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. 2018 Sep 12;16:179. doi: 10.1186/s12955-018-0994-8

Table 3.

Health state utility values by treatment line, health state and instrument

Study Health state Utility valuea Instrument Tariff Respondent details HTA suitability
1st line
 Nafees 2016 [68]
Metastatic NSCLCb
PD vs BL state 0.095 TTO N/A Patients (but not NSCLC patients) from the general public in UK, Australia, France, China, S. Korea, Taiwan No
RES no side effects vs BL 0.773
SDis no side effects vs BL 0.460
 Chevalier 2013c [38]
Advanced/metastatic NSCLC
1 L PF 0.69 (0.26) EQ-5D French (TTO) Stage I–Stage III/IV PF and PD Meets HAS requirements
1 L PD 0.61 (0.24)
 Chouaid 2013 [39]
Advanced/metastatic NSCLC
1 L PF 0.71 (0.24) (95% CI, 0.67–0.76) EQ-5D-3 L UK At time of advanced diagnosis, mean age 64.8 years
Adenocarcinoma: 65.2%
Large-cell carcinoma: 6.8%
SQ cell carcinoma: 17.1%
Other: 9.9%
Clinical stage at time of survey:
IIIb: 17.9%
IV: 82.1%
Meets NICE requirements
69.31 (18.33) (95% CI, 65.9–72.8) EQ-5D VAS N/A No
1 L PD 0.67 (0.2) (95% CI 0.59–0.75) EQ-5D-3 L UK Meets NICE requirements
58.67 (17.4) (95% CI 51.3–66.0) EQ-5D VAS N/A No
 Iyer 2013 [46]
Advanced/metastatic NSCLC
France, Germany 1 L 0.63 (0.31) EQ-5D UK1 Patients with:
Adenocarcinoma: 56.3%
Large-cell carcinoma: 11.8%
SQ cell carcinoma: 29.3%
Other: 2.5%
Stage IIIb: 15.4%
Stage: IV 84.6%
Meets NICE requirement
60.8 (19.9) EQ-5D VAS N/A No
≥ 1st line
 Iyer 2013 [46]
Advanced/metastatic NSCLC
France, Germany 1 L/2 L 0.58 (0.35) EQ-5D UK Patients with:
Adenocarcinoma: 56.3%
Large-cell carcinoma: 11.8%
SQ cell carcinoma: 29.3%
Other: 2.5%
Stage IIIb: 15.4%
Stage: IV 84.6%
Meets NICE and SMC requirements
France, 1 L/2 L 0.57 (0.41)
Germany, 1 L/2 L 0.59 (0.31)
France, Germany 1 L/2 L 58.0 (19.9) EQ-5D VAS No
France, 1 L/2 L 57.1 (21.1)
Germany, 1 L/2 L 58.6 (19.1)
2nd line
 Blackhall 2014 [41]
Advanced/metastatic ALK+ NSCLC
2 L BL CRZ 0.73 (0.24) EQ-5D-3 L NR Multinational patients, locally advanced/metastatic ALK+ NSCLC, 2 L Unclear as tariff NR
2 L BL chemotherapy (PEM or DOC) 0.70 (0.26)
2 L BL PEM 0.73 (0.24)
2 L BL DOC 0.67 (0.29)
2 L on CRZ 0.82 (SE, 0.01)
(95% CI, 0.79–0.85)
2 L on Chemotherapy 0.73 (SE, 0.02)
(95% CI, 0.70–0.77)
2 L on PEM 0.74 (SE, 0.02)
(95% CI, 0.70–0.79)
2 L on DOC 0.66 (SE, 0.04)
(95% CI, 0.58–0.74)
 Chevalier 2013c [38]
Advanced/metastatic NSCLC
2 L PF 0.70 (0.22) EQ-5D French (TTO) Stage I–Stage III/IV PF and PD Meets HAS requirements
2 L PD 0.55 (0.35)
 Chouaid 2013 [39]
Advanced/metastatic NSCLC
2 L PF 0.74 (0.18)
(95% CI, 0.68–0.80)
