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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, PhD Délégation à la Recherche Clinique (AP-HP) Hôpital Saint-Louis, Paris

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Page 1: 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

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

Page 2: 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

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

Page 3: 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

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

Page 4: 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

“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)

Page 5: 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

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

Page 6: 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

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

Page 7: 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

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 ?)

Page 8: 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

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

Page 9: 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

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.

Page 10: 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

-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

Page 11: 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

““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

Page 12: 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

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

Page 13: 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

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

Page 14: 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

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

Page 15: 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

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

Page 16: 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

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

Page 17: 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

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

Page 18: 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

Relation score FDDQL apprécié par le médecin / score FDDQL apprécié par le patient pour le retentissement sur l'activité quotidienne

0,00

10,00

20,00

30,00

40,00

50,00

60,00

70,00

80,00

90,00

100,00

0 1 2 3 4 5médecin

pat

ient

Score FDDQLactivitéquotidienne

Scores égaux

Relation score FDDQL apprécié par le médecin / score FDDQL apprécié par le patient pour le degré d'anxiété

0,00

10,00

20,00

30,00

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80,00

90,00

100,00

0 1 2 3 4 5

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

0,00

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20,00

30,00

40,00

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90,00

100,00

0 1 2 3 4 5médecin

pati

en

t

ScoreFDDQLalimentation

Scoreségaux

Relation score FDDQL apprécié par le médecin / score FDDQL apprécié par le patient pour le retentissement sur le sommeil

0,00

10,00

20,00

30,00

40,00

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60,00

70,00

80,00

90,00

100,00

0 1 2 3 4 5médecin

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

Page 19: 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

Relation score FDDQL apprécié par le médecin / score FDDQL apprécié par le patient pour le retentissement sur la vie sociale

0,00

10,00

20,00

30,00

40,00

50,00

60,00

70,00

80,00

90,00

100,00

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

0,00

10,00

20,00

30,00

40,00

50,00

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90,00

100,00

0 1 2 3 4 5

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

0,00

10,00

20,00

30,00

40,00

50,00

60,00

70,00

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90,00

100,00

0 1 2 3 4 5médecin

pat

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

0,00

10,00

20,00

30,00

40,00

50,00

60,00

70,00

80,00

90,00

100,00

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

Page 20: 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

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)

Page 21: 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

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

Page 22: 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

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

Page 23: 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

Relation score CIVIQ apprécié par le médecin / score CIVIQ apprécié par le patient pour le retentissement douleur

0,00

10,00

20,00

30,00

40,00

50,00

60,00

70,00

80,00

90,00

100,00

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

0,00

10,00

20,00

30,00

40,00

50,00

60,00

70,00

80,00

90,00

100,00

0 1 2 3 4 5 6 7 8 9 10

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

0,00

10,00

20,00

30,00

40,00

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60,00

70,00

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100,00

0 1 2 3 4 5 6 7 8 9

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

0,00

10,00

20,00

30,00

40,00

50,00

60,00

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80,00

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100,00

0 1 2 3 4 5 6 7 8 9 10

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]

Page 24: 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

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

0

10

20

30

40

50

60

70

80

90

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]

Page 25: 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

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

Page 26: 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

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

Page 27: 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

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

Page 28: 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

• 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

Page 29: 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

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) …

Page 30: 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

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

Page 31: 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

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.

Page 32: 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

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.

Page 33: 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

• 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

Page 34: 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

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.

Page 35: 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

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

Page 36: 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

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

Page 37: 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

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

Page 38: 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

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.

Page 39: 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

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.

Page 40: 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

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

Page 41: 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

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

Page 42: 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

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.

Page 43: 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

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

Page 44: 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

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

Page 45: 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

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

Page 46: 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

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

Page 47: 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

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.

Page 48: 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

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.

Page 49: 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

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 ?

Page 50: 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

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 ?

Page 51: 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

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

Page 52: 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

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

Page 53: 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

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.

Page 54: 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

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.

Page 55: 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

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 ?

Page 56: 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

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

Page 57: 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

• 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)

Page 58: 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

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 ?

Page 59: 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

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

Page 60: 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

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

Page 61: 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

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.

Page 62: 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

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 ?

Page 63: 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

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 ?

Page 64: 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

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 ?

Page 65: 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

N = 30

Who measures Well-Being ? Clinicians ??

Analysis of Well-Being between indapamide and captopril.Lacourciere Y. Am J Med 1988; 84: 47-51.

Page 66: 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

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

Page 67: 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

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

Page 68: 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

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

Page 69: 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

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

Page 70: 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

From Pr Ingela Wiklund (AstraZeneca)

Page 71: 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

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

Page 72: 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

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.

Page 73: 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

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

Page 74: 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

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

Page 75: 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

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

Page 76: 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

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

Page 77: 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

(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 ?

Page 78: 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

(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 ?

Page 79: 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

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 ?

Page 80: 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

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)

Page 81: 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

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)

Page 82: 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

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.

Page 83: 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

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)

Page 84: 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

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)

Page 85: 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

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

Page 86: 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

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

Page 87: 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

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

Page 88: 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

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

Page 89: 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

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

Page 90: 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

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.

Page 91: 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

• 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 »

Page 92: 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

• 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 »

Page 93: 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

• 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 »

Page 94: 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

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

Page 95: 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

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)

Page 96: 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

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

Page 97: 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

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

Page 98: 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

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

Page 99: 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

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

Page 100: 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

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

Page 101: 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

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.

Page 102: 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

“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…

Page 103: 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

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.

Page 104: 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

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.

Page 105: 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

• 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

Page 106: 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

• 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

Page 107: 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

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.

Page 108: 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

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

Page 109: 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

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.

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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?

Page 111: 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

• 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

Page 112: 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

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

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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

Page 114: 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

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

Page 115: 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

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.

Page 116: 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

(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)

Page 117: 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

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?

Page 118: 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

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 ?

Page 119: 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

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 ?

Page 120: 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

• 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…

Page 121: 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

• 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)

Page 122: 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

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

Page 123: 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

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 :

Page 124: 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

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

Page 125: 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

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

Page 126: 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

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

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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

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• 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 ?

Page 129: 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

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 !

Page 130: 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

PRO endpoint, as useful as spirometry

Page 131: 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

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

Page 132: 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

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 ?

Page 133: 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

• 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