- Clinical Study Protocol Development
A clinical study protocol should be development based on information from the medical literature, relevant guidelines and standards and interaction with the client. The protocol should meet the needs and limitations of the participating clinical sites, while complying with FDA standards and guidelines. The study protocol should also include the required input of a biostatistician, regarding the determination of the sample size and statistical considerations for data analysis and interpretation. A final study protocol and Informed Consent Form (ICF) are produced that may be submitted for review by the appropriate Institutional Review Boards (IRB) and/or as part of a Pre-Sub or IDE submitted to FDA.
- Institutional Review Board (IRB) / Helsinki Committee Submission
Institutional Review Board (IRB) approval or Hospital Ethics (Helsinki) Committee approval is required prior to initiating any clinical trial, in compliance with applicable FDA, /IVDR and other national regulatory requirements and Good Clinical Practice (GCP) standards. The clinical study protocol and all associated documents — including the investigator’s brochure, informed consent form, recruitment materials, and other relevant supporting documentation — must be submitted to the IRB for review and approval. During the conduct of the study, additional submissions to the IRB may be required, such as annual progress reports, notifications of protocol deviations, and serious adverse event reports.
- Study Management
The clinical investigation should be managed to ensure that it is conducted according to recognized Good Clinical Practice (GCP) standards and applicable regulatory requirements throughout the course of the study.
A comprehensive study documentation system — preferably an electronic Trial Master File (TMF) — should be established to define procedures for document control, record and report retention, investigator reporting, site monitoring, data collection, and other key study activities. This file should provide clear instructions for maintenance and retrieval of essential study documents demonstrating GCP compliance throughout the trial lifecycle. Study site personnel, including investigators, clinical staff, and study coordinators, should receive training on all aspects of study implementation during an Investigator Meeting and Site Initiation Visit (SIV). Additionally, the suitability of each clinical site to conduct the investigation in accordance with GCP requirements should be assessed prior to study initiation.
- Data Management and EDC Setup
- Electronic Case Report Forms
Case Report Forms (CRFs) should be designed to collect the demographic and clinical information defined in the clinical study protocol.
- Electronic Data Capture (EDC) System
Based on the CRFs, an appropriate Electronic Data Capture (EDC) system should be developed to support efficient data entry and processing of the collected data. The EDC should incorporate relevant data validation checks and rules to identify outliers and anomalous values. The EDC system must be 21 CFR Part 11 compliant.
The EDC should be validated in accordance with software validation requirements to ensure that all fields are suitable for the intended data capture and that outliers are appropriately detected through the implemented checks and rules. Validation activities should include in-house testing of all CRF fields and their corresponding rules, as well as Beta-site testing to confirm remote use by potential site users. All defects identified during testing should be resolved before the final working database is released. Study users should receive comprehensive EDC training.
- Data Monitoring
The clinical data entered into the EDC system should undergo appropriate post-entry quality assurance methods, according to a Risk-Based Monitoring Plan (RBMP). The RBMP should identify critical data and processes, based on the study protocol safety and effectiveness endpoints and should include a combination of centralized, off-site and on-site monitoring practices. The monitoring activities should verify that the clinical study is being conducted according to the clinical study protocol, study procedures, and applicable health and regulatory authority regulations at the study sites. Querying sites for missing, incorrect or illegible clinical data and missing clinical and/or regulatory documents should be performed, as required.
- Data Processing and Statistical Analysis
Clinical data processing and statistical support is required for any clinical study, including statistical analysis of the clinical data according to the data analysis and interpretation set forth in the study protocol. The statistical support should be provided by a qualified biostatistician with extensive experience in the preparation of regulatory submissions.
- Clinical Study Report Development
A Clinical Study Report (CSR) should be prepared at the conclusion of the clinical study, including statistical analyses of the clinical data. The CSR should include demographic information, endpoint evaluation findings and safety reporting, as well as a summary and conclusion of the trial based on the study results. The CSR should be prepared in a suitable format appropriate for inclusion in a regulatory submission.
Helpful tips when conducting a Clinical Study:
The clinical study should be listed on the NIH ClinicalTrials.Gov website (https://clinicaltrials.gov/) and in the Israeli MyTrials database (https://clinicaltrial.health.gov.il/clinicaltrials/?sort=experimentapproveddate_tdt+desc&page=1).