EQ-5D-3 L UK At time of advanced diagnosis, mean age 64.8 years
Adenocarcinoma: 65.2%
Large-cell carcinoma: 6.8%
SQ cell carcinoma: 17.1%
Other: 9.9%
Clinical stage at time of survey:
IIIb: 17.9%
IV: 82.1%
Meets NICE requirements
65.0 (19.6)
(95% CI, 59.2–70.8)
EQ-5D VAS N/A No
2 L PD 0.59 (0.34)
(95% CI, 0.42–0.77)
EQ-5D-3 L UK Meets NICE requirements
53.5 (23.3)
(95% CI, 41.5–65.4)
EQ-5D VAS N/A No
 Huang 2016c [45]
Advanced PD-L1+ NSCLC
2 L PF 0.76 (95% CI, 0.75–0.77) EQ-5D NR Multinational patients with advanced NSCLC and PD-L1+ tumours in 2 L on PEMB or DOC, after platinum-based chemotherapy Unclear as tariff NR
2 L PD 0.69 (95% CI, 0.66–0.71)
Advanced PD-L1+ NSCLC, 2 L, >  360 days from death 0.81 (0.79, 0.83) Patients with advanced NSCLC and PD-L1+ tumours in 2 L on PEMB or DOC, after platinum-based chemotherapy
Advanced PD-L1+ NSCLC, 2 L, 180–360 days from death 0.73 (0.71, 0.75)
Advanced PD-L1+ NSCLC, 2 L, 90–180 days from death 0.69 (0.66, 0.72)
Advanced PD-L1+ NSCLC, 2 L, 30–90 days from death 0.60 (0.56, 0.64)
Advanced PD-L1+ NSCLC, 2 L, <  30 days from death 0.40 (0.31, 0.48)
 Iyer 2013 [46]
Advanced/metastatic NSCLC
On treatment: 2 L only 0.53 (0.38) EQ-5D UK French and German patients Meets NICE and SMC requirements
54.9 (19.3) EQ-5D VAS N/A No
 Langley 2013 [48]
Stage IV NSCLC with brain metastases
NSCLC with BM, previous tx allowed, OSC + WBRT 0 days 0.63 EQ-5D NRd UK and Australian NSCLC patients with brain metastases No, as VAS tariff used
NSCLC with BM, previous tx allowed, OSC + WBRT 28 days 0.49
NSCLC with BM, previous tx allowed, OSC + WBRT 56 days 0.39
NSCLC with BM, previous tx allowed, OSC + WBRT 112 days 0.36
NSCLC with BM, previous tx allowed, OSC + WBRT 168 days 0.16
NSCLC with BM, previous tx allowed, OSC alone 0 days 0.60
NSCLC with BM, previous tx allowed, OSC alone 28 days 0.49
NSCLC with BM, previous tx allowed, OSC alone 56 days 0.44
NSCLC with BM, previous tx allowed, OSC alone 112 days 0.38
NSCLC with BM, previous tx allowed, OSC alone 168 days 0.36
 Lloyd 2008 [59]
Cancer with chemotherapy-related anaemia or fatigue
Anaemia, Hb level, ≥12.0 g/dL 0.708 (95% CI, 0.057) SG N/A General public sample from UK No
0.611 (95% CI, 0.112) TTO UK cancer patients who have recently experienced chemotherapy-related fatigue and anaemia completing vignette-based TTO Meets NICE/SMC requirements but still vignette-based health state rather than patient rating own health
 Nafees 2008 [59]
mNSCLC
2 L Stable diseasee 0.65 (SE, 0.02) SG N/A 100 members of general public in UK No, but used in multiple HTA submissions
2 L Responding diseasef 0.67
2 L Response gain 0.02 (SE, 0.01)
