Article: The cost-effectiveness of diagnostic management strategies for adults with minor head injury.[show abstract] [hide abstract]
ABSTRACT: To estimate the cost-effectiveness of diagnostic management strategies for adults with minor head injury. A mathematical model was constructed to evaluate the incremental costs and effectiveness (Quality Adjusted Life years Gained, QALYs) of ten diagnostic management strategies for adults with minor head injuries. Secondary analyses were undertaken to determine the cost-effectiveness of hospital admission compared to discharge home and to explore the cost-effectiveness of strategies when no responsible adult was available to observe the patient after discharge. The apparent optimal strategy was based on the high and medium risk Canadian CT Head Rule (CCHRhm), although the costs and outcomes associated with each strategy were broadly similar. Hospital admission for patients with non-neurosurgical injury on CT dominated discharge home, whilst hospital admission for clinically normal patients with a normal CT was not cost-effective compared to discharge home with or without a responsible adult at £39 and £2.5 million per QALY, respectively. A selective CT strategy with discharge home if the CT scan was normal remained optimal compared to not investigating or CT scanning all patients when there was no responsible adult available to observe them after discharge. Our economic analysis confirms that the recent extension of access to CT scanning for minor head injury is appropriate. Liberal use of CT scanning based on a high sensitivity decision rule is not only effective but also cost-saving. The cost of CT scanning is very small compared to the estimated cost of caring for patients with brain injury worsened by delayed treatment. It is recommended therefore that all hospitals receiving patients with minor head injury should have unrestricted access to CT scanning for use in conjunction with evidence based guidelines. Provisionally the CCHRhm decision rule appears to be the best strategy although there is considerable uncertainty around the optimal decision rule. However, the CCHRhm rule appears to be the most widely validated and it therefore seems appropriate to conclude that the CCHRhm rule has the best evidence to support its use.Injury 08/2011; 43(9):1423-31. · 1.98 Impact Factor
Article: Diagnostic management strategies for adults and children with minor head injury: a systematic review and an economic evaluation.[show abstract] [hide abstract]
ABSTRACT: Patients with minor head injury [Glasgow Coma Scale (GCS) score 13-15] have a small but important risk of intracranial injury (ICI) that requires early identification and neurosurgical treatment. Diagnostic assessment can use either a clinical decision rule or unstructured assessment of individual clinical features to identify those who are at risk of ICI and in need of computerised tomography (CT) scanning and/or hospital admission. Selective use of CT investigations helps minimise unnecessary radiation exposure and resource use, but can lead to missed opportunities to provide early treatment for ICI. To determine the diagnostic accuracy of decision rules, individual clinical characteristics, skull radiography and biomarkers, and the clinical effectiveness and cost-effectiveness of diagnostic management strategies for minor head injury (MHI). Several electronic databases [including MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, Cumulative Index to Nursing and Allied Health Literature (CINAHL), EMBASE and The Cochrane Library] were searched from inception to April 2009 (updated searches to March 2010 were conducted on the MEDLINE databases only). Searches were supplemented by hand-searching relevant articles (including citation searching) and contacting experts in the field. For each of the systematic reviews the following studies were included (1) cohort studies of patients with MHI in which a clinical decision rule or individual clinical characteristics (including biomarkers and skull radiography) were compared with a reference standard test for ICI or need for neurosurgical intervention and (2) controlled trials comparing alternative management strategies for MHI. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool (for the assessment of diagnostic accuracy) or criteria recommended by the Effective Practice and Organisation of Care Review Group (for the assessment of management practices). Where sufficient data existed, a meta-analysis was undertaken to generate pooled estimates of diagnostic parameters. A decision-analysis model was developed using Simul8 2008 Professional software (Simul8 Corporation, Boston, MA, USA) to estimate the costs and quality-adjusted life-years (QALYs) accrued by management strategies for MHI. The model took a lifetime horizon and NHS perspective. Estimates of the benefits of early treatment, harm of radiation exposure and long-term costs were obtained through literature reviews. Initial analysis was deterministic, but probabilistic sensitivity analysis was also performed. Secondary analyses