Clinical Trial Process: An Overview

Dennis R. DeRosia, PA, MA

Director, Business Development

Profil Institute for Clinical Research

dennis.derosia@profil-research.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

Phases of Drug Development

Phase 1 Phase 2 Phase 3 Phase 4

No. of Participants

15-30 100-300 100 to thousands

Several hundreds to several thousands

Purpose First in humanssafe dosePOC

1/3 fail

Determine efficacySafety

50% fail

Compare new agent with standard treatmentSafety1/3 fail

Post –marketLong-term safety and efficacy

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

Study Flow Chart

Study Flow Chart

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

Coalition of National Cancer Cooperative Groups

Pay Attention to the Clinical Research Around You

You may be the beneficiary some day!

Thank you