444
`
`Review
`
`Gut 2000;47:444–454
`
`Quality of life measurement in gastrointestinal and liver
`disorders
`
`Health related quality of life
`HEALTH RELATED QUALITY OF LIFE: A WORKING DEFINITION
`HRQOL is a concept which reflects the physical, social, and
`emotional attitudes and behaviours of an individual as they
`relate to their prior and current health state.3 HRQOL
`assessment describes health status from the patients’
`perspective and serves as a powerful tool to assess and
`explain disease outcomes.4 For example, two patients with
`ulcerative colitis (UC) may well have identical disease
`extent, severity, and medical therapy, yet one may hold a full
`time job with a vigorous social and family life while the other
`is unemployed, depressed, and receiving a disability pension.
`The functional domains that comprise HRQOL are outlined
`in table 1. Physical symptoms for a particular GID are more
`likely to be disease dependent, while the psychological and
`social eVects are disease independent and are better
`predicted by cognitive function, knowledge, socioeconomic
`status, education, personality, coping strategies, social
`support network, culture, beliefs, and so on.5
`
`1966–1975
`
`1976–1984
`
`1985–1990
`
`1991–1995
`
`1996–1999
`
`0
`
`100
`
`200
`
`400
`300
`No of citations
`Figure 1 Number of quality of life related citations in the fields of
`gastroenterology and hepatology obtained from MEDLINE searches over
`diVerent time intervals.
`
`500
`
`600
`
`700
`
`Summary
`Modern medicine has had a considerable impact on mor-
`tality rates for serious illness. Many chronic diseases which
`have previously been associated with an increased
`mortality now have survival rates approaching those of the
`background population. However, chronic diseases such as
`cancer, chronic pain syndromes, and chronic inflammatory
`conditions impose a considerable burden on families, the
`health care system, and society. Health related quality of
`life (HRQOL) is a concept that has developed from the
`need to estimate the impact of such chronic diseases.
`HRQOL measurement is a conceptual framework which
`attempts to predict daily function and well being based on
`subjective attitudes and experiences of physical, social, and
`emotional health. It has been evaluated predominantly
`from the patient’s viewpoint as proxy respondents appear
`to underestimate the full eVect of chronic illness on func-
`tional status. Measuring HRQOL in clinical research is
`most frequently undertaken using multi-item question-
`naires to estimate daily function. Factors which aVect
`HRQOL can be broadly classed as disease related and dis-
`ease independent. The use of diVerent assessment
`techniques permits comparisons between and within
`disorders. Generic and disease specific instruments used
`together enhance the ability to direct
`treatment
`for
`individuals and patient populations. Psychometrically
`sound questionnaires must be used. However, the type of
`instrument and research methods adopted depend on the
`question of interest. We have attempted to catalogue and
`critically assess the disease specific instruments used in the
`assessment of chronic gastrointestinal disease.
`
`Introduction
`Chronic gastrointestinal disorders (GID) such as gastro-
`oesophageal reflux disease (GORD), non-ulcer dyspepsia
`(NUD), irritable bowel syndrome (IBS), and inflammatory
`bowel disease (IBD) have mortality rates similar to the
`general population. Hospitalisation and surgical rates for
`these disorders are easily predicted by disease severity
`while daily functioning, well being, and life satisfaction,
`important features of HRQOL, are better predictors of
`ambulatory health services used.1 Direct costs in Canada
`for chronic GID were $3.32 billion in 1997, fourth after
`cardiovascular,
`respiratory,
`and mental
`disorders.2
`HRQOL assessment thus provides an important yardstick
`to assess these conditions by promoting patient involve-
`ment
`in management,
`fuller measurement of disease
`impact, and implementation of the most cost eVective
`strategies.
`The number of publications in gastroenterology claim-
`ing to address quality of life (QOL) and HRQOL has
`increased dramatically in recent decades, as shown in fig 1.
`However, most reports merely pander to the sensitive new
`age approach to chronic illness and do not truly evaluate
`HRQOL. We have therefore attempted to catalogue and
`critically evaluate the published HRQOL instruments per-
`taining to gastrointestinal diseases, particularly addressing
`their psychometric properties and clinical applications.