2 L Progressive diseaseg 0.47
 Novello 2015 [49]
Stage III/IV recurrent NSCLC (SQ and NSQ)h
2 L NIN + DOC, before treatment (week 0) 0.72 EQ-5D UK Multinational patients with stage III/IV recurrent NSCLC (SQ and NSQ) in 2 L after chemotherapy
Adenocarcinoma: 50.1%
Meets NICE/SMC requirements
2 L NIN + DOC, after treatment (week 30) 0.61
2 L PLA + DOC, before treatment (week 0) 0.72
2 L PLA + DOC, after treatment (week 30) 0.62
2 L NIN + DOC, before treatment (week 0) 69.0 EQ-5D VAS N/A No
2 L NIN + DOC, after treatment (week 30) 63.2
2 L PLA + DOC, before treatment (week 0) 69.0
2 L PLA + DOC, after treatment (week 30) 63.1
 Reck 2015 [50]
Advanced SQ NSCLC
2 L NIVO at BL 0.68 (0.208) EQ-5D NR Multinational patients with advanced SQ NSCLC Unclear as tariff NR
2 L DOC at BL 0.66 (0.284)
2 L NIVO at BL 63.7 (18.2) EQ-5D VAS N/A No
2 L DOC at BL 66.3 (20.5)
 Rudell 2016c [57]
Advanced NSCLC, EGFR+
2 L OSI at BL 65.2 (20.33) EQ-5D-5 L VAS N/A Multinational patients with EGFR+ advanced NSCLC, 2 L after previous TKI No
2 L OSI at 36 weeks 73.7 (17.33)
 Schuette 2012 [51]
NSCLC Stage IIIB–IV
2 L, PEM at BL 0.66 (0.256) EQ-5D UK TTO Austrian and German advanced/mNSCLC 2 L patients mainly after prior platinum treatment
(IIIa, 6.7%; IIIb, 19.8%;
IV, 73.5%)
Meets NICE/SMC requirements
2 L, PEM at 6 weeks (2nd cycle) 0.02 (0.214) EQ-5D gain
2 L, PEM at 6th cycle 0.11 (0.228)
2 L, PEM at BL 59.3 (17.8) EQ-5D VAS N/A No
2 L, PEM at 6 weeks (2nd cycle) 3.3 (12.58) EQ-5D VAS gain N/A
2 L, PEM at 6th cycle 12.8 (17.62)
 Vargas 2009c [72]
Advanced NSCLC
2 L, on ERL 0.81 Global QoL index NR Patients with advanced NSCLC, 2 L after previous chemotherapy No
2 L, on taxanes 0.62
≥ 2nd line
 Chen 2010c [73]
Advanced NSCLCd
2 L, DOC, during treatment 0.45i SG N/A UK general public (as algorithm based on Nafees 2008 data used to calculate utilities) Acceptable data for SMC
2 L, DOC, after treatment 0.57
2 L, PEM, during treatment 0.54
2 L, PEM, after treatment 0.59
3 L, ERL, during treatment 0.48
BSC, during treatment 0.47
 Chevalier 2013 [38]
Advanced/metastatic NSCLC
3/4 L PF 0.61 (0.3) EQ-5D French (TTO) Stage I–Stage III/IV PF and PD Meets HAS requirements
3/4 L PD 0.42 (0.40)
 Griebsch 2014 [37]
Stage IIIb (with pleural effusion)/IV NSCLC adenocarcinoma
(LUX-LUNG 1)j
Week 4, progression effect longitudinal model −0.1 EQ-5D UK Multinational advanced/metastatic NSCLC, 2 LL Meets NICE requirements
Mixed effect longitudinal model IRC −0.056 (95% CI,
− 0.083 to − 0.028)
Mixed effect longitudinal model IN −0.065 (95% CI,
− 0.092 to − 0.039)
Mixed effect longitudinal model IRC, AFA −0.06
