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The National Institute for Health and Care Excellence (NICE) invited the manufacturer of olaratumab (Lartruvo®), Eli Lilly & Company Limited, to submit evidence for the clinical and cost effectiveness of this drug, in combination with doxorubicin, for advanced soft tissue sarcoma (STS) not amenable to surgery or radiotherapy, as part of the Institute's Single Technology Appraisal. The Peninsula Technology Assessment Group critically reviewed the submitted evidence.
Clinical effectiveness was derived from an open-label, randomized controlled trial, JGDG. The economic analysis was based on a partitioned survival model with a time horizon of 25 years. The perspective was of the UK National Health Service (NHS) and Personal Social Services. Costs and benefits were discounted at 3.5 percent per year. The company's evidence was submitted in anticipation that olaratumab would be considered as an alternative to doxorubicin, which has been used as a first-line treatment for advanced STS. To improve the cost effectiveness of olaratumab, the company offered a discount through a Commercial Access Agreement with the NHS England.
In the company's submission, the mean base-case and probabilistic incremental cost-effectiveness ratios (ICERs) for olaratumab plus doxorubicin versus doxorubicin alone were GBP 46,076 (USD 61,403) and GBP 47,127 (USD 62,804) per quality-adjusted life-year (QALY) gained, respectively; the probability of this treatment being cost effective at the willingness-to-pay threshold of GBP 50,000 (USD 66,632) per QALY gained, applicable to end-of-life treatments, was 0.54. The respective estimates in our analysis were approximately GBP 60,000 (USD 79,959) per QALY gained, and the probability of cost-effectiveness was 0.21. The increase in the ICERs was primarily due to differences in extrapolation of overall survival, and drug administration costs.
Based on the available evidence, olaratumab in combination with doxorubicin improves the survival of patients with advanced STS. However, this treatment is unlikely to be cost-effective. Olaratumab is now recommended for use within the Cancer Drugs Fund.
Clover inclusion may increase the sustainability of certain low-maintenance turfgrasses. However, selective weed control within mixed turfgrass–clover swards proves problematic because of clover susceptibility to herbicides. Research was conducted to identify common turf herbicides that are tolerated by three Trifolium species, including white clover, ball clover, and small hop clover, within low-maintenance turfgrass. Leaf and flower density, as well as plant height, were measured 4 wk after treatment as indicators of clover response to 14 herbicides. The three Trifolium spp. were moderately tolerant of bentazon (< 35% decrease in leaf density, height, or flowering). Simazine was well tolerated by white clover (< 5% decrease in all response variables), yet moderate injury to ball clover and small hop clover was observed (> 32% decrease in leaf density and > 27% decrease in flower density). Pronamide was well tolerated by white and ball clovers, with no effect on measured response variables; however, pronamide decreased small hop clover height and flower density (38 and 42%, respectively). Imazethapyr and imazamox were moderately well tolerated by white clover and small hop clover (< 39% decrease by all response variables), yet ball clover may be more susceptible to these herbicides than was anticipated based on previously reported tolerance. The herbicides 2,4-DB, halosulfuron, and metribuzin were well tolerated by white clover, with no effect on measured response variables; however, results suggest ball and small hop clovers were less tolerant. Clopyralid, 2,4-D, glyphosate, imazaquin, metsulfuron-methyl, and nicosulfuron resulted in varying degrees of injury across clover species and response variables, but, in general, these herbicides may not be viable options when attempting to maintain any of the three clover species tested. Further research is needed to quantify long-term effects of herbicide application on sward composition and clover succession.