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Table 4 Disutilities and decrements for adverse event health states in patients with previously treated mNSCLC

From: Systematic review of health state utility values in metastatic non-small cell lung cancer with a focus on previously treated patients

Relevance

Author, year, country, referencea

Instrument and respondent

Utility type

Health state/disutility

Mean HSUV (SD) [SE] {95% CI}

HTA suitability

Advanced/mNSCLC

Nafees 2008, UK [69]

SG

General public

UID

Stage IV NSCLC, 2 L, stable disease

 

Does not meet HTA body reference case as vignette-based utility completed by general public respondents. Has been used in multiple HTA submissions, however. Specifically 2 L and UK, good sample size (n=100) and measure of dispersion available.

+ Diarrhoea

0.61

+ Fatigue

0.58

+ Febrile neutropenia

0.56

+ Hair loss

0.61

+ Nausea/vomiting

0.61

+ Neutropenia

0.56

+ Rash

0.62

Stage IV NSCLC, 2 L, responding disease

 

+ Diarrhoea

0.63

+ Fatigue

0.60

+ Febrile neutropenia

0.58

+ Hair loss

0.63

+ Nausea/vomiting

0.62

+ Neutropenia

0.58

+ Rash

0.64

D

Stage IV NSCLC, 2 L,

moving from stable to progressive

−0.18 [0.022]

Neutropenia

−0.09 [0.015]

Febrile neutropenia

−0.09 [0.016]

Fatigue

−0.07 [0.018]

Nausea and vomiting

−0.05 [0.016]

Diarrhoea

−0.05 [0.016]

Hair loss

−0.04 [0.015]

Rash

−0.03 [0.012]

Response gain

0.02 [0.007]

Tabberer 2006, UK [52]

EQ-5D (tariff NR but likely UK TTO tariff as UK sample)

General public

D

Compared with stable disease (advanced NSCLC, line not specified)

 

Not suitable as general public respondents, line of treatment not specified, and no measure of dispersion reported. Good sample size, however (n=154) and Nafees et al. 2008 in 2 L does not provide disutilities for neuropathy or stomatitis so these values from Tabberer et al. may be the best available.

Febrile neutropenia

−0.27

Rash

−0.06

Neuropathy

−0.15

Neutropenia

−0.14

Nausea

−0.14

Stomatitis

−0.14

Diarrhoea

−0.13

Doyle 2008, UK [65]

SG

General public

UID

Metastatic NSCLC, line not specified, SDis no additional symptoms

 

Does not meet reference case as general public respondents. However, these are the only disutilities for severe symptoms for cough, dyspnoea and pain in mNSCLC, so are best option in spite of not meeting HTA derivation method preferences (n=101)

+ Cough

0.58

+ Dyspnoea

0.58

+ Pain

0.56

+ Cough, dyspnoea and pain

0.46

D

Cough

−0.05 [0.011]

Dyspnoea

−0.05 [0.012]

Pain

−0.07 [0.012]

Cough, dyspnoea and painc

− 0.17 b

Responding disease gain vs SDis

0.09 [0.015]

As line not specified, data from Nafees et al. 2008 should be used in preference.

Handorf 2012, USA [70]

Expert opinion

UID

Stage IV NSCLC adenocarcinoma (1 L SDis)

  

+ neutropenia

0.67

Does not meet reference case as expert opinion-derived. This AE is covered by Nafees et al. 2008, which uses a better derivation method than expert opinion.

+ pneumothorax

0.63

Does not meet reference case as expert opinion-derived, but these are the only estimates for these AE health states. SDis estimate was 0.670 (oral therapy) and 0.653 (i.v. chemotherapy) for disutility calculation.

+ haemorrhage

0.63

+ thrombocytopenia

0.65

+ thrombosis

0.56

Earlier stage NSCLC (curative intent)

Grutters 2010, country NR [44]

EQ-5D-5 L (tariff NR)

Patients

UID

NSCLC, curative intent stage, line not specified, grade III+ dyspnoea

0.52 (median)

Patient-derived EQ-5D but tariff and measure of dispersion NR. Only source of grade III+ dyspnea. Utility for NSCLC patients without dyspnoea in this sample was 0.81, i.e. disutility − 0.29

Advanced/mLC (NSCLC+SCLC)

Yokoyama 2013, Japan [55]

EQ-5D (tariff NR)

Patients

D

Stage IIIB/IV NSCLC/SCLC with bone metastases + skeletal related event (pathologic fracture, radiation or surgery to bone lesion, spinal cord compression or hypercalcaemia)

− 0.05d

Provides NSCLC/SCLC (mixed) patient-derived EQ-5D decrement for (mixed) SREs. Data for these AEs are limited, so although this estimate is not robust (n=9 and response % low at 32%) it does provide an indication. No variability measure reported

Breast cancer and lung cancer

Grunberg 2009, USA [58]

