Clinical Trial Process: An Overview Dennis R. DeRosia, PA, MA Director, Business Development Profil Institute for Clinical Research email@example.com Past President & COB Association of Clinical Research Professionals www.acrpnet.org
What 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 life
Types 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 disease
Who 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, Professional
Evolution 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.gov
Human 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 subjects
What 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 Experiment
Research Protocol: Roadmap • Detailed Research Plan that Includes: • Objectives • Background and Rationale • Subject Selection Criteria • Treatment Plan • Study Procedures • Response Evaluation Criteria • Statistical Section
Protocols 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 insulin
Protocol 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 MELLITUS
Institutional 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 voluntary
Patient 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 referrals
Subject 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 players
Serious 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 are Page 1 stories, television news reports and magazine cover stories almost daily on medical breakthroughs - new treatments for everything from the flu, obesity, AIDS and heart disease.”
News Update • “Medical clinical research slows for lack of patients” • Los Angeles Times – March 14, 2009 • Enrollment problems delay more than 70% of clinical trials from one to six months • In cancer care, less than 5% of patients enter clinical trials • 700 cancer therapies in pipeline
News Update • “It’s time to speed up drug approvals” • The San DiegoUnion-Tribune – July 11,2008 • by Sally C. Pipes • FDA approved just 18 cancer drugs in past three years • CyberKnife shoots beams of radiation at tumors • Every day 1,500 Americans die from cancer
Pay Attention to the Clinical Research Around You You may be the beneficiary some day! Thank you