IMPACT OF CANCER ON HEALTH RELATED QUALITY OF LIFE: EVIDENCE USING THE EQ-5D

A. Simon Pickard1,2

Caitlyn Wilke1,2

Hsiang-Wen Lin1,2

Andrew Lloyd3

1Center for Pharmacoeconomic Research & Dept Pharmacy Practice, College of Pharmacy,Room 164, 833 S. Wood St (MC886), University of Illinois at Chicago, Chicago, IL, 60612

USA;2 Department of Pharmacy Administration, College of Pharmacy.

3Health Care Analytics Group, United BioSource Corporation, 20 Bloomsbury Square,London, UK

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AddressesA. Simon Pickard, PhD (Corresponding Author)College of PharmacyRm 164, MC 886 833 South Wood StreetUniversity of Illinois At ChicagoChicago, Illinois, 60612Ph: (312) 413-3357fax: (312) 996-0397 Email: pickard1@uic.edu

Key Words: HRQL, cancer, EQ-5D

In-Text Abbreviations:CHOP- cyclophosphamide, doxorubicin, vincristine, prednisone; CUA- cost utility analysis; HUI-health utilities index; HRQL- health related quality of life; IPI- International Prognostic Index; IQR-Inter-quartile range; nr- not reported; SD- standard deviation; SEER- Surveillance Epidemiology andEnd Results; QALY- quality adjusted life year; VAS- Visual analog scale; WHO- World HealthOrganization

Acknowledgements:The authors acknowledge funding support from the EuroQol Group Foundation.

••• ABSTRACT

••• BACKGROUND AND PURPOSE:

Cancer is one of the most frequent disease-specific applications of the EQ-5D. The objective of this study is to describe the burden of illness associatedwith various cancer types measured by the EQ-5D and to provide guidance forfuture studies to increase uniformity and comparability of EQ-5D results.

••• METHODS:

A structured literature search was conducted on EMBASE and MEDLINE toidentify papers using keywords related to cancer and the EQ-5D. Original rese-arch studies of patients with cancer that reported EQ-5D results or psychome-tric properties were included for the review.

Results: Of 57 identified articles, 31 studies were selected for inclusion. EQ-5D scores were reported in multiple studies of prostate cancer (n= 4), breastcancer (n= 4), cancers of the digestive system (n= 7), and Hodgkin and/or non-Hodgkin lymphoma (n= 3). Mean index-based scores ranged from 0.33 (SD 0.4)to 0.93 (SD 0.12) and VAS scores ranged from 43 (SD 13.3) to 84 (SD 12.0) acrosssubtypes of cancer.

••• CONCLUSIONS:

A substantial body of literature supports the use of the EQ-5D in cancer.EQ-5D index and VAS scores ranged widely due to heterogeneity of treatmentprotocols, cancer stage, and subtype of cancer. This summary of the availableliterature on utility-based estimates of HRQL in cancer using the EQ-5D is inten-ded as a resource for outcomes research and economic evaluations in this area.

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••• INTRODUCTION

In 2000, there were 22.4 million individuals living with cancer, 10.1million new cases diagnosed annually, and 6.2 million deaths worldwide1. Thelifetime probability of developing cancer in the United States is 46% for menand 38% for women2. According to the World Health Organization (WHO),“the average five-year survival rate for cancer patients is 50% in developedcountries, 30% in developing countries”1. In addition to the uncertainty ofsurvival time, cancer patients must attempt to strike a balance between thephysiological benefits of treatment and the negative impact of these thera-pies on daily life1. Assessment of health-related quality of life (HRQL) can helpto better understand the physical, mental, and emotional implications of thecancer itself as well as effects of treatments such as chemotherapy, radiothe-rapy, and/or surgery.

Measurement of HRQL in cancer may be assessed using cancer specific ins-truments such as the EORTC QLQ-C303,4 and the FACIT measurement system5.Alternatively, generic HRQL preference-based measures such as the HealthUtilities Index (HUI)6 and EQ-5D7 may be used. Preference-based measures areadvantageous because they are an appropriate means for calculating qualityadjusted life years (QALYs) for subsequent application to cost-utility analysis(CUA) and allow for easy comparisons of HRQL burden across different condi-tions and treatments.

Among the generic measures available, the EQ-5D is widely used and sim-ple to administer and score. A preference-based set of weights are used to con-vert patient responses to a health state classifier into a single index of HRQL.Each of the five dimensions (mobility, self care, usual activities, pain/discomfort,and anxiety/depression) on the health state classifier has three levels of respon-se: no problems, some problems, or extreme problems. In addition to the self-classifier, the EQ-5D contains a 20 centimeter visual analogue scale (VAS) ran-ging from 0 (worst imaginable health state) to 100 (best imaginable healthstate) on which an individual places their current health state. The index-basedscore is typically interpreted along a continuum where 1 represents best possi-ble health and 0 represents dead, with some health states being worst thandead (<0). The ability to convert self classifier responses into a single preferen-ce-based score makes the EQ-5D practical for clinical and economic evaluation7.Algorithms have been developed based on the preferences of the generalUnited Kingdom population8, and other country-specific algorithms have beendeveloped for further use9,10.

It is common, if not usual practice, to include HRQL measures in clinicaltrials in oncology. Such trials, as well as some cross-sectional studies intended todescribe burden of HRQL in a cancer, may include utility-based measures suchas EQ-5D which provide quality weights for the calculation of QALYs in econo-

mic evaluation. National catalogs of preference-based scores for chronic condi-tions have begun to appear in the literature11. A catalog of preference-basedscores for cancer-related conditions and stages/phases of treatment would beuseful to compare of the burden of specific cancers relative to the other healthconditions. A catalog of HRQL burden in cancer would help can help to informutilities assigned to different health state endpoints in decision models for eco-nomic evaluations of cancer therapy. Earle and colleagues (2000) previouslyreported a catalogue of utility weights in oncology12. Many advances haveoccurred since that review, including current practice in economic evaluation aswell as a greatly expanded literature using preference-based HRQL measures incancer13,14. A summary of studies that have applied a specific measure such asthe EQ-5D to describe the burden of cancer may further support consistency incost-effectiveness and cost-utility analysis.

This study had 2 objectives. First, the objective was to examine the eviden-ce to support the validity and reliability of the EQ-5D in cancer. Second, wesought to describe the burden of illness associated with various types of cancerin terms of HRQL as defined by the EQ-5D self-classifier and summary scores. Asecondary objective was to provide guidance for future studies to increase uni-formity and usefulness of results reported in cancer studies using the EQ-5D.

••• METHODS

DATA COLLECTION AND ASSESSMENT

A computerized search of the current published literature was performedusing MEDLINE and EMBASE for years 1988 to January 2006. The search strategycombined medical subject headings and keywords relating to cancer and theEQ-5D as follows: (‘cancer’/de OR ‘cancer’) OR (‘oncology’/de OR ‘oncology’) OR(‘neoplasms’/de OR ‘neoplasms’) AND Euroqol OR ‘EQ 5D’ OR ‘EQ5D’. Authorlibraries were also hand-searched for references. Only papers which werepublished in full were included for analysis. The inclusion criteria required thatthe paper was original research, patients had a diagnosis of cancer, and that thearticle reported EQ-5D psychometric properties or reported EQ-5D index, visualanalog scale, or % dimension scores for cancer patients. There were no langua-ge restrictions15. Study abstracts that potentially met the inclusion criteria wereidentified, and full text articles were retrieved for further review15. A standar-dized data abstraction form was developed to facilitate the structured review,which included study design, patient characteristics, intervention information,published source of index-based preference weights and EQ-5D scores. The abs-traction form is available upon request. Two of the authors reviewed abstractsof unique citations identified in the literature search (ASP, CTW). Articles mee-

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ting the inclusion criteria were abstracted and checked for veracity (CTW, HWL).Any disagreements between the reviewers in screening and selecting the arti-cles for review were resolved by consensus.

DATA ANALYSIS

Studies that reported EQ-5D index-based scores and/or VAS scores weresorted by cancer type and last name of the first author. Studies reporting mul-tiple cancer types were included at the end of the table. Standard deviationswere calculated from 95% confidence intervals when not reported directly inthe paper. Y-error bars in figures 3-5 represent the 95% confidence intervalabout the mean score, which was calculated from reported standard deviations.

