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Where Data Reside

There is an enormous amount of data collected in the course of doing pharmacovigilance work. Much of it is reliable and verified but much is not. The problem is obtaining access to the data, verifying that it is real and correct, ensuring that no duplicates occur, getting it into a database accurately, and making valid clinical judgments at the individual patient level and at the aggregate (public health) level. As with everything else in drug safety, this is a moving target.

Adverse event (AE) data are collected all over the world by many people and groups. There is little standardization in the way they are collected, how they are measured and graded, how they are stored, and how they are used. Some of the data are collected as a matter of public health, and some are collected by pharmaceutical companies or other companies or nongovernmental organizations that process the data and make available or sell them to others. In theory, with the International Conference on Harmonization (ICH), Council for International Organizations of Medical Sciences (CIOMS), Medical Dictionary for Regulatory Activities (MedDRA), and other standards, such as HL-7, we are moving toward improved standardization and use of these data.

AE data reside in several places. One main resource is the United States Food and Drug Administration.

The FDA has a large amount of data stored in four publicly accessible databases of primarily postmarketing safety data as well as other proprietary databases containing clinical trial information. The FDA drug database for all approved drug and therapeutic biologic products, the Adverse Event Reporting System (AERS), is discussed here.

AERS (Web Resource 8-1) collects information about AEs, medication errors, and product problems on marketed drug and therapeutic biologic products. It is ICH E2B compliant and MedDRA is used for coding. Quarterly (noncumulative) data files since January 2004 are available under the United States Freedom of Information Act for downloading as zipped SGML or ASCII files. Data include information on patient demographics, the drug(s) reported, the adverse reaction(s), patient outcome, and the source of the reports. The actual files can be downloaded directly. The data can be downloaded and manipulated (though not easily), and various companies offer services that include periodic updates, data searches, or repackaging of the data in a more user-friendly form. The database cannot be searched directly.

There is a variable lag of several months between AEs’ being reported to the FDA and their making it into the quarterly data files. Should further information be desired after reviewing the data from the quarterly report, the full MedWatch form (anonymized to protect the reporter and patient) can be obtained using the unique identification number assigned to each case by the FDA. Data can be obtained directly from the FDA under the Freedom of Information Act (Web Resource 8-2) or from private companies. Using the latter ensures the anonymity of the requester, and some companies use these services to obtain information on their competitors’ products.

Although getting and using the data can be difficult, it can be rewarding because large amounts of detailed data are available, particularly for newer products. The full MedWatch forms are available, and the narratives can be read to obtain clinical summaries of the cases.

This database is rather large, with some 4 million cases, and is growing by roughly half a million cases per year. About 35,000 are received directly by the FDA each year with the remainder from industry. Of the industry reports, about 300,000 are 15-day expedited reports and the rest are from periodic reporting. AERS contains primarily postmarketing data from prescription drugs, biologics, and over-the-counter drugs with an approved NDA sold in the United States, but it also contains some foreign reports of AEs for these drugs. Most of the industry reports are sent electronically, though paper reports (MedWatch 3500A forms) are still accepted at this writing. The data vary in quality, ranging from full due diligence inquiries and follow-ups with complementary data (laboratory reports, electrocardiograms, etc.) to lay consumer reports not validated by a medical professional. Note that FDA’s AERS database has nothing at all to do with the commercial product from Oracle also known as AERS.

There are few clinical trial data in the FDA AERS database. The clinical trial data are proprietary and are generally not available, although some advocacy groups would like to see a change in this. FDA’s new clinical trials registry will hold more data (including more safety information) in the next few years as the FDAAA requirements come into effect (many in 2012).

Some clinical trial safety data can be found in Summary Basis of Approval documents that the FDA sometimes releases after a drug is approved. They are not easily found on the website and need to be searched for using the search box. Postmarket Requirements and Commitments may be searched for at (Web Resource 8-3).

Potential Signals of Serious Risks/New Safety Information that FDA has found in AERS is available at (Web Resource 8-4).

Approved risk evaluation and mitigation strategies (with links to PDF files containing the full REMS documents in most cases) are available at (Web Resource 8-5).

Finally, FDA was required by the Food and Drug (FDAAA) of 2007 to do a periodic review of new drugs (New Molecular Entity Postmarketing Safety Evaluation), looking at all data within 5 years of first approval. A pilot program completed the review of three products: apomorphine, aripiprazole, and duloxetine (Web Resource 8-6). Further reviews may be undertaken.

FDA has a new project under way to redo the AERS database. The agency is developing an electronic system called MedWatchPlus for receiving, processing, evaluating, and analyzing AE reports and other safety information for all FDA-regulated products. Within this system will be FAERS (FDA Adverse Event Reporting System), FDA’s new database.

The FDA also has databases containing clinical trial information (Web Resource 8-7) as well as drug-specific information, including labeling for approved drugs (Web Resource 8-8).

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