Definition: The evaluation of whether an adverse event has a reasonable possibility to be caused by the investigational product or by other factors. Both Investigator and sponsor need to make an independent causality assessment including providing their rational for their judgement. The Investigators assessment is not allowed to be downgraded.
Why it matters: Accurate causality assessment underpins meaningful safety evaluation and regulatory credibility.
Definition: The determination whether an adverse event (AE) is consistent with the known safety profile of a drug, meaning it has been previously documented in the product’s reference safety information (RSI), such as the Investigator’s Brochure (for investigational drugs) or the approved label (for marketed drugs. The expectedness assessment is done by sponsor and is a” regulatory assessment not a clinical judgement.
Why it matters: It is the degree of predictability of an AE based on its mechanism of action and prior clinical data.
Definition: A medication error is an unintended failure in the drug treatment process that leads to, or has the potential to lead to, harm to the patient.
A failure in the drug treatment process does not refer to lack of efficacy of the drug, rather to human or process mediated failures. The concepts of intentional overdose, off-label use, misuse and abuse should be clearly distinguished from medication errors.
Why it matters: These errors are important because they are a leading cause of patient injury and death, with consequences ranging from minor side effects to life-threatening situations, and they also impose significant financial costs on healthcare systems. Understanding and preventing these errors is crucial for patient safety.
Definition: A physician acting as the Sponsor’s safety representative and qualified for medical monitoring according to regulatory requirements. The MM provides centralized medical oversight across a clinical trial. The MM ensures patient safety, medical consistency, and scientific integrity by reviewing safety data, advising investigators, and identifying emerging issues. The MM is not part of the team at the clinical study site and not involved as a Principal Investigator in the recruitment of the trial.
Why it matters: The MM bridges clinical judgment and regulatory compliance, safeguarding participants and strengthening study quality.
Definition: The MMP is a detailed document that outlines how a trial’s medical and safety aspects will be overseen to protect participants and ensure data integrity. It specifies the activities, roles, and responsibilities for medical monitoring, including the review of patient health, efficacy, safety data, and compliance with protocol and regulations. The plan defines the role of the medical monitor, who provides medical expertise, guidance on safety concerns, and supports decision-making throughout the trial.
Why it matters: The MMP ensures consistent medical oversight, timely identification of safety issues, and high-quality trial conduct, supporting both participant protection and reliable data.
Definition: an individual overall responsible for the conduct of a clinical trial at a clinical trial site. If a trial is conducted by a team of individuals at a trial site, the investigator is the responsible leader of the team and may be called the Principal Investigator
Why it matters: The PI’s role at site level complements the Medical Monitor’s centralized oversight on sponsor level by ensuring ethical, protocol-compliant and safe execution at the site level. Informed decisions about whether a study should continue, be modified, or stopped.
Definition: Any departure from the approved clinical study protocol, whether intentional or accidental, that may affect participant safety or data integrity.
Why it matters: Systematic review of deviations helps ensure study reliability and prevents small errors from compromising results.
Definition: The RSI shall contain product information on the investigational medicinal product and on how to determine what adverse reactions are to be considered as expected adverse reactions, and on the frequency and nature of those adverse reactions. The RSI is contained in the Summary of Product Characteristics (SmPC) or the IB.
Why it matters: The RSI defines expected adverse reactions, guiding safety assessment, causality evaluation, and regulatory reporting throughout the clinical trial.
Sponsor oversight is a fundamental concept within the ICH E6 (R3) guideline, reinforcing the sponsor’s pivotal role in ensuring trial integrity. As part of this Sponsor safety oversight involves the sponsor’s comprehensive management to ensure participant safety, rights, and data integrity are protected throughout the trial. This includes monitoring compliance with protocols and regulations, identifying and mitigating risks, and ensuring the quality of the trial and its data.
Definition: Any undesirable medical occurrence in a participant receiving a medicinal product, whether or not it is considered related to the product.
In accordance with ICH-E2A, an AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Definition: Any untoward medical occurrence, unintended disease or injury or any untoward clinical signs, including an abnormal laboratory finding, in subjects, users or other persons, in the context of a clinical investigation, whether or not related to the investigational device.
Definition: Any untoward medical occurrence, inappropriate patient management decision, unintended disease or injury or any untoward clinical signs, including an abnormal laboratory finding, in subjects, users or other persons, in the context of a performance study, whether or not related to the device for performance study.
Why it matters: Understanding and documenting AEs is central to monitoring drug tolerability, medical devices and invitro diagnostics and maintaining regulatory compliance.
Definition: An AE that results in death, is life-threatening, requires hospitalization or prolongs existing hospitalization, causes persistent or significant disability or incapacity, is a congenital anomaly or birth defect or is otherwise medically significant.
Why it matters: Prompt SAE assessment and reporting are critical to protecting participants and meeting safety obligations.
