a cost-effectiveness study of enteral immune modulating nutrition in intensive care patients...
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A cost-effectiveness study of enteral immune modulating nutrition in intensive care patients
Elizabeth CoatesClare Hibbert
Medical Economics and Research Centre, Sheffield (MERCS)
CIMC 2001
What is immunonutrition?
The term given to describe special enteral feeds containing:
– Arginine– Omega-3 fatty acids– Nucleotides– (and sometimes, glutamine)
Ref: Barbul A. Immunonutrition comes of age. Crit Care Med 2000;28:3:884-885 (editorial).
What is cost-effectiveness analysis?
Treatment ADifferences
Treatment B
Ref: Drummond MF, O’Brien B, Stoddart GL, Torrance GW. Methods for the economic evaluation of health care programmes. 2nd edition. Oxford University Press, 1997.
Rationale
1. The nature of critically ill patients’
conditions
–Malnutrition–Compromise of immune system
–Infection
All these increase:
• Length of ICU and hospital stay
• Morbidity• Mortality• Resource
consumption• Costs of care
2. Growing evidence on the benefits of immunonutrition…
3. Despite these findings, and the increasing pressure to curtail expenditure
The cost-effectiveness issue has rarely been explored…
Aim of the study
To estimate the cost-effectiveness of immunonutrition (IMN) in reducing infection rates in critically ill adult patientswhen compared with standard enteral nutrition.
Outcome measure
A reduction in the duration of days of
infection in ICU patients with sepsis
(from NHS perspective)
Literature review
Rationale
Literature searchDatabases
• MedLine• Embase• CINAHL
Search terms• Immunonutriton• Nutrition• Enteral feed• Intensive care• Critical care• Costs• Cost-effectiveness
(analysis)
Review of the literature…
Studies of IMN
• Atkinson (1998) reduced ICU & hospital LOS and duration of ventilation
• Bower (1995) reduction in acquired infections and hospital LOS
• Galban (2000) reduction in infection rate and lower mortality rate
Key paper
Beale et al. Immunonutrition
in the critically ill: A systematic review of clinical outcome.
Critical Care Medicine 1999; 27:12: 2799-2805.
Benefits of immunonutrition?
IMNHospital
LOS2.8 days,
CI=1.3, 4.4 daysP=0.0003
VentilatorDays
2.9 days, CI=0.1, 5.9 daysP=0.04
InfectionRelative risk
0.60, CI=0.41,0.86P=0.006
Ref: Beale et al. Immunonutrition in the critically ill: A systematic review of clinical outcome.Crit Care Med 1999;27:12:2799-2805
Rationale
Literature review
Methods
Methodology
The evaluation of cost-effectiveness was based on two factors:
1. Evidence of effectiveness of IMN from the 12 RCTs included in the meta-analysis (1482 patients)
2. Retrospective cost data on individual ICU patients at the Royal Hallamshire Hospital
Methods
Clinical effectiveness
Rationale
Literaturereview
RCTs included in the meta-analysis
• Atkinson S, Sieffert E, Bihari D on behalf of the Guy’s Hospital Intensive Care Group: A prospective randomised double-blind clinical trial of enteral immunonutrition in the critically ill. Critical Care Medicine 1998; 26:1164-1172
• Bower RH, Cerra FB, Bershadsky B et al: Early enteral administration of a formula (IMPACT) supplemented with arginine, nucleotides, and fish oil in intensive care unit patients: Results of a multicenter, prospective, randomised, clinical trial. Critical Care Medicine 1995; 23:436-449
• Cerra FB, Lehman S, Konstantinides N, et al: Effect of enteral nutrient on in vitro tests of immune function in ICU patients: A preliminary report. Nutrition 1990; 6:84-87
• Daly JM, Lieberman MD, Goldfine J, et al: Enteral nutrition with supplemental arginine, RNA and omega-3 fatty acids in patients after operation: Immunologic, metabolic, and clinical outcome. Surgery 1992; 112:56-67
• Daly JM, Weintraub FN, Shou J, et al: Enteral nutrition during multimodality therapy in upper gastrointestinal cancer patients. Annals of Surgery 1995; 221:327-338
• Galban C, Carlos Montejo J, Mesejo A, et al: An immune-enhancing enteral diet reduces mortality and episodes of bacteremia in septic intensive care unit patients. Critical Care Medicine 2000; 28, 3:643-648
• Kudsk KA, Minard G, Croce MA, et al: A randomised trial of isonitrogenous enteral diets after severe trauma: An immune-enhancing diet reduces septic complications. Annals of Surgery 1996; 224:531-540
• Moore FA, Moore EE, Kudsk KA, et al: Clinical benefits of an immune-enhancing diet for early post injury enteral feeding. Journal of Trauma 1994; 37:607-615
• Schilling J, Vranjes N, Fierz W et al: Clinical outcome and immunology of postoperative arginine, omega-3 fatty acids, and nucleotide-enriched enteral feeding: A randomised prospective comparison with standard enteral and low calorie/low fat solutions. Nutrition 1996; 12:423-429
• Senkal M, Mumme A, Eickhoff U, et al: Early postoperative enteral immunonutriton: Clinical outcome and cost-comparison analysis in surgical patients. Critical Care Medicine 1997; 25:1489-1496
• Weimann A, Bastian L, Grotz M, et al: Influence of arginine, omega-3 fatty acids and nucleotide-supplemented enteral support on systematic inflammatory response syndrome and multiple organ failure in patients after severe trauma. Nutrition 1998; 14:165-172
• Braga M, Gianotti L, Vignali A et al: Artificial nutrition after major abdominal surgery: Impact of route of administration and composition of the diet. Critical Care Medicine 1998; 26:24-30.
