Chapter 1 Introduction

1.1 Purpose of this Toolkit

This toolkit is a general guide for investigators and project staff at Hebrew SeniorLife Institute for Aging Research (HSL IFAR) conducting, managing or overseeing clinical trials in older populations. The toolkit is not intended be a comprehensive document. Rather it is meant to outline major considerations for all phases of a clinical trial. Suggested resources are provided for more detailed information you must consult and adhere to the latest federal, sponsor, institutional, state and regional regulations.

Whenever possible, sections of this toolkit follow a similar outline: What, Why, How, Special Considerations for Aging Populations, Common Pitfalls, and Resources.

1.2 Are you Doing a Clinical Trial?

Below is the National Institutes of Health (NIH) definition of a clinical trial. As clinical trials are subject to additional oversight, a clear definition helps investigators ensure that they are meeting all of their obligations, and help funders ensure that the additional oversight is occurring when it is needed.

A research studyin which one or more human subjects2 are prospectively assigned3 to one or more interventions4 (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes.5 ______________________________________________________________________

1See Common Rule definition of research at 45 CFR 46.102(d).

2See Common Rule definition of human subject at 45 CFR 46.102(f).

3Prospectively assigned refers to a pre-defined process (e.g., randomization) specified in a protocol that stipulates the assignment of research subjects (individually or in clusters) to one or more arms of a clinical trial.

4An intervention is defined as a manipulation of the subject or subject’s environment for the purpose of modifying one or more health-related biomedical or behavioral processes and/or endpoints. Examples include: drugs/small molecules/compounds; biologics; devices; procedures (e.g., surgical techniques); delivery systems (e.g., telemedicine); strategies to change health-related behavior (e.g., diet, cognitive therapy, exercise); treatment strategies; prevention strategies; and, diagnostic strategies.

5Health-related biomedical or behavioral outcome is defined as the pre-specified goal(s) or condition(s) that reflect the effect of one or more interventions on human subjects’ biomedical or behavioral status or quality of life. Examples include: positive or negative changes to physiological or biological parameters (e.g., improvement of lung capacity); positive or negative changes to psychological or neurodevelopmental parameters (e.g., mood management intervention for smokers; reading comprehension and /or information retention); positive or negative changes to disease processes; positive or negative changes to health-related behaviors; and, positive or negative changes to quality of life.

1.3 Clinical Trial Phases

Clinical trials are conducted in a series of steps, called phases - each phase is designed to answer a separate research question. These phases mostly apply to trials testing drugs or devices, rather than behavioral interventions.

  • Phase I: Researchers test a new drug or treatment in a small group of people for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.

  • Phase II: The drug or treatment is given to a larger group of people to see if it is effective and to further evaluate its safety.

  • Phase III: The drug or treatment is given to large groups of people to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.

  • Phase IV: Studies are done after the drug or treatment has been marketed to gather information on the drug’s/treatment’s effect in various populations and any side effects associated with long-term use.

1.4 Training Requirements and Opportunities:

Aside from clinical trial design and/or biostatistical training, there are varied practical, short-term courses for principal investigators and project personnel to enhance the conduct and rigor of their clinical trials.

  1. Good Clinical Practice (GCP) is an international quality standard that defines standards for clinical trials involving human subjects. The NIH require Certifications in Good Clinical Practice (GCP) for NIH-funded Investigators and clinical trial site staff who are responsible for the conduct, management and oversight of NIH-funded clinical trials. The FDA has a similar requirement.

    There are many other extensive courses offered to become GCP certified, both internet-based and on-site. Most have a tuition cost. It is a good idea, if resources are available, for Project Directors leading clinical trials to receive GCP certification. Below are examples of a few of these many opportunities.

    National Drug Abuse Treatment Clinical Trails Network (GCP) Course.

    Online GCP.

    Collaborative Institutional Training Initiative (CITI) GCP Course.

  2. Harvard Catalyst Clinical Trial Design is an opportunity for new clinical investigators, who have an idea for development of a clinical trial, to participate in an intensive eight-week course. It is offered at no cost to members of the Harvard Catalyst community or other Clinical and Translational Science Award(CTSA) usually in May/June, with an application due in March. Participants learn the fundamentals of clinical trial design, including instructions on how to design a protocol, information on IRB and regulatory topics, and on trial implementation. Additional course topics include statistical analysis, budgeting, and data management.

  3. NIH Clinical Research Training On-Line course is available 24/day at no cost with the following objectives: i. To raise awareness of the ethical issues involved in human subjects research; ii. To become familiar with the roles and responsibilities of the principal investigator and the institution when conducting clinical research in the NIH intramural research program; iii. To have an understanding of Food and Drug Administration (FDA) oversight of clinical research; and iv. To become familiar with how developments in science and health are reported by the media and how to work effectively with reporters.

  4. Barnett International Design and Conduct of Clinical Trials: Design Requirements, Statistical Issues, and Clinical Protocols is an on-site two-day course that provides an introduction to the scientific, statistical, and ethical aspects of clinical trials research. Cost (2016) = $1800.

1.5 Clinical Trial Planning Resources

Numerous resources are available to researchers as they plan and proceed with their clinical trial.

  1. One such resources is The NIA Clinical Trial Toolbox: A resource for quality studies. This toolbox provides researchers with a central source of materials to develop and manage clinical trials. The site includes: templates, forms, guidelines and other related information that can be very helpful throughout the research process and is referenced throughout the ISAC toolkit.