were undertaken to explore the trade-off between sensitivity and specificity in diagnostic strategies and to determine the cost-effectiveness of scenarios involving hospital admission. The literature searches identified 8003 citations. Of these, 93 full-text papers were included for the assessment of diagnostic accuracy and one for the assessment of management practices. The quality of studies and reporting was generally poor. The Canadian CT Head Rule (CCHR) was the most widely validated adult rule, with sensitivity of 99-100% and 80-100% for neurosurgical and any ICI, respectively (high- or medium-risk criteria), and specificity of 39-51%. Rules for children had high sensitivity and acceptable specificity in derivation cohorts, but limited validation. Depressed, basal or radiological skull fracture and post-traumatic seizure (PTS) [positive likelihood ratio (PLR) > 10]; focal neurological deficit, persistent vomiting, decrease in GCS and previous neurosurgery (PLR 5-10); and fall from a height, coagulopathy, chronic alcohol use, age > 60 years, pedestrian motor vehicle accident (MVA), any seizure, undefined vomiting, amnesia, GCS < 14 and GCS < 15 (PLR 2-5) increased the likelihood of ICI in adults. Depressed or basal skull fracture and focal neurological deficit (PLR > 10), coagulopathy, PTS and previous neurosurgery (PLR 5-10), visual symptoms, bicycle and pedestrian MVA, any seizure, loss of consciousness, vomiting, severe or persistent headache, amnesia, GCS < 14, GCS < 15, intoxication and radiological skull fracture (PLR 2-5) increased the likelihood of ICI in children. S100 calcium-binding protein B had pooled sensitivity of 96.8% [95% highest-density region (HDR) 93.8% to 98.6%] and specificity of 42.5% (95% HDR 31.0% to 54.2%). The only controlled trial showed that early CT and discharge is cheaper and at least as effective as hospital admission. Economic analysis showed that selective CT use dominated 'CT all' and 'discharge all' strategies. The optimal strategies were the CCHR (adults) and the CHALICE (Children's Head injury Algorithm for the prediction of Important Clinical Events) or NEXUS II (National Emergency X-Radiography Utilization Study II) rule (children). The sensitivity and specificity of the CCHR (99% and 47%, respectively) represented an appropriate trade-off of these parameters. Hospital admission dominated discharge home for patients with non-neurosurgical injury, but cost £39 M per QALY for clinically normal patients with a normal CT. The CCHR is widely validated and cost-effective for adults. Decision rules for children appear cost-effective, but need further validation. Hospital admission is cost-effective for patients with abnormal, but not normal, CT. The main research priorities are to (1) validate decision rules for children; (2) determine the prognosis and treatment benefit for non-neurosurgical injuries; (3) evaluate the use of S100B alongside a validated decision rule; (4) evaluate the diagnosis and outcomes of anticoagulated patients with MHI; and (5) evaluate the implementation of guidelines, clinical decision rules and diagnostic strategies. Formal expected value of sample information analysis would be recommended to appraise the cost-effectiveness of future studies. The National Institute for Health Research Health Technology Assessment programme.Health technology assessment (Winchester, England). 08/2011; 15(27):1-202.
Article: Prescribing high-dose lipid-lowering therapy early to avoid subsequent cardiovascular events: is this a cost-effective strategy?R Ara, A Pandor, J Stevens, R Rafia, S E Ward, A Rees, P N Durrington, T M Reynolds, A S Wierzbicki, M Stevenson[show abstract] [hide abstract]
ABSTRACT: While evidence shows high-dose statins reduce cardiovascular events compared with moderate doses in individuals with acute coronary syndrome (ACS), many primary care trusts (PCT) advocate the use of generic simvastatin 40 mg/day for these patients. Data from 28 RCTs were synthesized using a mixed treatment comparison model. A Markov model was used to evaluate the cost-effectiveness of treatments taking into account adherence and the likely reduction in cost for atorvastatin when the patent expires. There is a clear dose-response: rosuvastatin 40 mg/day produces the greatest reduction in low-density lipoprotein cholesterol (56%) followed by atorvastatin 80 mg/day (52%), and simvastatin 40 mg/day (37%). Using a threshold of £20,000 per QALY, if adherence levels in general practice are similar to those observed in RCTs, all three higher dose statins would be considered cost-effective compared to simvastatin 40 mg/day. Using the net benefits of the treatments, rosuvastatin 40 mg/day is estimated to be the most cost-effective alternative. If the cost of atorvastatin reduces in line with that observed for simvastatin, atorvastatin 80 mg/day is estimated to be the most cost-effective alternative. Our analyses show that current PCT policies intended to minimize primary care drug acquisition costs result in suboptimal care.European journal of preventive cardiology. 04/2011; 19(3):474-83.
