mesure de la qualité de vie liée à l’état de santé introduction to patient-reported outcomes...
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Mesure de la qualité de vie liée à l’état de santé
Introduction to Patient-Reported Outcomes (PROs)
March 2-4 2004, Karolinska Institutet, Sigtuna, Sweden
Olivier CHASSANY, MD, PhDDélégation à la Recherche Clinique (AP-HP)Hôpital Saint-Louis, Paris
Définition de l’OMS (dénominateur minimal commun)
« La santé, ce n’est pas seulement une absence de maladie, c’est aussi un état total de bien-être physique, psychologique et social »
« La qualité de vie est la perception qu’a un individu de sa place dans l ’existence, dans le contexte de la culture et du système de valeurs dans lesquels il vit en relation avec ses objectifs, ses attentes, ses normes et ses inquiétudes »
Définition de la Qualité de Vie liée à l’état de santé
La mesure de la qualité de vie est :
• Subjective (perception du patient)
• Se mesure idéalement par auto-questionnaire
• Multidimensionnelle• Dimensions minimales : physique, psychique et sociale• Dimensions spécifiques d’une pathologie ou condition
Définition de la Qualité de Vie liée à l’état de santé
“Health is a state of complete physical, mental, and social well-being and not merely the absence of disease”
(WHO 1948)
The value assigned to duration of life as modified by the impairments, functional states, perceptions and social opportunities that are influenced by disease, injury, treatment, or policy
(Pr Donald Patrick, Seattle USA)
Agreement on multidimensionality and subjective assessment
Definition of Health-Related Quality of Life (HRQL)
Une question unique ne suffit pas :
« Globalement, quelle est votre qualité de vie en ce moment ? »
Mesure de la Qualité de Vie liée à l’état de santé
PAST
• Health-Related Quality of Life (HRQL) is based on several decades of research
• Many studies, especially using generic questionnaires made it possible to appreciate how diseases affected HRQL
• Poor quality of clinical trials
• Abuse of “Quality of Life” trials
TODAY
• Rationale for the Added Value of HRQL in clinical trials
• Increased recognition of the patient’s perspective: Patient-Reported Outcomes (PRO)
• Agreement (more or less) on HRQL definition, multidimensionality and subjective assessment
• Availability of HRQL questionnaires correctly validated and translated for many diseases
• Guidelines on how measuring HRQL in clinical trials
• Increasing recognition of HRQL value by regulators
• Huge literature (too much ?)
Why should we measure the perception of patients ?
• Changes in the therapeutic targets in the growing context of chronic diseases and palliative treatment in a rising old population
• cancer• AIDS• heart failure• Parkinson’s disease • Alzheimer’s disease • asthma • COPD • osteoarthritis• diabetes …
• Nowadays, therapeutic benefits : • rarely curative, or prolonging survival, • but improving symptoms and functional status, and thus preserving or restoring HRQL
• Availability of PRO questionnaires correctly validated and translated for many diseases
The impact on HRQL is not always foreseeable
0 5 10 15 20 25 30 35
Overall Sickness Impact Profile score
Amyotrophic lateral sclerosis
Chronic pain non-responders
Oxygen dependent COPD
Chronic low back pain
Back pain
Physically disabled adults
Non-oxygen dependent COPD
Rheumatoid arthritis
End-stage hemodialysis
Hypothyroidism
Crohn's
Angina
Myocardial infarct
Ulcerative colitis
Moderate obesity
General population
Cardiac arrest
Group health enrolleesbetter HRQL lower HRQL
and is not systematically
correlated with the severity of the
disease as perceived by the medical
community
Patrick D, Erickson P. Health status and health policy. Quality of life in health care evaluation and resource allocation. Oxford University Press, 1993.
-40%
-30%
-20%
-10%
0%
10%
Physical
functioning
Role
functioning
Social
functioning Mental health
Health
perceptions Bodily pain
Patients w ith no chronic
conditions (n = 2595)Hypertension (n = 2706)
Diabetes (n = 844)
Congestive heart failure
(n = 297)Myocardial infarction (n
= 147)Arthritis (n = 2079)
Chronic lung problems
(n = 731)Gastrointestinal
disorders (n = 696) *Back problems (n = 486)
Angina (n = 532)
Stewart AL et al. Functional status and well-being of patients with chronic conditions. Results from the Medical Outcomes Study. JAMA 1989; 262: 907-913.
The impact on HRQL is not always foreseeable
““Objective” measureObjective” measure Exercise test versus physical functioning, r = 0.40
““Subjective” measureSubjective” measure
Wiklund I et al. Clin Cardiol 1991.
Which are the arguments in favour of HRQL ?
Slide presented with the authorization of Pr Ingela Wiklund
Weak correlation between Patient-Reported Outcomes and physiological endpoints
(n = 96) r BPQ CRQ
6-min walk test 0.17 0.07
Pre SaO2 0.14 0.17
Quality of life in elderly patients with COPD: measurement and predictive factors. Yohannes AM et al. Resp Med 1998.
Symptoms BPQ : Breathing Problems QuestionnaireHRQL CRQ : Chronic Respiratory Disease Questionnaire
Variability in exercise capacity contributed to only 3% of the variability in BPQ score
Correlation between glycemic control and perception of Quality of Life
Grey M, et al. Personal and family factors associated with quality of life in adolescents with diabetes. Diabetes Care. 1998 ;21: 909-914.
DQOLY (Diabetes Quality of Life for Youths)
Hb1Ac
Impact (23 items) r = - 0.21
Worry (23 items) r = - 0.28
Satisfaction (11 items) r = - 0.04
Niveau d’agrément de la perception d’un symptôme (douleur) entre patients et
médecins
Score de douleurs Agrément entre patients et leurs
médecins généralistes
Colopathie fonctionnelle r = 0,31
Maladie veineuse chronique r = 0,27
Chassany O, et al. Discrepancies between patient-reported outcomes (PROs) and clinician-reported outcomes in chronic venous disease (CVD), irritable bowel syndrome (IBS), and peripheral arterial occlusive disease (PAOD). Value in health. Under press
Niveau d’agrément de la perception de la qualité de vie entre patients et médecins
Score qualité de vie Agrément entre patients et leurs
médecins généralistes
Colopathie fonctionnelle (FDDQL)
r = 0,28
Maladie veineuse chronique (CIVIQ)
r = 0,17
Artériopathie chronique oblitérante des MI (CLAUS)
r = 0.26
Chassany O, et al. Discrepancies between patient-reported outcomes (PROs) and clinician-reported outcomes in chronic venous disease (CVD), irritable bowel syndrome (IBS), and peripheral arterial occlusive disease (PAOD). Value in health. Under press
Cross-sectional survey239 IBS patients57.5 ± 16 years64% women
-10
-8
-6
-4
-2
0
2
4
6
Phy
sici
an-P
atie
nt D
iffer
ence
-2 0 2 4 6 8 10 12Patient's VAS
Perception of pain : moderate agreement between IBS patients & physicians
r = 0.31
Chassany O, et ALFIS. Added value of patient’s perspective in irritable Bowel Syndrome. Qual Life Res 2003; 12: A821
Tendency of physician tounderestimate the pain
Tendency of physician tooverestimate the pain
The physician is more disposedto bear the pain of his/her patientthan the patient himself
IBS Patients Clinicians
VAS (0-10, worst) 3.9 ± 2.5 3.0 ± 2.1
Perception of Quality of Life by patients and clinicians in Irritable Bowel Syndrome
FDDQL (43 items) Patients (n = 239)
Clinicians (n = 163)
Daily activities 72 ± 21 58 ± 35 Anxiety 62 ± 22 54 ± 28 Diet 56 ± 23 60 ± 26 Sleep 59 ± 16 72 ± 26 Discomfort 55 ± 15 69 ± 25 Coping 49 ± 13 57 ± 26 Control 55 ± 23 59 ± 26 Stress 31 ± 25 43 ± 27
Global 56 ± 12 59 ± 19
Chassany O, Le Jeunne P, et ALFIS. Added value of patient’s perspective in Irritable Bowel Syndrome. Quality Life Res 2003; 12: A821
FDDQL : Functional Digestive Disorders Quality of Life 43 items / 8 domains, score 0-100 (best HRQL)
HRQL impairment is over/under estimated by clinicians in IBS
Relation score FDDQL apprécié par le médecin / score FDDQL apprécié par le patient pour le retentissement sur l'activité quotidienne
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pat
ient
Score FDDQLactivitéquotidienne
Scores égaux
Relation score FDDQL apprécié par le médecin / score FDDQL apprécié par le patient pour le degré d'anxiété
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médecin
patie
nt
Score FDDQLanxiété
Scores égaux
Relation score FDDQL apprécié par le médecin / score FDDQL apprécié par le patient pour le retentissement sur l'alimentation
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pati
en
t
ScoreFDDQLalimentation
Scoreségaux
Relation score FDDQL apprécié par le médecin / score FDDQL apprécié par le patient pour le retentissement sur le sommeil
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patie
nt
Score FDDQLsommeil
Scores égaux
r = 0.43r = 0.30
Perception of HRQL by patients and clinicians ? Survey among 239 IBS patients
and 163 clinicians
Daily Activities Diet
Anxiety Sleep
Relation score FDDQL apprécié par le médecin / score FDDQL apprécié par le patient pour le retentissement sur la vie sociale
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0 1 2 3 4 5médecin
patie
nt