Psychometric properties presented in table 2 were summarized as follows:type of validity/reliability, comparison performed, and statistical test result.Known-groups comparisons were not included in this summary of psychometricproperties unless clearly indicated for the purpose of psychometric evaluation.

An attempt was made to summarize the burden of cancer for each subty-pe by calculating pooled means across studies. Random effects-based pooledmeans were calculated using the DerSimonian and Laird method16 for thosetypes of cancer which had more than one reported mean/standard deviation,first calculating an inverse variance fixed effects pooled mean (1) and tau sta-tistic of heterogeneity (2):

(1) (2)

Where θi is the mean for each individual study, Q is a measure of hetero-geneity, k-1 is the degrees of freedom for the studies included in the pooledestimate, and wi is the weight of each term, calculated as follows:

(3)

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The Dersimonian and Laird random effects pooled mean is calculated witha weight adjusted for τ:

(4) (5)

with standard error calculation:

(6)

Serial assessments of HRQL reported in a paper were included in theresults, but only the baseline mean scores were included in pooled mean esti-mates. This was consistent with the objective of summarizing the burden of ill-ness attributed to different types of cancer without incorporating repeatedmeasurements into the pooled estimate of HRQL burden. When calculable, ran-dom effects pooled means were plotted alongside results for each cancer type.The formulas were inputted and statistics calculated with MS Office Excel ver-sion 2003.

••• RESULTS

The electronic search of databases on January 12, 2006 returned 57 papers.An additional 7 articles were identified in personal libraries for a total of 63articles. Of 46 publications retrieved for review, 34 papers met the selection cri-teria, 31 which reported an EQ-5D index score, VAS score, and/or responses tothe self-classifier system and 12 papers presented evidence of the psychometricproperties of the EQ-5D (Figure 1). The number of cancer-related studies thatreported HRQL using EQ-5D has increased over the past decade (Figure 2).

Measurement of HRQL using EQ-5D has been performed in a variety ofcancer subtypes, severities (tumor/cancer stages), and treatment regimens.HRQL assessments using the EQ-5D were reported primarily in studies of cancerof the breast11,18-23, digestive system24-30, Hodgkin and/or non-Hodgkin lymp-homas31-34, and prostate11,35-38. Other cancer studies using the EQ-5D includedpatients with neoplasms of the bones and joints, cranial nerves and other ner-

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vous system, multiple myelomas, and lung cancer39-42. Some studies did notreport the nature/location of the cancer, where patients were characterized aseither simply having ‘cancer’, or stating that multiple types of cancer weregrouped together11,32,43-48. Of studies reporting mode of administration (n=27,87%), 30% were on-site self-report, 52% were mailed-out questionnaires, and18% were administered by in-person interview. The study setting was prima-rily hospital-based (81% of studies). The majority of studies (57%) involved mul-tiple settings, while 43% were administered at a single setting. Most studies(88%) reported EQ-5D index scores using the York MVH derived algorithm.Study populations varied with respect to therapy, age distribution, and stage oftreatment (Table 1).

A wide range of mean/median EQ-5D scores were reported in the literatu-re (Table 3). The lowest five EQ-5D index scores reported occurred in the follo-wing populations: cancer-related anorexia cachexia syndrome patients measu-red at baseline44, multiple myeloma patients discharged after high dose che-motherapy41, patients receiving palliative treatment for oesophageal carcino-ma26, patients with Hodgkin or non-Hodgkin lymphoma 14 days post-autolo-gous peripheral blood stem cell transplantation or autologous bone marrowtransplantation33, and elderly non-Hodgkin lymphoma patients with age-adjus-ted IPI of 2-3 at baseline, prior to treatment with CHOP chemotherapy31. Lowscores were not related solely to one particular type of cancer, but rather variedaccording to treatment type and patient subgroup (Figures 3 - 5).

Most studies of cancer patients that reported psychometric properties ofthe EQ-5D investigated construct validity of the EQ-5D, typically through corre-lations with cancer-related clinical characteristics or with cancer-specific HRQLmeasures (Table 2). Evidence of validity and reliability were reported most fre-quently in breast and prostate cancer studies as well as studies that combinedcancer types. Convergent validity was the most common property assessed,typically reported in the form of association with another measure usingPearson’s correlation coefficient. Comparisons were made between the EQ-5Dand Musculoskeletal Tumor Society functional evaluation system (MTSS), TTOmeasurements, Functional Living Index- Cancer (FLIC), EORTC- QLQ C-30, SF-36,and simple VAS scales.

Of the 69 EQ-5D index-based scores shown in Figures 3, 4, and Table 3, 26studies (37.7%) did not report a standard deviation. Of studies that reportedEQ-5D index or VAS scores, 7 out of 31 studies (22.6%) did not report standarddeviations (Figure 5). The random effects pooled mean of prostate cancer EQ-5D mean index scores was 0.756 (SE 0.07) and 0.785 (SE 0.05) for cancers of thedigestive system. Insufficient statistical data were available from articles inother cancer types to enable the calculation of pooled mean summary scores.For instance, only one breast cancer study and no Hodgkin’s or Non-Hodgkinlymphoma studies reported standard deviations for mean EQ-5D index scores,

precluding the estimation of fixed or random effects pooled means. In exami-ning the dimension-specific burden of disease among studies that reported per-centage of problems by dimension, usual activities and anxiety/depression ten-ded to be more adversely affected by cancer (Figures 6 – 10).

••• DISCUSSION

The available literature on the HRQL burden of cancer using EQ-5D hasgreatly expanded in recent years. This trend is consistent with the acceptanceof patient reported outcomes and quality of life as a routine measures to beincorporated into clinical trials, and of the EQ-5D as one of the internationalstandard metric of health status. The catalog of preference-based summary sco-res based on the EQ-5D index-based and VAS reported in this paper for cancer-related conditions elaborates upon the more general catalogs of scores repor-ted by Sullivan et al11 and Tengs51. Cost-utility analyses rely heavily on genericmeasures such as the EQ-5D for the determination of quality adjusted life years(QALYs). This review expands upon Earle et al’s (2000) examination of cost-uti-lity assessment in the field of oncology, with an exclusive focus on studies usingthe EQ-5D12. The EQ-5D index values found in Figures 3 and 4 could be used tocalculate QALYs in a similar fashion to compliment the previous paper.

The number of studies published on the various types of cancer mirroredtheir relative prevalence. Breast cancer was the most prevalent cancer worldwi-de in 2000, followed by colorectal cancer and prostate cancer1. This reviewfound studies of those types of cancer to be the most common among the lite-rature that included the EQ-5D.

As would be expected, cancer patients had lower index and VAS scoreswhen compared to the studies of the general population using the EQ-5D.Across all cancer studies, the median index scores summarized was 0.75 (IQR0.61 - 0.84) and median VAS score was 71.5 (IQR 60.3 - 76.7), much lower thanmean scores reported for the US general population of 0.87 (SD 0.01)52 and 82(SD 14) with median score 8553, respectively. A general population survey fromAlberta, Canada reported an index-based mean score of 0.914 (SD 0.15) andVAS mean score of 84.8 (11.6) for individuals with no medical problems. Thatstudy also reported mean estimates index-based mean score of 0.77 (0.20) andVAS of 70.4 (SD 19.6) for community-based individuals with cancer,54 similar tothe average burden observed in studies included in this review. Among the can-cer studies reporting problems according to dimension, usual activities,pain/discomfort and anxiety/depression were the greatest sources of burden.

Psychometric properties, when reported, supported the use of the EQ-5Din the various types of cancer. There was evidence of agreement betweenresults reported by the EQ-5D and those reported by both generic and specific

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measures of HRQL in cancer populations. The validity and test-retest reliabilityof the EQ-5D was generally supported. Several studies used relationships bet-ween EQ-5D and other measures to support their validity, evidence that the EQ-5D is recognized as one of the standards in the field of HRQL and patient-repor-ted outcomes in oncology.

