Improving Inpatient REMS Documentation Compliance With a Wildcard Checkpoint

Abstract

Background

The risk evaluation and mitigation strategies (REMS) program is a medication safety program implemented by the FDA to ensure high-risk medications provide benefits that outweigh their risks. Manufacturers may be required to implement strategies that vary by medication, creating a challenging environment for health care providers and patients to ensure documentation compliance. Our institution, University of California San Diego Health, addressed this by implementing a standardized pharmacist workflow for REMS medications using a wildcard in the preparation instructions for certain REMS medications. The wildcard reminded pharmacists to fill out an intervention note and attest that all required documentation was completed before dispensing the medication. The objective of this study was to determine the effectiveness of the simple addition of a wildcard to the medication preparation instructions of a pharmacist’s medication verification activity to improve Risk Evaluation and Mitigation Strategy (REMS) documentation compliance.

Methods

We conducted a comparative study of the pre- and postimplementation periods. To assess compliance, we tracked the percentage of i-Vents completed by pharmacists for verified orders of the 3 REMS medications for which the wildcard was used. The study period was from March 25, 2021, to January 25, 2022, for the preimplementation period, and from January 26, 2022, to September 26, 2022, for the postimplementation period. A 2×2 χ² test for independence was conducted to assess the significance of the change in compliance rate before and after implementation.

Results

In the preimplementation period, 162 out of 226 orders (71.7%) had i-Vents documenting REMS elements necessary for compliance. In the postimplementation period, 191 out of 193 orders (99.0%) were compliant. The test revealed a statistically significant difference in the compliance rates between the pre- and postimplementation period (P < .000001).

Conclusion

Our institution’s solution of using a wildcard in the preparation instructions was effective in achieving nearly universal compliance.

Introduction

The FDA started the Risk Evaluation and Mitigation Strategy (REMS) program in 2008 to allow the prescribing of certain medications with serious safety concerns to help ensure the benefits of medications outweigh their risks. REMS are not designed to mitigate all the adverse effects of a medication but are focused on preventing, monitoring, and/or managing specific serious risks by informing, educating, and reinforcing actions to reduce the frequency and/or severity of the event.¹

An example of a medication that requires a REMS program is riociguat (Adempas; Bayer). Riociguat is a guanylate cyclase stimulator used to treat pulmonary hypertension. Riociguat is an efficacious medication, but it is associated with a risk of embryo-fetal toxicity.² The riociguat REMS program requires that the prescribing provider, patient, and pharmacy be enrolled before prescribing, taking, and dispensing this medication. Requiring training to participate in the use of a high-risk medication such as riociguat ensures that proper precautions and monitoring parameters are known to all before the patient begins pharmacotherapy.³

Adherence with REMS requirements can be challenging for several reasons. The program’s complexity makes it difficult for institutions to adopt a one-size-fits-all approach to complying with REMS requirements. Manufacturers are responsible for creating and curating their individual REMS programs under FDA oversight. Because each medication has different requirements due to varying risks, it can be difficult for health systems to adhere to all requirements. In a survey of 14 hospitals within the Vizient network, 10 responded that the REMS program’s lack of standardization and complexity were the most significant barriers to compliance.⁴

Noncompliance with REMS requirements can have large financial implications for health systems. Under the Federal Food, Drug, and Cosmetic Act, a drug is considered misbranded if there is a violation of 1 of 5 REMS observation requirements.⁵ An article by Regulatory Focus notes that the “FDA may impose civil monetary penalties of up to $250,000 per violation of REMS requirements and up to $1,000,000 in a single proceeding.”⁵ Therefore, it is of utmost importance that health systems be well aware of the requirements of REMS programs and the ramifications for failing to comply.

Our institution, University of California (UC) San Diego Health, developed and implemented a simple solution to address this issue within our electronic health record system, Epic. It was inspired by an unrelated process for documenting complex information on four-factor prothrombin complex concentrate that was required for billing. A wildcard hard stop (***) was added to the pharmacist preparation instructions during verification. By adding this wildcard, the pharmacist cannot proceed with verification until they open the preparation instructions and address the hard stop, prompting the user to document the actual units dispensed, as the factor products vary in the number of units per vial. The ordering provider is not hard-stopped from signing the order, as the pharmacy preparation instructions are not populated in the system until the point of pharmacist verification, making this hard stop specific to pharmacists.

Applying this same idea, the novel wildcard method was implemented in January 2022 to remind pharmacists to document a REMS intervention note (i-Vent) for certain medications. The implementation is defined as adding a wildcard attestation to the pharmacist preparation instructions for 3 medications in the REMS program: ambrisentan (Letairis; Gilead Sciences), macitentan (Opsumit; Johnson & Johnson), and riociguat. This prompts the pharmacist to attest that they have reviewed the REMS requirements prior to verifying the order. These medications were selected for the pilot study, as they are less well known for REMS documentation requirements, and previous audits showed failures to consistently document.

