Asthma Clinical Research Articles

Development and Deployment of an Internet-Based Data Management System for Use by the Asthma Clinical Research Network

Data management system development for the first Asthma Clinical Research Network (ACRN) study began at the data coordinating center (DCC) in May 1995 with the requirement for delivery of a production system by November 1995. Special methods had to be used to establish an internet local area network (LAN), place clinical client systems, and achieve an accelerated software development cycle. The development of a fully integrated data management system prior to the start of the study was not possible. Therefore an early analysis focused on identifying discrete groupings of data management functions that would allow development of distinct database modules to provide specific functionality such as subject randomization, subject registration, and data entry. The modules were categorized as either being associated with clinical centers or the DCC so that the clinical center modules could be developed and delivered to meet the start date of the study. In the second phase of development during the relatively slow patient-enrollment period, the DCC functional modules were delivered discretely over time. While at the time this development model was a necessity due to limited DCC resources, it continues to be used today as it permits the DCC to implement studies more rapidly and efficiently for the ACRN. This paper describes the methodologies used to develop an internet-based LAN, establish clinical center client systems, establish DCC client and server operations, and develop a data management system. It describes the circumstances that contributed to the development of these systems and the special methodologies developed. The technical aspects of the data management system and LAN are presented as well as a description of the requirements and constraints analysis used to develop the hardware and software systems. Control Clin Trials 2001; 22:135S–155S

The Organization of the Asthma Clinical Research Network: A Multicenter, Multiprotocol Clinical Trials Team

Asthma is an increasingly serious cause of morbidity and mortality in the United States, affecting approximately 12 million people, including men and women, children and adults, and all racial and ethnic groups. It is now recognized that asthma is a complex disease of varied etiology triggered by a number of factors such as allergens, drugs, chemicals, exercise, cold dry air, infections, and emotions. Asthma is a chronic disease requiring multiple medications to treat and control symptoms as well as medications thought to control the underlying inflammation. Despite major advances in understanding the etiology and pathophysiology of asthma and the development of new therapeutic modalities, the prevalence, severity, and mortality from asthma have all increased over the past decades in all age groups. Hospitalizations for asthma have doubled in adults and increased fivefold for children over the past 20 years. Mortality appears to be particularly high in urban and rural minority populations. Asthma continues to place a heavy burden on patients and their families as well as the health-care system. In an attempt to respond to the need for well-designed clinical trials to allow rapid evaluation of new and existing therapeutic approaches for asthma and for dissemination of laboratory and clinical findings to the health-care community, the Division of Lung Diseases, National Heart, Lung, and Blood Institute, established the Asthma Clinical Research Network. Control Clin Trials 2001;22:119S–125S

Implementing Randomization Procedures in the Asthma Clinical Research Network

Randomization is a required component for the success of most controlled clinical trials. To ensure that the benefits of randomization are realized, well defined and carefully planned procedures must be put in place prior to the start of a trial. This paper presents a detailed account of the registration and randomization procedures implemented for the first four clinical trials of the Asthma Clinical Research Network. Control Clin Trials (2001) 22:181S–195S

The Clinical Trials in the Initial Five-Year Award Period of the Asthma Clinical Research Network

During its first years of existence, the Asthma Clinical Research Network initiated four major clinical trials and one pilot clinical trial. The objective of this article is to describe briefly the specific aims, design, and conduct of those five trials. Control Clin Trials 2001; 22:126S–134S

Data Management Procedures in the Asthma Clinical Research Network

Well-designed data management processes are essential in ensuring the quality of data collected in multicenter clinical trials. This paper describes the data management processes and systems that were developed by the data coordinating center of the Asthma Clinical Research Network. A combination of manual and electronic processes has been designed to process clinical trial data from the point of collection to statistical analysis. A distributed database management system consisting of modular applications for separate data processing activities was developed to enter, track, verify, validate, and edit collected data. In addition, processes for monitoring and reporting data quality are discussed. Control Clin Trials 2001;22:168S–180S

