Publications

2022
Ward ZJ, Willett WC, Hu FB, Pacheco LS, Long MW, Gortmaker SL. Excess mortality associated with elevated body weight in the USA by state and demographic subgroup: A modelling study. EClinicalMedicine. 2022;48 :101429.Abstract
Background: The obesity epidemic in the USA continues to grow nationwide. Although excess weight-related mortality has been studied in general, less is known about how it varies by demographic subgroup within the USA. In this study we estimated excess mortality associated with elevated body weight nationally and by state and subgroup. Methods: We developed a nationally-representative microsimulation (individual-level) model of US adults between 1999 and 2016, based on risk factor data from 6,002,012 Behavioral Risk Factor Surveillance System respondents. Prior probability distributions for hazard ratios relating body-mass index (BMI) to mortality were informed by a global pooling dataset. Individual-level mortality risks were modelled accounting for demographics, smoking history, and BMI adjusted for self-report bias. We calibrated the model to empirical all-cause mortality rates from CDC WONDER by state and subgroup, and assessed the predictive accuracy of the model using a random sample of data withheld from model fitting. We simulated counterfactual scenarios to estimate excess mortality attributable to different levels of excess weight and smoking history. Findings: We estimated that excess weight was responsible for more than 1300 excess deaths per day (nearly 500,000 per year) and a loss in life expectancy of nearly 2·4 years in 2016, contributing to higher excess mortality than smoking. Relative excess mortality rates were nearly twice as high for women compared to men in 2016 (21·9% vs 13·9%), and were higher for Black non-Hispanic adults. By state, overall excess weight-related life expectancy loss ranged from 1·75 years (95% UI 1·57-1·94) in Colorado to 3·18 years (95% UI 2·86-3·51) in Mississippi. Interpretation: Excess weight has substantial impacts on mortality in the USA, with large disparities by state and subgroup. Premature mortality will likely increase as obesity continues to rise. Funding: The JPB Foundation, NIH, CDC.
Rittiphairoj T, Owais M, Ward ZJ, Reddy CL, Yeh JM, Atun R. Incidence and prevalence of type 1 diabetes and diabetic ketoacidosis in children and adolescents (0-19 years) in Thailand (2015-2020): A nationwide population-based study. Lancet Reg Health West Pac. 2022;21 :100392.Abstract
Background: There is a lack of published studies on incidence of type 1 diabetes (T1D) and diabetic ketoacidosis (DKA) in Thailand. We aimed to estimate the national prevalence and incidence of T1D and DKA. Methods: Using Thailand's nationwide population-based longitudinal data covering 69 million individuals, we included the entire children and adolescents recorded in the database. Diseases were identified using ICD-10 codes. We investigated the prevalence of T1D and cumulative incidence of T1D, T1D referral, DKA, and mortality risk of DKA in five years from 2015 to 2020. T1D and DKA annual incidence were also estimated. We present findings for the total population and by sex, age, and urban-rural residencies. Findings: A total of 19,784,781 individuals aged less than 20 years were identified in 2015. The crude T1D prevalence in 2015 was 17·6 per 100,000 and crude T1D incidence rate was 5·0 per 100,000. T1D prevalence and cumulative incidence were significantly higher in older children (p < 0·001) and females (p < 0·001) than their counterparts. Among those with T1D, cumulative incidence of T1D referral was 42·4%. It was highest amongst children aged 5-14 years and was significantly higher among females (all p < 0·05). The crude DKA incidence rate at any point after diagnosis was 10·8%. The cumulative incidence of DKA was significantly higher in females and peaked in individuals aged 5-14 years (all p < 0·001). The DKA mortality risk was 258·2 per 100,000. Interpretation: Older children and females had higher T1D prevalence. The DKA cumulative incidence and mortality risk were relatively low, and such incidence was peak in individuals aged 5-14 years. Funding: Harvard University.