METHODS

Study Design

This was a single-center, retrospective, observational, pre/post study conducted at UC San Diego Health, a large academic medical center. During the study period, there were 152,731,829 medication orders searched, for which there were 419 qualifying orders for the study medications: 226 in the preimplementation group, and 193 in the postimplementation group. The study periods were from March 25, 2021, to January 25, 2022, and January 26, 2022, to September 26, 2022 (preimplementation and postimplementation periods, respectively). Pharmacist documentation was assessed by searching for i-Vents with a standardized template for the study medications and prompts for all necessary information for regulatory compliance. Documentation compliance was defined as submission of an i-Vent using the appropriate template per patient, per encounter, for a patient with an ordered study medication.

Study Objectives

The primary objective was to determine the effectiveness of the simple addition of a wildcard to the medication preparation instructions of a pharmacist’s medication verification activity, as a method of improving REMS documentation compliance.

Data Collection and Analysis

The data were obtained from the medical center’s electronic health records by searching the Epic Chronicles database. Comparisons were performed between groups using a 2×2 χ²test of independence. A level of statistical significance of at least 0.05 was used in all statistical tests. Percentage change was calculated using Microsoft Excel software.

Ethics

Informed consent was waived due to the retrospective nature of the study. This was a quality improvement study deemed exempt from institutional review board approval.

Results

For the primary outcome, 162 out of 226 orders (71.7%) in the preimplementation period had i-Vents documenting REMS elements necessary for compliance. In contrast, in the postimplementation period, 191 out of 193 orders (99.0%) were compliant. (Figure 1). The test revealed a statistically significant difference in the compliance rates between the pre- and postimplementation periods (P < .000001).

Discussion

This study has shown the feasibility and effectiveness of implementing a simple wildcard hard stop to the pharmacist preparation instructions field with a reminder for pharmacists to ensure REMS requirements are met before verifying a medication. This approach is novel because it bypasses prescriber order entry, places a hard stop on verification to ensure that all REMS requirements and documentation are met before final dispensing of the medication, and allows the prescriber to continue without interrupting their workflow (Figures 2 and 3). Other institutions reported implementing best-practice alerts (BPAs) that automatically alert providers/pharmacists to address REMS requirements for each qualifying medication. The BPA method is more build-intensive for the project team, and is overall more disruptive to the user. The introduction of this simple wildcard on the pharmacist verification screen serves as a reminder to pharmacists about the need for additional precautions with REMS medications, thereby reducing reliance on individual pharmacist recollection for compliance.

This wildcard hard stop was easy to implement, required virtually no development time, and can be applied broadly to new REMS medications that require action and documentation. After implementation of this hard stop, our institution saw nearly universal compliance with REMS documentation for our study medications, with very minimal disruption to workflow.

Future directions for this study include expanding the use of the wildcard hard stop to other REMS medications, such as alvimopan and bosentan, in the next phase of development. Using a standardized approach to applying the wildcard to all REMS medications that require compliance documentation helps maintain consistent compliance. Pairing this with a template for the required REMS components is a highly effective way to ensure institutions are following safe medication practices and complying with regulatory requirements. Utilization of this wildcard in pharmacist preparation instructions also has the potential to optimize other areas of pharmacist practice that require consistent pharmacist intervention or documentation, such as factor unit tracking, with fewer interruptive alerts and without the need to target physicians.

Conclusion

The REMS program is intended to ensure the safe use of high-risk medications, but a lack of standardization creates challenges in documenting compliance. Our institution’s solution of using a wildcard in the preparation instructions was effective in achieving nearly universal compliance. The solution was simple to implement, applicable to all REMS requirements, and minimally disruptive to workflow.

REFERENCES

1. Risk Evaluation and Mitigation Strategies | REMS. FDA. Accessed March 3, 2023. https://www.fda.gov/drugs/drug-safety-and-availability/risk-evaluation-and-mitigation-strategies-rems

2. Lippmann E. Risk Evaluation and Mitigation Strategies (REMS). FDA. June 2017. Accessed August 17, 2023. https://www.fda.gov/media/105565/download

3. Riociguat Shared System REMS Accessed March 3, 2023. https://www.accessdata.fda.gov/scripts/cder/rems/index.cfm?event=RemsDetail.page&REMS=414

4. Pemmaraju AA, Stevens CA, Yam NT, Daniels CE. Challenges in REMS compliance. Am J Health Syst Pharm. 2021;78(12):1036-1037. doi:10.1093/ajhp/zxab075

5. Walsh AK. The enforcement of Risk Evaluation and Mitigation Strategy (REMS). Regulatory Focus. January 2019. Accessed May 8, 2023. https://hpm.com/wp-content/uploads/2019/02/RF-2019-01-Enforcement-of-REMS-00521473.pdf