Global funding for cancer research between 2016 and 2020: a content analysis of public and philanthropic investments.

BACKGROUND: Cancer is a leading cause of disease burden globally, with more than 19·3 million cases and 10 million deaths recorded in 2020. Research is crucial to understanding the determinants of cancer and the effects of interventions, and to improving outcomes. We aimed to analyse global patterns of public and philanthropic investment in cancer research. METHODS: In this content analysis, we searched the UberResearch Dimensions database and Cancer Research UK data for human cancer research funding awards from public and philanthropic funders between Jan 1, 2016, and Dec 31, 2020. Included award types were project and programme grants, fellowships, pump priming, and pilot projects. Awards focused on operational delivery of cancer care were excluded. Awards were categorised by cancer type, cross-cutting research theme, and research phase. Funding amount was compared with global burden of specific cancers, measured by disability-adjusted life-years, years lived with disability, and mortality using data from the Global Burden of Disease study. FINDINGS: We identified 66 388 awards with total investment of about US$24·5 billion in 2016-20. Investment decreased year-on-year, with the largest drop observed between 2019 and 2020. Pre-clinical research received 73·5% of the funding across the 5 years ($18 billion), phase 1-4 clinical trials received 7·4% ($1·8 billion), public health research received 9·4% ($2·3 billion), and cross-disciplinary research received 5·0% ($1·2 billion). General cancer research received the largest investment ($7·1 billion, 29·2% of the total funding). The most highly funded cancer types were breast cancer ($2·7 billion [11·2%]), haematological cancer ($2·3 billion [9·4%]), and brain cancer ($1·3 billion [5·5%]). Analysis by cross-cutting theme revealed that 41·2% of investment ($9·6 billion) went to cancer biology research, 19·6% ($4·6 billion) to drug treatment research, and 12·1% ($2·8 billion) to immuno-oncology. 1·4% of the total funding ($0·3 billion) was spent on surgery research, 2·8% ($0·7 billion) was spent on radiotherapy research, and 0·5% ($0·1 billion) was spent on global health studies. INTERPRETATION: Cancer research funding must be aligned with the global burden of cancer with more equitable funding for cancer research in low-income and middle-income countries (which account for 80% of cancer burden), both to support research relevant to these settings, and build research capacity within these countries. There is an urgent need to prioritise investment in surgery and radiotherapy research given their primacy in the treatment of many solid tumours. FUNDING: None.

Conversational Agents in Health Care: Expert Interviews to Inform the Definition, Classification, and Conceptual Framework.

BACKGROUND: Conversational agents (CAs), or chatbots, are computer programs that simulate conversations with humans. The use of CAs in health care settings is recent and rapidly increasing, which often translates to poor reporting of the CA development and evaluation processes and unreliable research findings. We developed and published a conceptual framework, designing, developing, evaluating, and implementing a smartphone-delivered, rule-based conversational agent (DISCOVER), consisting of 3 iterative stages of CA design, development, and evaluation and implementation, complemented by 2 cross-cutting themes (user-centered design and data privacy and security). OBJECTIVE: This study aims to perform in-depth, semistructured interviews with multidisciplinary experts in health care CAs to share their views on the definition and classification of health care CAs and evaluate and validate the DISCOVER conceptual framework. METHODS: We conducted one-on-one semistructured interviews via Zoom (Zoom Video Communications) with 12 multidisciplinary CA experts using an interview guide based on our framework. The interviews were audio recorded, transcribed by the research team, and analyzed using thematic analysis. RESULTS: Following participants' input, we defined CAs as digital interfaces that use natural language to engage in a synchronous dialogue using ≥1 communication modality, such as text, voice, images, or video. CAs were classified by 13 categories: response generation method, input and output modalities, CA purpose, deployment platform, CA development modality, appearance, length of interaction, type of CA-user interaction, dialogue initiation, communication style, CA personality, human support, and type of health care intervention. Experts considered that the conceptual framework could be adapted for artificial intelligence-based CAs. However, despite recent advances in artificial intelligence, including large language models, the technology is not able to ensure safety and reliability in health care settings. Finally, aligned with participants' feedback, we present an updated iteration of the conceptual framework for health care conversational agents (CHAT) with key considerations for CA design, development, and evaluation and implementation, complemented by 3 cross-cutting themes: ethics, user involvement, and data privacy and security. CONCLUSIONS: We present an expanded, validated CHAT and aim at guiding researchers from a variety of backgrounds and with different levels of expertise in the design, development, and evaluation and implementation of rule-based CAs in health care settings.

Scope, Characteristics, Behavior Change Techniques, and Quality of Conversational Agents for Mental Health and Well-Being: Systematic Assessment of Apps.