Score FDDQL viesociale/incofortScores égaux
Relation score FDDQL apprécié par le médecin / score FDDQL apprécié par le patient sur la réaction face à la maladie
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médecin
patie
nt Score FDDQLréactionmaladieScores égaux
Relation score FDDQL apprécié par le médecin / score FDDQL apprécié par le patient sur la maîtrise de sa maladie
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ien
t
Score FDDQLmaîtrise maladie
Scores égaux
Relation score FDDQL apprécié par le médecin / score FDDQL apprécié par le patient sur l'impact du stress
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0 1 2 3 4 5médecin
patie
nt
Score FDDQLstress
Scores égaux
Perception of HRQL by patients and clinicians ? Survey among 239 IBS patients
and 163 clinicians
Social Life Control
Coping Stress
0
10
20
30
40
50
60
70
80
90
100
FD
DQ
L G
loba
l Sco
re
0 2 4 6 8 10Patient's VAS
239 IBS patients57.5 ± 16 years 64% of women Global FDDQL: 56.1 ± 11.6
Perception of pain and HRQL by patients with IBS
r = 0.63, p < 0.0001
Chassany O, Le Jeunne P, et ALFIS. Added value of patient’s perspective in Irritable Bowel Syndrome. Quality Life Res 2003; 12: A821
FDDQL : Functional Digestive Disorders Quality of Life 43 items / 8 domains, score 0-100 (best HRQL)
Pain VAS Patients
109876543210
Pai
n V
AS
Phy
sici
ans
10
9
8
7
6
5
4
3
2
1
0
Perception of pain by patients and clinicians in Chronic Venous Insufficiency
Patients (n = 233)
Clinicians (n = 120)
4.22 ± 2.48 2.97 ± 1.92
Pain perception is underestimated by clinicians in CVI
0 [best Pain] – 10 [worst Pain]
r = 0.27
Perception of Quality of Life by patients and clinicians in Chronic Venous Insufficiency
CIVIQ Patients (n = 240)
Clinicians (n = 120)
Physical Function 44 ± 25 31 ± 22 Pain 45 ± 20 30 ± 20 Social Function 38 ± 24 24 ± 21 Psychological Impact 35 ± 23 26 ± 21
Global 39 ± 20 28 ± 19
Chassany O, Le Jeunne P, et ALFIS. Added value of patient’s perspective in Chronic Venous Insuffisiency
CIVIQ : 20 items / 4 domains, score 0-100 (worst HRQL)
HRQL impairment is underestimated by clinicians
Relation score CIVIQ apprécié par le médecin / score CIVIQ apprécié par le patient pour le retentissement douleur
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0 1 2 3 4 5 6 7 8
médecin
patie
nt
Score CIVIQ douleur Scores égaux
Relation score CIVIQ apprécié par le médecin / score CIVIQ apprécié par le patient pour le retentissement activité physique
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médecin
patie
nt
Score CIVIQ activité physique Scores égaux
r = 0.29
Physical Function
Perception of Quality of Life by patients and clinicians in Chronic Venous Insufficiency
Physicians
Pati
ents
Impact of pain
Physicians
Pati
ents
r = 0.28
Relation score CIVIQ apprécié par le médecin / score CIVIQ apprécié par le patient pour le retentissement vie sociale
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médecin
patie
nt
Score CIVIQ vie sociale Scores égaux
Social Function
Physicians
Pati
ents
r = 0.23
Relation score CIVIQ apprécié par le médecin / score CIVIQ apprécié par le patient pour le retentissement psychologique
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médecin
patie
nt
Score CIVIQ psychologique Scores égaux
Psychological Function
Physicians
Pati
ents
r = 0.23
CIVIQ patients : 0 [best QoL] – 100 [worst QoL] - QoL physicians : 0 – 10 [maximal impact]
Perception of Quality of Life by patients and clinicians in Chronic Venous Insufficiency
Relation entre le score global attribué par le patient et celui attribué par le médecin
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10
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60
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100
0 1 2 3 4 5 6 7 8 9 10
score médecin
scor
e pa
tient
nuage de points droite de régression
Global QoL score
Physicians
Pati
ents
r = 0.33
CIVIQ patients : 0 [best QoL] – 100 [worst QoL] QoL physicians : 0 – 10 [maximal impact]
Correlation of pain versus Quality of Life in patients with Chronic Venous Insufficiency
CIVIQ : 0 [best QoL] – 100 [worst QoL] Pain VAS : 0 – 10 [worst pain]
0
10
20
30
40
50
60
70
80
90
100
0 1 2 3 4 5 6 7 8 9 10
Pain VAS
CIV
IQ g
lob
al s
core
Patients : pain vs QoL
r = 0.78
Perception of pain by patients and clinicians Results of a survey in 3 chronic diseases
Patients Clinicians
IBS 3.9 ± 2.5 3.0 ± 2.1 Venous insufficiency 4.2 ± 2.5 3.0 ± 2.0 Arteriopathy 3.5 ± 2.0 4.3 ± 2.1
Pain : from 0 to 10 [worst pain]
Pain perception is underestimated by clinicians in irritable bowel syndrome (IBS) and chronic venous insufficiency and overestimated in peripheral arteriopathy
Perception of HRQL by patients and clinicians in Peripheral Arteriopathy Occlusive Disease
CLAU-S (43 items) Patients (n = 68)
Clinicians (n = 61)
Daily Life 57 ± 28 47 ± 27 Pain 64 ± 20 55 ± 21 Social Life 76 ± 18 57 ± 26 Fear 65 ± 28 56 ± 26 Mood 72 ± 24 63 ± 28
Global 66 ± 23 54 ± 21
Chassany O, Le Jeunne P, et ALFIS. Added value of patient’s perspective in Arteriopathy
CLAU-S : 43 items / 5 domains, score 0-100 (best HRQL)
HRQL impairment is over-estimated by clinicians
• Clinicians’ and patients’ perspectives although overlapping, are not similar
• Clinicians tend to underestimate the pain intensity of their patients
• Similarly, patient’s perception of pain cannot completely reflect the impact of QoL
• Symptoms (e.g. pain) and QoL although overlapping to some extent measure different concepts
• Patient’s perspective is a major outcome in the evaluation of therapies
Patient-reported Outcomes (PROs) are in many conditions as important as other
outcomes
Weak correlation between HRQL & symptoms
Chassany et al. Validation of a specific quality of life questionnaire in functional digestive disorders (FDDQL). Gut 1999.
• e.g. Irritable Bowel Syndrome (IBS)• The absence of abdominal pain (e.g. during a
consultation with a physician) may not be linked with a good HRQL. The patient :
• May be anxious not to know when the next bout will occur
• May be limited in his inter-personal life and his leisure's• Constrained to take drugs and to pay attention to food
• The same is true in asthma, migraine, osteoarthritis, acne, heart failure, HIV (e.g. impact of lipodystrophia induced by antiretroviral therapy, even in patients who have not yet the side effect) …
Highresolution
CT
SaO2
FEV1
MaximalCapacityExercise
MRCDyspnea
Scale
ProxyCaregiver
Family
Satisfaction HRQL(QWB,SIP)
Physiological
Clinician-Reported
CaregiverPatient-
Reported
0.84
0.750.57
0.33-0.40
0.40
Chassany O. De la maladie chronique à la qualité de vie. Méthodes d’évaluation. Rev Mal Respir 2003; 20: S38-41.
Cystic fibrosis : Correlation between different endpoints
24 adolescents (11-18 yrs) with CF, their mothers, and their fathers completed the Child Health Questionnaire during routine CF clinic visits at 2 urban hospitals.
Health Scale Adolescents Mothers Fathers General health 0.73 0.73 0.54 Physical functioning 0.37 0.70 0.64 Role/social-physical 0.47 0.73 0.60 Bodily pain 0.42 0.55 0.37 Role/social-emotional 0.39 -0.01 0.11 Role/social-behavior -0.21 0.03 0.06 Mental health 0.27 0.28 -0.05 Family activities 0.34 0.37 0.18 Self-esteem 0.24 0.05 -0.23 Behavior problems -0.04 -0.21 -0.36
Correlation between adolescent pulmonary function (FEV1) and perception of health
Adolescents with cystic fibrosis: family reports of adolescent quality of life and forced expiratory volume in one second. Powers PM et al. Pediatrics 2001; 107: E70.
24 adolescents (11-18 yrs) with CF, their mothers, and their fathers completed the Child Health Questionnaire during routine CF clinic visits at 2 urban hospitals.
Health Scale Mothers Fathers General health 0.66 0.57 Physical functioning 0.69 0.31 Role/social-physical 0.62 0.49 Bodily pain 0.69 0.37 Role/social-emotional -0.12 0.24 Role/social-behavior 0.48 0.17 Mental health 0.33 0.48 Family activities 0.45 -0.09 Self-esteem 0.41 0.65 Behavior problems 0.71 0.66
Correlation between adolescent vs mother and father reports of perceived adolescent
Health
Adolescents with cystic fibrosis: family reports of adolescent quality of life and forced expiratory volume in one second. Powers PM et al. Pediatrics 2001; 107: E70.
• Erosion of self-image and self-esteem
• Problems in social and sexual relations
• Threat to loss of control
• Forced HIV disclosure
• Demoralization and depression
• Clinicians’ minimization of the importance of lipodystrophy
Psycho-social impact of lipodystrophy
Collins E, Wagner C, Walmsley S. Psychosocial impact of the lipodystrophy syndrome in HIV infection. AIDS Read 2000; 10: 546-550
Factors associated with severe impact of lipodystrophy on the Quality of Life
• 84 asymptomatic HIV patients with clinical lipodystrophy (LD)
• Dermatology Life Quality of Life Index (DLQI)
• Impact of body fat changes on their HRQL– Influenced dressing 65%– Produced feeling of shame 49%– Disrupted Sexual life 27%
Blanch J et al. Factors associated with severe impact of lipodystrophy on the quality of life of patients infected with HIV-1. Clin Infect Dis 2004.
