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Cost-Effectiveness Studies in the ICU: A Systematic Review*

Wilcox, M. Elizabeth MD, MPH1; Vaughan, Kelsey MSc, MPP2; Chong, Christopher A. K. Y. MD3; Neumann, Peter J. ScD4; Bell, Chaim M. MD, PhD5

doi: 10.1097/CCM.0000000000003768
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Objectives: Cost-effectiveness analyses are increasingly used to aid decisions about resource allocation in healthcare; this practice is slow to translate into critical care. We sought to identify and summarize original cost-effectiveness studies presenting cost per quality-adjusted life year, incremental cost-effectiveness ratios, or cost per life-year ratios for treatments used in ICUs.

Design: We conducted a systematic search of the English-language literature for cost-effectiveness analyses published from 1993 to 2018 in critical care. Study quality was assessed using the Drummond checklist.

Setting: Critical care units.

Patients or Subjects: Critical care patients.

Interventions: Identified studies with cost-effectiveness analyses.

Measurements and Main Results: We identified 97 studies published through 2018 with 156 cost-effectiveness ratios. Reported incremental cost-effectiveness ratios ranged from –$119,635 (hypothetical cohort of patients requiring either intermittent or continuous renal replacement therapy) to $876,539 (data from an acute renal failure study in which continuous renal replacement therapy was the most expensive therapy). Many studies reported favorable cost-effectiveness profiles (i.e., below $50,000 per life year or quality-adjusted life year). However, several therapies have since been proven harmful. Over 2 decades, relatively few cost-effectiveness studies in critical care have been published (average 4.6 studies per year). There has been a more recent trend toward using hypothetical cohorts and modeling scenarios without proven clinical data (2014–2018: 19/33 [58%]).

Conclusions: Despite critical care being a significant healthcare cost burden there remains a paucity of studies in the literature evaluating its cost effectiveness.

1University Health Network and Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada.

2Bang for Buck Consulting, Amsterdam, The Netherlands.

3Section of General Internal Medicine, Lakeridge Health Oshawa, Oshawa, ON, Canada.

4Institute for Clinical Research and Health Policy Studies, Center for the Evaluation of Value and Risk in Health, Tufts Medical Center, Boston, MA.

5Sinai Health System and the Department of Medicine, University of Toronto, Toronto, ON, Canada.

*See also p. 1150.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal).

Dr. Bell disclosed that he is a medical consultant to the Ontario Ministry of Health and Long-Term Care. The remaining authors have disclosed that they do not have any potential conflicts of interest.

For information regarding this article, E-mail: elizabeth.wilcox@mail.utoronto.ca

Delivering critical care is expensive. Despite statements by both the United States Public Health Service Panel on Cost-Effectiveness in Health and Medicine and the American Thoracic Society endorsing cost-effectiveness analysis (CEA) as the primary method by which to measure the costs and effects of healthcare programs and medical therapies (1–3), a relative paucity of data exists for one of the highest cost services provided in healthcare. Although CEA are unable to determine the proportion of overall resources that should be spent on healthcare, they can inform what should be considered within a given healthcare budget. Ultimately, CEA should promote better choices, and in turn, improve overall public health. Critical care, with its inherent complexity, frequent innovations, and high cost, is well suited for CEA as a basis for improving healthcare quality.

A previous systematic review by Talmor et al (4) in 2006 was the first to synthesize published CEAs related to interventions for ICU patients. Given this article is now over a decade old and that many of the original studies that demonstrated good value for money have since demonstrated no mortality benefit, we set out to systematically review and synthesize the currently available evidence of the cost-effectiveness literature in critical care. Our objectives were to identify and summarize original cost-effectiveness studies presenting cost per quality-adjusted life year (QALY) or cost per life-year ratios for treatments used in critical care. In doing so, we aimed to provide a clearer picture of where cost-effectiveness research in ICU currently stands.

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METHODS

We searched a registry maintained by the Center for the Evaluation of Value and Risk in Health at Tufts Medical Center (https://research.tufts-nemc.org/cear4/) for original CEAs published in the medical literature through 2016 related to critical care. This registry compiles original CEAs published in the medical literature, is available on the Internet as a public-use file, and as it is an established cost evaluation specific site, it was used as a starting point to help identify studies as well as key terms to use in Medline and EMBASE (5). The registry searches Medline with the keywords, “QALYs,” “quality,” and “cost-utility analysis” and then screens the article abstracts to determine if the article contains an original cost-utility estimate. Studies relevant to critical care were then identified by database review of the titles and abstracts of all studies. Two reviewers (M.E.W., C.A.K.Y.C.) independently reviewed all citations; disagreements about inclusion were resolved by discussion. In cases of doubt, full-text articles were retrieved for review and discussion with third party (C.M.B.). In addition, the same search was run in EMBASE (1993 to June 24, 2018) and Medline (1993 to week 2, June 2018) databases (Fig. 1). For determining the number of randomized controlled trials in critical care over time the search terms “critical care,” “RCT,” and “randomized controlled trial” were combined in Medline (1993 to June 24, 2018) and EMBASE (1993 to week 2, June 2018). This search was not meant to be exhaustive but to crudely illustrate the rate of rise in the number of publications within the critical care literature over the last few decades.