Definition: A SUSAR is an adverse event in a clinical trial that is both serious and unexpected, and there is a reasonable possibility of a causal relationship to the investigational drug. It’s a critical safety report that is subject to expedited reporting to regulatory authorities and ethics committees.
Why it matters: They are crucial for monitoring the safety of participants in a clinical trial. In severe cases, the occurrence of a SUSAR can lead to the suspension or modification of a clinical trial while it is being investigated.
Definition: The individual, company, or organization that takes responsibility for initiating, managing, and financing a clinical study.
Why it matters: The sponsor relies on medical experts like Cornelia to provide objective safety oversight and ensure regulatory compliance.
Definition: A service organization contracted by a sponsor to perform one or more trial-related duties, such as monitoring, data management, or medical review.
Why it matters: Effective collaboration with CROs ensures that operational execution and medical oversight remain aligned.
Definition: The formal organizational framework that defines how a study, project, or safety function is directed, managed, and controlled.
A governance structure typically includes:
Why it matters: The purpose is to provide clarity, transparency, and oversight
Definition: The overarching system that ensures ongoing monitoring, evaluation, documentation, and communication of the safety profile of a medicinal product during clinical development and post-marketing.
It includes:
Why it matters: Safety governance safeguards patient protection, scientific integrity, and regulatory compliance.
Definition: The structured framework that ensures medical quality, scientific integrity, and accountable medical decision-making across the study or program.
Medical governance typically covers:
Why it matters: It ensures that medical decisions are consistent, evidence-based, and aligned with regulatory and ethical standards.
Definition: The discipline focused on preventing harm to participants and patients by ensuring that risks are recognized, managed, and minimized.
Why it matters: Patient safety is the ethical foundation of every service CLT Vigilance Consulting provides.
Definition: Any study relating to an authorised medicinal product conducted with the aim of identifying, characterising or quantifying a safety hazard, confirming the safety profile of the medicinal product, or of measuring the effectiveness of risk management measures [DIR 2001/83/EC Art 1(15)].
Why it matters: PASS generates real-world evidence on a product’s safety, helping confirm its safety profile, identify new risks, and evaluate the effectiveness of risk-minimization measures.
Definition: An evaluation of the positive therapeutic effects of the medicinal product in relation to the risks i.e. any risk relating to the quality, safety or efficacy of the medicinal product as regards patients’ health or public health. Benefit -risk evaluation can be done by structured approach with different methodologies.
Why it matters: Informed, ongoing benefit–risk evaluation guides sound medical and regulatory decisions. Regulatory agencies like the FDA and EMA use these methods for drug and product approvals. A structured benefit-risk analysis is required for medical device compliance under regulations like the EU MDR.
Definition: The science and set of activities dedicated to identify, evaluate, and prevent adverse effects or any other drug-related problems throughout a product’s life cycle.
Why it matters: PV ensures that patient safety remains central from early development through post-marketing surveillance.
Definition: Safety management in clinical trials is the overarching process of protecting trial participants, which includes pharmacovigilance. Key activities include establishing a Safety Management Plan (SMP), monitoring for adverse events, performing risk assessments, and reporting safety concerns to regulatory authorities.
Why it matters: Effective safety management protects trial participants, ensures timely detection of risks, and supports compliance with regulatory requirements throughout the study.
Definition: The Safety Management Plan that outlines responsibilities, communication lines, and procedures for handling safety data during a clinical trial.
Why it matters: The SMP ensures clear roles, efficient communication, and consistent handling of safety data, supporting participant protection and regulatory compliance.
Definition: A Safety Data Exchange Agreement (SDEA) is a legal written contract that clearly outlines the responsibilities, procedures, and timelines for sharing safety data between parties involved with a medicinal product to ensure that the Marketing Authorization Holder (MAH) can be regulatory compliant.
Why it matters: An SDEA ensures timely, compliant exchange of safety data between partners, enabling the MAH to meet regulatory obligations and maintain a complete safety profile of the product.
Definition: The QPPV is legally responsible for establishing and maintaining/managing the pharmacovigilance system of the company´s medicinal products within the European Economic Area (EEA). The QPPV must reside within the EEA, have continuous oversight of the company’s pharmacovigilance system, and act as the single point of contact for the EMA and other national competent authorities regarding drug safety.
Where the QPPV has not completed basic medical training the marketing authorisation holder shall ensure that the QPPV is assisted by a medically trained person.
Why it matters: This role was established to ensure that medicinal products are safe through continuous monitoring of drug safety and providing all necessary safety information to the EMA.
Definition: A detailed description of the pharmacovigilance system used by the marketing authorization holder with respect to one or more authorized medicinal products.
Why it matters: It is crucial for regulatory compliance, particularly in the EU, and for demonstrating that the company has a robust framework for pharmacovigilance. A PSMF is essential for regulatory inspections, internal quality control, and ensuring patient safety.