The Utility of Peak Flow, Symptom Scores, and β-Agonist Use as Outcome Measures in Asthma Clinical Research

Several methods of utilizing peak expiratory flow (PEF) and other markers of disease activity have been suggested as useful in the management of asthma. It remains unclear, however, as to which surrogate markers of disease status are discriminative indicators of treatment failure, suitable for use in clinical trials. We analyzed the operating characteristics of 66 surrogate markers of treatment failure using a receiver operating characteristic (ROC) curve analysis. Information regarding FEV(1), symptoms, beta(2)-agonist use, and PEF was available from 313 subjects previously enrolled in two Asthma Clinical Research Network trials, in which 71 treatment failures occurred (defined by a 20% fall in FEV(1) from baseline). None. None of the measures had an acceptable ability to discriminate subjects with a > or % fall in FEV(1) from those without, regardless of the duration of the period of analysis or the criteria for test positivity employed. Areas under the ROC curves generated ranged from 0.51 to 0.79, but none were statistically superior. Sensitivity and specificity combinations were generally poor at all cutoff values; true-positive rates could not be raised without unacceptably elevating false-positive rates concurrently. Studies that seek to detect treatment failure defined by a significant fall in FEV(1) should not use such individual surrogate measures to estimate disease severity.

Role of salmeterol in asthma becomes clear

With recognition that inflammation plays a major role in the pathogenesis of asthma, treatment paradigms have shifted to emphasise the early use of anti-inflammatory therapy. However, the role of anti-inflammatory agents and long-acting β2-agonists, and their impact on airway remodelling, remains controversial. At the Annual International Conference of the American Lung Association and the American Thoracic Society [San Diego, US; April 1999] delegates heard the first presentation of results from 2 long-term trials which examined the importance of inflammation in asthma and the role of inhaled corticosteroids and a long-acting β2-agonist. The trials were conducted by the US multicentre Asthma Clinical Research Network (ACRN) and examined the utility of treating patients with moderate asthma with a long-acting β-agonist in place of inhaled corticosteroids (Salmeterol Off CorticoSteroids; SOCS) or in addition to inhaled corticosteroids (SaLmeterol ± Inhaled Corticosteroids; SLIC). According to the results of the trials, patients whose asthma is well controlled by corticosteroids should not be switched to salmeterol monotherapy because of the risk of worsening airway inflammation and losing asthma control. Additionally, salmeterol can reduce the use of corticosteroids but total elimination of corticosteroids is not recommended.

Assessment of the AirWatch lung function monitoring system

Accuracy is defined by the median relative bias (MRB), with the initial acceptable range of ± 15% and repeat testing within ± 5% of the initial value.7 Precision is defined by the interquartile range (IQR), with the initial acceptable range less than 10% and repeat testing less than 5% greater than the initial value.7 Different peak expiratory flow (PEF) rates were created by 12 compressions of a Jones calibrating syringe connected in series to a pneumotachograph (standard) and 12 separate AW devices (Fig 1). This allowed for simultaneous recorded measurements of PEF and calculation of accuracy and precision. For FEV1 accuracy and precision, each of the 20 AW devices was placed in an airtight chamber in series between a spirometer and 3 different sources of flow generation: the Jones syringe, a 4-L syringe, and a wave form generator. AW durability was assessed by determining the MRB and IQR for 5 different flow rates at each of 6 clinic visits over a 10-week Abbreviations used ACRN: Asthma Clinical Research Network AW: AirWatch IQR: Interquartile range MRB: Median relative bias PEF: Peak expiratory flow

Scheduled and as-needed albuterol were equivalent for mild asthma

Source Citation Drazen JM, Israel E, Boushey HA, et al., for the National Heart, Lung, and Blood Institute's Asthma Clinical Research Network. Comparison of regularly scheduled with as-needed use o...

Measurement of quality of life in pediatric asthma clinical trials.