Article: Bevacizumab in combination with fluoropyrimidine-based chemotherapy for the first-line treatment of metastatic colorectal cancer.[show abstract] [hide abstract]
ABSTRACT: This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of bevacizumab in combination with fluoropyrimidine-based chemotherapy for the first-line treatment of metastatic colorectal cancer based on the manufacturer's submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. Evidence was available in the form of one phase III, multicentre, multinational, randomised, open-label study (NO16966 trial). This two-arm study was originally designed to demonstrate the non-inferiority of oral capecitabine plus oxaliplatin (XELOX) compared with 5-fluorouracil plus folinic acid plus oxaliplatin (FOLFOX)-4 in adult patients with histologically confirmed metastatic colorectal cancer who had not previously been treated. Following randomisation of 634 patients, the open-label study was amended to include a 2 × 2 factorial randomised (partially blinded for bevacizumab) phase III trial with the coprimary objective of demonstrating superiority of bevacizumab in combination with chemotherapy compared with chemotherapy alone. Measured outcomes included overall survival, progression-free survival, response rate, adverse effects of treatment and health-related quality of life. The manufacturer's primary pooled analysis of superiority (using the intention-to-treat population) showed that after a median follow-up of 28 months, the addition of bevacizumab to chemotherapy significantly improved progression-free survival and overall survival compared with chemotherapy alone in adult patients with histologically confirmed metastatic colorectal cancer who were not previously treated [median progression-free survival 9.4 vs 7.7 months (absolute difference 1.7 months); hazard ratio (HR) 0.79, 97.5% confidence interval (CI) 0.72 to 0.87; p = 0.0001; median overall survival 21.2 vs 18.9 months (absolute difference 2.3 months); HR 0.83, 97.5% CI 0.74 to 0.93; p = 0.0019]. The NO16966 trial was of reasonable methodological quality and demonstrated a significant improvement in both progression-free survival and overall survival when bevacizumab was added to XELOX or FOLFOX. However, the size of the actual treatment effect of bevacizumab is uncertain. The ERG believed that the modelling structure employed was appropriate, but highlighted several key issues and areas of uncertainty. At the time of writing, NICE was yet to issue the guidance for this appraisal.Health technology assessment (Winchester, England). 10/2010; 14(Suppl. 2):47-53.
Article: Febuxostat for the treatment of hyperuricaemia in people with gout: a single technology appraisal.M Stevenson, A Pandor[show abstract] [hide abstract]
ABSTRACT: This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of febuxostat for the management of hyperuricaemia in patients with gout based upon a review of the manufacturer's submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The submission's evidence came from two randomised controlled trials comparing the efficacy and safety of febuxostat with allopurinol. The trials were of reasonable methodological quality and measured a clinically relevant range of outcomes. A pooled clinical efficacy analysis showed that a daily dose of 80 mg or 120 mg of febuxostat was significantly more effective than fixed-dose allopurinol (300/100 mg/day) at lowering serum uric acid (sUA) levels to therapeutic targets (< 6 mg/dl); however, a large percentage of febuxostat patients did not achieve the primary end point and the fixed-dose allopurinol regimen may have introduced bias. There were no differences between treatments in more clinically important outcomes such as gout flares and tophi resolution after 52 weeks of treatment. No subgroup analyses were conducted for patients with renal impairment, non-responders to allopurinol or patients with severe disease. Supplementary data from a 2-year open-label extension study were also provided, but were difficult to interpret and poorly reported. The incidence of adverse events was similar between treatments, although more febuxostat recipients discontinued treatment prematurely. A decision tree model was developed to determine the cost-effectiveness of febuxostat. The scope was limited to the comparison of continual febuxostat treatment with continual allopurinol treatment. Switching between treatments or withdrawing treatment in patients whose sUA levels had not decreased was not permitted. The model predicted a cost-effectiveness of 16,324 pounds [95% confidence interval (CI) 6281 pounds to 239,928 pounds] per quality-adjusted life-year (QALY) gained for febuxostat compared with allopurinol after 2 years of treatment. The incremental cost per QALY was below 20,000 pounds in 63% of the simulations undertaken. Changes in the time horizon did not materially affect the results. The ERG believes that the modelling structure employed was not appropriate to estimate the cost-effectiveness of febuxostat within a treatment algorithm. In addition, there were concerns about the methodology used for collecting data on key model inputs. Given these reservations the cost-effectiveness of febuxostat could not be determined. The guidance issued by NICE in August 2008 as a result of the STA states that febuxostat is recommended as an option for the management of chronic hyperuricaemia in gout only for people who are intolerant of allopurinol or for whom allopurinol is contraindicated.Health technology assessment (Winchester, England). 10/2009; 13 Suppl 3:37-42.