Methodological and reporting standards for quality-of-life data eligible for European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS) credit.

BACKGROUND: The European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS) has been developed to grade clinical benefit of cancer therapies. Improvement in quality of life (QoL) is considered relevant, especially in the non-curative setting. This is reflected by an upgrade of the preliminary ESMO-MCBS score if QoL is improved compared to the control arm or a downgrade if an improvement in progression-free survival is not paralleled by an improvement in QoL or overall survival. Given the importance of QoL for the final score, a need to ensure the robustness of QoL data was recognised. DESIGN: A checklist was created based on existing guidelines for QoL research. Field testing was carried out using clinical trials that either received an adjustment of the preliminary ESMO-MCBS score based on QoL or had QoL as the primary endpoint. Several rounds of revision and re-testing of the checklist were undertaken until a final consensus was reached. RESULTS: The final checklist consists of four items and can be applied if three prerequisites are met: (i) QoL is at least a secondary endpoint, (ii) evidence of reliability and validity of the instrument is provided, and (iii) a statistically and clinically significant improvement in QoL is observed. The four items on the checklist pertain to the (i) hypothesis, (ii) compliance and missing data, (iii) presentation of the results, and (iv) statistical and clinical relevance. Field testing revealed that a clear QoL hypothesis and correction for multiple testing were mostly lacking, while the main statistical method was always described. CONCLUSIONS: Implementation of the ESMO-MCBS QoL checklist will facilitate objective and transparent decision making on QoL data within the ESMO-MCBS scoring process. Trials published until 1 January 2025 will have to meet the prerequisites and at least two items for crediting QoL benefit in the final ESMO-MCBS score. Trials published thereafter will have to meet all four items.

ESMO-Magnitude of Clinical Benefit Scale for haematological malignancies (ESMO-MCBS:H) version 1.0.

BACKGROUND: The European Society for Medical Oncology (ESMO)-Magnitude of Clinical Benefit Scale (MCBS) has been accepted as a robust tool to evaluate the magnitude of clinical benefit reported in trials for oncological therapies. However, the ESMO-MCBS hitherto has only been validated for solid tumours. With the rapid development of novel therapies for haematological malignancies, we aimed to develop an ESMO-MCBS version that is specifically designed and validated for haematological malignancies. METHODS: ESMO and the European Hematology Association (EHA) initiated a collaboration to develop a version for haematological malignancies (ESMO-MCBS:H). The process incorporated five landmarks: field testing of the ESMO-MCBS version 1.1 (v1.1) to identify shortcomings specific to haematological diseases, drafting of the ESMO-MCBS:H forms, peer review and revision of the draft based on re-scoring (resulting in a second draft), assessment of reasonableness of the scores generated, final review and approval by ESMO and EHA including executive boards. RESULTS: Based on the field testing results of 80 haematological trials and extensive review for feasibility and reasonableness, five amendments to ESMO-MCBS were incorporated in the ESMO-MCBS:H addressing the identified shortcomings. These concerned mainly clinical trial endpoints that differ in haematology versus solid oncology and the very indolent nature of nevertheless incurable diseases such as follicular lymphoma, which hampers presentation of mature data. In addition, general changes incorporated in the draft version of the ESMO-MCBS v2 were included, and specific forms for haematological malignancies generated. Here we present the final approved forms of the ESMO-MCBS:H, including instructions. CONCLUSION: The haematology-specific version ESMO-MCBS:H allows now full applicability of the scale for evaluating the magnitude of clinical benefit derived from clinical studies in haematological malignancies.

ESMO International Consortium Study on the availability, out-of-pocket costs and accessibility of antineoplastic medicines in countries outside of Europe.

BACKGROUND: The availability and affordability of safe, effective, high-quality, affordable anticancer therapies are a core requirement for effective national cancer control plans. METHOD: 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.

ESMO-Magnitude of Clinical Benefit Scale version 1.1.

BACKGROUND: The ESMO Magnitude of Clinical Benefit Scale (ESMO-MCBS) version 1.0 (v1.0) was published in May 2015 and was the first version of a validated and reproducible tool to assess the magnitude of clinical benefit from new cancer therapies. The ESMO-MCBS was designed to be a dynamic tool with planned revisions and updates based upon recognition of expanding needs and shortcomings identified since the last review. METHODS: The revision process for the ESMO-MCBS incorporates a nine-step process: Careful review of critiques and suggestions, and identification of problems in the application of v1.0; Identification of shortcomings for revision in the upcoming version; Proposal and evaluation of solutions to address identified shortcomings; Field testing of solutions; Preparation of a near-final revised version for peer review for reasonableness by members of the ESMO Faculty and Guidelines Committee; Amendments based on peer review for reasonableness; Near-final review by members of the ESMO-MCBS Working Group and the ESMO Executive Board; Final amendments; Final review and approval by members of the ESMO-MCBS Working Group and the ESMO Executive Board. RESULTS: Twelve issues for revision or amendment were proposed for consideration; proposed amendments were formulated for eight identified shortcomings. The proposed amendments are classified as either structural, technical, immunotherapy triggered or nuanced. All amendments were field tested in a wide range of studies comparing scores generated with ESMO-MCBS v1.0 and version 1.1 (v1.1). CONCLUSIONS: ESMO-MCBS v1.1 incorporates 10 revisions and will allow for scoring of single-arm studies. Scoring remains very stable; revisions in v1.1 alter the scores of only 12 out of 118 comparative studies and facilitate scoring for single-arm studies.