BACKGROUND: Mental disorders cause substantial health-related burden worldwide. Mobile health interventions are increasingly being used to promote mental health and well-being, as they could improve access to treatment and reduce associated costs. Behavior change is an important feature of interventions aimed at improving mental health and well-being. There is a need to discern the active components that can promote behavior change in such interventions and ultimately improve users' mental health. OBJECTIVE: This study systematically identified mental health conversational agents (CAs) currently available in app stores and assessed the behavior change techniques (BCTs) used. We further described their main features, technical aspects, and quality in terms of engagement, functionality, esthetics, and information using the Mobile Application Rating Scale. METHODS: The search, selection, and assessment of apps were adapted from a systematic review methodology and included a search, 2 rounds of selection, and an evaluation following predefined criteria. We conducted a systematic app search of Apple's App Store and Google Play using 42matters. Apps with CAs in English that uploaded or updated from January 2020 and provided interventions aimed at improving mental health and well-being and the assessment or management of mental disorders were tested by at least 2 reviewers. The BCT taxonomy v1, a comprehensive list of 93 BCTs, was used to identify the specific behavior change components in CAs. RESULTS: We found 18 app-based mental health CAs. Most CAs had <1000 user ratings on both app stores (12/18, 67%) and targeted several conditions such as stress, anxiety, and depression (13/18, 72%). All CAs addressed >1 mental disorder. Most CAs (14/18, 78%) used cognitive behavioral therapy (CBT). Half (9/18, 50%) of the CAs identified were rule based (ie, only offered predetermined answers) and the other half (9/18, 50%) were artificial intelligence enhanced (ie, included open-ended questions). CAs used 48 different BCTs and included on average 15 (SD 8.77; range 4-30) BCTs. The most common BCTs were 3.3 "Social support (emotional)," 4.1 "Instructions for how to perform a behavior," 11.2 "Reduce negative emotions," and 6.1 "Demonstration of the behavior." One-third (5/14, 36%) of the CAs claiming to be CBT based did not include core CBT concepts. CONCLUSIONS: Mental health CAs mostly targeted various mental health issues such as stress, anxiety, and depression, reflecting a broad intervention focus. The most common BCTs identified serve to promote the self-management of mental disorders with few therapeutic elements. CA developers should consider the quality of information, user confidentiality, access, and emergency management when designing mental health CAs. Future research should assess the role of artificial intelligence in promoting behavior change within CAs and determine the choice of BCTs in evidence-based psychotherapies to enable systematic, consistent, and transparent development and evaluation of effective digital mental health interventions.

Aspirin for Secondary Prevention of Cardiovascular Disease in 51 Low-, Middle-, and High-Income Countries.

Importance: Aspirin is an effective and low-cost option for reducing atherosclerotic cardiovascular disease (CVD) events and improving mortality rates among individuals with established CVD. To guide efforts to mitigate the global CVD burden, there is a need to understand current levels of aspirin use for secondary prevention of CVD. Objective: To report and evaluate aspirin use for secondary prevention of CVD across low-, middle-, and high-income countries. Design, Setting, and Participants: Cross-sectional analysis using pooled, individual participant data from nationally representative health surveys conducted between 2013 and 2020 in 51 low-, middle-, and high-income countries. Included surveys contained data on self-reported history of CVD and aspirin use. The sample of participants included nonpregnant adults aged 40 to 69 years. Exposures: Countries' per capita income levels and world region; individuals' socioeconomic demographics. Main Outcomes and Measures: Self-reported use of aspirin for secondary prevention of CVD. Results: The overall pooled sample included 124 505 individuals. The median age was 52 (IQR, 45-59) years, and 50.5% (95% CI, 49.9%-51.1%) were women. A total of 10 589 individuals had a self-reported history of CVD (8.1% [95% CI, 7.6%-8.6%]). Among individuals with a history of CVD, aspirin use for secondary prevention in the overall pooled sample was 40.3% (95% CI, 37.6%-43.0%). By income group, estimates were 16.6% (95% CI, 12.4%-21.9%) in low-income countries, 24.5% (95% CI, 20.8%-28.6%) in lower-middle-income countries, 51.1% (95% CI, 48.2%-54.0%) in upper-middle-income countries, and 65.0% (95% CI, 59.1%-70.4%) in high-income countries. Conclusion and Relevance: Worldwide, aspirin is underused in secondary prevention, particularly in low-income countries. National health policies and health systems must develop, implement, and evaluate strategies to promote aspirin therapy.

Variation in the Proportion of Adults in Need of Blood Pressure-Lowering Medications by Hypertension Care Guideline in Low- and Middle-Income Countries: A Cross-Sectional Study of 1 037 215 Individuals From 50 Nationally Representative Surveys.

BACKGROUND: Current hypertension guidelines vary substantially in their definition of who should be offered blood pressure-lowering medications. Understanding the effect of guideline choice on the proportion of adults who require treatment is crucial for planning and scaling up hypertension care in low- and middle-income countries. METHODS: We extracted cross-sectional data on age, sex, blood pressure, hypertension treatment and diagnosis status, smoking, and body mass index for adults 30 to 70 years of age from nationally representative surveys in 50 low- and middle-income countries (N = 1 037 215). We aimed to determine the effect of hypertension guideline choice on the proportion of adults in need of blood pressure-lowering medications. We considered 4 hypertension guidelines: the 2017 American College of Cardiology/American Heart Association guideline, the commonly used 140/90 mm Hg threshold, the 2016 World Health Organization HEARTS guideline, and the 2019 UK National Institute for Health and Care Excellence guideline. RESULTS: The proportion of adults in need of blood pressure-lowering medications was highest under the American College of Cardiology/American Heart Association, followed by the 140/90 mm Hg, National Institute for Health and Care Excellence, and World Health Organization guidelines (American College of Cardiology/American Heart Association: women, 27.7% [95% CI, 27.2-28.2], men, 35.0% [95% CI, 34.4-35.7]; 140/90 mm Hg: women, 26.1% [95% CI, 25.5-26.6], men, 31.2% [95% CI, 30.6-31.9]; National Institute for Health and Care Excellence: women, 11.8% [95% CI, 11.4-12.1], men, 15.7% [95% CI, 15.3-16.2]; World Health Organization: women, 9.2% [95% CI, 8.9-9.5], men, 11.0% [95% CI, 10.6-11.4]). Individuals who were unaware that they have hypertension were the primary contributor to differences in the proportion needing treatment under different guideline criteria. Differences in the proportion needing blood pressure-lowering medications were largest in the oldest (65-69 years) age group (American College of Cardiology/American Heart Association: women, 60.2% [95% CI, 58.8-61.6], men, 70.1% [95% CI, 68.8-71.3]; World Health Organization: women, 20.1% [95% CI, 18.8-21.3], men, 24.1.0% [95% CI, 22.3-25.9]). For both women and men and across all guidelines, countries in the European and Eastern Mediterranean regions had the highest proportion of adults in need of blood pressure-lowering medicines, whereas the South and Central Americas had the lowest. CONCLUSIONS: There was substantial variation in the proportion of adults in need of blood pressure-lowering medications depending on which hypertension guideline was used. Given the great implications of this choice for health system capacity, policy makers will need to carefully consider which guideline they should adopt when scaling up hypertension care in their country.

