Are $100,000-plus ICU drugs worth the cost?

Yes – Expensive drugs may offset other costs.

As in every aspect of medicine, there is a cost-benefit balance, with the cost of care being weighed against the benefits of a favorable outcome. The debate seems to be complex, but it can really be boiled down to a single question: Is the therapy worth using when compared with alternatives or to current practice?

It is incumbent upon us as clinicians to evaluate the appropriate use of both expensive and inexpensive drugs.

Drug costs in the ICU always involve more than meets the eye. If we take the traditional silo-based perspective and focus only on the acquisition cost of a drug, we’re ignoring the reality that the less expensive drug is not always the best drug for a condition and that health system costs are affected by the total cost of care. If a less expensive drug requires more patient monitoring, it offsets at least some of the cost advantage by adding higher laboratory or imaging costs.

Another consideration for the hospital is the reimbursement climate. Hospitals that receive low scores on pain management under the HCAHPS (Hospital Consumer Assessment of Healthcare Providers and Systems) survey may experience significant reductions in reimbursement. So if, say, an expensive nonopioid analgesic used as part of a multimodal therapy could significantly improve pain control and reduce opioid-related adverse events, the extra cost could be justified.

Acquisition costs are only part of a drug’s total cost, which also includes the costs of preparation, storage, administration (such as infusion devices), lab monitoring, treating adverse drug events, and, of course, failed therapy.

Costly drugs also may pay for themselves by offsetting other costs. A new, costly drug that reduces the patient’s length of ICU stay by 1 day would save $4,000 to $5,000, and a drug that reduces time spent on a mechanical ventilator could reduce costs by about $1,900 for each ventilator-free day. Ventilator-associated pneumonias cost approximately $50,000 more per case ($70,580 vs. $21,620), but prevention strategies, including the use of medications, could reduce these costs.

Our group recently did a study of ICU costs associated with acute kidney injury following coronary artery bypass grafts and found that costs were twice as high in patients with kidney injury ($25,950 vs. $13,830). If patients have even a 1.5-fold increase over baseline in serum creatinine, the associated cost is $21,775, compared with $13,830 in patients whose serum creatinine is controlled. We calculated that an effective drug, if it cost less than $12,000, would offset these costs (Textbook of Critical Care, 6th edition, 2011, pp. 1387-92).

A 2012 analysis of the cost offset of tolvaptan in patients with inappropriate antidiuretic hormone secretion indicated that the cost of treating hyponatremia was $1,694 and that tolvaptan, at a cost of $250 per day for 4 days, reduced the length of stay by an estimated 1.1 days, thereby providing a savings of $694 per patient (Hosp. Pract. 2012;40:7-14).

Similarly, recombinant factor VIIa costs $7,000 to $10,000 per dose, but when used for its approved indication – bleeding episodes in hemophilia A or B patients with inhibitors to factors VIII/IX and for prevention of bleeding during surgical intervention in these patients – costs per resolved bleeding episode were $3,000 to $17,000 lower than for patients given activated prothrombin complex concentrate (Haemophilia 2009;15:405-19).

Clinicians are excited when we have new options for therapy, but we have to figure out where a new, expensive therapy fits. Does it make sense to use it? What is the efficacy of the drug relative to its costs? The key to the appropriate use of drugs, both costly and cheap, is to develop a disease state–based protocol tailored to your institution’s specific usage patterns, case mix, economic climate, and politics.

Dr. Sandra Kane-Gill is associate professor of pharmacy and therapeutics at the University of Pittsburgh School of Pharmacy. She also serves as associate professor for the Center for Pharmacoinformatics and Outcomes Research at the School of Pharmacy.

No – With cost evaluations, the devil is in the details.

Drug-cost evaluations look great on paper, but they often don’t work in the real world. An expensive drug may let you take a patient off a ventilator earlier, but if you can’t send the patient to the floor because there is no available bed and you can’t let that patient’s nurse go home, there may not be a true savings in cost.

As Dr. Kane-Gill points out, the problem is complex and there are many analytic approaches. We can consider whether we have therapeutically equivalent options, balance the cost-effectiveness and cost-benefit ratios of treatments with different outcomes, or consider patient preference measured in cost-utility tradeoff and expressed as quality-adjusted life years (QALYs).

