Clinical trials are the cornerstone of medical research, providing crucial evidence for the safety and efficacy of new treatments and interventions. However, the value of these trials is only fully realized when their findings are effectively communicated to the broader scientific community, healthcare professionals, and regulatory bodies. This is where clinical trial reporting plays a pivotal role.

This article will guide you through the essential aspects of clinical trial reporting, from preparation to best practices and overcoming challenges. This guide aims to provide valuable insights and resources to help you navigate the complexities of clinical trial reporting effectively. 

 

Understanding Clinical Trial Reporting 

Clinical trial reporting that is clear, accurate, compliant with regulatory guidelines, and made public is essential as it informs clinical practice and public health decision-making. Patients, trial participants, researchers, clinicians, and policymakers rely on published clinical trial results to help make evidence-based decisions1. Public disclosure of clinical trial findings benefits stakeholders in health systems; however, pervasive incomplete reporting has left gaps in the scientific records. As the World Health Organization (WHO) indicates, an estimated 85% of health research is wasted, with half of the waste due to non-reporting results. For the industry, clinical trial transparency can elevate public perception and trust in trial sponsors, demonstrating the industry’s commitment to ethical standards, advancing scientific knowledge and patient care, and protecting patient safety. 

 

Regulatory framework 

Key regulatory guidelines and standards governing clinical trial reporting include the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH), Guideline for Good Clinical Practice (GCP) (ICH-GCP), Consolidated Standards of Reporting Trials (CONSORT), and Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT).

SPIRIT and CONSORT are evidence-based guidelines that provide authors with a checklist of essential items for protocols and primary reports of completed clinical trials, respectively. The SPIRIT and CONSORT statements provide guidance on the minimum information that should be included in trial reporting to ensure clarity, completeness, and transparency. The SPIRIT and CONSORT checklists have improved clinical trial design, conduct, and reporting.

Guidance for protocols, SPIRIT 2013 statement and SPIRIT-Outcomes 2022 extension, and guidance for trial reporting, CONSORT 2010 statement and CONSORT-Outcomes 2022 extension describe outcome-specific items that should be addressed in all trial protocols and clinical trial reports, respectively, to increase trial utility, replicability, and transparency. In addition, adherence to these guidelines may minimize the risk of selective nonreporting of trial results. 

 

Common clinical trial reports 

The most common types of clinical trial reports include clinical study protocols, which detail the study objectives, design, methodology, and statistical considerations of a clinical trial, and clinical study reports (CSRs), which summarize trial results and findings, including patient demographics, efficacy outcomes, safety data, and statistical analyses. Adverse events or side effects experienced by participants during a trial are documented in adverse event reports. An investigator’s brochure provides comprehensive information about the investigational product(s), including pharmacological and toxicological data. 

Data monitoring committee (DMC) reports summarize the data reviewed by the DMC, including safety and efficacy outcomes, to ensure participant safety and trial integrity. Data collected at predefined time points during the trial and analyzed to assess efficacy, safety, and the need for protocol amendments are presented in interim analysis reports. The final study report comprehensively summarizes all trial-related activities, including data analysis, conclusions, and recommendations for future research.

These reports are crucial for ensuring transparency, regulatory compliance, and the dissemination of trial results to the scientific community and regulatory authorities. 

 

Preparing for Clinical Trial Reporting 

Preparation is a crucial phase that sets the stage for transparent and comprehensive reporting, ensuring that the trial’s findings are accurately communicated and interpreted. In this section, we will explore the key steps involved in preparing for clinical trial reporting, from developing a detailed protocol to establishing robust data management and analysis procedures. By emphasizing the importance of thorough preparation, researchers can enhance the credibility and impact of their trial results, advancing scientific knowledge and improving patient care. 

Protocol development 

Clinical research to evaluate new therapies, devices, and other health interventions must follow a study protocol. According to the ICH E6 (R2) guidelines, developing a comprehensive study protocol includes outlining the study’s: 

• Trial objectives 
• Design 
• Methodology 
• Statistical considerations, and 
• Overall organization. 

 

Reference guidelines include the SPIRIT statement, ICH-GCP, and CONSORT reporting guidelines.

