Understanding how these costly pharmaceuticals are used clinically in the organization.
Adopting a systematic approach to the problem and involving key stakeholders in the implementation and design of the program by providing periodic data feedback.
Identifying the key areas in which continued use of the pharmaceutical is critical for patients.
Identifying and reducing waste in the delivery of pharmaceuticals.
Identifying and highlighting less-costly therapeutic alternatives to help physicians continue to provide effective treatment to patients.
Recent developments in the pharmaceutical market have led to major price increases for certain drugs. Such price increases can result in serious concerns about the affordability of critically needed medications for patients and also can have a substantial negative impact on hospital budgets, leading to the potential inability of hospitals to provide other important clinical services. Pharmacists and physicians at the Cleveland Clinic and its Heart and Vascular Institute recently developed a specific strategy to respond to the major price increases of 2 commonly used cardiovascular drugs, nitroprusside and isoproterenol, resulting in estimated cost savings of more than $8.5 million over 2 years.
Traditionally, health care providers have attempted to mitigate major increases in pharmaceutical prices by identifying additional manufacturers, generic substitutions, or therapeutic substitutions (i.e., drugs from the same class with a similar mechanism of action and similar clinical impact). However, these strategies cannot be used when a drug has only one manufacturer, with no generic or therapeutic substitution options.
Nitroprusside and isoproterenol are two such examples. Between 2012 and 2015, nitroprusside prices increased 30-fold (with the average wholesale acquisition cost [(WAC]) per 50 mg increasing from $27.46 to $880.88), and isoproterenol prices increased nearly 70-fold (with the average WAC per mg increasing from $26.20 to $1790.11).
Cleveland Clinic, a 1,437-bed tertiary care medical center in Cleveland, Ohio, is one of the highest utilizers of nitroprusside and isoproterenol in the United States. The lack of an effective strategy to respond to these price increases would have led to a marked increase in spending on these pharmaceuticals within the hospital, which would have negatively impacted the financial stability of the organization and potentially would have led to the need to reduce important clinical resources. As a result, Cleveland Clinic and its Heart and Vascular Institute sought to develop a strategy to respond to these price increases and to mitigate their financial impact.
The most significant challenge was the long-standing utilization of these two drugs for the treatment of many common clinical indications in our hospital. Thus, we knew that any changes would require a careful analysis of all issues and a structured approach to navigate the options.
Rather than eliminating these drugs from our formulary, we sought to develop a strategy for how to approach these price increases that would allow us to identify and protect the appropriate utilization of the drugs while eliminating waste and promoting appropriate alternatives.
The Heart and Vascular Institute Executive Council and the Department of Pharmacy authorized a review of nitroprusside and isoproterenol from 3 perspectives: (1) continuing utilization for critical drug indications, (2) reducing waste, and (3) identifying therapeutic alternatives. This review process was carried out by a team comprising key pharmacists, physicians, and administrators from throughout the organization.
Protecting Appropriate Use for Critical Indications
Through a clinical care review process, the team identified 3 common indications for the use of nitroprusside (acute heart failure, aortic dissection, and hypertensive emergency) and 3 common indications for the use of isoproterenol (electrophysiology testing, tilt testing in the syncope lab, and intraoperative testing of myectomy patients). The team worked to identify therapeutic substitutions (i.e. drugs from the same class with a similar mechanism of action and similar clinical impact) and therapeutic alternatives (i.e. drugs from a different class with a different mechanism of action but similar clinical impact) for both drugs. There were no therapeutic substitution options for either drug. Furthermore, no therapeutic alternatives to nitroprusside were identified for the indication of acute heart failure, and no therapeutic alternatives to isoproterenol were identified for the indication of electrophysiology testing; thus, it was agreed that both of these critical indications would be protected.
The team identified three specific steps to reduce waste: (1) discontinuation of the routine ordering of nitroprusside as a prechecked therapy for the treatment of hypertension following cardiac surgery, (2) removal of the high-concentration option for nitroprusside in the electronic medication order, and (3) reduction of the routine dispensing quantity of isoproterenol from 400 to 100 µg, in keeping with the typical patient dose.
Identifying Therapeutic Alternatives
The team subsequently identified 3 therapeutic alternatives for specific indications, including (1) the addition of IV nitroglycerin as an alternative to nitroprusside for the treatment of hypertension following cardiac surgery, (2) the addition of clevidipine as an alternative to nitroprusside for the treatment of aortic dissection, and (3) the addition of dobutamine as an alternative to isoproterenol for the intraoperative testing of myectomy patients.
Stakeholders received feedback on project performance in the form of monthly reports for senior physician leaders, quarterly reports for the Heart and Vascular Institute Executive Council, bimonthly reports for the senior leadership in the Department of Pharmacy, and quarterly reports for the intensive care unit operations group. Within the clinical care areas, the response to the new program was largely supportive. In some cases (e.g., the reduction in the standard dispensing quantity of isoproterenol), the changes were met with no resistance. Occasionally, reeducation was required to remind clinicians of the new protocols, particularly in the intensive care unit setting, where nitroprusside use had been the standard of care for many years.
