Trial reportClinical pharmacology and therapeutics2017
Between-Batch Pharmacokinetic Variability Inflates Type I Error Rate in Conventional Bioequivalence Trials: A Randomized Advair Diskus Clinical Trial.
Trial report in Clinical pharmacology and therapeutics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
8 citing papers in PubMed.
- Equivalent Systemic Exposure to Fluticasone Propionate/Salmeterol Following Single Inhaled Doses from Advair Diskus and Wixela Inhub: Results of Three Pharmacokinetic Bioequivalence Studies.Journal of aerosol medicine and pulmonary drug delivery · 2020Trial
- Exploration of the potential impact of batch-to-batch variability on the establishment of pharmacokinetic bioequivalence for inhalation powder drug products.CPT: pharmacometrics & systems pharmacology · 2025Article
- Microstructural Characterization of Dry Powder Inhaler Formulations Using Orthogonal Analytical Techniques.Pharmaceutical research · 2024Article
- iBCS: 2. Mechanistic Modeling of Pulmonary Availability of Inhaled Drugs versus Critical Product Attributes.Molecular pharmaceutics · 2022Article
- Performance of Multiple-Batch Approaches to Pharmacokinetic Bioequivalence Testing for Orally Inhaled Drug Products with Batch-to-Batch Variability.AAPS PharmSciTech · 2021Article
- Between-Batch Bioequivalence (BBE): a Statistical Test to Evaluate In Vitro Bioequivalence Considering the Between-Batch Variability.The AAPS journal · 2020Article
- Emerging trends in inhaled drug delivery.Advanced drug delivery reviews · 2020Review
- Clinical Pharmacology & Therapeutics: Past, Present, and Future.Clinical pharmacology and therapeutics · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We previously demonstrated pharmacokinetic differences among manufacturing batches of a US Food and Drug Administration (FDA)-approved dry powder inhalation product (Advair Diskus 100/50) large enough to establish between-batch bio-inequivalence. Here, we provide independent confirmation of pharmacokinetic bio-inequivalence among Advair Diskus 100/50 batches, and quantify residual and between-batch variance component magnitudes. These variance estimates are used to consider the type I error rate of the FDA's current two-way crossover design recommendation. When between-batch pharmacokinetic variability is substantial, the conventional two-way crossover design cannot accomplish the objectives of FDA's statistical bioequivalence test (i.e., cannot accurately estimate the test/reference ratio and associated confidence interval). The two-way crossover, which ignores between-batch pharmacokinetic variability, yields an artificially narrow confidence interval on the product comparison. The unavoidable consequence is type I error rate inflation, to ∼25%, when between-batch pharmacokinetic variability is nonzero. This risk of a false bioequivalence conclusion is substantially higher than asserted by regulators as acceptable consumer risk (5%).
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.