This topic will explain the importance of identifying and reporting Adverse Events and safety issues during the course of a clinical study.
You will need approximately 30 minutes to review the topic.
Click Next to continue. To follow along with the page audio, click the Notes link on the top right.
Hi, I’m Dr. Lisa Epps. I have been working as an Investigator for the last 10 years. During the course of my work, I’ve come to appreciate the importance of investigating, documenting, and reporting Adverse Events and safety issues, completely and correctly. Documenting and reporting Adverse Events, or AEs, during the course of a clinical study helps identify Adverse Drug Reactions, or ADRs. ADRs are AEs associated with a pharmaceutical product.
Sponsors are required to notify Investigators of all adverse drug reactions that are both serious and unexpected. Investigators are required to identify and report all Adverse Events from all sources to the Sponsor.
Failure to identify and report all Adverse Events during a clinical study is considered a critical regulatory deviation, and generates consistent findings from QA Audits and Regulatory Authority Inspections.
This topic will provide more information on:
· Adverse Events or AEs
· Assessment and identification of AEs
· Responsibilities of the Investigator and the Sponsor regarding AEs
· Serious Adverse Events, or SAEs, and their rapid reporting requirements
· Documentation, reporting, follow-up, and communication guidelines for AEs and SAEs
· Safety Reports
An AE is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which occurrence does not necessarily have a causal relationship with the treatment.
An AE can therefore be any unfavorable and unintended sign, including an abnormal laboratory finding, symptom, or disease temporally associated with the use of a medicinal or investigational product, whether or not related to the medicinal or investigational product.
Click next to continue. Note that the next page does not use audio. Pages that don’t use audio are indicated with a silent icon on the top right of the page.
No audio.
In order to find out about the existence of any Adverse Events, ask questions like:
· How are you feeling today?
· How have you been feeling since the last visit?
· How do you feel now, compared to before you started the study?
Avoid questions like:
· Have you had any Adverse Events since your last visit?
· Leading questions, for example: Have you had headaches since the last visit?
REMEMBER, subjects know how they feel, but they don’t know if how they feel meets the definition of an AE.
Click each numbered button to learn what to listen for in order to identify Adverse Events. Note that the rest of this page does not use audio.
No audio.
No audio.
During the study period, it is critical that the assessment of Adverse Events be promptly and correctly documented in the subject's source documents.
Click each tab above for some best practices for documenting Adverse Events. Note that the rest of this page does not use audio.
No audio.
The Investigator must be actively involved in assuring the subject’s safety. This includes identifying and assessing AEs, and evaluating the physical changes to subjects during the study period. The Investigator is also advised to periodically review Adverse Events by signing and dating such records in source documents.
Adverse events can include clinically significant laboratory values, ECG changes, and other safety related results. In case an Adverse Event does occur, the Sponsor should be contacted for guidance on any questions regarding subject safety and prior to discontinuing a subject except in emergency circumstances. Adequate medical care must be always provided to the subject. Medical care may include interrupting study medication or even ending the subject’s participation in the study.
Remember, the subject must be informed that an Adverse Event has occurred and that they will need medical care. Details of the AE, and its recommended follow-up, should be recorded in the source documents.
No audio.
Refer to the study protocol for rapid or expedited safety reporting requirements. Investigators must report serious Adverse Events, Adverse Events of special interest, and pregnancies, to the Sponsor within 24 hours of coming to know of these events. This includes holidays and weekends. So, if you learn of an event on Saturday, you must report it by Sunday, and not wait till Monday. In some cases, the IRB/IEC might need to be informed as well.
No audio.
No audio.
No audio.
Click the Forward button to learn reporting guidelines for serious adverse events, pregnancies, & other important medical events. Note that the rest of this page does not use audio.
No audio.
No audio.
The Sponsor is responsible for providing the Investigator with safety information for the Investigational Product or products in the form of a labeling document, for example an Investigational Brochure or the package insert for the compound.
The Investigator's Brochure is a compilation of the clinical and nonclinical data on the Investigational Product or products that is relevant to its study in human subjects. The Investigator should be thoroughly familiar with the appropriate use of the Investigational product or products as described in both the Study Protocol and the current Investigator's Brochure.