Evaluation of the clinical evidence
• Assessment of the studies’ quality using the CONSORT statement
• This provides a standard method for the reporting (and assessment) of randomised controlled trials
Ref: The Standards of Reporting Trials Group. Improving the quality of reporting of randomized controlled trials. The CONSORT statement. JAMA 1996; 28:8:637-9
Translate the benefits into %s
IMNInfectio
n40%
Reduction
Worst-caseScenario@ 14%
Best-caseScenario@ 59%
Ref: Beale et al. Immunonutrition in the critically ill: A systematic review of clinical outcome. Crit Care Med1999;27:12:2799-2805
Methods
Clinical effectiveness
Rationale
Literaturereview
Cost data
Infection
• Decided to use sepsis as the case study in my economic analysis for three reasons:
1. Most frequent type of infection in the meta-analysis
2. Availability of previously published data (from RHH) on costs of sepsis.
3. Significance of the infection
Ref: Edbrooke et al. The patient-related costs of care for sepsis patients in a United Kingdom adult general intensive care unit. Crit Care Med 1999; 27:9:1760-1767
What is sepsis?• Defined as severe sepsis; associated with at
least two of the following:– Elevated plasma lactate or metabolic acidosis, arterial pH <7.3 or base
excess -5mEq/L
– Hypoxemia, either PaO2/F102 <280 or hypoxemia requiring mechanical ventilation
– Platelet count decrease to less than half of a previous count or <100,000/mm3 or unexplained coagulopathy
– Oliguria, urine output <30 mL/hr or <0.5 mL/kg/hr for at least 2hrs that is refractory to an adequate fluid challenge (>500 mL)
• Or early septic shock:– Severe sepsis associated with hypotension (systolic blood
pressure <90 mm Hg or reduction in systolic blood pressure of >40 mm Hg in the absence of causes other than septic shock) receiving vasopressors at therapeutic doses for up to 2hrs before study drug dosing
Ref: American College of Chest Physicians and the Society of Critical Care Medicine held in August1991 and adapted by Hoffman La Roche AG
The patients
• 213 admitted to the ICU at RHH over ten months during 1995-96.
• 36 with evidence of sepsis at any point during their ICU stay (16.9%)
• 177 without evidence of sepsis (83.1%)
Ref: Edbrooke et al. The patient-related costs of care for sepsis patients in a United Kingdom adult general intensive care unit. Crit Care Med 1999; 27:9:1760-1767
Cost analysisCalculated total costs for each cost
component:
• Drugs
• Fluids
• Consumables
• Medical Imaging
300
280
260
240
220
200
180
160
140
120
100
80
60
40
20
290
270
250
230
210
190
170
150
130
110
90
70
50
30
10
Cost analysis
Calculated total costs for each cost component:
• Nurses
• Doctors
• Other staff (technical and admin)
Methods
Clinicaleffectiveness
Rationale
Literature review
Cost data
Results
Cost differencesSepsis patients Non-sepsis patients
£537 per day £425 per day
S
LOS = 14.08 days LOS = 3.31 days
£7560 per patient
£1407 per patient
Cost-Cost-effectiveness of effectiveness of
IMN?IMN?
Enteral Feed Reduction in rate of infection (%)
Cost (£) (per patient)
Estimated change in cost (£) (per patient)
Number of days of infection avoided
Estimated change in cost (£) (per day of infection avoided)
Daily additional cost of IMN=£35
Standard 7558
Immunonutrition
14 7830 +273 1.97 +138
40 7421 -137 5.63 -24
59 7122 -436 8.31 -52
Cost-effectiveness
Reduction in duration of sepsis
Sepsis rate 16.9% Using standard feed =
(cost per sepsis patient x 16.9)
+(cost per non-sepsis
patient x 83.1)
=£244,621
On a larger scale: per 100 patients
X 10
Costs Before (using standard enteral feed)
Reduction in duration of sepsis
Sepsis rate 16.9% Using IMN = (cost per
sepsis patient + cost of feed x 16.9)
+(cost per non-sepsis
patient x 83.1)
=£242,311
On a larger scale: per 100 patients
X 10
Costs After(using immunonutrition)
Methods
Clinical effectiveness
Rationale
Literaturereview
Cost data
Results
Sensitivity analysis
Sensitivity analysis
• With cheapest patients, IMN always more expensive, e.g.
• 14% reduction = +£469: per patient
• 40% reduction = +£425: per patient
• 59% reduction = +£393: per patient
Sensitivity analysis
• With most expensive patients, IMN can be cost-effective, e.g.
• 14% reduction = +£76: per patient
• 40% reduction = -£698: per patient
• 59% reduction = -£1265: per patient
Sensitivity analysis
Methods
Clinical effectiveness
Rationale
Literaturereview
Cost data
Results
Problems
Problems with this approach (i)
• Assumptions about:– Infection type– Duration of infection– Costs associated with treating
infection– Cost of the treatment
• These will all vary between ICUs
Problems with this approach
(ii)• Ignores the potential length of
stay reduction
• Therefore, small cost savings
• Doesn’t account for the recurrence of infection.
Sensitivityanalysis
Methods
Clinicaleffectiveness
Rationale
Literaturereview
Results
Problems Conclusion
Cost data
Conclusion
• IMN can be cost-effective
• Need to ensure a certain level of clinical efficacy
• Need to identify safe population who can demonstrate benefits worth the additional costs
Recommendation
In an ideal situation, an economic evaluation would be completed alongside a multicentre RCT…