To write a clear and accurate study protocol, principal investigators (PIs) must thoroughly understand the trial design and be ready to discuss with protocol-development teams. During the preparatory phase, due consideration should be given to potential administrative challenges, e.g., ethics, regulatory, and people-management barriers, and possible time-saving options, e.g., standardized procedures, collaborative training, and centralization.  

 

Data collection and management 

Data collection and management are crucial for the successful completion of clinical trials and clinical trial reporting. Sponsors must prepare to implement robust data collection and management systems to ensure the quality, integrity, accuracy, and reliability of data generated by clinical trials for valid conclusions from trial results.  

  

Essential Components of Clinical Trial Reports 

Clinical study protocol 

A clinical study protocol is essential to a research project as it describes the study in detail, allowing the research team to understand the steps and adhere to the methodology. The study protocol describes in detail each critical aspect of the study, including the scientific background, study design, study objectives, primary and secondary endpoints, statistical analysis plan, participant eligibility and exclusion criteria, and minimum participant enrollment required for statistical power. The study protocol also describes the corresponding actions, e.g., activities at each study visit and the schedule of tests and procedures. Additionally, the protocol includes information on previous study phases, risk-benefit assessments, data-collection methods, the data-analysis plan, and study duration. The clinical study protocol must also provide a clear and complete design flow to meet study objectives. Finally, the protocol must be validated by competent authorities and ethics committees (ECs).  

 

Clinical study report (CSR) 

Clinical study reports (CSR) are detailed documents that summarize trial results, including efficacy and safety outcomes, patient demographics, adverse events, and statistical analyses. Sponsors prepare a CSR to present study outcomes to regulatory authorities such as the U.S. Food and Drug Administration (FDA) or the European Medicines Agency (EMA). Regulatory authorities use the CSR to evaluate the intervention’s safety, efficacy, and quality and to determine regulatory approval. Other stakeholders use CSRs to make informed decisions about the tested intervention. The structure of the CSR is based on ICH guideline E3 on the Structure and Content of Clinical Study Reports (ICH E3).

The right medical writer for a CSR must know how clinical trials are planned and run and how trial results are reported. The medical writer must also have access to stakeholders involved in the study, namely, the clinicians, biostatisticians, regulatory specialists, safety experts, and the clinical study management team.  

 

Investigator’s brochure 

The Investigator’s Brochure (IB) provides comprehensive information on the intervention, including pharmacological and toxicology data relevant to the study. The purpose of the IB is to provide the investigators and others involved in the trial with information to facilitate their understanding of the rationale for and compliance with many key features of the protocol, such as the dose frequency/interval and safety monitoring procedures.  

 

Best Practices for Clinical Trial Reporting 

Ensuring clarity and transparency 

Trial findings should be communicated effectively using clear, concise language and incorporating visual aids to enhance comprehension. This ensures quality, clarity, and transparency for healthcare professionals to understand and implement in clinical practice or for researchers to replicate.

• Locate a reporting checklist (found on the EQUATOR website) that matches your study design, e.g., the CONSORT checklist.  
• Keep the trial protocol and registration close by as you draft the report. Your audience wants to know if your study proceeded as planned and, if not, why changes were made. Ensure consistency between information on important trial characteristics, such as aim, selection criteria, and outcomes, in the trial registry and the trial report.  
• Preferred trial report style follows the Introduction, Methods, Results, and Discussion (IMRaD) structure. 
• Adopt an engaging, informative writing style that allows creativity without diverging too far from reporting conventions. Use concrete language, write in active (not passive) sentences, and use active verbs. 

 

Maintaining accuracy 

Data management involves collecting, organizing, and analyzing clinical trial data that ensures trial data’s accuracy, integrity, and reliability. Rigorous data validation and quality control measures are essential for maintaining the accuracy and reliability of trial results. For trials that generate massive amounts of data, artificial intelligence (AI) tools can improve trial efficiency by rapidly and accurately analyzing patient data and medical records and finding patterns that may be missed by human analysis. Additionally, AI may be used to manage data, e.g., automatically checking all text submitted by patients or staff for adverse events.