The problem with cost modeling is that it is sensitive to input – garbage in means garbage out. Models are hampered by the limitations of what can be accomplished in clinical trials and by the assumptions made to create the model. Is it based on acquisition costs or on charges? How do practice variations within the institution (between the medical ICU and the surgical ICU, for example), or from one institution to the next, affect the assumptions in the model?

Cost comparisons must somehow reconcile data from conflicting studies and multiple treatment options, and they must be able to quantify the effects over time of a given intervention.

Clinical trials that are used to justify cost evaluations are performed in controlled settings. I wish that I could say that all my patients were uniform, but they are not. There is a substantial difference between a 24-year-old with a head injury and a 90-year-old with a head injury, or between a patient with a broken hip and one with end-stage liver disease. How do you begin to compare the effects of drugs across these populations? How do you judge the effect of a specific drug in an era of polypharmacy, when some patients seen in our unit have been on as many as 27 drugs at the same time?

Time can also fade the bloom of a once-promising drug, such as drotrecogin alfa (Xigris). An analysis of the PROWESS study (Crit. Care Med. 2003;31:12-9) appeared to show that drotrecogin alfa was helpful in patients with severe sepsis, and this drug’s alleged efficacy was balanced against its cost, which was estimated at $48,000 per QALY and considered to be in the acceptable range. As we all know, longer experience with this agent found no overall benefit and an association with higher bleeding risk (Cochrane Database Syst. Rev. 2012 Dec 12;12:CD004388). The drug was pulled from the market in late 2011.

Dr. Kane-Gill correctly notes that factor VIIa, when used for its rare indication, offers a benefit and saves money. But many ICUs were using this agent outside of its labeled indication (Ann. Intern. Med. 2011;154:516-22) and found that it caused emboli in patients already at risk for thromboembolic events (J. Trauma. 2010;69:489-500; N. Engl. J. Med. 2008;358:2127-37).

If a drug is in the formulary, and if it is new and more expensive than other therapeutic options, it is human nature to think that new and expensive must mean better than old and cheap. In Europe, ICUs routinely use injectable acetaminophen for nonopioid pain relief. In the United States, the intravenous formulations of this drug are costly – about $10 per dose, compared with about 50 cents for one dose of percocet. Yet the reduction in opioid use with the injectable agent is modest, there is no evidence to suggest reductions in opioid-related adverse events, and there are conflicting data on patient satisfaction (Cochrane Database Syst. Rev. 2011 Oct 5;(10):CD007126).

Economic evaluations of drugs should be viewed with caution because they require knowledge of the literature basis for the model, may exhibit considerable variation in estimates of indirect costs, and are subject to the vagaries of conflicting data as well as changes in data and practice over time. Additionally, estimates of drug cost and benefits can vary by country, region, or facility.

It’s clear that we need much more data about outcomes and the true costs of the care we give.

Dr. Christine C. Toevs is a trauma surgeon and director of the trauma ICU at Allegheny General Hospital in Pittsburgh. She also has a Masters degree in bioethics.

Yes – Expensive drugs may offset other costs.

As in every aspect of medicine, there is a cost-benefit balance, with the cost of care being weighed against the benefits of a favorable outcome. The debate seems to be complex, but it can really be boiled down to a single question: Is the therapy worth using when compared with alternatives or to current practice?

It is incumbent upon us as clinicians to evaluate the appropriate use of both expensive and inexpensive drugs.

Drug costs in the ICU always involve more than meets the eye. If we take the traditional silo-based perspective and focus only on the acquisition cost of a drug, we’re ignoring the reality that the less expensive drug is not always the best drug for a condition and that health system costs are affected by the total cost of care. If a less expensive drug requires more patient monitoring, it offsets at least some of the cost advantage by adding higher laboratory or imaging costs.

Another consideration for the hospital is the reimbursement climate. Hospitals that receive low scores on pain management under the HCAHPS (Hospital Consumer Assessment of Healthcare Providers and Systems) survey may experience significant reductions in reimbursement. So if, say, an expensive nonopioid analgesic used as part of a multimodal therapy could significantly improve pain control and reduce opioid-related adverse events, the extra cost could be justified.

Acquisition costs are only part of a drug’s total cost, which also includes the costs of preparation, storage, administration (such as infusion devices), lab monitoring, treating adverse drug events, and, of course, failed therapy.