I look like
a monster
I don’t recognize
Myself in mirror
Everybody can see
I’ve got HIV
I’m thinking aboutstoppingtreatment
Everything is all
right, CD4, viral load…
I need a plasticSurgery
Impact of Lipodystrophy (HIV) on Quality of Life
The impact of Lipodystrophy (HIV) on HRQL is not The impact of Lipodystrophy (HIV) on HRQL is not adequately captured by other criteriaadequately captured by other criteria
ViralLoad
CDC LipodystrophySign Score
LipodystrophySign Score
LipodystrophySatisfaction
Score Lipodystrophy
Specific HRQL
ABCD Score
BiologicalMarkers
InternationalClassification
Clinician- Reported
Patient-Reported Outcomes (PROs)
r=0.17
p=NSr=0.13
r=0.03
MOS-HIV
SF-12
r=0.58
r=0.2-0.7
r=0.65
r=0.39
CD4
r=0.43Duracinsky M, Chassany O. Agreement between patients’ and clinicians’-reported outcomes in lipodystrophy (HIV/AIDS). Value in Health 2004; 7: 641
Conclusion
• Clinicians’ and patients’ perspectives although overlapping, are not similar
• Lipodystrophy impacts QoL• Clinicians cannot infer the QoL of their patients
neither from a biological marker nor from a clinical exam
• The different PROs although overlapping, measure each a distinct concept
• The patient's perspective is essential in medical decision making : the psychological and social distress related to the body changes must be measured in clinical trials, to make sure that life is not lengthened at the expense of its quality
• ABCD questionnaire is validated in French
HRQL as a survival predictor for patients with advanced head and neck carcinoma treated with
radiotherapy
Changes in the HRQL scales during radiotherapy were not significantly correlated with survival
An increase in the baseline fatigue score of 10 points corresponded to a 17% reduction in the likelihood of survival (95%CI: 8-27%)
Fang FM, et al. Quality of life as a survival predictor for patients with advanced head and neck carcinoma treated with radiotherapy. Cancer 2004; 100: 425-432.
Health-Related Quality of Life predicts survival
• 957 patients• AIDS Clinical Trials Group Protocol 204• Randomized, double-blind comparing 3
prophylactic regimen against CMV• MOS-HIV
– Physical Health Summary (PHS)– Mental Health Summary (MHS)
• Each point increase in baseline decreased the risk of :
MHS PHSDeath 4% 4%CMV 2%Dropout 1% 1%
Jacobson DL et al. Health-Related Quality of Life predicts survival, cytomegalovirus disease, and study retention in clinical trial participants with advanced HIV disease. J Clin Epidemiol 2003.
Interview of a patient with pancreatic cancer Balance between aggressive therapy and
HRQL
55 year male patientDiagnosed with pancreatic cancer (median survival 5 months)Interview :
– “My Quality of Life is the most important” – “Chemotherapy will destroy everything”– “I want to investigate alternative therapies, such as
nutrition supplements”
• By the way, at the end of the consultation with Dr Gonzales, he had to pay 2800 $ (not taken in charge by any HMO/MCO, I presume)
• The cancer of the patient was so advanced that he died before he could even start Dr Gonzales treatment
Heard on Radio, 4 June 2004
Place of Patient-Reported Outcomes (PRO)
Patient-Reported Clinician-
Reported • Global Impression• Functional status• Well-being• Symptoms• HRQL• Satisfaction with TX• Treatment adherence
For example
• Global impression
• Observation & tests of function
Caregiver-Reported
For example
• Dependency
• Functional status
Physiological
For example
• FEV1
• HbA1c• Tumor size
Patient Outcomes Assessment
Sources and Examples
Acquadro C, et al. Incorporating the patient's perspective into drug development and communication: an ad hoc task force report of the Patient-Reported Outcomes (PRO) Harmonization Group meeting at the Food and Drug Administration, February 16, 2001. Value Health 2003; 6: 522-531.
Slide from Laurie Burke, Director, Office of New Drugs, CDER, FDA Washington
Define the conditions for which the measurement of HRQL/PRO in clinical trial is
useful• Patient’s self-report is the primary or sole indicator of disease
activity, e.g. dermatological disorders (psoriasis, acne), erection dysfunction
• No objective marker or several possible markers of disease activity (migraine, osteoarthritis, asthma, menopause, heart failure)
• Disease expressed by many symptoms (IBS)
• To ensure that treatments prolonging survival (AIDS), do not adversely affect patients’ lives due to morbidity, functional or psychological impairments or side effects
• The treatment does not seem to improve survival (cancer, rheumatoid arthritis, Parkinson’s disease), but it could improve HRQL, by reducing pain, anxiety, level of stress or by improving the functional status.
Chassany O et ERIQA Working Group. Patient Reported Outcomes (PRO) and Regulatory Issues : A European Guidance Document for the improved integration of health-related quality of life assessment in the drug regulatory process. Drug Information Journal 2002.
II. Recommended primary/secondary efficacy endpoints
a) Symptom modifying drugs
• Pain attributable to the target joint is recommended as primary endpoint. Functional disability is an important additional primary endpoint.Pain should be measured by self-assessment with validated methods, such as VAS or Likert scale.
• Functional disabilityA disease-specific and joint specific instrument such as the WOMAC…[…]…is recommended.
Secondary endpoints include:Global rating, Flares, Physical signs including range of motion, Quality of Life, Consumption of medications for pain relief
OsteoarthritisCPMP/EWP/784/97
PRO
HRQL
PRO
Irritable Bowel Syndrome (IBS)CPMP/EWP/785/97 (March 2003)
5. Recommended primary/secondary efficacy endpoints
Primary: The patient’s global assessment of symptoms and abdominal discomfort/pain should be used as the two primary endpoints. Statistically significant changes must be found in both parameters.
Secondary (supportive): choice of secondary efficacy variables should be justified by the applicant and should include variables such as bloating/distension, stool frequency and urgency, and quality of life parameters. Health-related quality of life must, however, be considered most important secondary endpoints.
PRO
HRQL
VI. Recommended Primary and secondary endpoints:
• In the major efficacy studies of symptomatic benefit the primary endpoint should reflect the clinical benefit the applicant wishes to claim in the future SPC.
• The Primary symptomatic benefit endpoint should be justified by referencing published data which support its validity; one example is the St George’s Respiratory Questionnaire.
• There are a number of secondary endpoints which may provide useful information. These measure different aspects of the disease but they should be justified by referencing published data which support their validity; examples include…..symptom scales, exacerbation rates and QoL assessment.
• Care should be taken with respect to statistical multiplicity if secondary endpoints become the basis for specific claims.
Chronic Obstructive Pulmonary Disease (COPD)CPMP/EWP/562/98 (Dec 1999)
PRO
HRQL
3. Tools to measure efficacy (primary or secondary endpoints)
d) Patient’s global assessment of disease activity (VAS)
e) Pain score (patient’s assessment : VAS, Likert Scale)
g) Physical function (assessed by patient, e.g. HAQ, AIMS)
4. Supportive evidence for efficacy
d) Emotional and social function (e.g. AIMS-1)e) Quality of life (RA-specific, e.g. AIMS, SF-36 or
generic…)
Rheumatoid arthritisCPMP/EWP/556/95 rev 1 (Dec 2003)
PRO
HRQL
Checklist for designing, conducting and reporting HRQL - PRO in clinical trials
HRQL / PRO objectives• Added value of HRQL / PRO• Choice of the questionnaires• Hypotheses of HRQL / PRO changes
Study design• Basic principles of RCT fulfilled ?• Timing and frequency of assessment• Mode and site of administration...
HRQL / PRO measure• Description of the measure (items, domains…)• Evidence of validity• Evidence of cultural adaptation
Statistical analysis plan• Primary or secondary endpoint • Superiority or equivalence trial• Sample size• ITT, type I error, missing data
Reporting of results• Participation rate, data completeness• Distribution of HRQL / PRO scores
Interpreting the results• Effect size • Minimal Important Difference• Number needed to treat…
Patient Reported Outcomes (PRO) and Regulatory Issues : A European Guidance Document for the improved integration of health-related quality of life assessment in the drug regulatory process. Chassany O et ERIQA Working Group. Drug Information Journal 2002.
Define the conditions for which the measurement of HRQL/PRO in clinical trial is
useful• Patient’s self-report is the primary or sole indicator of disease
activity, e.g. dermatological disorders (psoriasis, acne), erection dysfunction
• No objective marker or several possible markers of disease activity (migraine, osteoarthritis, asthma, menopause, heart failure)
• Disease expressed by many symptoms (IBS)
• To ensure that treatments prolonging survival (AIDS), do not adversely affect patients’ lives due to morbidity, functional or psychological impairments or side effects
• The treatment does not seem to improve survival (cancer, rheumatoid arthritis, Parkinson’s disease), but it could improve HRQL, by reducing pain, anxiety, level of stress or by improving the functional status.
Chassany O et ERIQA Working Group. Patient Reported Outcomes (PRO) and Regulatory Issues : A European Guidance Document for the improved integration of health-related quality of life assessment in the drug regulatory process. Drug Information Journal 2002.
Subjective, multidimensional, self-assessed (whenever possible)
QUESTIONNAIRE SF-36 (36 ITEMS, 8 DIMENSIONS)
Abréviation Libellé Anglais Libellé Français Nombre d’items
PF Physical Functioning Activités physiques 10
RP Role Physical Limitations dues à l’état physique 4
BP Bodily Pain Douleur physique 2
GH General Health Perception de l’état de santé 5
VT Vitality Vitalité 4
SF Social Functioning Vie et relations avec les autres 2
RE Role Emotional Limitations dues à l’état psychique 3
MH Mental Health Santé psychique 5
HT Health Transition Changement de l’état de santé 1
What is a HRQL questionnaire ?
