Standards for the development and methodology of the 2023 IWGDF guidelines.

AIMS: Diabetes-related foot disease is a major source of patient burden and societal costs. Investing in evidence-based international guidelines on diabetes-related foot disease is important to reduce this burden and costs, provided the guidelines are focused on outcomes important to key stakeholders and are evidence-based and properly implemented. MATERIALS AND METHODS: The International Working Group on the Diabetic Foot (IWGDF) has published and updated international guidelines since 1999. The 2023 updates were made using the Grading of Recommendations Assessment Development and Evaluation evidence-to-decision framework. This concerns formulating relevant clinical questions and important outcomes, conducting systematic reviews of the literature and meta-analyses where appropriate, completing summary of judgement tables, and writing recommendations that are specific, unambiguous and actionable, along with their transparent rationale. RESULTS: We herein describe the development of the 2023 IWGDF Guidelines on the prevention and management of diabetes-related foot disease, which consists of seven chapters, each prepared by a separate working group of international experts. These chapters provide guidelines related to diabetes-related foot disease on prevention; classification of diabetes-related foot ulcer, offloading, peripheral artery disease, infection, wound healing interventions, and active Charcot neuro-osteoarthropathy. Based on these seven guidelines, the IWGDF Editorial Board also produced a set of practical guidelines. Each guideline underwent extensive review by the members of the IWGDF Editorial Board as well as independent international experts in each field. CONCLUSIONS: We believe that the adoption and implementation of the 2023 IWGDF guidelines by healthcare providers, public health agencies, and policymakers will improve the prevention and management of diabetes-related foot disease, and subsequently reduce the worldwide patient and societal burden caused by this disease.

Practical guidelines on the prevention and management of diabetes-related foot disease (IWGDF 2023 update).

Diabetes-related foot disease results in a major global burden for patients and the healthcare system. The International Working Group on the Diabetic Foot (IWGDF) has been producing evidence-based guidelines on the prevention and management of diabetes-related foot disease since 1999. In 2023, all IWGDF Guidelines have been updated based on systematic reviews of the literature and formulation of recommendations by multidisciplinary experts from all over the world. In addition, a new guideline on acute Charcot neuro-osteoarthropathy was created. In this document, the IWGDF Practical Guidelines, we describe the basic principles of prevention, classification and management of diabetes-related foot disease based on the seven IWGDF Guidelines. We also describe the organisational levels to successfully prevent and treat diabetes-related foot disease according to these principles and provide addenda to assist with foot screening. The information in these practical guidelines is aimed at the global community of healthcare professionals who are involved in the care of persons with diabetes. Many studies around the world support our belief that implementing these prevention and management principles is associated with a decrease in the frequency of diabetes-related lower-extremity amputations. The burden of foot disease and amputations is increasing at a rapid rate, and comparatively more so in middle to lower income countries. These guidelines also assist in defining standards of prevention and care in these countries. In conclusion, we hope that these updated practical guidelines continue to serve as a reference document to aid healthcare providers in reducing the global burden of diabetes-related foot disease.

HTA model for laboratory medicine technologies: overview of approaches adopted in some international agencies.

The Health Technology Assessment (HTA) Working Group of the Emerging Technology Division of International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) aims to develop a methodological approach for producing structured HTA information for laboratory medicine technologies. This approach seeks to support decision-making processes at the country, regional, and/or hospital levels regarding the introduction of specific technologies. The focus of this model will primarily be on defining assessment elements within the domains of 'organizational aspects' and 'costs and economic evaluations', potentially differentiated by the type of diagnostic technology (e.g., genetic tests, molecular tests). To achieve this project's goal, a literature review and examination of websites of international HTA agencies have been conducted. The research aims to identify multidisciplinary methodological approaches used to assess laboratory diagnostic technologies and to pinpoint the domains and assessment elements utilized. We found 7 methodological articles describing methodological approaches adopted to assess laboratory diagnostic technologies. Among the HTA organizations considered, 23 reports were found, of which 7 were produced by the European Network of HTA (EUnetHTA), 4 by the National Institute for Health and Care Excellence Diagnostic Assessment Program (NICE DAP), and 12 by other HTA agencies. The EUnetHTA reports were rapid collaborative assessments covering various domains, while the NICE DAP reports focused on diagnostic guidances, including descriptions of technologies, clinical need and practice, diagnostic tests, accuracy, effectiveness, and cost-effectiveness. Finally, a survey targeting laboratory professionals will be conducted to introduce assessment elements, differentiated by the type of diagnostic technology, primarily for organizational and economic domains.