Mixed effect longitudinal model IRC, BSC −0.046
Mixed effect longitudinal model IINV, AFA −0.081
Mixed effect longitudinal model IINV, BSC −0.033
Week 4, progression effect longitudinal model −7.3 EQ-5D VAS N/A No
Mixed effect longitudinal model IRC −3.76 (95% CI, −5.19 to −2.32)
Mixed effect longitudinal model INV − 3.83 (95% CI, − 5.21 to − 2.44)
Mixed effect longitudinal model IRC, AFA 3.63
Mixed effect longitudinal model IRC, BSC −4.11
Mixed effect longitudinal model INV, AFA −4.42
Mixed effect longitudinal model INV, BSC −2.55
 Hirsh 2013 [40]
Stage IIIB/IV NSCLC
3 LL on AFA + BSC 0.71 EQ-5D UK 98% adenocarcinoma
PD following treatment lines
1–2, one of which was platinum based, plus PD after at least 12 weeks of ERL or GEF
Meets NICE requirements
3 LL on PLA + BSC 0.67
3 LL on AFA + BSC 67.4 EQ-5D VAS N/A No
3 LL on PLA + BSC 65.2
 Schwartzbergc 2015 [60]
Stage IIIb/IV NSCLC (SQ & NSQ)
All patients wk 6 1.0 (21.7) EQ-5D VAS N/A Patients, 2 LL, NIVO 3 mg/kg i.v. q2w No
wk 12 5.8 (21.3)
wk 18 8.2 (22.3)
wk 24 8.2 (23.9)
wk 30 8.4 (29.2)
SDis wk 6 3.8 (19.8)
wk 12 6.4 (21.9)
wk 18 8.2 (20.9)
wk 24 5.2(21.9)
wk 30 7.2 (28.5)
PR wk 6 7.3 (22.4)
wk 12 6.6 (24.7)
wk 18 8.1 (27.6)
wk 24 18.1 (31.0)
wk 30 13.7 (38.2)
PD wk 6 −5.8 (21.1)
wk 12 −3.0 (19.8)
wk 18 3.9 (24.3)
wk 24 6.8 (12.2)
wk 30 5.5 (15.7)
Treatment line not specified
 Bradbury 2008c [42]
Advanced NSCLC
On ERL 0.772 EQ-5D NR (possibly Canadian) Canadian patients Potentially relevant to CADTH
On BSC 0.754
 Chang 2016c [63]
Advanced NSCLC
> 360 days from death 0.904
(95% CI, 0.892–0.917)
TTO NR General public, South Korea No
180–360 days from death 0.720
(95% CI, 0.692–0.748)
90–180 days from death 0.627
(95% CI, 0.598–0.655)
30–90 days from death 0.379
(95% CI, 0.349–0.409)
< 30 days from death 0.195
(95% CI, 0.172–0.218)
 Dansk 2016c [43]
Advanced NSCLC
Synthesized PF Median, 0.706
Range, 0.620–0.815
Synthesized utility across > 1 instrument type NR Utilities synthesized included those where respondents were patients and those where they were the general public considering a hypothetical health state No
Synthesized PF trial-based Median, 0.750
Range, 0.627–0.815
Synthesized PF non-trial-based Median, 0.653
Range, 0.620–0.653
Synthesized PD Median, 0.565
Range, 0.470–0.688
Synthesized PD trial-based Median, 0.599
Range, 0.550–0.688
Synthesized PD non-trial-based Median, 0.473
Range, 0.470–0.530
 Doyle 2008 [65]
Metastatic NSCLC
SDis, no additional symptoms 0.626 SG N/A General public No
Treatment response, no additional symptoms 0.712
 Grunberg 2009c [58]
BC/LC
