Clinical study protocols serve as the foundation for conducting medical research and are critical for drug development and approval.

To ensure compliance with subject protection standards and statutory requirements, clinical study protocols are submitted to global health authorities, such as U.S. Food & Drug Administration (FDA) for rigorous review prior to a Sponsor being allowed to conduct a study.

In this article, the basic steps to write clear, concise clinical study protocols that meet regulatory guidelines are explained and examined in-depth.

Tips for writing great clinical study protocols

When drafting a clinical study protocol, medical writers should know the following key points:

• Understand all relevant regulatory requirements (refer to content guidelines such as ICH E6 [R2]¹ and FDA guidance²) before writing.
• Use the Protocol Concept Sheet as a starting tool. This is a draft clinical study protocol of the Sponsor Clinical Trial to explain what a proposed study is about, why it is being undertaken, and how it will be carried out.
• Develop the Synopsis and Schedule of Events early in the process. A concise synopsis provides an overview of all study aspects and mirrors the outline of the clinical study protocol
• Templates may be available online such as joint NIH/FDA clinical study protocol
  • The National Institutes of Health (NIH) and Food and Drug Administration (FDA) developed a clinical trial protocol template³ with instructional and example text for NIH-funded investigators to use when writing protocols for phase 2 and 3 clinical trials that require Investigational New Drug application (IND) or Investigational Device Exemption (IDE) applications.
  • Recommend use of a Smart template that provides automation and reduces the time needed to draft the protocol.
• Instead of copying text, consider cross-referencing to one appropriate location.
• Always take the necessary time to check that you are not missing critical details or even entire sections.
• Check for consistency between the clinical study protocol body and the synopsis.
• Submit the clinical study protocol for review by Quality Control (QC)/Quality Assurance (QA) before final approval to ensure quality and compliance.

Bearing the above in mind, clinical study protocols should also include the following features:

Clear and Specific Objectives

Begin by outlining the study’s objectives in a clear and specific manner.

• Define the primary research question, secondary objectives, and endpoints.
• Clearly state the hypothesis or research hypothesis tested during the study.

Comprehensive Background and Rationale

• Provide a concise yet comprehensive overview of the background and rationale for the study.
• Explain the necessity of the research and its contribution to the current body of knowledge.
• Describe how the study fulfils an unmet need.
• Cite relevant literature to support the rationale for the study.

Precise Study Design

Choose a study design that aligns with the stated research objectives.

Inclusion and Exclusion Criteria

Set forth the criteria that will be used to select participants for the study. These standards ensure that the study population is relevant to the research objectives. Inclusion and exclusion criteria should be well defined and based on medical and scientific justifications.

Ethical Considerations

Describe the ethical principles that will guide the study, including patient confidentiality, informed consent procedures, and participant safety. Adhere to the ethical guidelines and regulations set by relevant authorities.

Interventions and Procedures

Detail the interventions or treatments that participants will receive during the study. Outline the procedures, study visits, dosages, and frequency. This section should be comprehensive and provide a clear understanding of how the study will be conducted.

Data Collection and Analysis

Explain how data will be collected, including the types of data, measurement methods, and tools to be used. Describe the statistical methods that will be employed for data analysis, including sample size calculation and statistical tests.

Study Timeline

Create a detailed timeline that outlines key milestones of the study, from participant recruitment to data analysis and publication. A well-structured timeline helps manage expectations and ensures the study progresses smoothly.

Adverse Event Monitoring

Detail the procedures for monitoring and reporting adverse events during the study. This is crucial for participant safety and maintaining the integrity of the research.

Collaborator Roles and Responsibilities

Drafting a clinical study protocol is a team effort. A medical expert, a biostatistician, a pharmacokinetic expert, the clinical research coordinator, and the project manager all provide input to the medical writer to produce the final document. Clearly defined roles and responsibilities for each member of the research team, including study investigators, statisticians, and data managers ensures effective collaboration and accountability.

Conclusions

Writing an efficient clinical study protocol requires meticulous planning, a deep understanding of the research objectives, and adherence to ethical guidelines. A well-crafted clinical study protocol not only ensures the success of the study but also contributes to the advancement of medical knowledge. By following the strategies described above, researchers can create clinical study protocols that are clear, concise, and capable of yielding meaningful and impactful results.

References

1. ICH guideline for good clinical practice E6(R2).
2. https://www.fda.gov/science-research/clinical-trials-and-human-subject-protection/regulations-good-clinical-practice-and-clinical-trials.
3. Clinical Research – Office of Science Policy (nih.gov): Clinical trial E-protocol tool and template documents.

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Authored by: Anju Bhakri, Senior Medical Writer, Regulatory and Medical Writing at MMS Holdings