Critical reviews of exposure assessment in carcinogenic hazard identification: the IARC Monographs experience.

OBJECTIVES: To summarise the rationale, workflow and recommendations for the conduct of exposure assessment critiques in key human studies evaluated for International Agency for Research on Cancer (IARC) Monographs on the Identification of Carcinogenic Hazards. METHODS: Approaches to evaluating exposure assessment quality in human cancer and mechanistic studies were reviewed according to the precepts outlined in the IARC Monographs Preamble, using two agents as case studies. Exposure assessment 'domains', that is, salient aspects of exposure assessment for the agent under evaluation, were selected for review across the key human studies. RESULTS: The case studies of night shift work (volume 124) and 1,1,1-trichloroethane (volume 130) used a common approach, tailored to the agents' specific exposure scenarios, to evaluate exposure assessment quality. Based on the experiences of IARC Working Groups to date, the implementation of exposure assessment critique requires the need for agent-specific knowledge, consideration of the validity of time-varying exposure metrics related to duration and intensity, and transparent, concise reviews that prioritise the most important strengths and limitations of exposure assessment methods used in human studies. CONCLUSIONS: Exposure assessment has not historically been a fully appreciated component for evaluating the quality of epidemiological studies in cancer hazard identification. Exposure assessment critique in key human cancer and mechanistic studies is now an integral part of IARC Monographs evaluations and its conduct will continue to evolve as new agents are evaluated. The approaches identified here should be considered as a potential framework by others when evaluating the exposure assessment component of epidemiological studies for systematic reviews.

Review of ethical values across the ICRP's system of radiological protection.

In 2018, the International Commission on Radiological Protection (ICRP) released Publication 138, which highlights the ethical values foundational to the system of radiological protection. Additional work, both within and beyond the ICRP, has proposed or recommended ethical values associated with applications of the system in different areas, perhaps most notably in medical, veterinary, and environmental radiological protection. There are also existing ethical frameworks not specifically related to radiological protection that are nonetheless relevant to its practice; for example, the Beauchamp and Childress principles of biomedical ethics are of particular significance when it comes to medical uses of radiation and radioactivity. At first glance, it may seem as if there are unique or isolated sets of ethical values that need to be applied depending on the circumstance. Yet while each area of application will indeed have its own unique aspects and associated value judgements, there are consistent and complementary relationships between these ethical values. This paper reviews the work of the ICRP related to ethics, including brief historical context, and highlights the similarities and differences between sets of ethical values with emphasis on medical, veterinary, and environmental applications of radiological protection.

A practitioners view on the ICRP review of the system of radiological protection-feedback from SRP 2023 workshop.

In 2018 the International Commission on Radiological Protection (ICRP) initiated a review and revision of the System of Radiological Protection which will lay the foundation for radiation protection (RP) standards, regulations, guidance and practice worldwide for the next 40 years. On the 25 April 2023 the Society for Radiological Protection ran a workshop at their Annual Conference presenting the current status and progress in the ICRP Review and Revision, along with inviting a number of panellist's across different areas of the profession and wider audience to share their thoughts. The outputs of the workshop are summarised in this paper showing the views from a variety of practitioners working across the RP sectors on the key factors to be considered in the review.

Perspectives of the role of ICRP and the system of protection in meeting the United Nations sustainable development goals.

Established in 2015 the United Nations (UN) sustainable development goals (SDGs) were agreed with the aim to balance the need to address social and ethical obligations such as ending poverty and other deprivations, while tackling climate change and the other planetary boundaries. In 2018 the International Commission on Radiological Protection (ICRP) initiated a review and revision of the System of Radiological Protection which will lay the foundation for Radiation Protection standards, regulations, guidance and practice worldwide for the next 40 years. Recognising the importance of the UN SDG's the ICRP has started to consider what the role of the revised system of protection should be in enabling delivery. On the 15 May 2024 the Society for Radiological Protection and World Nuclear Association ran a workshop exploring the intersection of the System of Radiological Protection and the SDG's. The outputs of the workshop are summarised in this paper showing the views from a variety of practitioners working across the radiation protection sectors on the key factors to be considered in the revision of the system of radiological protection to enable delivery of the UN SDG's.