Much heterogeneity in scores was observed across studies. Differences inHRQL burden between cancer studies was not solely attributed to subtype ofcancer, as the diverse range of mean/median scores could have been due tostage of illness, treatment phase, and non-cancer related sample characteristicssuch as co-morbid conditions and age as well as other unmeasured factors. Inaddition, not all studies used the same algorithm to calculate index-based sco-res. The choice of algorithm used to convert self-classifier scores will affect theindex score presented, as seen in Hamashima et al’s study on rectal cancer inJapan, which reported index scores calculated by both the Ikeda and Dolanalgorithms24. Country specific scoring would be most useful to decision makersin health care that use evidence from CUA to guide allocation of resources. Forenhanced comparability between studies in the literature, however, a “com-mon currency” for calculating EQ-5D index-based scores for the classifier maybe a worthwhile consideration. The expanding body of literature in cancer stu-dies that employ the EQ-5D suggests that the EuroQol group establish an onco-logy repository for EQ-5D scores for the continuance of this review. While onlya handful of studies reported HRQL values according to stage of disease andlevel of toxicity at present, a repository would be important resource to thosewho wish to model cancer-related endpoints in economic evaluations of healthcare interventions.

Statistics for group level data as commonly reported in the literature is notconducive to meta-analysis. Studies often reported only medians, or meansunaccompanied by standard deviations. We calculated pooled mean estimatesfor several types of cancer, but acknowledge there were substantial and statis-tically significant heterogeneity between pooled studies, and many studiescould not be included in a pooled mean estimate due to the absence of a repor-ted mean and standard deviation. In addition to statistical heterogeneity, subs-tantial differences in study designs and patient demographic and clinical cha-racteristics were noted.

In summary, the number of published studies reporting the use of EQ-5Din cancer has increased in recent years. The broad range of EQ-5D index-basedand VAS mean scores in these studies likely reflects some systematic varianceattributable to stage of treatment protocols, progression of disease, and typeof cancer in addition to patient characteristics such as age. The report of bothmean (standard deviation) and median (interquartile range) EQ-5D scores instudies of cancer would facilitate comparisons burden of HRQL between studiesand conditions. There is an emerging interest in health state preferences as

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experienced by patients with the condition which may represent a future areafor research using the EQ-5D in cancer. There continues to be much opportunityfor research using EQ-5D in cancer that would fill gaps in knowledge relatingto values associated with cancer stage by type of cancer; values associated withcommon sites of metastases within various types of cancer; and values for com-mon treatment-induced toxicities.

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mai

ntai

ning

abi

lity

to w

alk

anot

her H

RQL

mea

sure

BRN

Van

Roje

n et

al,

Qua

si-e

xper

imen

tal

Activ

e tr

eatm

ent

Com

paris

on o

f mic

rosu

rger

y an

d M

icro

surg

ery

51/4

952

(11)

1997

40no

n-ra

ndom

ized

ra

diot

hera

py w

ith G

amm

a Kn

ifein

terv

entio

n tr

ial

Radi

othe

rapy

34/6

655

(14)

BRE

[Sta

ge II

Co

nner

-Spa

dy

Long

itudi

nal

Activ

e tr

eatm

ent

FAC

chem

othe

rapy

: 4

cycl

es

and

III]

et a

l, 20

0519

(repe

ated

eve

ry 2

1 da

ys);

incr

ease

d do

se m

itoxa

ntra

ne, v

inbl

astin

e, &

cy

clop

hosp

ham

ide;

loca

l rad

ioth

erap

yBR

EJa

nsen

et a

l, Cr

oss-

sect

iona

lPo

st tr

eatm

ent

38%

repo

rted

pre

viou

s ad

juva

nt20

0420

chem

othe

rapy

1/99

57 (1

1)BR

EPo

lsky

et a

l, Lo

ngitu

dina

lAc

tive

trea

tmen

tCh

oice

inSe

e or

igin

al p

aper

trea

tmen

t for

20

0221

stra

tifie

d ag

e di

strib

utio

nN

o ch

oice

Se

e or

igin

al p

aper

for s

trat

ified

in

trea

tmen

tag

e di

strib

utio

nVe

rkoo

jen

et a

l, Q

uasi

-exp

erim

enta

lPr

etre

atm

ent

Stud

y: L

arge

cor

e ne

edle

bio

psy

0/10

057

2002

22no

n-ra

ndom

ized

Co

ntro

l: O

pen

brea

st b

iops

y0/

100

58in

terv

entio

n tr

ial

GI-

CoRe

Ham

isha

ma

et a

l,Cr

oss-

sect

iona

lPo

st tr

eatm

ent-

54/4

669

(12)

2002

24po

stop

erat

ive

GI-C

oRe

Nor

um e

t al,

Post

test

-onl

y Ac

tive

trea

tmen

tSt

udy:

Adj

uvan

t che

mot

hera

py44

/56

Med

: 62

36-7

619

9725

Cont

rol G

roup

(5-fl

uoro

urac

il an

d le

vam

isol

e)De

sign

+ s

urge

ryCo

ntro

l: su

rger

y al

one

GI-

ESO

Hom

s et

al,

2004

26Ra

ndom

ized

Lo

ng Te

rm Tr

eatm

ent

12 G

y br

achy

ther

apy

75/2

569

(13)

cont

rol t

rial

(intr

alum

inal

radi

othe

rapy

)U

ltraf

lex

sten

t80

/20

69 (1

1)G

I- ES

OW

ildi e

t al,

2004

27Cr

oss-

sect

iona

l Pr

etre

atm

ent;

16/8

464

46-8

3Ac

tive

Trea

tmen

t

387

Tab

le 1

: Des

crip

tio

n o

f st

ud

y ch

arac

teri

stic

s

Canc

er T

ype

Aut

hor,

Year

St

udy

desi

gnD

isea

se/ t

reat

men

t Tr

eatm

ent

regi

men

Pati

ent

% M

/ %M

ean

Age

[Can

cer

Det

ails

][R

efer

ence

No]

stag

esu

bgro

upF

Age

(SD

)Ra

nge

GI-C

oRe

[with

Kr

abbe

et a

l, 20

0428

Pros

pect

ive

coho

rtAc

tive

trea

tmen

t;liv

er m

etas

tasi

s]Po

st tr

eatm

ent

All p

atie

nts

had

lapa

roto

my.

Gro

up I:

sur

gica

l liv

er re

sect

ion

with

or

with

out a

dditi

onal

abl

ativ

e th

erap

yG

roup

II: l

ocal

abl

ativ

e th

erap

y al

one

Gro

up II

I: no

trea

tmen

t (n

o su

rger

y co

uld

be p

erfo

rmed

)G

IM

cMill

an e

t al,

Rand

omiz

ed

Activ

e tr

eatm

ent

Stud

y: M

eges

trol

ace

tate

& ib

upro

fen

55/4

572

50-9

019

9929

cont

rol t

rial

Cont

rol:

Meg

estr

ol a

ceta

te &

pla

cebo

63/3

769

52-8

8G

IO

'Gor

man

et a

l, Cr

oss-

sect

iona

lAc

tive

trea

tmen

tO

vern

ight

fast

ing

befo

re te

stin

gW

eigh

t 55

/45

7049

-84

1998

30St

able

HdN

k [O

ral c

avity

Sch

neid

er e

t al,

Cros

s-se

ctio

nal

Activ

e tr

eatm

ent

Hom

e en

tera

l nut

ritio

n63

/37

56 (2

5)an

d ph

aryn

x;

2000

49

Head

and

nec

k]N

HL

Door

dujin

et a

l, Lo

ngitu

dina

lAc

tive

trea

tmen

tCy

clop

hosp

ham

ide,

dox

orub

icin

,56

/44

7265

-84

[Sta

ges

II, II

I, IV

]20

0531

vinc

ristin

e, p

redn

ison

e ch

emot

hera

pyHO

DN

orum

et a

l, 19

9634

Retr

ospe

ctiv

e Po

st tr

eatm

ent

Radi

othe

rapy

(10)

; ch

emot

hera

py (1

6);

43/5

738

15-7

0co

hort

: cos

t util

ityRa

diot

hera

py a

nd c

hem

othe

rapy

(16)

anal

ysis

HOD,

NHL

van

Agth

oven

et a

l,Ra

ndom

ized

con

trol

Ac

tive

trea

tmen

tIn

duct

ion

chem

othe

rapy

(DHA

P &

PBSC

T68

/32

Med

: 49

18-6

420

01 3

3tr

ial

VIM

cou

rse)

; Ran

dom

ized

to P

BSCT

or A

BMT;

Anot

her D

HAP

cour

se a

nd

high

-dos

e co

nditi

onin

g ch

emot

hera

pyAM

BT48

/52

Med

: 46

18-6

3M

TMY

Uyl

-de

Gro

ot e

t al,

Long

itudi

nal

Activ

e tr

eatm

ent

2 co

urse

s VAD

or v

incr

istin

e, a

dria

myc

in,

64/3

653

(8)

