Highly Automated QT Measurement Techniques in 7 Thorough QT Studies Implemented under ICH E14 Guidelines
Thorough QT (TQT) studies are designed to evaluate potential effect of a novel drug on the ventricular repolarization process of the heart using QTc prolongation as a surrogate marker for torsades de pointes. The current process to measure the QT intervals from the thousands of electrocardiograms is...
Saved in:
| Published in | Annals of noninvasive electrocardiology Vol. 16; no. 1; pp. 13 - 24 |
|---|---|
| Main Authors | , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Malden, USA
Blackwell Publishing Inc
01.01.2011
|
| Subjects | |
| Online Access | Get full text |
Cover
Loading…
| Abstract | Thorough QT (TQT) studies are designed to evaluate potential effect of a novel drug on the ventricular repolarization process of the heart using QTc prolongation as a surrogate marker for torsades de pointes. The current process to measure the QT intervals from the thousands of electrocardiograms is lengthy and expensive. In this study, we propose a validation of a highly automatic‐QT interval measurement (HA‐QT) method. We applied a HA‐QT method to the data from 7 TQT studies. We investigated both the placebo and baseline‐adjusted QTc interval prolongation induced by moxifloxacin (positive control drug) at the time of expected peak concentration. The comparative analysis evaluated the time course of moxifloxacin‐induced QTc prolongation in one study as well. The absolute HA‐QT data were longer than the FDA‐approved QTc data. This trend was not different between ECGs from the moxifloxacin and placebo arms: 9.6 ± 24 ms on drug and 9.8 ± 25 ms on placebo. The difference between methods vanished when comparing the placebo‐baseline‐adjusted QTc prolongation (1.4 ± 2.8 ms, P = 0.4). The differences in precision between the HA‐QT and the FDA‐approved measurements were not statistically different from zero: 0.1 ± 0.1 ms (P = 0.7). Also, the time course of the moxifloxacin‐induced QTc prolongation adjusted for placebo was not statistically different between measurements methods.
Ann Noninvasive Electrocardiol 2011;16(1):13–24 |
|---|---|
| AbstractList | Thorough QT (TQT) studies are designed to evaluate potential effect of a novel drug on the ventricular repolarization process of the heart using QTc prolongation as a surrogate marker for torsades de pointes. The current process to measure the QT intervals from the thousands of electrocardiograms is lengthy and expensive. In this study, we propose a validation of a highly automatic-QT interval measurement (HA-QT) method. We applied a HA-QT method to the data from 7 TQT studies. We investigated both the placebo and baseline-adjusted QTc interval prolongation induced by moxifloxacin (positive control drug) at the time of expected peak concentration. The comparative analysis evaluated the time course of moxifloxacin-induced QTc prolongation in one study as well. The absolute HA-QT data were longer than the FDA-approved QTc data. This trend was not different between ECGs from the moxifloxacin and placebo arms: 9.6 ± 24 ms on drug and 9.8 ± 25 ms on placebo. The difference between methods vanished when comparing the placebo-baseline-adjusted QTc prolongation (1.4 ± 2.8 ms, P = 0.4). The differences in precision between the HA-QT and the FDA-approved measurements were not statistically different from zero: 0.1 ± 0.1 ms (P = 0.7). Also, the time course of the moxifloxacin-induced QTc prolongation adjusted for placebo was not statistically different between measurements methods. Thorough QT (TQT) studies are designed to evaluate potential effect of a novel drug on the ventricular repolarization process of the heart using QTc prolongation as a surrogate marker for torsades de pointes. The current process to measure the QT intervals from the thousands of electrocardiograms is lengthy and expensive. In this study, we propose a validation of a highly automatic‐QT interval measurement (HA‐QT) method. We applied a HA‐QT method to the data from 7 TQT studies. We investigated both the placebo and baseline‐adjusted QTc interval prolongation induced by moxifloxacin (positive control drug) at the time of expected peak concentration. The comparative analysis evaluated the time course of moxifloxacin‐induced QTc prolongation in one study as well. The absolute HA‐QT data were longer than the FDA‐approved QTc data. This trend was not different between ECGs from the moxifloxacin and placebo arms: 9.6 ± 24 ms on drug and 9.8 ± 25 ms on placebo. The difference between methods vanished when comparing the placebo‐baseline‐adjusted QTc prolongation (1.4 ± 2.8 ms, P = 0.4). The differences in precision between the HA‐QT and the FDA‐approved measurements were not statistically different from zero: 0.1 ± 0.1 ms (P = 0.7). Also, the time course of the moxifloxacin‐induced QTc prolongation adjusted for placebo was not statistically different between measurements methods. Ann Noninvasive Electrocardiol 2011;16(1):13–24 Thorough QT (TQT) studies are designed to evaluate potential effect of a novel drug on the ventricular repolarization process of the heart using QTc prolongation as a surrogate marker for torsades de pointes. The current process to measure the QT intervals from the thousands of electrocardiograms is lengthy and expensive. In this study, we propose a validation of a highly automatic-QT interval measurement (HA-QT) method. We applied a HA-QT method to the data from 