Lesson 7 – Systematic Literature Review Course: Adverse Event Search

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Mastering Adverse Event (AE) and Recall Searches for Efficient Literature Reviews

Adverse event (AE) searches are a crucial part of the regulatory process when evaluating the safety of medical devices. While not technically a part of the “literature” search, collecting and reviewing AE data for your device is an essential step for ensuring compliance with clinical evaluation and Post Market Surveillance (PMS) requirements. In this lesson, we’ll walk you through how to efficiently conduct AE and recall searches to prepare for your Clinical Evaluation Report (CER) or Performance Evaluation Report (PER).

Focus on Deaths and Serious Adverse Events (SAEs)

When conducting AE searches, the first priority should be identifying serious adverse events, particularly deaths. It’s important to investigate what caused these outcomes and to categorize them based on their severity and type. Serious AEs often lead to complications that require deeper scrutiny. For example, if a device malfunction leads to significant bleeding or injury, this information must be thoroughly categorized and addressed in your report.

Categorizing Adverse Events

As you conduct AE searches, it’s essential to categorize the events. Separate them into categories such as deaths, injuries, malfunctions, or other types of adverse events. This categorization allows you to track the types of events more efficiently and identify any systemic issues with your device. For example, if several reports indicate that a needle malfunctioned during use, resulting in bleeding, this is an issue that needs to be addressed with the Notified Body (NB) and in your report.

Comparisons with Other Devices

One of the key aspects of AE searching is comparing the reported events for your device with those reported for similar devices or competitors. Highlight the differences in AE profiles to demonstrate how your device performs in comparison to others in the market. This can provide valuable insights into the relative safety of your device.

How to Perform AE and Recall Searches

A robust AE and recall search strategy should include searching several key databases. Here are the steps for an efficient search:

1. FDA MAUDE Database
   The FDA MAUDE database is crucial for identifying AEs and recalls related to your device and its comparators. Use this database to search for significant events, especially deaths and SAEs. It is also important to filter results by device name and manufacturer for accurate results.
2. Country-Specific Databases
   Conduct searches in the databases of every country where your device is sold. For example, databases such as BfArM (Germany), MHRA (UK), and ANSM (France) should be searched. Keep in mind that not all countries have publicly accessible AE databases, so be sure to check the specific requirements for each region.
3. Search Terms and Strategy
   Precision is key when searching for adverse events. Here are some tips for refining your search:
   • Use the manufacturer name.
   • Include variations of the device name.
   • For MAUDE, search using the three-digit code and filter the results based on device name and manufacturer.

What to Look for in AE and Recall Data

When reviewing the search results, focus on the following:

• Deaths and Serious AEs: Prioritize identifying and categorizing serious adverse events, particularly those resulting in death.
• Event Categorization: Categorize the events into deaths, injuries, malfunctions, and other types to provide a comprehensive overview.
• Narrative Details: Examine the context of each report to understand the underlying causes of the adverse events. This will help in assessing the risks associated with your device.

Country-Specific Search Considerations

Different countries may have different ways of categorizing and reporting adverse events. Make sure to adapt your search strategy depending on the database and country you’re searching. Many databases, such as those in the EU, allow you to categorize events into types like death, injury, and malfunction, which makes it easier to organize the data.

Documentation and Tracking of Searches

Documenting your search queries is critical for transparency and reproducibility. Be sure to record the following:

• The search terms used.
• The date of the search.
• The version of the database.
• The specific filters applied.

This detailed record helps ensure that your search strategy can be replicated and reviewed if necessary.

Writing the Adverse Event Section for Your Report

Once you have gathered all the relevant AE data, the next step is writing the AE section of your report. Here’s a suggested structure for presenting your findings:

1. Introduction: Provide a brief overview of the device and the objective of the AE search.
2. Search Methodology: Describe the databases searched, the search terms used, and the date of the search.
3. Findings: Summarize the events found, categorizing them into deaths, injuries, malfunctions, and others.
4. Discussion: Analyze the findings, highlighting any significant trends or safety concerns.
5. Conclusion: Summarize the overall safety profile of the device based on the AE data and propose any necessary actions or further monitoring.

Example Writeup

Let’s take a look at an example AE writeup:

Introduction
In this report, we review the adverse events related to the ABC Medical Device, focusing on serious incidents reported in various national databases.

Search Methodology
We conducted a search in the FDA MAUDE database, as well as databases from the UK, Germany, and France. The search was conducted using the device name, manufacturer, and the relevant three-digit code.

Findings
A total of 15 adverse events were reported, with 3 resulting in death, 5 injuries, and 7 malfunctions.

Discussion
The deaths were linked to device malfunction in two cases, and one incident was related to improper usage. Malfunctions primarily involved faulty needle punctures, leading to bleeding in 5 cases.

Conclusion
The device shows a relatively low incidence of serious adverse events compared to competitors, but the recurring needle puncture issues need to be addressed. Further investigations and product modifications may be necessary.

Conclusion

AE and recall searches are an essential part of your clinical evaluation and post-marketing reports. By conducting thorough searches and categorizing the results, you can provide a clear picture of the safety profile of your device and highlight any necessary actions or improvements. Remember, accurate data and clear reporting are key to regulatory compliance and ensuring the safety of your device in the market.

By following these guidelines, you’ll ensure that your AE and recall search strategies are effective and compliant with regulatory standards. Stay diligent, and your device will be better prepared for clinical evaluation and post-marketing surveillance.