Slide 1What Is a Clinical Trial?Types of Clinical TrialsPhases of Drug DevelopmentSlide 5Who are the Players?Evolution of RegulationsHuman Research is Highly RegulatedWhat About International Regulation?Why is Human Research Highly Regulated?Research Protocol: RoadmapProtocolsProtocol MouthfulStudy Flow ChartStudy Flow ChartInstitutional Review Board (IRB)Informed ConsentPatient Recruitment ChallengeRecruitment StrategiesSubject Data CollectionSerious Adverse EventsClinical Trial End ProductSlide 23News UpdateNews UpdateCoalition of National Cancer Cooperative GroupsPay Attention to the Clinical Research Around YouClinical Trial Process: An OverviewDennis R. DeRosia, PA, MADirector, Business DevelopmentProfil Institute for Clinical [email protected] President & COBAssociation of Clinical Research Professionalswww.acrpnet.orgWhat Is a Clinical Trial?Effectiveness of intervention to treat a diseaseSafety of a new drug or deviceDefining dose administrationTesting drug formulationExploring combination therapiesEvaluating effect of therapies on quality of lifeTypes of Clinical TrialsTreatment–Test new approaches to treat a diseasePrevention–What approaches can prevent diseaseEarly-detection/screening–What are new ways to find hidden diseaseDiagnostic–How can new tests or procedures ID diseasePhases of Drug DevelopmentPhase 1 Phase 2 Phase 3 Phase 4No. of Participants15-30 100-300 100 to thousandsSeveral hundreds to several thousandsPurpose First in humanssafe dosePOC1/3 failDetermine efficacySafety50% failCompare new agent with standard treatmentSafety1/3 failPost –marketLong-term safety and efficacyWho are the Players?Human Subject VolunteersPhysician Investigators & StaffNIH – National Institutes for HealthManufacturing companies (Sponsor)OHRP - Office for Human Research Protections FDA – Food & Drug Administration (CDER, CBER, CDRH)Settings: Academic, Private Practice, ProfessionalEvolution of Regulations1938 – Food, Drug & Cosmetic ACT1962 – Kefauver-Harris Amendment1968 – Drug Efficacy Study Implementation1981 – IRB Review Required1983 – Orphan Drug Act1997 – ICH-E6 Good Clinical Practice (GCP)1998 – Pediatric Rule2000 – NIH launches www.clinicaltrials.govHuman Research is Highly RegulatedCode of Federal Regulations (CFR)–Title 21- Food and Drugs»Part 50 Informed Consent»Part 56 IRB»Part 312 IND»Part 314 NDA»Part 600, 6001 Biologics»Part 812, 813, 814 Medical Devices–Title 45- Public Welfare»Part 46 (subparts B, C, D) DHHS, Protection of Human subjectsWhat About International Regulation?International Conference on HarmonizationE6 Good Clinical Practice (GCP): Consolidated Guidance–International ethical and scientific quality standard for designing, conducting, recording and reporting trial results. (US, EU & Japan)Why is Human Research Highly Regulated?Past transgressions lead to the need for laws that protect the rights and welfare of human subjects.–Nuremberg Doctors Trial of 1946 (Nuremberg Code)–Thalidomide Tragedy (Kefauver-Harris Amendment)–Tuskegee Experiments (Belmont Report)–Human Radiation Experiments–Gene Transfer ExperimentResearch Protocol: Roadmap Detailed Research Plan that Includes:–Objectives–Background and Rationale–Subject Selection Criteria–Treatment Plan–Study Procedures–Response Evaluation Criteria–Statistical SectionProtocolsA Phase I, Double-blind, Placebo-controlled, Dose-escalation Study of the Safety and Pharmacokinetics of Drug A31 in Subjects with Type 2 Diabetes MellitusA randomized, double-blind, placebo-controlled study assessing the effect of (study drug) Controlled-Release Tablet on hypoglycemia in type 1 diabetic subjects intensively treated with insulinProtocol MouthfulA PHASE 1, RANDOMIZED, PLACEBO-CONTROLLED, SEQUENTIAL PARALLEL GROUP, MULTIPLE DOSE ESCALATION TRIAL TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS, AND PHARMACODYNAMICS OF 28 DAYS OF ADMINISTRATION OF ND- 00254 TABLETS TO SUBJECTS WITH TYPE 2 DIABETES MELLITUSStudy Flow ChartStudy Flow ChartInstitutional Review Board(IRB)All clinical trials must be approved and monitored by an IRB.IRB is an independent committee of physicians, nurses, statisticians, community advocates and others.The function of the IRB is to ensure that a clinical trial is ethical and the rights welfare of study participants are protected.Informed ConsentLearning the key facts about a trial before deciding whether to participate.–Research study purpose–Risks/Benefits–Alternative treatments–Confidentiality of records–Medical treatment available if injury occurs–Whom to contact for answers to questions–Statement that participation is voluntaryPatient Recruitment ChallengePoor patient recruitment is the number one reason that trials fail.Only 3 to 5 percent of newly diagnosed adult cancer patients participate in a clinical trial.Reasons for this relatively low number are many.Recruitment StrategiesPhysician trust and contactStudy staff contactSpeaking to community groupsNewspaper and radio AdsInternet websites Physician referralsSubject Data CollectionData is collected on case report forms (CRF)Much of clinical data is taken from the subjects medical record (source documents)Pharmaceutical and device trials, data is verified by multiple playersSerious Adverse EventsEvents that results in any of the following:–Death or life-threatening–Hospitalization or prolonged hospitalization–Persistent or significant disability/incapacity–Congenital anomaly/birth defectEvents that are serious, unexpected, and related or possibly related to participation in the research must be reported to the Sponsor, FDA and IRB in a timely manner.Clinical Trial End ProductIdeal: Unambiguous conclusion regarding the clinical outcome of the test treatment/device. Always strive for the ideal, but in most cases have to settle for the best comprise.Positive-leaning articles tend to focus on gains made in fighting particular diseases.“Alzheimer’s vaccine study promising”“Treatment for cancer advances in trials”“A promising weapon in the fight against MS”* * * * * * * * * * * * * * * * * * * * *“Medical Miracles or Misguided Media”The Los Angeles Times“It sometimes seems as if there