BACKGROUND: For time-to-event endpoints, three additional benefit assessment methods have been developed aiming at an unbiased knowledge about the magnitude of clinical benefit of newly approved treatments. The American Society of Clinical Oncology (ASCO) defines a continuous score using the hazard ratio point estimate (HR-PE). The European Society for Medical Oncology (ESMO) and the German Institute for Quality and Efficiency in Health Care (IQWiG) developed methods with an ordinal outcome using lower and upper limits of the 95% HR confidence interval (HR-CI), respectively. We describe all three frameworks for additional benefit assessment aiming at a fair comparison across different stakeholders. Furthermore, we determine which ASCO score is consistent with which ESMO/IQWiG category.
METHODS: In a comprehensive simulation study with different failure time distributions and treatment effects, we compare all methods using Spearman\'s correlation and descriptive measures. For determination of ASCO values consistent with categories of ESMO/IQWiG, maximizing weighted Cohen\'s Kappa approach was used.
RESULTS: Our research depicts a high positive relationship between ASCO/IQWiG and a low positive relationship between ASCO/ESMO. An ASCO score smaller than 17, 17 to 20, 20 to 24, and greater than 24 corresponds to ESMO categories. Using ASCO values of 21 and 38 as cutoffs represents IQWiG categories.
CONCLUSIONS: We investigated the statistical aspects of the methods and hence implemented slightly reduced versions of all methods.
CONCLUSIONS: IQWiG and ASCO are more conservative than ESMO, which often awards the maximal category independent of the true effect and is at risk of overcompensating with various failure time distributions. ASCO has similar characteristics as IQWiG. Delayed treatment effects and underpowered/overpowered studies influence all methods in some degree. Nevertheless, ESMO is the most liberal one.
CONCLUSIONS: For the additional benefit assessment, the American Society of Clinical Oncology (ASCO) uses the hazard ratio point estimate (HR-PE) for their continuous score. In contrast, the European Society for Medical Oncology (ESMO) and the German Institute for Quality and Efficiency in Health Care (IQWiG) use the lower and upper 95% HR confidence interval (HR-CI) to specific thresholds, respectively. ESMO generously assigns maximal scores, while IQWiG is more conservative.This research provides the first comparison between IQWiG and ASCO and describes all three frameworks for additional benefit assessment aiming for a fair comparison across different stakeholders. Furthermore, thresholds for ASCO consistent with ESMO and IQWiG categories are determined, enabling a comparison of the methods in practice in a fair manner.IQWiG and ASCO are the more conservative methods, while ESMO awards high percentages of maximal categories, especially with various failure time distributions. ASCO has similar characteristics as IQWiG. Delayed treatment effects and under/-overpowered studies influence all methods. Nevertheless, ESMO is the most liberal one. An ASCO score smaller than 17, 17 to 20, 20 to 24, and greater than 24 correspond to the categories of ESMO. Using ASCO values of 21 and 38 as cutoffs represents categories of IQWiG.

BACKGROUND: The availability and affordability of safe, effective, high-quality, affordable anticancer therapies are a core requirement for effective national cancer control plans.
METHODS: Online survey based on a previously validated approach. The aims of the study were to evaluate (i) the availability on national formulary of licensed antineoplastic medicines across the globe, (ii) patient out-of-pocket costs for the medications, (iii) the actual availability of the medication for a patient with a valid prescription, (iv) information relating to possible factors adversely impacting the availability of antineoplastic agents and (v) the impact of the country\'s level of economic development on these parameters. A total of 304 field reporters from 97 countries were invited to participate. The preliminary set of data was posted on the ESMO website for open peer review and amendments have been incorporated into the final report.
RESULTS: Surveys were submitted by 135 reporters from 63 countries and additional peer-review data were submitted by 54 reporters from 19 countries. There are substantial differences in the formulary availability, out-of-pocket costs and actual availability for many anticancer medicines. The most substantial issues are in lower-middle- and low-income countries. Even among medications on the WHO Model List of Essential Medicines (EML) the discrepancies are profound and these relate to high out-of-pocket costs (in low-middle-income countries 32.0% of EML medicines are available only at full cost and 5.2% are not available at all, and for low-income countries, the corresponding figures are even worse at 57.7% and 8.3%, respectively).
CONCLUSIONS: There is wide global variation in formulary availability, out-of-pocket expenditures and actual availability for most licensed anticancer medicines. Low- and low-middle-income countries have significant lack of availability and high out-of-pocket expenditures for cancer medicines on the WHO EML, with much less availability of new, more expensive targeted agents compared with high-income countries.

The management of cancer is predicated on the availability and affordability of anticancer therapies, which may be either curative or noncurative.
The primary aims of the study were to evaluate (i) the formulary availability of licensed antineoplastic medicines across Europe; (ii) patient out-of-pocket costs for the medications and (iii) the actual availability of the medication for a patient with a valid prescription.
The survey tool was based on the previous ESMO studies that addressed the availability and accessibility of opioids for the management of cancer pain. A total of 185 field reporters from 49 countries were invited to participate. The preliminary set of data was posted on the ESMO website for open peer-review, and amendments have been incorporated into the final report.
There are substantial differences in the formulary availability, out-of-pocket costs and actual availability for many anticancer medicines. The most profound lack of availability is in countries with lower levels of economic development, particularly in Eastern Europe, and these are largely related to the cost of targeted agents approved in the last 10 years. Discrepancies are less profound among medications on the WHO model essential medicines list (EML) for cancer and in curative settings. However, medicine shortages also affect WHO EML medicines, with relevant therapeutic implications for many patients.
The cost and affordability of anticancer treatments with recent market approval is the major factor contributing to inequity of access to anticancer medications. This is especially true with regards to new medications used in the management of EGFR- or ALK-mutated non-small-cell lung cancer, metastatic melanoma, metastatic renal cell cancer, RAS/RAF wild-type metastatic colorectal cancer, HER2 overexpressed breast cancer and castration-resistant metastatic prostate cancer.