Estimated economic burden of genital herpes and HIV attributable to herpes simplex virus type 2 infections in 90 low- and middle-income countries: A modeling study.

BACKGROUND: Economic losses due to herpes simplex infections in low- and middle-income countries (LMICs) are unknown. We estimated economic and quality-of-life losses due to genital herpes in 2019, in 90 LMICs, and from 2020 to 2030 in 45 countries in the World Health Organization (WHO) Africa. We additionally estimated economic losses due to human immunodeficiency virus (HIV) attributable to herpes simplex virus type 2 (HSV-2) infections. METHODS AND FINDINGS: We estimated genital herpes-related spending on treatment, wage losses due to absenteeism, and reductions in quality of life, for individuals aged 15 to 49 years, living with genital herpes. Had HSV-2 had contributed to the transmission of HIV, we estimated the share of antiretroviral treatment costs and HIV-related wage losses in 2019 that can be attributed to incident and prevalent HSV-2 infections in 2018. For the former, we used estimates of HSV-2 incidence and prevalence from the global burden of disease (GBD) study. For the latter, we calculated population attributable fractions (PAFs), using the classic (Levin's) epidemiological formula for polytomous exposures, with relative risks (RRs) reported in literature. To extend estimates from 2020 to 2030, we modeled the transmission of HSV-2 in 45 African countries using a deterministic compartmental mathematical model, structured by age, sex, and sexual activity, which was fitted to seroprevalence gathered from a systematic review and meta-regression analysis. In the 90 LMICs, genital herpes contributed to US$813.5 million in treatment and productivity losses in 2019 (range: US$674.4 to US$952.2 million). Given observed care-seeking and absenteeism, losses are in the range of US$29.0 billion (US$25.6 billion to US$34.5 billion). Quality-of-life losses in the amount of 61.7 million quality-adjusted life years (QALYs) are also possible (50.4 million to 74.2 million). The mean annual cost of treatment and wage losses per infection is US$183.00 (95% CI: US$153.60 to US$212.55); the mean annual cost of quality-of-life losses is US$343.27 (95% CI: 272.41 to 414.14). If HSV-2 has fueled the transmission of HIV, then seroprevalent HSV-2 cases in 2018 can account for 33.2% of the incident HIV infections in 2019, with an associated antiretroviral therapy (ART) cost of US$186.3 million (range: US$163.6 to US$209.5 million) and 28.6% of HIV-related wage losses (US$21.9 million; range: US$19.2 to US$27.4 million). In the WHO Africa region, the 3.9 million seroprevalent genital herpes cases from 2020 to 2030 contributed to US$700.2 million in treatment and productivity losses. Additionally, quality-of-life losses in the range of 88 million to 871 million QALYs are also possible. If HSV-2 has contributed to the transmission of HIV, then in 2020, the PAF of HIV due to prevalent HSV-2 will be 32.8% (95% CI: 26.7% to 29.9%) and due to incident infections will be 4.2% (95% CI: 2.6% to 3.4%). The PAF due to prevalent infections will decline to 31.0% by 2030 and incident infections to 3.6%. Though we have accounted for the uncertainty in the epidemiological and economic parameter values via the sensitivity analysis, our estimates still undervalue losses due to limiting to the 15- to 49-year-old population. CONCLUSIONS: Economic losses due to genital herpes in LMICs can be large, especially when considering the lifelong nature of the disease. Quality-of-life losses outweigh spending on treatment and reductions in productivity. If HSV-2 has contributed to the spread of HIV in LMICs, then nearly one third of antiretroviral costs and HIV-related wage losses can be attributed to HSV-2. Given the magnitude of the combined losses, a vaccine against HSV-2 must be a global priority.

Body-mass index and diabetes risk in 57 low-income and middle-income countries: a cross-sectional study of nationally representative, individual-level data in 685 616 adults.