Figure 1.

Figure 1.

Two reviewers (M.E.W., K.V.) independently abstracted data including descriptive characteristics of the studies (funding source, perspective, time horizon, discount rate, and performance of sensitivity analysis) and methodology used in conducting cost-effectiveness studies including performance of sensitivity analyses using a standard data collection form. A variety of methodologic perspectives were employed, in which perspective refers to point of view from which costs and benefits have been considered. From narrowest to broadest, we defined the perspectives as follows: payer and purchaser perspectives include costs associated with care that are to be reimbursed; a hospital perspective includes costs incurred by the hospital that may or may not be reimbursed; a healthcare or health services perspective includes in- and out-of-hospital costs incurred by the healthcare system such as post-hospital follow-up or future healthcare expenses; a patient perspective includes charges to be paid out-of-pocket by the patient; a societal perspective includes both healthcare and patient costs; and a policy maker perspective. We used the Drummond checklist to assess study quality (handbook.cochrane.org/).

We compiled the cost-effectiveness ratios (CERs) from each study in tabular format in order to facilitate comparisons between interventions. It was not uncommon for a cost-effectiveness study to present several CERs (the ratio of dollars expended to obtain the specific health outcome) or incremental CERs (ICERs; the difference in costs between the proposed and comparator therapies divided by the difference in effectiveness of the two therapies). All CERs or ICERs in this review were converted into U.S. dollars within the year that they were performed using historical values and then inflated to 2016 U.S. dollars using the consumer price index (https://www.bls.gov/cpi/tables.htm; accessed July 25, 2018).

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RESULTS

We identified 97 original cost-effectiveness studies published between 1993 and 2018 that were directly related to the care of patients admitted to the ICU (6–102) (Supplemental Tables 1–3, Supplemental Digital Content 1, http://links.lww.com/CCM/E530). The average number of published cost-effectiveness studies was 4.9 studies per year. Comparing the proportion of cost-effectiveness studies to the absolute number of randomized controlled trials in critical care published every 5 years over the past 2 decades showed a small trend toward increased publication rates (1998–2002 1.2% [8/661]; 2003–2007 3.6% [19/531]; 2008–2013 3.3% [31/930]; and 2014–2018 4.0% [33/833]). In the last 5 years (2014–2018), 20 (61%) of the 33 studies published in critical care used hypothetical cohorts and modeling scenarios (20577477–79828388–919394969799102103).

One-hundred fifty-six values for cost per QALY, cost per life saved, or an ICER comparing two interventions are presented. Twelve studies were funded by a foundation or a healthcare organization, 22 were government funded, and 19 were funded by the pharmaceutical industry or other commercial corporation. Seven studies were funded by a combination of government and healthcare organization funds. Healthcare was the most common perspective employed (51/97; 53%). In two cases, the purchaser was defined as an insurer (2837). A policy maker perspective was taken by Robotham et al (67); however, this was not well defined. The lifetime perspective was most commonly employed (n = 46). Costs and/or benefits were discounted at a rate of 3–6% in 59 studies (61%). Sensitivity analyses for treatment effectiveness or cost were conducted in 76 studies (78%).

The studies reviewed resulted in 156 CERs (51 cost per QALY; 37 cost per life-year saved; 2 CERs; and 66 ICERs) pertaining to the treatment of severe sepsis (n = 20), acute respiratory failure (n = 16), and general intensive care interventions (n = 61). Five studies (eight ICERs) demonstrated a cost savings of which three were based on hypothetical cohorts. CERs per QALY reported by each study ranged from –$1,363 per QALY (extracorporeal membrane oxygenation for patients with refractory hypoxemia and acute respiratory distress syndrome [ARDS] with expected survival of 40%) (74) to $266,470 per QALY (mechanical ventilation for patients ≥ 40 yr old hospitalized for stroke) (16). ICERs ranged from –$119,635 (hypothetical cohort of patients requiring either intermittent or continuous renal replacement therapy) (78) to $876,539 (continuous as compared with intermittent renal replacement therapy for acute renal failure) (70). Using the ratios reported by each study yielded a median ratio (interquartile range) of $29,952 ($6,052 to $70,178); one third (38/119: 33%) were below $20,000 per QALY, almost two-thirds (72/119: 61%) were below $50,000 per QALY, and more than three-quarters were below $100,000 per QALY (99/119: 80%). Twenty studies (17%) reported CERs greater than $100,000 per QALY (Figs. 2 and 3).

Figure 2.

Figure 2.

Figure 3.

Figure 3.