`
`Abbreviations used in this paper: HRQOL, health related quality
`of life; QOL, quality of life; IBD, inflammatory bowel disease;
`GORD, gastro-oesophageal reflux disease; NUD, non-ulcer
`dyspepsia; IBS, irritable bowel syndrome; CDAI, Crohn’s disease
`activity index; SF, short form; SIP, sickness impact profile; PGWB,
`psychological general well being; GID, gastrointestinal disorder; GI,
`gastrointestinal; GIQLI, gastrointestinal quality of life index; ICC,
`intraclass correlation coeYcient; GSRS, gastrointestinal symptom
`rating scale; PUD, peptic ulcer disease; GORQ, gastro-oesophageal
`reflux questionnaire; MOS, medical outcomes study; HBQOL,
`heartburn quality of Life; QPD, quality of life in peptic disease;
`FDDQL, functional digestive disorders quality of life questionnaire;
`DU, duodenal ulcer; QOLRAD, quality of life in reflux and
`dyspepsia; QLDUP, quality of life in duodenal ulcer patients; HPAG,
`Helicobacter pylori associated gastritis; SCL90-R, symptom checklist;
`IBSQ, irritable bowel syndrome questionnaire; RFIPC, rating form
`of inflammatory bowel disease patient concerns; UC, ulcerative
`colitis; CD, Crohn’s disease; IBDQ, inflammatory bowel disease
`questionnaire; STAI, state-trait anxiety inventory; NTC, normal
`transit constipation; STC, slow transit constipation; EORTC
`QLQ-C30, European Organisation for Research and Treatment of
`Cancer core quality of life questionnaire; TG, total gastrectomy; SG,
`subtotal gastrectomy; TG+R, total gastrectomy plus gastric
`reconstruction; RSC, Rotterdam symptom checklist; HPN, home
`parenteral nutrition; QALY, quality adjusted life year; CLDQ,
`chronic liver disease questionnaire; HCV, hepatitis C virus; HBV,
`hepatitis B virus; IFN, interferon.
`
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`
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`QOL in GI disease
`
`445
`
`Table 1 Specific problems, issues and domains of health related quality of
`life (HRQOL) instruments
`
`Leisure and recreation
`xTravel
`xFood/drink
`xVisit friends’ homes
`xVacation
`xNearness to toilet facilities
`xHobbies and sports
`Relationships
`xIntimacy and sexual function
`xBody image
`xUnderstanding from others
`xCoping and support
`xRelations with children and extended family
`xFriendships
`Pain and discomfort
`xChest pain
`xAbdominal pain
`xAbdominal cramps
`xAbdominal discomfort
`xRectal pain
`xBack pain
`xHeadaches
`xExtraintestinal pain
`xJoint pain
`Well being
`xEnergy
`xFatigue
`xSleep
`xSelf-control
`
`Mobility and self-care
`xWalking
`xRunning
`xClimbing
`xEating
`xGrooming
`xPhysical endurance
`Emotional
`xAnger
`xEmbarrassment
`xAnxiety
`xIrritability
`xHappiness
`xWorries or fears
`xAbility to relax
`xFrustration
`xDepression/sadness
`xSatisfaction
`Job-education
`xSatisfaction
`xAttendance
`xConcentration
`Task completion
`xAchievement/promotion
`xFinancial reward
`Treatment
`xEYcacy
`xAdverse eVects
`
`APPLYING HRQOL MEASUREMENT
`HRQOL measurement is important to patients, clinicians,
`researchers, and policy makers. Potential applications
`include identification of the problems of individuals or
`populations, assessment of quality of health care delivery,
`enhancement of disease related knowledge, and measure-
`ment of treatment eYcacy or disease outcome.6 HRQOL
`assessment is also a critical component of pharmaco-
`economic evaluation.
`
`HRQOL MEASUREMENT
`The development and full psychometric testing of a new
`HRQOL instrument generally takes several years to
`complete. Excellent review articles4–7 have addressed the
`detailed methodological process, which we will briefly
`summarise.
`The three main types of HRQOL instrument are global,
`generic, and disease specific and the benefits of each are
`shown in table 2.8 The global assessment measures a single
`attribute using a visual analogue or graded scale to
`summarise overall function. For example, 80% of patients
`have “good” HRQOL. These assessments, although easy
`to perform, do not identify specific areas of dysfunction.3
`Generic instruments are multi-item questionnaires address-
`ing various aspects of health and well being and have been
`derived in the general population, which includes both
`healthy subjects and people with acute or chronic illnesses.
