© e.s.i.F.T. srl - Firenze issn 1120-009x inTrodUcTion The prices of innovative anticancer agents are very similar in european countries, despite there being differences in the deci- sion processes adopted by different countries for price determi- nation. some countries employ value-based procedures, while others do not. 1,2 The group of countries that do not adopt the value-for-money approach tends in fact to converge on the same price values adopted by the group of countries that use value-for-money, probably because the latter acts as a reference point for the former. similar to on-label uses, the price of off-label uses should in theory reflect clinical benefit, i.e. a value-based price. however, employing the on-label price to pay for off-label uses is inap- propriate because there is no direct relationship between the on-label price of a drug and the clinical benefit resulting from its off-label use. in addition, the presence of payment by result mechanisms 3 for numerous on-label uses makes this problem even more pronounced because, in these cases, on-label uses are paid at prices reduced by the payback process, whereas off- label uses of the same drug are paid at full price. Using the value-based approach to price on-label indications is likely to produce robust decisions because in these cases the clinical benefit has reliably been determined, e.g. through con- trolled clinical trials. on the other hand, using this methodology for off-label indications tends to increase the risk of inappropri- ate decisions because the effectiveness data for off-label uses are generally less sound than the data for on-label uses. hence, off-label uses need more flexible schemes depending on the amount of effectiveness data available. in this context, our paper focuses on the methods that can be used for applying the value-for-money approach 4-6 to the off-label use of oncology drugs, particularly the most expensive ones. deTerMininG The ValUe-based price For oFF-label TreaTMenT: Trial-based VersUs indi- VidUalized payMenT-by-resUlTs approach according to the schemes presented in this paper, when the value-for-money approach is applied to the off-label uses of on- cology drugs two different approaches can be used for tailoring the price to the magnitude of the clinical benefit: a trial-based approach and an individualized payment by results approach. both of these approaches are evidence-based. in the trial-based approach, the magnitude of the effective- ness of the off-label drug is assessed from the results of the orig- inal clinical trial, while in the individual-based approach the clinical benefit is measured from individual cases. in both cases, the valued-based price is determined by applying the cost-ef- fectiveness ratio, wherein the drug price is the parameter to be calculated. Trial-based approach in this case the value-based price is calculated using the fol- lowing equation: sUGGesTed payMenT a = c b + 5000 x (s a -s b ) (equation 1) where Treatment a is the potentially innovative off-label thera- peutic modality, Treatment b is the standard therapeutic modal- A Uniform Procedure for Reimbursing the Off-Label Use of Antineoplastic Drugs According to the Value-for-Money Approach Messori - V. Fadda - s. Trippoli laboratorio di Farmacoeconomia, University of Florence, italy. Correspondence: dr. andrea Messori, Via Guimaraes 5-7, 59100 prato, italy. e-mail: messoriandrea@interfree.it Summary National healthcare systems as well as local institutions generally reimburse numerous off-label uses of anticancer drugs, but an explicit framework for managing these pay- ments is still lacking. As in the case of on-label uses, an op- timal management of off-label uses should be aimed at a direct proportionality between cost and clinical benefit. Within this framework, assessing the incremental cost/ef- fectiveness ratio becomes mandatory, and measuring the magnitude of the clinical benefit (e.g. gain in overall sur- vival or progression-free survival) is essential. This paper discusses how the standard principles of cost-effectiveness and value-for-money can be applied to manage the reimbursement of off-label treatments in on- cology. It also describes a detailed operational scheme to appropriately implement this aim. Two separate ap- proaches are considered: a) a trial-based approach, which is designed for situations where enough information is available from clinical studies about the expected effec- tiveness of the off-label treatment; b) an individualized payment-by-results approach, which is designed for situa- tions in which adequate information on effectiveness is lacking; this latter approach requires that each patient re- ceiving off-label treatment is followed-up to determine in- dividual outcomes and tailor the extent of payment to individual results. Some examples of application of both approaches are presented in detail, which have been extracted from a list of 184 off-label indications approved in 2010 by the Re- gion of Tuscany in Italy. These examples support the fea- sibility of the two methods proposed. In conclusion, the scheme described in this paper rep- resents an operational solution to an unsettled problem in the area of oncology drugs. Key words: Off-label pricing, anticancer drug pricing. MINI-REVIEW Journal of Chemotherapy Vol. 23 - n. 2 (48-?) - 2011