Chassany O, et al. Gut 1999.
- Fonction physique- Limitations physiques- Douleur- Santé générale- Vitalité- Fonction sociale- Etat émotionnel- Santé mentale
36 items (8 dimensions)
Sommeil perturbé : 83%Prise d ’hypnotiques : 65%
SF-36questionnaire
générique
Étude chez 1032 patients ayant une colopathie fonctionnelle
Functional Digestive Disorders Quality of
Life (FDDQL)
- Activités quotidiennes- anxiété- Sommeil- Alimentation- Réaction face à la maladie- Contrôle de la maladie- Impact du stress
43 items (8 dimensions)
Restrictions alimentaires : 83%Très gênantes : 65%
Faut-il choisir un questionnaire générique ou spécifique de qualité de vie ?
When impact of lipodystrophy is measured by a generic instrument
Blanch J et al. Impact of lipodystrophy on the quality of life of HIV-1 infected patients. JAIDS 2002.
• 84 patients with lipodystrophy (LD)• HRQL measure : Spanish version of the Profil des
Lebensqualität Chronichkranker (PLC)– 40 items– 6 dimensions : Physical Capacity,
Psychological functioning, positive mood, social functioning, social well-being
– Self-administered, but interviewer supervised to ensure that the questions were correctly understood and answered
• LD had no influence on overall quality of life
What is not quality of life ?
• The abuse of the term HRQL in some clinical trials, whereas the questionnaire measured anything else – A listing of symptoms or of side effects cannot
claim to measure HRQL – Satisfaction *
• The following concepts cannot alone explore all HRQL : – physical or intellectual performance scale – handicap or functional incapacity scale – anxiety or depression scale– tiredness or pain scale– symptom bother scale
* Treatment of penile curvature with Essed-Schroder tunical plication: aspects of quality of life from the patients' perspective. BJU Int 2004
What are we measuring ? HRQL or side-effects
Measurement of quality of life in hypertensive patients. Bulpitt CJ et al. Br J Clin Pharmacol 1990; 30: 353-364.
Randomized, DB, placebo-controlled study of GH replacement in 40 patients with acquired GH deficiency
• Assessment at baseline and 18 months :• NHP (Nottingham Health Profile)• PGWB (Psychological General Well-being)• GHQ (General Health Questionnaire)• MMPI-2 (Minnesota Multiphasic Personality inventory)
• Selection made on what ?• Psychometrics properties ?• Prior use in a similar population ?• Cover several different concepts ?
• What where the hypotheses of score changes ?
Justification of choice of instruments ? What are the
hypotheses ?
Baum HBA et al. Effects of physiological growth hormone therapy on cognition and quality of life in patients with adult-onset GH deficiency. J Clin Endocrinol Metab 1998; 83: 3184-9.
Name Items Dimensions Answers
SIP Sickness Impact Profile 136 12 Yes/No*
NHP Nottingham Health Profile 38 7 Yes/No*
SF-36 Short-Form 36 (MOS) 36 8 Likert(Medical outcomes Survey)
PGWB Psychological General 22 6Likert
Well-Being
* Binary responses are unlikely to be sensible enough to detect a small change
Examples of generic HRQL questionnaires ?
Attention à la longueur des questionnaires
Nom du questionnaire Nb d’items
SIP Sickness Impact Profile (questionnaire générique)
136
DSQOLS Diabetes Specific Quality of Life Scale
64
DCP Diabetes Care Profile 234
NEWSQOL
Newcastle Stroke-Specific Quality of Life Measure
56
SIS Stroke Impact Scale 64
HOPES HIV Overview of Problem situations 103-176
AIDS-HAQ
AIDS – Health Assessment Questionnaire
116
• Je me sens seul• Je suis de plus en plus découragé• Je me rends compte que plus rien ne me fait plaisir• J’ai des difficultés à entrer en contact avec les autres• J’ai l’impression de n’avoir personne de proche à qui parler• J’ai du mal à faire face aux événements• J’ai l’impression d’être une charge pour les autres• Je trouve que la vie ne vaut pas la peine d’être vécue !
c’est plus une échelle de dépression que de qualité de vie
Content of HRQL questionnaires : Nottingham Health Profile (NHP)
The influence of an inhaled steroid on quality of life in patients with asthma or COPD. Van Schayck CP et al. Chest 1995; 107: 1199-205.
Improvement of lung function (FEV1, p < 0.0001) with added beclomethasone dipropionate (BDP)
Temporary decrease of symptoms
HRQL assessment : No improvement of NHP and ISP
– NHP : 38 statements, 6 dimensions : physical mobility, pain, social isolation , emotional reactions, energy, sleep.
• Answer by YES / NO
– ISP (Inventory of Subjective Health) : 21 items related to subjective complaints : tiredness, chest and heart problems, gastric problems, indigestion, headache…
• Is that measuring HRQL ?
What are we measuring ?
FatigueItems related to intensity, circumstances, and consequences of fatigue.Psychometric properties of the HIV-related fatigue scale. Barroso J et al. J Assoc Nurses AIDS Care 2002.
Cognitive functionDutch four-item MOS-HIV cognitive functional status subscale.The importance of cognitive self-report in early HIV-1 infection: validation of a cognitive functional status subscale. Knippels HM et al. AIDS 2002.
Treatment satisfactionWeak correlation between severity of side-effects and score of satisfaction concerning these side-effects (r = 0.18) Validation of the HIV treatment satisfaction questionnaire. Woodcock A et al. Qual Life Res 2001.
Doctor-Patient satisfactionSatisfaction among HIV-infected patients was not associated with QOLThe doctor-patient relationship and HIV-infected patients’ satisfaction with primary care physicians. Sullivan LM et al. J Gen Intern Med 2000.
Choice of PRO instrument - What are we measuring ? Example of HIV / AIDS
MOS-HIV AIDS-HAQ HOPES FACIT (FAHI)
HAT-QoL MQoL-HIV WHOQOL-HIV
Medical Outcomes Study HIV Health Survey
AIDS-Health Assessment Questionnaire
HIV Overview of Problem Situations
Functional Assessment HIV specific subscale
HIV/AIDS-Targeted Quality of Life
Multidimensional Quality of Life Questionnaire for HIV/AIDS
World Health Organisation’s Quality of Life HIV instrument
Author Wu A Lubeck Ganz PA Cella D Holmes WC Smith WHO Year 1991 1992 1993 1996 1988 (1997) 1997 2003 Nb Items 35 116 103-176 55 34 (76?) 40 31
Dimensions 11 8 5 6 5 10 Gal Health
Perception Physical Function Role Function Social function Cognitive function Pain Mental Health Energy/fatigue Health Distress Quality of Life Health Transition
Gal Health Perception Disability Social Function Mental Health Cognitive Function Energy/Fatigue Pain Disease Worry
Physical Function Psychosocial Function Sexual Function Medical interaction Marital Relationship
Overall Function Disclosure worries Health Worries Financial Worries Life Satisfaction
Mental Health Physical Health Physical Functioning Social Function Social Support Cognitive Function Financial Status Partner Intimacy Sexual Function Medical Care
Based SF-36 Functional Assessment of Cancer Treatment (FACT-G)
Cancer Rehabilitation Evaluation System (CARES)
WHOQOL
Languages Danish, Dutch, English UK, French, German, Italian, Portuguese, Spanish
Dutch, Spanish French Italian, Portuguese, Spanish
German, Spanish French
MOS-HIV
• “Très” SF-36• “Très” physique• Reflètant plus l’état de santé que la qualité
de vie• Pas de question sur
– Le sommeil– Le traitement– La lipodystrophie
Grossman HA et al. Quality of Life and HIV : current assessment tools and future directions for clinical practice. AIDS Read 2003.
WHOQOL-HIV
O’ Connell K et al. Preliminary development of the World Health Organisation’s Quality of Life HIV instrument (WHOQOL-HIV). Analysis of the pilot version. Social Science & Medicine 2003.
• Culturellement universel (Inde, Afrique, Asie, Amérique du Sud, …)
• Multidimensionnel :– Vos croyances personnelles donnent-elles un sens à votre
vie ?– Vous sentez-vous en sécurité dans votre vie de tous les jours
?– Votre environnement est-il sain ? (pollution, bruit, salubrité,
etc…)– Avez-vous besoin d’argent pour satisfaire vos besoins ?– Êtes-vous satisfait de vos moyens de transport ?– Êtes-vous satisfait de l’endroit où vous vivez ?
WHOQOL-HIV
O’ Connell K et al. Preliminary development of the World Health Organisation’s Quality of Life HIV instrument (WHOQOL-HIV). Analysis of the pilot version. Social Science & Medicine 2003.
• Spécifique du VIH ?– Un traitement médical vous est-il nécessaire pour
faire face à la vie de tous les jours ?
• Libellé compréhensible ?– Dans quelle mesure, êtes-vous tracassé par tout
problème physique lié à votre infection par le VIH ?– Avez-vous assez d’énergie dans la vie de tous les
jours ?– Avez-vous le sentiment d’être assez informé pour
faire face à la vie de tous les jours ?– Comment trouvez-vous votre capacité à vous
déplacer seul ?
Complaint score (32 items) SelfHealth Status Index (5 items) InterWork satisfaction (7 items) InterPsychological General Well-Being (22 items)
SelfProfile of Mood Status SelfLife satisfaction (3 items) SelfPsychomotor function InterSleep (7 items) SelfSexual function (6 items) SelfLife events (8 items)
Quality of life with three antihypertensive treatments.Fletcher AE et al. Hypertension 1999; 19: 499-507.