Transfer functions forQA/QBinternational regulatory limits for the safe transport of radioactive materials.

This paper presents a proposed revision of the International Atomic Energy Agency transport regulations, related to theA1andA2limit values used to determine the radioactive transport classification. Based on the 'Qsystem', a novel methodology was introduced to deriveQAandQBvalues related to scenarios involving external exposure from a distant source. These values are key parameters that respectively represent the total effective dose and total equivalent dose to the skin, from all primary and secondary particles contributing to radiation exposure. The International Working Group (WGA1/A2) is established and associated with the TRANSSC Technical Expert Group on Radiation Protection. A review of theA1andA2values is performed in response to identified limitations within the existingQsystem. The followed approach is based on Monte Carlo simulations that enabled the development of transfer functions aimed at reducing computational time and increasing the flexibility of dose evaluations for any radionuclide with known particle emission spectra. This method allows updating theQAandQBvalues to account for future data evolutions (decay data, fluence-to-dose conversion coefficients) and standardizing the calculation of regulation limits across all referenced radionuclides and scenarios related to external exposure. The transfer functions are established using three Monte Carlo simulation codes-FLUKA, Geant4, and MCNP-and address the previous limitations of the 'Qsystem', reflecting the latest International Commission for Radiation Protection recommendations and improvements in calculation techniques. The results of the WG show consistent agreement across the codes, with minor discrepancies observed at low primary energies due to statistical uncertainties and different handling of stopping power for electrons/positrons in the codes. This revised approach aligns with current standards and recommendations, ensuring that the radiological consequences of transport accidents are acceptable for the newA1andA2limits from a radiological protection perspective.

Validating the application of the revised ICRP's biokinetic models for organic14C and organically bound tritium to members of the public.

In 2016, the International Commission on Radiological Protection (ICRP) has revised the biokinetic models for carbon and tritium in Publication 134 to calculate the dose coefficients of these radionuclides for workers. The following publication for members of the public is now in the process of revising by the ICRP. According to the draft manuscript published for consultation in 2023, the same models will be adopted for members of the public, although the parameters in these models are not corroborated by the metabolic data of radionuclides in foods. Dose coefficients for adult were estimated using modified models developed in this study to validate the application of the revised ICRP models to members of the public. In the modified models, several parameters were replaced based on the metabolic data of these nuclides in foods and compartments of radio-insensitive tissues were introduced. For these estimations, we utilised an inhouse program for internal-dose calculation developed by the Japan Atomic Energy Agency. The estimated dose coefficient values for ingestion of organic14C and organically bound tritium (OBT) ranged from 3.2 × 10-11-7.6 × 10-11Sv Bq-1and from 3.5 × 10-11-5.4 × 10-11Sv Bq-1, respectively. We concluded that the dose coefficient value of 1.6 × 10-10Sv Bq-1obtained by the revised ICRP's carbon model was conservative for members of the public, while the value of 5.1 × 10-11Sv Bq-1for OBT was appropriate.

Health technology assessment of diagnostic tests: a state of the art review of methods guidance from international organizations.

OBJECTIVES: To identify which international health technology assessment (HTA) agencies are undertaking evaluations of medical tests, summarize commonalities and differences in methodological approach, and highlight examples of good practice. METHODS: A methodological review incorporating: systematic identification of HTA guidance documents mentioning evaluation of tests; identification of key contributing organizations and abstraction of approaches to all essential HTA steps; summary of similarities and differences between organizations; and identification of important emergent themes which define the current state of the art and frontiers where further development is needed. RESULTS: Seven key organizations were identified from 216 screened. The main themes were: elucidation of claims of test benefits; attitude to direct and indirect evidence of clinical effectiveness (including evidence linkage); searching; quality assessment; and health economic evaluation. With the exception of dealing with test accuracy data, approaches were largely based on general approaches to HTA with few test-specific modifications. Elucidation of test claims and attitude to direct and indirect evidence are where we identified the biggest dissimilarities in approach. CONCLUSIONS: There is consensus on some aspects of HTA of tests, such as dealing with test accuracy, and examples of good practice which HTA organizations new to test evaluation can emulate. The focus on test accuracy contrasts with universal acknowledgment that it is not a sufficient evidence base for test evaluation. There are frontiers where methodological development is urgently required, notably integrating direct and indirect evidence and standardizing approaches to evidence linkage.

Vancouver call for action to strengthen expertise in radiological protection worldwide.