2005

41&

met

hyl p

redn

ison

e ch

emot

hera

py;

HDM

follo

wed

by

tran

spla

ntat

ion

of

who

le b

lood

; col

lect

ion

of r-

met

Hu

G-C

SF m

obili

sed

perip

hera

l blo

od

prog

enito

r cel

ls b

y le

ukop

here

sis;

high

-do

se c

hem

othe

rapy

; rei

nfus

ion

of

prev

ious

ly c

olle

cted

per

iphe

ral s

tem

cel

ls

388

Tab

le 1

: Des

crip

tio

n o

f st

ud

y ch

arac

teri

stic

s

Canc

er T

ype

Aut

hor,

Year

St

udy

desi

gnD

isea

se/ t

reat

men

t Tr

eatm

ent

regi

men

Pati

ent

% M

/ M

ean

Age

[Can

cer

Det

ails

][R

efer

ence

No]

stag

esu

bgro

up%

FA

ge (S

D)

Rang

ePR

O [N

on-

Bert

acci

ni e

t al,

Cros

s-se

ctio

nal

Stag

e no

t rep

orte

d10

0/0

68 (7

)m

etas

tatic

]20

03 3

7

PRO

Korfa

ge e

t al,

Pros

pect

ive

coho

rtAc

tive

trea

tmen

tPr

osta

tect

omy

100/

062

(5)

49-7

420

05 3

8

Radi

othe

rapy

100/

068

(6)

49-8

2PR

OSa

ndbl

om e

t al,

Cros

s-se

ctio

nal

Activ

e tr

eatm

ent;

77(8

)20

01 3

6Po

st tr

eatm

ent;

Long

term

trea

tmen

tPR

OSa

ndbl

om e

t al,

Cros

s-se

ctio

nal

2004

35Ac

tive

trea

tmen

t;76

(10)

Post

trea

tmen

t;Lo

ng te

rm tr

eatm

ent

LUN

GTr

ippo

li et

al,

Cros

s-se

ctio

nal

Activ

e tr

eatm

ent;

See

orig

inal

pap

er fo

r pre

viou

s su

rger

y,93

/762

(9)

2001

42Po

st tr

eatm

ent

radi

othe

rapy

, and

che

mot

hera

py re

gim

ens

GEN

Anan

th e

t al,

Activ

e tr

eatm

ent;

2003

43Ca

se-c

ontr

olLo

ng te

rm tr

eatm

ent

Palli

ativ

e Ca

re38

/63

57 (1

4)O

ncol

ogy

48/5

259

(13)

Gen

eral

Pra

ctic

e37

/63

57 (1

5)G

EN [S

tom

ach;

Man

tova

ni e

t al,

Qua

si-e

xper

imen

tal

Activ

e tr

eatm

ent

Poly

phen

ols,

p.o.

pha

rmac

onut

ritio

nal

Colo

n an

d re

ctum

;200

444

non

rand

omiz

edsu

pple

men

t, m

etro

xipr

oges

tero

ne

40/ 6

058

(9)

Panc

reas

; Lun

g an

d in

terv

entio

n tr

ial

acet

ate

bron

chus

; Bre

ast;

Ova

ry; U

terin

e;

Head

and

nec

k]HO

D (n

=9)

; NHL

Sl

ovac

ek e

t al,

Cros

s-se

ctio

nal

Prev

ious

aut

olog

us/ a

lloge

nous

71/2

956

(n=

15);

MTM

Y 20

0545

hem

atop

olet

ic s

tem

cel

l tra

nspl

anta

tion

(n=

32)

; LEU

(n

=15

) Lo

w-r

isk

[incl

udes

Rav

asco

et a

l,Pr

ospe

ctiv

e co

hort

Activ

e tr

eatm

ent

Radi

othe

rapy

66/3

463

(11)

33-8

6LU

NG,

BRE

, PRO

, 20

02 4

6

BRAI

N, fe

mal

e ge

nita

l sys

tem

]; ES

O; S

TO; C

oRe

389

Tab

le 1

: Des

crip

tio

n o

f st

ud

y ch

arac

teri

stic

s

Canc

er T

ype

Aut

hor,

Year

St

udy

desi

gnD

isea

se/ t

reat

men

t Tr

eatm

ent

regi

men

Pati

ent

% M

/ M

ean

Age

[Can

cer

Det

ails

][R

efer

ence

No]

stag

esu

bgro

up%

FA

ge (S

D)

Rang

eBR

E;Su

lliva

n et

al,

Cros

s-se

ctio

nal

Canc

er o

f Bre

ast

6420

05 1

1

PRO

Canc

er o

f Pro

stat

e70

SKIN

Canc

er o

f the

Ski

n66

GEN

[Doe

sO

ther

Can

cers

44no

t inc

lude

br

east

, pro

stat

e,

skin

can

cers

]G

I- Co

Re; H

OD

Nor

um e

t al,

Cros

s-se

ctio

nal

Post

trea

tmen

t19

9632

GEN

[GI (

n=3)

; W

eze

et a

l,Pr

ospe

ctiv

e co

hort

Com

plem

enta

ry c

are

Gen

tle to

uch-

4 s

essi

ons;

See

orig

inal

LUN

G (n

=1)

; 20

04 4

7pa

per f

or o

ther

regi

men

s31

/66

Med

:57

24-8

0BR

E (n

=17

); PR

O (n

=2)

; BR

AIN

(n=

1);

LEU

(n=

1);

Fem

ale

geni

tal

syst

em (n

=1)

; un

disc

lose

d (2

0)]

GEN

Desa

ndes

et a

l,20

0548

36/6

455

(13)

See

Appe

ndix

5 fo

r Abb

revi

atio

ns

390

Tab

le 2

: Su

mm

ary

of

stu

die

s ex

amin

ing

val

idit

y an

d r

elia

bili

ty o

f EQ

-5D

in c

ance

r

Canc

er

Auth

or, Y

ear

Relia

bilit

yVa

lidity

Resp

onsi

vene

ss

Type

[Ref

eren

ce]

BON

JNT

Lee

et a

l, 2

003

39In

tern

al c

onsi

sten

cy:

• Co

nver

gent

val

idity

: MTS

S an

d EQ

-5D

Cron

bach

a fo

r ful

l EQ

-5D

= 0

.71.

rela

ted

dim

ensi

ons

com

pare

d us

ing

Pear

son

corr

elat

ion.

Mod

erat

e to

str

ong

corr

elat

ions

(R

ange

: 0.3

9-0.

6).

• Di

scrim

inan

t val

idity

: MTS

S an

d EQ

-5D

rela

ted

dim

ensi

ons

com

pare

d us

ing

Pear

son

corr

elat

ion.

La

ck o

f dis

crim

inat

ion

in a

ll bu

t Pai

n di

men

sion

of M

TSS.

BR

ECo

nner

-Spa

dy e

t al,

• Co

nstr

uct v

alid

ity: F

LIC

and

EQ-5

D co

mpa

red.

Ef

fect

Siz

e fo

r EQ

-5D

inde

x. B

asel

ine

2001

18Si

mila

r pat

tern

s of

cha

nge

over

tim

e.to

3 w

k po

st H

DC is

larg

e (1

.16)

; 3

wk

to 8

wk

post

HDC

is m

oder

ate

(0.6

6).

BRE

Ger

ard

et a

l, 19

9923

Test

-ret

est:

40%

agr

eem

ent (

with

in.

• Co

nver

gent

val

idity

: EQ

-5D

and

TTO

com

pare

d1

of th

e m

ean

diffe

renc

e) a

fter 4

wks

fo

r sho

rt te

rm a

nd lo

ng te

rm o

f tru

e ne

gativ

efo

r val

uatio

ns o

f fal

se p

ositi

ve a

nd tr

ue

(tn) a

nd fa

lse

posi

tive

(fp) %

agr

eem

ent.

nega

tive

and

26%

agr

eem

ent f

or tr

ue

Shor

t ter

m: 3

2% (t

n), 1

8% (f

p);

posi

tive

and

fals

e ne

gativ

e br

east

Lo

ng te

rm: 2

0% (t

n), 2

2% (f

p).

scre

enin

g sc

ores

.Pa

ired

rank

s: Sh

ort-

term

agr

eem

ent

Inte

rnal

con

sist

ency

: Con

ditio

n ra

nkin

g be

twee

n EQ

-5D

and

TTO.

tn>

fp:

and

EQ-5

D sc

ore

% a

gree

men

t com

pare

d.56

.7%

; tn≥

fp: 3

1.2%

;Tr

ue n

egat

ive

: 69.