BACKGROUND: The prevalence of overweight, obesity, and diabetes is rising rapidly in low-income and middle-income countries (LMICs), but there are scant empirical data on the association between body-mass index (BMI) and diabetes in these settings. METHODS: In this cross-sectional study, we pooled individual-level data from nationally representative surveys across 57 LMICs. We identified all countries in which a WHO Stepwise Approach to Surveillance (STEPS) survey had been done during a year in which the country fell into an eligible World Bank income group category. For LMICs that did not have a STEPS survey, did not have valid contact information, or declined our request for data, we did a systematic search for survey datasets. Eligible surveys were done during or after 2008; had individual-level data; were done in a low-income, lower-middle-income, or upper-middle-income country; were nationally representative; had a response rate of 50% or higher; contained a diabetes biomarker (either a blood glucose measurement or glycated haemoglobin [HbA1c]); and contained data on height and weight. Diabetes was defined biologically as a fasting plasma glucose concentration of 7·0 mmol/L (126·0 mg/dL) or higher; a random plasma glucose concentration of 11·1 mmol/L (200·0 mg/dL) or higher; or a HbA1c of 6·5% (48·0 mmol/mol) or higher, or by self-reported use of diabetes medication. We included individuals aged 25 years or older with complete data on diabetes status, BMI (defined as normal [18·5-22·9 kg/m2], upper-normal [23·0-24·9 kg/m2], overweight [25·0-29·9 kg/m2], or obese [≥30·0 kg/m2]), sex, and age. Countries were categorised into six geographical regions: Latin America and the Caribbean, Europe and central Asia, east, south, and southeast Asia, sub-Saharan Africa, Middle East and north Africa, and Oceania. We estimated the association between BMI and diabetes risk by multivariable Poisson regression and receiver operating curve analyses, stratified by sex and geographical region. FINDINGS: Our pooled dataset from 58 nationally representative surveys in 57 LMICs included 685 616 individuals. The overall prevalence of overweight was 27·2% (95% CI 26·6-27·8), of obesity was 21·0% (19·6-22·5), and of diabetes was 9·3% (8·4-10·2). In the pooled analysis, a higher risk of diabetes was observed at a BMI of 23 kg/m2 or higher, with a 43% greater risk of diabetes for men and a 41% greater risk for women compared with a BMI of 18·5-22·9 kg/m2. Diabetes risk also increased steeply in individuals aged 35-44 years and in men aged 25-34 years in sub-Saharan Africa. In the stratified analyses, there was considerable regional variability in this association. Optimal BMI thresholds for diabetes screening ranged from 23·8 kg/m2 among men in east, south, and southeast Asia to 28·3 kg/m2 among women in the Middle East and north Africa and in Latin America and the Caribbean. INTERPRETATION: The association between BMI and diabetes risk in LMICs is subject to substantial regional variability. Diabetes risk is greater at lower BMI thresholds and at younger ages than reflected in currently used BMI cutoffs for assessing diabetes risk. These findings offer an important insight to inform context-specific diabetes screening guidelines. FUNDING: Harvard T H Chan School of Public Health McLennan Fund: Dean's Challenge Grant Program.

Which countries need COVID-19 vaccines the most? Development of a prioritisation tool.

BACKGROUND: The COVID-19 pandemic and associated non-pharmaceutical interventions (NPIs) have affected all countries. With a scarcity of COVID-19 vaccines there has been a need to prioritize populations, but assessing relative needs has been challenging. The COVAX Facility allocates vaccines to cover 20% of each national population, followed by a needs assessment that considers five quantitative metrics alongside a qualitative assessment. The objective of this study was to identify the most important factors for assessing countries' needs for vaccines, and to weight each, generating a scoring tool for prioritising countries. METHODS: The study was conducted between March and November 2021. The first stage involved an online Delphi survey with a purposive and snowball sample of public health experts, to reach consensus on country-level factors for assessing relative needs for COVID-19 vaccines. The second stage involved a discrete choice experiment (DCE) to determine weights for the most important factors. RESULTS: Responses were received from 28 experts working across 13 different countries and globally. The most common job titles reported were director and professor, with most based in national public health institutes (n = 9) and universities (n = 8). The Delphi survey found 37 distinct factors related to needs. Nine of the most important factors were included in the DCE. Among these, the most important factor was the 'proportion of overall population not fully vaccinated' (with a mean weight of 19.5), followed by 'proportion of high-risk population not fully vaccinated' (16.1), 'health system capacity' (14.2), 'capacity to purchase vaccines' (11.9) and the 'proportion of the population clinically vulnerable' (11.3). CONCLUSIONS: Several factors exist, extending beyond those currently used, which may lead to some countries having a greater need for vaccines compared to others. By assessing relative needs, this scoring tool can build on existing methods to further the role of equity in global COVID-19 vaccine allocation.

Conversational Agents in Health Care: Scoping Review of Their Behavior Change Techniques and Underpinning Theory.

BACKGROUND: Conversational agents (CAs) are increasingly used in health care to deliver behavior change interventions. Their evaluation often includes categorizing the behavior change techniques (BCTs) using a classification system of which the BCT Taxonomy v1 (BCTTv1) is one of the most common. Previous studies have presented descriptive summaries of behavior change interventions delivered by CAs, but no in-depth study reporting the use of BCTs in these interventions has been published to date. OBJECTIVE: This review aims to describe behavior change interventions delivered by CAs and to identify the BCTs and theories guiding their design. METHODS: We searched PubMed, Embase, Cochrane's Central Register of Controlled Trials, and the first 10 pages of Google and Google Scholar in April 2021. We included primary, experimental studies evaluating a behavior change intervention delivered by a CA. BCTs coding followed the BCTTv1. Two independent reviewers selected the studies and extracted the data. Descriptive analysis and frequent itemset mining to identify BCT clusters were performed. RESULTS: We included 47 studies reporting on mental health (n=19, 40%), chronic disorders (n=14, 30%), and lifestyle change (n=14, 30%) interventions. There were 20/47 embodied CAs (43%) and 27/47 CAs (57%) represented a female character. Most CAs were rule based (34/47, 72%). Experimental interventions included 63 BCTs, (mean 9 BCTs; range 2-21 BCTs), while comparisons included 32 BCTs (mean 2 BCTs; range 2-17 BCTs). Most interventions included BCTs 4.1 "Instruction on how to perform a behavior" (34/47, 72%), 3.3 "Social support" (emotional; 27/47, 57%), and 1.2 "Problem solving" (24/47, 51%). A total of 12/47 studies (26%) were informed by a behavior change theory, mainly the Transtheoretical Model and the Social Cognitive Theory. Studies using the same behavior change theory included different BCTs. CONCLUSIONS: There is a need for the more explicit use of behavior change theories and improved reporting of BCTs in CA interventions to enhance the analysis of intervention effectiveness and improve the reproducibility of research.

Digital Education for Health Professionals: An Evidence Map, Conceptual Framework, and Research Agenda.