This review will provide the reader a current appraisal of attempts to measure quality of life (QoL) in pediatric asthma and guidelines toward making a discriminating selection from available QoL questionnaires. A MEDLINE literature search was performed using the index terms quality of life and asthma. Reference lists from articles identified through this search were also perused. References that did not include the term "quality of life" but clearly addressed this topic were included. Nine questionnaires employed in studies evaluating life quality associated with pediatric asthma were identified. Five of the questionnaires are parent-completed and four are child-completed. The instruments vary considerably in length and content areas, and most have been used in a single study. The science of measuring QoL change associated with pediatric asthma is in its infancy and the decision to use any single QoL instrument should be made cautiously. Investigators seeking to employ a QoL questionnaire in pediatric asthma clinical trials must consider several problems specific to evaluation with children, including age effects, reading ability, impact of adult assistance upon responses, and the inclusion of mother- versus father-completed questionnaires. The selected QoL questionnaire should address specific hypotheses and be piloted by the investigator before inclusion in a planned investigation.

Issues in the use of inhaled glucocorticoids. The Asthma Clinical Research Network.

Issues in the use of inhaled glucocorticoids. The Asthma Clinical Research Network.

Measures for use in asthma clinical research. Overview of the NIH workshop.

Asthma is a major health problem in the United States; both mortality and morbidity are increasing. Approximately 12million Americans, including 4 million under the age of 18 years, are affected. People with asthma experience more than 100 days of restricted activity annually, and costs for asthma care exceed $4.6 billion a year (1). The National Asthma Education Program (NAEP) was established by the National Heart, Lung, and Blood Institute (NHLBI) in 1989 in recognition of the impact of asthma on individuals, their families, the medical care system, and society. The goals of the program are to educate patients, health professionals, and the public about asthma. Effective control of asthma is promoted through modern, science-based treatment and education programs and by encouraging a partnership among patients, physicians, and other health professionals (2). The first major task of the NAEP was to develop and disseminate Guidelines for the Diagnosis and Management of Asthma (3). Rather than just relieving acute exacerbations of respiratory distress with bronchodilator therapy, first-line therapy now aims to control inflammation by use of cromolyn and inhaled corticosteroids. That report, which is changing clinical management of the disease, was followed in 1992 by Management of Asthma During Pregnancy (4). Another report in preparation focuses on management of asthma in the elderly.

8 Effects of diethylstilbestrol and its mono- and diphospate on experimental mammary and prostatic tumors

Quality control and assurance are very important issues for multicenter clinical investigation. Although such investigation usually states that those factors are part of the investigation, at best this occurs to a minimal extent. Indeed, to ensure the best possible investigatory results with the least amount of variance between centers, the Asthma Clinical Research Network (ACRN) instituted strict written criteria that were continually overviewed. This article describes the ACRN's quality control of: clinic procedures and equipment, training and certification of study personnel, site visit evaluations, and the procedures of bronchoscopy and sputum induction. The examples given in this report demonstrate how various aspects of our investigation are performed. Controlled Clinical Trials 22:207S–221S (2001)

7 Prospective study of diethylstilbestrol-diphosphate in the treatment of prostatic cancer in relapse

Quality control and assurance are very important issues for multicenter clinical investigation. Although such investigation usually states that those factors are part of the investigation, at best this occurs to a minimal extent. Indeed, to ensure the best possible investigatory results with the least amount of variance between centers, the Asthma Clinical Research Network (ACRN) instituted strict written criteria that were continually overviewed. This article describes the ACRN's quality control of: clinic procedures and equipment, training and certification of study personnel, site visit evaluations, and the procedures of bronchoscopy and sputum induction. The examples given in this report demonstrate how various aspects of our investigation are performed. Controlled Clinical Trials 22:207S–221S (2001)

Book ReviewThe Practical Management of Asthma Clinical Allergy and Immunology

Book ReviewThe Practical Management of Asthma Clinical Allergy and Immunology