7 TQT studies. We investigated both the placebo and baseline-adjusted QTc interval prolongation induced by moxifloxacin (positive control drug) at the time of expected peak concentration. The comparative analysis evaluated the time course of moxifloxacin-induced QTc prolongation in one study as well. The absolute HA-QT data were longer than the FDA-approved QTc data. This trend was not different between ECGs from the moxifloxacin and placebo arms: 9.6 ± 24 ms on drug and 9.8 ± 25 ms on placebo. The difference between methods vanished when comparing the placebo-baseline-adjusted QTc prolongation (1.4 ± 2.8 ms, P = 0.4). The differences in precision between the HA-QT and the FDA-approved measurements were not statistically different from zero: 0.1 ± 0.1 ms (P = 0.7). Also, the time course of the moxifloxacin-induced QTc prolongation adjusted for placebo was not statistically different between measurements methods.Thorough QT (TQT) studies are designed to evaluate potential effect of a novel drug on the ventricular repolarization process of the heart using QTc prolongation as a surrogate marker for torsades de pointes. The current process to measure the QT intervals from the thousands of electrocardiograms is lengthy and expensive. In this study, we propose a validation of a highly automatic-QT interval measurement (HA-QT) method. We applied a HA-QT method to the data from 7 TQT studies. We investigated both the placebo and baseline-adjusted QTc interval prolongation induced by moxifloxacin (positive control drug) at the time of expected peak concentration. The comparative analysis evaluated the time course of moxifloxacin-induced QTc prolongation in one study as well. The absolute HA-QT data were longer than the FDA-approved QTc data. This trend was not different between ECGs from the moxifloxacin and placebo arms: 9.6 ± 24 ms on drug and 9.8 ± 25 ms on placebo. The difference between methods vanished when comparing the placebo-baseline-adjusted QTc prolongation (1.4 ± 2.8 ms, P = 0.4). The differences in precision between the HA-QT and the FDA-approved measurements were not statistically different from zero: 0.1 ± 0.1 ms (P = 0.7). Also, the time course of the moxifloxacin-induced QTc prolongation adjusted for placebo was not statistically different between measurements methods. |
| Author | Couderc, Jean-Philippe Xia, Xiajuan Handzel, Robert Li, Mike Zareba, Wojciech Garnett, Christine McNitt, Scott Polonsky, Slava |
| AuthorAffiliation | 4 School of Biomedical Engineering, University of Rochester, NY 1 Heart Research Follow‐up Program, Cardiology Department, University of Rochester Medical Center, Rochester, NY 2 Division of Pharmacometrics, Office of Clinical Pharmacology 3 Division of Cardiovascular and Renal Products, Office of New Drugs, Center for Drug Evaluation and Research, FDA, Silver Spring, MD |
| AuthorAffiliation_xml | – name: 2 Division of Pharmacometrics, Office of Clinical Pharmacology – name: 4 School of Biomedical Engineering, University of Rochester, NY – name: 3 Division of Cardiovascular and Renal Products, Office of New Drugs, Center for Drug Evaluation and Research, FDA, Silver Spring, MD – name: 1 Heart Research Follow‐up Program, Cardiology Department, University of Rochester Medical Center, Rochester, NY |
| Author_xml | – sequence: 1 givenname: Jean-Philippe surname: Couderc fullname: Couderc, Jean-Philippe organization: Heart Research Follow-up Program, Cardiology Department, University of Rochester Medical Center, Rochester, NY – sequence: 2 givenname: Christine surname: Garnett fullname: Garnett, Christine organization: Division of Pharmacometrics, Office of Clinical Pharmacology – sequence: 3 givenname: Mike surname: Li fullname: Li, Mike organization: Division of Cardiovascular and Renal Products, Office of New Drugs, Center for Drug Evaluation and Research, FDA, Silver Spring, MD – sequence: 4 givenname: Robert surname: Handzel fullname: Handzel, Robert organization: School of Biomedical Engineering, University of Rochester, NY – sequence: 5 givenname: Scott surname: McNitt fullname: McNitt, Scott organization: Heart Research Follow-up Program, Cardiology Department, University of Rochester Medical Center, Rochester, NY – sequence: 6 givenname: Xiajuan surname: Xia fullname: Xia, Xiajuan organization: Heart Research Follow-up Program, Cardiology Department, University of Rochester Medical Center, Rochester, NY – sequence: 7 givenname: Slava surname: Polonsky fullname: Polonsky, Slava organization: Heart Research Follow-up Program, Cardiology Department, University of Rochester Medical Center, Rochester, NY – sequence: 8 givenname: Wojciech surname: Zareba fullname: Zareba, Wojciech organization: Heart Research Follow-up Program, Cardiology Department, University of Rochester Medical Center, Rochester, NY |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/21251129$$D View this record in MEDLINE/PubMed |
| BookMark | eNpVUclu2zAQJYoUzdZfKHjrSS5JLZQOLWA4ju3USRFEQIxeBrQ4tuhKlKultf8-lJ0YLS8czFuGw3dJzmxlkRDK2YC782Uz4GEgvEAGi4FgrstYwMRg945cnIAzV7NYeFKwxTm5bJoNY0IEQn4g54KLkHORXJB8atZ5safDrq1K1aKmjym9R9V0NZZoW5pillvzu8OGGkslTfOqrrp13vOe2k4bB8zKbXFgO3lnNdZ0NprSMQ_opDMaC2OxuSbvV6po8OPrfUXS23E6mnrzH5PZaDj3jB9K4aEOpFoqpTGScsWUCJeJL3WCwg-ZSGKeST-LGGa-FmoVaozVkgmteL8PS_wr8u1ou-2WJerMPapWBWxrU6p6D5Uy8D9iTQ7r6g_4TEaMRc7g86tBXfVbt1CaJsOiUBarroE4iOIkCQ-jPv076jTj7XMd4euR8NcUuD_hnEEfImygzwr6rKAPEQ4hwg6GD-ORq5zeO-pN0-LupFf1L4ikL0N4fpjAzdPt43zx_Sfc-S9NoaI5 |