2%, F

alse

pos

itive

: 30.

7%.

tn=

fp: 5

.6%

. Dis

agre

emen

t in

7.6%

.Be

twee

n si

te a

gree

men

t: TT

O =

EQ

-5D

test

ed b

y F-

ratio

s fo

r bet

wee

n-si

te

varia

tion.

Fai

led

to re

ject

the

null.

GI-C

oRe

Krab

be e

t al,

2004

28•

Conv

erge

nt v

alid

ity: E

Q- 5

D in

dex

and

EORT

C Ef

fect

siz

e: m

oder

ate

to la

rge

for S

C,Q

LQ C

-30

com

pare

d. E

ffect

siz

es c

ompa

rabl

e UA

, MO

and

PD

dim

ensi

ons

and

smal

lfo

r cor

resp

ondi

ng d

omai

ns.

for A

D. E

ffect

siz

e de

crea

ses

as ti

me

past

sur

gery

incr

ease

s.HO

DN

orum

et a

l, 19

9634

• Co

nver

gent

Val

idity

: Si

mpl

e VA

S sc

ores

and

EQ

-5D

scor

es c

ompa

red.

Hig

h co

rrel

atio

n re

port

ed, b

ut P

ears

on c

orre

latio

n no

t giv

en.

391

Tab

le 2

: Su

mm

ary

of

stu

die

s ex

amin

ing

val

idit

y an

d r

elia

bili

ty o

f EQ

-5D

in c

ance

r

Canc

er

Auth

or, Y

ear

Relia

bilit

yVa

lidity

Resp

onsi

vene

ss

Type

[Ref

eren

ce]

PRO

Bert

acci

ni e

t al,

2003

37•

Cons

truc

t val

idity

: Bon

ian

Satis

fact

ion

Prof

ile-

Pros

tate

Can

cer c

ompa

red

to E

Q-5

D us

ing

Pear

son

corr

elat

ion.

Item

s w

ith r≥

0.5

(p<

0.00

5)

sele

cted

for B

SP-P

C.

• Kn

own-

grou

ps: B

onfe

rron

i pos

t hoc

test

co

mpa

ring

pros

tate

can

cer w

ith h

ealth

y su

bjec

ts

and

othe

r dis

ease

s. Si

gnifi

cant

diff

eren

ce fr

om

heal

thy

(M=

0.84

vs.

M=

0.94

, p<

0.00

1) b

ut n

ot

sign

ifica

nt fr

om o

ther

dis

ease

s (M

=0.

84 v

s M

=0.

85, p

=1)

.PR

OSa

ndbl

om e

t al,

• Pr

edic

tive

valid

ity: S

core

of E

Q-5

D VA

S pr

edic

ted

by20

0435

regr

essi

on. I

tem

s w

ith p

<.0

1 si

gnifi

canc

e fo

r pr

edic

tion

incl

uded

: wor

st p

ain

last

wee

k, D

ied

befo

re

31 D

ecem

ber 2

000,

Age

(yea

rs),

Heal

th-c

are

avai

labi

lity

and

palli

ativ

e tr

eatm

ent.

LUN

GTr

ippo

li et

al,

• Co

nstr

uct v

alid

ity: E

Q-5

D re

sults

com

pare

d to

oth

er

2001

42st

udie

s. Fo

und

com

para

ble

with

Kur

tz, M

agio

ne,

and

Wan

g st

udie

s. •

Conv

erge

nt v

alid

ity: P

ears

on c

orre

latio

n us

ed to

co

mpa

re E

Q-5

D in

dex,

EQ

5D V

AS, a

nd S

F-36

dom

ains

. St

rong

inde

x co

rrel

atio

n w

ith V

AS(r

= 0

.54)

.M

oder

ate

to s

tron

g re

latio

nshi

p fo

r SF-

36 d

omai

ns

and

inde

x sc

ore

(rang

e: .3

5-.7

32) w

ith h

ighe

st c

orre

latio

n fo

r SF-

36 p

hysi

cal f

unct

ioni

ng; m

oder

ate

to s

tron

g re

latio

nshi

p fo

r EQ

-VAS

and

SF-

36 d

omai

ns (r

ange

: .40

1-.6

85) w

ith h

ighe

st

corr

elat

ion

for S

F-36

Vita

lity.

GEN

Anan

th e

t al,

Test

-ret

est r

elia

bilit

y: k

>0.

720

0343

for p

atie

nts

test

ed (n

= 1

6).

392

Tab

le 2

: Su

mm

ary

of

stu

die

s ex

amin

ing

val

idit

y an

d r

elia

bili

ty o

f EQ

-5D

in c

ance

r

Canc

er

Auth

or, Y

ear

Relia

bilit

yVa

lidity

Resp

onsi

vene

ss

Type

[Ref

eren

ce]

HOD,

Slov

acek

et a

l,•

Disc

rimin

ant v

alid

ity: H

RQL

diffe

renc

e in

pat

ient

s w

ith d

iffer

ent

NHL

,20

0545

num

ber o

f dis

ease

s an

d hi

gher

age

at h

emat

opoi

etic

ste

m c

ell

MTM

Y,tr

ansp

lant

atio

n.LE

UG

I-ESO

Rava

sco

et a

l, 20

0246

• Co

nten

t val

idity

: wor

se m

obili

ty a

nd u

sual

act

iviti

es s

core

s as

soci

ated

with

mal

nutr

ition

or r

educ

ed e

nerg

y; S

tron

g co

rrel

atio

n be

twee

n nu

triti

onal

inta

ke p

ost-

radi

othe

rapy

and

impr

ovem

ent

with

QO

L.G

I-N

orum

et a

l,•

Conv

erge

nt v

alid

ity: E

Q-5

D in

dex

com

pare

d w

ith E

ORT

CCo

Re;

1996

32Q

LQ-C

30 a

nd s

impl

e VA

S sc

ale.

HOD

High

cor

rela

tion

(p <

0.0

001

for r

2 ).

GEN

Desa

ndes

et a

l,•

Conv

erge

nt v

alid

ity: E

Q-5

D in

dex

and

Patie

nt Ju

dgm

ents

of H

ospi

tal

2005

48Q

ualit

y co

mpa

red

usin

g Pe

arso

n co

rrel

atio

n.Lo

w c

orre

latio

n (r2

= 0

.10

– 0.

16).

393

Tab

le 3

: Su

mm

ary

of

EQ-5

D a

sses

smen

ts r

epo

rted

in c

ance

r st

ud

ies

Auth

or, Y

ear

Canc

er ty

pe:

nIn

dex

VAS

%%

%%

%Sc

orin

gAu

thor

Revi

ewer

(Ref

eren

ce N

o)Su

bgro

up

mea

nm

ean

MO

SCUA

PDAD

Algo

rithm

Com

men

tsCo

mm

ents

[Ref

eren

ce]

(SD)

(SD)

Leee

t al,

2003

39BO

NJN

T 49

0.68

73

(19)

Dola

n 19

97,

Conc

entr

atio

n on

the

(0.2

2)U

nite

d M

uscu

losk

elet

al Tu

mor

King

dom

Soci

ety

Func

tiona

l (U

K)Ev

alua

tion

Syst

em.

Van

Roje

n et

al,

BRAI

N: M

icro

surg

ery;

530.

77

Dola

n 19

97,

1997

401

of 2

(0

.18)

UK

EQ-5

D no

t a m

ain

focu

s.BR

AIN

: Rad

iosu

rger

y;92

0.89

2 of

2

(0.1

5)Co

nner

-Spa

dy e

t al,

Dola

n 19

97,

Som

e da

ta p

rese

nted

2001

18U

Kbe

low

was

giv

en in

this

pre

limin

ary

pape

r.Co

nner

-Spa

dy e

t al,

BRE-

Base

line:

480.

78 (0

.18)

1-98

1-98

1-60

1-56

1-31

Dola

n 19

97,

The

EQ-5

D in

dex

resu

lts20

0519

Pret

reat

men

t;2-

22-

22-

382-

442-

64U

Kar

e ta

ken

from

the

sam

e1

of 7

3-0

3-0

3-2

3-0

3-4

coho

rt a

s th

e ch

arac

teris

tics

pres

ente

d ab

ove.

BRE:

1st

day

of 3

rd

480.