Who measures what ?
N = 30
Who measures Well-Being ? Clinicians ??
Analysis of Well-Being between indapamide and captopril.Lacourciere Y. Am J Med 1988; 84: 47-51.
Who should fill-in questionnaire ?
In studies evaluating sexual impairment induced by antihypertensive treatment in male patients, the answers given to nurses, by patients themselves and by their spouses were quite different...
Rate of sexual dysfunction
Nurses Low
Who should fill-in questionnaire ?
In studies evaluating sexual impairment induced by antihypertensive treatment in male patients, the answers given to nurses, by patients themselves and by their spouses were quite different...
Rate of sexual dysfunction
Nurses Low
Patients Moderate
Who should fill-in questionnaire ?
In studies evaluating sexual impairment induced by antihypertensive treatment in male patients, the answers given to nurses, by patients themselves and by their spouses were quite different...
Rate of sexual dysfunction
Nurses Low
Patients Moderate
Patients (palm pilot) Higher
Who should fill-in questionnaire ?
In studies evaluating sexual impairment induced by antihypertensive treatment in male patients, the answers given to nurses, by patients themselves and by their spouses were quite different...
Rate of sexual dysfunction
Nurses Low
Patients Moderate
Patients (palm pilot) Higher
Spouses Very high
From Pr Ingela Wiklund (AstraZeneca)
Number of lipodystrophy regions
6543210
Me
an
AB
CD
sco
re 100
90
80
70
60
50
40
30
20
10
0
4245
5456
64
71
85
Score de qualité de vie ABCD
100806040200Score
résum
é m
enta
l du S
F-1
2 (
MC
S)
70
60
50
40
30
20
10
ABCD vs Mental Component Summary (MCS) SF-12, r=0.65
To follow the rigorous procedures of development of HRQL or PRO questionnaires
• Item generation• Scaling• Item reduction• Reproductibility• Content validity• Construct validity• Discriminant validity• Convergent validity• Responsiveness• Cultural adaptation
Scientific Advisory Committee of the Medical Outcomes Trust. Assessing health status and quality-of-life instruments: attributes and review criteria. Qual Life Res 2002
Factorial analysis ABCD Score FactorABCD
20items 1 2 3 4a ,723 ,084 ,284 ,177
b ,529 ,067 ,427 ,293
c ,696 ,359 ,152 ,290
d ,580 ,488 ,149 ,318
e ,625 ,143 ,471 ,096
f ,684 ,118 ,347 -,105
g ,609 ,195 ,381 ,125
h ,767 ,417 -,050 ,089
i ,181 ,323 ,728 ,132
j ,387 ,697 ,369 ,104
k ,110 ,293 ,740 ,119
l ,174 ,732 ,317 ,000
m ,181 ,775 ,298 ,121
n ,542 ,611 -,078 ,358
o ,195 ,731 ,265 ,249
p ,378 ,490 ,123 ,478
q ,778 ,412 -,101 ,290
r ,149 ,136 ,505 ,221
s ,241 ,247 ,339 ,662
t ,100 ,089 ,166 ,821
ABCD score vs nb of lipodystrophy regions
Multiple causes• Lack of rest or exercise• Improper or inadequate diet• Psychological stress
(depression, anxiety)• Use of recreational
substances• Anemia• Abnormalities of the thyroid
gland and hypogonadism• Infections• Side effects of medications• Sleep disturbances• Fever
Fatigue description• Lack of energy• Sleepiness• Tiredness• Exhaustion• Inability to get enough rest• Weakness
Specific fatigue questionnaire
HRQL questionnaire : must have items related to fatigue
How measuring fatigue ? Identification of concepts
Assessment and treatment of HIV-related fatigue. Adinofi A. J Assoc Nurses AIDS Care 2001.
Determinants of the Quality of Life
Control of disease
Coping with
disease
Personalitytraits
Social suppor
t
2nd illness
Diabetes burden
Rose M, et al. Determinants of the quality of life of patients with diabetes under intensified insulin therapy. Diabetes Care. 1998; 21: 1876-85.
Various factors involved in the multidimensional HRQL construct
Control of disease / self-management
Items about DIET can express different concepts Input of patients in item
generation is criticalDiabetes --> Cause --> Food --> consequence --> DIET
Watkins KW, et al. Effect of adults' self-regulation of diabetes on quality-of-life outcomes. Diabetes Care 2000; 23: 1511-5.
I am able to keep my diet regimen under control
My diabetes and its treatment (e.g. diet) keeps me going out with friends / to restaurant / as much as I want
I find it hard to do all the things (e.g. diet) I have to do for my diabetes
Interference with social and personal relationships
Coping with disease
Première version du questionnaire spécifique FDDQL dans les Troubles Fonctionnels Intestinaux (TFI) : les exemples suivants correspondent à des items peu clairs, doublement négatifs …
• Il m'est facile de me décontracter et de ne plus penser à rien
• Je n'angoisse pas à l’idée que mes vacances avec le changement des habitudes alimentaires, risquent d'aggraver ma maladie (douleurs, constipation ou au contraire diarrhée)
• Je ne pense pas que ma maladie retentisse négativement sur mon travail
Chassany O, et al. Gut 1999.
Item generation of the FDDQL questionnaire
Fatigue Symptom Inventory
• Combien de temps dans la journée, en moyenne, vous êtes vous senti(e) fatigué(e) durant la dernière semaine ?Rate how much of the day, on average, you felt fatigued in the past week
St-George Respiratory Questionnaire (50 items)
• Sur l’année dernière, en moyenne sur une semaine, combien de “bons jours” vous avez eu ?Over the last year, in an average week, how many good days (with little chest trouble) have you had
Fatigue symptom inventory
Attention au libellé des questions
(Please check one box for each statement.)
All of the time Most of the time Some of the time A little of the time None of the time
(5)
(4)
(3)
(2)
(1)
Item scaling of HRQL questionnaires ?
(Please check one box for each statement.)
All of the time Most of the time Some of the time A little of the time None of the time
(5)
(4)
(3)
(2)
(1)
Tout letemps
JamaisQuelquefois RarementTrèssouvent
Item scaling of HRQL questionnaires ?
Les modalités de réponses doivent permettre de détecter des petits changements
• Réponse binaire : YES / NO peu sensible• Echelle verbale Likert en 5 à 7 points• Echelle visuelle analogique
Généralement, la réponse à un item est transformée en une valeur : entre 0 et 4 pour une échelle verbale à 5 points
Les scores des dimensions sont obtenus par sommation des réponses aux items
Pour faciliter la présentation des résultats, les scores des dimensions peuvent être transformés entre 0 et 100
0 Pas du tout 1 Un petit peu 2 Moyen 3 Beaucoup4 Enormément
Item scaling and scoring of HRQL questionnaires ?
Factorial analysis (n = 143)Lipodystrophy score (6 items)
Factorial analysis of Assessment of Body Change and Distress (ABCD) in
Lipodystrophy (HIV/AIDS)
Q2 Q3 Q4 Q5 Q6
Q1 0,512 -0,175 -0,117 -0,049 0,227
Q2 -0,151 0,070 0,188 0,260
Q3 0,231 0,327 -0,006
Q4 0,671 0,101
Q5 0,028
Facteurs
1 2
Q1 -,210 ,789
Q2 ,065 ,841
Q3 ,573 -,265
Q4 ,855 ,090
Q5 ,882 ,151
Q6 ,088 ,558
Correlation matrixFactors
2-factor structure1- Lipoatrophy2- Lipoaccumulation
Duracinsky M, Chassany O. Linguistic and psychometric validation in french of a specific quality of life questionnaire in Lipodystrophy (ABCD)
Factorial analysis (n = 143)ABCD Quality of life score (20 items)
4-factor structure :1- Acceptation, coping, satisfaction of appearance
2- Psychological, social and relational impact
3- Fear of future
4- Compliance with the treatment
Composante
1 2 3 4 a ,723 ,084 ,284 ,177
b ,529 ,067 ,427 ,293
c ,696 ,359 ,152 ,290
d ,580 ,488 ,149 ,318
e ,625 ,143 ,471 ,096
f ,684 ,118 ,347 -,105
g ,609 ,195 ,381 ,125
h ,767 ,417 -,050 ,089
i ,181 ,323 ,728 ,132
j ,387 ,697 ,369 ,104
k ,110 ,293 ,740 ,119
l ,174 ,732 ,317 ,000
m ,181 ,775 ,298 ,121
n ,542 ,611 -,078 ,358
o ,195 ,731 ,265 ,249
p ,378 ,490 ,123 ,478
q ,778 ,412 -,101 ,290
r ,149 ,136 ,505 ,221
s ,241 ,247 ,339 ,662
t ,100 ,089 ,166 ,821
Factors
Duracinsky M, Chassany O. Linguistic and psychometric validation in french of a specific quality of life questionnaire in Lipodystrophy (ABCD)
Factorial analysis of Assessment of Body Change and Distress (ABCD) in Lipodystrophy (HIV/AIDS)
Iterative process based on :• Distribution of answers• Content analysis (items and response options are relevant
and comprehensive of the dimensions)
• Factorial analysis (to support the hypothesized scale structure, i.e. the combination of items into dimensions)
Item reduction
During the development of a HRQL questionnaire in irritable bowel syndrome, patients were asked to answer these items ranging from “not at all” to “extremely.” Results are presented as a percentage of patients.
International study : France, Germany, Great Britain391 IBS and dyspeptic patients
0
20
40
60
80
100
Sco
res
mo
yen
s F
DD
QL
Activ ité
quotidiennes
Anx iété Alimentation Sommeil Inconfort Réaction face
à la maladie
Contrôle de
la maladie
Stress
[1-5]
[6-10]
> 10
Number ofsymptoms
Chassany O, et al. Gut 1999.
