Editorial <\/p>\n\n\n\n
May 19, 2025<\/p>\n\n\n\n
In this edition of JAMA Network Open,<\/em> the article \u201cCost-Effectiveness of \u03b12-Agonists for Intravenous Sedation in Patients With Critical Illness\u201d1<\/a><\/sup> derives from an in-trial cost-utility analysis of a 3-drug regimen for sedation in patients who are critically ill and mechanically ventilated. This is the health economic analysis of a no-effect pragmatic trial (A2B) comparing dexmedetomidine, clonidine, and propofol-based sedation with the duration of mechanical ventilation as the primary outcome.2<\/a><\/sup> The economic analysis, using quality-of-life measurements collected directly from patients, found no difference in the cost-utility, that is, dollars or pounds per quality-adjusted life-year (QALY), of these regimens. Given the results of the primary trial, the surprise to some readers may not be that the economic analysis shows no impact on the cost per QALY but it may be that a formal economic analysis was conducted and that JAMA Network Open<\/em> has chosen to publish it. We will try to persuade you that not only should the economic analysis have been done but that for this research topic, it might be the more important question.<\/a><\/p>\n\n\n\n So why should a health economic analysis be done when the efficacy trial finds no effect? The rationale behind cost-effectiveness analysis is that the information is used to spend health care resources on more cost-effective treatments to maximize the health of a population. It presumes a structure that allocates health care resources from treatments that are not cost-effective to treatments that are cost-effective. The National Health Service (NHS) in the UK has this mandate, which guided by the National Institute for Health and Clinicial Excellence (NICE) and uses trials like the one under consideration.3<\/a><\/sup> If a trial shows benefit in terms of its effect on the selected primary outcome, then a cost-effectiveness analysis will determine whether the NHS will fund this benefit. Since researchers do not know when they design or conduct the trial and whether it will show benefit, it is felt (in the UK at least) that it is best to design and conduct the economic analysis from the start. If the effectiveness trial finds an effect, funders need not wait to develop new information to decide whether to fund (or defund) the treatment.<\/a><\/p>\n\n\n\n A challenging question\u2014and one well beyond this editorial\u2014is what purpose cost-effectiveness analyses serve in the US and other countries where there is arguably no population-based system to assess treatments and redistribute health care resources based on economic analyses.4<\/a><\/sup> Demand for health care services will always exceed available resources, even in fragmented or market-based systems. And while the mechanisms of resource allocation differ, the fundamental need remains: to decide not just whether an intervention works, but whether it represents value for money. In that context, economic analyses are the only way to compare the value of competing interventions across different dimensions of outcome\u2014survival, function, time to recovery, quality of life, and cost. They offer a structured, evidence-based tool for navigating inevitable trade-offs and making better-informed decisions at the bedside, in hospitals, and at the level of health policy.<\/a><\/p>\n\n\n\n The A2B trial found no significant difference in the duration of mechanical ventilation across the 3 sedation strategies.1<\/a><\/sup> This was a reasonable primary outcome for the investigators to select\u2014prior studies had suggested that \u03b12-agonists might shorten ventilation by enabling finer control of sedation, agitation, and pain. But how meaningful is a modest reduction in ventilator hours from a patient\u2019s perspective? In our experience, patients recall very little from this phase of their critical illness. Would they accept the trade-off of fewer hours on a ventilator if it came with an increased risk of bradycardia, as observed in the trial? However, from the intensivist\u2019s standpoint outcomes like duration of mechanical ventilation and intensive care unit (ICU) length of stay are meaningful. Most trials of sedation and weaning protocols use duration of mechanical ventilation and ICU length of stay as outcomes. Not only do they reflect efficiency in care delivery, but they are also linked to the risk of ICU-acquired complications such as delirium and nosocomial infections. Had the underlying trial showed an effect on duration of mechanical ventilation, this economic analysis would have been crucial to persuade others of its value (both economic and on quality of life). But the trial showed no effect, so why the economic analysis?