BACKGROUND: Health professions education has undergone major changes with the advent and adoption of digital technologies worldwide. OBJECTIVE: This study aims to map the existing evidence and identify gaps and research priorities to enable robust and relevant research in digital health professions education. METHODS: We searched for systematic reviews on the digital education of practicing and student health care professionals. We searched MEDLINE, Embase, Cochrane Library, Educational Research Information Center, CINAHL, and gray literature sources from January 2014 to July 2020. A total of 2 authors independently screened the studies, extracted the data, and synthesized the findings. We outlined the key characteristics of the included reviews, the quality of the evidence they synthesized, and recommendations for future research. We mapped the empirical findings and research recommendations against the newly developed conceptual framework. RESULTS: We identified 77 eligible systematic reviews. All of them included experimental studies and evaluated the effectiveness of digital education interventions in different health care disciplines or different digital education modalities. Most reviews included studies on various digital education modalities (22/77, 29%), virtual reality (19/77, 25%), and online education (10/77, 13%). Most reviews focused on health professions education in general (36/77, 47%), surgery (13/77, 17%), and nursing (11/77, 14%). The reviews mainly assessed participants' skills (51/77, 66%) and knowledge (49/77, 64%) and included data from high-income countries (53/77, 69%). Our novel conceptual framework of digital health professions education comprises 6 key domains (context, infrastructure, education, learners, research, and quality improvement) and 16 subdomains. Finally, we identified 61 unique questions for future research in these reviews; these mapped to framework domains of education (29/61, 47% recommendations), context (17/61, 28% recommendations), infrastructure (9/61, 15% recommendations), learners (3/61, 5% recommendations), and research (3/61, 5% recommendations). CONCLUSIONS: We identified a large number of research questions regarding digital education, which collectively reflect a diverse and comprehensive research agenda. Our conceptual framework will help educators and researchers plan, develop, and study digital education. More evidence from low- and middle-income countries is needed.

Global costs, health benefits, and economic benefits of scaling up treatment and imaging modalities for survival of 11 cancers: a simulation-based analysis.

BACKGROUND: In addition to increased availability of treatment modalities, advanced imaging modalities are increasingly recommended to improve global cancer care. However, estimates of the costs and benefits of investments to improve cancer survival are scarce, especially for low-income and middle-income countries (LMICs). In this analysis, we aimed to estimate the costs and lifetime health and economic benefits of scaling up imaging and treatment modality packages on cancer survival, both globally and by country income group. METHODS: Using a previously developed model of global cancer survival, we estimated stage-specific cancer survival and life-years gained (accounting for competing mortality) in 200 countries and territories for patients diagnosed with one of 11 cancers (oesophagus, stomach, colon, rectum, anus, liver, pancreas, lung, breast, cervix uteri, and prostate) representing 60% of all cancer diagnoses between 2020 and 2030 (inclusive of full years). We evaluated the costs and health and economic benefits of scaling up packages of treatment (chemotherapy, surgery, radiotherapy, and targeted therapy), imaging modalities (ultrasound, x-ray, CT, MRI, PET, single-photon emission CT), and quality of care to the mean level of high-income countries, separately and in combination, compared with no scale-up. Costs and benefits are presented in 2018 US$ and discounted at 3% annually. FINDINGS: For the 11 cancers studied, we estimated that without scale-up (ie, with current availability of treatment, imaging, and quality of care) there will be 76·0 million cancer deaths (95% UI 73·9-78·6) globally for patients diagnosed between 2020 and 2030, with more than 70% of these deaths occurring in LMICs. Comprehensive scale-up of treatment, imaging, and quality of care could avert 12·5% (95% UI 9·0-16·3) of these deaths globally, ranging from 2·8% (1·8-4·3) in high-income countries to 38·2% (32·6-44·5) in low-income countries. Globally, we estimate that comprehensive scale-up would cost an additional $232·9 billion (95% UI 85·9-422·0) between 2020 and 2030 (representing a 6·9% increase in cancer treatment costs), but produce $2·9 trillion (1·8-4·0) in lifetime economic benefits, yielding a return of $12·43 (6·47-33·23) per dollar invested. Scaling up treatment and quality of care without imaging would yield a return of $6·15 (2·66-16·71) per dollar invested and avert 7·0% (3·9-10·3) of cancer deaths worldwide. INTERPRETATION: Simultaneous investment in cancer treatment, imaging, and quality of care could yield substantial health and economic benefits, especially in LMICs. These results provide a compelling rationale for the value of investing in the global scale-up of cancer care. FUNDING: Harvard TH Chan School of Public Health and National Cancer Institute.

The impact of scaling up access to treatment and imaging modalities on global disparities in breast cancer survival: a simulation-based analysis.