| ContentType | Journal Article |
| Copyright | 2011, Wiley Periodicals, Inc. |
| Copyright_xml | – notice: 2011, Wiley Periodicals, Inc. |
| DBID | BSCLL CGR CUY CVF ECM EIF NPM 7X8 5PM |
| DOI | 10.1111/j.1542-474X.2010.00402.x |
| DatabaseName | Istex Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed MEDLINE - Academic PubMed Central (Full Participant titles) |
| DatabaseTitle | MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) MEDLINE - Academic |
| DatabaseTitleList | MEDLINE MEDLINE - Academic |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: EIF name: MEDLINE url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search sourceTypes: Index Database |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Medicine |
| DocumentTitleAlternate | Couderc, et al |
| EISSN | 1542-474X |
| EndPage | 24 |
| ExternalDocumentID | PMC3076006 21251129 ANEC402 ark_67375_WNG_DSFQLXKZ_J |
| Genre | article Validation Study Journal Article Research Support, N.I.H., Extramural |
| GrantInformation_xml | – fundername: NHLBI NIH HHS grantid: R01 HL084402 – fundername: NHLBI NIH HHS grantid: R01HL084402 |
| GroupedDBID | --- .3N .GA .Y3 05W 0R~ 10A 1OB 1OC 23M 24P 31~ 33P 36B 3SF 4.4 50Y 50Z 51W 51X 52M 52N 52O 52P 52R 52S 52T 52U 52V 52W 52X 53G 5GY 5HH 5LA 5VS 66C 702 7PT 7X7 8-0 8-1 8-3 8-4 8-5 8FI 8FJ 8UM 930 A01 A03 AAESR AAEVG AAHHS AAONW AAWTL AAZKR ABCQN ABCUV ABEML ABJNI ABPVW ABUWG ACBWZ ACCFJ ACGFS ACMXC ACPOU ACSCC ACXQS ADBBV ADEOM ADIZJ ADMGS ADPDF ADXAS ADZOD AEEZP AEIMD AENEX AEQDE AEUQT AFBPY AFEBI AFGKR AFKRA AFPKN AFPWT AFZJQ AHEFC AIURR AIWBW AJBDE ALAGY ALMA_UNASSIGNED_HOLDINGS ALUQN AMBMR ASPBG ATUGU AVWKF AZBYB AZFZN AZVAB BAFTC BBNVY BDRZF BENPR BFHJK BHBCM BHPHI BMXJE BPMNR BROTX BRXPI BSCLL BY8 C45 CAG CCPQU COF CS3 D-6 D-7 D-E D-F DC6 DCZOG DPXWK DR2 EBS EJD EMB EMOBN EX3 F00 F01 F04 F5P FEDTE FUBAC FYUFA FZ0 G-S G.N GODZA GROUPED_DOAJ H.X HCIFZ HF~ HMCUK HVGLF HZI HZ~ IAO IHE IHR INH J0M K48 LC2 LC3 LH4 LITHE LOXES LP6 LP7 LUTES LW6 LYRES M7P MK4 MRFUL MRMAN MRSTM MSFUL MSMAN MSSTM MXFUL MXMAN MXSTM N04 N05 N9A NF~ O66 O9- OIG OK1 OVD OVEED P2P P2W P2X P2Z P4B P4D PALCI PIMPY Q.N Q11 QB0 R.K RIWAO RJQFR ROL RPM RX1 SAMSI SUPJJ SV3 TEORI UB1 UKHRP W8V W99 WBKPD WHWMO WIH WIJ WIK WIN WOHZO WOW WQJ WRC WUP WVDHM WXI WXSBR XG1 ZZTAW ~IA ~WT AANHP ACCMX ACRPL ACYXJ ADNMO AAFWJ AAMMB AEFGJ AGQPQ AGXDD AIDQK AIDYY CGR CUY CVF ECM EIF NPM PHGZM PHGZT PQGLB 7X8 5PM |
| ID | FETCH-LOGICAL-i3572-ed47abaade677f0a25b937d9e23502981c73c60ec3d2af5de8ab02da15112093 |
| IEDL.DBID | DR2 |
| ISSN | 1082-720X 1542-474X |
| IngestDate | Thu Aug 21 18:42:52 EDT 2025 Fri Jul 11 16:06:34 EDT 2025 Mon Jul 21 05:56:23 EDT 2025 Wed Jan 22 16:57:22 EST 2025 Wed Oct 30 09:53:20 EDT 2024 |
| IsDoiOpenAccess | false |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 1 |
| Language | English |
| License | 2011, Wiley Periodicals, Inc. |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-i3572-ed47abaade677f0a25b937d9e23502981c73c60ec3d2af5de8ab02da15112093 |
| Notes | ark:/67375/WNG-DSFQLXKZ-J ArticleID:ANEC402 istex:D9258EC6DCD6B68DFFBB10080BD166D31DA70782 This work was funded by the National Institute for Health through the R01HL084402 award. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Undefined-3 |
| PMID | 21251129 |
| PQID | 846899509 |
| PQPubID | 23479 |
| PageCount | 12 |
| ParticipantIDs | pubmedcentral_primary_oai_pubmedcentral_nih_gov_3076006 proquest_miscellaneous_846899509 pubmed_primary_21251129 wiley_primary_10_1111_j_1542_474X_2010_00402_x_ANEC402 istex_primary_ark_67375_WNG_DSFQLXKZ_J |
| PublicationCentury | 2000 |
| PublicationDate | January 2011 |
| PublicationDateYYYYMMDD | 2011-01-01 |
| PublicationDate_xml | – month: 01 year: 2011 text: January 2011 |
| PublicationDecade | 2010 |
| PublicationPlace | Malden, USA |
| PublicationPlace_xml | – name: Malden, USA – name: United States |
| PublicationTitle | Annals of noninvasive electrocardiology |
| PublicationTitleAlternate | Ann Noninvasive Electrocardiol |
| PublicationYear | 2011 |
| Publisher | Blackwell Publishing Inc |
| Publisher_xml | – name: Blackwell Publishing Inc |
| References | Hulhoven R, Rosillon D, Bridson WE, et al. Effect of levetiracetam on cardiac repolarization in healthy subjects: A single-dose, randomized, placebo- and active-controlled, four-way crossover study. Clin Ther 2008;30:260-270. Chen X, Cass JD, Bradley JA, et al. QT prolongation and proarrhythmia by moxifloxacin: Concordance of preclinical models in relation to clinical outcome. Br J Pharmacol 2005;146:792-799. Darpo B, Agin M, Kazierad DJ, et al. Man versus machine: Is there an optimal method for QT measurements in thorough QT studies? J Clin Pharmacol 2006;46:598-612. Mortara DW. Automated QT measurement and application to detection of moxifloxacin-induced changes. Ann Noninvasive Electrocardiol 2009;14(Suppl 1):S30-S34. Noel GJ, Natarajan J, Chien S, et al. Effects of three fluoroquinolones on QT interval in healthy adults after single doses. Clin Pharmacol Ther 2003;73:292-303. Couderc JP, Zareba W. An update on QT measurement and interpretation methodologies. Ann Noninvasive Electrocardiol 2009;14(Suppl 1):S1-S2. Couderc JP, Kaab S, Hinterseer M, et al. Baseline values and sotalol-induced changes of ventricular repolarization duration, heterogeneity, and instability in patients with a history of drug-induced torsades de pointes. J Clin Pharmacol 2009;49:6-16. Badilini F, Maison-Blanche P, Childers R, et al. QT interval analysis