Ross C, Ward ZJ, Gomber A, Owais M, Yeh JM, Reddy C-L, Atun R. The Prevalence of Islet Autoantibodies in Children and Adolescents With Type 1 Diabetes Mellitus: A Global Scoping Review. Front Endocrinol (Lausanne). 2022;13 :815703.Abstract
Background and Purpose: Pancreatic islet autoantibodies (iAb) are the hallmark of autoimmunity in type 1 diabetes. A more comprehensive understanding of the global iAb prevalence could help reduce avertible morbidity and mortality among children and adolescents and contribute to the understanding in the observed differences in the incidence, prevalence and health outcomes of children and adolescents with type 1 diabetes across and within countries. We present the first scoping review that provides a global synthesis of the prevalence of iAb in children and adolescents with type 1 diabetes. Research Design and Methods: We searched Ovid MEDLINE® with Daily Update, Embase (Elsevier, embase.com) and PubMed (National Library of Medicine -NCBI), for studies pertaining to prevalence in children and adolescents (0-19) with type 1 diabetes published between 1 Jan 1990 and 18 June 2021. Results were synthesized using Covidence systematic review software and meta-analysis was completed using R v3·6·1. Two reviewers independently screened abstracts with a third reviewer resolving conflicts (k= 0·92). Results: The review revealed 125 studies from 48 different countries, with 92 from high-income countries. Globally, in new-onset type 1 diabetes, IA-2A was the most prevalent iAb 0·714 [95% CI (0·71, 0·72)], followed by ICA 0·681 [95% CI (0·67, 0·69)], ZnT8A was 0·654 [95% CI (0·64, 0·66)], GADA 0·636 [95% CI (0·63, 0·66)] and then IAA 0·424 [95% CI (0·42, 0·43)], with substantial variation across world regions. The weighted mean prevalence of IA-2A was more variable, highest in Europe at 0·749 [95% CI (0·74, 0·76)] followed by Northern America 0·662 [95% CI (0·64, 0·69)], Latin America and the Caribbean 0·632 [95% CI (0·54, 0·72)], Oceania 0·603 [95% CI (0·54, 0·67)], Asia 0·466 [95% CI (0·44, 0·50)] and Africa 0·311 [95% CI (0·23, 0·40)]. In established cases of type 1 diabetes, GADA was the most prevalent iAb 0·407 [95% CI (0·39, 0·42)] followed by ZnT8A 0·322 [95% CI (0·29, 0·36)], IA-2A 0·302 [95% CI (0·29, 0·32)], IAA 0·258 [95% CI (0·24, 0·26)] and ICA 0·145 [95% CI (0·13, 0·16)], again with substantial variation across world regions. Conclusion: Understanding the global prevalence of iAb in children and adolescents with type 1 diabetes could help with earlier identification of those at-risk of developing type 1 diabetes and inform clinical practice, health policies, resource allocation, and targeted healthcare interventions to better screen, diagnose and manage children and adolescents with type 1 diabetes.
Ward ZJ, Gortmaker SL. A rigorous evaluation of a method to adjust BMI for self-report bias. Obesity (Silver Spring). 2022.
2021
Hricak H, Ward ZJ, Atun R, Abdel-Wahab M, Muellner A, Scott AM. Increasing Access to Imaging for Addressing the Global Cancer Epidemic. Radiology. 2021 :211351.
Ward ZJ, Walbaum M, Walbaum B, Guzman MJ, Jimenez de la Jara J, Nervi B, Atun R. 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. Lancet Oncol. 2021.Abstract
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.
Ward ZJ, Atun R, Hricak H, Asante K, McGinty G, Sutton EJ, Norton L, Scott AM, Shulman LN. The impact of scaling up access to treatment and imaging modalities on global disparities in breast cancer survival: a simulation-based analysis. Lancet Oncol. 2021.Abstract
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.
Lansdorp-Vogelaar I, Meester RGS, Laszkowska M, Escudero FA, Ward ZJ, Yeh JM. Cost-effectiveness of prevention and early detection of gastric cancer in Western countries. Best Pract Res Clin Gastroenterol. 2021;50-51 :101735.Abstract
Gastric cancer (GC) is a significant global health problem, with Helicobacter pylori infection estimated to be responsible for 89% of non-cardiac GC cases, or 78% of all GC cases. The International Agency for Research on Cancer has called for Helicobacter pylori test-and-treat strategies in countries with high rates of GC. However, for countries with low rates of GC, such as most Western countries, the balance between benefits, harms and costs of screening is less clear-cut. GC is a disease with a well-characterized precancerous process, providing the basis for primary and secondary prevention efforts. However, rigorous data assessing the impact of such interventions in Western countries are lacking. In the absence of clinical trials, modelling offers a unique approach to evaluate the potential impact of various screening and surveillance interventions. In this paper, we provide an overview of modelling studies evaluating the cost-effectiveness of GC screening and surveillance in Western countries.