75 (0

.18)

1-96

1-90

1-44

1-35

1-46

FAC

cycl

e; 2

of 7

2-4

2-10

2-52

2-65

2-52

3-0

3-0

3-4

3-0

3-2

BRE:

3 w

k po

st48

0.61

(0.2

9)1-

641-

851-

151-

401-

51HD

C; 3

of 7

2-36

2-15

2-52

2-58

2-42

3-0

3-0

3-33

3-2

3-7

BRE:

6 m

o po

st45

0.79

(0.1

9)1-

931-

100

1-40

1-47

1-51

HDC;

4 o

f 72-

72-

02-

532-

532-

423-

03-

03-

43-

03-

7BR

E: 1

2 m

o po

st40

0.84

(0.1

9)1-

881-

100

1-73

1-48

1-60

HDC;

5 o

f 72-

122-

02-

252-

532-

353-

03-

03-

33-

03-

5BR

E: 1

8 m

o po

st

360.

84 (0

.13)

1-92

1-97

1-66

1-47

1-61

HDC;

6 o

f 72-

82-

32-

342-

532-

393-

03-

03-

03-

03-

0BR

E: 2

4 m

o po

st

370.

89 (0

.13)

1-92

1-97

1-76

1-62

1-68

HDC;

7 7

of 7

2-

82-

32-

242-

382-

303-

03-

03-

03-

03-

3

394

Tab

le 3

: Su

mm

ary

of

EQ-5

D a

sses

smen

ts r

epo

rted

in c

ance

r st

ud

ies

Auth

or, Y

ear

Canc

er ty

pe:

nIn

dex

VAS

%%

%%

%Sc

orin

gAu

thor

Revi

ewer

(Ref

eren

ce N

o)Su

bgro

up

mea

nm

ean

MO

SCUA

PDAD

Algo

rithm

Com

men

tsCo

mm

ents

[Ref

eren

ce]

(SD)

(SD)

Ger

ard

et a

l,19

99 2

344

0EQ

-5D

scor

es w

ere

spec

ulat

ive

from

wom

en

elig

ible

for b

reas

t ca

ncer

scr

eeni

ng.

Jans

en e

t al,

BRE:

Che

mo

540.

84

7720

04 2

0+

cho

ice

in tr

eatm

ent;

Dola

n 19

97,

Non

resp

onde

rs C

hoic

e in

trea

tmen

t was

1 of

4 *

*U

Kw

ere

slig

htly

repo

rted

by

the

patie

nt. T

heBR

E: N

o ch

emo

280.

7469

olde

r and

3rd

purp

ose

of th

is s

tudy

+ c

hoic

e in

trea

tmen

t;tr

eate

d w

ith"w

heth

er th

e pr

opor

tion

of

2 of

4**

chem

othe

rapy

trea

tmen

t cho

ice

is re

late

d to

BRE:

Che

mo

105

0.82

75le

ss fr

eque

ntly

satis

fact

ion

with

the

assi

g-+

no

choi

ce in

ne

d tx

, exp

erie

nced

che

mot

-tr

eatm

ent;

3 of

4**

hera

py b

urde

n an

d cu

rren

t BR

E: N

o ch

emo

174

0.83

77Q

OL"

is re

late

d to

our

stu

dy

+ n

o ch

oice

inpu

rpos

e.tr

eatm

ent;

4 of

4 *

*

Pols

ky e

t al,

BRE:

Cho

ice

in56

679

(16

Dola

n 19

97,

2002

21

trea

tmen

t; 1

of 2

)U

KBR

E: N

o ch

oice

in11

775

(17)

trea

tmen

t; 2

of 2

Verk

ooje

n et

al,

BRE:

Bef

ore

need

le30

0.73

80Do

lan

1997

,20

0222

biop

sy; 1

of 4

*U

KBR

E: A

fter n

eedl

e 30

0.71

80bi

opsy

; 2 o

f 4*

BRE:

Bef

ore

open

27

0.69

80br

east

bio

psy;

3 o

f 4*

BRE:

Afte

r ope

n 27

0.61

76br

east

bio

psy;

4 o

f 4*

Ham

isha

ma

et a

l,G

I-CoR

e: S

tom

a;72

0.87

72

(16)

2/3-

202/

3-7

2/3-

292/

3-21

2/3-

14Ik

eda

1999

,20

0224

Iked

a; 1

of 4

(0.1

6)Ja

pan

395

Tab

le 3

: Su

mm

ary

of

EQ-5

D a

sses

smen

ts r

epo

rted

in c

ance

r st

ud

ies

Auth

or, Y

ear

Canc

er ty

pe:

nIn

dex

VAS

%%

%%

%Sc

orin

gAu

thor

Revi

ewer

(Ref

eren

ce N

o)Su

bgro

up

mea

nm

ean

MO

SCUA

PDAD

Algo

rithm

Com

men

tsCo

mm

ents

[Ref

eren

ce]

(SD)

(SD)

GI-C

oRe:

No

380.

84

70 (1

5)2/

3-26

2/3-

132/

3-32

2/3-

342/

3-24

Stom

a; Ik

eda;

2 o

f 4

(0.1

7)G

I-CoR

e: S

tom

a;

720.

87

Dola

n 19

97,

Dola

n; 3

of 4

(0.2

2)U

KG

I-CoR

e: N

o St

oma;

380.

84

Dola

n al

gorit

hm;

(0.1

9)4

of 4

Nor

um e

t al,

GI-C

oRe

62M

ed: 0

.78)

Dola

n 19

97,

1997

25(0

.33

to 1

UK

Hom

s et

al,

GI-E

SO: A

ll pa

tient

s0.

42

59Do

lan

1997

,N

o si

gnifi

cant

diff

eren

ce20

04 2

6po

st tr

eatm

ent;

1 of

3*

(0.3

6)U

Kbe

twee

n EQ

-5D

scor

es o

f th

e 2

trea

tmen

ts; B

asel

ine

core

s fo

r the

se p

atie

nts

are

belo

w th

e po

pula

tion

norm

s.G

I-ESO

:; 10

147

(13)

Brac

hyth

erap

y 2

of 3

GI-E

SO: S

tent

10

843

(13)

Plac

emen

t; 3

of 3

Wild

i et a

l,G

I-ESO

: SEE

R 50

0.93

20

0427

Stag

e 0;

1 o

f 4(0

.12)

GI-E

SO: S

EER

0.6

Stag

e 1;

2 o

f 4(0

.29)

GI-E

SO: S

EER

0.71

St

age

2; 3

of 4

(0.2

1)G

I-ESO

: SEE

R 0.

69

Stag

e 3;

4 o

f 4(0

.31)

Krab

be e

t al,

GI-L

IV :

Base

line

750.

84

75 (1

4)1-

891-

100

1-76

1-83

1-61

Dola

n 19

97,

Post

3 m

onth

s al

so re

port

ed.

2004

28

pre-

surg

ery;

1 o

f 3(0

.12)

UK

EQ-5

D is

com

para

ble

to

2-10

2-0

2-21

2-17

2-36

dise

ase-

spec

ific

HRQ

L.3-

03-

03-

33-

03-

3G

I-LIV

: Pos

t 1/2

74

0.68

58

(19)

1-55

1-78

1-19

1-38

1-69

mon

th; 2

of 3

(0.2

3)

396

Tab

le 3

: Su

mm

ary

of

EQ-5

D a

sses

smen

ts r

epo

rted

in c

ance

r st

ud

ies

Auth

or, Y

ear

Canc

er ty

pe:

nIn

dex

VAS

%%

%%

%Sc

orin

gAu

thor

Revi

ewer

(Ref

eren

ce N

o)Su

bgro

up

mea

nm

ean

MO

SCUA

PDAD

Algo

rithm

Com

men

tsCo

mm

ents

[Ref

eren

ce]

(SD)

(SD)

2-39

2-18

2-42

2-61

2-13

3-5

3-4

3-39

3-1

3-0

GI-L

IV: P

ost 6

69

0.84

75

(14)

1-81

1-97

1-64

1-71

1-78

mon

ths;

3 of

3(0

.11)

2-18

2-3

2-35

2-29

2-22

3-0

3-0

3-1

3-0

3-0

McM

illan

et a

l,G

I :M

A+ p

lace

bo;

38M

ed:

Dola

n 19

97,

Sign

ifica

nt im

prov

emen

t19

99 2

91

of 2

0.63

UK

in E

Q-5

D sc

ore

of ib

upro

fen

(-0.1

to

grou

p (p

<.0

5),

1.00

)va

lues

not

sho

wn.

