Costs and consequences in perioperative care: Analytic models in studies on pain treatment and on haemodynamic optimization of elderly patients

ABSTRACT Background Because resources are scarce in health care, costs and consequences of new interventions must be assessed to support informed policy decisions. This thesis analyses the cost-effectiveness of advanced postoperative pain treatment and perioperative haemodynamic optimization by applying decision modelling as an analytic framework. 1. Postoperative pain treatment refers to epidural analgesia and to patient-controlled in travenous analgesia. Based on the superior analgesic effect found in clinical trials, epidural analgesia is regarded as the gold standard following major surgery, but a drawback is the high failure rate (10–15%). Considering that approximately 40 000 patients are treated by epidural analgesia per year in Sweden, costs and consequences of this clinical problem are substantial. 2. Haemodynamic optimization refers to fluid protocols targeted to increase blood flow, referred to as goal-directed haemodynamic treatment. These protocols are beneficial in the perioperative care of high-risk patients, but there is lack of evidence in elderly patients. In Sweden 20 000 patients are operated on each year for proximal femoral fracture, with poor postoperative outcome. Large trials are required to assess whether any protocol of the goaldirected haemodynamic treatment is beneficial in the elderly population, in terms of outcome and health care costs. Considering the cost and complexity of such a trial, a prior costeffectiveness analysis might be adequate to guide the initiation of such a trial. Methods 1. Epidural analgesia vs. patient-controlled intravenous analgesia: Paper I: A decision-analytic cost-effectiveness model was developed to analyse data of a clinical database on pain treatment following major abdominal surgery. Paper II: Postoperative intensive care costs were analysed on data from patients included in a previously published trial on postoperative pain treatment following thoracoabdominal oesophagectomy. 2. Goal-directed haemodynamic treatment vs. traditional fluid treatment in elderly patients: Paper III: A decision-analytic cost-effectiveness model was developed, and relevant data from published trials and national registries were analysed. As the clinical outcome for elderly patients was previously unknown, reasonable estimates are applied in the model. Paper IV: The prior cost-effectiveness analysis (Paper III) guided the initiation of a large (n = 460) randomized clinical trial in elderly patients with proximal femoral fracture, and interim analyses of safety and efficacy were conducted (n = 100). Given the interim efficacy data, the monetary value of further data collection was analysed by calculating the expected value of perfect information. Results 1. The epidural analgesia is not cost-effective and no saving of the postoperative costs can be achieved, given the available evidence in Swedish clinical routine (Papers I–II). 2. The goal-directed haemodynamic treatment is predicted to be cost-effective in elderly patients, based on the available evidence and on the prior estimates of clinical outcome before the initiation of the trial. The expected value of perfect information is high, indicating that collecting further data by continuing the trial is potentially worthwhile (Papers III–IV). Conclusions 1. The analyses of epidural analgesia challenge its position as the gold standard and may assist revision of clinical policy decisions on postoperative pain treatment. 2. The analyses of the goal-directed haemodynamic treatment in elderly patients using a decision-analytic cost-effectiveness model suggest the usefulness of the initiation and continuation of a large clinical trial

Value of information: interim analysis of a randomized, controlled trial of goal-directed hemodynamic treatment for aged patients

Background A randomized, controlled trial, intended to include 460 patients, is currently studying peroperative goal-directed hemodynamic treatment (GDHT) of aged hip-fracture patients. Interim efficacy analysis performed on the first 100 patients was statistically uncertain; thus, the trial is continuing in accordance with the trial protocol. This raised the present investigation’s main question: Is it reasonable to continue to fund the trial to decrease uncertainty? To answer this question, a previously developed probabilistic cost-effectiveness model was used. That model depicts (1) a choice between routine fluid treatment and GDHT, given uncertainty of current evidence and (2) the monetary value of further data collection to decrease uncertainty. This monetary value, that is, the expected value of perfect information (EVPI), could be used to compare future research costs. Thus, the primary aim of the present investigation was to analyze EVPI of an ongoing trial with interim efficacy observed. Methods A previously developed probabilistic decision analytic cost-effectiveness model was employed to compare the routine fluid treatment to GDHT. Results from the interim analysis, published trials, the meta-analysis, and the registry data were used as model inputs. EVPI was predicted using (1) combined uncertainty of model inputs; (2) threshold value of society’s willingness to pay for one, quality-adjusted life-year; and (3) estimated number of future patients exposed to choice between GDHT and routine fluid treatment during the expected lifetime of GDHT. Results If a decision to use GDHT were based on cost-effectiveness, then the decision would have a substantial degree of uncertainty. Assuming a 5-year lifetime of GDHT in clinical practice, the number of patients who would be subject to future decisions was 30,400. EVPI per patient would be €204 at a €20,000 threshold value of society’s willingness to pay for one quality-adjusted life-year. Given a future population of 30,400 individuals, total EVPI would be €6.19 million. Conclusions If future trial costs are below EVPI, further data collection is potentially cost-effective. When applying a cost-effectiveness model, statements such as ‘further research is needed’ are replaced with ‘further research is cost-effective and ‘further funding of a trial is justified’.Funding Agencies|Stockholm County Council, Sweden|SLL 20080063|</p

Cost-effectiveness Analysis of Goal-directed Hemodynamic Treatment of Elderly Hip Fracture Patients: Before Clinical Research Starts.

BACKGROUND: Health economic evaluations are increasingly used to make the decision to adopt new medical interventions. Before such decisions, various stakeholders have invested in clinical research. But health economic factors are seldom considered in research funding decisions. Cost-effectiveness analyses could be informative before the launch of clinical research projects, particularly when a targeted intervention is resource-intensive, total cost for the trial is very high, and expected gain of health benefits is uncertain. This study analyzed cost-effectiveness using a decision analytic model before initiating a large clinical research project on goal-directed hemodynamic treatment of elderly patients with hip fracture. METHODS:: A probabilistic decision analytic cost-effectiveness model was developed; the model contains a decision tree for the postoperative short-term outcome and a Markov structure for long-term outcome. Clinical effect estimates, costs, health-related quality-of-life measures, and long-term survival constituted model input that was extracted from clinical trials, national databases, and surveys. Model output consisted of estimated medical care costs related to quality-adjusted life-years. RESULTS:: In the base case analysis, goal-directed hemodynamic treatment reduced average medical care costs by &OV0556;1,882 and gained 0.344 quality-adjusted life-years. In 96.5% of the simulations, goal-directed hemodynamic treatment is less costly and provides more quality-adjusted life-years. The results are sensitive to clinical effect size variations, although goal-directed hemodynamic treatment seems to be cost-effective even with moderate clinical effect. CONCLUSION:: This study demonstrates that cost-effectiveness analysis is feasible, meaningful, and recommendable before launch of costly clinical research projects