BIOE 301Overview of TodayREVIEW OF LAST TIMEProgression of Heart DiseaseHeart Failure ReviewWhich one is a healthy heart?Slide 7CLINICAL TRIALSTake-Home MessageSlide 10Slide 11Types of Clinical StudiesTypes of Clinical TrialsSingle and Two Arm StudiesPhases of Clinical TrialsCLINICAL TRIAL DATA AND REPORTINGExamples of Biological DataBiological VariabilityDescriptive StatisticsExample: Blood PressureEXAMPLE: ABIOCOR TRIALClinical Trial of AbioCorSlide 23Slide 24Consent FormEXAMPLE: VITAMIN EThe StudyFollow-UpPLANNING A CLINICAL TRIALSlide 30Planning a Clinical TrialExample – Planning a Clinical TrialDesign ConstraintsSample Size CalculationTypes of Errors in Clinical TrialSlide 36How do we calculate n?Drug Eluting Stent – Sample SizeHow to Get InvolvedAssignments Due Next TimeBIOE 301Lecture Twenty:Clinical TrialsMike [email protected] of TodayReview of Last Time (Heart Disease)What is a Clinical Trial?Clinical Trial Data and ReportingClinical Trial Example: Artificial HeartClinical Trial Example: Vitamin EPlanning a Clinical TrialREVIEW OF LAST TIMEProgression of Heart DiseaseHigh Blood PressureHigh Cholesterol LevelsAtherosclerosisIschemiaHeart AttackHeart FailureHeart Failure ReviewWhat is heart failure?Occurs when left or right ventricle loses the ability to keep up with amount of blood flowhttp://www.kumc.edu/kumcpeds/cardiology/movies/sssmovies/dilcardiomyopsss.htmlHow do we treat heart failure?Heart transplantRejection, inadequate supply of donor heartsLVADCan delay progression of heart failureArtificial heartWhich one is a healthy heart?Heart Failure Heart FailureHealthy Heart Atrial Fibrilationhttp://static.howstuffworks.com/gif/artificial-heart-abiocor-diagram.gif http://www.ps-lk3.de/images/ABIOCOR.JPGCLINICAL TRIALSTake-Home MessageClinical trials allow us to measure the difference between two groups of human subjectsThere will always be some difference between selected groupsBy using statistics and a well designed study, we can know if that difference is meaningful or notScience of Understanding DiseaseEmerging Health TechnologiesPreclinical TestingClinical TrialsAdoption & DiffusionAbandoned due to:• poor performance• safety concerns• ethical concerns• legal issues• social issues• economic issuesBioengineeringEthics of researchCost-EffectivenessClinical StudiesEpidemiologicClinical TrialsObservationalControlledTwo-ArmSingle-ArmTypes of Clinical StudiesEpidemiologic - Hypothesis GenerationObserve a group of patients and look for common factorsAIDS in the 1980sDr. Snow and the Broad St. PumpClinical Trial - Hypothesis TestingDetermine the difference, if any, between two groups of patientsTypes of Clinical TrialsObservational StudiesObserve two groups already existing, and review data to determine differing factors between groupsEx. What behaviors are prevalent in lung cancer patients but not in those without the diseaseProblems – Bias, and lack of controlControlled StudyIntroduce difference between two selected groupsSingle and Two Arm StudiesSingle-Arm StudyGive treatment to all patientsCompare outcome before and after treatment for each patientCan also compare against literature valueTwo Arm StudySplit patients in trial into a control group and an experimental groupCan blind study to prevent the placebo affectPhases of Clinical TrialsPhase IAssess safety of drug on 20-80 healthy volunteersPhase IIDrug given to larger group of patients (100-300) and both safety and efficacy are monitoredPhase IIIVery large study monitoring side affects as well as effectiveness versus standard treatmentsPhase IV (Post-Market Surveillance)Searches for additional drug affects after drug has gone to marketCLINICAL TRIAL DATA AND REPORTINGExamples of Biological DataContinuously variableCore body temperature, height, weight, blood pressure, ageDiscreteMortality, gender, blood type, genotype, pain levelBiological VariabilityVariabilityMost biological measurement vary greatly from person to person, or even within the same person at different timesThe ChallengeWe need some way of knowing that the differences we’re seeing are due to the factors we want to test and not some other effect or random chance.Descriptive StatisticsModeMost common valueMeanStandard Deviationn1iinxxn1i2n)x(xσExample: Blood PressureMeasurementGet into groups of 4 and take each others blood pressure for the next 5-10minReportingIn those same groups, calculate the mean, mode and standard deviation of the classAnalysisIs the data normally distributed?Is there a difference between sides of the classroom?Does it mean anything?EXAMPLE: ABIOCOR TRIALClinical Trial of AbioCorGoals of Initial Clinical TrialDetermine whether AbioCor™ can extend life with acceptable quality for patients with less than 30 days to live and no other therapeutic alternative To learn what we need to know to deliver the next generation of AbioCor, to treat a broader patient population for longer life and improving quality of life.Clinical Trial of AbioCorPatient Inclusion Criteria (highlights)Bi-ventricular heart failure Greater than eighteen years old High likelihood of dying within the next thirty daysUnresponsive to maximum existing therapies Ineligible for cardiac transplantation Successful AbioFit™ analysis Patient Exclusion Criteria (highlights)Heart failure with significant potential for reversibility Life expectancy >30 days Serious non-cardiac disease Pregnancy Psychiatric illness (including drug or alcohol abuse) Inadequate social support systemClinical Trial of AbioCorClinical Trial EndpointsAll-cause mortality through sixty days Quality of Life measurementsRepeat QOL assessments at 30-day intervals until death Number of patients Initial authorization for five (5) implants Expands to fifteen (15) patients in increments of five (5) if 60-day experience is satisfactory to FDAConsent FormLink to Consent Form:http://www.sskrplaw.com/gene/quinn/informedconsent.pdfLink to other Documents about lawsuithttp://www.sskrplaw.com/gene/quinn/index.htmlEXAMPLE: VITAMIN EThe StudyPilot StudyIn the early 1990’s, small study done which showed taking vitamin E reduced risk of heart diseaseRegularly taking high doses
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