Discriminant validity of the Functional Digestive Disorders Quality of Life
questionnaire (FDDQL)
0
0,5
1
1,5
2
2,5
3
SSc HAQ HAQ-DI
6
5
4
3
2
1
0
Validation of French version of the scleroderma health assessment questionnaire (SSc HAQ).Georges C, Chassany O et al. Clinical Rheumatology, Under press.
Comparison using ANOVA (p < 0.0001 for both scores) (n=100 patients)HAQ-DI: Health Assessment Questionnaire – Disability Index; Global SSc HAQ = (8 HAQ-DI domains + 5 VAS)/13.
Score values (m ± SD) of the global SSc HAQ and HAQ-DI, according to the number of the following organ involvements (n=6): • Raynaud’s phenomenon• Digital ulcers• Gastro-intestinal • Pulmonary• Musculoskeletal• Hand contracture
Discriminant validity of the Health Assessment questionnaire adapted to
Sclerodermia (SSc HAQ)
Number of lipodystrophy regions
6543210
Me
an
AB
CD
sco
re 100
90
80
70
60
50
40
30
20
10
0
4245
5456
64
71
85
Discriminant validity of a Lipodystrophy specific quality of life questionnaire
Global Quality of Life score (ABCD)impairs with the number of
sites of lipodystrophy(n = 155)
score min-max : 0-100 [0 = worse quality of life, 100 = good quality of life]ANOVA, p < 0.001
Duracinsky M, Chassany O. Linguistic and psychometric validation in french of a specific quality of life questionnaire in Lipodystrophy (ABCD)
r = 0.39
Score de qualité de vie ABCD
100806040200Sco
re r
ésum
é m
enta
l du
SF
-12
(MC
S) 70
60
50
40
30
20
10
Score de qualité de vie ABCD
100806040200
Sco
re r
ésum
é ph
ysiq
ue d
u S
F-1
2 (P
CS
) 60
50
40
30
20
Logical correlation between Global ABCD score and generic quality of life (SF-12) (n = 155)
Convergent validity of a Lipodystrophy specific quality of life questionnaire
vs Physical Component Summary (PCS), r = 0.101
Duracinsky M, Chassany O. Linguistic and psychometric validation in french of a specific quality of life questionnaire in Lipodystrophy (ABCD)
vs Mental Component Summary (MCS), r = 0.65
MOS-HIVABCD QoL
score
General Health 0.51
Physical Function 0.37
Role Physical 0.21
Social Function 0.63
Cognitive Function 0.48
Pain 0.48
Mental Health 0.68
Energy/Fatigue 0.59Health Distress 0.70Global QoL 0.56Health Transition 0.22
Logical correlation between some dimensions of the MOS-HIV, e.g. the health distress, mental health and social function (r > 0.6)
Convergent validity of a Lipodystrophy specific quality of life questionnaire
0
20
40
60
80
100
AC
1
AC
2
AC
3
B1
B2
B3
D1
D2
D3
E1
E2
E3
F1
F2
F3
G1
G2
G3 0
20
40
60
80
100
H1 H2 H3 I1 I2 I3
Sensibilité au changement - Questionnaire d’éducation dans l’asthme (CHU Montpellier)
Scores des 6 domaines explorant le comportement face à des scénarios cliniques
Évolution des scores entre la première (n = 96), la 2e (n = 67) et la 3e visite (n = 21) au cours d’un programme d’éducation
Scores des 2 domaines explorant les connaissances
0
10
20
30
40
50
60
70
SG
CO
MP
1
SG
CO
MP
2
Sg
CO
MP
3
SG
CO
MP
ALT
1
SG
CO
MP
ALT
2
SG
CO
MP
ALT
3
0
20
40
60
80
100
SG
CO
NN
1
SG
CO
NN
2
SG
CO
NN
3
SG
CO
NN
ALT
1
SG
CO
NN
ALT
2
SG
CO
NN
ALT
3
Score global
Cultural adaptation and Linguistic validation
• Objective: Conceptual equivalence between the source questionnaire and the target version
• There is no consensus, however the major steps recommended remain the same
• Forward translation:– independent translations (source target language)– Reconciliation meeting to obtain a consensual version
• Backward translation:– independent translation (target source language)– Comparison of the source questionnaire with the
"backward" translation to check the conceptual content of forward version
• Cognitive debriefing:– Structured and in-depth interviews to test their
understanding / interpretation of the translation of each item
Source (FR) Vous êtes-vous senti(e) mal dans votre peau ?
Problem idiomatic expression
Forward Have you felt ill at ease ?
backward Vous êtes-vous senti mal à l’aise ?
Problem Original concept is not correctly translated
Final Have you felt unhappy with yourself ?
Chassany O, et al. Gut 1999.
Cultural adaptation - forward/backward translation
Chassany O, et al. Validation of a specific quality of life questionnaire in functional digestive disorders (FDDQL). Gut 1999.
• Canada (US) Shoveling the snow
• Japan
• Norwegian
Cultural adaptation - forward/backward
Disease: Asthma - Original version developed in CanadaItem: Here is a list of activities in which some people with asthma are limited, among them: « shoveling snow »
• Canada (US) Shoveling the snow
• Japan Beat futons
• Norwegian
Cultural adaptation - forward/backward
Disease: Asthma - Original version developed in CanadaItem: Here is a list of activities in which some people with asthma are limited, among them: « shoveling snow »
• Canada (US) Shoveling the snow
• Japan Beat futons
• Norwegian Going fishing
Cultural adaptation - forward/backward
Disease: Asthma - Original version developed in CanadaItem: Here is a list of activities in which some people with asthma are limited, among them: « shoveling snow »
All of the time
Most of the time
Some of the time
A little of the time
None of the time
a. … feel frustrated because clothes don’t fit
right.
c. … upset that I can’t control my body.
f. … confused about how much to exercise.
g. … feel discomfort or pain.
h. … embarrassed about how I look.
i. … worry that my HIV is getting worse.
j. … upset that people may think I am sick.
Cultural Adaptation
Cultural adaptation
Questionnaire ABCD : Item Q8c (Problème de la traduction de “upset”)
Def : To distress or perturb mentally or emotionally, to disturb, to sadden, to trouble, to offend, to disappoint
Original c. … upset that I can’t control my body.
MB c …. je me suis senti(e) triste parce que je ne pouvais pas contrôler mon corps
CE c. … j’ai été contrarié/e de me rendre compte que je n’avais plus le contrôle de mon corps
Version 1 c. … j’ai été contrarié/e inquiet(e) de me rendre compte que je n’avais plus le contrôle de mon corps.
Version 4 c. … j’ai été contrarié/e de ne plus avoir le contrôle de mon corps.
Back DE c. … I was upset about losing control of my body
Finale c. … j’ai été contrarié/e de ne plus avoir le contrôle de mon corps.
Cultural adaptation of Assessment of Body Change and Distress (ABCD) in
Lipodystrophy (HIV/AIDS)
Duracinsky M, Chassany O. Linguistic and psychometric validation in french of a specific quality of life questionnaire in Lipodystrophy (ABCD)
Cultural adaptation
How often did your asthma make you feel frustrated during the past week?
To prevent from accomplishing a purpose or fulfilling a desire. To cause feelings of discouragement
Literal translation in French : frustréBackward translation : offended, dispossessed,
injured, shocked
Bristow MR et al. Circulation 1996.
0
2
4
6
8
10
12
14
16
Mo
rtal
ity
at 6
mo
nth
s
Double-blind, placebo-controlled trial (n=345), 6 months, 3 doses of carvedilol (beta-blocker)
MLwHF (0-105)
Placebo 6.25 mg 12.5 mg 25 mg
Baseline 47.7 45.8 43.9 43.6
Endpoint 40.4 38 36.5 38.2
Minnesota Living with Heart FailureMLwHF : 21 items, 0 (best) - 105 (worst)
Specific questionnaire : responsiveness ?HRQL is not improved by drugs in Chronic heart failure ?
Responsiveness - specific questionnaires
22
42
62
82
102
122
Glo
bal P
GW
B s
core
Ome20mg
Ome10mg
Cis 10mg
J0
4 semaines
24% difference in pyrosis relief
0%
20%
40%
60%
80%
Ome 20mg Ome 10mg Cis 10mg
Résolution des symptômes à 4 semaines
Galmiche JP, et al. Aliment Pharmacol Ther 1997. .
Responsiveness - generic questionnairesPsychological General Well-Being (PGWB) & GERD
HRQL is not improved by gastro-oesophageal reflux disease drugs ?
No difference in PGWB score
Is health-related quality of life among older, chronically ill patients associated with unplanned readmission to hospital ?
163 Australian, chronically ill patients (67 ± 16) discharged to home following acute hospitalization
HRQL (SF-36) assessed at one month post-hospital
Patients were followed-up for six months thereafter to determine subsequent incidence of unplanned readmission
On multivariate analysis :
SF-36 physical component score < 40 (OR = 2.2, p = 0.05)
Predictive value of Quality of Life ?
Is health-related quality of life among older, chronically ill patients associated with unplanned readmission to hospital ? Pearson S et al. Aust N Z J Med 1999; 29: 701-706
Specific Cystic Fibrosis Questionnaire (CFQ)
French Cystic Fibrosis Questionnaire :• CFQ-14 for teenagers & adults• CFQ Child P : a parent-proxy
evaluation for children aged 8-13 • 33 interviews patients & parents :
- Item generation• Cross-sectional survey among 393
patients & parents :- Item reduction - Internal consistency, convergent and discriminant validity
• 124 patients & 85 parents :- Subscale structure (Rasch analysis…)- Reproducibility and responsiveness
Development of the Cystic Fibrosis Questionnaire (CFQ) for assessing quality of life in pediatric and adult patients. Henry B, et al. Qual Life Res 2003; 12: 63-76.