on ambulatory electrocardiogram recordings: A selective beat averaging approach. Med Biol Eng Comput 1999;37:71-79. Dota CD, Edvardsson N, Skallefell B, et al. PC-Based ECG waveform recognition-validation of novel software against a reference ECG database. Ann Noninvasive Electrocardiol 2009;14(Suppl 1):S42-S47. Hulhoven R, Rosillon D, Letiexhe M, et al. Levocetirizine does not prolong the QT/QTc interval in healthy subjects: Results from a thorough QT study. Eur J Clin Pharmacol 2007;63:1011-1017. Hnatkova K, Gang Y, Batchvarov VN, et al. Precision of QT interval measurement by advanced electrocardiographic equipment. Pacing Clin Electrophysiol 2006;29:1277-1284. Malhotra BK, Glue P, Sweeney K, et al. Thorough QT study with recommended and supratherapeutic doses of tolterodine. Clin Pharmacol Ther 2007;81:377-385. Malik M. The imprecision in heart rate correction may lead to artificial observations of drug induced QT interval changes. Pacing Clin Electrophysiol 2002;25:209-216. Xue JQ. Robust QT interval estimation-from algorithm to validation. Ann Noninvasive Electrocardiol 2009;14(Suppl 1):S35-S41. Zhou SH, Helfenbein ED, Lindauer JM, et al. Philips QT interval measurement algorithms for diagnostic, ambulatory, and patient monitoring ECG applications. Ann Noninvasive Electrocardiol 2009;14(Suppl 1):S3-S8. Bloomfield DM, Kost JT, Ghosh K, et al. The effect of moxifloxacin on QTc and implications for the design of thorough QT studies. Clin Pharmacol Ther 2008 ;84:475-480. Iwamoto M, Kost JT, Mistry GC, et al. Raltegravir thorough QT/QTc study: A single supratherapeutic dose of raltegravir does not prolong the QTcF interval. J Clin Pharmacol 2008;48:726-733. Strachan IG, Hughes NP, Poonawala MH, et al. Automated QT analysis that learns from cardiologist annotations. Ann Noninvasive Electrocardiol 2009;14(Suppl 1):S9-S21. Porta A, Baselli G, Lombardi F, et al. Performance assessment of standard algorithms for dynamic R-T interval measurement: Comparison between R-Tapex and R-T(end) approach. Med Biol Eng Comput 1998;36:35-42. Fossa AA, Wisialowski T, Crimin K, et al. Analyses of dynamic beat-to-beat QT-TQ interval (ECG restitution) changes in humans under normal sinus rhythm and prior to an event of torsades de pointes during QT prolongation caused by sotalol. Ann Noninvasive Electrocardiol 2007;12:338-348. Hoffmann M, Himmel HM, Kubitza D. Moxifloxacin: Translating preclinical findings into QT-prolongation detectable in human thorough QT/QTC studies. J Pharmacol Toxicol Methods 2008;58:158 (abstract). Garnett CE, Beasley N, Bhattaram VA, et al. Concentration-QT relationships play a key role in the evaluation of proarrhythmic risk during regulatory review. J Clin Pharmacol 2008;48:13-18. Rosillon D, Astruc B, Hulhoven R, et al. Effect of brivaracetam on cardiac repolarisation-a thorough QT study. Curr Med Res Opin 2008;24:2327-2337. Lepeschkin E, Surawicz B. The measurement of the Q-T interval of the electrocardiogram. Circulation 1952;6:378-388. McLaughlin NB, Campbell RW, Murray A. Accuracy of four automatic QT measurement techniques in cardiac patients and healthy subjects. Heart 1996;76:422-426. Roden DM. Drug-induced prolongation of the QT interval. N Engl J Med 2004;350:1013-1022. Morganroth J, Ilson BE, Shaddinger BC, et al. Evaluation of vardenafil and sildenafil on cardiac repolarization. Am J Cardiol 2004;93:1378-1383, A6 (abstract). Couderc JP, McNitt S, Hyrien O, et al. Improving the detection of subtle i(kr)-inhibition: Assessing electrocardiographic abnormalities of repolarization induced by moxifloxacin. Drug Saf 2008;31:249-260. McLaughlin NB, Campbell RW, Murray A. Comparison of automatic QT measurement techniques in the normal 12 lead electrocardiogram. Br Heart J 1995;74:84-89. Pueyo E, Malik M, Laguna P. Beat-to-beat Adaptation of QT Interval to Heart Rate. Conf Proc IEEE Eng Med Biol Soc 2005;3:2475-2478. Stramba-Badiale M, Locati EH, Martinelli A, et al. Gender and the relationship between ventricular repolarization and cardiac cycle length during 24-h Holter recordings. Eur Heart J 1997;18:1000-1006. Fridericia LS. Die Systolendauer im Elekrokardiogramm bei normalen Menschen und bei Herzkranken. Acta Med Scand 1920;53:469-486. Sherazi S, DiSalle M, Daubert JP, et al. Moxifloxacin-induced torsades de pointes. Cardiol J 2008;15:71-73. Andersen MP, Xue JQ, Graff C, et al. New descriptors of T-wave morphology are independent of heart rate. J Electrocardiol 2008;41:557-561. Malik M. Problems of heart rate correction in assessment of drug-induced QT interval prolongation. J Cardiovasc Electrophysiol 2001;12:411-420. Halamek J, Jurak P, Villa M, et al. Dynamic coupling between heart rate and ventricular repolarisation. Biomed Tech (Berl) 2007;52:255-263. Bland JM, Altman DG. Measuring agreement in method comparison studies. Stat Methods Med Res 1999;8:135-160. Dale KM, Lertsburapa K, Kluger J, et al. Moxifloxacin and torsade de pointes. Ann Pharmacother 2007;41:336-340. Badilini F, Vaglio M, Dubois R, et al. Automatic analysis of cardiac repolarization morphology using Gaussian mesa function modeling. J Electrocardiol 2008;41:588-594. Goldenberg I, Moss AJ, Zareba W. QT interval: How to measure it and what is "normal." J Cardiovasc Electrophysiol 2006;17:333-336. Davis JD, Hackman F, Layton G, et al. Effect of single doses of maraviroc on the QT/QTc interval in healthy subjects. Br J Clin Pharmacol 2008;65(Suppl 1):68-75. Kubitza D, Mueck W, Becka M. Randomized, double-blind, crossover study to investigate the effect of rivaroxaban on QT-interval prolongation. Drug Saf 2008;31:67-77. Couderc JP, Vaglio M, Xia X, et al. Impaired T-amplitude adaptation to heart rate characterizes I(Kr) inhibition in the congenital and acquired forms of the long QT syndrome. J Cardiovasc Electrophysiol 2007;18:1299-1305. Kors JA, van HG. Methodology of QT-interval measurement in the modular ECG analysis system (MEANS). Ann Noninvasive Electrocardiol 2009;14(Suppl 1):S48-S53. 1995; 74 2007; 18 2006; 17 2008; 58 2008; 15 2008; 30 2008; 31 2007; 52 1999; 8 2003; 73 2007; 12 1996; 76 2009; 49 2009; 14 2002; 25 2004; 93 1920; 53 2006; 46 2005; 146 2004; 350 1999; 37 2008; 48 1997; 18 2006; 29 2008; 24 2007; 81 2008; 65 1952; 6 2005; 3 2008; 41 2007; 41 2007; 63 2008; 84 2001; 12 1998; 36 |
