The impact of adding an extra dimension to a preference-based measure

The ability to compare incremental changes in Quality Adjusted Life Years (QALYs) generated by different condition-specific preference-based measures (CSPBMs), or indeed between generic measures, is often criticised even where the valuation methods and source of values are the same. A key concern is the impact of excluding key dimensions from a descriptive system. This study examines the impact of adding a generic pain/discomfort dimension to a CSPBM, the AQL-5D (an asthma-specific CSPBM), by valuing samples of states from the AQL-5D with and without the new dimension using an interviewer administered time trade-off with a sample of the UK general public. 180 respondents provided 720 valuations for states with and without pain/discomfort. As expected the additional pain/discomfort dimension was found to have a significant and relatively large coefficient. More importantly for comparing changes in QALYs across populations the addition of pain/discomfort significantly impacts on the coefficients of the other dimensions and the degree of impact differs by dimension and severity level. The net effect on the utility value depends on the severity of their state: the addition of pain/discomfort at level 1 (no pain/ discomfort) or 2 (moderate pain/discomfort) significantly increased the mean health state values in an asthma patient population; whereas level 3 pain/discomfort (extreme) reduced values. Comparability between measures requires that the impact of different dimensions on preferences is additive, whether or not they are included in the classification system. Our results cast doubt on this assumption, implying that the chosen measure must contain all important and relevant dimensions in its classification system

Simultaneous but not prior inhibition of VEGF165 enhances the efficacy of photodynamic therapy in multiple models of ocular neovascularization

PURPOSE: To investigate the effect of the combined treatment of photodynamic therapy and specific VEGF165 inhibition with pegaptanib sodium (Macugen; Eyetech Pharmaceuticals, Lexington, MA) on ocular neovascularization. METHODS: Photodynamic therapy's (PDT's) effects on the integrity of pegaptanib sodium were analyzed by HPLC, a VEGF165-binding assay, and a VEGF165-induced tissue factor gene expression assay. The effects of mono- or combined treatment on vessel growth and regression were determined in a murine corneal neovascularization model. The effects of combined treatment on vessel growth were also determined in a murine choroidal neovascularization model. RESULTS: PDT did not affect the chemical composition of pegaptanib sodium nor the efficacy of pegaptanib sodium in the inhibition of VEGF165 binding to Flt-1 and VEGF165-induced gene expression. In an animal model of effects on existing ocular neovascular lesions (corneal neovascularization), PDT monotherapy yielded an initial regression of these vessels, but there followed a rapid regrowth. In contrast, pegaptanib sodium monotherapy yielded little regression but potently abrogated further vessel growth. The combination of pegaptanib sodium and PDT resulted in the regression of the neovascular lesions, as observed with PDT alone, but also prevented significant vessel regrowth, leading to a significantly greater reduction in lesion size than did each monotherapy. In addition, there was a significantly greater effect of the combination of pegaptanib sodium and PDT on lesion size in choroidal neovascularization than with each monotherapy. Pretreatment with pegaptanib sodium appeared to decrease the efficacy of PDT-induced vessel regression in corneal neovascularization, and as such the enhanced efficacy over monotherapy when the agents were delivered simultaneously was not observed. CONCLUSIONS: Although the combined simultaneous treatment of ocular neovascularization with PDT and pegaptanib sodium may provide a more effective approach for the regression and overall treatment of CNV associated with AMD, the order of addition of these treatments may play a role in achieving optimal efficacy