Incurred Sample Reanalysis: Time to Change the Sample Size Calculation?

Piotr J. Rudzki , Przemysław Biecek , Michał Kaza


Reliable results of pharmacokinetic and toxicokinetic studies are vital for correct decision making during drug discovery and development. Thus, ensuring high quality of bioanalytical methods is of critical importance. Incurred sample reanalysis (ISR)-one of the tools used to validate a method-is included in the bioanalytical regulatory recommendations. The methodology of this test is well established, but the estimation of the sample size is still commented on and contested. We have applied the hypergeometric distribution to evaluate ISR test passing rates in different clinical study sizes. We have tested both fixed rates of the clinical samples-as currently recommended by FDA and EMA-and a fixed number of ISRs. Our study revealed that the passing rate using the current sample size calculation is related to the clinical study size. However, the passing rate is much less dependent on the clinical study size when a fixed number of ISRs is used. Thus, we suggest using a fixed number of ISRs, e.g., 30 samples, for all studies. We found the hypergeometric distribution to be an adequate model for the assessment of similarities in original and repeated data. This model may be further used to optimize the sample size needed for the ISR test as well as to bridge data from different methods. This paper provides a basis to re-consider current ISR recommendations and implement a more statistically rationalized and risk-controlled approach.
Author Piotr J. Rudzki
Piotr J. Rudzki,,
, Przemysław Biecek (FMIS / DCSDCAM)
Przemysław Biecek,,
- Department of CAD/CAM Systems Design and Computer-Aided Medicine
, Michał Kaza
Michał Kaza,,
Journal seriesAAPS Journal, ISSN 1550-7416
Issue year2019
Publication size in sheets0.5
Keywords in Polishkalkulacja wielkości próby, validacja bioanalityczna, rozkłąd hipergeometryczny
Keywords in Englishincurred sample reanalysis (ISR), bioanalysis, hypergeometric distribution, bioanalytical method validation, bridging data
ASJC Classification3003 Pharmaceutical Science
Abstract in PolishPraca przedstawia nowe wyniki dotyczące szacowania wielkości próby dla walidacji bioanalitycznej w oparciu o rozkład hipergeometryczny
Languageen angielski
Score (nominal)100
Score sourcejournalList
ScoreMinisterial score = 100.0, 16-06-2020, ArticleFromJournal
Publication indicators WoS Citations = 1; Scopus Citations = 5; Scopus SNIP (Source Normalised Impact per Paper): 2018 = 1.346; WoS Impact Factor: 2018 = 3.545 (2) - 2018=4.25 (5)
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