| References_xml | – reference: Halamek J, Jurak P, Villa M, et al. Dynamic coupling between heart rate and ventricular repolarisation. Biomed Tech (Berl) 2007;52:255-263. – reference: Lepeschkin E, Surawicz B. The measurement of the Q-T interval of the electrocardiogram. Circulation 1952;6:378-388. – reference: Malhotra BK, Glue P, Sweeney K, et al. Thorough QT study with recommended and supratherapeutic doses of tolterodine. Clin Pharmacol Ther 2007;81:377-385. – reference: Badilini F, Maison-Blanche P, Childers R, et al. QT interval analysis on ambulatory electrocardiogram recordings: A selective beat averaging approach. Med Biol Eng Comput 1999;37:71-79. – reference: Morganroth J, Ilson BE, Shaddinger BC, et al. Evaluation of vardenafil and sildenafil on cardiac repolarization. Am J Cardiol 2004;93:1378-1383, A6 (abstract). – reference: Couderc JP, Zareba W. An update on QT measurement and interpretation methodologies. Ann Noninvasive Electrocardiol 2009;14(Suppl 1):S1-S2. – reference: Darpo B, Agin M, Kazierad DJ, et al. Man versus machine: Is there an optimal method for QT measurements in thorough QT studies? J Clin Pharmacol 2006;46:598-612. – reference: Porta A, Baselli G, Lombardi F, et al. Performance assessment of standard algorithms for dynamic R-T interval measurement: Comparison between R-Tapex and R-T(end) approach. Med Biol Eng Comput 1998;36:35-42. – reference: Malik M. Problems of heart rate correction in assessment of drug-induced QT interval prolongation. J Cardiovasc Electrophysiol 2001;12:411-420. – reference: Sherazi S, DiSalle M, Daubert JP, et al. Moxifloxacin-induced torsades de pointes. Cardiol J 2008;15:71-73. – reference: Fridericia LS. Die Systolendauer im Elekrokardiogramm bei normalen Menschen und bei Herzkranken. Acta Med Scand 1920;53:469-486. – reference: Pueyo E, Malik M, Laguna P. Beat-to-beat Adaptation of QT Interval to Heart Rate. Conf Proc IEEE Eng Med Biol Soc 2005;3:2475-2478. – reference: Kors JA, van HG. Methodology of QT-interval measurement in the modular ECG analysis system (MEANS). Ann Noninvasive Electrocardiol 2009;14(Suppl 1):S48-S53. – reference: Noel GJ, Natarajan J, Chien S, et al. Effects of three fluoroquinolones on QT interval in healthy adults after single doses. Clin Pharmacol Ther 2003;73:292-303. – reference: Hulhoven R, Rosillon D, Bridson WE, et al. Effect of levetiracetam on cardiac repolarization in healthy subjects: A single-dose, randomized, placebo- and active-controlled, four-way crossover study. Clin Ther 2008;30:260-270. – reference: Stramba-Badiale M, Locati EH, Martinelli A, et al. Gender and the relationship between ventricular repolarization and cardiac cycle length during 24-h Holter recordings. Eur Heart J 1997;18:1000-1006. – reference: Iwamoto M, Kost JT, Mistry GC, et al. Raltegravir thorough QT/QTc study: A single supratherapeutic dose of raltegravir does not prolong the QTcF interval. J Clin Pharmacol 2008;48:726-733. – reference: Roden DM. Drug-induced prolongation of the QT interval. N Engl J Med 2004;350:1013-1022. – reference: Goldenberg I, Moss AJ, Zareba W. QT interval: How to measure it and what is "normal." J Cardiovasc Electrophysiol 2006;17:333-336. – reference: Bloomfield DM, Kost JT, Ghosh K, et al. The effect of moxifloxacin on QTc and implications for the design of thorough QT studies. Clin Pharmacol Ther 2008 ;84:475-480. – reference: Couderc JP, McNitt S, Hyrien O, et al. Improving the detection of subtle i(kr)-inhibition: Assessing electrocardiographic abnormalities of repolarization induced by moxifloxacin. Drug Saf 2008;31:249-260. – reference: McLaughlin NB, Campbell RW, Murray A. Accuracy of four automatic QT measurement techniques in cardiac patients and healthy subjects. Heart 1996;76:422-426. – reference: McLaughlin NB, Campbell RW, Murray A. Comparison of automatic QT measurement techniques in the normal 12 lead electrocardiogram. Br Heart J 1995;74:84-89. – reference: Couderc JP, Vaglio M, Xia X, et al. Impaired T-amplitude adaptation to heart rate characterizes I(Kr) inhibition in the congenital and acquired forms of the long QT syndrome. J Cardiovasc Electrophysiol 2007;18:1299-1305. – reference: Dale KM, Lertsburapa K, Kluger J, et al. Moxifloxacin and torsade de pointes. Ann Pharmacother 2007;41:336-340. – reference: Garnett CE, Beasley N, Bhattaram VA, et al. Concentration-QT relationships play a key role in the evaluation of proarrhythmic risk during regulatory review. J Clin Pharmacol 2008;48:13-18. – reference: Badilini F, Vaglio M, Dubois R, et al. Automatic analysis of cardiac repolarization morphology using Gaussian mesa function modeling. J Electrocardiol 2008;41:588-594. – reference: