dme臨床科研設(shè)計與評價轉(zhuǎn)化醫(yī)學(xué)和精準(zhǔn)醫(yī)學(xué)translational-medicine課件

1、Translational Medicine & Precision Medicine轉(zhuǎn)化醫(yī)學(xué)和精準(zhǔn)醫(yī)學(xué)廣東省肺癌研究所 Guangdong Lung Cancer Institute循證醫(yī)學(xué)雜志 Journal of Evidence-based MedicineTranslational Medicine & PreClinical Research: NIH DefinitionEpidemiologic and behavioral studiesOutcomes research and health services research Patient-oriented resear

2、ch - Research conducted with human subjects, tissues, specimens, or cognitive phenomena for which an investigator directly interacts with human subjects Healthy volunteer: person with no known significant health problem who participates in clinical research to test a drug, device, or interventionCli

3、nical Research: NIH DefinitClinical TrialsA prospective study involving human subjects that is designed to answer specific questions about the effects or impact of particular biomedical or behavioral interventionsNOT healthy volunteer studies, which are designed to develop new knowledge, but provide

4、 no direct benefits to the subjectsClinical TrialsA prospective sTranslational Research: NIH DefinitionThe process of applying discoveries generated during research in the laboratory, and in preclinical studies, to development of trials and studies in humansLeveraging the observations made in clinic

5、al practice to drive new mechanistic investigations at the bench Enhancing the adoption of best practices in the communityTranslational Research: NIH DeBackgroundIn the past 30 years，NCI $200 BillionsResults：1.56million articles80 on mice, fruit fly and round worm。No change on cancer related mortali

6、ty rateBackgroundIn the past 30 yearsBackgroundBackgroundBackgroundNew biotechnologyGenomics(基因組), Proteomics(蛋白質(zhì)組)Bioinformatics(生物信息學(xué))Increasing complexity of clinical researchBackgroundNew biotechnologyDefinitionTranslational research, “transforms scientific discoveries arising from the laborator

7、y, clinical, or population studies into clinical applications”Include：bench to bedside(基礎(chǔ)研究到臨床應(yīng)用)bedside to bench(臨床治療結(jié)果促進(jìn)基礎(chǔ)研究)Source: National Cancer Institute, National Institutes of HealthDefinitionTranslational researBasic and Clinical Research are InterdependentTranslation from basic science to

8、 human studiesTranslation ofnew knowledgeinto clinical practiceBasicResearchClinical ResearchImprovedHealthAdapted from Sung et al. (2003) JAMA, 289, 1278-89. Copyright (2003) American Medical Association. All Rights reserved.“T1”“T2”The production of a promising new treatment/method that can be use

9、d clinically or commercialized. Ensure that new treatments and research knowledge actually reach the patients or populations for whom they are intended and are implemented correctlyBasic and Clinical Research arTranslational MedicineTranslate the success in genomic medicine into clinical application

10、sEvidence-based medicine develop rationale and theory for drug design and therapeutic interventionDevelop personal medicine and preventive medicineTranslational MedicineTranslatTranslational MedicineTranslational Research -hot spotGenomic and gene diagnosis and treatment基因組研究及基因診斷治療Phase I trial for

11、 drugs 藥物一期臨床試驗Genomic Pharmocology and personalized medicine 基因組藥理學(xué)與個體化醫(yī)學(xué)Biomarks 生物標(biāo)記物Signal transducting pathway and clinical applications 信號傳導(dǎo)通路的研究及其臨床應(yīng)用Stem cell干細(xì)胞Translational MedicineTranslatTranslational MedicineThe heart of translational research resides in Phase I trials where novel treat

12、ments are ：tested for feasibility and toxicitypreparation for a Phase II trial in which therapeutic effectiveness is testedMarincola, FMTranslational Medicine: A two -w ay road, JTM, 2006Translational MedicineThe hearClinical Research Training ProgramComputer SkillsClinical Research MethodsBiostatis

13、tics: Statistical Approach in Clinical ResearchMeasurements in Clinical ResearchEthics and Regulations of Clinical ResearchResearch Design and DevelopmentCost-effectiveness AnalysisRegression and ANOVALogistic RegressionClinical TrialsClinical Research Training ProEarly study on nitric oxide Synthas

