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Compliance In Focus
Posted by Kelly Schindelholz on Mon, Dec 21, 2020

Serious Adverse Event Reporting: Everything You Need To Know

Reporting serious adverse events is a critical part of conducting a clinical trial. As important as this responsibility is, it can be confusing at times.

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The FDA regulations for adverse event reporting leave some room for interpretation, and the requirements in the United States differ from those of other nations. Resource-conscious sponsors, on the other hand, are always seeking to do the right thing and avoid unnecessarily burdening investigators. 

Here is a detailed review of the international standards and U.S. regulations to guide clinical trial associates in reporting serious adverse events.

How to Report A Serious Adverse Event

Reporting serious adverse events is a critical part of conducting a clinical trial. As important as this responsibility is, it can be confusing at times.

The FDA regulations for adverse event reporting leave some room for interpretation, and the requirements in the United States differ from those of other nations. Resource-conscious sponsors, on the other hand, are always seeking to do the right thing and avoid unnecessarily burdening investigators.

Here is a detailed review of the international standards and U.S. regulations to guide clinical trial associates in reporting serious adverse events.

What Is an Adverse Event?

The FDA’s definition of an adverse event is any “untoward medical occurrences” associated with the use of a drug or medical device. You can also call it an unwanted effect that occurs, whether or not it's determined to be caused by the drug or device.

Here are the various adverse events associated with safety reporting that you should know:

Life-Threatening Adverse Event

This is also referred to as a life-threatening suspected adverse reaction. An event may be deemed as life-threatening by the clinical trial sponsor or investigator if the subject or patient faces an immediate risk of death due to the occurrence. This level does not comprise an adverse event that may have led to death or if the occurrence was more severe.

Serious Adverse Event

This is also referred to as a serious suspected adverse reaction. An event can be referred to as "serious" by the investigator or sponsor if it brings about the following results:

  • Death
  • A life-threatening adverse effect
  • Prolonged hospitalization of existing patient or inpatient hospitalization of the subject
  • Persistent or substantial incapacitation or a significant disruption in day-to-day functions
  • A congenital disability

If an adverse event doesn't cause death, require hospitalization, or threaten the subject's life, it may still be considered serious. This applies when the event can jeopardize the patient and may call for surgical or medical intervention.

Examples of other serious adverse events include:

  • Convulsions or blood dyscrasias that don't lead to subject hospitalization
  • Allergic bronchospasm that calls for intensive treatment at home or in the emergency room
  • Development of drug abuse or dependency

Unexpected Adverse Events

These also go by the name “unexpected suspected adverse reaction”. An event may fall under this category if it doesn't appear in the protocol or hasn't been listed at the observed severity or specificity.

An adverse event may also be considered "unexpected" if an investigator brochure is missing or isn't necessary, or if it doesn't show consistency with the risk information provided in the investigational plan or anywhere within the current application.

For instance, by virtue of greater severity, hepatic necrosis would be considered unexpected if the possible side effects listed in the investigator’s brochure only mention hepatitis or elevated hepatic enzymes. Also, by virtue of greater specificity, cerebral vasculitis and cerebral thromboembolism would fall in the same category if only cerebral vascular accidents are listed.

You can also use the term "unexpected" to refer to suspected adverse reactions or adverse events that aren't explicitly mentioned to occur with the investigated drug or device.

Recording and Reporting Adverse Events in the U.S.

Here are the requirements for recording and reporting serious adverse events in the United States:

Investigator Requirements

The reporting responsibility for investigators requires them to record and document any device-related adverse events. They must also report any results that are unanticipated and serious to the institutional review board and sponsor within ten days. Most of the time sponsors issue even shorter deadlines for reporting adverse events.

Sponsor Requirements

Once the sponsor learns of an adverse event via the investigator’s report, their next step is to record every adverse effect and report unanticipated and severe impacts to the FDA, participating investigators, and other IRBs within ten working days. If you determine that subjects will face unreasonable risks if the study continues, you have five working days to terminate the investigation.

Clinical trials that encompass NSR (non-significant-risk) devices can be initiated even without submitting an IDE application to FDA. Consequently, sponsors may be unsure whether they should report any profound, unanticipated adverse effect to the federal agency. The FDA, however, doesn't expect any reports of adverse effects of this nature.

The Office of Device Evaluation will review the adverse event report to determine whether the device in question should be considered to be of significant risk. They also determine whether any additional safeguards should be included in a particular study design.

Reporting Adverse Events in The European Union

This region of the world has a unique set of requirements for clinical trial associates to report serious adverse events.

Investigator Requirements

Any investigator taking part in a clinical trial must follow a set of procedures for recording and documenting adverse events. The medical device- or drug-related adverse events reports are kept in separate files.

Investigators are also required to report every device-related adverse effect and severe adverse events to the sponsor. Both severe and device-related effects are usually reviewed by the ethics committee.

Sponsor Requirements

The sponsor must always consult with the reporting investigators when considering each adverse event. They are also required to report this information to the appropriate, authorities as determined by the different EU member states.

Sponsors are required to report device-related adverse effects separately. This, as well as the report of severe adverse events from investigators, must be reported within ten days.

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After Reporting Adverse Events, What Next?

It's essential to document and report any adverse event that occurs when conducting a clinical trial. Once reported, these effects will be reviewed to ensure subject safety.

Investigators who agree to perform ethical and just research are required by law to halt an investigation once they realize that the drug or medical device being investigated presents an adverse event that's previously unknown or anticipated.

If you realize an unanticipated adverse effect, you'll have ten days to report it to the FDA or other appropriate IRBs. The sponsor must compile adverse event data and send it for review to the clinical events committee (CEC) or data safety and monitoring board (DSMB). You must also include an overview of the event in your FDA annual progress report.

The federal agency will ultimately decide whether the drug or device is safe before it enters the market.

The Role of Clinical Events Committees

Clinical events are what drive clinical trials, and these may be subject to interpretation since they may not have standard definitions. Sponsors should use an approach that significantly reduces how this potential variability impacts the conclusions derived from the information on outcomes. This is where CECs can help.

This independent group consists of diagnostic and clinical exerts with the following responsibilities:

  • Reviewing and classifying possible efficacy or safety endpoints in a confidential, unbiased, blinded, and consensus-based fashion.
  • Determining whether the potential endpoints match the provided endpoint criteria and protocol definitions.
  • Providing standardized outcomes to aid statistical analysis
  • Classifying events that relate to a study procedure or device

Besides the endpoint-specific information, CECs are also responsible for reviewing general subject information. The review may include death reports, serious adverse events, and any adverse event with the potential of becoming a clinical study endpoint.

Why You Should Work with an Independent CRO

Reporting adverse events is a crucial part of ensuring safety, and working with a third-party contract research organization (CRO) can significantly improve your safety monitoring processes. The CRO can create a "firewall" between the safety management board and the sponsor. They will promote objectivity to ensure the subjects' safety and the clinical trial's integrity.

CROs also assess conflicts of interests and manage member agreements and compensation to offer an additional layer of independence. They bring consistency and keep trials organized with the help of standard operating procedures.

Instead of having a CEC or DSMB operate with busy physicians, a CRO can offer the best results promptly.

If you're looking for an independent CRO to serve as your trusted compliance partner, IMARC can help. We can recruit physicians for your safety monitoring board, schedule meetings, and manage any follow-up communications to ensure your trial stays on track.

This allows you to focus on earning approval and bringing your device to market faster.

Contact us today to learn more about our services.

Topics: Safety Monitoring

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