Ionising radiation has been used for over a century for peaceful purposes, revolutionising health care and promoting well-being through its application in industry, science, and medicine. For almost as long, the International Commission on Radiological Protection (ICRP) has promoted understanding of health and environmental risks of ionising radiation and developed a protection system that enables the safe use of ionising radiation in justified and beneficial practices, providing protection from all sources of radiation. However, we are concerned that a shortage of investment in training, education, research, and infrastructure seen in many sectors and countries may compromise society's ability to properly manage radiation risks, leading to unjustified exposure to or unwarranted fear of radiation, impacting the physical, mental, and social well-being of our peoples. This could unduly limit the potential for research and development in new radiation technologies (healthcare, energy, and the environment) for beneficial purposes. ICRP therefore calls for action to strengthen expertise in radiological protection worldwide through: (1) National governments and funding agencies strengthening resources for radiological protection research allocated by governments and international organisations, (2) National research laboratories and other institutions launching and sustaining long-term research programmes, (3) Universities developing undergraduate and graduate university programmes and making students aware of job opportunities in radiation-related fields, (4) Using plain language when interacting with the public and decision makers about radiological protection, and (5) Fostering general awareness of proper uses of radiation and radiological protection through education and training of information multipliers. The draft call was discussed with international organisations in formal relations with ICRP in October 2022 at the European Radiation Protection Week in Estoril, Portugal, and the final call announced at the 6th International Symposium on the System of Radiological Protection of ICRP in November 2022 in Vancouver, Canada.

Radiological protection in human research ethics using a case study: toward update of the ICRP Publication 62.

The benefits of biomedical research involving humans are well recognised, along with the need for conformity to international standards of science and ethics. When human research involves radiation imaging procedures or radiotherapy, an extra level of expert review should be provided from the point of view of radiological protection. The relevant publication of the International Commission for Radiological Protection (ICRP) is now three decades old and is currently undergoing an update. This paper aims to provoke discussions on how the risks of radiation dose and the benefits of research should be assessed, using a case study of diagnostic radiology involving volunteers for whom there is no direct benefit. Further, the paper provides the current understanding of key concepts being considered for review and revision-such as the dose constraint and the novel research methods on the horizon, including radiation biology and epidemiology. The analysis revisits the perspectives described in the ICRP Publication 62, and considers the recent progress in both radiological protection ethics and medical research ethics.

Showcasing the international atom: the IAEA Bulletin as a visual science diplomacy instrument, 1958-1962.

When the International Atomic Energy Agency (IAEA) began operations in 1958, one of its first routine tasks was to create and circulate a brief non-technical periodical. This article analyses the creation of the IAEA Bulletin and its circulation during its first years. It finds that diplomatic imperatives both in IAEA leadership circles and in the networks outside them shaped the form and appearance of the bulletin. In the hands of the IAEA's Division of Public Information, the bulletin became an instrument of science diplomacy, its imagery conveying the motivations for member states to strengthen ties with the IAEA, while simultaneously persuading them to accept the hierarchies and geopolitical logics implicit in those relations, as well as to endorse the central position of the IAEA as a clearing house and authority of globally circulating nuclear objects and information.

Evolution of the joint International Atomic Energy Agency (IAEA), International Agency for Research on Cancer (IARC), and WHO cancer control assessments (imPACT Reviews).

Before 2005, cancer and other non-communicable diseases were not yet health and development agenda priorities. Since the 2005 World Health Assembly Resolution, which encouraged WHO, the International Agency for Research on Cancer (IARC), and the International Atomic Energy Agency (IAEA) to jointly work on cancer control, progress was achieved in low-income and middle-income countries on a small scale. Recently, rapid acceleration in UN collaboration and global cancer activities has focused attention in global cancer control. This Policy Review presents the evolution of the IAEA, IARC, and WHO joint advisory service to help countries assess needs and capacities throughout the comprehensive cancer control continuum. We also highlight examples per country, showcasing a snapshot of global good practices to foster an exchange of experiences for continuous improvement in the integrated mission of Programme of Action for Cancer Therapy (imPACT) reviews and follow-up support. The future success of progress in cancer control lies in the high-level political and financial commitments. Linking the improvement of cancer services to the strengthening of health systems after the COVID-19 pandemic will also ensure ongoing advances in the delivery of care across the cancer control continuum.

Commentary: Role and communications of cancer hazard determinations.