Kenney EL, Mozaffarian RS, Long MW, Barrett JL, Cradock AL, Giles CM, Ward ZJ, Gortmaker SL. Limiting Television to Reduce Childhood Obesity: Cost-Effectiveness of Five Population Strategies. Child Obes. 2021.Abstract
To quantify the potential population-wide costs, number of individuals reached, and impact on obesity of five effective interventions to reduce children's television viewing if implemented nationally. Utilizing evidence from systematic reviews, the Childhood Obesity Intervention Cost Effectiveness Study (CHOICES) microsimulation model estimated the cost, population reach, and impact on childhood obesity from 2020 to 2030 of five hypothetical policy strategies to reduce the negative impact of children's TV exposure: (1) eliminating the tax deductibility of food and beverage advertising; (2) targeting TV reduction during home visiting programs; (3) motivational interviewing to reduce home television time at Women, Infants, and Children (WIC) clinic visits; (4) adoption of a television-reduction curriculum in child care; and (5) limiting noneducational television in licensed child care settings. Eliminating the tax deductibility of food advertising could reach the most children [106 million, 95% uncertainty interval (UI): 105-107 million], prevent the most cases of obesity (78,700, 95% UI: 30,200-130,000), and save more in health care costs than it costs to implement. Strategies targeting young children in child care and WIC also cost little to implement (between $0.19 and $32.73 per child reached), and, although reaching fewer children because of the restricted age range, were estimated to prevent between 25,500 (95% UI: 4600-59,300) and 35,400 (95% UI: 13,200-62,100) cases of obesity. Home visiting to reduce television viewing had high costs and a low reach. Interventions to reduce television exposure across a range of settings, if implemented widely, could help prevent childhood obesity in the population at relatively low cost.
Hughes TM, Empringham B, Wagner AK, Ward ZJ, Yeh J, Gupta S, Frazier LA, Denburg AE. Forecasting essential childhood cancer drug need: An innovative model-based approach. Cancer. 2021.Abstract
BACKGROUND: Childhood cancer outcomes in low-income and middle-income countries have not kept pace with advances in care and survival in high-income countries. A contributing factor to this survival gap is unreliable access to essential drugs. METHODS: The authors created a tool (FOR ECAST) capable of predicting drug quantity and cost for 18 pediatric cancers. FOR ECAST enables users to estimate the quantity and cost of each drug based on local incidence, stage breakdown, treatment regimen, and price. Two country-specific examples are used to illustrate the capabilities of FOR ECAST to predict drug quantities. RESULTS: On the basis of domestic public-sector price data, the projected annual cost of drugs to treat childhood cancer cases is 0.8 million US dollars in Kenya and 3.0 million US dollars in China, with average median price ratios of 0.9 and 0.1, respectively, compared with costs sourced from the Management Sciences for Health (MSH) International Medical Products Price Guide. According to the cumulative chemotherapy cost, the most expensive disease to treat is acute lymphoblastic lymphoma in Kenya, but a higher relative unit cost of methotrexate makes osteosarcoma the most expensive diagnosis to treat in China. CONCLUSIONS: FOR ECAST enables needs-based estimates of childhood cancer drug volumes to inform health system planning in a wide range of contexts. It is broadly adaptable, allowing decision makers to generate results specific to their needs. The resultant estimates of drug need can help equip policymakers and health governance institutions with evidence-informed data to advance innovative procurement strategies that drive global improvements in childhood cancer drug access.
