CVS Caremark-sponsored research finds FDA drug warnings can fuel medication nonadherence

WOONSOCKET, R.I. — Food and Drug Administration drug warnings can have an immediate negative impact on medication adherence among patients, even if the warnings are not safety related, according to new research sponsored by CVS Caremark.

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%. In addition, of those patients who stopped taking the drug after the FDA warning, only 16.5% switched to another clinically appropriate therapy.

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.

"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," stated study co-author Niteesh Choudhry, who is with Brigham and Women's Hospital. "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 Jan. 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 its communication, but did not advise healthcare 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 healthcare practitioners and patients about the effectiveness of a drug can impact patient behavior and result in nonadherence," added Troyen A. Brennan, EVP 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 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: before the FDA communication (January 2006 to December 2007), during the transition period when the FDA communication was issued (December 2007 to January 2008) and after the communication (January 2008 to 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% lower rate of discontinuation compared with patients living in the highest income areas; female patients had a 6.9% lower rate of discontinuation compared with male patients; and younger patients had lower rates of discontinuation, with patients ages 18 to 34 years old having a 32.4% lower rate of discontinuation compared with patients older than 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 healthcare costs due to medication nonadherence in the United States are estimated to be as much as $300 billion annually.