GI:

MA+

ibup

rofe

n;35

Med

:1

of 2

0.

69

(-0.2

6 to

1.

01)

O'G

orm

an e

t al,

GI:

Wei

ght S

tabl

e;22

M

ed:

Dola

n 19

97,

No

sign

ifica

nt d

iffer

ence

1998

301

of 2

0.85

U

Kin

EQ

-5D

betw

een

(0.0

3 to

gr

oups

.1.

00)

GI:

Wei

ght L

osin

g;

97M

ed:

2 of

20.

52

(-0.2

6 to

1.00

)

Door

dujin

et a

l,N

HL: B

asel

ine,

630.

74Do

lan

1997

,Li

ttle

focu

s on

EQ

-5D;

2005

31aa

IPI 0

-1; 1

of 4

U

KAf

ter 2

nd a

nd 4

th C

HOP

NHL

: Bas

elin

e,53

0.44

cycl

e re

port

ed a

s w

ell.

aaIP

I 2-3

; 2 o

f 4

NHL

: pos

t 6th

CHO

P54

0.69

cycl

e, a

aPI 0

-1; 3

of 4

NHL

: pos

t 6th

CHO

P 44

0.53

cycl

e, a

aPI 2

-3; 4

of 4

397

Tab

le 3

: Su

mm

ary

of

EQ-5

D a

sses

smen

ts r

epo

rted

in c

ance

r st

ud

ies

Auth

or, Y

ear

Canc

er ty

pe:

nIn

dex

VAS

%%

%%

%Sc

orin

gAu

thor

Revi

ewer

(Ref

eren

ce N

o)Su

bgro

up

mea

nm

ean

MO

SCUA

PDAD

Algo

rithm

Com

men

tsCo

mm

ents

[Ref

eren

ce]

(SD)

(SD)

Nor

um e

t al,

HOD

420.

7880

Dola

n 19

97,

1996

34**

Uni

ted

King

dom

van

Agth

oven

et a

l,N

HL, H

OD:

PBS

CT, D

ay

620.

7568

Dola

n 19

97,

Two

time

poin

ts n

ot

2001

33be

fore

tran

spla

ntat

ion;

Uni

ted

pres

ente

d in

this

tabl

e.1

of 4

*Ki

ngdo

mN

HL, H

OD:

ABM

T, Da

y29

0.78

66be

fore

tran

spla

ntat

ion;

2

of 4

*N

HL, H

OD:

PBS

CT, 1

462

0.53

55da

ys p

ost t

rans

plan

ta-

tion;

3 o

f 4*

NHL

, HO

D: A

BMT,

14

290.

4250

days

pos

t tra

nspl

anta

-tio

n; 4

of 4

*U

yl-d

e G

root

et a

l,M

TMY:

Bas

elin

e;25

0.52

2005

41

1 of

4(0

.33)

Dola

n 19

97,

Not

bas

ed o

n a

Ther

e w

ere

a to

tal o

f 7U

nite

d pr

etre

atm

ent

time

poin

ts re

port

ed;

King

dom

base

line,

so

this

Base

line,

T3,

T5,

T7

inM

TMY:

dis

char

ge24

0.38

stud

y pr

obab

ly

tabl

e.HD

M; 2

of 4

unde

rest

imat

e M

TMY:

dis

char

ge14

0.66

impr

ovem

ents

in

PSCT

]; 3

of 4

qual

ity o

f life

.M

TMY:

12

mo

120.

69fo

llow

up; 4

of 4

Bert

acci

ni e

t al,

PRO

: Hea

lthy;

570.

94

Dola

n 19

97,

Sign

ifica

nt d

iffer

ence

EQ-5

D us

ed p

rimar

ily20

0337

1 of

3

(0.0

2)U

Kin

pat

ient

s w

ith

to e

nsur

e th

e va

lidity

PRO

: Pro

stat

e Ca

ncer

;10

30.

84pr

osta

te c

ance

r vs.

of B

onia

n Sa

tisfa

ctio

n2

of 3

he

alth

y in

divi

dual

s, Pr

ofile

- Pro

stat

ePR

O: O

ther

Dis

ease

s;10

10.

85

but n

ot s

igni

fican

t Ca

ncer

.3

of 3

(0.0

2)co

mpa

red

to in

divi

dual

sw

ith o

ther

dis

ease

s.

398

Tab

le 3

: Su

mm

ary

of

EQ-5

D a

sses

smen

ts r

epo

rted

in c

ance

r st

ud

ies

Auth

or, Y

ear

Canc

er ty

pe:

nIn

dex

VAS

%%

%%

%Sc

orin

gAu

thor

Revi

ewer

(Ref

eren

ce N

o)Su

bgro

up

mea

nm

ean

MO

SCUA

PDAD

Algo

rithm

Com

men

tsCo

mm

ents

[Ref

eren

ce]

(SD)

(SD)

Korfa

ge e

t al,

PRO

: Pro

stat

ecto

my

127

0.89

79

(17)

2005

38

-pre

trea

tmen

t; 1

of 6

*(0

.15)

Dola

n 19

97,

Data

from

Rot

terd

amU

Kst

udy;

Tim

e po

int a

t 12

PRO

: Pro

stat

ecto

my

0.91

84m

onth

s no

t in

this

tabl

e.po

st-6

mo;

2 o

f 6*

(0.1

6)(1

2)PR

O: P

rost

atec

tom

y,0.

8881

post

-52

mo;

3 o

f 6*

(0.1

6)(1

3)PR

O: R

adio

ther

apy,

187

0.81

72pr

etre

atm

ent;

4 of

6*

(0.2

0)(1

7)PR

O: R

adio

ther

apy-

0.83

76po

st 6

mo;

5 o

f 6*

(0.2

1)(1

7)PR

O: R

adio

ther

apy-

0.76

74po

st 5

2 m

onth

s; 6

of 6

*(0

.23)

(16)

Sand

blom

et a

l,PR

O12

431-

621-

871-

751-

381-

66Do

lan

1997

,EQ

-5D

resu

lts in

2001

36U

Kgr

aphi

cal f

orm

,2-

362-

112-

182-

572-

32by

age

.3-

153-

23-

73-

53-

2

Sand

blom

et a

l,PR

O:

660.

538

54 (2

2)Do

lan

1997

,Pa

tient

s dy

ing

of o

ther

2004

35

Died

of P

RO b

y 31

(0.3

2)U

Kca

uses

not

pre

sent

edDe

c 20

01; 1

of 2

in

this

tabl

e.PR

O: S

till A

live

3110

760.

7770

(20)

Dec

2001

; 2 o

f 2

(0.2

5)Tr

ippo

li et

al,

LUN

G92

/94

0.58

58 (2

)Do

lan

1997

,Goo

d ag

reem

ent

Scor

es w

ere

divi

ded

by20

0142

(0.3

3)U

Kw

ith W

ang,

Kur

tz,

gend

er, s

urge

ry, c

he-

& M

angi

one

stud

ies.

mot

hera

py, r

adio

ther

apy

met

asta

sis,

age,

and

time

sinc

e di

agno

sis.

Anan

th e

t al,

GEN

: Pal

liativ

e Ca

re;

640.

52Do

lan

1997

,EQ

-5D

inco

rpor

ated

into

2003

431

of 3

*(0

.18)

UK

anot

her q

uest

ionn

aire

.G

EN: O

ncol

ogy;

560.

67

2 of

3*

(0.1

9)

399

Tab

le 3

: Su

mm

ary

of

EQ-5

D a

sses

smen

ts r

epo

rted

in c

ance

r st

ud

ies

Auth

or, Y

ear

Canc

er ty

pe:

nIn

dex

VAS

%%

%%

%Sc

orin

gAu

thor

Revi

ewer

(Ref

eren

ce N

o)Su

bgro

up

mea

nm

ean

MO

SCUA

PDAD

Algo

rithm

Com

men

tsCo

mm

ents

[Ref

eren

ce]

(SD)

(SD)

GEN

: Gen

eral

67

0.75

Prac

tice;

3 o

f 3*

(0.1

5)M

anto

vani

et a

l,G

EN: B

asel

ine;

250.

3344

(2.2

)20

0444

1 of

4(0

.4)

Not

repo

rted

EQ-5

D in

dex

impr

oved

at 4

mon

ths;

VAS

impr

oved

at

1 an

d 2

mon

ths.