Chemotherapy-induced nausea and vomiting of differing severity Reported graphically SG N/A Patients BC/LC Meets NICE requirements
 Grutters 2010c [44]
NSCLC (stage unspecified)
NSCLC with grade 3+ dyspnoea, stage unspecified Median, 0.52 EQ-5D-5 L NR Patients at an early treatment stage No
 Jang 2010 [47]
Stage IV NSCLC
Stage IV NSCLC 0.75 (0.15) EQ-5D US Patients with NSCLC attending a major Canadian cancer center outpatient clinic No
 Linnet 2015c [62]
Stage IV NSCLC on oral VINO
PCS, cycle 2 37.0 SF-12 N/A Patients No
PCS, cycle 3 38.6
MCS, cycle 2 47.7
MCS, cycle 3 44.2
PCS, cycle 2 52.9 Caregivers Potential to estimate SF-6D for caregivers to mNSCLC patients, for SMC or CADTH
PCS, cycle 3 53.4
MCS, cycle 2 46.2
MCS, cycle 3 44.6
 Lloyd 2005c [66]
Stage IV NSCLC
RES 0.70 SGk N/A General public No
SDis, oral treatment 0.63
SDis, i.v. treatment 0.58
PD 0.42
End of life 0.33
 Manser 2006 [61]
Stage IV NSCLC
Stage IV Median, 0.68
(IQR, 0.54–0.82)
AQoL Australia Mixed stage enrolled:
I, 31.5%; II, 17.4%; IIIa, 16.3%; IIIb, 7.6%; IV, 25.0%
No
 Matza 2014 [67]
Stage IV cancer with bone metastases
Cancer with bone metastases and no SRE 0.47 (0.41) TTO N/A General public, UK
(Edinburgh and London)
No
0.47 (0.45) General public, Canada
(Montreal and Toronto)
0.47 (0.42) General public, UK and Canada
 Stewart 2015 [56]
EGFR+ Stage IV NSCLC
PR/SDis on EGFR TKIs (GEF, ERL, AZD9291) 0.82 (SE, 0.16) EQ-5D-3 L NR Patients, eligible for or on TKI tx, 55% Asian, 45% male, median age 60, 66% never smokers. Stage IV:
at diagnosis, 80%
when surveyed, 100%
Unclear
Responded to standard chemotherapy 0.80 (SE, 0.12)
EGFR+, responded to GEF 0.84 (SE, 0.14)
EGFR+, responded to ERL 0.82 (SE, 0.17)
EGFR+, responded to AZD9291 0.83 (SE, 0.16)
EGFR+, PD during TKI treatment (GEF, ERL, AZD9291) 0.74 (SE, 0.08)
EGFR+, all patients (PR/SDis/PD), 25% 3LL 0.802
 Tabberer 2006 [52]
Advanced NSCLC
RES 0.49 EQ-5D NR General public, UK
(Cardiff, Glasgow, London and Oxford)
No
SDis 0.46
SDis + oral treatment 0.45
SDis + i.v. treatment 0.43
PD 0.22
Near death 0.15
 Trippoli 2001 [53]
Metastatic NSCLC
Metastatic NSCLC 0.53 (0.36) EQ-5D UK (TTO) Italian patients Meets NICE and SMC reference cases
0.55 (0.22)l EQ-5D VAS N/A No
 Yang 2014 [54]
Stage IIIB/IV NSCLC
Stage IV inoperable, performance status 0–1 0.75 (0.22) EQ-5D Taiwan Patients, mixed NSCLC stages: I, 0.8%; II, 0%; IIIA, 4.5%; IIIB, 16.9%; IV, 77.8% No
Stage IV inoperable, performance status 0–4 0.75 (0.22)
 Yokoyama 2013c [55]
Advanced NSCLC/SCLC
Stage IIIB/IV NSCLC/SCLC with bone metastasis and SRE NR EQ-5D NR Patients, advanced NSCLC, 72%, SCLC, 28%
NSCLC and SCLC: IIIB, 37%; IV, 63%
No