As clinical trials generate more data, sponsors may incorporate AI and machine learning (ML) into data validation to increase efficiency and accuracy, improve prediction accuracy, and retain institutional knowledge while enhancing the user experience. 

 

Achieving regulatory compliance 

Researchers or medical writers tasked with clinical trial reporting are experienced in preparing quality EMA- and FDA-compliant documentation. Adherence to regulatory guidelines and standards is imperative to ensure the integrity and transparency of trial reporting. Keeping up to date with changes or updates in guidelines is necessary, as well as awareness of modifications like CONSORT-DEFINE. Recognizing that a modified guideline was required to improve Phase I/II trial reporting, especially dose (de)-escalation trials, the CONSORT – DosE FIndiNg Extension (CONSORT-DEFINE) reporting guideline was developed and published.  

 

Overcoming Challenges in Clinical Trial Reporting 

Addressing missing data 

Missing data is pervasive in clinical trials, so it is essential to develop strategies to handle missing data through sensitivity analyses and imputation methods to address it adequately. Firstly, it is necessary to determine the missing data mechanism: Is it completely at random (MCAR), at random (MAR), or not at random (MNAR)? In most situations, missing data imputation methods should be used. Sensitivity analyses are also recommended for different missing data mechanisms, e.g., MAR vs. MNAR. 

The growing adoption of digital health technologies (DHTs) to measure outcomes remotely, objectively, and continuously has implications for missing data. There is a need to identify statistical approaches to address missing data generated by DHTs and to ensure that the derived endpoints are accurate, valid, and reliable. Aside from a statistical approach, strategies to minimize missing data may, for example, benefit from including patients’ perspectives in the study design.  

 

Dealing with conflicting results 

To critically evaluate and use trial results, stakeholders require complete and transparent information on what was planned, executed, and discovered. Conflicting or unexpected results must be dealt with to reduce deficient reporting that obscures related issues, e.g., outcome selection, assessment, and analysis. Conflicting or unexpected results may not answer research questions or disprove the initial hypothesis but may still shed light on something novel. In this situation, trial reporting requires a clear and transparent explanation for the discrepancies, of how and why the intervention did not work as intended, or why it produced undesirable outcomes. Such findings may still make valuable contributions to research in the field. Recognizing the gap in standard methods and guidelines for reconciling conflicting results from randomized controlled trials, ongoing research explores the use of ML as a potential solution.  

 

Managing regulatory changes 

Keeping informed of evolving regulatory requirements is paramount for managing regulatory changes and adapting reporting practices to maintain compliance. Experts anticipate changes in the regulatory environment, including a growing number of clinical trial registries worldwide and intensified transparency requirements, such as new reporting requirements, more stringent enforcement of existing regulations, or increased penalties for non-compliance.

In addition to CONSORT-DEFINE, further reporting guidelines have been established for specific study types and designs, e.g., STaRT-RWE guidelines for reporting real-world evidence (RWE) studies and pharmacogenetics studies (STROPS). 

 

Leveraging Medical Writers and Contract Research Organizations (CROs) 

The role of medical writers 

Medical writers translate complex scientific data into clear, consistent, and comprehensible language by creating well-structured, clear, and concise reports that effectively communicate research findings for regulatory submissions and publication in scientific journals.  

 

How medical writers help 

Medical writers help enhance clinical trial efficiency, quality, and adaptability. With their expertise in medical and scientific writing, they ensure that trial results are communicated accurately and consistently while adhering to regulatory guidelines and publication standards.  

 

Hiring medical writers through CROs 

By selecting reputable contract research organizations (CROs) with experienced medical writers like TFS HealthScience and outsourcing this critical service, sponsors can ensure essential documents like clinical study protocols and investigator brochures are prepared successfully. TFS medical writers provide sponsors with documents written clearly in the required languages and compliant with all ICH guidelines and regulatory requirements. They are experienced in writing for key therapeutic areas covering all phases of clinical development, including RWE.

The TFS global medical writing team comprises professionals, including MDs and others with advanced training in health science, such as biomedics and biologists. As quality EMA- and FDA-compliant documentation writing is imperative to us, they were chosen because of their strong research background, excellent language skills, and knowledge of biostatistics. Many are members of the European Medical Writers Association (EMWA).

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