A clinical trial protocol is a document which serves as the step-by-step playbook for running the trial. The clinical trial protocol guides the study researchers to run the clinical trial effectively within a stipulated period. The prime focus of the clinical trial protocol is to ensure patients’ safety and data security. [1, 2]
As the clinical trial protocol is an essential document for the seamless execution of the clinical trial, reviewing (peer-reviewing) the protocol is essential to ensure the scientific validity/viability/quality of the protocol. Though clinical trials enable the medical community to make evidence-based decisions, the quality of the reviewing process/monitoring of trial protocols is not always considered by many contract research organizations (CROs). This issue could affect the strength of the evidence and the quality/rationale of the study. The methods of clinical trial protocol review have not been rigorously tested to find the critical errors and biases of the study. [3, 4].
This article highlights the need for effective clinical trial protocol reviewing methods and workflows.
Clinical trial protocol reviewing or assessment involves reviewing all the sections, including double-checking the informed consent template, to ensure patient safety. While reviewing the protocol, suggestions, amendments and improvements should be mentioned as side notes to seamlessly incorporate the peer reviewers’ suggestions.
Check your trial design
The purpose of the clinical trial protocol review and the roles involved in the process are as follows:
The expert reviewers initially review the scientific rationale of the experimental study, testing methods of the hypothesis and research methodologies to ensure the study has scientific viability with a valid study design to generate desirable outcomes. Some of the important considerations of clinical trial protocol review are:
The foremost priority of the clinical trial protocol review is to ensure and protect study volunteers’ safety by minimizing or eliminating the potential risks and benefits of the participants. This key step ensures strict adherence to regulatory standards, ethical committee recommendations and relevant safety measures.
The feasibility of the clinical trial can be assessed and guaranteed by assessment of availability of the participants, time to complete the study and availability of the resources.
The clinical trial protocol review ensures strict compliance and adherence to regulatory guidelines for seamless and quick regulatory decisions without the need for additional meetings and subsequent delays.
The peer reviewers examine the clinical trial study design to estimate the power of the study, statistical methodologies employed and sample size to ensure the scientific viability of the study.
The clinical trial protocol review assesses the inclusion and exclusion criteria of the study volunteers to ensure the patient recruitment has relevance to the study theme.
The clinical trial protocol reviewers evaluate the study procedures to make sure they match the original protocol without deviation in any means including safety signal detection.
The safety issues and emergence of unexpected adverse events must be addressed by having adequate safety measures in place.
To ensure strict compliance and adherence to ethical standards, patient-centric informed consent and upholding their rights must be considered.
The statistical methodologies must be scientifically relevant and appropriate to the study design and to analyze the data.
Peer reviewers or the clinical trial protocol review experts in the clinical trial niche with decades of experience; provide feedback and suggestions for protocol improvement.
The principal investigator and the team of study coordinators are primarily responsible for the development and fine-tuning of the clinical trial protocol based on the feedback from the peer reviewers.
The purpose of these independent monitoring board members is to monitor the patients’ safety and data security/integrity when the clinical trial is underway.
These committee members periodically review the protocol to uphold study volunteers safety and ethical compliance, by regulatory agencies' standards.
Finally, regulatory agencies such as the USFDA, EMA etc may perform clinical trial protocol reviews to ensure regulatory compliance and suggest amendments, if required.
While performing the clinical trial protocol review, the peer reviewers identify potential scientific weaknesses and unviable parts of the study design, prompting suggestions for improvements.
With suggestions from experts and subsequent amendments, the review process helps to improve the overall quality of the study and robustness.
By identifying the potential risks and safety signals, the clinical trial protocol review can suggest and ensure appropriate safety measures.
Peer reviewing of the clinical trial protocol can ensure the study feasibility within the purview of given resources and period of time.
The clinical trial protocol review ensures strict adherence to ethical standards and study volunteers’ safety.
Clinical trial protocol peer review promotes collaboration and knowledge sharing among the study investigators. The real-time collaboration can identify potential problems and suggest ways to address the issues to strengthen the protocol.
Rigorous peer reviewing of the clinical trial protocol can add more scientific credibility to the protocol and among the stakeholders during regulatory submissions. Peer reviewing reflects a commitment to the quality and integrity of the clinical trial. [5]
Clinical trial protocol review aids the successful submission of systematically reviewed clinical trial protocols to regulatory agencies for approval. [6].
The process involves reviewing the submitted (draft) protocol by several experts to examine and propose amendments to the study design, inclusion and exclusion criteria, study endpoints etc. Based on the feedback, the regulatory medical writer will generate a high-quality clinical trial protocol for the submission process. The regulatory medical writer works in tandem with other teams and peer reviewers to create the final document and to achieve desired regulatory outcomes.
