Developing and interpreting models to improve diagnostics in developing countries.
Explore the source record for details and available documents.
Developing Countries↗
Biomedical subjects
Rob Boer
Publications and source records attributed to Rob Boer.
Reducing the global burden of acute lower respiratory infections in children: the contribution of new diagnostics.
Explore the source record for details and available documents.
Anti-Bacterial Agents↗
How much can current interventions reduce colorectal cancer mortality in the U.S.? Mortality projections for scenarios of risk-factor modification, screening, and treatment.
BACKGROUND: Although colorectal cancer (CRC) is the second leading cause of cancer death in the U.S., available interventions to reduce CRC mortality are disseminated only partially throughout the population. This study assessed the potential reduction in CRC mortality that may be achieved through further dissemination of current interventions for risk-factor modification, screening, and treatment. METHODS: The MISCAN-COLON microsimulation model was used to simulate the 2000 U.S. population with respect to CRC risk-factor prevalence, screening use, and treatment use. The model was used to project age-standardized CRC mortality from 2000 to 2020 for 3 intervention scenarios. RESULTS: Without changes in risk-factor prevalence, screening use, and treatment use after 2000, CRC mortality would decrease by 17% by the Year 2020. If the 1995 to 2000 trends continue, then the projected reduction in mortality would be 36%. However, if trends in the prevalence of risk-factors could be improved above continued trends, if screening use increased to 70% of the target population, and if the use of chemotherapy increased among all age groups, then a 49% reduction would be possible. Screening drove most (23%) of the projected mortality reduction with these optimistic trends; however, decreasing risk-factors (16%) and increasing use of chemotherapy (10%) also contributed substantially. The contribution of risk-factors may have been overestimated, because effect estimates could not be obtained from randomized controlled trials. CONCLUSIONS: Currently available interventions for risk-factor modification, screening, and treatment have the potential to reduce CRC mortality by almost 50% by the Year 2020. However, without action now to further increase the uptake of current effective interventions, the reduction in CRC mortality may be only 17%.
Colorectal Neoplasms↗
Transmission patterns of smallpox: systematic review of natural outbreaks in Europe and North America since World War II.
BACKGROUND: Because smallpox (variola major) may be used as a biological weapon, we reviewed outbreaks in post-World War II Europe and North America in order to understand smallpox transmission patterns. METHODS: A systematic review was used to identify papers from the National Library of Medicine, Embase, Biosis, Cochrane Library, Defense Technical Information Center, WorldCat, and reference lists of included publications. Two authors reviewed selected papers for smallpox outbreaks. RESULTS: 51 relevant outbreaks were identified from 1,389 publications. The median for the effective first generation reproduction rate (initial R) was 2 (range 0-38). The majority outbreaks were small (less than 5 cases) and contained within one generation. Outbreaks with few hospitalized patients had low initial R values (median of 1) and were prolonged if not initially recognized (median of 3 generations); outbreaks with mostly hospitalized patients had higher initial R values (median 12) and were shorter (median of 3 generations). Index cases with an atypical presentation of smallpox were less likely to have been diagnosed with smallpox; outbreaks in which the index case was not correctly diagnosed were larger (median of 27.5 cases) and longer (median of 3 generations) compared to outbreaks in which the index case was correctly diagnosed (median of 3 cases and 1 generation). CONCLUSION: Patterns of spread during Smallpox outbreaks varied with circumstances, but early detection and implementation of control measures is a most important influence on the magnitude of outbreaks. The majority of outbreaks studied in Europe and North America were controlled within a few generations if detected early.
Communicable Disease Control↗
Seventy-five years is an appropriate upper age limit for population-based mammography screening.
In this study, we assessed the results of the Dutch breast cancer screening programme for women aged 70-75, and discussed the current upper age limit of the women invited. We compared the main outcome parameters of the screening programme 1998-2000 for women aged 70-75, with those in women aged 50-69. Breast cancer detection rates were also compared with prediction from 2 variants of a simulation model of breast cancer screening, assuming the mean sojourn time, i.e., the duration of the preclinical detectable phase, to increase or not with age above the age of 65. The underlying idea is that an increase of the sojourn time with age will lead to a less favourable balance between screening benefits and harms from a certain age on. Of the 315,103 women (aged 70-75) invited, 65.6% participated. The attendance increased from 1998 to 2000. For women aged 74 and 75 years, this increase was almost 10%. As a result of the 187,207 screening examinations performed within this age group, 18.3 per 1,000 women were referred and 10.3 per 1,000 breast cancer were diagnosed. Detection rates in both initial and subsequent screens increased steadily with age and got close to those model-simulated rates, which assume a continuously increasing sojourn time with age. A major finding of this study is that the screening participation among elderly women is high. The outcomes of our study suggest a steadily increasing sojourn time of breast tumours beyond the age of 69, leading to a strong increase in detection of cancers, and therefore, disfavouring the balance with the benefits of screening. At present, 75 years of age can be regarded as an appropriate upper age limit for the Dutch programme.
