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What is a Protocol in Clinical Trials?

As a clinical trial participant, you attend clinic appointments, provide information about your experience and take routine tests such as blood draws. Ever wondered how those schedules, tests and information all come together? There is a method, and it all starts with a clinical trial protocol.

You can think of the clinical trial protocol as a recipe for cooking or instructions on how to put together a piece of furniture. A protocol is a written document that serves many purposes:

  1. It instructs the physician (primary investigator) and staff (study coordinators) how to execute the trial.
  2. It describes how a trial is conducted, ensures the safety of study participants and ensures the integrity of the data collected throughout the trial.
  3. It is also a communication tool with regulators and ethical review boards to share the intent and desired outcomes of a study.

There are many elements to a clinical trial protocol, but there are some key elements which potential participants should know more about. These include why the study is being conducted, what the desired outcomes are, how the outcomes will be measured and who can participate.

Purpose of the Trial

The study background and rationale describe why the clinical trial is being conducted. Depending on the phase of the trial, it may be designed to determine if the investigational drug is safe (drug safety study), better understand the drug’s activity in the body (pharmacokinetics and pharmacodynamics, or PK/PD) and indicate if it is promising or effective in a particular disease being studied (drug efficacy trial). An investigational drug is one that is currently being tested and has not been approved for sale in the United States by the Food and Drug Administration (FDA). All of these reasons describe the purpose of clinical trials that are sponsored by Lilly.

Outcomes and Measures

A protocol must describe the measure(s) that will define whether the trial is successful or not. Protocols must define measures to assess safety and often efficacy. Sometimes, Lilly uses CoDESIGN workshops to get input from patients and research site staff to help determine the outcomes that matter most to them. Sometimes, we have to build the outcomes based on requirements from the U.S. FDA or other similar regulatory agencies in other countries.

Generally, there are one or two major (primary) objectives and several minor (secondary and exploratory) objectives. For example, in a trial for alopecia areata, the primary objective may be to have more hair at the end of the trial compared to the beginning of the trial. In such a trial, a secondary objective may be a patient reported outcome such as a quality-of-life questionnaire that measures whether endpoints of mental health, social function and emotional impact improve during the trial.

Who Can Participate?

The inclusion and exclusion criteria describe the people that are allowed to participate in the trial. These criteria cover details each participant must have, such as the disease being studied, and restrictions, such as medications which a participant cannot have taken in the past. Describing the group of people that are eligible to participate is important because it helps scientists determine that the outcomes are actually caused by the effects of the investigational drug and not by some other confounding factor.

Additional Study Design Elements

The study design has several additional elements that impact participants and should be considered in any decision about joining a clinical trial. These additional elements include the length of the trial, the number of clinic visits, the number of participants needed for the trial and whether some participants will receive placebo.

A clinical trial protocol is a scientific document intended for research personnel, so it’s not likely that clinical trial participants will be able to read the full protocol. Still, it’s important to understand the role of the protocol as a key source of information.

For example, the key elements from a clinical trial protocol are also provided in the trial summary pages on Lilly TrialGuide (see this example for a lupus trial) and on These elements are also provided to clinical trial participants through the informed consent form, which is a summary written in more patient-friendly terms. People who attend CoDESIGN workshops may also get a summary of the draft protocol in preparation for the workshop discussions and activities.

Knowing the key elements of a protocol is important for your understanding of clinical trial participation, so remember, you can always ask if you have questions about the information provided.

Read the resources below for more information on clinical trial protocols:

  3. Acad Emerg Med. 1998 Dec;5(12):1218-23. Research fundamentals: III. elements of a research protocol for clinical trials. Silverman R1, Kwiatkowski T.
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