GEN

: Af

ter 1

mon

th;

250.

4556

(2.2

)2

of 4

(0

.3)

GEN

: Afte

r 2 m

onth

s;18

0.59

62 (2

)3

of 4

(0

.3)

GEN

: Afte

r 4 m

onth

s;12

0.54

62 (2

)4

of 4

(0

.3)

Slov

acek

et a

l,HO

D, N

HL, M

TMY,

30

0.84

76 (1

2)Da

nkov

ain

fluen

ce o

f pol

ymor

bidi

ty,

Resu

lts a

lso

sum

ma-

2005

45LE

U: 0

Ass

oc. D

isea

ses;

(0.1

6)20

01,C

zech

age

, and

relig

ion

on E

Q 5

Driz

ed b

y be

lief i

n G

od1

of 3

*Re

publ

icin

dex

and

Visu

al A

nalo

g HO

D, N

HL, M

TMY

130.

7572

(18)

Scal

e ar

e st

atis

tical

ly

LEU

: 1 A

ssoc

. Dis

ease

s(0

.19)

sign

ifica

nt (P

<.0

1).

2 of

3*

HOD,

NHL

, MTM

Y 14

0.71

66 (1

3)LE

U: 2

Ass

oc. D

isea

ses;

(0.1

5)3

of 3

*Ra

vasc

o et

al,

GI –

ESO

; 1 o

f 56

1-83

1-66

1-0

1-67

1-50

Reco

mm

enda

tion

that

Onl

y en

d re

sults

repo

rted

2002

462-

172-

172-

502-

332-

33Eu

roqo

l sho

uld

be u

sed

to c

onse

rve

spac

e.3-

03-

173-

503-

03-

17as

a ro

utin

e in

suc

h Pa

tient

s gr

oupe

d as

GI –

STO

; 2 o

f 55

1-10

01-

100

1-40

1-80

1-80

patie

nts,

sinc

e qu

ality

of

"hig

h ris

k" o

r "lo

w ri

sk".

2-0

2-0

2-60

2-20

2-20

life

is a

maj

or o

utco

me.

3-0

3-0

3-0

3-0

3-0

GI-C

oRe;

3 o

f 546

1-63

1-89

1-26

1-83

1-16

2-22

2-7

2-41

2-15

2-43

3-15

3-4

3-33

3-2

3-41

HdN

k; 4

of 5

231-

531-

481-

51-

831-

02-

302-

302-

432-

132-

483-

173-

223-

523-

43-

52

400

Tab

le 3

: Su

mm

ary

of

EQ-5

D a

sses

smen

ts r

epo

rted

in c

ance

r st

ud

ies

Auth

or, Y

ear

Canc

er ty

pe:

nIn

dex

VAS

%%

%%

%Sc

orin

gAu

thor

Revi

ewer

(Ref

eren

ce N

o)Su

bgro

up

mea

nm

ean

MO

SCUA

PDAD

Algo

rithm

Com

men

tsCo

mm

ents

[Ref

eren

ce]

(SD)

(SD)

GEN

: Low

Ris

k; 5

of 5

45

1-94

1-10

01-

941-

891-

842-

42-

02-

22-

72-

93-

23-

03-

43-

43-

7Sc

hnei

der e

t al,

2000

49Hd

Nk

110.

54

56Do

lan

1997

,Sm

all s

ampl

e si

ze fo

r can

cer.

(0.3

3)(2

.3)

UK

Sulli

van

et a

l,20

05 1

1BR

E; 1

of 4

236

0.81

Shaw

200

5,Co

ncer

n ab

out c

eilin

gDi

sutil

ity o

f con

ditio

n re

por-

Uni

ted

effe

cts

and

pote

ntia

lte

d fo

r all

grou

ps; 2

5%,

Stat

esla

ck o

f dis

crim

inat

ion.

50%

, and

75%

EQ

-5D

PRO

; 2 o

f 4

171

0.77

scor

es a

lso

give

n.G

EN: O

ther

Can

cer;

132

0.85

3 of

4

SKIN

; 4 o

f 450

50.

82N

orum

et a

l,G

I-CoR

e; H

OD*

*98

0.79

80 (2

0)19

9632

(0.2

3)W

eze

et a

l,20

0447

GEN

: Pre

-tre

atm

ent;

351-

381-

741-

141-

201-

9Do

lan

1997

,In

fo o

n M

O, S

C, a

nd U

A w

as1

of 2

U

Kon

ly fo

und

in a

bar

gra

ph.

2-62

2-23

2-63

2-71

2-77

3-0

3-3

3-23

3-9

3-14

GEN

: Pos

t- tr

eatm

ent;

1-50

1-74

1-14

1-23

1-34

2 of

22-

472-

262-

692-

662-

573-

33-

03-

173-

113-

9De

sand

es e

t al,

GEN

2005

48

62 (1

9)

* in

dex

sco

res

wer

e tr

ansf

orm

ed w

ith

in t

able

s to

a 0

-1 s

cale

fo

r co

nsi

sten

cy**

V

AS

sco

res

wer

e tr

ansf

orm

ed w

ith

in t

able

s an

d f

igu

res

to a

0-1

00 s

cale

fo

r co

nsi

sten

cySe

e A

pp

end

ix f

or

abb

revi

atio

ns

Figure 1: Summary of Article Retrieval

401

Fig

ure

2:

Tren

ds

in P

ub

licat

ion

s o

f C

ance

r St

ud

ies

usi

ng

EQ

-5D

402

403

Fig

ure

3:

EQ-5

D In

dex

Mea

n/M

edia

n S

core

s fo

r B

reas

t, P

rost

ate

and

Dig

esti

ve S

yste

m C

ance

rs

�M

ean

(95

% C

I);

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edia

n; �

Poo

led

mea

n

404

Fig

ure

4:

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D In

dex

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n/M

edia

n S

core

s fo

r A

ll O

ther

Can

cer

Typ

es

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ean

(95

% C

I);

405

Fig

ure

5:

Vis

ual

An

alo

g S

cale

Mea

n/M

edia

n S

core

s fo

r A

ll C

ance

r Ty

pes

�M

ean

(95

% C

I);

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edia

n;

406

Fig

ure

6:

Dis

trib

uti

on

of

Res

po

nse

s to

Mo

bili

ty D

imen

sio

n o

f EQ

-5D

407

Fig

ure

7:

Dis

trib

uti

on

of

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po

nse

s to

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f C

are

Dim

ensi

on

of

EQ-5

D

408

Fig

ure

8:

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trib

uti

on

of

Res

po

nse

s to

Usu

al A

ctiv

itie

s D

imen

sio

n o

f EQ

-5D

409

Fig

ure

9:

Dis

trib

uti

on

of

Sco

res

for

Pain

/ Dis

com

fort

Dim

ensi

on

of

EQ-5

D

410

Fig

ure

10:

D

istr

ibu

tio

n o

f Sc

ore

s fo

r A

nxi

ety/

Dep

ress

ion

Dim

ensi

on

of

EQ-5

D

411

••• APPENDIX 1:

ABBREVIATIONS USED IN TABLES/FIGURES

Cancer TypesBONJNT Bones and jointsBRE BreastGI Digestive SystemCoRe Colon and Rectum (Colorectal)ESO EsophagusLIV LiverSTO StomachNHL Non-Hodgkin LymphomaHOD Hodgkin’s DiseaseMTMY Multiple MyelomaPROS ProstateLUNG LungGEN General cancer – no type specifiedLEU LeukemiaHdNk Head and Neck

Study AbbreviationsaaIPI age-adjusted International Prognostic IndexABMT autologous bone marrow transplantationAssoc. associatedchemo chemotherapyCHOP cyclophosphamide, doxorubicin, vincristine, prednisoneDHAP cisplatin, cytarabine, dexamethasoneHDC High dose chemotherapyHDM high-dose melphalanFAC Fluorouracil, adriamycin, cyclosphosphamideFLIC Functional Living Index- CancerMA Megestrol acetateMed MedianMTSS Musculoskeletal Tumor Society functional evaluation systemPBSCT (PSCT) peripheral blood stem cell transplantationSEER Surveillance Epidemiology and End ResultsTTO time tradeoffTx treatmentVAD vincristine, adriamycin and dexamethasonVAS visual analog scaleVIM etoposide, ifosfamide, methotrexate