This commentary is written in response to a recent commentary in Carcinogenesis that provides several viewpoints on the International Agency for Research on Cancer's (IARC) Monographs program on cancer hazard identification. This commentary offers an alternative viewpoint of the role of cancer hazard identification derived from cancer epidemiology studies in risk characterization, as well as clarification on the previous commentary's interpretation of the purpose of the Monographs and other programs of cancer hazard identification and how IARC communicates the findings of the Monographs.

Estimating total spending by source of funding on routine and supplementary immunisation activities in low-income and middle-income countries, 2000-17: a financial modelling study.

BACKGROUND: Childhood immunisation is one of the most cost-effective health interventions. However, despite its known value, global access to vaccines remains far from complete. Although supply-side constraints lead to inadequate vaccine coverage in many health systems, there is no comprehensive analysis of the funding for immunisation. We aimed to fill this gap by generating estimates of funding for immunisation disaggregated by the source of funding and the type of activities in order to highlight the funding landscape for immunisation and inform policy making. METHODS: For this financial modelling study, we estimated annual spending on immunisations for 135 low-income and middle-income countries (as determined by the World Bank) from 2000 to 2017, with a focus on government, donor, and out-of-pocket spending, and disaggregated spending for vaccines and delivery costs, and routine schedules and supplementary campaigns. To generate these estimates, we extracted data from National Health Accounts, the WHO-UNICEF Joint Reporting Forms, comprehensive multi-year plans, databases from Gavi, the Vaccine Alliance, and the Institute for Health Metrics and Evaluation's 2019 development assistance for health database. We estimated total spending on immunisation by aggregating the government, donor, prepaid private, and household spending estimates. FINDINGS: Between 2000 and 2017, funding for immunisation totalled US$112·4 billion (95% uncertainty interval 108·5-118·5). Aggregated across all low-income and middle-income countries, government spending consistently remained the largest source of funding, providing between 60·0% (57·7-61·9) and 79·3% (73·8-81·4) of total immunisation spending each year (corresponding to between $2·5 billion [2·3-2·8] and $6·4 billion [6·0-7·0] each year). Across income groups, immunisation spending per surviving infant was similar in low-income and lower-middle-income countries and territories, with average spending of $40 (38-42) in low-income countries and $42 (39-46) in lower-middle-income countries, in 2017. In low-income countries and territories, development assistance made up the largest share of total immunisation spending (69·4% [64·6-72·0]; $630·2 million) in 2017. Across the 135 countries, we observed higher vaccine coverage and increased government spending on immunisation over time, although in some countries, predominantly in Latin America and the Caribbean and in sub-Saharan Africa, vaccine coverage decreased over time, while spending increased. INTERPRETATION: These estimates highlight the progress over the past two decades in increasing spending on immunisation. However, many challenges still remain and will require dedication and commitment to ensure that the progress made in the previous decade is sustained and advanced in the next decade for the Immunization Agenda 2030. FUNDING: Bill & Melinda Gates Foundation.

Tracking development assistance for health and for COVID-19: a review of development assistance, government, out-of-pocket, and other private spending on health for 204 countries and territories, 1990-2050.