Peer review process ensures high standards compliance while cutting off unacceptable interpretations, claims without scientific rationale, views without scientific backing etc. [7]
Lack of real-time communication between the regulatory medical writers and peer reviewers can lead to gaps in the peer review process. Thus, effective coordination and communication among these stakeholders is critical to generate desired outcomes. Incorporation of feedback by regulatory medical writers can add credibility and scientific value to the clinical trial protocol and thus meets regulatory, legal and ethical standards with utmost precision. [3, 7, 8]
Peer reviewing involves the participation of multiple roles and the stakeholders may vary depending on the type of the clinical trial, scope of the study, research proposal and study design. [9, 10, 11]
To kick-start a meeting, the regulatory medical writer should get feedback from peer reviewers. Setting up a kick-off meeting can be helpful to have face-to-face meetings and communicative collaboration.[12] The agenda of the meeting should focus on review cycles, feedback resolution and respective timeframe, ways to incorporate the feedback, further instructions from peer reviewers, and task responsibilities of other team members. Multi-centric clinical trials involve stakeholders across the globe, thus prompting regular virtual meetings for smooth workflow.
After confirming the meeting date and time by sending an invitation to all experts and team members, it is important to ensure all invitees have access to the meeting (in case of a virtual meeting). After checking functionalities of e-meet, Upon confirming the contact details of the attendees, a kick-off meeting checklist should be prepared for discussion.
Ensuring to check and clear the discussion session in case of direct meetings and in case of online meetings, ensuring stable internet connection and clear communications are the keys for fruitful discussion. It is important to keep the minutes of the meeting for future reference.
Once the meeting is over, distribute the minutes of the meeting to all the stakeholders to communicate the feedback and to enable them for further actions and planning.
Upon receiving feedback from various stakeholders and team members, the regulatory medical writer receives multiple versions from the team. It is crucial to manage the created versions during the clinical trial protocol review. This process involves consolidating and incorporating the critical comments from different stakeholders to reconcile into a protocol draft. During the drafting process, the regulatory medical writer may miss a critical part and thus require a peer reviewer to do quality control. The team of reviewers use common document management software to maintain and amend the different versions of the protocol.
In addition to clinical study reports, it is essential to provide standard operating procedures, work instructions, guidance and training materials required for protocol development. The peer reviewers primarily focus on the study’s validity and patient safety. Thus, the regulatory medical writer should include the minutes of the meeting and comments from various stakeholders in the protocol.
To ensure Good Clinical Practice (GCP), the sponsors must consider utilizing GCP-compliant systems for peer reviewing and risk assessment of study subjects’ safety and reliability of study results. Some of the best GCP-compliant systems are Lotus Notes, Veeva Vault, Documentum etc. These tools support rapid and serial peer review processes as well as to see team members’ comments. The time-stamped document management system allows others to see the chronology of edits and amendments, which ensures transparency and team collaboration with assured on-time delivery of the reviewed document.
Though the peer reviewers are experts in reviewing the clinical trial protocol, most often, their expectations are not communicated. Hence, the regulatory medical writer should communicate the expectations and to-do list clearly and concisely during the kick-off meeting with the reviewers. The to-do list may include the reviewer’s responsibilities, process involved, regulatory standards and SOP, protocol synopsis with the latest version of the complete protocol with literature research, expectations or the thrust area to focus on for critical assessment etc.
Taken together, the clinical trial protocol is an essential document in the clinical trial and peer reviewing the document improves the likelihood of clinical trial and regulatory outcomes. The peer review process ensures clinical trial scientific rigour, regulatory compliance and volunteers’ safety without compromising the quality of the study. The peer reviewers are from diverse backgrounds such as clinical trial investigators, regulatory affairs consultants and regulatory medical writers to collaboratively perform the quality check of the protocol to expedite clinical trial outcomes and regulatory approval in a timely fashion.
https://trialsjournal.biomedcentral.com/submission-guidelines/preparing-your-manuscript/study-protocol (Accessed: May 11, 2025)
The Medicines for Human Use (Clinical Trials) Regulations 2004 UK Statutory Instruments 2004 No. 1031 PART 1 Regulation 2 {#the-medicines-for-human-use-clinical-trials-regulations-2004-uk-statutory-instruments-2004-no.-1031-part-1-regulation-2} https://www.legislation.gov.uk/uksi/2004/1031/regulation/2/made
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Guest post by Safeer Khan, Lecturer at Department of Pharmaceutical Sciences, Government College University, Lahore, Pakistan Introduction As we move toward 2025, clinical trial regulations are undergoing significant transformation. This shift is being fueled by technological advancements, changing healthcare needs, and an increasing emphasis on transparency and patient safety. In this post, we will explore the key clinical trial regulations shaping the clinical trial landscape, the challenges professionals face, and the strategies they must adopt to navigate this ever-evolving environment.
Thomas Wood has recently joined the Clinical Trial Files podcast with Karin Avila and Taymeyah Al-Toubah, discussing the inception of the Clinical Trial Risk Tool, what impact AI can make in clinical trials, and what Alan Turing would make of it all. This is an episode dedicated to Alan Turing’s 113th birthday on 23 June 2025. You can find the episode on Spotify Apple Podcasts Amazon Music Podcast Index Fountain Podcast Addict Podverse.
Guest post by Youssef Soliman, medical student at Assiut University and biostatistician Before launching a clinical study, even the most promising idea must be vetted for feasibility. In other words, can this trial be executed successfully in the real world? Feasibility assessments examine practical factors like available patients, site capabilities, timelines, and budget. This step is crucial. A majority of trials encounter delays or enrollment shortfalls (by some estimates, 70–80% of trials) [1], driving up costs and risking failure.