Ward ZJ, Bleich SN, Long MW, Gortmaker SL. Association of body mass index with health care expenditures in the United States by age and sex. PLoS One. 2021;16 (3) :e0247307.Abstract
BACKGROUND: Estimates of health care costs associated with excess weight are needed to inform the development of cost-effective obesity prevention efforts. However, commonly used cost estimates are not sensitive to changes in weight across the entire body mass index (BMI) distribution as they are often based on discrete BMI categories. METHODS: We estimated continuous BMI-related health care expenditures using data from the Medical Expenditure Panel Survey (MEPS) 2011-2016 for 175,726 respondents. We adjusted BMI for self-report bias using data from the National Health and Nutrition Examination Survey (NHANES) 2011-2016, and controlled for potential confounding between BMI and medical expenditures using a two-part model. Costs are reported in $US 2019. RESULTS: We found a J-shaped curve of medical expenditures by BMI, with higher costs for females and the lowest expenditures occurring at a BMI of 20.5 for adult females and 23.5 for adult males. Over 30 units of BMI, each one-unit BMI increase was associated with an additional cost of $253 (95% CI $167-$347) per person. Among adults, obesity was associated with $1,861 (95% CI $1,656-$2,053) excess annual medical costs per person, accounting for $172.74 billion (95% CI $153.70-$190.61) of annual expenditures. Severe obesity was associated with excess costs of $3,097 (95% CI $2,777-$3,413) per adult. Among children, obesity was associated with $116 (95% CI $14-$201) excess costs per person and $1.32 billion (95% CI $0.16-$2.29) of medical spending, with severe obesity associated with $310 (95% CI $124-$474) excess costs per child. CONCLUSIONS: Higher health care costs are associated with excess body weight across a broad range of ages and BMI levels, and are especially high for people with severe obesity. These findings highlight the importance of promoting a healthy weight for the entire population while also targeting efforts to prevent extreme weight gain over the life course.
Hricak H, Abdel-Wahab M, Atun R, Lette MM, Paez D, Brink JA, Donoso-Bach L, Frija G, Hierath M, Holmberg O, et al. Medical imaging and nuclear medicine: a Lancet Oncology Commission. Lancet Oncol. 2021.Abstract
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 $2·46. These improved health and economic outcomes hold true across all geographical regions. We propose actions and investments that would enhance access to imaging equipment, workforce capacity, digital technology, radiopharmaceuticals, and research and training programmes in LMICs, to produce massive health and economic benefits and reduce the burden of cancer globally.
Ward ZJ, Scott AM, Hricak H, Atun R. Global costs, health benefits, and economic benefits of scaling up treatment and imaging modalities for survival of 11 cancers: a simulation-based analysis. Lancet Oncol. 2021;22 (3) :341-350.Abstract
BACKGROUND: In addition to increased availability of treatment modalities, advanced imaging modalities are increasingly recommended to improve global cancer care. However, estimates of the costs and benefits of investments to improve cancer survival are scarce, especially for low-income and middle-income countries (LMICs). In this analysis, we aimed to estimate the costs and lifetime health and economic benefits of scaling up imaging and treatment modality packages on cancer survival, both globally and by country income group. METHODS: Using a previously developed model of global cancer survival, we estimated stage-specific cancer survival and life-years gained (accounting for competing mortality) in 200 countries and territories for patients diagnosed with one of 11 cancers (oesophagus, stomach, colon, rectum, anus, liver, pancreas, lung, breast, cervix uteri, and prostate) representing 60% of all cancer diagnoses between 2020 and 2030 (inclusive of full years). We evaluated the costs and health and economic benefits of scaling up packages of treatment (chemotherapy, surgery, radiotherapy, and targeted therapy), imaging modalities (ultrasound, x-ray, CT, MRI, PET, single-photon emission CT), and quality of care to the mean level of high-income countries, separately and in combination, compared with no scale-up. Costs and benefits are presented in 2018 US$ 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.
Rodriguez PJ, Ward ZJ, Long MW, Austin BS, Wright DR. Applied Methods for Estimating Transition Probabilities from Electronic Health Record Data. Med Decis Making. 2021;41 (2) :143-152.Abstract
BACKGROUND: Electronic health record (EHR) data contain longitudinal patient information and standardized diagnostic codes. EHR data may be useful for estimating transition probabilities for state-transition models, but no guidelines exist on appropriate methods. We applied 3 potential methods to estimate transition probabilities from EHR data, using pediatric eating disorders (EDs) as a case study. METHODS: We obtained EHR data from PEDsnet, which includes 8 US children's hospitals. Data included inpatient, outpatient, and emergency department visits for all patients with an ED. We mapped diagnoses to 3 ED health states: anorexia nervosa, bulimia nervosa, and other specified feeding or eating disorder. We estimated 1-y transition probabilities for males and females using 3 approaches: simple first-last proportions, a multistate Markov (MSM) model, and independent survival models. RESULTS: Transition probability estimates varied widely between approaches. The first-last proportion approach estimated higher probabilities of remaining in the same health state, while the MSM and independent survival approaches estimated higher probabilities of transitioning to a different health state. All estimates differed substantially from published literature. LIMITATIONS: As a source of health state information, EHR data are incomplete and sometimes inaccurate. EHR data were especially challenging for EDs, limiting the estimation and interpretation of transition probabilities. CONCLUSIONS: The 3 approaches produced very different transition probability estimates. Estimates varied considerably from published literature and were rescaled and calibrated for use in a microsimulation model. Estimation of transition probabilities from EHR data may be more promising for diseases that are well documented in the EHR. Furthermore, clinicians and health systems should work to improve documentation of ED in the EHR. Further research is needed on methods for using EHR data to inform transition probabilities.
