Safe Use Initiative: How the FDA is Reducing Preventable Harm Through Nonregulatory Partnerships

ABSTRACT: The FDA’s role in ensuring the safety of over-the-counter and prescription medications has historically focused on regulatory activities related to drug development, quality, promotion, and postmarketing studies. However, preventing harm from medications also requires the FDA to partner with healthcare professionals to influence practices it does not regulate. 

As a regulatory agency, the FDA manages the risks of over-the-counter and prescription drugs through premarket evaluation of safety and effectiveness and postmarketing surveillance for adverse events. Historically, the FDA works to safeguard the accuracy and completeness of drug labeling, assess drug quality, approve advertising and promotional campaigns, and conduct studies to ensure the safety of drugs following approval. Despite these activities, however, the Center for Drug Evaluation and Research’s (CDER) regulatory authority still may not be sufficient to prevent harm once a drug is brought to market. 

Preventing harm from medications requires more than regulatory action alone. It also entails nonregulatory partnering with all those involved in healthcare—ie, manufacturers, pharmacies, and especially physicians—to control, modify, or influence the behaviors and practices the FDA does not regulate. The FDA’s Safe Use Initiative (SUI) was created to develop, implement, and evaluate programs with stakeholders to measurably reduce preventable harm from medications and improve patient health. The SUI is unique within CDER in that, rather than exerting authority through regulatory oversight and enforcement, it seeks to work with and learn from those who are actually present when medications are prescribed and used—the healthcare providers and their patients—in a nonregulatory fashion.

Addressing the Problem

With over 3 billion prescriptions written annually in the United States,1 it is imperative that drug safety be a priority for physicians and patients alike. Millions of Americans rely upon prescription and OTC medicines2 and numerous stakeholders—including manufacturers, pharmacies, prescribers, and the FDA itself—are accountable for identifying and managing drug risks. But despite the best efforts of these groups, patients still face the possibility of injuries due to preventable medication misuse or errors. Thus, guaranteeing the safe use of approved drugs is best done by determining which therapeutic areas are in the greatest need of further research and subsequentally defining the specific interventions that would have the most likely impact. 

Since its inception in November 2009, the SUI has sought to address a number of priority questions: 

•What is the drug, drug class, or therapeutic area that is associated with preventable harm? How significant is the harm? What is the public health impact? 

•What is the potential that interventions will help manage risks of the medication use process, reduce preventable harm, and complement ongoing regulatory actions?

•Is the timing appropriate for an intervention, based on the other activities the FDA is engaged in or anticipating?

•What is the ability to engage stakeholders for collaboration?

•Is there an ability to measure outcomes and impact?

These core issues, which helped set SUI’s initial agenda, continue to guide the team as its areas of focus evolve with new and emerging drug safety concerns. SUI’s work with stakeholders on acetaminophen safety—one of its first projects and one it continues to support today—is a prime example. 

The Acetaminophen Example

Public health drug safety nets can only work when there is shared responsiblilty across all health- and medical-related sectors.3 

Acetaminophen is one of the most widely used medicines in the United States, found in more than 600 prescription and OTC medicines.4 The drug has a well-established record of safety and efficacy, but overdose can be toxic and is the leading cause of acute liver failure. To prevent acetaminophen overdose, physicians and consumers must be able to read labels and recognize when their medicines contain acetaminophen. However, container labels on prescription medicines that contain acetaminophen do not always clearly identify it as an active ingredient.

Over the past 5 years, the agency has worked within its regulatory framework to strengthen labeling warnings, distribute drug safety communications, and conduct educational outreach for patients taking acetaminophen-containing products. However, the agency does not have the authority to dictate the practice of medicine. 

To help influence the behaviors of physicians and patients in a nonregulatory fashion, the SUI has worked to build external relationships and discuss ideas that complement the FDA’s regulatory efforts. For example, the SUI partnered with the National Council for Prescription Drug Programs (NCPDP) and other stakeholders to form the Acetaminophen Best Practices Task Group, who collaboratively produced a white paper entitled, “NCPDP recommendations for improved prescription container labels for medicines containing acetaminophen,” that was updated in January 2013.5 

The recommendations make it easier for consumers to: 

•Identify which of their prescription pain reliever contains acetaminophen

•Compare active ingredients on their prescription to OTC labels

•Take action to avoid taking 2 medicines with acetaminophen 

The improved clarity in labeling allows patients and physicians to more easily work together to identify a risk for acetaminophen toxicity. It also fosters discussion regarding appropriate treatment, as well as alternate options that would reduce the risk of overdose and potential for liver failure. 