The primary endpoints of our study were the absolute and relative cost savings on nitroprusside and isoproterenol. Using the pharmaceutical utilization patterns from 2012-2013 as the baseline, we created (1) a projected utilization model for 2014-2015 by transferring the 2012-2013 utilization patterns and assuming no change in the patterns and (2) an actual utilization model for 2014-2015 by recording the actual utilization of both drugs during this time period.
We determined the cost of the pharmaceuticals by multiplying each patient’s utilization of the drug (i.e., the total amount of drug administered) by the WAC at the time of medication administration. We then calculated the cumulative projected and actual drug expenditures for 2014-2015. The absolute cost savings was defined as the difference between the projected cumulative costs for 2014-2015 minus the actual cumulative costs for 2014-2015, and the relative cost savings was defined as the absolute cost savings for 2014-2015 divided by the projected cumulative costs for 2014-2015.
From 2012 to 2015, a total of 12,790 unique patients were treated with nitroprusside and 4,074 unique patients were treated with isoproterenol. Our strategy led to an absolute cost savings of $8,067,551 and a relative cost savings of 56% for nitroprusside as well as to an absolute cost savings of $581,986 and a relative cost savings of 55% for isoproterenol.
Clinical outcomes were monitored by regular feedback between pharmacists and physicians and through safety-event reporting systems. No major patient-safety or clinical-outcome issues were noted. Detailed comparative studies of clinical outcomes associated with the therapeutic alternatives are ongoing.
Where to Start
Organizations that are interested in pursuing this strategy need to:
- Have a pharmacy and physician leadership structure that is supportive of the endeavor.
- Understand the clinical use of pharmaceuticals within the organization and develop metrics to measure utilization.
- Identify areas of waste and highlight therapeutic alternatives that may be different from those in our experience.
- Have feedback mechanisms in place to ensure accountability with the implemented strategy.
We developed a novel strategy that was successful in reducing the negative financial impact of the major pricing increases for nitroprusside and isoproterenol. The implementation of this strategy by a multidisciplinary team of pharmacists and physicians was highly successful in reducing utilization of these two drugs. We believe that our strategy can be implemented for other pharmaceuticals associated with large price increases. Ultimately, this strategy can be used by other health care systems to help manage rising pharmaceutical costs.
Also see the authors’ letter in the New England Journal of Medicine: Khot, Umesh N., Eric D. Vogan, and Michael A. Militello. “Nitroprusside and Isoproterenol Use after Major Price Increases.” New England Journal of Medicine 377, no. 6 (2017): 594-595.
The authors wish to acknowledge the important contributions of the following individuals: Joyce Velazquez, Heart and Vascular Institute Center for Healthcare Delivery Innovation, Cleveland Clinic; Andrew Toth, MS, Quantitative Health Sciences, Cleveland Clinic; Jeevanantham Rajeswaran, PhD, Quantitative Health Sciences, Cleveland Clinic; Steven Nissen, MD, Department of Cardiovascular Medicine, Cleveland Clinic; Eric Kaiser, MD, Department of Cardiothoracic Anesthesiology, Cleveland Clinic; Venu Menon, MD, Department of Cardiovascular Medicine, Cleveland Clinic; Randall C. Starling, MD, MPH, Department of Cardiovascular Medicine, Cleveland Clinic; Mariana P. Carrera, PhD, Department of Economics, Case Western Reserve University; Bruce Lindsay, MD, Department of Cardiovascular Medicine, Cleveland Clinic; Walid Saliba, MD, Department of Cardiovascular Medicine, Cleveland Clinic; Nicholas Smedira, MD, Department of Cardiothoracic Surgery, Cleveland Clinic; Mandy Leonard, PharmD, Department of Pharmacy, Cleveland Clinic; Lars Svensson, MD, PhD, Heart and Vascular Institute Center for Healthcare Delivery Innovation, Cleveland Clinic.
Funding Sources: The primary funding source was unrestricted philanthropic support to the Heart and Vascular Institute Center for Healthcare Delivery Innovation, Cleveland Clinic. The funding source had no role in the design or conduct of the study; collection, management, analyses, or interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.
Disclosures: Umesh N. Khot has served as consultant to AstraZeneca. Walid Saliba has served as consultant to Biosense Webster, Boston scientific, and BIOTRONIK. Randall C. Starling has served a consultant to Medtronic, Inc., and Novartis International, AG, but has instructed that compensation be donated to not-for-profit causes or to the Cleveland Clinic to support research and education.
This case study originally appeared in NEJM Catalyst on September 7, 2017.