To the best of our knowledge, the present study is the first to examine the impact of Hb level at DA initiation on the cost of treating chemotherapy-induced anemia. The findings suggest that RBC transfusion incidence decreases with higher Hb levels at the time of DA initiation and that a reduction in transfusion rate is associated with reduced costs, although the actual cost savings varied between the studies examined. Although we would have preferred to combine the studies in a meta-analysis to provide more precise estimates, the heterogeneity of the studies in terms of their study designs and reporting of transfusion rates stratified by Hb level made this impossible. It should also be noted that the measurement period of transfusion rates and the analytical method used to report transfusion rates (Kaplan–Meier or raw percentages) also varied between studies. As Kaplan–Meier estimates account for dropouts from the studies, risk differences calculated from such estimates of transfusion rates are more likely to reflect a population estimate, and cost savings calculated on this basis are, therefore, more likely to reflect real-life clinical practice.
While the present study showed that early initiation of DA can lead to a reduction in the costs associated with RBC transfusion, there are other important potential benefits from reducing transfusion rates. For example, there are risks associated with blood transfusions [1
], and blood used for transfusion is also a scarce resource that must be managed efficiently. Thus, a reduction in transfusions may improve the efficient allocation of scarce resources. Furthermore, studies have shown that patients report a strong desire to avoid transfusions [42
]. While such outcomes are beyond the scope of the present study, this preference can be measured using “willingness-to-pay” (WTP) analysis and can be included in the calculation of cost savings. The purpose of WTP measurements is to ascertain individual’s maximum WTP for some—usually nonmarketed—good through hypothetical survey questions [43
]. Per the recommendation of clinical guidelines, not only Hb levels but also patient symptoms and circumstances should be considered when deciding on the most appropriate treatment.
While effort should be made to reduce transfusion burden, use of ESA should follow current clinical guideline and label recommendations. Some years ago, several clinical studies and meta-analyses suggested that ESAs may reduce survival or increase disease progression [44
]. More recent studies and meta-analyses, however, have found no negative impact upon survival [32
]. Overall consensus has been that, when used in accordance with the prescribing information, ESA therapy is well tolerated, does not negatively affect survival, and provides important clinical benefits for patients with CIA by reducing the need for RBC transfusions and exposure to associated risks [6
Previously published cost-effectiveness analyses of ESAs and RBC transfusions have generally been conducted on the basis that ESAs are an alternative to RBC transfusion, and have given conflicting results [50
]. For example, Borget et al. [52
] and Borg et al. [51
] both showed that use of an ESA was cost-effective compared with RBC transfusion, while Klarenbach et al. found that ESA use was not [50
]. The validity of these studies in real-life practice is, however, limited as guidelines state that ESAs and transfusions are complementary, rather than mutually exclusive, in the management of chemotherapy-induced anemia [6
Costs of transfusion varied between countries and also from study to study, depending on the cost derivers included in the analyses and the initial economic perspective taken. While all direct labor and material costs incurred during the three main phases of the transfusion process (collection from the donor, preparation of the blood by running the necessary tests for safety, and transfusion to the recipient) should have been considered when reporting costs, other cost derivers are more dependent on the perspective taken.
The cost of DA treatment has been estimated at €2,094 in Belgium [53
] and ranged from €1,659 to €2,378 across different European countries [54
]. Considering differences in the length of treatment (12–16 weeks in clinical trials and 6 weeks in DA cost analyses), the potential cost savings of up to €3,895 for every ten patients demonstrated in the present study could be used to treat approximately one additional patient with DA. Decrease in transfusion costs could offset the increase in DA costs.
Limitations of the present study include the potential for publication selection bias arising from the use of a single publication database (PubMed). For instance, retrieved articles are highly dependent on the search strategy used, and use of multiple sources may, therefore, have reduced this effect [55
]. The review of clinical studies found a trend in transfusion reduction related to Hb level at DA initiation, although it should be noted there were differences in baseline patient characteristics, lengths of the studies, and analytical techniques used to report transfusion incidence. In addition, it was assumed that the cost of RBC transfusion was constant for the first and subsequent units. The costs for the second unit of transfused blood, however, were found in some of the cited studies to be slightly less expensive than the first unit. The calculated cost savings reported here may, therefore, slightly overestimate the actual cost savings in clinical practice.
In conclusion, the findings of the clinical systematic review showed that transfusion incidence increases when DA is initiated at lower versus higher Hb levels. The cost of transfusion was found to vary from country to country and was dependent on the cost items included (e.g., direct and indirect costs). Overall, this study shows that the Hb level at DA initiation has a cost implication in the treatment of chemotherapy-induced anemia: the lower the Hb level, the greater the number of transfusions and the larger the overall cost of treatment. In patients for whom DA treatment is appropriate, treatment should, therefore, be initiated as early as possible within guideline-defined Hb levels, to reduce the need for transfusion and to decrease the overall cost of treatment. Clinical circumstances and symptoms of the patient should be considered while deciding on the most appropriate treatment of CIA.