Surgery Versus 5% Imiquimod for Nodular and Superficial Basal Cell Carcinoma: 5-Year Results of the SINS Randomized Controlled Trial.

We previously reported modest clinical 3-year benefit for topical imiquimod compared with surgery for superficial or nodular basal cell carcinoma at low-risk sites in our noninferiority randomized controlled SINS trial. Here we report 5-year data. Participants were randomized to imiquimod 5% cream once daily (superficial basal cell carcinoma, 6 weeks; nodular basal cell carcinoma, 12 weeks) or excisional surgery (4-mm margin). The primary outcome was clinical absence of initial failure or signs of recurrence at the 3-year dermatology review. Five-year success was defined as 3-year success plus absence of recurrences identified through hospital, histopathology, and general practitioner records. Of 501 participants randomized, 401 contributed to the modified intention-to-treat analyses at year 3 (primary outcome), 383 (96%) of whom had data at year 5. Five-year success rates for imiquimod were 82.5% (170/206) compared with 97.7% (173/177) for surgery (relative risk of imiquimod success = 0.84, 95% confidence interval = 0.77-0.91, P < 0.001). These were comparable to year 3 success rates of 83.6% (178/213) and 98.4% (185/188) for imiquimod and surgery, respectively. Most imiquimod treatment failures occurred in year 1. Although surgery is clearly superior to imiquimod, this study shows sustained benefit for lesions that respond early to topical imiquimod.

Nocturia Work Productivity and Activity Impairment Compared with Other Common Chronic Diseases.

OBJECTIVES: The International Continence Society defines nocturia as the need to void one or more times during the night, with each of the voids preceded and followed by sleep. The chronic sleep disturbance and sleep deprivation experienced by patients with nocturia affects quality of life, compromising both mental and physical well-being. This paper aims to characterise the burden of nocturia by comparing published data from patients with nocturia with data from patients with any of 12 other common chronic conditions, specifically focusing on its impact on work productivity and activity impairment, as measured by the instrument of the same name (WPAI). METHODS: A systematic literature review of multiple data sources identified evaluable studies for inclusion in the analysis. Study eligibility criteria included use of the WPAI instrument in patients with one of a predefined list of chronic conditions. We assessed the quality of each included study using the Newcastle-Ottawa scale and extracted basic study information, work and activity impairment data. To assess how work and activity impairment from nocturia compares with impairment from other common chronic diseases, we conducted two data syntheses (pooled and unpooled). RESULTS: The number of evaluable studies and the range of overall work productivity impairment reported, respectively, were as follows: nocturia (3; 14-39 %), overactive bladder (5; 11-41 %), irritable bowel syndrome/constipation (14; 21-51 %), gastroesophageal reflux disease (GERD) (13; 6-42 %), asthma/allergies (11; 6-40 %), chronic obstructive pulmonary disease (COPD) (7; 19-42 %), sleep problems (3; 12-37 %), arthritis (13; 21-69 %), pain (9; 29-64 %), depression (4; 15-43 %) and gout (2; 20-37 %). CONCLUSIONS: The overall work productivity impairment as a result of nocturia is substantial and was found to be similar to impairment observed as a result of several other more frequently researched common chronic diseases. Greater awareness of the burden of nocturia, a highly bothersome and prevalent condition, will help policy makers and healthcare decision makers provide appropriate management of nocturia.

Surgical excision versus imiquimod 5% cream for nodular and superficial basal-cell carcinoma (SINS): a multicentre, non-inferiority, randomised controlled trial.

BACKGROUND: Basal-cell carcinoma is the most common form of skin cancer and its incidence is increasing worldwide. We aimed to assess the effectiveness of imiquimod cream versus surgical excision in patients with low-risk basal-cell carcinoma. METHODS: We did a multicentre, parallel-group, pragmatic, non-inferiority, randomised controlled trial at 12 centres in the UK, in which patients were recruited between June 19, 2003, and Feb 22, 2007, with 3 year follow-up from June 26, 2006, to May 26, 2010. Participants of any age were eligible if they had histologically confirmed primary nodular or superficial basal-cell carcinoma at low-risk sites. We excluded patients with morphoeic or recurrent basal-cell carcinoma and those with Gorlin syndrome. Participants were randomly assigned (1:1) via computer-generated blocked randomisation, stratified by centre and tumour type, to receive either imiquimod 5% cream once daily for 6 weeks (superficial) or 12 weeks (nodular), or surgical excision with a 4 mm margin. The randomisation sequence was concealed from study investigators. Because of the nature of the interventions, masking of participants was not possible and masking of outcome assessors was only partly possible. The trial statistician was masked to allocation until all analyses had been done. The primary outcome was the proportion of participants with clinical success, defined as absence of initial treatment failure or signs of recurrence at 3 years from start of treatment. We used a prespecified non-inferiority margin of a relative risk (RR) of 0.87. Analysis was by a modified intention-to-treat population and per protocol. This study is registered as an International Standard Randomised Controlled Trial (ISRCTN48755084), and with ClinicalTrials.gov, number NCT00066872. FINDINGS: 501 participants were randomly assigned to the imiquimod group (n=254) or the surgical excision group (n=247). At year 3, 401 (80%) patients were included in the modified intention-to-treat group. At 3 years, 178 (84%) of 213 participants in the imiquimod group were treated successfully compared with 185 (98%) of 188 participants in the surgery group (RR 0.84, 98% CI 0.78-0.91; p<0.0001). No clear difference was noted between groups in patient-assessed cosmetic outcomes. The most common adverse events were itching (211 patients in the imiquimod group vs 129 in the surgery group) and weeping (160 vs 81). We recorded serious adverse events in 99 (40%) of 249 participants in the imiquimod group and 97 (42%) of 229 in the surgery group had serious adverse events, but none were regarded as related to treatment. 12 (5%) participants in the imiquimod group withdrew because of adverse events compared with four (2%) in the surgery group. INTERPRETATION: Imiquimod was inferior to surgery according to our predefined non-inferiority criterion. Although excisional surgery remains the best treatment for low-risk basal-cell carcinoma, imiquimod cream might still be a useful treatment option for small low-risk superficial or nodular basal-cell carcinoma dependent on factors such as patient preference, size and site of the lesion, and whether the patient has more than one lesion. FUNDING: Cancer Research UK.