`They are the most likely to detect an unexpected disease
`
`impact but may be unable to quantify clinically important
`dysfunction or change in function.4 For example, a generic
`instrument will not address abdominal pain, urgency, or
`fear of leaving the house, problems experienced by many
`IBS patients, but does emphasise mobility and grooming,
`which are not common IBS problems. Until recently,
`generic assessments have represented the predominant
`method of measuring HRQOL in GID. Instruments such
`as the sickness impact profile (SIP),9 psychological general
`well being (PGWB) scale,10 and short form 36 (SF-36)11
`are the most commonly used and allow a direct
`comparison between individuals or populations with
`diVerent diseases. Several, together with their psychomet-
`ric properties, are listed in table 2. Disease
`specific
`instruments are designed for patients with a particular dis-
`ease to identify the most
`relevant problems. Such
`instruments are generally more sensitive to patient
`concerns and changes in health status.4 The major
`disadvantages are that no specific instrument is available
`for many disorders and that some unanticipated problems
`may be easily overlooked. To optimise HRQOL assess-
`ment, many studies now use both generic and disease spe-
`cific instruments.
`The important steps to develop and psychometrically
`test a HRQOL instrument are outlined in tables 3 and
`4.4 7 12 13 We will focus primarily on disease specific instru-
`ments but highlight a few important studies that have used
`generic instruments.
`
`Search methods
`To identify all disease specific HRQOL measures used in
`gastrointestinal
`(GI) or
`liver disease,
`a
`thorough
`MEDLINE search from 1966 to September 1999 of fully
`published articles in English using the search terms “qual-
`ity of life”, “liver disease”, and “gastrointestinal disease”
`was performed. Reference lists of relevant citations were
`also reviewed to ensure complete retrieval. Studies
`combining previously validated questionnaires were not
`considered as separate instruments.
`
`The GIQLI
`The gastrointestinal quality of life index (GIQLI) was
`developed by Eypasch and colleagues to measure HRQOL
`in multiple GIDs.14 The questionnaire contains up to 36
`items, scored on a five point Likert scale (range 0–144,
`higher score=better QOL), in which additional modules,
`specified by the particular GID, supplement a set of core
`questions. Construct validity was supported by demon-
`strating a reasonable correlation with the Spitzer quality of
`life index (r=0.53) and the Bradburn aVect balance scale
`(r=0.42) in 204 German patients with a variety of GI
`illnesses. Patients with the most severe GID had a mean
`GIQLI score of 45 (14.8) compared with healthy controls
`
`Table 2 Commonly used health related quality of life (HRQOL) instruments in gastrointestinal disorders
`
`Global assessment
`Visual analogue scale (10 cm line)
`Graded scale (excellent, very good, good, poor, extremely poor)
`Utility (standard gamble or time trade oV; 0.0 death to 1.0
`perfect health)
`Generic instrument
`Sickness impact profile132 (136 items, 12 subscores; higher
`score=poorer HRQOL)
`Short form 36133 (36 items, 8 subscores; score 0, worst–100 best)
`Grogono and Woodgate134 (20 items, 10 subscales)
`Psychological general well being135 (22 items; 6 subscales
`(anxiety, depression, well being, self-control, health, vitality);
`reliability 0.61–0.89; score 22–132, lower score better)
`Euro-QOL136 (5 items utility)
`Disease specific instrument
`See specific tables
`
`Advantage
`Simple summary
`Easily administered and scored
`Important for economic analysis
`
`Disadvantage
`Reasons for dysfunction not clear
`May not detect small but important diVerences
`
`Permits comparison among diseases. May
`detect unanticipated eVects
`
`Complex to administer and score. May miss
`important clinical change
`
`Reflects problems most important to a
`specific population. May be more
`sensitive to change with time or treatment
`
`Complex to administer and score. May miss
`unexpected eVects
`
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`
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`446
`
`Borgaonkar, Irvine
`
`Table 3 Steps in developing a generic or disease specific health related
`quality of life (HRQOL) instrument
`
`Step
`
`Method
`
`Item generation12
`
`Item reduction12
`
`Pre-testing12
`
`Psychometric
`assessment4
`
`Cross cultural
`adaptation13
`
`Identify all possible consequences of a particular disorder
`Literature review
`Patient focus groups
`Expert opinion
`Reduce items to a manageable number.
