FDA Drug Warnings Can Negatively Impact Patient Adherence

New research sponsored by CVS Caremark examined the effects of Food and Drug Administration (FDA) drug warnings on medication adherence when the warnings are not delivered with clear clinical recommendations. The research found that immediately following a high-profile FDA communication questioning the efficacy for a cholesterol-lowering drug, the monthly level of patients who stopped filling their prescription increased by nearly 6 percent. In addition, of those patients who stopped taking the drug after the FDA warning, only 16.5 percent switched to another clinically appropriate therapy.

"These findings suggest that when an FDA communication about a prescription drug is widely reported in the news media and is not related to a safety issue or accompanied by clear guidelines about how to apply this information, the resulting confusion can bluntly reduce overall rates of treatment," said Niteesh Choudhry, MD, PhD of Brigham and Women's Hospital, a study co-author.  "Furthermore, if patients respond to this information by stopping therapy altogether and do not switch to another clinically appropriate medication there could be a negative impact on health outcomes which runs contrary to the intent of the initial communication."  

Researchers from Harvard University, Brigham and Women's Hospital and CVS Caremark, reviewed the impact of an FDA communication made on January 25, 2008 regarding the cholesterol-lowering medication, ezetimibe. The FDA issued an early communication after results from the ENHANCE trial indicated that adding ezetimibe (known as either Zetia or the ezetimibe-simvastatin combination, Vytorin) to a treatment regimen including simvastatin did not appear to improve patient outcomes. The FDA raised questions about the effectiveness of the drug in their communication, but did not advise health care professionals to discontinue prescribing these products. The communication received substantial media attention.

"This study provides an interesting perspective on how information made available to both health care practitioners and patients about the effectiveness of a drug can impact patient behavior and result in nonadherence," said Troyen A. Brennan, MD, MPH, executive vice president and chief medical officer of CVS Caremark. "The results suggest that a more robust understanding of how and why patients respond to drug information could lead to even more effective public health warnings regarding new data about medications."

The study, entitled "Warnings without guidance: Patient responses to an FDA warning about ezetimibe," was conducted by researchers at Harvard University, Brigham and Women's Hospital and CVS Caremark and was published in the June 2012 issue of the journal Medical Care. The researchers reviewed de-identified claims data for more than 860,000 patients identified as new users of ezetimibe between January 2006 and August 2008. The researchers estimated trends in discontinuation rates of ezetimibe during three time periods: 1) before the FDA communication (January 2006 – December 2007), 2) during the transition period when the FDA communication was issued (December 2007 – January 2008), and 3) after the communication (January 2008-July 2008).

In addition to the key findings related to drug discontinuation and low levels of drug switching to a clinically appropriate alternative, the researchers found that several patient characteristics were associated with discontinuation rates after the FDA warning had been issued. Overall, patients who resided in lower-income areas had a 12.9 percent lower rate of discontinuation compared with patients living in the highest income areas; female patients had a 6.9 percent lower rate of discontinuation compared with male patients and younger patients had lower rates of discontinuation with patients ages 18-34 having a 32.4 percent lower rate of discontinuation compared with patients over 65 years of age.

This study is a product of a research collaboration between CVS Caremark, Harvard and Brigham and Women's Hospital that is focused on understanding why many consumers do not take their prescriptions as directed, and developing solutions to assist patients in using their medications effectively. Excess health care costs due to medication non-adherence in the U.S. are estimated to be as much as $300 billion annually.

Source: CVS Caremark