BACKGROUND: Female breast cancer is the most commonly diagnosed cancer in the world, with wide variations in reported survival by country. Women in low-income and middle-income countries (LMICs) in particular face several barriers to breast cancer services, including diagnostics and treatment. We aimed to estimate the potential impact of scaling up the availability of treatment and imaging modalities on breast cancer survival globally, together with improvements in quality of care. METHODS: For this simulation-based analysis, we used a microsimulation model of global cancer survival, which accounts for the availability and stage-specific survival impact of specific treatment modalities (chemotherapy, radiotherapy, surgery, and targeted therapy), imaging modalities (ultrasound, x-ray, CT, MRI, PET, and single-photon emission computed tomography [SPECT]), and quality of cancer care, to simulate 5-year net survival for women with newly diagnosed breast cancer in 200 countries and territories in 2018. We calibrated the model to empirical data on 5-year net breast cancer survival in 2010-14 from CONCORD-3. We evaluated the potential impact of scaling up specific imaging and treatment modalities and quality of care to the mean level of high-income countries, individually and in combination. We ran 1000 simulations for each policy intervention and report the means and 95% uncertainty intervals (UIs) for all model outcomes. FINDINGS: We estimate that global 5-year net survival for women diagnosed with breast cancer in 2018 was 67·9% (95% UI 62·9-73·4) overall, with an almost 25-times difference between low-income (3·5% [0·4-10·0]) and high-income (87·0% [85·6-88·4]) countries. Among individual treatment modalities, scaling up access to surgery alone was estimated to yield the largest survival gains globally (2·7% [95% UI 0·4-8·3]), and scaling up CT alone would have the largest global impact among imaging modalities (0·5% [0·0-2·0]). Scaling up a package of traditional modalities (surgery, chemotherapy, radiotherapy, ultrasound, and x-ray) could improve global 5-year net survival to 75·6% (95% UI 70·6-79·4), with survival in low-income countries improving from 3·5% (0·4-10·0) to 28·6% (4·9-60·1). Adding concurrent improvements in quality of care could further improve global 5-year net survival to 78·2% (95% UI 74·9-80·4), with a substantial impact in low-income countries, improving net survival to 55·3% (42·2-67·8). Comprehensive scale-up of access to all modalities and improvements in quality of care could improve global 5-year net survival to 82·3% (95% UI 79·3-85·0). INTERPRETATION: Comprehensive scale-up of treatment and imaging modalities, and improvements in quality of care could improve global 5-year net breast cancer survival by nearly 15 percentage points. Scale-up of traditional modalities and quality-of-care improvements could achieve 70% of these total potential gains, with substantial impact in LMICs, providing a more feasible pathway to improving breast cancer survival in these settings even without the benefits of future investments in targeted therapy and advanced imaging. FUNDING: Harvard T H Chan School of Public Health, and National Cancer Institute P30 Cancer Center Support Grant to Memorial Sloan Kettering Cancer Center.

Estimating the impact of the COVID-19 pandemic on diagnosis and survival of five cancers in Chile from 2020 to 2030: a simulation-based analysis.

BACKGROUND: The COVID-19 pandemic has strained health system capacity worldwide due to a surge of hospital admissions, while mitigation measures have simultaneously reduced patients' access to health care, affecting the diagnosis and treatment of other diseases such as cancer. We estimated the impact of delayed diagnosis on cancer outcomes in Chile using a novel modelling approach to inform policies and planning to mitigate the forthcoming cancer-related health impacts of the pandemic in Chile. METHODS: We developed a microsimulation model of five cancers in Chile (breast, cervix, colorectal, prostate, and stomach) for which reliable data were available, which simulates cancer incidence and progression in a nationally representative virtual population, as well as stage-specific cancer detection and survival probabilities. We calibrated the model to empirical data on monthly detected cases, as well as stage at diagnosis and 5-year net survival. We accounted for the impact of COVID-19 on excess mortality and cancer detection by month during the pandemic, and projected diagnosed cancer cases and outcomes of stage at diagnosis and survival up to 2030. For comparison, we simulated a no COVID-19 scenario in which the impacts of COVID-19 on excess mortality and cancer detection were removed. FINDINGS: Our modelling showed a sharp decrease in the number of diagnosed cancer cases during the COVID-19 pandemic, with a large projected short-term increase in future diagnosed cases. Due to the projected backlog in diagnosis, we estimated that in 2021 there will be an extra 3198 cases (95% uncertainty interval [UI] 1356-5017) diagnosed among the five modelled cancers, an increase of nearly 14% compared with the no COVID-19 scenario, falling to a projected 10% increase in 2022 with 2674 extra cases (1318-4032) diagnosed. As a result of delayed diagnosis, we found a worse stage distribution for detected cancers in 2020-22, which is estimated to lead to 3542 excess cancer deaths (95% UI 2236-4816) in 2022-30, compared with the no COVID-19 scenario, among the five modelled cancers, most of which (3299 deaths, 2151-4431) are projected to occur before 2025. INTERPRETATION: In addition to a large projected surge in diagnosed cancer cases, we found that delays in diagnosis will result in worse cancer stage at presentation, leading to worse survival outcomes. These findings can help to inform surge capacity planning and highlight the importance of ensuring appropriate health system capacity levels to detect and care for the increased cancer cases in the coming years, while maintaining the timeliness and quality of cancer care. Potential delays in treatment and adverse impacts on quality of care, which were not considered in this model, are likely to contribute to even more excess deaths from cancer than projected. FUNDING: Harvard TH Chan School of Public Health. TRANSLATIONS: For the Spanish and Portuguese translations of the abstract see Supplementary Materials section.

Medical imaging and nuclear medicine: a Lancet Oncology Commission.

The diagnosis and treatment of patients with cancer requires access to imaging to ensure accurate management decisions and optimal outcomes. Our global assessment of imaging and nuclear medicine resources identified substantial shortages in equipment and workforce, particularly in low-income and middle-income countries (LMICs). A microsimulation model of 11 cancers showed that the scale-up of imaging would avert 3·2% (2·46 million) of all 76·0 million deaths caused by the modelled cancers worldwide between 2020 and 2030, saving 54·92 million life-years. A comprehensive scale-up of imaging, treatment, and care quality would avert 9·55 million (12·5%) of all cancer deaths caused by the modelled cancers worldwide, saving 232·30 million life-years. Scale-up of imaging would cost US$6·84 billion in 2020-30 but yield lifetime productivity gains of $1·23 trillion worldwide, a net return of $179·19 per $1 invested. Combining the scale-up of imaging, treatment, and quality of care would provide a net benefit of $2·66 trillion and a net return of $12·43 per $1 invested. With the use of a conservative approach regarding human capital, the scale-up of imaging alone would provide a net benefit of $209·46 billion and net return of $31·61 per $1 invested. With comprehensive scale-up, the worldwide net benefit using the human capital approach is $340·42 billion and the return per dollar invested is $2·46. These improved health and economic outcomes hold true across all geographical regions. We propose actions and investments that would enhance access to imaging equipment, workforce capacity, digital technology, radiopharmaceuticals, and research and training programmes in LMICs, to produce massive health and economic benefits and reduce the burden of cancer globally.