Best supportive care in clinical trials: review of the inconsistency in control arm design.

BACKGROUND: Best supportive care (BSC) as a control arm in clinical trials is poorly defined. We conducted a review to evaluate clinical trials' concordance with published, consensus-based framework for BSC delivery in trials. METHODS: A consensus-based Delphi panel previously identified four key domains of BSC delivery in trials: multidisciplinary care; supportive care documentation; symptom assessment; and symptom management. We reviewed trials including BSC control arms from 2002 to 2014 to assess concordance to BSC standards and to selected items from the CONSORT 2010 guidelines. RESULTS: Of 408 articles retrieved, we retained 18 after applying exclusion criteria. Overall, trials conformed to the CONSORT guidelines better than the BSC standards (28% vs 16%). One-third of articles offered a detailed description of BSC, 61% reported regular symptom assessment, and 44% reported using validated symptom assessment measures. One-third reported symptom assessment at identical intervals in both arms. None documented evidence-based symptom management. No studies reported educating patients about symptom management or goals of therapy. No studies reported offering access to palliative care specialists. CONCLUSIONS: Reporting of BSC in trials is incomplete, resulting in uncertain internal and external validity. Such studies risk systematically over-estimating the net clinical effect of the comparator arms.

A standardised, generic, validated approach to stratify the magnitude of clinical benefit that can be anticipated from anti-cancer therapies: the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS).

The value of any new therapeutic strategy or treatment is determined by the magnitude of its clinical benefit balanced against its cost. Evidence for clinical benefit from new treatment options is derived from clinical research, in particular phase III randomised trials, which generate unbiased data regarding the efficacy, benefit and safety of new therapeutic approaches. To date, there is no standard tool for grading the magnitude of clinical benefit of cancer therapies, which may range from trivial (median progression-free survival advantage of only a few weeks) to substantial (improved long-term survival). Indeed, in the absence of a standardised approach for grading the magnitude of clinical benefit, conclusions and recommendations derived from studies are often hotly disputed and very modest incremental advances have often been presented, discussed and promoted as major advances or 'breakthroughs'. Recognising the importance of presenting clear and unbiased statements regarding the magnitude of the clinical benefit from new therapeutic approaches derived from high-quality clinical trials, the European Society for Medical Oncology (ESMO) has developed a validated and reproducible tool to assess the magnitude of clinical benefit for cancer medicines, the ESMO Magnitude of Clinical Benefit Scale (ESMO-MCBS). This tool uses a rational, structured and consistent approach to derive a relative ranking of the magnitude of clinically meaningful benefit that can be expected from a new anti-cancer treatment. The ESMO-MCBS is an important first step to the critical public policy issue of value in cancer care, helping to frame the appropriate use of limited public and personal resources to deliver cost-effective and affordable cancer care. The ESMO-MCBS will be a dynamic tool and its criteria will be revised on a regular basis.

Formulary availability and regulatory barriers to accessibility of opioids for cancer pain in Asia: a report from the Global Opioid Policy Initiative (GOPI).

Asia is a heterogeneous region with substantial variability in economic, social and palliative care development. While the global consumption of opioids has increased, the consumption in most Asian countries has not increased at the same rate. This is the first comprehensive study of opioid availability and accessibility for cancer patients in Asia. Data are reported on the availability and accessibility of opioids for the management of cancer pain in 20 of 28 countries. The countries in the report represent 2515 million of the region's 2612 million people (96%). With the exception of Japan and South Korea, opioid availability continues to be low throughout most of Asia. Formulary deficiencies are severe in several countries, in particular Bangladesh, Myanmar, Afghanistan, Kazakhstan and Laos. Even when opioids are on formulary, they are often unavailable, particularly in the same countries. Access is significantly impaired by widespread over-regulation that continues to be pervasive across the region.

Next steps in access and availability of opioids for the treatment of cancer pain: reaching the tipping point?

The reports of the Global Opioid Policy Initiative (GOPI) project to evaluate the availability and accessibility of opioids for the management of cancer pain in Africa, Asia, Latin America and the Caribbean, and the Middle East, together with the previous 2010 European Society for Medical Oncology (ESMO)/European Association for Palliative Care (EAPC) report from Europe, have provided critical data in demonstrating the deficiencies in many countries throughout the world. Formulary deficiencies and over-regulation are pandemic and must be addressed. This process is challenging and will require concerted and sustained efforts by clinical leaders and advocacy groups partnering with international and regional organizations and, of course, with national governments and their competent authorities. There is a growing international expertise and infrastructure to coordinate advocacy and strategic planning based on the World Health Organization (WHO) Model of Education, Policy Reform and Medication Availability.