SG

Patients

UID

Base state: continuous nausea and vomiting

0.53f

Nafees et al. 2008 provide data for nausea and vomiting but if different levels of nausea and vomiting need to be discerned then these utilities can be considered. Patient-derived SG but mixed lung/breast cancers. Good sample size (n=96) but no measure of dispersion. As the Copyright fee for Grunberg 2009 was high, these data are reported from Shabaruddin 2013 [79] (a previous SR that extracted the graphical data from Grunberg 2009)

Increment

Limited nausea and limit vomiting vs continuous nausea and vomiting

+ 0.53f

Increment

Limited nausea vs continuous nausea and vomiting

+ 0.55f

Increment

Limited vomiting vs continuous nausea and vomiting

+ 0.50f

Advanced Cancer

Matza 2014, UK [67]

TTO

General public

U

Stage IV cancer with bone metastases (no skeletal-related events)

0.47 (0.41)

Does not meet reference case as general population respondents. However, as there are no alternative utilities for bone metastases these UK utilities could be considered for NICE or SMC. Good sample size (n=126), SD available.

UID

+ spinal cord compression without paralysis

0.25 (0.50)

+ spinal cord compression with paralysis

0.13 (0.49)

+ fracture of the leg

0.42 (0.41)

+ fracture of the rib

0.44 (0.42)

+ fracture of the arm

0.44 (0.41)

+ radiation treatment (2 weeks, 5 appointments/week)

0.42 (0.42)

+ radiation treatment (2 appointments)

0.45 (0.41)

+ surgery to stabilize bone

0.40 (0.44)

Matza 2014, Canada [67]

TTO

General public

U

Stage IV cancer with bone metastases (no skeletal-related events)

0.47 (0.45)

Does not meet reference case as general population respondents. However, as there are no alternative utilities for bone metastases these Canadian utilities could be considered for CADTH. Reasonable sample size (n=61), SD available.

UID

+ spinal cord compression without paralysis

0.25 (0.54)

+ spinal cord compression with paralysis

0.19 (0.53)

+ fracture of the leg

0.40 (0.48)

+ fracture of the rib

0.43 (0.47)

+ fracture of the arm

0.43 (0.48)

+ radiation treatment (2 weeks, 5 appointments/week)

0.41 (0.50)

+ radiation treatment (2 appointments)

0.45 (0.45)

+ surgery to stabilize bone

0.39 (0.50)

Matza 2014, UK and Canada [67]

TTO

General public

U

Stage IV cancer with bone metastases (no skeletal-related events)

0.47 (0.42)

Does not meet reference case as general population respondents. However, as there are no alternative utilities for bone metastases these UK+Canadian utilities could be considered for NICE, SMC or CADTH. Good sample size (n=187), SD available.

UID

+ spinal cord compression without paralysis

0.25 (0.21)

+ spinal cord compression with paralysis

0.15 (0.50)

+ fracture of the leg

0.41 (0.43)

+ fracture of the rib

0.44 (0.43)

+ fracture of the arm

0.43 (0.43)

+ radiation treatment (2 weeks, 5 appointments/week)

0.41 (0.45)

+ radiation treatment (2 appointments)

0.45 (0.42)

+ surgery to stabilize bone

0.40 (0.46)

Matza 2014, UK [67]

TTO

General public

D

Stage IV cancer with bone metastases

 

As above

+ spinal cord compression without paralysis

−0.22 (0.31)

+ spinal cord compression with paralysis

−0.34 (0.36)

+ fracture of the leg

−0.05 (0.09)

+ fracture of the rib

−0.03 (0.08)

+ fracture of the arm

−0.03 (0.07)

+ radiation treatment (2 weeks, 5 appointments/week)

−0.05 (0.12)

+ radiation treatment (2 appointments)

−0.02 (0.07)

+ surgery to stabilize bone

−0.07 (0.17)

Matza 2014, Canada [67]

TTO

General public

D

Stage IV cancer with bone metastases

 

As above

+ spinal cord compression without paralysis

−0.22 (0.32)

+ spinal cord compression with paralysis

−0.28 (0.30)

+ fracture of the leg

−0.07 (0.19)

+ fracture of the rib

−0.04 (0.17)

+ fracture of the arm

−0.04 (0.07)

+ radiation treatment (2 weeks, 5 appointments/week)

−0.06 (0.21)

+ radiation treatment (2 appointments)

−0.02 (0.11)

+ surgery to stabilize bone

−0.08 (0.21)

Matza 2014, UK and Canada [67]

TTO

General public

D

Stage IV cancer with bone metastases

 

As above

+ spinal cord compression without paralysis

−0.22 (0.31)

+ spinal cord compression with paralysis

−0.32 (0.34)

+ fracture of the leg

−0.06 (0.13)

+ fracture of the rib

−0.03 (0.12)

+ fracture of the arm

−0.04 (0.11)

+ radiation treatment (2 weeks, 5 appointments/week)

−0.06 (0.15)

+ radiation treatment (2 appointments)

−0.02 (0.08)

+ surgery to stabilize bone

−0.07 (0.18)

Cancer, unclear stage

Lloyd 2008, UK [59]

SG

General public

UID

Anaemia associated with cancer treatment

 

Does not meet reference case as general population sample respondent for SG exercise.

