Pulmonary-Allergy Drugs Advisory Committee September 6, 2002 1 SGRQSGRQ 3 Domains: –Symptoms:...

1Pulmonary-Allergy Drugs Advisory Committee Pulmonary-Allergy Drugs Advisory Committee September 6, 2002September 6, 2002

SGRQSGRQSGRQSGRQ• 3 Domains:– Symptoms: cough, sputum production,

wheeze, breathlessness, duration and frequency of attacks of breathlessness

– Activity: physical activities that either cause or are limited by breathlessness

– Impacts: employment, being in control of health, panic, stigmatization, need for medication, side effects of medication, expectations for health, disturbance of daily life

• 3 Domains:– Symptoms: cough, sputum production,

wheeze, breathlessness, duration and frequency of attacks of breathlessness

– Activity: physical activities that either cause or are limited by breathlessness

– Impacts: employment, being in control of health, panic, stigmatization, need for medication, side effects of medication, expectations for health, disturbance of daily life


SGRQSGRQSGRQSGRQ

• Included at baseline and at the following visits: – 114/115: Weeks 7, 13, 25, 37, 49– 122A/122B: Weeks 7, 13, 26, 39, 52– 130/137: Weeks 8, 16, and 24

• Total Score: Tiotropium statistically and clinically ( 4 units) superior to comparator:– 114/115: 2/10– 122A/122B: 1/10– 130/137: 0/6

• Included at baseline and at the following visits: – 114/115: Weeks 7, 13, 25, 37, 49– 122A/122B: Weeks 7, 13, 26, 39, 52– 130/137: Weeks 8, 16, and 24

• Total Score: Tiotropium statistically and clinically ( 4 units) superior to comparator:– 114/115: 2/10– 122A/122B: 1/10– 130/137: 0/6


SGRQ: Activity ScoreSGRQ: Activity ScoreSGRQ: Activity ScoreSGRQ: Activity Score

Tiotropium was statistically superior to comparator:• Study 114: 2/5• Study 115: 4/5• Study 122A: 0/5• Study 122B: 1/5• Study 130: 0/3• Study 137: 1/3



SGRQ: SymptomsSGRQ: SymptomsSGRQ: SymptomsSGRQ: Symptoms




BDI/TDIBDI/TDIBDI/TDIBDI/TDI

• Interviewer asks open-ended questions. Interviewer interprets responses and selects a score.

• The majority of other dyspnea indices are completed by the patient.

• Interviewer asks open-ended questions. Interviewer interprets responses and selects a score.

• The majority of other dyspnea indices are completed by the patient.


Dyspnea IndicesDyspnea IndicesDyspnea IndicesDyspnea Indices• BDI/TDI [Interviewer]• Medical Research Council Breathlessness Scale [Patient]• American Thoracic Society Dyspnea Scale [Patient]• Chronic Respiratory Questionnaire (Dyspnea component)

[Patient]• UCSD Shortness of Breath Questionnaire [Patient]• Modified Borg Dyspnea Scale [Patient]• Shortness of Breath Questionnaire (Archibald, 1987)

[Patient]• Dyspnea Index (Lareau, 1994) [Patient]• Oxygen-cost diagram (visual analog) [Patient]• Visual Analog Scale [Patient]

• BDI/TDI [Interviewer]• Medical Research Council Breathlessness Scale [Patient]• American Thoracic Society Dyspnea Scale [Patient]• Chronic Respiratory Questionnaire (Dyspnea component)

[Patient]• UCSD Shortness of Breath Questionnaire [Patient]• Modified Borg Dyspnea Scale [Patient]• Shortness of Breath Questionnaire (Archibald, 1987)

[Patient]• Dyspnea Index (Lareau, 1994) [Patient]• Oxygen-cost diagram (visual analog) [Patient]• Visual Analog Scale [Patient]


““Reliability and Validity of Dyspnea Reliability and Validity of Dyspnea Measures in Patients with Obstructive Lung Measures in Patients with Obstructive Lung

Disease”Disease”



• BDI– “In our experience, to use this instrument

reliably, it was necessary for our four raters to discuss and standardize questions and to come to some consensus as to how ratings should be made on each one of the three scales. Ongoing assessment of inter-rater reliability to check for tendencies of each rater to stray from initial standardization was also needed.”

• BDI– “In our experience, to use this instrument

reliably, it was necessary for our four raters to discuss and standardize questions and to come to some consensus as to how ratings should be made on each one of the three scales. Ongoing assessment of inter-rater reliability to check for tendencies of each rater to stray from initial standardization was also needed.”

[Eakin EG, et al. International Journal of Behavioral Medicine, 1995]






• TDI– “may be affected by bias on the part of the

patient and interviewer because it asks both individuals to make judgements about improvement versus deterioration in the patient’s status since baseline. Like the BDI, the TDI lacks standardized questions for raters.”

• TDI– “may be affected by bias on the part of the

patient and interviewer because it asks both individuals to make judgements about improvement versus deterioration in the patient’s status since baseline. Like the BDI, the TDI lacks standardized questions for raters.”

[Eakin EG, et al. International Journal of Behavioral Medicine, 1995]


Mean Trough FEV1, by TDI ResponseMean Trough FEV1, by TDI Response(Study 137, at 6 months)(Study 137, at 6 months)

Mean Trough FEV1, by TDI ResponseMean Trough FEV1, by TDI Response(Study 137, at 6 months)(Study 137, at 6 months)

• TDI “non-responders”Tiotropium Placebo Salmeterol

Trough FEV1: 0.029L -0.056L 0.038L

• TDI “responders”Tiotropium Placebo Salmeterol

Trough FEV1: 0.107L 0.032L 0.087L

• TDI “non-responders”Tiotropium Placebo Salmeterol

Trough FEV1: 0.029L -0.056L 0.038L

• TDI “responders”Tiotropium Placebo Salmeterol

Trough FEV1: 0.107L 0.032L 0.087L


FEV1 Response* by TDI ResponseFEV1 Response* by TDI Response(Study 130, at 6 months)(Study 130, at 6 months)


*defined as improvement 12% in trough FEV1, compared to baseline*defined as improvement 12% in trough FEV1, compared to baseline

Tiotropium

TDIResponse

FEV1Response No Yes Total

No 67 39 106Yes 40 38 78

Total: 107 77 184

Placebo

TDIResponse


No 88 30 118Yes 21 9 30

Total 109 39 148




*defined as improvement 12% in trough FEV1, compared to baseline*defined as improvement 12% in trough FEV1, compared to baseline

Tiotropium

TDIResponse


No 67 39 106Yes 40 38 78

Total: 107 77 184

Salmeterol

TDIResponse


No 75 36 111Yes 41 27 68

Total 116 63 179




*defined as improvement 12% in trough FEV1, compared to baseline


Tiotropium

TDIResponse


No 62 44 106Yes 29 29 58

Total: 91 73 164

Placebo

TDIResponse


No 93 41 134Yes 15 12 27

Total 108 53 161






Tiotropium

TDIResponse


No 62 44 106Yes 29 29 58

Total: 91 73 164

Salmeterol

TDIResponse


No 60 50 110Yes 24 27 51

Total 84 77 161

Pulmonary-Allergy Drugs Advisory Committee September 6, 2002 1 SGRQSGRQ 3 Domains: –Symptoms:...

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