2020
Ward ZJ, Gortmaker SL. Sugar-Sweetened Beverage Taxes Are a Sweet Deal: Improve Health, Save Money, Reduce Disparities, and Raise Revenue. JNCI Cancer Spectr. 2020;4 (6) :pkaa075.
Sruamsiri R, Ferrario A, Ross-Degnan D, Denburg AE, Frazier LA, Gupta S, Ward ZJ, Yeh JM, Wagner AK. What are the volume and budget needs to provide chemotherapy to all children with acute lymphoblastic leukaemia in Thailand? Development and application of an estimation tool. BMJ Open. 2020;10 (10) :e041901.Abstract
OBJECTIVE: Insufficient access to anticancer medicines may contribute to the wide survival differences of children with cancers across the globe. We developed a tool to estimate the volume of medicines and budget requirements to provide chemotherapy to children with acute lymphoblastic leukaemia (ALL). DESIGN: Development and application of an estimation tool. SETTING: Paediatric oncology hospital departments in Thailand. PARTICIPANTS: 318 children aged 0-14 years diagnosed with ALL and 215 children with undiagnosed ALL. INTERVENTIONS: Estimates of volume and budget requirements for administering a full course of chemotherapy for ALL and a further course for children who relapse, according to National Treatment Guidelines. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome measures were the volume (mg) and cost (US$) of medicines needed to treat children with ALL. For medicines whose main indication is paediatric ALL (asparaginase and 6-mercaptopurine), we estimated the difference between volume needed and actual sales in 2017 (secondary outcome). RESULTS: Ten anticancer medicines and four chemoprotective agents are needed for the treatment of paediatric ALL according to the Thai treatment guidelines. Of these 14 medicines, 13 are included in the WHO essential medicines list for children. All are available as generics. We estimated that essential chemotherapy and chemoprotective agents to treat all children diagnosed with ALL in Thailand in 2017 would cost US$ 814 952 (US$ 1 365 422 for diagnosed and undiagnosed children), which corresponds to 0.005% (0.008%) of the country's total health expenditure. The volumes of asparaginase and 6-mercaptopurine available on the Thai market in 2017 were more than sufficient (2.3 and 1.5 times the amounts needed, respectively) to treat all children diagnosed with ALL. CONCLUSIONS: Procuring sufficient quantities of essential medicines to treat children with ALL requires relatively modest resources. Medicine cost should not be a major barrier to ALL treatment in similar settings.