9 dimensions : • physical functioning• energy/well-being• emotions• social limitations• role,
embarrassment• body image• eating disturbances• treatment burden
Cross-cultural adaptation of questionnaires is not enough ?
• Specific CFQ-14 developed in France• Translated in German• Studies in n = 197 and n = 103
adolescents/adults• Construct validity : same 9 HRQL domains as in
the French original CFQ-14• Internal consistency : ranged from 0.71 to 0.94• Clinical validity : supported by severely ill
patients reporting lower HRQL than less ill patients
The revised German Cystic Fibrosis Questionnaire: validation of a disease-specific health-related quality of life instrument. Wenninger K et al. Qual Life Res 2003; 12: 77-85.
“Validated” scale is not enough
• A validated scale doesn’t imply systematically that it is relevant for the population studied
• e.g. even for the so well-known SF-36 applied in a given condition, the issue of its relevance should be addressed…– e.g. SF-36 in IBS– MOS-HIV validated before HAART
• Moreover some scales are getting old…
Importance of various areas of limitations due
to asthma among Harlem emergency
department users (n =247)
mostly Afro-american patients with a low
socio-economic status and a lower compliance8,1%
10,9%
17,0%
17,4%
19,4%
20,2%
23,9%
26,3%
26,7%
26,7%
27,9%
27,9%
28,7%
28,7%
29,1%
31,6%
32,4%
37,2%
41,7%
Playing w ith pets
Bicycling
Singing
Playing sports
Jogging, exercising, or running
Mopping or scrubbing the f loor
Visiting w ith friends or relatives
Going for a w alk
Dancing
Doing home maintenance
Doing regular social activities
Cooking
Carrying groceries
Talking
Playing w ith children
Walking one block
Having sex
Doing housew ork
Climbing upstairs
Choice of a PRO questionnaire - Importance of the sample included during the validation
process
Asthma-related limitations in sexual functioning: an important but neglected area of quality of life. Meyer IH, et al. Am J Public health 2002; 92: 770-772.
Study Design : specific issues related to HRQL / PRO measure
• Eligibility criteria : if HRQL primary endpoint, set a minimal impairment of HRQL (as for other criteria, e.g. pain, asthma onset… )
• Timing and frequency of HRQL assessment : – At baseline, at the end of the study or at withdrawal
• Length of the trial (relevance of short term trials ?)
• Mode and site of HRQL administration : – Self-administered whenever possible – Assure the confidentiality– Before the medical consultation
• Data monitoring and quality assurance
• Procedures for prevention and handling of missing data
Chassany O et ERIQA Working Group. Patient Reported Outcomes (PRO) and Regulatory Issues : A European Guidance Document for the improved integration of health-related quality of life assessment in the drug regulatory process. Drug Information Journal 2002.
• Double-blind sham surgery-controlled trial designed to determine the effectiveness of transplantation of human embryonic dopamine neurons into the brains of persons with advanced Parkinson's disease
• Study investigated the quality of life (HRQL) of participants during the 1 year of double-blind follow-up
• In all cases, those who thought they received the transplant reported better HRQL (physical, emotional and social) scores
Basic principles of RCTs fulfilled ? Placebo effect is also strong for HRQL
McRae C, et al. Effects of perceived treatment on quality of life and medical outcomes in a double-blind placebo surgery trial. Arch Gen Psychiatry 2004; 61: 412-420
• HSQ (Health Status Questionnaire) • before / after scores on 1300 patients• All p values < 0.0001• Conclusion: all HRQL domains were
significantly different across treatment groups
• Problem: 1300 provide 80% power to detect a change of 1 unit on a 0-100 point scale
JCO 2001 (anonymous)
Statistical analysis plan : Estimating the adequate sample size
N = 365 (394 randomized)
Poorer HRQL scores
Importance of withdrawals and missing data
Assessment of quality of life by patient and spouse... Testa MA et al. Am J Hypertens 1991; 4: 363-73.
Statistical analysis plan : PRO multiplicity
Salmeterol / COPD• Open label• Salmeterol 50 g • or SR Theophylline bid• Randomized (n = 178)• Completers (n = 145)• HRQL (secondary) : SF-36• Mean changes between baseline and the 4 assessments over
time, for each dimension : Student t test
Efficacy, tolerability and effects on HRQL of inhaled Salmeterol in COPD. Di Lorenzo G et al. Clin Ther 1998.
(n = ???) in favor of Salmeterol Assessment p
Physical Functioning (PF) 3 months 0.02Change in Health Perception (HT) 9 months 0.03
Social Functioning (SF) 12 months 0.04
SF-36 Assessment
8 (+1) dimensions 3 months
" 6 months" 9 months" 12 months
Number of tests 36
Interpreting PRO results ?
Zafirlukast improves asthma symptoms and HRQL in patients with moderate reversible airflow obstruction. Nathan RA et al. J Allergy Clin Immunol 1998.
Zk vs Pl p
Daytime symptoms (0 to 3 (severe)) - 0.14 < 0.001
Nighttime awakening (per wk) - 0.63 < 0.001
2 agonist use (puffs/day) - 0.64 < 0.001
FEV1 0.05 0.331
Morning PEF (BL : 362) + 13,1 L/min < 0.001
Evening PEF (BL : 398 + 11,5 L/min < 0.001
Global AQLQ score (BL : 4.28) + 0.26 0.004
Marquis P, Chassany O, Abetz L. A comprehensive strategy for the interpretation of quality of life data based on existing methods. Value in Health 2004 ; 7 : 93-104.
How to evaluate drugs when clinical relevance of results is not obvious ?
Mean score ± SD
p < 0.05and IC95
Pain VAS
OK
YES
p < 0.05
HRQL Responders
MID?
• Treatment in claudication (Peripheral Arterial Occlusive Disease)
• Phase III, randomized, double-blind, vs placebo
File for Approval - AFSSAPS
Interpretation of results - Effect size
Endpoint Effect Size
Walking distance 2.13Specific HRQL questionnaire (CLAUS) 0.48
Dossier for Drug Approval
Effect Size Small Moderate Large
Benchmark > 0.20 > 0.50 > 0.80
Effect size (Distribution-based approach)Dividing a difference between 2 groups by the SD
File for Approval - AFSSAPS
Interpretation of results - Effect size
Effect Size Small Moderate Large
Benchmark > 0.20 > 0.50 > 0.80Effect size (Distribution-based approach)Dividing a difference between 2 groups by the SD
0 0,5 1 1,5 2
Illusion ofmovement
Duration of illusion
Motion intolerance
Neurovegetativesigns
Instability
Global score
European Evaluation of Vertigo (EEV)
0 0,2 0,4 0,6 0,8
Physical Functioning
Role Physical
Bodily Pain
Health Perception
Vitality
Social Functioning
Role Emotional
Mental Health
Generic quality of life SF-36
Longitudinal validation study : Effect Size (ES) of a symptomatic specific questionnaire (EEV) and the SF-36 calculated from the change as perceived by over 100 patients with vertigo after 4 weeks of treatment
Minimal Important Difference (MID)
MID obtained from comparison with a Global Rating
Guyatt GH, Juniper EF. Several publications
* “Overall, has there been any change in your shortness of breath during your daily activities since the last time you saw us ?”
Answer to the GLOBAL RATING change*
Worse Better Interpretation of change
Mean change in HRQL scale (range 1-7)
A very great deal - 7 + 7 Large 1.5
A great deal A good deal Moderately
- 6 - 5 - 4
+ 6 + 5 + 4
Moderate 1.0
Somewhat A little
- 3 - 2
+ 3 + 2
Small 0.5
Almost the same - 1 + 1
About the same
DEPENDS ON WORDINGChanges in AQLQ symptom-domain anchored to global
Asthma control global
Asthma change global
Global category Average n Average n
Worse - 0.04 3 - 1.05 3
Minimally worse 0.13 49 0.18 11
No change 0.35 102 0.33 45
Minimally improved 0.78 135 0.42 86
Improved 1.48 18 0.85 121
n = 343 (mild to moderate asthma)Global asthma control question : “How well is your asthma controlled?”Global asthma change question : “Overall has there been any change in
your asthma since the beginning of the study ?”AQLQ : Response from 0 to 6 (poorly controlled / much worse)
Barber BL et al. Qual Life Res 1996.
Minimal Important Difference (MID) or change
Minimal Important Difference (MID)
MID obtained from comparison with a Global Rating may be different according to :• Wording of the Global Rating • Improvement vs. worsening • Characteristics of patients (age, gender…)• Characteristics of disease (severity …)• Setting of the trial, type of intervention• Cross-cultural differences• Baseline level of scores …
Currently, there is no consensus, whether to be relevant, MID should be > 0.5 on a range score
from 1 to 7Impact of the global on patient perceivable change in an asthmatic specific QOL questionnaire. Barber BL et al. Qual Life Res 1996.
(1) Informal meeting with Harold Dupuy (Paris, June 2003), (2) group level, (3) individual level(4) values obtained by correlation with a global rating (GR)(5) Baseline and transitional dyspnoea index (BDI/TDI)
MID [range of the scale]
Corresponding MID on a range scale 0-100
PGWB (1) 3 [0-110] (2)
8 [0-110] (3) 2.7 7.3
SGRQ 4 [0-100] 4
AQLQ (4) 0.5 [1-7] 7
CRQ 4) 0.5 [0-6] 7
I-QOL (4) 6 [0-100] (GR : little better) 13 [0-100] (GR : much better)
6 13
SF-36 10 [0-100] 10
Dyspnoea index (5) 1 [-3, +3] 14
VAS pain (4) 2 [0-10] 18
Minimal Important Difference (MID)
How many and which PRO domains should improve for a claim ?