Evidence-based policymaking when evidence is incomplete: The case of HIV programme integration.

Jan Hontelez and co-authors discuss the use of different types of evidence to inform HIV program integration.

Integrating HIV services and other health services: A systematic review and meta-analysis.

BACKGROUND: Integration of HIV services with other health services has been proposed as an important strategy to boost the sustainability of the global HIV response. We conducted a systematic and comprehensive synthesis of the existing scientific evidence on the impact of service integration on the HIV care cascade, health outcomes, and cost-effectiveness. METHODS AND FINDINGS: We reviewed the global quantitative empirical evidence on integration published between 1 January 2010 and 10 September 2021. We included experimental and observational studies that featured both an integration intervention and a comparator in our review. Of the 7,118 unique peer-reviewed English-language studies that our search algorithm identified, 114 met all of our selection criteria for data extraction. Most of the studies (90) were conducted in sub-Saharan Africa, primarily in East Africa (55) and Southern Africa (24). The most common forms of integration were (i) HIV testing and counselling added to non-HIV services and (ii) non-HIV services added to antiretroviral therapy (ART). The most commonly integrated non-HIV services were maternal and child healthcare, tuberculosis testing and treatment, primary healthcare, family planning, and sexual and reproductive health services. Values for HIV care cascade outcomes tended to be better in integrated services: uptake of HIV testing and counselling (pooled risk ratio [RR] across 37 studies: 1.67 [95% CI 1.41-1.99], p < 0.001), ART initiation coverage (pooled RR across 19 studies: 1.42 [95% CI 1.16-1.75], p = 0.002), time until ART initiation (pooled RR across 5 studies: 0.45 [95% CI 0.20-1.00], p = 0.050), retention in HIV care (pooled RR across 19 studies: 1.68 [95% CI 1.05-2.69], p = 0.031), and viral suppression (pooled RR across 9 studies: 1.19 [95% CI 1.03-1.37], p = 0.025). Also, treatment success for non-HIV-related diseases and conditions and the uptake of non-HIV services were commonly higher in integrated services. We did not find any significant differences for the following outcomes in our meta-analyses: HIV testing yield, ART adherence, HIV-free survival among infants, and HIV and non-HIV mortality. We could not conduct meta-analyses for several outcomes (HIV infections averted, costs, and cost-effectiveness), because our systematic review did not identify sufficient poolable studies. Study limitations included possible publication bias of studies with significant or favourable findings and comparatively weak evidence from some world regions and on integration of services for key populations in the HIV response. CONCLUSIONS: Integration of HIV services and other health services tends to improve health and health systems outcomes. Despite some scientific limitations, the global evidence shows that service integration can be a valuable strategy to boost the sustainability of the HIV response and contribute to the goal of 'ending AIDS by 2030', while simultaneously supporting progress towards universal health coverage.

Unmet need for hypercholesterolemia care in 35 low- and middle-income countries: A cross-sectional study of nationally representative surveys.

BACKGROUND: As the prevalence of hypercholesterolemia is increasing in low- and middle-income countries (LMICs), detailed evidence is urgently needed to guide the response of health systems to this epidemic. This study sought to quantify unmet need for hypercholesterolemia care among adults in 35 LMICs. METHODS AND FINDINGS: We pooled individual-level data from 129,040 respondents aged 15 years and older from 35 nationally representative surveys conducted between 2009 and 2018. Hypercholesterolemia care was quantified using cascade of care analyses in the pooled sample and by region, country income group, and country. Hypercholesterolemia was defined as (i) total cholesterol (TC) ≥240 mg/dL or self-reported lipid-lowering medication use and, alternatively, as (ii) low-density lipoprotein cholesterol (LDL-C) ≥160 mg/dL or self-reported lipid-lowering medication use. Stages of the care cascade for hypercholesterolemia were defined as follows: screened (prior to the survey), aware of diagnosis, treated (lifestyle advice and/or medication), and controlled (TC <200 mg/dL or LDL-C <130 mg/dL). We further estimated how age, sex, education, body mass index (BMI), current smoking, having diabetes, and having hypertension are associated with cascade progression using modified Poisson regression models with survey fixed effects. High TC prevalence was 7.1% (95% CI: 6.8% to 7.4%), and high LDL-C prevalence was 7.5% (95% CI: 7.1% to 7.9%). The cascade analysis showed that 43% (95% CI: 40% to 45%) of study participants with high TC and 47% (95% CI: 44% to 50%) with high LDL-C ever had their cholesterol measured prior to the survey. About 31% (95% CI: 29% to 33%) and 36% (95% CI: 33% to 38%) were aware of their diagnosis; 29% (95% CI: 28% to 31%) and 33% (95% CI: 31% to 36%) were treated; 7% (95% CI: 6% to 9%) and 19% (95% CI: 18% to 21%) were controlled. We found substantial heterogeneity in cascade performance across countries and higher performances in upper-middle-income countries and the Eastern Mediterranean, Europe, and Americas. Lipid screening was significantly associated with older age, female sex, higher education, higher BMI, comorbid diagnosis of diabetes, and comorbid diagnosis of hypertension. Awareness of diagnosis was significantly associated with older age, higher BMI, comorbid diagnosis of diabetes, and comorbid diagnosis of hypertension. Lastly, treatment of hypercholesterolemia was significantly associated with comorbid hypertension and diabetes, and control of lipid measures with comorbid diabetes. The main limitations of this study are a potential recall bias in self-reported information on received health services as well as diminished comparability due to varying survey years and varying lipid guideline application across country and clinical settings. CONCLUSIONS: Cascade performance was poor across all stages, indicating large unmet need for hypercholesterolemia care in this sample of LMICs-calling for greater policy and research attention toward this cardiovascular disease (CVD) risk factor and highlighting opportunities for improved prevention of CVD.

