NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

Norris SL, Yen PY, Dana TL, et al. Drug Class Review: Beta2-Agonists: Final Report [Internet]. Portland (OR): Oregon Health & Science University; 2006 Nov.

  • This publication is provided for historical reference only and the information may be out of date.

This publication is provided for historical reference only and the information may be out of date.

Cover of Drug Class Review: Beta2-Agonists

Drug Class Review: Beta2-Agonists: Final Report [Internet].

Show details


Literature Search

To identify relevant citations, two independent reviewers identified potentially relevant titles and abstracts from the Cochrane Central Register of Controlled Trials (Issue 1, 2006), Cochrane Database of Systematic Reviews, DARE, and MEDLINE (1966 to February, week 4, 2006). Search terms included drug names and indications (see Appendix A for complete search strategies). To identify additional studies, we also searched reference lists of included studies and reviews, and we reviewed dossiers submitted by pharmaceutical companies. All citations were imported into an electronic database (EndNote 9.0.0, Thompson Scientific).

Articles deemed potentially relevant after review of titles and abstracts were then retrieved in full-text form. Two independent reviewers achieved consensus on all included and excluded articles. Excluded articles were coded in the EndNote database with the reason for exclusion.

Study Selection

The pharmacotherapeutic agents reviewed were a selection of drugs currently available in the United States and of interest to the Drug Effectiveness Review Stakeholders (Table 2). In addition, we were asked to review two drugs available only in Canada: terbutaline (Bricanyl™) and fenoterol (Berotec™).

Table 2. Inclusion and exclusion criteria.

Table 2

Inclusion and exclusion criteria.

We included all formulations of the included drugs reviewed in the literature, including formulations not currently available in the U.S. (for example, salmeterol as a MDI).

Participants in included studies were adults or children with asthma or exercise-induced asthma, and adults with COPD. Studies were excluded which examined mixed populations where outcomes were not presented for subgroups of interest to us.

We examined studies that present one or more of the primary outcomes of interest to this review: effectiveness outcomes and outcomes related to safety and harms. For both effectiveness as well as safety, published and as well as unpublished English-language reports in any geographic setting were included if they had a total sample size ≥ 10. We included letters if primary data were presented and there was sufficient detail to evaluate quality. We excluded abstracts and conference proceedings, as these publications generally do not have sufficient detail to assess internal or external validity. Theses were not included as the full-text is frequently difficult to retrieve.

For the assessment of efficacy and effectiveness, we included reports of randomized controlled trials (RCTs) and controlled clinical trials which made direct comparison between the drugs of interest to us (i.e., head-to-head trials). For the assessment of adverse effects, we examined studies with head-to-head comparisons only, but we included a broad range of study designs: observational studies, before-after studies, and case series with a sample size ≥ 10, in addition to RCTs and controlled clinical trials. Clinical trials are often not designed to assess adverse events, may select low-risk patients (in order to minimize drop-out rates), or may have too short a follow-up period in which to adequately assess safety. Observational studies designed to assess adverse event rates may include broader populations, carry out observations over a longer time period, utilize higher quality methodological techniques for assessing adverse events, or examine larger sample sizes.

Data Abstraction

We abstracted relevant descriptive and outcomes data into a relational database developed for this review. We recorded results achieved with an intention-to-treat analytic approach, when reported. If only per-protocol results were reported, we specified the nature of these results and reported them. In trials with crossover, outcomes for the first intervention were recorded if available. This was because of the potential for bias due to differential withdrawal prior to crossover, the possibility of a "carryover effect" (from the first treatment) in studies without a washout period, and a "rebound" effect from withdrawal of the first intervention.

Quality Assessment

We assessed the internal validity (quality) of controlled clinical trials using the predefined criteria listed in the quality assessment tool found in Appendix B. These criteria are based on those used by the U.S. Preventive Services Task Force and the National Health Service Centre for Reviews and Dissemination. For each included trial, we assessed the following criteria: methods used for randomization; allocation concealment; blinding of participants, investigators, and assessors of outcomes; the similarity of comparison groups at baseline; adequate reporting of attrition, crossover, adherence, and contamination; post-allocation exclusions, and the use of intention-to-treat analysis.

We assessed observational and other study designs with adverse event data based on non-biased selection of patients, loss to follow-up, non-biased and accurate ascertainment of events, and control for potential confounders (Appendix B).

These criteria were then used to categorize studies into good, fair, and poor quality studies. Studies that had a significant flaw in design or implementation such that the results were potentially not valid were categorized as "poor". Studies which met all quality criteria were rated good quality; the remainder were rated fair. As the "fair quality" category is broad, studies with this rating vary in their strengths and weaknesses. Studies rated of poor quality are presented in the in-text tables and the evidence tables, but do not contribute to the conclusions of this report.

External validity of studies was assessed by examining the following: whether the study population was adequately described; inclusion and exclusion criteria; and whether the treatment received by the comparison group was reasonably representative of standard practice.

Systematic reviews which fulfilled inclusion criteria were rated for quality using predefined criteria (see Appendix B): a clear statement of the questions and inclusion criteria; adequacy of the search strategy; quality assessment of individual trials; the adequacy of information provided; and appropriateness of the methods of synthesis.

Data Analysis and Synthesis

We compared LABA to LABA and SABA to SABA, as these two types of inhaled beta2-agonists are indicated in different situations which are not generally considered interchangeable.1 The LABA are indicated for maintenance treatment in persistent asthma and for chronic use in some patients with COPD, whereas the SABA are used for rescue (acute symptomatic) treatment and are not generally recommended for regularly scheduled daily use.1

Important descriptive information about the population, setting, and intervention, as well as quality assessment are presented in tabular format. Data were synthesized and are presented in a narrative fashion as there was too much clinical and methodologic diversity to pool the data in a meta-analysis.

Copyright © 2006, Oregon Health & Science University, Portland, Oregon.
Bookshelf ID: NBK10435


Other titles in this collection

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...