Monitoring a high-cost drug in critical care units

Introduction

Recombinant human activated protein C (APC) (Drotrecogin-alfa activated) was licensed for the treatment of severe sepsis following the large randomised controlled trial, PROWESS [1]. Subgroup analysis of PROWESS and the subsequent ADDRESS [2] study have shown that only the sickest patients (at least two organ failures or APACHE II score >25) benefit from APC. Treatment is associated with an increased risk of serious bleeding, and so the use of APC is contraindicated in patients at high risk for this complication. The cost of using APC is high, both financially and in terms of possible adverse effects, thus appropriate patient selection is crucial. Upon European Licensing in 2002, the South East London Critical Care Network (SELCCN) successfully bid for funding to use APC on the understanding that the hospital Trusts would provide regular usage reports.

Objective

To collect post-licence surveillance data of APC use in severe sepsis across a network of six ICUs (SELCCN). To certify adherence to agreed prescribing guidelines, and to monitor outcome (mortality), adverse events and financial data, thus ensuring best clinical practice and continued funding.

Methods

Guidelines for APC were agreed by the SELCCN. A reporting tool and supporting database reflecting these guidelines was designed and implemented to prospectively collect clinical and financial data. The collated data were reported monthly and progress was discussed at local and network meetings.

Results

Data were collected and analysed for 249 patients from November 2002 to June 2005. A total of 87% of patients met the agreed criteria for APC with an average expenditure of €7658 ± €3451 per patient. During treatment, 30 haemorrhagic events were cited with four reported as serious. Of those receiving APC, 126 (51%) where discharged home, 85 (34%) died in the ICU and nine (4%) died as post-ICU patients. Forty per cent of patients with ≥ 4 organs in failure at the time of APC administration were discharged home. Funding was retrieved in at least one site for all patients who received APC.

Discussion

These results demonstrate that it is possible to develop and ensure excellent adherence to consensus guidelines for the use of a high-cost, life-saving drug. A simple reporting tool allowed easy monitoring of selection criteria, patient outcome, and adverse events across the critical care network. The data show favourable patient outcome especially in those with ≥ 4 organs in failure (40% surviving) when compared with the average survival (19.4%) of a similar group of patients as measured in 91 ICUs throughout the UK [3]. This process of ongoing monitoring of essential data, including cost, ensured a continuous funding stream for this effective therapy and is the first report of such a process in critical illness.