Clinical Trial Process: An Overview John O. Naim, Ph.D. Director,

Clinical Trial Process: An Overview John O. Naim, Ph.D. Director, Clinical Trials Research Unit West Virginia University Mary Babb Randolph Cancer Center

What Is a Clinical Trial? Effectiveness of intervention to treat a disease Safety of a new drug 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

Phases of Drug Development Phase 1 Phase 2 Phase 3 Phase 4 No. of 15-30 Participants 100 100 to thousands Several hundreds to several thousands Purpose Determine efficacy Compare new agent with standard treatment Post –market Long-term safety and efficacy First in humans Find safe dose

Who are the Players? Human Subject Volunteers Physician Investigators Research Nurses Pharmacists Lab Techs Social Workers Data Managers

Research Protocol: Roadmap Detailed Research Plan that Includes: – – – – – – – Objectives Background and Rationale Subject Selection Criteria Treatment Plan Study Procedures Response Evaluation Criteria Statistical Section

Human Research is Highly Regulated Code of Federal Regulations (CFR) – Title 21- Food and Drugs » » » » » » Part 50 Part 56 Part 312 Part 314 Part 600, 6001 Part 812, 813, 814 Informed Consent IRB IND NDA Biologics Medical Devices – Title 45- Public Welfare » Part 46 (subparts B, C, D) DHHS, Protection of Human subjects

What About International Regulation? E6 Good Clinical Practice (GCP): Consolidated Guidance – International ethical and scientific quality standard for designing, conducting, recording and reporting trial results.

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

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

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.

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.