In Supplement Table 1 (Supplemental Digital Content 1, http://links.lww.com/CCM/E530), we present 20 published studies examining the CERs of sepsis therapies, including activated protein C (APC; n = 11: 1 study was a complex intervention that included early goal-directed therapy [EGDT], antibiotics, assessment for APC, tight glycemic control, and low tidal volume ventilation [LTVV]), EGDT or other resuscitation protocol (n = 7), polymerase chain reaction-based rapid adjustment of antibiotic therapy (n = 1), procalcitonin-guided treatment (n = 1), and ICU care as compared with ward care for severe sepsis (n = 1). Of interest, ICU care for severe sepsis report a cost per QALY of $3,338, although this cost is higher for older age groups reporting a range in cost per QALY of $507 to $19,429.

The CERs from mechanical ventilation studies range from $2,030 per QALY (intervention of ventilatory support for more than 6 hr) (53) to $266,470 per QALY (intervention of mechanical ventilation for acute stroke in patients > 40 yr old [16]; Supplement Table 2, Supplemental Digital Content 1, http://links.lww.com/CCM/E530). When looking at the provision of mechanical ventilation for acute respiratory failure in low, as compared with medium- and high-risk patients (based on Acute Physiology and Chronic Health Evaluation II score ≥ 10 and probability of survival) irrespective of age, the ICERs were $42,701 per QALY, $64,787 per QALY, and $161,968 per QALY, respectively (12). Patients receiving LTVV as compared to usual care had an ICER of $13,031 per QALY favoring a LTVV strategy (51). As a rescue therapy for intractable hypoxemia in severe ARDS, extracorporeal membrane oxygenation predicted the cost of $43,040 per QALY in a lifetime model, favoring its application as compared with standard mechanical ventilation practices (54).

Finally, admission to ICUs versus ward care was studied, and a wide range in costs can be seen for different interventions. This ranged from a cost savings of –$119,635 favoring continuous renal replacement therapy over intermittent renal replacement therapy in a hypothetical cohort of patients with acute renal failure to $207,617 per QALY for seriously ill hospitalized patients with new onset renal failure requiring dialysis (11) (Supplemental Table 3, Supplemental Digital Content 1, http://links.lww.com/CCM/E530). In the past few years, there was a trend toward publishing CEAs associated with quality improvement interventions or educational initiatives to promote best practices: implementation of a central line bundle (2476838592100) and multifaceted infection prevention programs that include promotion of hand hygiene (91), resuscitation bundles for sepsis (6973), and antibiotic stewardship (3891).

The majority of studies met all criteria for good study design on the Drummond checklist (Supplemental Tables 4–6, Supplemental Digital Content 1, http://links.lww.com/CCM/E530). For data collection, no studies reported productivity changes; variability in stating of methods to value benefits was seen as well as in the description of methods used for quantities and unit cost. Last, for analysis and interpretation of results, reporting of time horizons and discount rates was variable.

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DISCUSSION

We synthesized the results of published cost-effectiveness studies related to interventions for ICU patients and found that within the span of 25 years, 97 such studies were published with five studies reporting a cost savings (5%). In comparison, for diabetes-related ICERs 20% (n = 98/498) of studies demonstrate a cost savings (73% below the most often used threshold of $50,000 per QALY gained) and 8.2% (n = 52/636) are cost saving and more effective, that is, dominant (104). In addition to highlighting the paucity of cost-effectiveness literature in the ICU, our review also demonstrates the variability of methods that are used.

Why are there so few cost-effectiveness studies in critical care? One reason may be that in order to evaluate cost-effectiveness an intervention must first be of proven benefit. Unfortunately, few interventions have demonstrated improved outcomes in critical care. Second, critical care patients require many different interventions and have a variety of diagnoses; this heterogeneity makes it difficult to conduct CEAs focused on single items. Finally, there may be an unspoken acceptance within the ICU community that the specialty is just inherently expensive. Such a belief is dangerous, however, as escalating costs may eventually drive external organizations to perform such studies and shape debate. Timely exploration of the attitudes and cultural beliefs of the cost of critical care may be of benefit.

Outlining the current state of the literature provides insights into how the field might further mature. First, future research may benefit from the adoption of standards that both improve the quality of the studies and allow for greater ease of comparison of costs and effectiveness. For example, routine reporting of and accounting for severity of illness in cost-effectiveness models may allow for more meaningful comparisons across studies. Second, the fact that several of the ICERs showing good value actually are for therapies that ultimately proved to have no clinical benefit (e.g., the 11 studies of APC for sepsis) emphasizes the importance of completing analyses only for interventions with strongly proven utility. Completing CEA based on something less than two or three well-conducted trials can prematurely promote unproven therapies. Finally, it is important to note that critical care is often a supportive care field, and in this broader context, it may be interesting to consider its value for facilitating complex procedures or surgeries. In an increasingly resource-constrained environment and in the face of an aging/aged population, clinicians, administrators, and policy makers will all require results from economic analyses to make better-informed decisions regarding resource allocation across a spectrum of care (1105106).

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Keywords:

cost effectiveness; economic evaluation; intensive care

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