | €9100 (€7,900–€10,300) | €10,600 (€8800–€12,400) | − €1500 (− €3600– + €600) | 0.17 |
Other health care consumption | €36,250 (− €121,200–€193,700) | €39,500 (− €119,800–€198,800) | − €3300 (− €8900– + €2300) | 0.25 |
SUBTOTAL Medical costs | €45,300 (− €112,100– + €202,800) | €50,100 (− €109,200– + €209,400) | − €4800 (− 11,600– + €2,000) | 0.17 |
Patient costs | ||||
Travel expenses | €1900 (− €2700– + €6400) | €2000 (− €2600– + €6600) | − €150 (− €300– + €50) | 0.11 |
Informal care | €10,800 (− €35,300– + €57,000) | €12,400 (− €34,000– + €58,800) | − €1500 (− €4000– + €1000) | 0.23 |
SUBTOTAL Patient costs | €12,700 (− €33,600– + €59,000) | €14,400 (− €32,200– + €60,900) | − €1700 (− €4300– + €900) | 0.21 |
Productivity losses | ||||
Paid productivity losses | €27,200 (− €90,500– + €144,900) | €29,400 (− €89,700– + €148,500) | − €2200 (− €7400– + €2900) | 0.40 |
Unpaid productivity loss | €18,200 (− €39,900– + €76,400) | €19,500 (− €39,300– + €78,300) | − €1200 (− €3300– + €800) | 0.25 |
SUBTOTAL Productivity losses | €45,500 (− €85,500–€176,400) | €48,900 (− €83,500– + €181,300) | − €3500 (− €9600– + €2600) | 0.27 |
TOTAL Lifelong societal costs | €103,500 (− €105,500– + €312,500) | €113,400 (− €98,200– + €325,000) | − €9900 (− €23,100– + €3200) | 0.14 |