`Most prevalent issues (frequency)
`Greatest impact (important)
`Facilitated by factor analysis
`Ensure clear wording, patient understanding, and
`acceptability
`Validity
`Reliability
`Responsiveness
`Independent forward and backward translation.
`Harmonisation among questionnaires.
`Pre-testing and examining score weighting.
`
`who had a mean score of 125.8 (13). The GIQLI also dis-
`criminated well between patient groups when stratified by
`illness severity. The test-retest reliability was excellent
`(intraclass correlation coeYcient (ICC) 0.92), as was
`internal consistency (Cronbach’s alpha >0.90). In 194
`patients who underwent laparoscopic cholecystectomy for
`biliary colic, a significant improvement (responsiveness)
`was observed from a mean score preoperatively of 87.3
`(17.3)
`to 111.7 (14.6)
`six weeks postoperatively
`(p<0.001), although changes in specific subscores were not
`reported. The concept of a modular questionnaire, similar
`to combining disease specific and generic instruments,
`holds promise if it is shown to be psychometrically robust
`in other GIDs.
`
`Harris and colleagues used decision modelling to
`compare three medical strategies for preventing recurrence
`of erosive oesophagitis.19 They determined that the degree
`of QOL impairment could be used to select the optimum
`therapy; that subjects with poor QOL could be treated
`more cost eVectively with an initial proton pump inhibitor
`and those with less impaired QOL should receive a H2
`receptor antagonist first. Such findings, using generic
`measures, can be greatly complemented by applying
`disease specific instruments. To date, five disease specific
`HRQOL instruments for GORD have been published and
`are shown in table 5.
`The gastrointestinal symptom rating scale (GSRS) was
`developed by Svedlund et al
`in 1988 to discriminate
`between several GIDs.20 Items were selected primarily from
`IBS and peptic ulcer disease (PUD) symptoms, using
`clinical experience and a literature review. Initial validation
`was performed for a physician administered 15 item ques-
`tionnaire, with items such as epigastric pain, heartburn,
`and eructation scored on a four point Likert scale. A sub-
`sequent self-administered version, using a seven point Lik-
`ert scale, was shown to have good internal consistency, and
`factor analysis identified five important domains: abdomi-
`nal pain syndrome, reflux syndrome, indigestion syndrome, diar-
`rhoea syndrome, and constipation syndrome.21 In a mixed
`patient population, the GSRS discriminated well between
`patients with PUD, oesophagitis, and a normal endoscopy
`on all domains (p<0.01) except the constipation syndrome,
`with the most marked diVerence being noted in the reflux
`syndrome (p<0.00001).21 Revicki et al recently undertook
`further validation and responsiveness testing in 516
`GORD patients before and six weeks after administration
`HRQOL in gastro-oesophageal reflux disease
`of
`ranitidine 150 mg twice daily.22 They observed
`Symptoms of GORD occur monthly in approximately 40%
`significant correlations between subscores of the GSRS,
`and daily in 7% of the adult population.15 Twenty four per
`SF-36, and PGWB index (r =−0.43 to −0.21; p<0.0001).
`cent of suVerers will consult a physician, often fearing a
`Mean subscores in all five domains significantly discrimi-
`serious condition such as cancer.16 Specific symptoms,
`nated between responders and non-responders (2.79 v
`such as heartburn, regurgitation, or chest pain, substan-
`3.24, respectively; p<0.0001). The greatest improvement
`tially impair HRQOL and over half of patients require
`occurred in the reflux domain, with therapy producing a
`intermittent or continuous therapy.17 McDougall et al
`mean decrease in score of 1.23 in responders and 0.46 in
`assessed long term HRQOL in GORD using a postal
`non-responders (p<0.0001). This identified a clinically
`survey.11 After 10 years, 70% of 101 respondents reported
`important score change of approximately 1.0 and sug-
`persistent symptoms or the need for ongoing therapy. The
`gested the reflux subscore as the most important for GORD.