aMean, or mean (SD) unless stated otherwise

bVAS scores were also reported in this study but unclear whether this was EQ-VAS

cThese studies were published as abstracts or posters

dThis referenced article (https://www.ncbi.nlm.nih.gov/pubmed/10109801) is for a VAS valuation

e SDis vignette:

• You have a life-threatening illness that is stable on treatment. You are receiving cycles of treatment that require you to go to the outpatient clinic

• You have lost weight, and your appetite is reduced. You sometimes experience pain or discomfort in your chest or under your ribs, which can be treated with painkillers. You have shortness of breath, and breathing can be painful. You have a persistent nagging cough

• You are able to wash and dress yourself and do jobs around the home. Shopping and daily activities take more effort than usual

• You are able to visit family and friends but often have to cut it short because you get tired

• You sometimes feel less physically attractive than you used to. Your illness has affected your sex drive

• You worry about dying and how your loved ones will cope

f Second-line responding vignette:

• You have a life-threatening illness that is responding to treatment. You are receiving cycles of treatment which require you to go to the outpatient clinic

• You are gaining back your weight and your appetite is returning. You occasionally experience pain or discomfort in your chest or under your ribs which can be treated with painkillers. You sometimes have shortness of breath. You occasionally have a nagging cough

• You are able to wash and dress yourself and do jobs around the home. Shopping and daily activities can sometimes be tiring

• You are able to visit family and friends but sometimes have to cut it short because you get tired

• You occasionally feel less physically attractive than you used to. Your illness has somewhat affected your sex drive

• You sometimes worry about dying and how your loved ones will cope

g Second-line PD vignette:

• You have a life-threatening illness, and your condition is getting worse

• You have lost your appetite and have experienced significant weight loss. You experience pain and discomfort in your chest or under your ribs. You frequently have shortness of breath, and breathing is often painful. You have a persistent nagging cough and sometimes cough up blood. You may experience some difficulty swallowing

• You experience severe fatigue and feel too tired to go out or to see family and friends. It has affected your relationships with them

• You need assistance to wash and dress yourself. You are often unable to do jobs around the house or other daily activities. You are dependent on others to do your shopping and are unable to do your usual daily activities

• You often feel less physically attractive than you used to. You have little or no sexual drive

• You are depressed, and dying is always on your mind. You worry about how your loved ones will cope

hThis study also has utilities available every 3 weeks between week 0 and week 30 for all treatments

iAll utilities in this paper assumed to be the mean, although it is not clearly stated in the paper

j1 L data also reported from LUX-LUNG 3

kIndividual country values are also available in this publication

lThis value is reported as in the original publication

Abbreviations: 1 L first line, 2 L second line, 2 LL second and subsequent line, 3 LL third and subsequent line, AFA afatinib, ALK+ anaplastic lymphoma kinase mutation positive, AQoL Assessment of Quality of Life instrument, BC breast cancer, BL baseline, BSC best supportive care, CADTH Canadian Agency for Drugs and Technologies in Health, CI confidence interval, CRZ crizotinib, DOC docetaxel, EGFR epidermal growth factor receptor, EGFR+ epidermal growth factor receptor mutation positive, EORTC QLQ European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire, EQ-VAS EuroQol visual analogue scale, ERL erlotinib, GEF gefitinib, HAS Haute Autorité de Santé, HTA health technology assessment, IQR interquartile range, i.v. intravenous, LC lung cancer, MCS mental component summary, mNSCLC metastatic non-small cell lung cancer, N/A not applicable, NICE National Institute for Health and Care Excellence, NIN nintedanib, NIVO nivolumab, NR not reported, NSCLC non-small cell lung cancer, NSQ non-squamous, NTS not treatment-specific, OSC optimal standard care, OSI osimertinib, PCS physical component summary, PD progressive disease, PEM pemetrexed, PF progression-free, PLA placebo, PR partial response, PSS progression-status specific, q2w once every 2 weeks, QoL quality of life, RES response, SCLC small-cell lung cancer, SD standard deviation, SDis stable disease, SE standard error, SF-6D 6-dimension Short-Form Health Survey, SF-12/36 12-/36-item Short-Form Health Survey, SG standard gamble, SMC Scottish Medicines Consortium, SQ squamous, SRE skeletal-related event, TKI tyrosine kinase inhibitor, TTO time trade-off, VAS visual analogue scale, VINO vinorelbine, WBRT whole-brain radiotherapy