Haemoglobin level (g/dL)

7.0–8.0

0.58 {0.067}

8.0–9.0

0.61 {0.064}

9.0–10.0

0.64 {0.060}

10.0–10.5

0.64 {0.062}

10.5–11.0

0.66 {0.061}

11.0–12.0

0.70 {0.056}

 

>12.0

0.71 {0.057}

VAS

General public

UID

Haemoglobin level (g/dL)

7.0–8.0

16.9 {2.6}

8.0–9.0

22.3 {3.0}

9.0–10.0

27.6 {2.9}

10.0–10.5

32.9 {3.4}

10.5–11.0

38.8 {3.6}

11.0–12.0

45.9 {4.2}

 

>12.0

51.2 {4.3}

TTO

Cancer patients with recent experience of chemotherapy-related anaemia or fatigue

UID

Haemoglobin level (g/dL)

7.0–8.0

0.30 {0.127}

8.0–9.0

0.36 {0.126}

9.0–10.0

0.41 {0.125}

10.0–10.5

0.45 {0.122}

10.5–11.0

0.45 {0.111}

11.0–12.0

0.55 {0.105}

>12.0

0.61 {0.112}

U

Own current health

0.85 {0.034}

EQ-5D current health

0.87 {0.076}

VAS

Cancer patients with recent experience of chemotherapy-related anaemia or fatigue

UID

Haemoglobin level (g/dL)

7.0–8.0

21.7 {5.7}

8.0–9.0

32.4 {6.6}

9.0–10.0

34.2 {6.7}

10.0–10.5

41.9 {6.6}

10.5–11.0

44.7 {6.6}

11.0–12.0

52.2 {6.8}

>12.0

62.4 {7.9}

U

Own current health

87.6 {4.9}

EQ-5D current health

84.2 {4.57}

NR

Westwood 2014, NR [71]

NR

D

Anaemia

0.073 [0.018]

Disutilities for anaemia and treatment mode have been used in previous NICE submissions. However, there is no information concerning their derivation.

2 L NSCLC

Oral therapy (ERL)

0.014 [0.012]

2 L NSCLC

i.v. therapy

0.043 [0.020]

Patients without NSCLC

1 L setting

Nafees 2016, Multinational and UK [68]g

TTO

Patients (but not NSCLC patients) from the general public in UK, Australia, France, China, S. Korea, Taiwan

D

Bleeding vs BL (stable no side effects)

−0.25

No

Hypertension vs BL (stable no side effects)

−0.03

UID

Responding + bleeding vs BL

0.534

Responding + hypertension vs BL

0.749

Stable + bleeding vs BL

0.508

Stable + hypertension vs BL

0.729

  1. aSome studies identified in this systematic review were not included in this table for the following reasons: Grunberg 2009 [58] and Grutters 2010 [44] did not report values
  2. bThe italics indicate a calculated utility. This is calculated from the values reported in Doyle 2008 [65] Table 3 (difference between stable disease no other symptoms and stable disease with cough, dyspnoea and pain, to obtain the disutility). It is not calculated by adding the disutilities, as this would not be valid
  3. cValues were calculated from ‘SDis + cough, dyspnea and pain’ utility minus ‘SDis no additional symptoms’ utility
  4. dThe study did not indicate if mean or median
  5. eSome studies identified in this systematic review were not included in this table for the following reasons: Grunberg 2009 [58] and Grutters 2010 [44] did not report values, and Nafees 2016 [68] reported variation in two decrements (bleeding, hypertension) based on the different populations in which valuation was undertaken
  6. fAs reported in Shabarruddin 2013 [79], base state and utility increments were presented on different scales: base state was based on standard gamble scale between perfect health (arbitrary score of 100) or immediate death (arbitrary score of 0) while the utility increments were based on a scale between perfect health (arbitrary score of 100) and the surrogate negative anchor of continuous nausea/vomiting (re-set to an arbitrary score of 0)
  7. gValues are presented for global population (United Kingdom, Australia, France, China, Taiwan, Korea). Note that country-specific data are also available
  8. Abbreviations: 1 L first line, BL baseline, CI confidence interval, D decrement, ERL erlotinib, HSUV health state utility value, HTA health technology assessment, i.v. intravenous, LC lung cancer, mLC metastatic lung cancer, mNSCLC metastatic non-small cell lung cancer, NICE National Institute for Health and Care Excellence, NR not reported, NSCLC non-small cell lung cancer, SCLC small cell lung cancer, SD standard deviation, SE standard error, SG standard gamble, TTO time trade-off, U utility, UID utility incorporating decrement for adverse events, VAS visual analogue scale