Hnatkova K, Gang Y, Batchvarov VN, et al. Precision of QT interval measurement by advanced electrocardiographic equipment. Pacing Clin Electrophysiol 2006;29:1277-1284. – reference: Mortara DW. Automated QT measurement and application to detection of moxifloxacin-induced changes. Ann Noninvasive Electrocardiol 2009;14(Suppl 1):S30-S34. – reference: Kubitza D, Mueck W, Becka M. Randomized, double-blind, crossover study to investigate the effect of rivaroxaban on QT-interval prolongation. Drug Saf 2008;31:67-77. – reference: Hoffmann M, Himmel HM, Kubitza D. Moxifloxacin: Translating preclinical findings into QT-prolongation detectable in human thorough QT/QTC studies. J Pharmacol Toxicol Methods 2008;58:158 (abstract). – reference: Davis JD, Hackman F, Layton G, et al. Effect of single doses of maraviroc on the QT/QTc interval in healthy subjects. Br J Clin Pharmacol 2008;65(Suppl 1):68-75. – reference: Couderc JP, Kaab S, Hinterseer M, et al. Baseline values and sotalol-induced changes of ventricular repolarization duration, heterogeneity, and instability in patients with a history of drug-induced torsades de pointes. J Clin Pharmacol 2009;49:6-16. – reference: Bland JM, Altman DG. Measuring agreement in method comparison studies. Stat Methods Med Res 1999;8:135-160. – reference: Hulhoven R, Rosillon D, Letiexhe M, et al. Levocetirizine does not prolong the QT/QTc interval in healthy subjects: Results from a thorough QT study. Eur J Clin Pharmacol 2007;63:1011-1017. – reference: Dota CD, Edvardsson N, Skallefell B, et al. PC-Based ECG waveform recognition-validation of novel software against a reference ECG database. Ann Noninvasive Electrocardiol 2009;14(Suppl 1):S42-S47. – reference: Malik M. The imprecision in heart rate correction may lead to artificial observations of drug induced QT interval changes. Pacing Clin Electrophysiol 2002;25:209-216. – reference: Andersen MP, Xue JQ, Graff C, et al. New descriptors of T-wave morphology are independent of heart rate. J Electrocardiol 2008;41:557-561. – reference: Rosillon D, Astruc B, Hulhoven R, et al. Effect of brivaracetam on cardiac repolarisation-a thorough QT study. Curr Med Res Opin 2008;24:2327-2337. – reference: Zhou SH, Helfenbein ED, Lindauer JM, et al. Philips QT interval measurement algorithms for diagnostic, ambulatory, and patient monitoring ECG applications. Ann Noninvasive Electrocardiol 2009;14(Suppl 1):S3-S8. – reference: Strachan IG, Hughes NP, Poonawala MH, et al. Automated QT analysis that learns from cardiologist annotations. Ann Noninvasive Electrocardiol 2009;14(Suppl 1):S9-S21. – reference: Chen X, Cass JD, Bradley JA, et al. QT prolongation and proarrhythmia by moxifloxacin: Concordance of preclinical models in relation to clinical outcome. Br J Pharmacol 2005;146:792-799. – reference: Xue JQ. Robust QT interval estimation-from algorithm to validation. Ann Noninvasive Electrocardiol 2009;14(Suppl 1):S35-S41. – reference: Fossa AA, Wisialowski T, Crimin K, et al. Analyses of dynamic beat-to-beat QT-TQ interval (ECG restitution) changes in humans under normal sinus rhythm and prior to an event of torsades de pointes during QT prolongation caused by sotalol. Ann Noninvasive Electrocardiol 2007;12:338-348. – volume: 25 start-page: 209 year: 2002 end-page: 216 article-title: The imprecision in heart rate correction may lead to artificial observations of drug induced QT interval changes publication-title: Pacing Clin Electrophysiol – volume: 14 start-page: S9 issue: Suppl 1 year: 2009 end-page: S21 article-title: Automated QT analysis that learns from cardiologist annotations publication-title: Ann Noninvasive Electrocardiol – volume: 48 start-page: 726 year: 2008 end-page: 733 article-title: Raltegravir thorough QT/QTc study: A single supratherapeutic dose of raltegravir does not prolong the QTcF interval publication-title: J Clin Pharmacol – volume: 8 start-page: 135 year: 1999 end-page: 160 article-title: Measuring agreement in method comparison studies publication-title: Stat Methods Med Res – volume: 65 start-page: 68 issue: Suppl 1 year: 2008 end-page: 75 article-title: Effect of single doses of maraviroc on the QT/QTc interval in healthy subjects publication-title: Br J Clin Pharmacol – volume: 73 start-page: 292 year: 2003 end-page: 303 article-title: Effects of three fluoroquinolones on QT interval in healthy adults after single doses publication-title: Clin Pharmacol Ther – volume: 15 start-page: 71 year: 2008 end-page: 73 article-title: Moxifloxacin‐induced torsades de pointes publication-title: Cardiol J – volume: 14 start-page: S1 issue: Suppl 1 year: 2009 end-page: S2 article-title: An update on QT measurement and interpretation methodologies publication-title: Ann Noninvasive Electrocardiol – volume: 49 start-page: 6 year: 2009 end-page: 16 article-title: Baseline values and sotalol‐induced changes of ventricular repolarization duration, heterogeneity, and instability in patients with a history of drug‐induced torsades de pointes publication-title: J Clin Pharmacol – volume: 41 start-page: 336 year: 2007 end-page: 340 article-title: Moxifloxacin and torsade de pointes publication-title: Ann Pharmacother – volume: 52 start-page: 255 year: 2007 end-page: 263 article-title: Dynamic coupling between heart rate and ventricular repolarisation publication-title: Biomed Tech (Berl) – volume: 3 start-page: 2475 year: 2005 end-page: 2478 article-title: Beat‐to‐beat Adaptation of QT Interval to Heart