The Sourcebook for Clinical Research

A Practical Guide for Study Conduct

Natasha Martien, Jeff Nelligan

• Publisher: Academic Press
• Year: 2018
• Print ISBN: 9780128162422
• eBook ISBN: 9780128162439
• Topic: Medicine
• Subtopic: Medical Theory, Practice & Reference

A single trial is complex, with numerous regulations, administrative processes, medical procedures, deadlines and specific protocol instructions to follow. And yet, there has existed no single-volume, comprehensive clinical research reference manual for investigators, medical institutions, and national and international research personnel to keep on the shelf as a ready reference to navigate through trial complexities and ensure compliance with U.S. Federal Regulations and ICH GCP until The Sourcebook for Clinical Research. An actionable, step-by-step guide through beginning to advanced topics in clinical research with forms, templates and checklists to download from a companion website, so that study teams will be compliant and will find all the necessary tools within this book. Additionally, the authors developed Display Posters for Adverse Events Plus Reporting and Medicare Coverage Analysis that can be purchased separately here: https://www.elsevier.com/books-and-journals/book-companion/9780128162422/order-display-posters. Moreover, The Sourcebook for Clinical Research contains clear information and guidance on the newest changes in the industry to keep seasoned investigators and staff current and compliant, in addition to providing detailed information regarding the most complex topics.This book serves as a quick, actionable, off-the-shelf resource to keep by your side at the medical clinic.- Makes vital trial conduct information easy to understand and instructs on how to practically apply current Federal regulations and Good Clinical Practice (ICH GCP)- Offers extensive guidance that is crucial for guaranteeing compliance to clinical research regulations during each step of the clinical research process- Provides up-to-date and extensive coverage of beginning to advanced topics, and, step-by-step actions to take during exceptional circumstances, including compassionate use, emergency use, human subjects protections for vulnerable populations, and federal audits- Furnishes a detailed clinical research Glossary, and a comprehensive Appendix containing ready-to-use forms, templates, and checklists for clinical trial personnel to download and begin using immediately.- Written for the fast-paced clinic environment with action steps and forms in the book to respond to a research subject's needs urgently and compliantly

Chapter 1

Foundational Elements and Regulatory Requirements

Abstract

This chapter introduces basic elements and regulatory guidelines of clinical research. It begins with definitions of the various types of research studies, delineates the differences between a clinical research study and a clinical trial, and provides an overview of the regulations and ethical guidelines governing research found in the U.S. Code of Federal Regulations and the International Council for Harmonisation Good Clinical Practice (ICH GCP). The chapter then offers useful guidance to medical institutions and physicians seeking to attract trial Sponsors and funding and provides an overview of Principal Investigator and Research Coordinator responsibilities once a study is secured. The chapter concludes with an explanation of the role of the landmark Health Insurance Portability and Accountability Act (HIPAA) and the requirements for Protected Health Information (PHI).

Keywords

Medical Research, Clinical Research, Clinical Trial; U.S. Code of Federal Regulations (CFR); International Council for Harmonisation Good Clinical Practice (ICH GCP); medical facility marketing; Principal Investigator; Research Coordinator; Health Insurance Portability and Accountability Act (HIPAA); Protected Health Information (PHI)

Purpose of chapter:

• • Describes the purpose of medical research
• • Defines the Types of Research Studies
• • Provides the definition of a Clinical Trial
• • Explains how a Clinical Trial differs from Clinical Research
• • Provides overview of Mandatory Regulations and Ethical Guidelines for Use in Clinical Research: Code of Federal Regulations and ICH GCP (International Council for Harmonisation Good Clinical Practice)
  1. a. Explains FDA versus HHS regulations
• • Describes How to Secure a Clinical Trial and Market your Medical Facility to Sponsors
• • Explains Principal Investigator Responsibilities
• • Explains Research Coordinator Responsibilities
• • Describes the Role of HIPAA and PHI in Clinical Research

1.1 What is the Purpose of Medical Research?

Purpose of section:

• • Explains why medical research is conducted

Clinical studies are designed to add to medical knowledge related to the treatment, diagnosis, and prevention of diseases or conditions. Some common reasons for conducting clinical studies include:

• • Evaluating one or more interventions (for example, drugs, medical devices, approaches to surgery or radiation therapy) for treating a disease, syndrome, or condition;
• • Discovering ways to prevent the initial development or recurrence of a disease or condition;
• • Evaluating one or more interventions aimed at identifying or diagnosing a particular disease or condition;
• • Examining methods for identifying a condition or the risk factors for that condition, and,
• • Exploring and measuring ways to improve the comfort and quality of life through supportive care for people with a chronic illness.¹

In these textbook-like bullet points, however, the heart and soul of why we conduct studies is not truly conveyed. When you are working in a hospital and see the pain in a patient’s eyes, see their family grieving and anxious, or a child in a wheelchair with a shaved head, you want to do anything you can to help. You want to find a cure for what afflicts the people in your care. You want to relieve a family of its burdens. When you see up close this suffering and anxiety, it becomes very easy to understand why medical research is conducted: to find relief or better treatments, so that people can lead a better quality of life or so they can continue to live.

1.2 Defining the Types of Research Studies

Purpose of section:

• • Defines the various types of research studies
• • Defines the term “clinical trial”
• • Explains the difference between a clinical trial and clinical research

Types of research studies

1. Adaptive clinical trial

An Adaptive Design Clinical Study is a study that includes a prospectively planned opportunity for modification of one or more specified aspects of the study design and hypotheses based on analysis of data (usually interim data) from subjects in the study. Analyses of the accumulating study data are performed at prospectively planned time points within the study, can be performed in a fully blinded manner or in an unblinded manner (see Chapter 4, Section 4.3 for definitions), and can occur with or without formal statistical hypothesis testing.²

An adaptation can be a revision to any part of the protocol. Examples include the eligibility criteria; the treatment duration; the lab tests required; sample size; the data-monitoring schedule; or, statistical analysis.

2. Ascending dose studies

a. Single ascending dose (SAD)

“Single ascending dose” is a part of the clinical trial design for Phase I trials. The SAD tests what the maximum tolerated IND (Investigational New Drug) dose is for subjects. When approximately 1/3 of research subjects experience unacceptable toxicity, the maximum tolerated dose is declared. SAD also serves to identify side effects.

b. Multiple ascending dose (MAD)

After these SAD results are documented, “multiple ascending dose” testing begins. MAD utilizes pharmacokinetics (PK) and pharmacodynamics (PD) to test the safety and tolerability of multiple low doses of an IND. MAD also serves to identify side effects.

3. Blinded study

A study in which the subject, the investigator, or anyone assessing the outcome is unaware of the treatment assignment(s). NOTE: Blinding is used to reduce the potential for bias.³

With single blinding, the patient is unaware whi...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• Dedication
• About the Authors
• Preface
• Chapter 1: Foundational Elements and Regulatory Requirements
• Chapter 2: Preparation Before a Clinical Trial Begins
• Chapter 3: Recruiting Clinical Research Subjects
• Chapter 4: Clinical Trial Conduct—A Daily Perspective
• Chapter 5: Organizations With Oversight Responsibility in Clinical Research
• Chapter 6: Exceptional Circumstances in Clinical Research
• Chapter 7: Education and Certification in Clinical Research
• Chapter 8: The Newest Changes in Clinical Research
• Chapter 9: After the Study Has Ended
• Clinical Trials Glossary
• Index