`mean SF-36 physical function subscore was significantly
`Galmiche et al used the GSRS as an outcome in a double
`worse in GORD patients than in the general population
`blind trial of omeprazole 10 mg or 20 mg daily versus
`(65.4 v 79.7; p=0.038) but was similar to that of patients
`cisapride 10 mg four times daily in 424 patients with mild
`with acute myocardial infarction (69.7). The mean social
`GORD.23 The global GSRS score improved in all treatment
`function was even lower for GORD than for congestive
`groups while the reflux domain improved significantly in the
`heart
`failure (71.3)18 and was significantly impaired
`omeprazole 20 mg group compared with the cisapride group
`compared with the general population (62.5 v 83.3;
`(−1.50 v −0.98; p=0.001). In a similar trial, Havelund et al
`p<0.001). These results suggest that patients with GORD
`compared omeprazole 10 mg or 20 mg daily with placebo in
`feel as seriously aVected as do patients with important
`408 endoscopically normal GORD patients.24 After four
`cardiovascular disease.
`Table 4 Key properties of a methodologically robust health related quality of life (HRQOL) instrument
`
`Property
`
`Definition
`
`Method of assessment
`
`Measures what it is supposed to measure
`Adequately samples most important areas of interest
`Relationship between score and a hypothesis of what is being
`measured
`Criterion12 (convergent) Relationship between new questionnaire and an accepted
`reference
`Instrument can distinguish between two groups of dissimilar
`patients
`
`Validity
`Face12
`Content12
`Construct12
`
`Discriminative4
`
`Reliability
`Test-retest4
`
`Ratio of between patient variation to total variation in score
`
`Internal consistency4
`
`Responsiveness4
`
`Correlation of items within same domain or with the full
`questionnaire score
`Signal to noise ratio of change with time
`
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`
`Full literature review, expert opinion, patient input (eg focus groups)
`Pre-testing with item reduction or augmentation
`Instrument compared with another marker of illness to determine if
`it behaves as predicted
`Instrument compared to an accepted reference measure that
`evaluates the same or similar features
`QOL scores for patients with diVerent disease severity or diVerent
`patterns of disease should diVer significantly
`
`Patients who remain stable should have little change in QOL scores
`on repeated measures. Described by intraclass correlation coeYcient
`(ICC) (0–1, 1 perfect agreement)
`Cronbach’s alpha coeYcient (0–1, 1 excellent)
`
`Patients with clinically important change (improve or deteriorate)
`should have significant change in QOL score
`
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`QOL in GI disease
`
`447
`
`Table 5 Gastro-oesophageal reflux disease (GORD) specific health related quality of life (HRQOL) instruments
`
`Instrument
`
`Items/scoring* Domains
`
`GSRS20 22
`GORQ26
`
`15/105–15
`76/NS
`
`GORD-HRQL27 10/45–0
`
`HBQOL30
`QOLRAD32
`
`15/0–100
`25/25–175
`
`Reflux, diarrhoea, constipation, pain, indigestion
`Heartburn, regurgitation, eVect of heartburn, pain,
`dysphagia, UGI, respiratory, past history, medications,
`past treatments, miscellaneous
`NS
`
`Validity
`
`Face
`
`L, E
`L, E
`
`Reliability
`
`Content
`
`Construct
`
`IC
`
`TR
`
`Factor analysis SF-36, PGWB
`3 field tests
`NT
`
`0.60–0.85 ICC 0.42–0.6
`♭ 0.70
`NT
`
`Endoscopic
`oesophagitis
`SF-36
`NT
`L, E
`Role physical, pain, sleep, diet, social, mental health
`Emotional, sleep, eating problems, physical/social, vitality L, E, P Factor analysis SF-36, GSRS
`
`E
`
`NT
`
`NT
`
`NT
`
`0.75–0.91 NT
`0.89–0.94 NT
`
`*Scores range from worst to best QOL.
`NS, not stated; NT, not tested; IC, internal consistency (Cronbach’s alpha); TR, test-retest.
`L, literature review; E, expert opinion; P, patient interviews.
