Design of the clinical trial: As described in the earlier section “Choosing the structure of a

clinical trial,” the clinical trial’s design defines its structure. This includes the number of treatment

groups as well as consecutive stages of the study. These stages could include eligibility screening,

washout, treatment, follow-up, and so on. This section often includes a schematic diagram of the

structure of the study.

Drug description: This description details each drug that will be administered to the participants.

This includes the chemical composition with the results of chemical analysis of the drug, if

available. It also includes instructions about how to store, prepare, and administer the drug

correctly.

Blinding and randomization schemes: These schemes include descriptions of how and when the

study will be unblinded. This includes the emergency unblinding of individual participants if

necessary. See the earlier section “Using randomization” for more information.

Procedural descriptions: This section describes every procedure that will be performed at every

visit. These include administrative procedures, such as enrollment and informed consent, and

diagnostic procedures, such as physical exams and measuring vital signs. It covers all activities

where data are collected from participants in the study.

Safety considerations: These factors include the known and potential side effects of each drug

included. This section also includes the known and potential side effects of each procedure in the

study, including X-rays, MRI scans, and blood draws. It also describes steps taken to minimize the

risk to the participants.

Handling of adverse events: This section describes how adverse events will be addressed

should they occur during the study. It includes a description of the data that will be recorded,

including the nature of the adverse event, severity, dates and times of onset and resolution, any

medical treatment given for the event, and whether or not the investigator thinks the event was

related to the study drug. It also explains how the research study will support the participant after

the adverse event.

Definition of safety, efficacy, and other analytical populations: This section includes definitions

of safety and efficacy variables and endpoints. In other words, this section defines variables or

changes in variables that serve as indicators of safety or efficacy.

Planned enrollment and analyzable sample size: Justification for these numbers must also be

provided.

Proposed statistical analyses: Some protocols describe, in detail, every analysis for every

objective. Others include only a summary and refer to a separate Statistical Analysis Plan (SAP)

document for details of the proposed analysis. This section should also include descriptions of

how missing data will be handled analytically, adjustments for multiple testing to control Type I

errors (see Chapter 3), and whether any interim analyses are planned. If a separate SAP is used, it

typically contains a detailed description of all the calculations and analyses that will be carried

out on the data, including the descriptive summaries of all data and the testing of all the hypotheses

specified in the protocol. The SAP also usually contains mock-ups called shells of all the tables,

listings, and figures (referred to as TLFs) that will be generated from the data.

It will also contain administrative details, like names and contact information for the research team, a