Costly drugs also may pay for themselves by offsetting other costs. A new, costly drug that reduces the patient’s length of ICU stay by 1 day would save $4,000 to $5,000, and a drug that reduces time spent on a mechanical ventilator could reduce costs by about $1,900 for each ventilator-free day. Ventilator-associated pneumonias cost approximately $50,000 more per case ($70,580 vs. $21,620), but prevention strategies, including the use of medications, could reduce these costs.

Our group recently did a study of ICU costs associated with acute kidney injury following coronary artery bypass grafts and found that costs were twice as high in patients with kidney injury ($25,950 vs. $13,830). If patients have even a 1.5-fold increase over baseline in serum creatinine, the associated cost is $21,775, compared with $13,830 in patients whose serum creatinine is controlled. We calculated that an effective drug, if it cost less than $12,000, would offset these costs (Textbook of Critical Care, 6th edition, 2011, pp. 1387-92).

A 2012 analysis of the cost offset of tolvaptan in patients with inappropriate antidiuretic hormone secretion indicated that the cost of treating hyponatremia was $1,694 and that tolvaptan, at a cost of $250 per day for 4 days, reduced the length of stay by an estimated 1.1 days, thereby providing a savings of $694 per patient (Hosp. Pract. 2012;40:7-14).

Similarly, recombinant factor VIIa costs $7,000 to $10,000 per dose, but when used for its approved indication – bleeding episodes in hemophilia A or B patients with inhibitors to factors VIII/IX and for prevention of bleeding during surgical intervention in these patients – costs per resolved bleeding episode were $3,000 to $17,000 lower than for patients given activated prothrombin complex concentrate (Haemophilia 2009;15:405-19).

Clinicians are excited when we have new options for therapy, but we have to figure out where a new, expensive therapy fits. Does it make sense to use it? What is the efficacy of the drug relative to its costs? The key to the appropriate use of drugs, both costly and cheap, is to develop a disease state–based protocol tailored to your institution’s specific usage patterns, case mix, economic climate, and politics.

Dr. Sandra Kane-Gill is associate professor of pharmacy and therapeutics at the University of Pittsburgh School of Pharmacy. She also serves as associate professor for the Center for Pharmacoinformatics and Outcomes Research at the School of Pharmacy.

No – With cost evaluations, the devil is in the details.

Drug-cost evaluations look great on paper, but they often don’t work in the real world. An expensive drug may let you take a patient off a ventilator earlier, but if you can’t send the patient to the floor because there is no available bed and you can’t let that patient’s nurse go home, there may not be a true savings in cost.

As Dr. Kane-Gill points out, the problem is complex and there are many analytic approaches. We can consider whether we have therapeutically equivalent options, balance the cost-effectiveness and cost-benefit ratios of treatments with different outcomes, or consider patient preference measured in cost-utility tradeoff and expressed as quality-adjusted life years (QALYs).

The problem with cost modeling is that it is sensitive to input – garbage in means garbage out. Models are hampered by the limitations of what can be accomplished in clinical trials and by the assumptions made to create the model. Is it based on acquisition costs or on charges? How do practice variations within the institution (between the medical ICU and the surgical ICU, for example), or from one institution to the next, affect the assumptions in the model?

Cost comparisons must somehow reconcile data from conflicting studies and multiple treatment options, and they must be able to quantify the effects over time of a given intervention.

Clinical trials that are used to justify cost evaluations are performed in controlled settings. I wish that I could say that all my patients were uniform, but they are not. There is a substantial difference between a 24-year-old with a head injury and a 90-year-old with a head injury, or between a patient with a broken hip and one with end-stage liver disease. How do you begin to compare the effects of drugs across these populations? How do you judge the effect of a specific drug in an era of polypharmacy, when some patients seen in our unit have been on as many as 27 drugs at the same time?

Time can also fade the bloom of a once-promising drug, such as drotrecogin alfa (Xigris). An analysis of the PROWESS study (Crit. Care Med. 2003;31:12-9) appeared to show that drotrecogin alfa was helpful in patients with severe sepsis, and this drug’s alleged efficacy was balanced against its cost, which was estimated at $48,000 per QALY and considered to be in the acceptable range. As we all know, longer experience with this agent found no overall benefit and an association with higher bleeding risk (Cochrane Database Syst. Rev. 2012 Dec 12;12:CD004388). The drug was pulled from the market in late 2011.