`
`weeks, the reflux dimension improved significantly in both
`omeprazole groups (p=0.003—10 mg, p=0.0001—20 mg)
`as well as in the omeprazole 20 mg compared with the 10 mg
`group (p=0.04). These data provide further evidence that
`the GSRS, particularly the reflux domain, can measure clini-
`cally important changes in HRQOL.
`Locke et al focused on GORD related symptoms from a
`general bowel questionnaire25 adding the medical out-
`comes study (MOS) short form 20 (SF-20) to produce the
`gastro-oesophageal reflux questionnaire (GORQ).26 The
`final 76 item instrument had acceptable test-retest reliabil-
`ity (kappa 0.70) but
`the authors have not yet
`fully
`examined the validity or responsiveness, thereby limiting
`the current usefulness of this instrument.
`the gastro-
`A third GORD specific
`instrument,
`oesophageal reflux disease health related quality of life scale
`(GORD-HRQL), was developed by Velanovich and
`colleagues.27 This 10 item questionnaire was drafted using
`clinician opinion (face validity), scored using a six point
`Likert scale, and administered to 72 patients with severe
`GORD before and after medical or surgical therapy. The
`GORD-HRQL score discriminated well between individu-
`als based on their satisfaction with current symptoms
`(median score 26 in the unsatisfied v 5 in the satisfied
`group; p<0.0001). Surgical patients were more greatly
`improved than medical patients (median improvement 27.5
`v 11, respectively; p=0.002). However, the scores correlated
`poorly with pretreatment 24 hour pH testing (r=0.09;
`p=0.7), lower oesophageal sphincter pressures (r= −0.21;
`p=0.24), and the SF-36 and subscores.28 Although scores
`correlated moderately with the endoscopic oesophagitis
`grade (r=0.53; p<0.001),29 further assessment is clearly
`needed before it can be recommended for clinical research.
`A fourth disease specific instrument, the heartburn
`quality of life (HBQOL), was developed by Young and
`colleagues.30 Validation of the 15 items against the SF-36
`was undertaken but raw data supporting a claim of moder-
`ate correlation were not provided. A 12 item version with
`six domains was later used in a randomised trial.31 Dimen-
`sional scores were significantly better than placebo in
`patients given ranitidine 150 mg twice daily for six weeks
`for heartburn pain (72.4 v 62.8; p<0.001), sleep (87.6 v
`80.8; p<0.001), diet (83.7 v 76.0; p<0.001), and mental
`
`health (73.8 v 67.2; p<0.001). Unfortunately, the HBQOL
`was not administered before treatment thereby precluding
`full responsiveness assessment. This questionnaire will
`require further psychometric testing.
`The final GORD specific HRQOL instrument is the
`quality of life in reflux and dyspepsia (QOLRAD), a 25
`item questionnaire, with each item scored on a seven point
`Likert scale, and five subscores.32 Items were generated
`using “focus groups” of patients with GORD or NUD and
`were then tested in 759 patients referred for endoscopy in
`five countries. Construct validity was supported by its cor-
`relation with almost all domains of the SF-36 (r=0.44–
`0.71), GSRS (r=0.29–0.63), and severity (r=−0.31 to
`−0.38) or frequency of symptoms (r= −0.27 to −0.34), as
`judged by clinicians. QOLRAD scores also significantly
`discriminated between patients who did or did not use
`concomitant sedatives for anxiety (mean emotional scores
`3.4 v 4.2, respectively). Responsiveness of the QOLRAD
`has not yet been determined.
`Disease specific instruments can therefore discriminate
`GORD from other disorders, can stratify patients by sever-
`ity, and are useful as outcomes in clinical trials and decision
`modelling. Overall,
`the GSRS has been the most
`extensively evaluated of the GORD instruments and has
`favourable psychometric properties, making it more attrac-
`tive currently than the other questionnaires.
`
`Dyspepsia
`Functional dyspepsia, or NUD, occurs in approximately
`25% of the general population.33 Despite normal investiga-
`tions, subjects experience considerable anxiety and dem-
`onstrate health care seeking behaviour.34 Patients with
`NUD describe abdominal pain,
`interruption of daily
`activities,35 and decreased sexual drive.36 An important
`barrier to dyspepsia research has been the diYculty in
`quantifying the severity of the subjective complaints,37
`which has led to the development of several disease specific
`instruments, shown in table 6.