BACKGROUND: The rapid spread of COVID-19 renewed the focus on how health systems across the globe are financed, especially during public health emergencies. Development assistance is an important source of health financing in many low-income countries, yet little is known about how much of this funding was disbursed for COVID-19. We aimed to put development assistance for health for COVID-19 in the context of broader trends in global health financing, and to estimate total health spending from 1995 to 2050 and development assistance for COVID-19 in 2020. METHODS: We estimated domestic health spending and development assistance for health to generate total health-sector spending estimates for 204 countries and territories. We leveraged data from the WHO Global Health Expenditure Database to produce estimates of domestic health spending. To generate estimates for development assistance for health, we relied on project-level disbursement data from the major international development agencies' online databases and annual financial statements and reports for information on income sources. To adjust our estimates for 2020 to include disbursements related to COVID-19, we extracted project data on commitments and disbursements from a broader set of databases (because not all of the data sources used to estimate the historical series extend to 2020), including the UN Office of Humanitarian Assistance Financial Tracking Service and the International Aid Transparency Initiative. We reported all the historic and future spending estimates in inflation-adjusted 2020 US$, 2020 US$ per capita, purchasing-power parity-adjusted US$ per capita, and as a proportion of gross domestic product. We used various models to generate future health spending to 2050. FINDINGS: In 2019, health spending globally reached $8·8 trillion (95% uncertainty interval [UI] 8·7-8·8) or $1132 (1119-1143) per person. Spending on health varied within and across income groups and geographical regions. Of this total, $40·4 billion (0·5%, 95% UI 0·5-0·5) was development assistance for health provided to low-income and middle-income countries, which made up 24·6% (UI 24·0-25·1) of total spending in low-income countries. We estimate that $54·8 billion in development assistance for health was disbursed in 2020. Of this, $13·7 billion was targeted toward the COVID-19 health response. $12·3 billion was newly committed and $1·4 billion was repurposed from existing health projects. $3·1 billion (22·4%) of the funds focused on country-level coordination and $2·4 billion (17·9%) was for supply chain and logistics. Only $714·4 million (7·7%) of COVID-19 development assistance for health went to Latin America, despite this region reporting 34·3% of total recorded COVID-19 deaths in low-income or middle-income countries in 2020. Spending on health is expected to rise to $1519 (1448-1591) per person in 2050, although spending across countries is expected to remain varied. INTERPRETATION: Global health spending is expected to continue to grow, but remain unequally distributed between countries. We estimate that development organisations substantially increased the amount of development assistance for health provided in 2020. Continued efforts are needed to raise sufficient resources to mitigate the pandemic for the most vulnerable, and to help curtail the pandemic for all. FUNDING: Bill & Melinda Gates Foundation.

Management of thrombotic microangiopathy in pregnancy and postpartum: report from an international working group.

Pregnancy and postpartum are high-risk periods for different forms of thrombotic microangiopathy (TMA). However, the management of pregnancy-associated TMA remains ill defined. This report, by an international multidisciplinary working group of obstetricians, nephrologists, hematologists, intensivists, neonatologists, and complement biologists, summarizes the current knowledge of these potentially severe disorders and proposes a practical clinical approach to diagnose and manage an episode of pregnancy-associated TMA. This approach takes into account the timing of TMA in pregnancy or postpartum, coexisting symptoms, first-line laboratory workup, and probability-based assessment of possible causes of pregnancy-associated TMA. Its aims are: to rule thrombotic thrombocytopenic purpura (TTP) in or out, with urgency, using ADAMTS13 activity testing; to consider alternative disorders with features of TMA (preeclampsia/eclampsia; hemolysis elevated liver enzymes low platelets syndrome; antiphospholipid syndrome); or, ultimately, to diagnose complement-mediated atypical hemolytic uremic syndrome (aHUS; a diagnosis of exclusion). Although they are rare, diagnosing TTP and aHUS associated with pregnancy, and postpartum, is paramount as both require urgent specific treatment.

International prognostic indices in diffuse large B-cell lymphoma: a comparison of IPI, R-IPI, and NCCN-IPI.

Great heterogeneity in survival exists for patients newly diagnosed with diffuse large B-cell lymphoma (DLBCL). Three scoring systems incorporating simple clinical parameters (age, lactate dehydrogenase, number/sites of involvement, stage, performance status) are widely used: the International Prognostic Index (IPI), revised IPI (R-IPI), and National Comprehensive Cancer Network IPI (NCCN-IPI). We evaluated 2124 DLBCL patients treated from 1998 to 2009 with frontline rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP; or variant) across 7 multicenter randomized clinical trials to determine which scoring system best discriminates overall survival (OS). Median age was 63 years, and 56% of patients were male. Five-year OS estimates ranged from 54% to 88%, from 61% to 93%, and from 49% to 92% using the IPI, R-IPI, and NCCN-IPI, respectively. The NCCN-IPI had the greatest absolute difference in OS estimates between the highest- and lowest-risk groups and best discriminated OS (concordance index = 0.632 vs 0.626 [IPI] vs 0.590 [R-IPI]). For each given IPI risk category, NCCN-IPI risk categories were significantly associated with OS (P ≤ .01); the reverse was not true, and the IPI did not provide additional significant prognostic information within all NCCN-IPI risk categories. Collectively, the NCCN-IPI outperformed the IPI and R-IPI. Patients with low-risk NCCN-IPI had favorable survival outcomes with little room for further improvement. In the rituximab era, none of the clinical risk scores identified a patient subgroup with long-term survival clearly <50%. Integrating molecular features of the tumor and microenvironment into the NCCN-IPI or IPI might better characterize a high-risk group for which novel treatment approaches are most needed.