Dr. Kane-Gill correctly notes that factor VIIa, when used for its rare indication, offers a benefit and saves money. But many ICUs were using this agent outside of its labeled indication (Ann. Intern. Med. 2011;154:516-22) and found that it caused emboli in patients already at risk for thromboembolic events (J. Trauma. 2010;69:489-500; N. Engl. J. Med. 2008;358:2127-37).

If a drug is in the formulary, and if it is new and more expensive than other therapeutic options, it is human nature to think that new and expensive must mean better than old and cheap. In Europe, ICUs routinely use injectable acetaminophen for nonopioid pain relief. In the United States, the intravenous formulations of this drug are costly – about $10 per dose, compared with about 50 cents for one dose of percocet. Yet the reduction in opioid use with the injectable agent is modest, there is no evidence to suggest reductions in opioid-related adverse events, and there are conflicting data on patient satisfaction (Cochrane Database Syst. Rev. 2011 Oct 5;(10):CD007126).

Economic evaluations of drugs should be viewed with caution because they require knowledge of the literature basis for the model, may exhibit considerable variation in estimates of indirect costs, and are subject to the vagaries of conflicting data as well as changes in data and practice over time. Additionally, estimates of drug cost and benefits can vary by country, region, or facility.

It’s clear that we need much more data about outcomes and the true costs of the care we give.

Dr. Christine C. Toevs is a trauma surgeon and director of the trauma ICU at Allegheny General Hospital in Pittsburgh. She also has a Masters degree in bioethics.

Yes – Expensive drugs may offset other costs.

As in every aspect of medicine, there is a cost-benefit balance, with the cost of care being weighed against the benefits of a favorable outcome. The debate seems to be complex, but it can really be boiled down to a single question: Is the therapy worth using when compared with alternatives or to current practice?

It is incumbent upon us as clinicians to evaluate the appropriate use of both expensive and inexpensive drugs.

Drug costs in the ICU always involve more than meets the eye. If we take the traditional silo-based perspective and focus only on the acquisition cost of a drug, we’re ignoring the reality that the less expensive drug is not always the best drug for a condition and that health system costs are affected by the total cost of care. If a less expensive drug requires more patient monitoring, it offsets at least some of the cost advantage by adding higher laboratory or imaging costs.

Another consideration for the hospital is the reimbursement climate. Hospitals that receive low scores on pain management under the HCAHPS (Hospital Consumer Assessment of Healthcare Providers and Systems) survey may experience significant reductions in reimbursement. So if, say, an expensive nonopioid analgesic used as part of a multimodal therapy could significantly improve pain control and reduce opioid-related adverse events, the extra cost could be justified.

Acquisition costs are only part of a drug’s total cost, which also includes the costs of preparation, storage, administration (such as infusion devices), lab monitoring, treating adverse drug events, and, of course, failed therapy.

Costly drugs also may pay for themselves by offsetting other costs. A new, costly drug that reduces the patient’s length of ICU stay by 1 day would save $4,000 to $5,000, and a drug that reduces time spent on a mechanical ventilator could reduce costs by about $1,900 for each ventilator-free day. Ventilator-associated pneumonias cost approximately $50,000 more per case ($70,580 vs. $21,620), but prevention strategies, including the use of medications, could reduce these costs.

Our group recently did a study of ICU costs associated with acute kidney injury following coronary artery bypass grafts and found that costs were twice as high in patients with kidney injury ($25,950 vs. $13,830). If patients have even a 1.5-fold increase over baseline in serum creatinine, the associated cost is $21,775, compared with $13,830 in patients whose serum creatinine is controlled. We calculated that an effective drug, if it cost less than $12,000, would offset these costs (Textbook of Critical Care, 6th edition, 2011, pp. 1387-92).

A 2012 analysis of the cost offset of tolvaptan in patients with inappropriate antidiuretic hormone secretion indicated that the cost of treating hyponatremia was $1,694 and that tolvaptan, at a cost of $250 per day for 4 days, reduced the length of stay by an estimated 1.1 days, thereby providing a savings of $694 per patient (Hosp. Pract. 2012;40:7-14).

Similarly, recombinant factor VIIa costs $7,000 to $10,000 per dose, but when used for its approved indication – bleeding episodes in hemophilia A or B patients with inhibitors to factors VIII/IX and for prevention of bleeding during surgical intervention in these patients – costs per resolved bleeding episode were $3,000 to $17,000 lower than for patients given activated prothrombin complex concentrate (Haemophilia 2009;15:405-19).