`An Italian group, led by Bamfi, developed the quality of
`life in peptic disease questionnaire (QPD).38 Items were
`generated by patients with confirmed PUD, oesophagitis,
`or NUD. A 30 item questionnaire was then administered to
`several patient groups and validation by factor analysis
`
`Table 6 Dyspepsia specific health related quality of life (HRQOL) instruments
`
`Instrument
`
`Items/scoring* Domains
`
`Face
`
`Content
`
`Construct
`
`IC
`
`TR
`
`30/NS
`QPD38
`FDDQL39
`43/0–100
`QOLRAD32
`25/25–175
`QLDUP40
`54/NS
`Not named42 8/40–8
`
`SF-36
`L, E, P 2 field tests
`Anxiety, social, symptom perception
`SF-36
`Activities, anxiety, diet, sleep, discomfort, coping, control, stress L, E, P 3 field tests
`Emotional, sleep, eating problems, physical/social, vitality
`L, E, P Factor analysis SF-36, GSRS
`SF-36 + PGWBI, family circle, food, drink, coVee-tobacco, pain E, P
`NT
`NT
`NS
`L, E
`1 field test
`NT
`
`0.73–0.91 NT
`0.69–0.89
`0.98
`0.89–0.94 NT
`>0.70
`0.73
`NT
`0.69–0.82
`
`Validity
`
`Reliability
`
`*Scores range from worst to best QOL.
`NS, not stated; NT, not tested; IC, internal consistency (Cronbach’s alpha); TR, test-retest.
`L, literature review; E, expert opinion; P, patient interviews.
`
`www.gutjnl.com
`
`Bausch Health Ireland Exhibit 2048, Page 4 of 11
`Mylan v. Bausch Health Ireland - IPR2022-00722
`
`

`

`448
`
`Borgaonkar, Irvine
`
`Table 7 Irritable bowel symdrome (IBS) specific health related quality of life (HRQOL) instruments
`
`Instrument
`
`Items/scoring* Domains
`
`Face
`
`Content
`
`Construct
`
`IC
`
`TR
`
`Validity
`
`Reliability
`
`IBS-QOL51
`
`34/0–100
`
`IBSQ52
`IBSQOL49
`
`26/26–182
`30/0–100
`
`FDDQL39
`
`43/0–100
`
`Dysphoria, activity, body image, anxiety, food avoidance,
`social, sexual relations, relationships
`Symptoms, fatigue, activity, emotional
`Emotional, mental health, health belief, sleep, energy, physical
`functioning, diet, social role, physical role, sexual relations
`Activity, anxiety, diet, sleep, discomfort, coping, control, stress L, E, P 3 field tests
`
`L, E, P 2 field tests
`
`SF-36, PGWB,
`SCL90-R
`NT
`L, E, P 1 field test
`L, E
`2 field tests NT
`
`0.65–0.92
`
`0.69–0.89
`
`NT
`NT
`0.66–0.93 NT
`
`SF-36
`
`0.69–0.89
`
`0.98
`
`*Scores range from worst to best QOL.
`NT, not tested; IC, internal consistency (Cronbach’s alpha); TR, test-retest.
`L, literature review; E, expert opinion; P, patient interviews.
`
`demonstrated three domains: anxiety induced by pain, social
`restrictions, and symptom perception. Low to moderate corre-
`lations were observed with all domains of the SF-36
`(r=0.26–0.60)
`(construct validity). Responsiveness
`to
`change was shown by a significant improvement in the total
`score (mean change 11.5; p=0.001) and dimensional
`scores (mean change 2.8–4.9; p=0.001) four weeks after
`Helicobacter pylori eradication. Cross cultural adaptation in
`non-Italian patients has not yet been reported.
`life
`The functional digestive disorders quality of
`questionnaire (FDDQL), developed by Chassany et al to
`measure QOL in patients with functional dyspepsia or IBS,
`has been assessed in French, German, and English patients
`with dyspepsia.39 Seventy four items were later reduced to
`43 and scored using a five point Likert scale within eight
`domains. The FDDQL discriminated well among patients
`with diVerent degrees of handicap as assessed by the inves-
`tigators. This was most marked for the mean daily activity
`score (80 in patients with no handicap v 36 for extreme
`handicap; p<0.05). Construct validity of the FDDQL was
`supported by significant correlations between its subscores
`and those of the SF-36. The correlation was strongest
`between the daily activity score and both the SF-36 physi-
`cal
`role limitation and bodily pain subscores (r=0.63,
`p<0.0001). The FDDQL is currently being evaluated to
`determine its ability to detect change.