The effects of naftidrofuryl on quality of life. Liard F et al. Dis Manage Health Outcomes 1997.
-2
0
2
4
6
8
10
Ch
an
ge
sco
re
Daily l
ifePain
Compl
aints
Social
life
Anxiet
y
Depre
ssion
Fatig
ue
Vitality
Anger
Domains
Naftidrofuryl
Placebo
• 234 Patients with Peripheral
Arteriopathy Occlusive Disease
(PAOD)
• HRQL primary endpoint
using the specific questionnaire
: CLAU-S (9 domains, 80 items)
• Results : 2 domains
significantly improved with drug
(daily life, p=0.004; pain,
p=0.001)
• Should the planners have
hypothesized that only
these 2 domains would
improve?
J3 J12Symptoms
- Chest pain NS NS - Shortness of breath <0.05 NS- Dizziness NS NS
- Palpitation <0.05 NS- Cognitive ability NS NS
Alertness NS NSQuality of sleep NS NSPhysical ability NS NSDaily ability NS NSDepression NS NSSelf perceived health NS NSLadder of life: future NS NSFitness <0.05 NSPhysical activity <0.01 NS
• 90 (6 x 15) statistical tests• Difference of 0.2 (range 1-7) at 3 months• No difference at 12 months
Abstract “Aerobic group-training of elderly patients recovering from an acute coronary event beneficially influences physical fitness and several parameters expressing quality of life”
Stahle A et al. Improved physical fitness and HRQL following training after acute coronary events. Eur Heart J 1999.
How many and which PRO domains should improve for a claim ?
Antacid in GERD• Randomized, placebo-controlled, double-blind trial• Primary endpoint : heartburn (diary)• Secondary endpoint : SF-36 questionnaire• Sample size > 230• Duration : 28 days
SF-36 domains
Score differences at 4 wks antacid vs
placebo
p Effect size
PF < 3 NS 0.15 RP < 7 NS < 0.15 BP < 3 NS 0.20 HP < 3 NS < 0.15 VT < 3 < 0.04 < 0.25 SF < 3 < 0.05 < 0.10 RE < 3 NS 0.20 MH < 4 < 0.03 < 0.20
• Justification of measuring HRQL at 4-wk (and not after 6 months of taking 3 to 6 pills/day) ?
• Why no difference with placebo on Bodily Pain domain (BP) ?• Number Needed to Treat on the primary endpoint is 20
patients for one to reduce its heartburn by over 50%French Drug Agency 2003
How many and which PRO domains should improve for a claim ?
• Many PROs such as symptom scales are well-established since decades
• But, nobody knows how to assess Pain :– Which tool ? (evidence of validation)– When ?– Period of time ?– Which question ?– Minimal important change ?
• Osteoarthritis (10 mm on 0-100 mm VAS ?)• Irritable Bowel Syndrome (10%
difference ?)
PROs are not a regulatory issue for EMEA, but…
• Tegaserod / Irritable Bowel Syndrome• Endpoints:
– “did you have satisfactory relief of your overall IBS symptoms during last week?”
– “did you have satisfactory relief of your abdominal discomfort or pain symptoms during last week?”
• Responder : satisfactory relief for at least 3 out of the 4 first 4 weeks
• Relief of overall IBS symptoms 33.7 vs 24.2 (placebo) 9.3%
• Relief of abdominal discomfort/pain : 31.3 vs 22.1 9.1%
Nobody knows if a 9 % difference of responders in IBS is worth giving a claim?
European mutual procedure (2004-2005)
Example of an IBS drug (mutual recognition)
• Small difference on pain versus placebo (primary endpoint)
• Tertiary endpoints (quality of life, satisfaction, utility and work productivity) bring consistency with the other endpoints, and they may thus reinforce the rather small clinical benefit observed on the co-primary endpoints, and thus enhance the benefit/risk ratio
• Not only patients tend to feel a little bit better for pain and symptoms, but they express a small improvement in some aspects of their daily life, and they are a little bit more productive for work
Because PROs (including HRQL) are unavoidably part of the Approval decision
January 2005
5 key issues for Drug Approval Process
Based on a meeting with representatives of AFSSAPS, EMEA and ERIQA Working Group, Paris, 1999
1- Added-value of HRQL/PRO with respect to other criteria
2- Psychometric properties of the HRQL/PRO instruments
3- International validation of the HRQL/PRO instruments
4- Adequacy of the statistical analysis plan
5- Clinical significance of observed changes
Chassany O et ERIQA Working Group. Patient Reported Outcomes (PRO) and Regulatory Issues : A European Guidance Document for the improved integration of health-related quality of life assessment in the drug regulatory process. Drug Information Journal 2002.
HRQL (and PRO) to be considered as a credible criterion if there is enough evidence (in the file) about the :
Anti-emetic (chimiotherapy) • National procedure• Module 2 (clinical overview)
• Claim wanted : « XX gets an advantage in term of quality of life … »
• Functional Living Index Emesis (FLIE) questionnaire presented as HRQL (secondary endpoint)→ 18 items (9 same items for nausea and
vomiting)→ Certainly not multidimensional HRQL
• Interest of measuring so-called HRQL the day after 5 days of anti-emetic treatment ?→ very small if any
Review of a dossier : Example of misuse/abuse
September 2004
What are the results 1st study ?• 2 items with a statistical difference (+ 1 or 2 points
on a 7-point scale at p = 0.07) XX vs comparator• No double-blind• At least 18 tests• Relevance of difference ?• Global score : statistical difference (p = 0.0885)
What are the results 2nd study ?• No difference XX vs comparator• Double-blind• Intent to treat : 200• FLIE analyzed in only 151-177 patients (n = 131 for
global score)– Where are patients and why are they
missing ?
Review of a dossier : Example of misuse/abuse
Conclusions
• Useless to measure HRQL at 5 days• FLIE is not measuring HRQL but impact on daily
function*• Methodological flaws• The allegation « XX gets an advantage in term of
quality of life … » is not supported by data
• A similar dossier of another anti-emetic (aprepitant) presented FLIE more as what it is really measuring : Patient-Reported Impact on Daily Life
* Guideline on non-clinical and clinical development of medicinal products for the treatement of nausea and vomiting with cancer chemotherapy, CPMP/EWP/4937/03, February 2005
Review of a dossier : Example of misuse/abuse
EMEA/CHMP/EWP/139391/2004
Reflection paper on the regulatory guidance for the use of health-related quality of life (HRQL) measures in the
evaluation of medicinal products
Adoption by CHMP : July 2005Date for coming into effect : January 2006http://www.emea.eu.int
Guideline européenne sur la qualité de vie
• The lack of experience and training of the reviewers and regulators
• The fears (legitimate) of the regulatory authorities to officially acknowledge the PRO and to take into account a subjective criterion by nature :– Whose clinical interpretation remains difficult– Whose good practices of advertising remain to
be specified in a market where competition is rough
– Without counting the possibility for a drug which would have shown a substantial benefit on HRQL/PRO, to have claim in terms of rate of refunding, or price
Why there are so few HRQL mention in labelling ?
Need for improving advertisements
French Drug Approval (1999)
Comparison of Proton Pump Inhibitors in Gastro-oesophageal Reflux Disease
Physical Well-Being
What were hypotheses ?How is defined a
upholding of Well-Being ?
1 single item rangingfrom 0 (very good)
to 4 (very poor)
In protocol : Quality of life = “Time lost from
usual daily activities”
Better result in placebo
group : less time lost (not
disclosed in the publication)
Seen on
TVThis Drug
improves your
Quality of lif
e !
PRO endpoint, as useful as spirometry
What can one wish for the future ?
• Training of reviewers and regulators to HRQL & PROWORKMAT : Educational Program for Reviewers
• Appropriation and adaptation by regulatory agencies of the published recommendationsGuidelines FDAEuropean Position Paper (EWP) ?
• Questionnaires constantly in adequacy with the beneficial and harmful effects of the new treatments
• Choice among the various questionnaires, of those which have the best psychometric properties (responsiveness)
• That HRQL and PRO be part of the daily medical-decision making
Should we develop questionnaires for specific subgroups (e.g HIV) ?Women
Quality of life among women living with HIV: the importance violence, social support, and self-care behaviors. Gielen AC et al. Soc Sci Med 2001.
Injection drug usersPsychological distress and quality of life in drug-using and non-drug-using HIV-infected women. Vaarwerk MJ et al. Eur J Public Health 2001.
AgingSuccessful aging among people with HIV / AIDS. Kahana E et al. J Clin Epidemiol 2001.
Children - adolescentsEvaluation of life quality for children infected by HIV: validation of a method and preliminary results. Nicolas J et al. Pediatr AIDS HIV Infect 1996.
FamilyThe family context of HIV: a need for comprehensive health. De Matteo D et al. AIDS Care 2002.
According to religionRelationships of religion, health status, and socioeconomic status to the quality of life of individuals who are HIV positive. Flannelly LT et al. Issues Ment Health Nurs 2001.
What can one wish for the future ?
• Routine assessment of cancer patients' HRQL had an impact on physician-patient communication and resulted in benefits for some patients, who had better HRQL and emotional functioning
Velikova G, et al. Measuring quality of life in routine oncology practice improves communication and patient well-being: a randomized controlled trial. J Clin Oncol 2004; 22: 714-724
Measuring HRQL in routine oncology practice improves communication and patient well-being