Clinicians are excited when we have new options for therapy, but we have to figure out where a new, expensive therapy fits. Does it make sense to use it? What is the efficacy of the drug relative to its costs? The key to the appropriate use of drugs, both costly and cheap, is to develop a disease state–based protocol tailored to your institution’s specific usage patterns, case mix, economic climate, and politics.

Dr. Sandra Kane-Gill is associate professor of pharmacy and therapeutics at the University of Pittsburgh School of Pharmacy. She also serves as associate professor for the Center for Pharmacoinformatics and Outcomes Research at the School of Pharmacy.

No – With cost evaluations, the devil is in the details.

Drug-cost evaluations look great on paper, but they often don’t work in the real world. An expensive drug may let you take a patient off a ventilator earlier, but if you can’t send the patient to the floor because there is no available bed and you can’t let that patient’s nurse go home, there may not be a true savings in cost.

As Dr. Kane-Gill points out, the problem is complex and there are many analytic approaches. We can consider whether we have therapeutically equivalent options, balance the cost-effectiveness and cost-benefit ratios of treatments with different outcomes, or consider patient preference measured in cost-utility tradeoff and expressed as quality-adjusted life years (QALYs).

The problem with cost modeling is that it is sensitive to input – garbage in means garbage out. Models are hampered by the limitations of what can be accomplished in clinical trials and by the assumptions made to create the model. Is it based on acquisition costs or on charges? How do practice variations within the institution (between the medical ICU and the surgical ICU, for example), or from one institution to the next, affect the assumptions in the model?

Cost comparisons must somehow reconcile data from conflicting studies and multiple treatment options, and they must be able to quantify the effects over time of a given intervention.

Clinical trials that are used to justify cost evaluations are performed in controlled settings. I wish that I could say that all my patients were uniform, but they are not. There is a substantial difference between a 24-year-old with a head injury and a 90-year-old with a head injury, or between a patient with a broken hip and one with end-stage liver disease. How do you begin to compare the effects of drugs across these populations? How do you judge the effect of a specific drug in an era of polypharmacy, when some patients seen in our unit have been on as many as 27 drugs at the same time?

Time can also fade the bloom of a once-promising drug, such as drotrecogin alfa (Xigris). An analysis of the PROWESS study (Crit. Care Med. 2003;31:12-9) appeared to show that drotrecogin alfa was helpful in patients with severe sepsis, and this drug’s alleged efficacy was balanced against its cost, which was estimated at $48,000 per QALY and considered to be in the acceptable range. As we all know, longer experience with this agent found no overall benefit and an association with higher bleeding risk (Cochrane Database Syst. Rev. 2012 Dec 12;12:CD004388). The drug was pulled from the market in late 2011.

Dr. Kane-Gill correctly notes that factor VIIa, when used for its rare indication, offers a benefit and saves money. But many ICUs were using this agent outside of its labeled indication (Ann. Intern. Med. 2011;154:516-22) and found that it caused emboli in patients already at risk for thromboembolic events (J. Trauma. 2010;69:489-500; N. Engl. J. Med. 2008;358:2127-37).

If a drug is in the formulary, and if it is new and more expensive than other therapeutic options, it is human nature to think that new and expensive must mean better than old and cheap. In Europe, ICUs routinely use injectable acetaminophen for nonopioid pain relief. In the United States, the intravenous formulations of this drug are costly – about $10 per dose, compared with about 50 cents for one dose of percocet. Yet the reduction in opioid use with the injectable agent is modest, there is no evidence to suggest reductions in opioid-related adverse events, and there are conflicting data on patient satisfaction (Cochrane Database Syst. Rev. 2011 Oct 5;(10):CD007126).

Economic evaluations of drugs should be viewed with caution because they require knowledge of the literature basis for the model, may exhibit considerable variation in estimates of indirect costs, and are subject to the vagaries of conflicting data as well as changes in data and practice over time. Additionally, estimates of drug cost and benefits can vary by country, region, or facility.

It’s clear that we need much more data about outcomes and the true costs of the care we give.

Dr. Christine C. Toevs is a trauma surgeon and director of the trauma ICU at Allegheny General Hospital in Pittsburgh. She also has a Masters degree in bioethics.