Ehrhardt MJ, Ward ZJ, Liu Q, Chaudhry A, Nohria A, Border W, Fulbright JM, Mulrooney DA, Oeffinger KC, Nathan PC, et al. Cost-Effectiveness of the International Late Effects of Childhood Cancer Guideline Harmonization Group Screening Guidelines to Prevent Heart Failure in Survivors of Childhood Cancer. J Clin Oncol. 2020 :JCO2000418.Abstract
PURPOSE: Survivors of childhood cancer treated with anthracyclines and/or chest-directed radiation are at increased risk for heart failure (HF). The International Late Effects of Childhood Cancer Guideline Harmonization Group (IGHG) recommends risk-based screening echocardiograms, but evidence supporting its frequency and cost-effectiveness is limited. PATIENTS AND METHODS: Using the Childhood Cancer Survivor Study and St Jude Lifetime Cohort, we developed a microsimulation model of the clinical course of HF. We estimated long-term health outcomes and economic impact of screening according to IGHG-defined risk groups (low [doxorubicin-equivalent anthracycline dose of 1-99 mg/m and/or radiotherapy < 15 Gy], moderate [100 to < 250 mg/m or 15 to < 35 Gy], or high [≥ 250 mg/m or ≥ 35 Gy or both ≥ 100 mg/m and ≥ 15 Gy]). We compared 1-, 2-, 5-, and 10-year interval-based screening with no screening. Screening performance and treatment effectiveness were estimated based on published studies. Costs and quality-of-life weights were based on national averages and published reports. Outcomes included lifetime HF risk, quality-adjusted life-years (QALYs), lifetime costs, and incremental cost-effectiveness ratios (ICERs). Strategies with ICERs < $100,000 per QALY gained were considered cost-effective. RESULTS: Among the IGHG risk groups, cumulative lifetime risks of HF without screening were 36.7% (high risk), 24.7% (moderate risk), and 16.9% (low risk). Routine screening reduced this risk by 4% to 11%, depending on frequency. Screening every 2, 5, and 10 years was cost-effective for high-risk survivors, and every 5 and 10 years for moderate-risk survivors. In contrast, ICERs were > $175,000 per QALY gained for all strategies for low-risk survivors, representing approximately 40% of those for whom screening is currently recommended. CONCLUSION: Our findings suggest that refinement of recommended screening strategies for IGHG high- and low-risk survivors is needed, including careful reconsideration of discontinuing asymptomatic left ventricular dysfunction and HF screening in low-risk survivors.
Ward ZJ, Scott AM, Hricak H, Abdel-Wahab M, Paez D, Lette MM, Vargas AH, Kingham PT, Atun R. Estimating the impact of treatment and imaging modalities on 5-year net survival of 11 cancers in 200 countries: a simulation-based analysis. Lancet Oncol. 2020;21 (8) :1077-1088.Abstract
BACKGROUND: Accurate survival estimates are important for cancer control planning. Although observed survival estimates are unavailable for many countries, where they are available, wide variations are reported. Understanding the impact of specific treatment and imaging modalities can help decision makers to effectively allocate resources to improve cancer survival in their local context. METHODS: We developed a microsimulation model of stage-specific cancer survival in 200 countries and territories for 11 cancers (oesophagus, stomach, colon, rectum, anus, liver, pancreas, lung, breast, cervix uteri, and prostate) comprising 60% of global diagnosed cancer cases. The model accounts for country-specific availability of treatment (chemotherapy, surgery, radiotherapy, and targeted therapy) and imaging modalities (ultrasound, x-ray, CT, MRI, PET, single-photon emission CT), as well as quality of care. We calibrated the model to reported survival estimates from CONCORD-3 (which reports global trends in cancer survival in 2000-14). We estimated 5-year net survival for diagnosed cancers in each country or territory and estimated potential survival gains from increasing the availability of individual treatment and imaging modalities, and more comprehensive packages of scale-up of these interventions. We report the mean and 95% uncertainty intervals (UIs) for all outcomes, calculated as the 2·5 and 97·5 percentiles of the simulation results. FINDINGS: The estimated global 5-year net survival for all 11 cancers combined is 42·6% (95% uncertainty interval 40·3-44·3), with survival in high-income countries being an average of 12 times (range 4-17) higher than that in low-income countries. Expanding availability of surgery or radiotherapy or improving quality of care would yield the largest survival gains in low-income (2·5-3·4 percentage point increase in survival) and lower-middle-income countries (2·4-6·1 percentage point increase), whereas upper-middle-income and high-income countries are more likely to benefit from improved availability of targeted therapy (0·7 percentage point increase for upper-middle income and 0·4 percentage point increase for high income). Investing in medical imaging will also be necessary to achieve substantial survival gains, with traditional modalities estimated to provide the largest gains in low-income settings, while MRI and PET would yield the largest gains in higher-income countries. Simultaneous expansion of treatment, imaging, and quality of care could improve 5-year net survival by more than ten times in low-income countries (3·8% [95% UI 0·5-9·2] to 45·2% [40·2-52·1]) and could more than double 5-year net survival in lower-middle-income countries (20·1% [7·2-31·7] to 47·1% [42·8-50·8]). INTERPRETATION: Scaling up both treatment and imaging availability could yield synergistic survival gains for patients with cancer. Expanding traditional modalities in lower-income settings might be a feasible pathway to improve survival before scaling up more modern technologies. FUNDING: Harvard T H Chan School of Public Health.
