Ght to be respected. There is no injustice there. However, that conclusion is too quick. The fact is that these wealthier individuals are paying only 30 of the cost of these targeted therapies from their own pockets; the remainder of the cost is actually being covered by all the individuals who were unable to afford the drug themselves in the form of their basic insurance premiums. To correct for what seems like an obvious injustice, these targeted therapies and other such costly marginally beneficial interventions would have to be accessible only through a separate insurance mechanism with premiums paid out of pocket by individuals who believed such benefits were worth it to them. Most European nations do not have to address the above issue because copays are a rare phenomenon. However, Europe and the US will have to address what I have discussed elsewhere as the ragged edge issue. This is a term that Daniel Callahan introduced into the literature [21]. It means that there are often no bright lines in nature that separate health care interventions that are cost-effective from those that are not cost-effective. Consequently, when health care rationing decisions need to be made and some sort of cutoff for social funding is put in place there will be patients on the other side of that line who will wonder how it could possibly be just to deny them what they might regard as the only life-prolonging resource available for their medical problem. That sort of political and ethical awkwardness can be avoided by not drawing any lines and funding everything that does any medical good for any patient in specific medical circumstances. That, however, represents a denial of the need to control escalating health care costs. In the UK the National Institute for Clinical Excellence (NICE) uses roughly 50,000 per Quality-Adjusted Life-Year as a criterion for determining which new therapeutic interventions wouldJ. Pers. Med. 2013,be funded by the National Health Service [49]. In the US the present consensus would Mangafodipir (trisodium) custom synthesis endorse a figure around 100,000 for making the same judgments, though this does not represent any official commitment to such a figure by either government or business. However, as the genomic revolution in medicine advances the ragged edge is appearing (or threatens to appear) in numerous medical circumstances. Schneider et al., for example, looked at bevacizumab and paclitaxel as a treatment for metastatic purchase BQ-123 breast cancer compared to paclitaxel alone [50]. Median survival in these two arms was virtually indistinguishable, 25.2 months vs. 26.7 months. It would cost 100,000 to buy those six extra weeks, which is equal to a cost per QALY of 800,000. However, 7 of the women in the bevacizumab cohort with a specific VEGF genotype achieved median survival of 50 months. They gained more than two extra years of life for a cost per QALY of only 50,000, which seems quite reasonable. Another 11 of these women with a different VEGF genotype achieved a median survival gain of 30.5 months, or five extra months relative to the paclitaxel group alone. That works out to a cost per QALY of 240,000, much less of a reasonable use of limited health care resources. All the other genotypes achieved lower gains in survival (and higher cost-effectiveness numbers). The ethical issue is this: If we have reliable predictive biomarkers for such large differences in outcomes, then is it just enough if we only provide public funding for a drug such as bevacizumab fo.Ght to be respected. There is no injustice there. However, that conclusion is too quick. The fact is that these wealthier individuals are paying only 30 of the cost of these targeted therapies from their own pockets; the remainder of the cost is actually being covered by all the individuals who were unable to afford the drug themselves in the form of their basic insurance premiums. To correct for what seems like an obvious injustice, these targeted therapies and other such costly marginally beneficial interventions would have to be accessible only through a separate insurance mechanism with premiums paid out of pocket by individuals who believed such benefits were worth it to them. Most European nations do not have to address the above issue because copays are a rare phenomenon. However, Europe and the US will have to address what I have discussed elsewhere as the ragged edge issue. This is a term that Daniel Callahan introduced into the literature [21]. It means that there are often no bright lines in nature that separate health care interventions that are cost-effective from those that are not cost-effective. Consequently, when health care rationing decisions need to be made and some sort of cutoff for social funding is put in place there will be patients on the other side of that line who will wonder how it could possibly be just to deny them what they might regard as the only life-prolonging resource available for their medical problem. That sort of political and ethical awkwardness can be avoided by not drawing any lines and funding everything that does any medical good for any patient in specific medical circumstances. That, however, represents a denial of the need to control escalating health care costs. In the UK the National Institute for Clinical Excellence (NICE) uses roughly 50,000 per Quality-Adjusted Life-Year as a criterion for determining which new therapeutic interventions wouldJ. Pers. Med. 2013,be funded by the National Health Service [49]. In the US the present consensus would endorse a figure around 100,000 for making the same judgments, though this does not represent any official commitment to such a figure by either government or business. However, as the genomic revolution in medicine advances the ragged edge is appearing (or threatens to appear) in numerous medical circumstances. Schneider et al., for example, looked at bevacizumab and paclitaxel as a treatment for metastatic breast cancer compared to paclitaxel alone [50]. Median survival in these two arms was virtually indistinguishable, 25.2 months vs. 26.7 months. It would cost 100,000 to buy those six extra weeks, which is equal to a cost per QALY of 800,000. However, 7 of the women in the bevacizumab cohort with a specific VEGF genotype achieved median survival of 50 months. They gained more than two extra years of life for a cost per QALY of only 50,000, which seems quite reasonable. Another 11 of these women with a different VEGF genotype achieved a median survival gain of 30.5 months, or five extra months relative to the paclitaxel group alone. That works out to a cost per QALY of 240,000, much less of a reasonable use of limited health care resources. All the other genotypes achieved lower gains in survival (and higher cost-effectiveness numbers). The ethical issue is this: If we have reliable predictive biomarkers for such large differences in outcomes, then is it just enough if we only provide public funding for a drug such as bevacizumab fo.