Original article
Quality assurance of asthma clinical trials

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Abstract

Accuracy and repeatability of spirometry measurements are essential to obtain reliable efficacy data in randomized asthma clinical trials. We report our experience with a centralized spirometry quality assurance program that we implemented in our phase III asthma trials. Six asthma trials of 4 to 21 weeks in duration were conducted at 232 clinical centers in 31 countries. Approximately 23,100 prebronchodilator and 13,700 postbronchodilator spirometry tests were collected from 2523 adult and 336 pediatric asthmatic patients. The program used a standard spirometer (the Renaissance™ spirometry system) with maneuver quality messages and automated quality grading of the spirometry tests. Each clinical center transmitted spirometry data weekly to a central database, where uniform monitoring of data quality was performed and feedback was provided in weekly quality reports. Seventy-nine percent of all patients performed spirometry sessions with quality that either met or exceeded American Thoracic Society standards and improved over time. Good-quality spirometry was associated with (1) less severe asthma; (2) active treatment; (3) infrequent nocturnal awakenings; (4) age above 15 years; and (5) low body weight. Maneuver-induced bronchospasm was rare. Good-quality spirometry was observed in multicenter asthma clinical trials that employed a standard spirometer and continuous monitoring. Both within- and between-patient variability decreased. Spirometry quality improved with time as study participants and technicians gained experience.

Introduction

By enhancing the precision and accuracy of endpoint measurement in clinical trials, the ability to demonstrate treatment effects can be improved and study costs can be reduced. Comprehensive spirometry quality control programs have proven to be beneficial for longitudinal, multicenter, epidemiologic studies of chronic obstructive pulmonary disease (COPD) 1, 2; however, such programs have been implemented infrequently in asthma clinical trials when forced expiratory volume in 1 second (FEV1) is a key endpoint.

Early in our asthma program we hypothesized that by increasing the attention to the spirometry data quality, we would reduce the measurement variability and thereby improve the efficiency of the asthma clinical trials. We designed and piloted a quality control program in two early asthma studies 3, 4. In these studies we used a standard spirometer with built-in quality control according to the 1987 American Thoracic Society (ATS) standards [5]. Each study site was provided with this standard spirometer and quality grades were monitored centrally. Monitoring was performed by retrieving the memory cards on a weekly basis, printing the spirometry reports, and reviewing the data manually. For our phase III asthma program, we implemented a comprehensive centralized spirometry quality control program in both the adult and pediatric trials conducted worldwide. This program used the same standard spirometer as our earlier trials; however, it also included extensive site training and direct data transmission to an electronic database. The central database made the data easily accessible for central review of quality and completeness using summary reports. The quality control monitoring was expanded to occur, as much as possible, in “real time.” This report summarizes our experience with, and the characterization of, the spirometry quality control system.

Section snippets

Spirometry system

Each study site was supplied with the Renaissance Spirometry System (Mallincrodt Nellcor/Puritan Bennett-Kansas City, KS, US), which consisted of a handheld spirometer (model PB100), a base station (PB110), data memory cards (PB130), and a 3.0 L calibration syringe. The spirometer, which complies with ATS standards, uses “single patient use” disposable flow sensors and has built-in software with test quality messages and FEV1 and forced vital capacity (FVC) quality grades 5, 6. The test quality

Spirometry data

Spirometry data from six randomized clinical trials conducted worldwide at 232 study sites in 31 countries in North, Central, and South America, Europe, Africa, Asia, Australia, and New Zealand were collected between October 1994 and May 1996 (Table 1). Spirometry data from 2523 adult patients (aged 15 to 85 years) were collected in five trials and 336 pediatric patients (aged 6–14 years) in one trial 8, 9, 10, 11, 12, 13. The patients were randomly allocated in a blinded manner according to

Discussion

In this paper, we report on the spirometry data quality of five adult and one pediatric asthma clinical trials. The spirometry data were collected using a standard spirometer and were transmitted weekly to a centralized quality control center for continuous monitoring of the quality, completeness, and consistency. Our experience suggests that by using these standardization procedures, spirometry data with consistently high quality can be obtained. The value of immediate quality-grade assessment

Acknowledgements

We thank Michael Fuh and John Bowen for their contribution to the design of the spirometry database, patients and study coordinators for performing and collecting the spirometry data and the medical program coordinators in the Respiratory Group at Merck Research Laboratories for monitoring spirometry quality. This investigation was supported by grants from Merck Research Laboratories.

References (23)

  • M Laviolette et al.

    Montelukast added to inhaled beclomethasone in the treatment of asthma

    Am J Resp Crit Care Med

    (1999)
  • Cited by (0)

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