Ward ZJ, Grover S, Scott AM, Woo S, Salama DH, Jones EC, El-Diasty T, Pieters BR, Trimble EL, Vargas AH, et al. The role and contribution of treatment and imaging modalities in global cervical cancer management: survival estimates from a simulation-based analysis. Lancet Oncol. 2020;21 (8) :1089-1098.Abstract
BACKGROUND: Cervical cancer is the fourth most common cancer among women worldwide, causing more than 300 000 deaths globally each year. In addition to screening and prevention, effective cancer treatment is needed to reduce cervical cancer mortality. We discuss the role of imaging in cervical cancer management and estimate the potential survival effect of scaling up imaging in several different contexts. METHODS: Using a previously developed microsimulation model of global cancer survival, we estimated stage-specific cervical cancer 5-year net survival in 200 countries and territories. We evaluated the potential survival effect of scaling up treatment (chemotherapy, surgery, radiotherapy, and targeted therapy), and imaging modalities (ultrasound, x-ray, CT, MRI, PET, and single photon emission CT [SPECT]) to the mean level of high-income countries, both individually and in combination. FINDINGS: We estimate global cervical cancer 5-year net survival as 42·1% (95% uncertainty interval [UI] 33·8-48·5). Among individual imaging modalities, expanding MRI would yield the largest 5-year survival gains globally (data are absolute percentage point increase in survival 0·6, 95% UI 0·1-2·1), scaling up ultrasound would yield the largest gains in low-income countries (0·5, 0·0-3·7), expanding CT and x-ray would have the greatest effect in Latin America (0·8, 0·0-3·4) and Oceania (0·4, 0·0-3·2), and expanding PET would yield the largest gains in high-income countries (0·2, 0·0-0·8). Scaling up SPECT did not show major changes in any region. Among individual treatment modalities, scaling up radiotherapy would yield the largest absolute percentage point gains in low-income countries (5·2, 0·3-13·5), and expanding surgery would have the largest effect in lower-middle-income countries (7·4, 0·3-21·1) and upper-middle-income countries (0·8, 0·0-2·9). Estimated survival gains in high-income countries were very modest. However, the gains from expanding any single treatment or imaging modality individually were small across all income levels and geographical settings. Scaling up all treatment modalities could improve global 5-year net survival to 52·4% (95% UI 44·6-62·0). In addition to expanding treatment, improving quality of care could raise survival to 57·5% (51·2-63·5), and the cumulative effect of scaling up all imaging modalities together with expanded treatment and quality of care could improve 5-year net survival for cervical cancer to 62·5% (57·7-67·8). INTERPRETATION: Comprehensive scale-up of treatment, imaging, and quality of care could substantially improve global cervical cancer 5-year net survival, with quality of care and imaging improvements each contributing about 25% of the total potential gains. These findings suggest that a narrow focus on the availability of treatment modalities could forgo substantial survival gains. Investments in imaging equipment, personnel, and quality of care efforts will also be needed to successfully scale up cervical cancer treatment worldwide. FUNDING: Harvard T H Chan School of Public Health and National Cancer Institute.
Kenney EL, Barrett JL, Bleich SN, Ward ZJ, Cradock AL, Gortmaker SL. Impact Of The Healthy, Hunger-Free Kids Act On Obesity Trends. Health Aff (Millwood). 2020;39 (7) :1122-1129.Abstract
The Healthy, Hunger-Free Kids Act of 2010 strengthened nutrition standards for meals and beverages provided through the National School Lunch, Breakfast, and Smart Snacks Programs, affecting fifty million children daily at 99,000 schools. The legislation's impact on childhood obesity is unknown. We tested whether the legislation was associated with reductions in child obesity risk over time using an interrupted time series design for 2003-18 among 173,013 youth in the National Survey of Children's Health. We found no significant association between the legislation and childhood obesity trends overall. For children in poverty, however, the risk of obesity declined substantially each year after the act's implementation, translating to a 47 percent reduction in obesity prevalence in 2018 from what would have been expected without the legislation. These results suggest that the Healthy, Hunger-Free Kids Act's science-based nutritional standards should be maintained to support healthy growth, especially among children living in poverty.

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