Enhancing Collaboration with Physicians

Despite successful engagement efforts with a number of stakeholder groups, SUI has previously faced several challenges attempting to collaborate with physicians. In fact, while many current projects have been funded through grants and cooperative agreements awarded to patient safety organizations or academic institutions, less input has come from physician groups themselves. In fact, preliminary findings from an ongoing, SUI-funded study on physician engagement with the FDA finds that healthcare providers seldom visit the FDA website, are unaware of its drug safety communications, and do not look to FDA as their primary source of drug safety information. 

To address these concerns, the SUI has begun working proactively to improve its outreach to and partnerships with physicians and their specialty societies. As part of this effort, it has begun to seek out and connect with healthcare providers who share an interest in drug safety and investigating ways to reduce preventable harm from medications. With the goal of setting an agenda for research and collaboration that will better serve the needs of the physician community, the SUI reached out to large organizations (eg, American Medical Association, American Academy of Pediatrics, and American Association of Family Physicians) as well as individual practitioners to better understand the community’s priorities and concerns.

In addition to working with physicians to establish a scientific agenda, SUI must address the gaps that exist in their awareness of and access to key drug safety information. Discussions about medication safety often focus on procedural and process errors—such as confusing similar drug names, administering incorrect doses, or writing illegibly. While these types of errors are often easy to identify and understand, studies show that errors which occur when a prescriber has incomplete access to or does not effectively use existing information about the drug, the patient, or the condition can lead to significantly more harm.6 The SUI is committed to provide education to practitioners on these types of informational medication errors so that another source of preventable harm from drugs can be mitigated.

New and Emerging Areas for the SUI

There are several examples of how the SUI has successfully been leveraging its position within CDER to create and facilitate public and private collaborations within the healthcare community. Over the past 5 years, the SUI has worked with healthcare professionals to better understand the reasons behind the increasing use of atypical antipsychotic medications in children, collaborated to improve the safety of oral liquid medications, convened an expert panel to discuss the topic of neurological adverse events following epidural steroid injections, and targeted opioid use and misuse (Table). 

In the latter example, the SUI worked with stakeholders on projects ranging from understanding and improving urine drug testing for detecting opioid levels to development of a patient-prescriber agreement as a tool for shared decision-making in the treatment of pain. Furthermore, the agency recently funded 2 separate projects that will research new tools for the assessment of pain and safe delivery of opioids to patients both in the outpatient and postsurgical settings. These studies will help clinicians better understand which patients are at highest risk for opioid misuse and how to prescribe these drugs in a safe and pragmatic manner that maximizes safety and prevents adverse events.    

Through the Broad Agency Announcement (BAA), a funding mechanism for government agencies to contract for basic and applied research, the SUI will work with researchers in the fields of opioid, antidiabetic, and antibiotic drug safety over the next several years to learn more about the causes of preventable harm in patients receiving these medications and ways to improve current prescribing practices. The SUI is committed to funding new and innovative BAA projects in 2015 and beyond that will continue to broaden its research portfolio to further its role as a thought leader in the area of preventable drug harm. 

Each of these projects are rooted in the SUI’s mission to create collaborative, cross-sector projects to better manage specific risks and reduce preventable harm from medication use and each has the potential to truly improve the well-being of the American patient.

John Whyte, MD, MPH, is the director of Professional Affairs and Stakeholder Engagement at the FDA.

Ali Mohamadi, MD, is the lead medical officer for Professional Affairs and Stakeholder Engagement at the FDA.



1. IMS Institute for Healthcare Informatics. Medicine use and shifting costs of healthcare: a review of the use of medicines in the US in 2013. IMS Health. 2014 Apr.  www.imshealth.com/deployedfiles/imshealth/Global/Content/Corporate/IMS%20Health%20Institute/Reports/Secure/IIHI_US_Use_of_Meds_for_2013.pdf2014.
Accessed January 2015.

2. National Center for Health Statistics. Health, United States, 2013: with special feature on prescription drugs. 2014. www.cdc.gov/nchs/hus/chartbook.htm#chartbook_special_feature. Accessed April 2015.

3. Agency for Healthcare Research and Quality. Stakeholder Guide 2014. www.ahrq.gov/research/findings/evidence-based-reports/stakeholderguide/stakeholdr.pdf. Accessed April 2015.

4. FDA. Don’t double up on acetaminophen. 2013 Jan. www.fda.gov/ForConsumers/ConsumerUpdates/ucm336581.htm. Accessed November 2014. 

5. National Council for Prescription Drug Programs. NCPDP recommendations for improved prescription container labels for medicines containing acetaminophen. 2013 Jan. http://ncpdp.org/NCPDP/media/pdf/wp/NCPDPacetaminophenWPv1.1_31jan2013.pdf. Accessed April 2015.

6. Woolf SH, Kuzel AJ, Dovery SM, Phillip RL Jr. A string of mistakes: the importance of cascade analysis in describing, counting, and preventing medical errors. Ann Fam Med. 2004;2(4):317-326.