Clinical study reports relevant to the development of your investigational product that have been discussed in Module 2.5: Clinical overview should be provided in Module 5.3: Protocol for initial clinical study. For novel therapies, there typically are no reports unless the product is approved for compassionate use and/or studied in a foreign jurisdiction. See Module 2.5: Clinical overview guidelines on what clinical information to include.
Module 5.3: Protocol for Initial Clinical Study
In this section you should plan to provide complete protocols for each study you intend to conduct and include:
Form FDA 1572 for each investigator participating in the study [2]
The CV of the Principal Investigator (PI) (primary doctor leading the study) and any sub-investigators
Please refer to the sample outline below, for guidance on the Clinical Study Protocol. Sample template for a Clinical Study Protocol. The template and sample outline are intended as guidelines and not all sections in either document may be applicable to your drug product or study design.
Clinical study protocol example
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Introduction
The purpose of the introduction is to provide an overview of the clinical trial, as well as the rationale for conducting the clinical trial. [1]
Trial objectives and purpose
Here, you want to provide a detailed description of the specific objectives and the purpose of the trial. You may include primary and secondary objectives, as well as any exploratory or safety objectives. The objectives should be clearly defined and measurable.
Investigational plan
The investigational plan outlines the specific procedures, tests, and assessments that will be conducted during the course of the trial. It provides detailed information on how the investigational product (e.g., gene therapy) will be studied, including its administration, dosing, monitoring, and evaluation.
Selection and withdrawal of subjects
For this section, you want to include detailed plans that outline how a clinical trial will be conducted in terms of candidate selection. You will need to include the inclusion/exclusion criteria and ensure that it’s in accordance with good clinical practice (GCP) guidelines. You should also include the circumstances under which a subject may be withdrawn from the trial, as well as the procedures for handling withdrawals.
Treatment of subjects
This covers information on how the clinical trial participants will be managed and cared for throughout the duration of the study. It includes various aspects related to the intervention(s) being tested, as well as the overall management of participants' health and well-being.
Study drug materials and management
This section of the protocol outlines the specific requirements and procedures that need to be followed to ensure that your study drug is used safely, correctly, and in compliance with the study protocol and regulatory guidelines.
Pharmacokinetic assessments
All assessments involving measuring the time course and extent of drug absorption, distribution, metabolism, and excretion (ADME) in humans or animals go in this section. The purpose of these assessments is to help determine the pharmacokinetic profile of a drug, which in turn informs dosing recommendations, safety, and efficacy.
Assessment of safety
Here, you will have to outline the procedures for monitoring the safety of trial participants, including the collection and reporting of adverse events (AEs) or serious adverse events (SAEs), as well as any safety assessments or laboratory tests that will be conducted to monitor for potential safety concerns.
Statistical analysis
This includes details on the statistical methods that will be used to analyze the trial data, including the primary and secondary endpoints, sample size calculations, and any planned interim or final analyses.
Direct access to source data/documents
You should ensure that it is specified in your protocol or other written agreement that the investigator(s)/institution(s) will permit trial-related monitoring, audits, IRB/IEC review, and regulatory inspection(s), providing direct access to source data/documents. [1]
Quality control and quality assurance
You (or study sponsor) are responsible for implementing and maintaining quality assurance and quality control systems with written SOPs to ensure that trials are conducted, and data is generated, documented, and reported in compliance with the protocol, good clinical practices (GCPs), and other regulatory requirements. Quality control should be applied to each stage of data handling to ensure that all data is reliable and has been processed correctly.
Ethics
Here, you will include a description of ethical considerations relating to the clinical trial, including the protection of human subjects, informed consent procedures, and any additional ethical requirements or considerations specific to the trial.
Data handling and recordkeeping
This section will describe the overall process and responsibilities of parties involved in the management, recording, verification of data, including statistical analyses and preparation of trial reports. If you (or study sponsor) decide to use an independent data-monitoring committee (IDMC) to assess the progress, safety, endpoints, and study stop/start, this should be described in this section. If data is captured electronically, information on the tools, programs, and procedures for this should be provided in this section.
Publication policy
If not addressed in a separate agreement, the Publication policy goes here.
Long-term follow-up studies
For certain gene therapy products, the FDA expects to see long-term follow-up (LTFU) after administration of the investigational product in humans. The purpose of LTFU is to monitor subjects (patients) for any potential latent adverse events due to the investigational treatment. These studies are typically designed as extended clinical assessments and may include other methods for patient monitoring. The duration of LTFU studies depends on the type of gene therapy, so we recommend consulting the latest FDA Guidance on this topic: Long Term Follow- Up After Administration of Human Gene Therapy Products; Guidance for Industry (fda.gov). You can also refer to the Long-Term Follow-Up section in this playbook.
Module 5.4: Literature
In this section you must include all publications cited in any clinical protocols, the Investigational Brochure, or the General Investigational Plan. Any referenced literature needs to include their full copies in this section (as separate pdf files – include links).