To improve your experience on Lilly TrialGuide, please use the latest version of Chrome, Firefox, Safari, or Internet Explorer, with JavaScript enabled.
This website is not optimized for your browser, as configured.

What is a Protocol in Clinical Trials?

BackToSchool Protocol FeatureImage 27Aug2019-01

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.
Tags: Why We Do Research,

Recent Articles

TheCOVID-19PandemicChangedHowSitesConductClinicalTrialsForever FeatureImage 22July2021-01

The COVID-19 Pandemic Changed How Sites Conduct Clinical Trials Forever

Kevin Hudziak Photo
Kevin Hudziak
July 29th, 20213 minute read

To better understand how various countries adapted to execute clinical trials during a pandemic, we conducted a series of virtual feedback sessions with clinicians from all over the world.

ThePathFromHCPtoResearcher FeatureImage 24Feb2021-01

The Path from HCP to Researcher: A Word of Advice

LTGBlogAuthors LillyGuestAuthorIcon 20July2018
Lilly Guest Author
April 21st, 20215 minute read

If you’re a physician interested in getting involved in clinical research, you must understand that it can be a big career shift. Luckily, Kamnesh Pradhan has valuable advice to share.

WeMustIncreaseDiversityInClinicalTrials FeatureImage 24Feb2021-01

Paving the Way to Better Diversity in Clinical Trials

LTGBlogAuthors LillyGuestAuthorIcon 20July2018
Lilly Guest Author
February 26th, 20218 minute read

To discuss what Lilly is doing to increase diversity in clinical trials, we spoke with two outstanding women who are leading the charge.

ResourcesToHelpAspiringClinicalResearchers FeatureImage 3Feb2021-01

Resources to Help Aspiring Clinical Researchers

Leigh Anne Naas Headshot
Leigh Anne Naas
February 10th, 20214 minute read

If you’re thinking about becoming a clinical researcher, it might be hard to know where to begin. We’ve outlined several resources to help you understand what to expect in a clinical research role.

StudyCoordinatorPatientPartnerThroughClinicalTrials FeatureImage 15Dec2020

Study Coordinator: Patient Partner Through Clinical Trials

LTGBlogAuthors GuestAuthorIcon 20July2018
Guest Author
January 13th, 20217 minute read

Study coordinators are a key part of the clinical trial journey. To learn more about what they do, read our interview with study coordinator, Kelly Roberts.