Rate publication-title: Conf Proc IEEE Eng Med Biol Soc – volume: 350 start-page: 1013 year: 2004 end-page: 1022 article-title: Drug‐induced prolongation of the QT interval publication-title: N Engl J Med – volume: 6 start-page: 378 year: 1952 end-page: 388 article-title: The measurement of the Q‐T interval of the electrocardiogram publication-title: Circulation – volume: 14 start-page: S35 issue: Suppl 1 year: 2009 end-page: S41 article-title: Robust QT interval estimation–from algorithm to validation publication-title: Ann Noninvasive Electrocardiol – volume: 12 start-page: 338 year: 2007 end-page: 348 article-title: Analyses of dynamic beat‐to‐beat QT‐TQ interval (ECG restitution) changes in humans under normal sinus rhythm and prior to an event of torsades de pointes during QT prolongation caused by sotalol publication-title: Ann Noninvasive Electrocardiol – volume: 14 start-page: S42 issue: Suppl 1 year: 2009 end-page: S47 article-title: PC‐Based ECG waveform recognition‐validation of novel software against a reference ECG database publication-title: Ann Noninvasive Electrocardiol – volume: 41 start-page: 588 year: 2008 end-page: 594 article-title: Automatic analysis of cardiac repolarization morphology using Gaussian mesa function modeling publication-title: J Electrocardiol – volume: 31 start-page: 67 year: 2008 end-page: 77 article-title: Randomized, double‐blind, crossover study to investigate the effect of rivaroxaban on QT‐interval prolongation publication-title: Drug Saf – volume: 81 start-page: 377 year: 2007 end-page: 385 article-title: Thorough QT study with recommended and supratherapeutic doses of tolterodine publication-title: Clin Pharmacol Ther – volume: 18 start-page: 1000 year: 1997 end-page: 1006 article-title: Gender and the relationship between ventricular repolarization and cardiac cycle length during 24‐h Holter recordings publication-title: Eur Heart J – volume: 37 start-page: 71 year: 1999 end-page: 79 article-title: QT interval analysis on ambulatory electrocardiogram recordings: A selective beat averaging approach publication-title: Med Biol Eng Comput – volume: 41 start-page: 557 year: 2008 end-page: 561 article-title: New descriptors of T‐wave morphology are independent of heart rate publication-title: J Electrocardiol – volume: 29 start-page: 1277 year: 2006 end-page: 1284 article-title: Precision of QT interval measurement by advanced electrocardiographic equipment publication-title: Pacing Clin Electrophysiol – volume: 12 start-page: 411 year: 2001 end-page: 420 article-title: Problems of heart rate correction in assessment of drug‐induced QT interval prolongation publication-title: J Cardiovasc Electrophysiol – volume: 24 start-page: 2327 year: 2008 end-page: 2337 article-title: Effect of brivaracetam on cardiac repolarisation–a thorough QT study publication-title: Curr Med Res Opin – volume: 14 start-page: S30 issue: Suppl 1 year: 2009 end-page: S34 article-title: Automated QT measurement and application to detection of moxifloxacin‐induced changes publication-title: Ann Noninvasive Electrocardiol – volume: 93 start-page: 1378 year: 2004 end-page: 1383 article-title: Evaluation of vardenafil and sildenafil on cardiac repolarization publication-title: Am J Cardiol – volume: 46 start-page: 598 year: 2006 end-page: 612 article-title: Man versus machine: Is there an optimal method for QT measurements in thorough QT studies? publication-title: J Clin Pharmacol – volume: 48 start-page: 13 year: 2008 end-page: 18 article-title: Concentration‐QT relationships play a key role in the evaluation of proarrhythmic risk during regulatory review publication-title: J Clin Pharmacol – volume: 31 start-page: 249 year: 2008 end-page: 260 article-title: Improving the detection of subtle i(kr)‐inhibition: Assessing electrocardiographic abnormalities of repolarization induced by moxifloxacin publication-title: Drug Saf – volume: 76 start-page: 422 year: 1996 end-page: 426 article-title: Accuracy of four automatic QT measurement techniques in cardiac patients and healthy subjects publication-title: Heart – volume: 58 start-page: 158 year: 2008 article-title: Moxifloxacin: Translating preclinical findings into QT‐prolongation detectable in human thorough QT/QTC studies publication-title: J Pharmacol Toxicol Methods – volume: 63 start-page: 1011 year: 2007 end-page: 1017 article-title: Levocetirizine does not prolong the QT/QTc interval in healthy subjects: Results from a thorough QT study publication-title: Eur J Clin Pharmacol – volume: 74 start-page: 84 year: 1995 end-page: 89 article-title: Comparison of automatic QT measurement techniques in the normal 12 lead electrocardiogram publication-title: Br Heart J – volume: 17 start-page: 333 year: 2006 end-page: 336 article-title: QT interval: How to measure it and what is “normal.” publication-title: J Cardiovasc Electrophysiol – volume: 53 start-page: 469 year: 1920 end-page: 486 article-title: Die Systolendauer im Elekrokardiogramm bei normalen Menschen und bei Herzkranken publication-title: Acta Med Scand – volume: 14 start-page: S48 issue: Suppl 1 year: 2009 end-page: S53 article-title: Methodology of QT‐interval measurement in the modular ECG analysis system (MEANS) publication-title: Ann Noninvasive Electrocardiol – volume: 146 start-page: 792 year: 2005 end-page: 799 article-title: QT prolongation and proarrhythmia by moxifloxacin: Concordance of preclinical models in relation to clinical outcome publication-title: Br J Pharmacol – volume: 36 start-page: 35 year: 1998 end-page: 42 article-title: Performance assessment of standard algorithms for dynamic R‐T interval measurement: Comparison between R‐Tapex and R‐T(end) approach publication-title: Med Biol Eng Comput – volume: 18 start-page: 1299 year: 2007 end-page: 1305 article-title: Impaired T‐amplitude adaptation to heart rate characterizes I(Kr) inhibition in the congenital and acquired forms of the long QT syndrome publication-title: J Cardiovasc Electrophysiol – volume: 30 start-page: 260 year: 2008 end-page: 270 article-title: Effect of levetiracetam on cardiac repolarization in healthy subjects: A single‐dose, randomized, placebo‐ and active‐controlled, four‐way crossover study publication-title: Clin Ther – volume: 84 start-page: 475 year: 2008 end-page: 480 article-title: The effect of moxifloxacin on QTc and implications for the design of thorough QT studies publication-title: Clin Pharmacol Ther – volume: 14 start-page: S3 issue: Suppl 1 year: 2009 end-page: S8 article-title: Philips QT interval measurement algorithms for diagnostic, ambulatory, and patient monitoring ECG applications publication-title: Ann Noninvasive Electrocardiol |
| SSID | ssj0022427 |
| Score | 2.0419383 |
| Snippet | Thorough QT (TQT) studies are designed to evaluate potential effect of a novel drug on the ventricular repolarization process of the heart using QTc... |
| SourceID | pubmedcentral proquest pubmed wiley istex |
| SourceType | Open Access Repository Aggregation Database Index Database Publisher |
| StartPage | 13 |
| SubjectTerms | Anti-Infective Agents - pharmacology Aza Compounds - pharmacology Cardiotoxins drug cardiotoxicity Drug Evaluation, Preclinical drug safety electrocardiogram Electrocardiography Female Fluoroquinolones Guidelines as Topic Heart Conduction System - drug effects Humans Long QT Syndrome - chemically induced Male Models, Biological Moxifloxacin Neuromuscular Nondepolarizing Agents - administration & dosage Original QT interval Quinolines - pharmacology Sex Factors thorough QT study |
| Title | Highly Automated QT Measurement Techniques in 7 Thorough QT Studies Implemented under ICH E14 Guidelines |
| URI | https://api.istex.fr/ark:/67375/WNG-DSFQLXKZ-J/fulltext.pdf https://onlinelibrary.wiley.com/doi/abs/10.1111%2Fj.1542-474X.2010.00402.x https://www.ncbi.nlm.nih.gov/pubmed/21251129 https://www.proquest.com/docview/846899509 https://pubmed.ncbi.nlm.nih.gov/PMC3076006 |
| Volume | 16 |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV3Pa9swGBWjh7HL1v12uxUdxm4OsiRb8TFkSbO2CXTzmNlFSJZMQopTkhja_vXTJztus_U0Bj4YLAnsp896kp7eh9CnhIkiMroIhRJlyK1JQy10HDIlUpUISo3P1jCdJZMf_CyP81b_BGdhGn-IbsENIsP_ryHAld7sB3nMacgFz3cKLTcX6gGfBOkW8KNvnZOUG6h89taIAKGkJN8X9TzakKOr8KVvHuOef0soH1JbPzaNX6Dl7q0aScqyV291r7j7w_Dx_7z2IXreUlg8aPrcS_TEVq_Q02m7Sf8azUE7cnWLB_V25fiwNfgyw9P7tUic7XxjN3hRYYGz-conC4Jyra4Re9dibxhqMJxzW-OvwwkeRRyf1uDMBWr9Nygbj7LhJGwTOoQLFgsaWsOF0koZmwhREkVj7diRSS1lMVjBR4VgRUJswQxVZWxsX2lCjYqAFZKUvUUH1aqy7xEm1k1sbSqUtZwTY7SNVF8Rrgtbln3NAvTZYyevG88OqdZLkLCJWP6cncov38eXF_n5L3kWILwDV7rAgt0SVdlVvZGOmLm5qONTAXrXYN01RoEVOqIUILHXC7oC4Nm9_6RazL13N_M7oUmAEg9yV-PBXMzBKwFeCfBKD6-8kYPZaOjujv614jF61iyHw_UBHWzXtf3o-NRWn_hI-Q0YXRUG |
| linkProvider | Wiley-Blackwell |
| linkToHtml | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV3Pb9MwFLbQkIALjF8jMMAHxC2VYztxc6y6dt3WVhoEEXGx7NhRq00p6hpp8Nfj56Rh3XZCSDlEim0peX7x954_fw-hTwkTRWR0EQolypBbk4Za6DhkSqQqEZQaX61hNk8m3_hpHudtOSA4C9PoQ3QJN_AM_78GB4eE9K6Xx5yGXPB8S9FywVDPAcqHUOAbhPSPvnRaUm6p8vVbIwKQkpJ8l9Zz70gOsMK3vr4Pfd4lUd4Et351Gj9Dl9v3akgpF716o3vF71uSj__pxffR0xbF4kEz7Z6jB7Z6gR7N2n36l2gB9JHLX3hQb1YOEluDzzM8-5uOxNlWOvYKLysscLZY-XpB0K6lNmIvXOw1Qw2Go25rfDKc4FHE8XEN4lxA2H-FsvEoG07CtqZDuGSxoKE1XCitlLGJECVRNNYOIJnUUhaDGnxUCFYkxBbMUFXGxvaVJtSoCIAhSdlrtFetKvsGYWJdbGtToazlnBijbaT6inBd2LLsaxagz9548mcj2yHV-gJYbCKW3-fH8ujr-Hyan_2QpwHCW-tK51uwYaIqu6qvpMNmLhx1kCpAB42xu8EoAEOHlQIkdqZB1wBku3efVMuFl-9mfjM0CVDirdz1uBGOOfNKMK8E80pvXnktB_PR0N29_deOH9HjSTabyunJ_OwdetJkx-E6RHubdW3fO3i10R-82_wBZNsZIg |
| linkToPdf | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV1bb9MwGLXQkCZeYNzDuPgB8ZbKsZ24eax6WXdpxSCIiBfLjh21KkqnrpEGvx5_ThpW2BNCykOk2JaS4y8-to_Ph9D7hIkiMroIhRJlyK1JQy10HDIlUpUISo3P1jCbJ9Mv_CyP81b_BGdhGn-IbsENIsP_ryHAr0y5H-QxpyEXPN8ptNxcqOf45H2ekBTSOIw-dVZSbqTy6VsjAoySknxf1XNnS46vwqe-uYt8_q2hvM1t_eA0eYRWu9dqNCmrXr3VveLnH46P_-e9j9DDlsPiQdPpHqN7tnqCDmftLv1TtADxyPcfeFBv144QW4MvMzz7vRiJs51x7DVeVljgbLH22YKgXCtsxN622DuGGgwH3Tb4dDjF44jjkxqsuUCu_wxlk3E2nIZtRodwyWJBQ2u4UFopYxMhSqJorB09MqmlLAYv-KgQrEiILZihqoyN7StNqFER0EKSsufooFpX9iXCxLqZrU2FspZzYoy2keorwnVhy7KvWYA-eOzkVWPaIdVmBRo2Ecuv8xM5-jy5vMjPv8mzAOEduNJFFmyXqMqu62vpmJmbjDpCFaAXDdZdYxRooWNKARJ7vaArAKbd-0-q5cKbdzO_FZoEKPEgdzVuTcYcvBLglQCv9PDKGzmYj4fu7tW_VnyHDj-OJvLidH5-jB40S-NwvUYH201t3zhutdVvfdD8AgCaF9E |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Highly+automated+QT+measurement+techniques+in+7+thorough+QT+studies+implemented+under+ICH+E14+guidelines&rft.jtitle=Annals+of+noninvasive+electrocardiology&rft.au=Couderc%2C+Jean-Philippe&rft.au=Garnett%2C+Christine&rft.au=Li%2C+Mike&rft.au=Handzel%2C+Robert&rft.date=2011-01-01&rft.issn=1542-474X&rft.eissn=1542-474X&rft.volume=16&rft.issue=1&rft.spage=13&rft_id=info:doi/10.1111%2Fj.1542-474X.2010.00402.x&rft.externalDBID=NO_FULL_TEXT |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1082-720X&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1082-720X&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1082-720X&client=summon |