Age Factors↗
The MISCAN-Fadia continuous tumor growth model for breast cancer.
The MISCAN-Fadia model was used to analyze the impact of screening and adjuvant treatment on U.S. breast cancer mortality between 1975 and 2000. MISCAN-Fadia uses the concept of "fatal diameter" to model survival and screening benefit and is based on continuous tumor growth. It consists of four major components: population, natural history, screening, and treatment. Population parameters were quantified using U.S. population data. Most natural history and screening parameters were fitted to the Swedish Two County screening trial data; some were based on Surveillance, Epidemiology, and End Results data. Adjuvant treatment parameters were quantified using data from the Early Breast Cancer Trialists' Collaborative Group's meta-analysis. The simulated trend in incidence matches the observed trend reasonably well; the simulated mortality is equal to the observed in 1975 but becomes increasingly too high in 2000. We estimate that screening leads to a 15% and adjuvant treatment to a 21% mortality reduction in the year 2000.
Antineoplastic Combined Chemotherapy Protocols↗
A comparative review of CISNET breast models used to analyze U.S. breast cancer incidence and mortality trends.
The CISNET Breast Cancer program is a National Cancer Institute-sponsored collaboration composed of seven research groups that have modeled the impact of screening and adjuvant treatment on trends in breast cancer incidence and mortality over the period 1975-2000 (base case). This collaboration created a unique opportunity to make direct comparison of results from different models of population-based cancer screening produced in response to the same question. Comparing results in all but the most cursory way necessitates comparison of the models themselves. Previous chapters have discussed the models individual in detail. This chapter will aid the reader in understanding key areas of difference between the models. A focused analysis of differences and similarities between the models is presented with special attention paid to areas deemed most likely to contribute substantially to the results of the target analysis.
Breast Neoplasms↗
National Polyp Study data: evidence for regression of adenomas.
The data of the National Polyp Study, a large longitudinal study on surveillance of adenoma patients, is used for testing assumptions on the adenoma-carcinoma sequence. The observed adenoma and colorectal cancer incidence in the National Polyp Study were compared with the simulated outcomes of the MISCAN-COLON model of epidemiology and control of colorectal cancer for the U.S. population based on expert opinion. Variants of this model were explored in order to identify assumptions on the adenoma-carcinoma sequence that are consistent with the study observations. The high observed adenoma detection rates at surveillance and low observed colorectal cancer incidence in the National Polyp Study could only be explained by assuming a high incidence rate of adenomas accompanied by regression of adenomas. The National Polyp Study data suggest that adenoma prevalence results from a dynamic process of both formation as well as regression of adenomas. This lowers the expectations for the effects of colorectal cancer screening strategies that focus on adenoma detection.
Adenoma↗
Mammography benefit in the Canadian National Breast Screening Study-2: a model evaluation.
The CNBSS-2 among women aged 50-59 did not show any significant difference in breast cancer mortality between a control arm screened annually by CBE and a study arm screened by CBE and mammography. Because of this design, the benefit of screening compared to no screening could not be evaluated. We therefore conducted a modeling effort to estimate the benefit of mammography or CBE compared to no screening. We incorporated demographic, epidemiologic and screening characteristics of the CNBSS-2 in MISCAN. Stage-specific sensitivities of CBE, with and without mammography, and breast cancer incidence rate in the trial were estimated by comparing observed trial data with model predictions. We predicted the number of breast cancer deaths for both study arms of the CNBSS-2 and in the absence of screening, assuming improvement in prognosis by early detection. We estimated a 24-29% higher breast cancer incidence rate in the CNBSS-2 than the average Canadian rate. Estimated sensitivity of CBE (control arm) varied from 0.29 to 0.48 for stage T1c and from 0.6 to 0.65 for stage T2+. Estimated sensitivity of CBE supplemented with mammography (study arm) varied from 0.5 to 0.79 for stage T1c and was 0.95 for stage T2+. Expected breast cancer mortality reduction by annual CBE screening is 20.5% compared to no screening. Estimated breast cancer mortality reduction by mammography screening compared to no screening for the CNBSS-2 fell within the range 13.6-34.1%. Enrolled women had above average risk. Screening sensitivity in both arms was high. A benefit of mammography screening is supported by our modeling of the CNBSS-2 results.
Breast Neoplasms↗
Diversity of model approaches for breast cancer screening: a review of model assumptions by the Cancer Intervention and Surveillance Network (CISNET) Breast Cancer Groups.
