AJ Harrison¹, G Sowman², H Kaur-Nagra PhD², D Price³, M Brown³, P Ford MD³.
Spirometry is one of the few clinical measurements that requires maximum patient effort in order to achieve acceptable and repeatable results. Obtaining valid Spirometry data from chronic obstructive pulmonary disease (COPD) patients who present to the clinic with an exacerbation can be challenging.
Pharmaceutical trials are reliant on accurate data to meet endpoints. We will demonstrate that by using standardised equipment and Over-Reading² we can maintain excellent data quality in this challenging patient population. The patient factor is significant when low values are expected for COPD patients struggling with an exacerbation. Having well-trained clinical staff who can coach these patients correctly can have a significant impact on the quality of Spirometry. The accuracy and quality of Spirometry is also particularly important in clinical trials where Spirometry data are used as primary endpoints.
A total of 93 moderate to very severe COPD patients performed 672 Spirometry sessions. Out of those sessions, 96% met the ATS/ERS FVC repeatability criteria¹ and 99% met the FEV1 repeatability criteria¹. The ATS/ERS 2005 criteria are widely used in clinical trials as a benchmark for the quality of Spirometry.
In an international multicentre trial, 93 COPD patients (Gold II – IV) aged 43-80 years old and presenting with a COPD exacerbation were randomised into a clinical trial. Spirometry was performed at both the initial visit and subsequent sessions over a 6 month follow-up period. The Spirometry was conducted by well-trained technicians in 8 centres in 3 European countries. In total, 672 Spirometry sessions were performed. An average patient therefore performed 7 Spirometry sessions. At all sites, the Spirometry was performed using the Vitalograph Spirometry System (including Vitalograph Pneumotrac™ (Fleisch) spirometer run on Spirotrac® software customised for the trial) with Over-Reading.
Before the trial commenced all technicians were trained in the correct use of the equipment and
trial specific procedures. In addition, all technicians were required to demonstrate their ability to perform acceptable and repeatable Spirometry sessions prior to gaining trial accreditation. Throughout the trial
each centre was monitored for spirometric quality to ensure that site re-training was undertaken if required.
After primary review by the technician, the sessions were transmitted to a central
Vitalograph and QA reviewed ("Over-Read") by one of three expert Over-Readers within 1-2 business
days of receipt. All of the Over-Readers reviewed each session according to the trial-specific
acceptability criteria (based on the ATS/ERS Guidelines¹).
As per the ATS/ERS standards¹, the protocol allowed up to eight manoeuvres
per session which
needed to meet the FVC and FEV1 acceptability criteria. The repeatability for both FEV1 and FVC
was calculated as the difference between the two highest acceptable readings of a session.
A total of 672 (100%) spirometric sessions were recorded at 8 sites in 3 European countries by 93 patients (Country A – 41 patients, Country B - 30, Country C - 22) presenting with a COPD exacerbation. The repeatability for both FEV1 and FVC was calculated as the difference between the two highest acceptable readings (Figure 1).
The mean figures for each country's repeatability (Figure 1) are within the ATS/ERS recommendation of 150ml. The overall mean repeatability was 69 for FVC and 40 for FEV1. Country C had both the lowest FVC and FEV1 mean repeatability (but also the fewest patients).
|TABLE 1: % OF TOTAL SESSIONS WITHIN REPEATABILITY GRADE BY COUNTRY|
|Repeatability (ml)||Country A (%)||Country B (%)||Country C (%)||Overall (%)|
Overall 4% of FVC manoeuvres were outside the ATS/ERS repeatability limit and just 1% for FEV1.
With standardised equipment, well-trained technicians and QA review by independent Over-Readers, patients presenting to clinic with COPD exacerbations can produce reliable and repeatable data in clinical trials.
1. M.R. Miller et al. ATS/ERS Task Force: Standardisation of Spirometry, Eur Respir J 2005; 26: 319-338 2. AJ Harrison, et al. Quality control of respiratory measurements in global trials. ERJ 2006; 28: S50, 984
Novartis International AG for use of their data.