Evidence map›Paper›PMID 35501412›Full record

ArticleThe AAPS journal2022

Application of Modeling and Simulation to Identify a Shortened Study Duration and Novel Bioequivalence Metric for a Long-Acting Intrauterine System.

Satish Sharan, Sungwoo Choi, Yuan Zou, Yan Wang, Myong-Jin Kim, Lanyan Fang, Stephanie Choi, Fairouz Makhlouf, Stella C Grosser, Xinyuan Zhang and 1 more

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Article in The AAPS journal, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Satish Sharan *Office of Research and Standards (ORS), Office of Generic Drugs (OGD), Center for Drug Evaluation and Research (CDER), U.S. Food and Drug Administration (FDA), Building 75, Room 4702, 10903 New Hampshire Avenue, Silver Spring, Maryland, 20993, USA.
Sungwoo Choi *Division of Biometrics VIII, Office of Biostatistics, Office of Translational Sciences (OTS), CDER, FDA, Silver Spring, Maryland, USA.
Yuan ZouOffice of Research and Standards (ORS), Office of Generic Drugs (OGD), Center for Drug Evaluation and Research (CDER), U.S. Food and Drug Administration (FDA), Building 75, Room 4702, 10903 New Hampshire Avenue, Silver Spring, Maryland, 20993, USA.
Yan WangOffice of Research and Standards (ORS), Office of Generic Drugs (OGD), Center for Drug Evaluation and Research (CDER), U.S. Food and Drug Administration (FDA), Building 75, Room 4702, 10903 New Hampshire Avenue, Silver Spring, Maryland, 20993, USA.
Myong-Jin KimOffice of Research and Standards (ORS), Office of Generic Drugs (OGD), Center for Drug Evaluation and Research (CDER), U.S. Food and Drug Administration (FDA), Building 75, Room 4702, 10903 New Hampshire Avenue, Silver Spring, Maryland, 20993, USA.
Lanyan FangOffice of Research and Standards (ORS), Office of Generic Drugs (OGD), Center for Drug Evaluation and Research (CDER), U.S. Food and Drug Administration (FDA), Building 75, Room 4702, 10903 New Hampshire Avenue, Silver Spring, Maryland, 20993, USA.
Stephanie ChoiOffice of Research and Standards (ORS), Office of Generic Drugs (OGD), Center for Drug Evaluation and Research (CDER), U.S. Food and Drug Administration (FDA), Building 75, Room 4702, 10903 New Hampshire Avenue, Silver Spring, Maryland, 20993, USA.
Fairouz MakhloufDivision of Biometrics VIII, Office of Biostatistics, Office of Translational Sciences (OTS), CDER, FDA, Silver Spring, Maryland, USA.
Stella C GrosserDivision of Biometrics VIII, Office of Biostatistics, Office of Translational Sciences (OTS), CDER, FDA, Silver Spring, Maryland, USA.
Xinyuan ZhangOffice of Research and Standards (ORS), Office of Generic Drugs (OGD), Center for Drug Evaluation and Research (CDER), U.S. Food and Drug Administration (FDA), Building 75, Room 4702, 10903 New Hampshire Avenue, Silver Spring, Maryland, 20993, USA.
Liang ZhaoOffice of Research and Standards (ORS), Office of Generic Drugs (OGD), Center for Drug Evaluation and Research (CDER), U.S. Food and Drug Administration (FDA), Building 75, Room 4702, 10903 New Hampshire Avenue, Silver Spring, Maryland, 20993, USA. Liang.Zhao@fda.hhs.gov.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

An intrauterine system (IUS) can be implanted in the uterus and deliver drug directly at the site of pharmacological action. Mirena was the first FDA-approved levonorgestrel (LNG) releasing IUS without an approved generic form. Its 5-year application duration presents challenges for bioequivalence (BE) assessment using the conventional in vivo studies with pharmacokinetic and/or comparative clinical endpoints. Conventionally, along with other conditions, BE could be established if the 90% confidence interval (CI) of the ratio of geometric means of residual LNG at the end of 5 years is within the BE limits of 80.00% and 125.00%. Modeling and simulation were conducted to identify a shortened BE study duration and its corresponding BE acceptance limit that can be used as a surrogate for the conventional limit for a 5-year study. Simulation results suggest that having the 90% CI of the residual LNG 12 months post insertion within 95.00-105.26% would ensure that residual LNG amount at 5 years to be within 80.00-125.00%. This modeling and simulation practice leads to the current BE recommendation: if a test IUS is made of the same material in the same concentration and has the same physical dimensions as the Mirena, its BE could be established by showing (1) comparative physicochemical and mechanical properties; (2) comparative in vitro drug release behavior for 5 years; and (3) performance in a comparative short-term in vivo study and BE based on 90% confidence interval of test and reference ratio of residual LNG to be within 95.00-105.26% at month 12.

Indexed as

Contraceptive Agents, FemaleIntrauterine Devices, MedicatedFemaleHumansLevonorgestrelTherapeutic EquivalencyTime FactorsContraceptive Agents, FemaleLevonorgestrelbioequivalenceintrauterine systemlevonorgestrelMirenamodeling and simulationproduct-specific guidanceshortened study duration

Identifiers

PMID35501412

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

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.