`Martin et al developed the quality of life in duodenal
`ulcer patients (QLDUP) by combining the SF-36, PGWB
`index, and 13 disease specific items derived from patient
`and clinician interviews.40 The 54 item instrument with 15
`dimensions was administered to French patients with acute
`duodenal ulcer (DU), a prior history of DU, or NUD, and
`showed good internal consistency (ICC >0.70) and
`test-retest reliability (Spearman’s coeYcient 0.73). Validity
`was claimed by identifying significant diVerences in scores
`between groups. However,
`the data to support
`this
`assertion were not provided. A subsequent trial by Rampal
`et al in 581 patients with a recently healed DU compared
`maintenance nizatidine (150 mg/day) with intermittent
`nizatidine therapy (300 mg/day as needed).41 Patients
`receiving daily maintenance therapy had significantly
`better HRQOL compared with the intermittent treatment
`group in seven of the 15 dimensions at one year follow up
`(p<0.05). Although these studies support the construct
`validity of the QLDUP, responsiveness and assessment in
`other languages are lacking at this time.
`A short eight item questionnaire using a five point
`response scale, developed by Veldhuyzen van Zanten et al,
`was pilot tested in 10 patients with NUD and 14 with
`H pylori associated gastritis (HPAG).42 It was then admin-
`istered to 55 patients with NUD or HPAG before and four
`weeks after antacid or H pylori eradication therapy, respec-
`tively. The instrument was responsive to change for both
`NUD (mean change −2.7; p=0.003) and HPAG (mean
`change −3.6; p=0.002) showing a significant improvement
`in scores, which correlated with the patient’s self-reported
`global response (p<0.0001).
`
`The QOL-RAD, discussed above, has also been
`validated in dyspeptic patients (table 6).
`Each of the six disease specific HRQOL questionnaires
`for dyspepsia has undergone some psychometric evalua-
`tion supporting both validity and responsiveness. However,
`none has been satisfactorily assessed to warrant a
`recommendation for preferred use.
`
`Irritable bowel syndrome
`IBS is characterised by abdominal pain, altered bowel
`habit, and disturbed sensory and motor function with nor-
`mal bowel morphology.43 The prevalence ranges from 6.6%
`to 21.6% of
`the general population44 and results in
`approximately 3.5 million physician visits and 2.9 million
`prescriptions annually in the USA.45 Whitehead et al have
`shown that IBS patients have significantly poorer SF-36
`scores than healthy controls (general health 62.3 v 85.6;
`p<0.001).46 These patients have diYculty travelling,
`participating in sports, and attending social gatherings.
`Extraintestinal symptoms, such as back pain, headache,
`dyspareunia, urinary symptoms, and sleep disturbance are
`also more frequent
`in IBS patients than in healthy
`controls.47 These symptoms result in work absenteeism, job
`changes, and premature termination of employment.48 The
`lack of objective parameters to assess health status has
`prompted several groups to develop disease specific meas-
`ures of HRQOL for IBS, as shown in table 7.
`The first, the IBSQOL, was developed at UCLA by
`Hahn and colleagues.49 Each of 30 items is scored on a five
`or six point Likert scale and summed in nine subscores.
`The IBSQOL discriminated well between a control group
`with non-IBS GI disorders and unselected patients with
`IBS. A later study showed that the IBSQOL could also dis-
`criminate between IBS patients with diVerent disease
`severity.50 However, no data regarding the construct valid-
`ity or responsiveness have been published.
`The IBS-QOL, a 34 item instrument developed by
`Patrick et al, was reviewed by European gastroenterologists
`in Britain, Germany, Italy, and France during the item
`reduction phase to ensure cross cultural validity.51 A cross
`sectional survey of 169 patients with IBS demonstrated
`moderate construct validity with the SF-36 (r=0.30–0.44),
`PGWB (r=0.31–0.45), and the symptom check list
`(SCL90-R) (r =−0.27 to −0.46). The I