This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn.

The study assessed the cost-effectiveness of meropenem versus piperacillin/tazobactam antibiotics to treat severe pneumonia in patients in intensive care units after failing on first-line antibiotics. The authors concluded that meropenem was the preferred treatment as it was more likely to be more beneficial and less expensive than piperacillin/tazobactam. The study used valid and transparent cost-effectiveness methods that investigated uncertainty, which enhances the robustness of the authors’ conclusions.

Cost-utility analysis

The objective was to assess the cost-effectiveness of meropenem versus piperacillin/tazobactam for the treatment of severe pneumonia in patients in the intensive care unit after failure of first-line antibiotics (before or after admission to the intensive care unit).

Intravenous meropenem (1g/8 hours) was compared with piperacillin/tazobactam (4.5g/8 hours). Both treatments were administered for at least five days and a maximum of 14 days.

UK/hospital (critical care).

Analytical approach:

The analysis was based on a Markov model with a lifetime horizon. The authors stated that the analysis was carried out from the perspective of the UK NHS.

Effectiveness data:

Clinical inputs were from various sources, including a systematic review, evidence-based guidelines, analyses of Hospital Episode Statistics (HES), and other published studies. In particular, treatment effect, which represented the key input of the model, was from a published mixed-treatment comparison with data for piperacillin/tazobactam being obtained from a randomised clinical trial. Experts’ opinions were used to decide patients’ pathways. The only severe adverse events considered were Clostridium difficile–associated diarrhoea and the risk of acquiring ventilator-associated pneumonia

Monetary benefit and utility valuations:

Utility valuations were derived from published sources that assessed health-related quality-of-life (HRQoL) weights for patients in critical care centres or recovering on ward, as well as for discharged patients. The SF-36 (Short Form 36 Health Survey) and the EQ-5D (European Quality of life at five dimensions) questionnaires were used in these publications. Patients in critical care were assumed to have the same utility as unconscious individuals.

Measure of benefit:

Quality-adjusted life-years (QALYs) were used as the summary benefit measure and were discounted at an annual rate of 3.5%.

Cost data:

The economic analysis included two main cost categories: drugs (acquisition and administration) and health care (in critical care for ventilated and non-ventilated patients, in general ward, and post-discharge follow-up appointments). Drug costs were derived from the British National Formulary. Costs of inpatient stay and follow-up appointments were taken from the NHS Reference Costs. Costs of stay in general/respiratory wards were derived from the Personal Social Services Research Unit. Resource quantities were based on published sources. Costs were in UK pounds sterling (£). The price year was 2008.

Analysis of uncertainty:

A probabilistic sensitivity analysis was conducted to investigate uncertainty by assigning a distribution to each input of the model. Most of the probability distributions were derived from the same sources as the base case analysis. When these data were not available, specific assumptions were made. Drug acquisition costs were not subjected to uncertainty analysis as they were explicit values.

Treatment with piperacillin/tazobactam had an expected cost of £19,978 and QALYs were 4.654. Treatment with meropenem had an expected cost of £19,026 and QALYs were 4.768. Thus, meropenem was the dominant strategy as it was both less expensive and more effective.

The probabilistic analysis showed that meropenem was the dominant strategy in 94% of the simulations. Changes in the age of the patient population or the price of piperacillin/tazobactam did not alter substantially the base case findings.

The authors concluded that meropenem was the preferred treatment as it was more likely to be more beneficial and less expensive than piperacillin/tazobactam from the perspective of the UK NHS.

Interventions:

The rationale for the selection of the comparators was clear. Drug dosages were clearly reported and appear generalisable to other health care settings.

Effectiveness/benefits:

Clinical data were from several sources which were selected by the authors. The main clinical input, treatment effect, was taken from a mixed-treatment comparison, due to the lack of head-to-head clinical trials between the two options considered. Data for piperacillin/tazobactam were taken from a randomised clinical trial, while less information was provided about the sources of estimates for meropenem. The authors stated that this might be seen as a limitation of the analysis, but extensive sensitivity analyses were conducted on clinical parameters. QALYs were a valid benefit measure as infections have a strong impact on mortality and morbidity in this patient population. Utility weights were obtained using appropriate instruments and reflect the UK population, although some estimates were not available for critically-ill patients.

Costs:

The cost categories were consistent with the perspective of the study. Typical NHS sources were used to estimate costs and appear appropriate. Unit costs and resource quantities were presented separately for drug costs. Hospital stay was reported as total costs. Costs were not discounted as they were accrued only during the first year of the simulation. Probability distributions assigned to each cost item were reported and justified. The price year was stated, so reflation exercises in other time periods should be possible. Overall, the economic analysis was transparent and satisfactorily conducted.

Analysis and results:

An incremental approach was used to identify the optimal treatment but cost-effectiveness ratios were not calculated because of the dominance of meropenem. A full description of the simulation model (treatment pathways and clinical assumptions) was provided. Uncertainty was satisfactorily investigated using a Monte Carlo simulation, the methods and results being clearly described. The results were extensively presented. The authors acknowledged some limitations of the analysis in the lack of direct clinical comparison between the two antibiotics and the lack of some utility values. The study results appeared to be specific to the UK setting and might not be transferable to other jurisdictions.

Concluding remarks:

The study used valid and transparent cost-effectiveness methods that investigated uncertainty, which enhances the robustness of the authors’ conclusions.

Funded mainly by the Department of Health, UK. One author was an employee of AstraZeneca UK Ltd (distributors of meropenem) and received some support from AstraZeneca for work on the economic evaluation.