Cardiovascular disease risk profile and management practices in 45 low-income and middle-income countries: A cross-sectional study of nationally representative individual-level survey data.

BACKGROUND: Global cardiovascular disease (CVD) burden is high and rising, especially in low-income and middle-income countries (LMICs). Focussing on 45 LMICs, we aimed to determine (1) the adult population's median 10-year predicted CVD risk, including its variation within countries by socio-demographic characteristics, and (2) the prevalence of self-reported blood pressure (BP) medication use among those with and without an indication for such medication as per World Health Organization (WHO) guidelines. METHODS AND FINDINGS: We conducted a cross-sectional analysis of nationally representative household surveys from 45 LMICs carried out between 2005 and 2017, with 32 surveys being WHO Stepwise Approach to Surveillance (STEPS) surveys. Country-specific median 10-year CVD risk was calculated using the 2019 WHO CVD Risk Chart Working Group non-laboratory-based equations. BP medication indications were based on the WHO Package of Essential Noncommunicable Disease Interventions guidelines. Regression models examined associations between CVD risk, BP medication use, and socio-demographic characteristics. Our complete case analysis included 600,484 adults from 45 countries. Median 10-year CVD risk (interquartile range [IQR]) for males and females was 2.7% (2.3%-4.2%) and 1.6% (1.3%-2.1%), respectively, with estimates indicating the lowest risk in sub-Saharan Africa and highest in Europe and the Eastern Mediterranean. Higher educational attainment and current employment were associated with lower CVD risk in most countries. Of those indicated for BP medication, the median (IQR) percentage taking medication was 24.2% (15.4%-37.2%) for males and 41.6% (23.9%-53.8%) for females. Conversely, a median (IQR) 47.1% (36.1%-58.6%) of all people taking a BP medication were not indicated for such based on CVD risk status. There was no association between BP medication use and socio-demographic characteristics in most of the 45 study countries. Study limitations include variation in country survey methods, most notably the sample age range and year of data collection, insufficient data to use the laboratory-based CVD risk equations, and an inability to determine past history of a CVD diagnosis. CONCLUSIONS: This study found underuse of guideline-indicated BP medication in people with elevated CVD risk and overuse by people with lower CVD risk. Country-specific targeted policies are needed to help improve the identification and management of those at highest CVD risk.

A global investment framework for the elimination of hepatitis B.

BACKGROUND & AIMS: More than 292 million people are living with hepatitis B worldwide and are at risk of death from cirrhosis and liver cancer. The World Health Organization (WHO) has set global targets for the elimination of viral hepatitis as a public health threat by 2030. However, current levels of global investment in viral hepatitis elimination programmes are insufficient to achieve these goals. METHODS: To catalyse political commitment and to encourage domestic and international financing, we used published modelling data and key stakeholder interviews to develop an investment framework to demonstrate the return on investment for viral hepatitis elimination. RESULTS: The framework utilises a public health approach to identify evidence-based national activities that reduce viral hepatitis-related morbidity and mortality, as well as international activities and critical enablers that allow countries to achieve maximum impact on health outcomes from their investments - in the context of the WHO's 2030 viral elimination targets. CONCLUSION: Focusing on hepatitis B, this health policy paper employs the investment framework to estimate the substantial economic benefits of investing in the elimination of hepatitis B and demonstrates how such investments could be cost saving by 2030. LAY SUMMARY: Hepatitis B infection is a major cause of death from liver disease and liver cancer globally. To reduce deaths from hepatitis B infection, we need more people to be tested and treated for hepatitis B. In this paper, we outline a framework of activities to reduce hepatitis B-related deaths and discuss ways in which governments could pay for them.

The association between mental-physical multimorbidity and disability, work productivity, and social participation in China: a panel data analysis.

BACKGROUND: The co-occurrence of mental and physical chronic conditions (mental-physical multimorbidity) is a growing and largely unaddressed challenge for health systems and wider economies in low-and middle-income countries. This study investigated the independent and combined (additive or synergistic) effects of mental and physical chronic conditions on disability, work productivity, and social participation in China. METHODS: Panel data study design utilised two waves of the China Health and Retirement Longitudinal Study (2011, 2015), including 5616 participants aged ≥45 years, 12 physical chronic conditions and depression. We used a panel data approach of random-effects regression models to assess the relationships between mental-physical multimorbidity and outcomes. RESULTS: After adjusting for socio-economic and demographic factors, an increased number of physical chronic conditions was independently associated with a higher likelihood of disability (Adjusted odds ratio (AOR) = 1.39; 95% CI: 1.33, 1.45), early retirement (AOR = 1.37 [1.26, 1.49]) and increased sick leave days (1.25 days [1.16, 1.35]). Depression was independently associated with disability (AOR = 3.78 [3.30, 4.34]), increased sick leave days (2.18 days [1.72, 2.77]) and a lower likelihood of social participation (AOR = 0.57 [0.47, 0.70]), but not with early retirement (AOR = 1.24 [0.97, 1.58]). There were small and statistically insignificant interactions between physical chronic conditions and mental health on disability, work productivity and social participation, suggesting an additive effect of mental-physical multimorbidity on productivity loss. CONCLUSION: Mental-physical multimorbidity poses substantial negative health and economic effects on individuals, health systems, and societies. More research that addresses the challenges of mental-physical multimorbidity is needed to inform the development of interventions that can be applied to the workplace and the wider community in China.