14、eEarly study on nitric oxide SyUses for a cloned geneHomology comparisonQuantitate gene expressionChromosomal mappingDetermine transcriptional regulationPrepare recombinant proteinAntibody developmentTissue localizationDevelop transgenic/knockout animalsGene transfer/gene therapy studiesIntellectual

15、 property / technology transferUses for a cloned geneHomologydme臨床科研設(shè)計與評價轉(zhuǎn)化醫(yī)學(xué)和精準(zhǔn)醫(yī)學(xué)translational-medicine課件Explore Gene and DiseasesExplore Gene and Diseasesdme臨床科研設(shè)計與評價轉(zhuǎn)化醫(yī)學(xué)和精準(zhǔn)醫(yī)學(xué)translational-medicine課件Physiopathological StudyBench:Vasoprotective Properties of Nitric OxideInhibits platelet aggregatio

16、nInhibits leukocyte chemotaxisInhibits VSMC proliferationInhibits VSMC migrationPromotes EC growthInhibits EC apoptosisPotent vasodilatorPhysiopathological StudyBench:Cell and AnimalAdenoviral Vector (type 5, E1-, E3-)腺病毒載體Cell and AnimalAdenoviral VectSmall AnimalsSmall AnimalsBigger AnimalsBigger

17、AnimalsAnimal Experiment2005年Animal Experiment2005年dme臨床科研設(shè)計與評價轉(zhuǎn)化醫(yī)學(xué)和精準(zhǔn)醫(yī)學(xué)translational-medicine課件PhaseClinical TrialClinical Trial: AdiNOS gene therapy to block AV fistula neointimal hyperplasia in hemodialysis patients2006PhaseClinical TrialClinical TCurrent State of Translational Medicine17 year in

18、novation adoption curve from discovery into accepted standards of practiceEven if a standard is accepted, patients have a 50:50 chance of receiving appropriate care, a 5-10% probability of incurring a preventable, anticipatable adverse eventThe market is balking at healthcare inflation, new diagnost

19、ics and therapeutics will find increasing resistance for reimbursementCurrent State of TranslationalPrecision medicine 2015-1-20Precision medicine 2015-1-20Precision MedicinePrecision Medicine(personalized medicine): a form of medicine that uses information about a persons genes, proteins, and envir

20、onment to prevent diagnose, and treat disease.(NCI) Specific markers diagnose & treatment decisions Precision Cancer Medicine(PCM )Right DrugRight PatientRight TimeRight DoseMolecular eventKnowledgedecisionClinical TrialPrecision MedicinePrecision MeImatinib for GISTGIST genesis Key process： c-kit m

21、utation-KIT TK activationPDGFR mutation86% GIST kit mutation，prognosis factorImatinibOral small molecule TKIInhibit TK activation抑制酪氨酸激酶活化Design for chronic myeloid leukemia (CML)Imatinib for GISTGIST genesis Imatinib for GISTImatinib for GISTImatinib for GISTJoensuu H，et al. 2001Imatinib for GISTJo

22、ensuu H，et PretreatmentOne month of therapyH&E (at diagnosis)H&EKi 67CD117Joensuu H et al. N Engl J Med. 2001;344:1052-1056.The First GIST Patient: HistologyImatinib for GISTPretreatmentOne month H&E (at Imatinib for GISTJoensuu H，et al. 2001Theory：Imatinib could target GISTEasy Detected tumor marke

23、r：CD117Tissue from the patientResponse confirmed by pathology Dynamic monitored by tumor markerEthics：IRBImatinib for GISTJoensuu H，et Imatinib 治療 GIST2000.3： Joensuu H. first case2000.7： phase II study(B2222) 2001 autumn：phase II study (S0033,EORTC)2002.2：FDAImatinib 治療 GIST2000.3： Joensudme臨床科研設(shè)計與

24、評價轉(zhuǎn)化醫(yī)學(xué)和精準(zhǔn)醫(yī)學(xué)translational-medicine課件Imatinib for GIST5-year survivalKit mutation predict Imatinib responseImatinib for GIST5-year survivImatinib for GISTImatinib for GISTImatinib for GISTImatinib resistance cliniclabOvercome Imatinib resistance lab clinicMechanism of Imatinib resistance cliniclabImatinib for GISTImatinib resiImatinib for GISTSurgery in advance GISTWhen to stop?Imatinib for GISTSurgery in adChois Imatinib for GISTChoi et al, J Clin Oncology, 2007;25:1753-1759Chois Imatinib for GISTChoi eImatinib for GISTC-kit a