Flaws in Adverse Drug Reaction Reporting: A Matter of Patient Communication

There are plenty of reports that suggest that adverse events are not reported to the FDA. Specifically, these reports indicate that, despite the presence of established hospital/medical facility AE reporting systems, most adverse events are still going unreported. A 2012 report from the Office of Inspector General (OIG) suggested that 86% of hospital staff did not report adverse events because of misconceptions related to perceiving patient harm,^[1] and there are no established methods to measure harm incidence in patients.^[2]

While the issue of adverse drug reaction (ADR) reporting is apparent in hospital systems, a deeper and uninvestigated problem resides within the process of ADRs: the patient. Feedback from patients suggest that they are not properly informed about what an ADR is, what types of reactions they should expect from taking specific medications (despite pharmacist consultations) and how to report those effects. This article will analyze drug data from FDA’s Adverse Event Reporting System (AERS) compared to a drug’s expected side effect profile, analyze patient feedback, and identify methods to improve adverse drug reaction reporting.

ADR Reports are Not Consistent with FDA Approved Drug Trends

In order to verify the effectiveness of the ADR reporting system, we evaluated the expected adverse effect profile for Lyrica and the actual adverse effect data received in AERS. In this analysis, we chose Lyrica as a test case. Table 1 demonstrates Lyrica’s expected side effect profile,^[3] and Table 2 delineates expected ADRs compared to what was received in AERS. Upon evaluating the AERS database, a total of 162,029 ADR cases associated with Lyrica were reported, which is far from expected ADR rates.

It is important to emphasize that this analysis contains gaps; specifically, clinical trial side effect profiles may differ from one disease indication to another, and ADR interpretation and categorization may vary in post-marketing settings compared to clinical trial settings. However, the fact that only 162,029 ADR cases were reported in AERS demonstrates a large discrepancy. When evaluating ADR profiles for other medical products in AERS, we have observed similar discrepancies between clinical trial and post-marketing ADR adverse event data.

The Patient’s Perspective

What factors might be contributing towards the ADR discrepancy? In clinical trials, biopharmaceutical sponsors employ a variety of tools to enhance ADR detection and reporting from both clinical staff (i.e., training) and patients (i.e., PRO surveys). 

However, in post-marketing settings, ADRs oftentimes go undetected and unreported for several reasons including physicians and clinical staff ignoring and misinterpreting patient symptom reports.^[4] “Healthcare professionals aren’t out there to detect adverse events, and I had issues with the dialogue between healthcare professionals,” said T.J. Sharpe, a patient and clinical trial participant.  Moreover, patients tend not to report their symptoms in post-marketing settings.  “Before I started participating in clinical trials, I never paid attention to or worried about reporting adverse events of FDA approved medications,” said Sharpe.

Sharpe indicated that physicians’ main focus is a patient’s wellbeing.  “Doctors lean more on trying to heal the patient and not necessarily focus on adverse event detection,” said Sharpe.  “During a clinical trial, when the investigational drug was working, and I got a case of shingles, my doctor took preventative measures (i.e., prescribing tolerable doses of Valtrex) to keep me in the trial,” added Sharpe.
 

ADR Reporting Systems Are in the Spotlight

The OIG has put AE reporting in the spotlight because of its impact on subsequent treatment and hospitalization costs,^[5] and is recommending that hospitals develop a list of potentially reportable medical events to help clinical staff.  However, not reporting ADRs has an even more serious impact on drug effect profiles, as ADRs with serious safety risks may go unreported.

The FDA is currently planning and implementing the Sentinel Initiative, which is an Electronic Medical Record (EMR) based directive that is designed to uncover ADRs via patients’ EMR data.^[6]  The risk for biopharmaceutical sponsors is that enhancing post-marketing setting ADR reporting may lead to adverse event data discrepancies compared to clinical trial settings, which may influence payer decision making in evaluating outcomes for medical product coverage, especially since payers’ level of scrutiny on new medical products is increasing.^[7]

Patients feel that ADR reporting is a personal and educational matter, “Healthcare professionals should focus on education because it would help me feel more comfortable; they should explain the adverse event reporting process to the patient,” said Sharpe.

* Assumes equivalent distribution of sales per year on 9 million patient sales from 2005 – 2014^[7].  Analysis assumes 7 million patients were prescribed Lyrica from 2005-2012 ^[7]

** AERS data extrapolated from 2005 – 2012

References:

[1] http://oig.hhs.gov/oei/reports/oei-06-09-00091.asp?goback=%2Egmr_4418518%2Egde_4418518_member_140184035

[2] http://oig.hhs.gov/oei/reports/oei-06-07-00470.pdf

[3] http://www.drugs.com/sfx/lyrica-side-effects.html#refs

[4] http://www.haiweb.org/14012010/14Jan2010ReportDirectPatientReportingofADRsFINAL.pdf

[5] http://oig.hhs.gov/newsroom/spotlight/2012/adverse.asp

[6] http://www.appliedclinicaltrialsonline.com/node/244575

[7] http://www.lyrica.com/frequently-asked-questions