Statin's cost-effectiveness: a Canadian analysis of commonly prescribed generic and brand name statins.

BACKGROUND: Generic statins may be considered as a compelling treatment option for managing dyslipidemia, due to their reduced cost, compared to their brand name equivalent. However, further assessment is needed to determine whether using a particular generic statin is more cost-effective relative to other brand-name statins. OBJECTIVE: The purpose of this study is to compare the cost-effectiveness of the most commonly prescribed statins in Canada with respect to 1) lowering low-density lipoprotein cholesterol level (LDL-C) and 2) achieving National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) LDL-C goal. METHODS: The study was conducted from the perspective of Canadian payers over a 1-year time horizon. Clinical data were obtained from the STELLAR trial (n=2268) in which patients received fixed doses of rosuvastatin, atorvastatin, simvastatin and pravastatin. Brand and generic drug costs were based on wholesale acquisition costs. Relative cost-effectiveness was assessed using the net monetary benefit approach (NMB), which allows probabilistic cost-effectiveness comparison of the various treatment options over a wide range of willingness-to-pay (WTP) values for a unit of clinical effect. RESULTS: Rosuvastatin 10mg was the most cost-effective statin over the largest range of WTP values. Pravastatin 10mg was cost-effective when the clinical outcomes had little or no monetary value. Rosuvastatin 20 mg was more cost-effective at the highest end of the WTP spectrum. CONCLUSION: The result of this analysis provides evidence that prescribing generic statins in Canada does not necessarily translate into the most cost-effective option for treating dyslipidemia; especially as the monetary value of 1% decrease in LDL-C or patients achieving NCEP ATP III target increases.

Cost effectiveness of rosuvastatin in treating patients to low-density lipoprotein cholesterol goals compared with atorvastatin, pravastatin, and simvastatin (a US Analysis of the STELLAR Trial).

Statin therapy decreases low-density lipoprotein cholesterol levels and the risk of coronary heart disease but has a considerable short-term effect on health care budgets. The cost effectiveness of rosuvastatin (Crestor) has been compared with those of atorvastatin, pravastatin, and simvastatin in lowering low-density lipoprotein cholesterol levels and achieving National Cholesterol Education Program Adult Treatment Panel III low-density lipoprotein cholesterol goals. The analysis was conducted from the perspective of health care payers in the United States. Clinical data were obtained from the Statin Therapies for Elevated Lipid Levels Compared Across Doses to Rosuvastatin (STELLAR) trial. Drug costs were based on wholesale acquisition costs. Cost effectiveness was assessed with the net monetary benefit approach and a 1-year time horizon. Rosuvastatin at 10 mg, the recommended starting dose, was the most cost-effective statin over a large range of "willingness-to-pay" values for a unit of clinical effect (i.e., a 1% decrease in low-density lipoprotein cholesterol or a patient achieving the goal).

Are cost benefits of anticoagulation for stroke prevention in atrial fibrillation underestimated?

BACKGROUND AND PURPOSE: Stroke outcomes in patients with atrial fibrillation (AF) tend to be worse than those in patients without AF. The objective of this study was to evaluate whether the cost benefits of anticoagulation for stroke prevention in AF may currently be underestimated by existing economic models that do not distinguish between different stroke outcomes. METHODS: A literature review was conducted in 3 areas: (1) studies comparing stroke outcomes in AF and non-AF patients; (2) studies providing long-term cost of stroke estimates; and (3) studies modeling the cost-effectiveness of anticoagulation with a vitamin K antagonist (eg, warfarin) in AF patients. RESULTS: There is considerable evidence that stroke in AF patients has a worse outcome than in patients without AF, including higher mortality, severity, and recurrence rates, and greater functional impairment and dependency. Estimates of the long-term cost of stroke of different severities were between US 24,991 dollars for a mild stroke over 5 years and US 142,251 dollars for a major ischemic stroke over a lifetime (2004 prices). The cost of a severe ischemic stroke may typically be 3-times that of mild stroke. However, cost-effectiveness models for anticoagulation in patients with AF have used average (not AF-specific) cost-of-stroke data, and most have used stroke severity distributions derived from clinical trials, which may differ from those in clinical practice. CONCLUSIONS: Existing economic models underestimate the cost benefits of anticoagulation for stroke prevention because they do not adjust for poorer outcomes associated with cardioembolic strokes.