26 July 2008 Imaging and Cardiology Jonathan Goldman ... - ICON plc

More documents

Recommendations

Info

Pg 02Table 1: Application of Imaging in Clinical TrialsImaging Modality Mode of Action Measurements Strengths ChallengesEchocardiographyUltrasound reflects offmyocardium. Can alsodetect microspheres formarkers of blood in cavitiesor in heart muscle(“perfusion”).Cardiac cavity size, function(especially left ventricularfunction), filling pressures(“diastolic function”), valvefunction, fluid around heart(“pericardial effusion”),pressure in the pulmonaryartery, resistance in thelungs, and cardiac output.Widely available, easy, nopost processing required.No radiation.Good screening test forabnormal function.Handheld transducer bytechnologist.Operator dependent.May be limited by patientfactors such as obesity,lung disease, and poorwindows.Need to control qualityat entry.SPECTIsotope taken up by heartcells, proportional to bloodflow. Gamma camera detectsemitted radioactivity.Heart perfusion at restand stress.Perfusion defects at stress,but not rest, imply significantcoronary disease.Widely available, easy, hugeclinical experience.Can quantitate images withsemi-automated software.Images must be post processed.Substantial readervariability exists.High radiation dose.Cardiac cavity size, function(especially left ventricularfunction).Cardiac CT High resolution CT scan. Image coronary arterieswith high resolution.Cardiac cavity size, function.Quick to do. Potentiallya non-invasive test todetect CAD.Could replace highly riskyinvasive alternative.Cannot overcomecalcification. Motionartifacts troublesome.Cannot differentiatemoderate from severecoronary obstructions.High radiation dose.MRIMagnet assesses musclemotion, sometimes withcontrast agent.Cardiac cavity size, function(especially left ventricularfunction), filling pressures(“diastolic function”), valvefunction, fluid around heart(“pericardial effusion”),pressure in the pulmonaryartery, resistance in thelungs, cardiac output.High technology.Standard of truth for leftventricular size, functionand mass.Can detect perfusion.Very sensitive to smallinfarcts.Software settings at site.Specialized equipment.Not suitable as screeningtest.Contrast may be toxic tokidney.Coronary AngiographyInject dye directly intocoronary artery.Severity of coronarynarrowing.Assessment of patency ofcoronary stents.Widely available.Gold standard for presenceand severity of coronaryartery disease.Invasive.High morbidity fromvascular access andcardiac complications.Diagnostic procedure toplan for revascularization orsurgery.44021 US.indd 4 12/1/08 10:19:46 AM
Pg 03Table 2: Examples of Primary diagnostic studiesProduct Imaging Mode EndpointNew adenosinereceptor agonistNew CT Angiocontrast agentNew Ultrasoundcontrast agentRest/stress cardiacSPECTCT AngioX Ray AngioRest/stress perfusionEchoRest/stress SPECTX Ray AngioSensitivity and specificityof SPECT for CAD diagnosis,compared to existingstress method.Sensitivity and specificityof CTA for CAD diagnosis,compared to X Ray Angio.Equivalence of Echo andSPECT to diagnose CADcompared to X Ray angio.Figure 2: Cardiac SPECT and perfusionechocardiography imagesImaging has an increasing role in the evaluation of cardiac safetywhere it is used together with adverse events, ECG, and laboratorytests for cardiac enzymes to assess for cardiac toxicity. This ismost often found where animal studies suggest possible signal forsafety concern, or where cardiac toxicity is a known class effect fortoxicity. Some examples are shown in Table 4.Role of the Central Imaging Core LaboratoryImaging studies in some clinical trials are performed and interpretedat clinical sites according to standard of care. This is not idealin the clinical trial setting, since it introduces bias in the way thatimages may be acquired or interpreted, without the use of a singlemethodology or ability to query potentially erroneous findings (orbeneficial ones). In the worst case, false documentation of asafety concern could mean withholding of chemotherapy.Conversely, missed cardiac toxicity could lead to early mortalityinduced by an experimental drug. The role of a central lab is toprovide medical, technical, statistical, operational and regulatoryexpertise to the imaging study. Good standardization and trainingshould avoid such false signals and ensure high quality data.It is clearly essential that sites have adequate equipment to acquireand archive images, and have adequately qualified staff, who areprepared to be trained on the particular protocol. This can beproblematic, as in some studies the Imaging laboratory has onlylimited relation to the investigator. Good communication betweenthe clinical CRO, core laboratory, imaging laboratory and studycoordinator is key.It is very important for the core laboratory to consult with thesponsor in the objectives of the study so that the most suitableIt is clearly essential that sites have adequateequipment to acquire and archive images, andhave adequately qualified staff, who are preparedto be trained on the particular protocol.Table 3: Examples of use of Imaging as a biomarker of EfficacyProduct Indication ImagingModeIntracardiac deviceto exclude cardiacaneurysm from thecirculationHeart FailureEchoMRICTEndpointImprovement inventricular functionor cardiacoutput.Novel inotropes Heart Failure Echo Improvement inventricular functionor cardiacoutput.Novel gene therapy Heart Failure EchoMRICTSPECTPETPulmonaryvasodilatorLipid loweringtherapyPulmonaryhypertensionHyperlipidemiaEchoIntravascularultrasoundImprovement inventricular functionor cardiacoutput or perfusion,or viability.Effect on pulmonarypressure andresistance.Reduction inatheroscleroticplaque.continued on page 444021 US.indd 5 12/1/08 10:19:46 AM
Page 1: Vol. 14Winter Issue 2008Technology
Page 5 and 6: Pg 05Conventional Safety Markers an
Page 7 and 8: Pg 07Hepatotoxicity is the single m
Page 9 and 10: Pg 09Technological advances in clin
Page 11 and 12: Pg 11ICON Profile: Jonathan Goldman

26 July 2008 Imaging and Cardiology Jonathan Goldman ... - ICON plc

Create successful ePaper yourself

Delete template?

Save as template?