Definition: A detailed report about a suspected adverse drug reaction for a single patient. It contains the four basic elements of an identifiable patient, identifiable reporter, suspect drug, and an adverse event, and is fundamental to drug safety monitoring. These reports are collected from various sources, processed, and submitted to regulatory authorities.
Why it matters: ICSRs are crucial for pharmacovigilance (PV) because they are the primary way to collect, evaluate, and report drug-related side effects to regulatory authorities. This helps pharmaceutical companies and regulators monitor the ongoing safety and efficacy of a drug, detect potential safety signals, and protect patients from harm.
Definition: Information suggesting a new potential causal link—or a new aspect of a known link—between a drug and an adverse event.
Why it matters: Detecting and evaluating safety signals early allows proactive risk mitigation and protects public trust.
Definition: The international ethical and scientific standard for designing, conducting, and reporting trials involving human subjects.
Why it matters: Compliance with ICH-GCP ensures that participant rights, safety, and data credibility are protected throughout every project Cornelia supports.
Definition: A family of ICH guidelines (E2A–E2F) describing international standards for clinical safety data management and pharmacovigilance reporting.
Why it matters: Familiarity with ICH E2 principles enables consistent, high-quality safety documentation and regulatory alignment.
Definition: A set of guidelines for the conduct of pharmacovigilance in the European Union (EU) applying to marketing authorization holders in the EU, the Agency and competent authorities in the Member States.
Why it matters: GVP ensures consistent, high-quality pharmacovigilance across the EU, safeguarding patient safety and supporting compliance with regulatory requirements.
Definition: Refers to the EU’s Medical Device Regulation (MDR) 2017/745, a European Union law that governs the placing on the market of medical devices. It replaced previous directives and imposes stricter requirements for safety, performance, and traceability, with full application in May 2021. In the United States, “MDR” can also stand for Medical Device Reporting, a system for reporting adverse events to the FDA.
Why it matters: MDR strengthens the safety, quality, and traceability of medical devices, ensuring better patient protection and clearer regulatory expectations for manufacturers and sponsors.
Definition: The In Vitro Diagnostic Regulation (IVDR) is the European Union (EU) regulation (Regulation (EU) 2017/746) for in vitro diagnostic medical devices, which fully applied on May 26, 2022, replacing the previous directive. It establishes a harmonized framework for the conformity assessment, certification, and post-market surveillance of these devices across all EU member states and EEA countries.
Why it matters: The IVDR aims to enhance the safety and performance of diagnostic tests, such as pregnancy tests, COVID-19 tests, and genetic tests.
Definition: An international standard for good clinical practice in clinical trials of medical devices in humans.
Why it matters: This standard provides guidelines to ensure that trials are conducted ethically and scientifically, to protect the rights and safety of human subjects, and to ensure that the results are reliable. It covers the entire process from design to reporting.
Definition: A group of independent or sponsor-appointed experts who periodically review cumulative safety data for a product or program. Safety Comittees can be held as internal Safety Review Comittees (iSRC) supporting for example dose escalation in First in Human (FIH) or phase I trials or as regulatory independent Data Monitoring Comittees/Data Safety Monitoring Boards (DMC/DSMB).
Why it matters: Safety Committees strengthen governance by providing independent perspectives on ongoing or emerging risks.
Definition: The formal document defining a Safety Committee’s composition, roles, responsibilities, decision criteria, and operational procedures.
Why it matters: A clear charter ensures transparency, accountability, and consistent safety decision-making.
Definition: An independent, external and free of conflict group of experts who periodically review accumulating trial data to protect participant safety and assess the ongoing risk–benefit balance.
Why it matters: DMCs provide objective safety surveillance, supporting informed decisions about whether a study should continue, be modified, or stopped.
Definition: Risk governance in clinical trials is the strategic, overarching framework that ensures a systematic process for identifying, assessing, and mitigating risks throughout the trial’s lifecycle. It involves establishing accountability, transparency, and responsibility to protect participant safety and ensure the integrity and reliability of trial data. This framework is a core part of a quality management system and is crucial for meeting ethical, regulatory, and quality standards.
Why it matters:
Protocol development: Risk assessment and management are integrated into the initial design of the trial protocol.
Sponsorship: The sponsorship application process requires risk assessment and management to ensure appropriate oversight.
Trial conduct: Risk management continues through ongoing activities such as monitoring and safety reporting.
Definition: Any deviation of the approved protocol version or the clinical trial regulation that is likely to affect the safety, rights of trial participants and/or data reliability and robustness to a significant degree in a clinical trial. Sponsors are required to report serious breaches to regulatory authorities, often within a specific timeframe like 7 days of awareness, as outlined in the EU’s Clinical Trials Regulation
Why it matters: Serious breach reporting safeguards participant safety and data integrity, ensuring prompt regulatory action and maintaining compliance with clinical trial requirements.