Sarah Richards

Evaluating the use of plerixafor in stem cell mobilisation - an economic analysis of the PHANTASTIC trial.

Plerixafor is an effective haematopoietic stem cell mobilising agent in candidates for autologous transplantation, including patients with myeloma and lymphoma. Here we compare 98 plerixafor recipients in the PHANTASTIC trial with 151 historic controls mobilised by conventional chemotherapy (each with granulocyte colony‐stimulating factor, G‐CSF). Seventy (71.4%) plerixafor‐mobilised patients achieved the composite primary endpoint of ≥4 × 106 CD34+ cells kg−1 in ≤2 aphereses and no clinically significant neutropenia, compared to 48 (31.8%) historic controls (P < 0.001), and this significant advantage was maintained in scenario analyses testing components of this composite endpoint. A patient‐level cost analysis was undertaken for 249 patients, which included the cost of remobilising patients where initial mobilisation had failed. Combined mean treatment cost for plerixafor mobilised patients was £12,679 compared with £11,694 for historical controls. However, plerixafor produces an average saving of £3,828 per lymphoma patient but average cost increase by £5,245 per myeloma patient. The present data demonstrate cost‐effectiveness for plerixafor as a first line mobilisation agent, certainly for lymphoma patients, where substantial resource savings and achievement of the primary endpoint are likely. J. Clin. Apheresis 31:434–442, 2016.

Through a Glass Darkly: Economics and Personalised Medicine

Personalised medicine and pharmacogenetic-test-guided treatment strategies will be of increasing importance in the future, both in terms of healthcare provision and evaluation. It is well recognised that significant variability exists in the response of patients to drugs resulting from genetic or biological variations; however, we are only now gradually becoming aware of the complexities involved. Enormous variability occurs in the risk-benefit ratio that will be experienced by each individual patient as a consequence of their overall genetic make-up. Although not a panacea, enhanced scientific knowledge of the genetic basis for such variability offers the potential for a more ‘tailored’ approach to prescribing in the future, making it more closely attuned to the needs of the individual patient. Such ‘personalised’ medicine has the potential to revolutionise care provision in a manner that provides a range of challenges to current structures and processes of ‘conventional’ healthcare delivery. The aim of this paper is to outline such challenges and analyse potential ways in which they may be addressed in the future. It provides non-expert readers with a non-technical case study of the complexities inherent in the evaluation of a pharmacogenetic-test-guided treatment strategy from a health economic perspective. Wherever possible, technical issues have been minimised; however, references are provided for readers who wish to enhance their knowledge of the pharmacological basis of the case study of cytochrome P450 test-guided treatment. The case study aims simply to illustrate the approach and difficulties encountered in the health economic evaluation of complex pharmacogenetic technologies. Such technologies present a range of new and complex issues which have crucial implications for health economists attempting to obtain an accurate assessment of the ‘value’ of the technology in clinical practice in an array of patient subgroups. Personalised medicine is the future and this paper highlights how pharmaceutical manufacturers, clinicians, regulators and other stakeholders must all play their part in the inevitable and accelerating move into this complex and uncertain future.

Plerixafor is cost‐effective compared to conventional chemotherapy for first‐line haematopoietic stem cell mobilization: Data from the PHANTASTIC trial

Plerixafor is an effective haematopoietic stem cell mobilising agent in candidates for autologous transplantation, including patients with myeloma and lymphoma. Here we compare 98 plerixafor recipients in the PHANTASTIC trial with 151 historic controls mobilised by conventional chemotherapy (each with granulocyte colony‐stimulating factor, G‐CSF). Seventy (71.4%) plerixafor‐mobilised patients achieved the composite primary endpoint of ≥4 × 106 CD34+ cells kg−1 in ≤2 aphereses and no clinically significant neutropenia, compared to 48 (31.8%) historic controls (P < 0.001), and this significant advantage was maintained in scenario analyses testing components of this composite endpoint. A patient‐level cost analysis was undertaken for 249 patients, which included the cost of remobilising patients where initial mobilisation had failed. Combined mean treatment cost for plerixafor mobilised patients was £12,679 compared with £11,694 for historical controls. However, plerixafor produces an average saving of £3,828 per lymphoma patient but average cost increase by £5,245 per myeloma patient. The present data demonstrate cost‐effectiveness for plerixafor as a first line mobilisation agent, certainly for lymphoma patients, where substantial resource savings and achievement of the primary endpoint are likely. J. Clin. Apheresis 31:434–442, 2016.

A Single-Center Randomized Trial of Intraoperative Zero-Balanced Ultrafiltration During Cardiopulmonary Bypass for Patients With Impaired Kidney Function Undergoing Cardiac Surgery.

OBJECTIVES The authors investigated whether zero-balance ultrafiltration (Z-BUF) during bypass significantly improves clinical and cost outcomes or biomarkers of kidney injury for patients with preoperative kidney impairment (estimated glomerular filtration rate [eGFR]<60 mL/minute) undergoing cardiac surgery. DESIGN A single-center randomized controlled trial recruited, patients between 2010 and 2013, with a 12-months follow-up. SETTING Hospital. PARTICIPANTS One hundred ninety-nine patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). INTERVENTIONS Patients were assigned randomly to receive zero-balance ultrafiltration (Z-BUF) or not, with stratification for degree of kidney dysfunction and diabetes. MEASUREMENTS AND MAIN RESULTS The authors assessed clinical efficacy and kidney function biomarkers. Cumulative probability of discharge from the intensive care unit (ICU) was assessed by Kaplan-Meier plots and was found not to be significantly different between the two trial arms (p = 0.61). After adjusting for EuroSCORE, diabetes, eGFR, cardioplegia types and type of surgery in a Cox proportional hazard model, hazard ratios (HR) for ICU length of stay between the Z-BUF and no-Z-BUF groups was not significantly different: HR (95% CI): 0.89 (0.66, 1.20; p = 0.44). In contrast, significant reductions in postoperative chest infections and the composite of clinical endpoints (death, strokes, and myocardial infarctions) in the Z-BUF group were observed. In addition, Z-BUF significantly abrogated the rise in the kidney damage markers urinary NGAL/creatinine ratio, urea, creatinine and eGFR during CPB and adverse events risks. CONCLUSIONS Z-BUF during bypass surgery is associated with significant reductions in morbidity and biomarkers of CPB-induced acute kidney injury soon after CPB, which are indicative of clearance of inflammatory/immune mediators from the circulation.