The (ab)use of symptom scores in asthma clinical trials: a systematic review Geoff Frampton & Jonathan Shepherd Southampton Health Technology Assessments

The (ab)use of symptom scores in asthma clinical trials: a systematic review

Geoff Frampton & Jonathan Shepherd

Southampton Health Technology Assessments Centre

Background


Symptom scores in asthma clinical research

Symptoms are important to patients

Goal of therapy is asthma control

The multidimensional character of asthma is best captured using multiple outcomes

- binary (yes/no) scales

- symptoms combined with other variables

- summary proportions (e.g. % symptom-free days)

Excluded:

Any numeric symptom scales

Included:

0 31 2

Scope of this presentation

Background


Ideal features of patient-reported outcomes

Validity

Responsiveness

Reliability (internal consistency, reproducibility)

Interpretability


To determine by systematic review:

Do they fulfil the requirements of patient-reported outcomes ?

How are the scores interpreted clinically ?

What types of symptom score scales are used in asthma clinical trials ?

Objective

Do they reflect circadian variation in asthma ?

How are they analysed ?

Methods

National Institute for Health and Clinical Excellence(NICE) review and update of guidelines on inhaled corticosteroids and long-acting beta agonists for management of asthma in adults and children

Systematic reviews of asthma drug effectiveness and safety (SHTAC and PenTAG)

Source of evidence:

www.hta.ac.uk

Systematic extraction of symptoms data



Results

87 randomized controlled trials (RCTs) published in 32 English language journals, 1985 to 2006

0

2

4

6

8

10

12

14

1981 1986 1991 1996 2001 2006

Total number of RCTs

RCTs that used tested scales

RCTs that measured symptom scores

J:\SHTAC\Projects\Research\Healthcare Associated Infections\Catheter education in critical care\Correspondence with experts

78 RCTs (90%)

Principal symptom domains in 78 asthma RCTs

Overall asthma severity

Not reported

Dyspnoea

Wheeze

Cough

Asthma duration or frequency

Multiple domains

Other

32%

15%

13%

9%

9%

8%

7%

7%


21 different symptom domains

Results – symptom assessments

Numerical symptom scales used in 78 asthma RCTs

4-item

6-item

7-item

Scale not reported

> 7 items

5-item

Other

Type of scale

46%

19%

12%

10%

6%

5%

3%


10 unique numeric scales



Timing of symptom assessments in 78 asthma RCTs

Day

Night

Unclear

Not reported

Sum of (day + night)

32%

28%

5%

8%

6%

am

pm

other

8%

7%

7%

8 different timings of symptom assessments


1 2 3 4 5 6 7 8 9 10 11

11 randomized controlled trials

-6

2

1

0

134

Symptom score


Results – circadian patterns

Asthma severity scores Day Night

134Southampton Health Technology Assessments Centre

Method of analysis of symptom scores

1986 2006200119961991

Number of RCTs

0

2

4

6

8

10

Parametric Nonparametric

Not reported

Results – analysis methods

Statistically significant effects of inhaler treatment on scores

76% 37%

Discussion


Asthma symptom scales appear to be almost all unique

How should we interpret the numeric scores clinically ? (e.g. minimal important difference; NNT)

There is hardly any information on their reliability, validity and responsiveness

Which are the correct statistical analyses?

What do the robust diurnal patterns in symptom scores mean ?


In conclusion, asthma clinical trials should…

2. Provide guidance on clinical interpretation

1. Share the use of fewer, tested, symptom score instruments

4. Explain the statistical testing rationale and any assumptions

The views and opinions expressed in this presentation are those of the authors and do not necessarily reflect those of the UK Department of Health

Thank you for your attention!

3. Precisely report the timing of symptom assessments

Documents

The (ab)use of symptom scores in asthma clinical trials: a systematic review Geoff Frampton & Jonathan Shepherd Southampton Health Technology Assessments