The Global Opioid Policy Initiative (GOPI) project to evaluate the availability and accessibility of opioids for the management of cancer pain in Africa, Asia, Latin America and the Caribbean, and the Middle East: introduction and methodology.

Opioid analgesics are critical to the effective relief of cancer pain. Effective treatment is predicated on sound assessments, individually tailored analgesic therapy, and the availability and accessibility of the required medications. In some countries, pain relief is hampered by the lack of availability or barriers to the accessibility of opioid analgesics. As the follow-up to a successful project to evaluate the availability and accessibility of opioids and regulatory barriers in Europe, the European Society for Medical Oncology (ESMO) and the European Association for Palliative Care (EAPC) undertook to expand their research to those parts of the world where data were lacking regarding these aspects of care, in particular Africa, Asia, the Middle East, Latin America and the Caribbean, and the states of India. This project has been undertaken in collaboration with the Union for International Cancer Control (UICC), the Pain and Policy Studies Group (PPSG) of the University of Wisconsin, and the World Health Organization (WHO), together with a consortium of 17 international oncology and palliative care societies. This article describes the study methodology.

Formulary availability and regulatory barriers to accessibility of opioids for cancer pain in India: a report from the Global Opioid Policy Initiative (GOPI).

India is the world's largest democracy with control of opioids divided between the national and state governments. While the global consumption of opioids has increased, the consumption has not increased at the same rate. This is the first comprehensive study of opioid availability and accessibility for cancer patients in India. Data are reported on the availability and accessibility of opioids for the management of cancer pain in 24 of the states that make up India and the Administrative area around Delhi. About 1061 million of the nation's 1189 million people (89%) are covered by this survey. Without exception, opioid availability continues to be low throughout all of India. Even when opioids are on formulary, they are often unavailable. Access is significantly impaired by widespread over-regulation that continues to be pervasive across the nation.

Formulary availability and regulatory barriers to accessibility of opioids for cancer pain in Latin America and the Caribbean: a report from the Global Opioid Policy Initiative (GOPI).

The nations of the Caribbean, Central America and South America form a heterogeneous region with substantial variability in economic, social and palliative care development. Palliative care provision is at varied stages of development throughout the region. The consumption of opioids in Latin America and the Caribbean is variable with moderate levels of consumption by international standards (1-10 mg morphine equivalents/capita/year) observed in Argentine, Brazil, Chile, Colombia, Cuba, Mexico, Costa Rica, Uruguay and most of the Caribbean but relatively low levels of consumption in other countries particularly Guatemala, Honduras and Bolivia. Data for Latin American and Caribbean is reported on the availability and accessibility of opioids for the management of cancer pain in 24 of the 33 countries surveyed. The results of this survey are relevant to 560 million of the region's 595 million people (94%). Opioid availability continues to be low throughout most of Latin America and the Caribbean. While formularies in this region generally include all recommended morphine formulations, access is significantly impaired by widespread over-regulation that continues to be pervasive across the region.

Formulary availability and regulatory barriers to accessibility of opioids for cancer pain in the Middle East: a report from the Global Opioid Policy Initiative (GOPI).

The Middle East is a heterogeneous region with substantial variability in social development, wealth and palliative care development. The region has few democracies, strong but diverse religious affiliations, and many of the region's counties are involved in political upheavals or regional conflicts. While the global consumption of opioids has increased throughout the last 30 years, there has been little increase in opioid consumption in the Middle East. This is the first comprehensive study of opioid availability and accessibility of opioids in the Middle East. Data are reported on the availability and accessibility of opioids for the management of cancer pain in 16 of 24 countries. The data are relevant to 329 million of the region's 403 million people (82%). The survey found that with the exception of Israel, opioid availability continues to be low throughout most of the Middle East. Formulary deficiencies are severe in several countries in particular Afghanistan, Iraq, Lebanon, Libya, Palestine and Tunisia. Even when opioids are on formulary, they are often unavailable, particularly in these same countries. Access is also significantly impaired by widespread over-regulation that is pervasive across the region.

Formulary availability and regulatory barriers to accessibility of opioids for cancer pain in Africa: a report from the Global Opioid Policy Initiative (GOPI).

With nearly 1.1 billion inhabitants living in more than 50 countries, Africa is the world's poorest and most socioeconomically underdeveloped continent. Despite some advances for individual states, many African countries have very low opioid consumption and, overall, the continent has the lowest consumption per capita of any in the world. This article presents the findings of the first systematic study of the availability and accessibility of opioids for the management of cancer pain across the continent. Data are reported on the availability and accessibility of opioids for the management of cancer pain in 25 of 52 countries, with 744 million of the region's 1127 million people (66%) covered by the survey. Many countries had severely restricted formularies of opioids and only 15 of 25 had morphine available in oral IR, CR and injectable formulations. Even when opioids are on formulary they are often unavailable, and access is significantly impaired by widespread over-regulation that is pervasive across the region.