No audio.
In summary, Adverse Events, or AEs, are unfavorable and unintended signs, clinically significant lab findings, symptoms, or diseases temporally associated with the use of a pharmaceutical product. An AE may or may not be considered as related to the pharmaceutical product as defined in the study protocol. Adverse events that can be considered as serious, or SAEs, must be reported to the Sponsor within 24 hours of the site staff becoming aware. In case of pregnancy of the subject herself or of the subject’s partner, the Sponsor must be informed, again, within 24 hours.
The Sponsor will provide specific instructions regarding the reporting of SAEs at the start of the study. The Sponsor is required to promptly notify all concerned Investigators, institutions, and regulatory authorities of all adverse drug reactions that are both serious and unexpected. These are commonly referred to as Investigator notifications or Safety Reports. The Investigator should be familiar with this information and report to it the IRB/IEC as applicable.
Remember: You play a primary and crucial role in the identification and reporting of Adverse Events during the course of a clinical study.
No audio.
Congratulations!
You have now reviewed all pages in this topic. Please type your name below, and click Certificate for the Topic Completion Certificate.
Click the Exit link (top right) to close this window.
Attributable, legible, contemporaneous, original, accurate
A procedure in which one or more parties in the trial are kept unaware of the treatment assignment(s). Single blinding usually refers to the subject(s) being unaware, and double blinding usually refers to the subject(s), investigator(s), monitor, and, in some cases, data analyst(s) being unaware of the treatment assignment(s).
Complete, consistent, enduring, available
A paper or electronic copy of the original record that has been verified (e.g. by a dated signature) or has been generated through a validated process to produce an exact copy having all of the same attributes and information as the original.
Code of Federal Regulations
Collaborative Institutional Training Initiative
Federal Commission for the Protection against Sanitary Risk (Mexico)
Action to eliminate a detected nonconformity
Clinical Research Coordinator
Case Report Form
Contract Research Organization
Clinical trial agreement or study contract
Curriculum vitae
Electronic Data Capture
European Medicines Agency (Europe)
Electronic Medical Record
Food and Drug Administration (USA)
Good Clinical Practice; A standard for the design, conduct, performance, monitoring, auditing, recording, analyses, and reporting of clinical trials that provides assurance that the data and reported results are credible and accurate, and that the rights, integrity, and confidentiality of trial subjects are protected
Investigator Brochure
Informed Consent Form
The short form of ‘International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use’. ICH is unique in bringing together the regulatory authorities and pharmaceutical industry of Europe, Japan and the US to discuss scientific and technical aspects of drug registration.
Independent Ethics Committee
A person, who is independent of the trial, who cannot be unfairly influenced by people involved with the trial, who attends the informed consent process if the subject of the subject’s legally acceptable representative cannot read, and who reads the informed consent form and any other written information supplied to the subject
Investigational New Drug
Any public or private entity of agency or medical or dental facility where clinical trials are conducted
A person responsible for the conduct of the clinical trial at a trial site.
Investigational Product
Institutional Review Board
Investigator Study File
Interactive Response Technology, also referred to as IRT or IWRS depending on the type of technology used
Medicines and Healthcare Products Regulatory Agency (United Kingdom)
New Drug Application
National Institute for the Control of Pharmaceutical and Biological Products (China)
Notice of Initiation of Disqualification Proceedings and Opportunity to Explain
National Institute of Health
Non Investigational Product
Notice of Opportunity for Hearing
Action to eliminate the cause of a potential non-conformity or other undesirable situation
The process of assigning trial subjects to treatment or control groups using an element of chance to determine the assignments in order to reduce bias
A method of problem solving used for identifying the underlying causal factor of the noncompliance. If the root cause is removed the error is prevented from recurring.
Serious Adverse Event
Standard Operating Procedure; detailed written instructions to achieve uniformity of the performance of a specific function
An individual, company, institution, or organization that takes responsibility for the initiation, management, and/or financing of a clinical trial
The term unmasked is equivalent to the term unblinded. Unblinded/ unmasked can refer to a role in the study execution in which one party involved in the trial does know the treatment assignment. This strategy may be used for studies where a matching comparator is not available.