The Life-cycle of a Clinical Trial

Beginning with preclinical research and progressing through human trials, clinical trials assess the safety and efficacy of medical interventions. Ethical considerations, regulatory compliance, and data integrity are central throughout this life cycle, influencing the advancement of medical knowledge and patient care.

 The major steps within the properly designed and executed clinical trials involves the following steps:

 1.     Trial design and registration:

Clinical trials are meticulously planned, with protocols and statistical analysis plan (SAP) established before enrolling participants. Protocol and SAP amendments must be documented prior to seeking study approval from relevant authorities. Budgeting for the trials is looked upon for its feasibility.

 The International Clinical Trials Registry Platform (the Registry Platform ), based at WHO, has worked over the past 17 years to achieve consensus on a minimum trial registration dataset of 20 items. In the quest for transparency and accountability, the Registry Platform has explored mechanisms to support fair and uniform disclosure of all trials. It collaborates with patients’ groups, existing registers, industry, academia, and other key stakeholders to effectively implement trial registration worldwide.

2.     Participant recruitment and enrolment:

 Clinical trial data are derived from the participation of both patients and healthy volunteers in research studies. Participant recruitment for clinical trials encompasses identifying, sourcing, and educating potential participants, leading to pre-screening discussions. The recruitment process spans activities up to the patient’s informed consent, marking them as officially recruited and prepared for screening.

 On the other hand, participant enrolment in clinical trials involves recruitment, screening, and randomization processes, all in one. A patient is enrolled upon completing screening and meeting eligibility criteria. Having signed informed consent for screening, passing all tests automatically finalizes their enrolment.

3.     Data Collection and Analysis:

 Data in clinical trials, can be both qualitative (i.e., contextual) or quantitative (meaning numeric). It involves systematically gathering and recording participant information through documents like Case Report Forms (CRFs), electronic data capture systems, and source documents such as medical records. Baseline assessments, randomization details, safety reports, and efficacy endpoints are meticulously documented, with participant-reported outcomes and follow-up data providing valuable insights. Throughout the process, monitoring and auditing, as well as a well-defined data management plan, contribute to maintaining the integrity and reliability of the collected data, supporting the generation of meaningful and credible results for analysis and interpretation.

 Clinical trial data analysis utilizes statistical methods like descriptive and inferential statistics, survival analysis, regression models, ANCOVA, and repeated measures analysis. Logistic regression handles binary outcomes, while meta-analysis pools data from multiple studies. Careful planning with a statistical analysis plan ensures methodological rigor and transparent result interpretation.

4.     Study completion:

Study completion is defined as either “the study has concluded normally; participants are no longer being examined or treated,” or the study has been terminated. It involves the finalization of data collection, locking the database to prevent further modifications. The subsequent phase focuses on thorough data analysis using statistical methods to evaluate primary and secondary endpoints. The findings are compiled into a final study report, which is submitted to regulatory authorities for evaluation.

5.     Publication:

 A portion of the analyzable dataset is selectively used to create tables, figures, and results for published articles during or after the clinical trial. Publication typically occurs post-study completion, but it can happen at any stage of the trial known as ‘interim’ findings. One trial may yield multiple publications.

 In case of RCTs, The CONSORT statement includes a 25-item checklist and a flowchart, helping authors present clinical trial protocols, results, and outcomes in a scientific and ethical manner. The checklist covers key elements, ensuring transparency, while the flowchart visually represents the trial’s design and participant progression.

 When publishing a clinical trial, it is advisable to incorporate the term “clinical trial” in the manuscript title. This practice enhances the manuscript’s visibility and ensures accurate indexing in electronic databases. Proper indexing is crucial for easy identification of the publication as a clinical trial, contributing to its visibility and accessibility within the scientific community and beyond.

6.     Regulatory application:

 This application typically includes the completed study results, detailed analyses, safety assessments, and any other relevant data. The purpose is to demonstrate the trial’s adherence to Good Clinical Practice (GCP), ethical conduct, and compliance with applicable regulations. The regulatory review evaluates the study’s outcomes, ensuring their validity, reliability, and relevance. Approval supports the integration of the trial’s findings into regulatory decisions, impacting medical practices, and potentially leading to the approval or modification of healthcare interventions.