1:Foundation of clinical trialsA medicine interventionisthe science or practice ofthe diagnosis,treatment,andpreventionofdisease,and canbedrugs,surgicalprocedures,medicaldevice,dietarycounseling,physiotherapy,sleeping,or(amongNorthAmericanIndiansandsomeotherpeoples)evena spell,charm,orfetishbelievedtohavehealing,protective,orother power.Goals of patientcare:the safestand most effective therapy,tomakethepatientfeel better (e.g.,painkiller)toimprovesurvivalandreducetheriskoffuturediseasecomplications(e.g.,drugsforhypertension,cancerorcardiovasculardisease),JNIVERSITtoachieveboth(e.g.,antibiotic)LMANITOSXikui Wang (University of Manitoba)Statistical Decision Analysis14/1982013
1. Foundation of clinical trials A medicine intervention is the science or practice of the diagnosis, treatment, and prevention of disease, and can be drugs, surgical procedures, medical device, dietary counseling, physiotherapy, sleeping, or (among North American Indians and some other peoples) even a spell, charm, or fetish believed to have healing, protective, or other power. Goals of patient care: the safest and most effective therapy, to make the patient feel better (e.g., painkiller), to improve survival and reduce the risk of future disease complications (e.g., drugs for hypertension, cancer or cardiovascular disease), to achieve both (e.g., antibiotic) Xikui Wang (University of Manitoba) Statistical Decision Analysis 2013 14 / 198
1.Foundation of clinicaltrialsAdverseeffectsareharmfulandundesiredeffectsresultingfrommedicalinterventions.Othernamesaresideeffects andadverseevents.The most serious side effects include mortality, morbidity,permanentdamage,birthdefects,hospitalization,toxicity,complicationsandsoon.ExamplesofadverseeffectsDeath,followingsedation,inchildrenusingpropofolDeafnessandkidneyfailureassociatedwithgentamicinBleeding of the intestine associatedwithaspirintherapyhighcosts(incrementalbenefitovergenericdrugs),Addiction to many sedatives and analgesics, such asdiazepamandmorphine,JNIVERSITLMANITOS.andmanymore...Xikui Wang (University of Manitoba)Statistical Decision Analysis15/1982013
1. Foundation of clinical trials Adverse effects are harmful and undesired effects resulting from medical interventions. Other names are side effects and adverse events. The most serious side effects include mortality, morbidity, permanent damage, birth defects, hospitalization, toxicity, complications and so on. Examples of adverse effects: Death, following sedation, in children using propofol, Deafness and kidney failure associated with gentamicin, Bleeding of the intestine associated with aspirin therapy, high costs (incremental benefit over generic drugs), Addiction to many sedatives and analgesics, such as diazepam and morphine, and many more . Xikui Wang (University of Manitoba) Statistical Decision Analysis 2013 15 / 198
1.Foundation of clinical trialsTheoverarchinggoal of medical researchistodevelop newinterventionsforthe diagnosis,treatment orpreventionofdiseaseandevaluatetheirbenefits(effectiveness)andrisks(safety).Thegoalofmedical researchandscientificinquiryistobettertreatpatientsandmostimportantly,toacquirenewknowledgeandinfluencefuturepractice.Specificrequirementsformedicalresearch:eliminatebias,quantifyandreduceerrors,produceaccurateestimatesoftreatmenteffectsandtheassociatedprecisionprovideahighdegree of credibility,reproductivity,as wellasinternalandexternalvalidityMethodsofmedical research:observational(epidemiologicalstudies)JNIVERSITTIMANITOSexperimental(clinicaltrialsXikui Wang (University of Manitoba)Statistical Decision Analysis16/1982013
1. Foundation of clinical trials The overarching goal of medical research is to develop new interventions for the diagnosis, treatment or prevention of disease and evaluate their benefits (effectiveness) and risks (safety). The goal of medical research and scientific inquiry is to better treat patients and most importantly, to acquire new knowledge and influence future practice. Specific requirements for medical research: eliminate bias, quantify and reduce errors, produce accurate estimates of treatment effects and the associated precision provide a high degree of credibility, reproductivity, as well as internal and external validity Methods of medical research: observational (epidemiological studies) experimental (clinical trials) Xikui Wang (University of Manitoba) Statistical Decision Analysis 2013 16 / 198
1.Foundation of clinical trialsObservational studiesare characterized bydata ona cohort of individuals with theintentofcorrelatingpotentialriskfactorswithclinicaloutcomes.Theycanprovidevaluableinformationabouttreatmenteffectsandsafety,especiallywithregardtoserious adversereactions.Commontypesofobservationalstudies:casereportsandcaseseries,cross-sectionalstudies(retrospective)case-controlstudies(prospective)cohortstudies,registrystudies,qualitativestudies(e.g.,interviews),JNIVERSITY.meta-analysis.IMANITOSXikui Wang (University of Manitoba)Statistical Decision Analysis17/1982013
1. Foundation of clinical trials Observational studies are characterized by data on a cohort of individuals with the intent of correlating potential risk factors with clinical outcomes. They can provide valuable information about treatment effects and safety, especially with regard to serious adverse reactions. Common types of observational studies: case reports and case series, cross-sectional studies, (retrospective) case-control studies, (prospective) cohort studies, registry studies, qualitative studies (e.g., interviews), meta-analysis. Xikui Wang (University of Manitoba) Statistical Decision Analysis 2013 17 / 198
1.Foundation of clinicaltrialsMajorlimitationsofobservationalstudiesObservational studiesareexploratoryinnatureandcanatmostestablishassociation,notcausation,betweenriskfactorsandmedical conditions.Strengthsofobservationalstudies:greateraccesstolarge,diverse,groupsofpatientsethical,manageable,quickdatacollectionandanalysisusefultomotivatenewmedicaltreatments.Weaknessesofobservationalstudies:vulnerabletoselectionbiaspublicationbias,recallbiasindicationbiasandascertainmentbias,JNIVERSITY福oftenoflargescale,butoflimitedscopeLMANITOAXikui Wang (Universityof Manitoba)StatisticalDecision Analysis18/1982013
1. Foundation of clinical trials Major limitations of observational studies Observational studies are exploratory in nature and can at most establish association, not causation, between risk factors and medical conditions. Strengths of observational studies: greater access to large, diverse, groups of patients, ethical, manageable, quick data collection and analysis, useful to motivate new medical treatments. Weaknesses of observational studies: vulnerable to selection bias, publication bias, recall bias, indication bias and ascertainment bias, often of large scale, but of limited scope. Xikui Wang (University of Manitoba) Statistical Decision Analysis 2013 18 / 198