<\/a><\/p>\n\n\n\n First, the researchers did not know when they designed the economic analysis that the effectiveness analysis would show no effect, and building this analysis prospectively is essential. Prospectively embedding cost-effectiveness work ensures that high-quality, contemporaneous data\u2014particularly around health-related quality of life\u2014are available at the time of trial completion. Without it, investigators are forced to model quality of life and survival using other data. Second, even when a trial shows no clinical advantage, economic analysis can uncover hidden costs or inefficiencies. For example, had the bradycardia observed with \u03b12-agonists in this trial resulted in frequent pacing or downstream complications, those costs would have meaningfully altered the comparison. Without formal analysis, these ripple effects are invisible to the bedside clinician and easily missed in aggregate. Third, economic evaluation can help test critical secondary hypotheses, such as whether shorter ICU stays lead to better long-term outcomes. Previous studies have raised the possibility that reducing time on a ventilator may improve long-term quality of life by decreasing the risk of delirium and ICU-acquired weakness. Had dexmedetomidine or clonidine improved quality of life, the economic analysis might have answered an important scientific question that the primary clinical outcome would have missed entirely. Fourth, economic analyses of interventions that show no clinical effect help make the opportunity cost of continuing their use explicit and arguments for de-adoption more compelling. For example, take pulmonary artery catheters.5<\/a><\/sup> While recent trials have shown no meaningful clinical benefit, some clinicians still value the information these devices provide and may argue that with absent evidence of harm, the modest device cost justifies their continued use. However, a formal economic analysis quantifies the total cost of that preference, including not only the device itself, but also the associated nursing time, monitoring requirements, potential complications, and downstream use of additional therapies guided by catheter-derived data. Similarly, in the PRaCTICaL trial of intensive care follow-up clinics, the primary outcome of quality of life showed no difference but the cost-effectiveness analysis suggested withdrawing intensive care follow-up clinics from practice was cost-effective.6<\/a><\/sup> In this way, economic analyses help reveal what\u2019s being sacrificed, not just in dollars, but in clinical and operational opportunities.<\/a><\/p>\n\n\n\n Finally, we must consider the role of economic analysis within the broader landscape of critical care\u2014a field that has struggled to identify treatments that reduce mortality. Lung-protective ventilation and prone positioning for severe acute respiratory distress syndrome (ARDS), corticosteroids in selected forms of ARDS, and extracorporeal membrane oxygenation are a short list of therapies with probable survival benefits.7<\/a><\/sup> Beyond this, our greatest successes have come from strategies that reduce complications and ICU exposure rather than save lives directly. Weaning protocols, sedation minimization, early mobilization, ulcer and deep vein thrombosis prophylaxis, fluid deresuscitation, and corticosteroids for septic shock fall into this category.8<\/a><\/sup>,9<\/a><\/sup> These are not high-cost, high-tech innovations; they are labor-intensive interventions delivered by interprofessional teams and supported by sustained quality improvement. So how do we compare them? How do we judge the value of a sedative that reduces mechanical ventilation by a single day, against a complex delirium-reduction bundle that cuts delirium incidence in half, or corticosteroids that increase vasopressor-free days by 3? These effects are meaningful, but disparate\u2014and rarely reflected in a single, dominant outcome. When mortality is unchanged and benefits are measured in days, symptoms, or downstream utilization, we need tools to make sense of trade-offs that are clinical, operational, and economic. That tool is cost-minimization.10<\/a><\/sup><\/a><\/p>\n\n\n\n Cost-minimization analysis is an economical method used when competing interventions have been shown to, or we can assume, produce equivalent outcomes. In these cases, the analysis shifts focus entirely to cost.10<\/a><\/sup>-12<\/a><\/sup> It asks: given that both options are equally effective and safe, which achieves those results at a lower expense to the health system? By design, it avoids assumptions about marginal benefit and allows us to make evidence-based choices grounded solely in efficiency. Cost-minimization provides a framework for comparing these interventions on the 1 outcome that cuts across systems, patients, and policymakers: the total cost of achieving safe recovery. It also offers a way to prioritize interventions that require coordination, staffing, and infrastructure, precisely the interventions that are difficult to commercialize but essential to high-quality critical care. For most patients, the ICU is just one part, a particularly expensive part, of their health care journey\u2014a stop on their way to recovery from a stroke, a cancer surgery, or a car crash. Of course, we should not give up on looking for mortality reducing effects, but while we are looking for these, rigorous economic evaluation of our care to identify the most efficient ways to safely heal our patients provide very high value information, even when the trials show no effect.<\/p>\n","protected":false},"excerpt":{"rendered":" Editorial May 19, 2025 The Case for Eco […]<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":[],"categories":[24,23],"tags":[],"_links":{"self":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts\/28443"}],"collection":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=28443"}],"version-history":[{"count":1,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts\/28443\/revisions"}],"predecessor-version":[{"id":28445,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts\/28443\/revisions\/28445"}],"wp:attachment":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=28443"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=28443"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=28443"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}