Assay sensitivity in "Hybrid thorough QT/QTc (TQT)" study
A concurrent positive control should be included in a thorough QTc clinical trial to validate the study according to ICH E14 guidance. Some pharmaceutical companies have started to use "hybrid TQT" study to meet ICH E14 regulatory requirements since the release of ICH E14 Q&A (R3). The "hybrid TQT" study includes the same treatment arms (therapeutic and/or supratherapeutic dose of investigational drug, placebo, and positive control) with sample size less than traditional TQT studies, but use concentration-QTc (C-QTc) analysis as primary analysis and assay sensitivity analysis. To better understand the statistical characteristics of assay sensitivity with a commonly used positive control - Moxifloxacin - in "hybrid TQT" studies, we examined the original and subsampled moxifloxacin and placebo data from more than a hundred of TQT studies submitted to FDA. The assay sensitivity results are quite consistent between classical E14 analysis and C-QTc analysis using the original datasets. Performance of assay sensitivity in "hybrid TQT" studies using subsampled data depends on number of moxifloxacin subjects, study design (crossover design and parallel design), and C-QTc model. The results presented here can aid the design of future "hybrid TQT" studies.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2019 |
|---|---|
| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:29 |
|---|---|
| Enthalten in: |
Journal of biopharmaceutical statistics - 29(2019), 2 vom: 20., Seite 378-384 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Huang, Dalong Patrick [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Assay sensitivity |
|---|
| Anmerkungen: |
Date Completed 09.06.2020 Date Revised 09.06.2020 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1080/10543406.2018.1535498 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM289812844 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM289812844 | ||
| 003 | DE-627 | ||
| 005 | 20231225063356.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2019 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1080/10543406.2018.1535498 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0966.xml |
| 035 | |a (DE-627)NLM289812844 | ||
| 035 | |a (NLM)30346877 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Huang, Dalong Patrick |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Assay sensitivity in "Hybrid thorough QT/QTc (TQT)" study |
| 264 | 1 | |c 2019 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 09.06.2020 | ||
| 500 | |a Date Revised 09.06.2020 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a A concurrent positive control should be included in a thorough QTc clinical trial to validate the study according to ICH E14 guidance. Some pharmaceutical companies have started to use "hybrid TQT" study to meet ICH E14 regulatory requirements since the release of ICH E14 Q&A (R3). The "hybrid TQT" study includes the same treatment arms (therapeutic and/or supratherapeutic dose of investigational drug, placebo, and positive control) with sample size less than traditional TQT studies, but use concentration-QTc (C-QTc) analysis as primary analysis and assay sensitivity analysis. To better understand the statistical characteristics of assay sensitivity with a commonly used positive control - Moxifloxacin - in "hybrid TQT" studies, we examined the original and subsampled moxifloxacin and placebo data from more than a hundred of TQT studies submitted to FDA. The assay sensitivity results are quite consistent between classical E14 analysis and C-QTc analysis using the original datasets. Performance of assay sensitivity in "hybrid TQT" studies using subsampled data depends on number of moxifloxacin subjects, study design (crossover design and parallel design), and C-QTc model. The results presented here can aid the design of future "hybrid TQT" studies | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Assay sensitivity | |
| 650 | 4 | |a Moxifloxacin | |
| 650 | 4 | |a TQT | |
| 650 | 4 | |a concentration-QTc modeling | |
| 650 | 4 | |a hybrid TQT | |
| 650 | 7 | |a Drugs, Investigational |2 NLM | |
| 650 | 7 | |a Moxifloxacin |2 NLM | |
| 650 | 7 | |a U188XYD42P |2 NLM | |
| 700 | 1 | |a Chen, Janell |e verfasserin |4 aut | |
| 700 | 1 | |a Dang, Qianyu |e verfasserin |4 aut | |
| 700 | 1 | |a Tsong, Yi |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Journal of biopharmaceutical statistics |d 1991 |g 29(2019), 2 vom: 20., Seite 378-384 |w (DE-627)NLM012811432 |x 1520-5711 |7 nnns |
| 773 | 1 | 8 | |g volume:29 |g year:2019 |g number:2 |g day:20 |g pages:378-384 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1080/10543406.2018.1535498 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 29 |j 2019 |e 2 |b 20 |h 378-384 | ||