The National Cancer Institute-sponsored Cancer Intervention and Surveillance Network program on breast cancer is composed of seven research groups working largely independently to model the impact of screening and adjuvant therapy on breast cancer mortality trends in the US from 1975 to 2000. Each of the groups has chosen a different modeling methodology without purposeful attempt to be in contrast with each other. The seven groups have met biannually since November 2000 to discuss their methodology and results. This article investigates the differences in methodology. To facilitate this comparison, each of the groups submitted a description of their model into a uniformly structured web based 'model profiler'. Six of the seven models simulate a preclinical natural history that cannot be observed directly with parameters estimated from published evidence concerning screening and therapy effects. The remaining model regards published evidence on intervention effects as prior information and updates that with information from the US population in a Bayesian type analysis. In general, the differences between the models appear to be small, particularly among the models driven by natural history assumptions. However, we demonstrate that such apparently small differences can have a large impact on surveillance of population trends. We describe a systematic approach to evaluating differences in model assumptions and results, as well as differences in modeling culture underlying the differences in model structure and parameters.
Breast Neoplasms↗
Lead times and overdetection due to prostate-specific antigen screening: estimates from the European Randomized Study of Screening for Prostate Cancer.
BACKGROUND: Screening for prostate cancer advances the time of diagnosis (lead time) and detects cancers that would not have been diagnosed in the absence of screening (overdetection). Both consequences have considerable impact on the net benefits of screening. METHODS: We developed simulation models based on results of the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer (ERSPC), which enrolled 42,376 men and in which 1498 cases of prostate cancer were identified, and on baseline prostate cancer incidence and stage distribution data. The models were used to predict mean lead times, overdetection rates, and ranges (corresponding to approximate 95% confidence intervals) associated with different screening programs. RESULTS: Mean lead times and rates of overdetection depended on a man's age at screening. For a single screening test at age 55, the estimated mean lead time was 12.3 years (range = 11.6-14.1 years) and the overdetection rate was 27% (range = 24%-37%); at age 75, the estimates were 6.0 years (range = 5.8-6.3 years) and 56% (range = 53%-61%), respectively. For a screening program with a 4-year screening interval from age 55 to 67, the estimated mean lead time was 11.2 years (range = 10.8-12.1 years), and the overdetection rate was 48% (range = 44%-55%). This screening program raised the lifetime risk of a prostate cancer diagnosis from 6.4% to 10.6%, a relative increase of 65% (range = 56%-87%). In annual screening from age 55 to 67, the estimated overdetection rate was 50% (range = 46%-57%) and the lifetime prostate cancer risk was increased by 80% (range = 69%-116%). Extending annual or quadrennial screening to the age of 75 would result in at least two cases of overdetection for every clinically relevant cancer detected. CONCLUSIONS: These model-based lead-time estimates support a prostate cancer screening interval of more than 1 year.
Aged↗
Initiation of population-based mammography screening in Dutch municipalities and effect on breast-cancer mortality: a systematic review.
BACKGROUND: More than a decade ago, a mammography screening programme for women aged 50-69 years was initiated in the Netherlands. Our aim was to assess the effect of this programme on breast-cancer mortality rates. METHODS: We examined data for 27948 women who died of breast-cancer aged 55-74 years between 1980 and 1999 (30560 cases until 2001). We grouped individuals into 93 clusters, depending on where they lived, and analysed data by use of national population statistics. We analysed time trends in breast-cancer mortality, adjusting for gradual implementations at municipality level, taking as year 0 the month and year in which screening began in a particular municipality. We used a Poisson regression model to estimate the time at which the trend started to turn. We assessed indirectly whether this turning point was related to initiation of screening or adjuvant systemic therapy in four clusters defined according to when screening was implemented. FINDINGS: Compared with rates in 1986-88, breast-cancer mortality rates in women aged 55-74 years fell significantly in 1997 and subsequent years as predicted, reaching -19.9% in 2001. Mortality rates had been increasing by an annual 0.3% until screening was introduced; thereafter we noted a decline of 1.7% per year (95% CI 2.39-0.96) in women aged 55-74 years and of 1.2% in those aged 45-54 (2.40 to 0.07). The turning point in mortality trends arose at around year 0. Adjuvant systemic therapy is unlikely to be the cause of this turning point, since the mortality rates continued to rise up to 1 year after implementation in municipalities where screening began after 1995. INTERPRETATION: Routine mammography screening can reduce breast-cancer mortality rates in women aged 55-74 years.
Age Distribution↗
A model for a smallpox-vaccination policy.
BACKGROUND: The new reality of biologic terrorism and warfare has ignited a debate about whether to reintroduce smallpox vaccination. METHODS: We developed scenarios of smallpox attacks and built a stochastic model of outcomes under various control policies. We conducted a systematic literature review and estimated model parameters on the basis of European and North American outbreaks since World War II. We assessed the trade-offs between vaccine-related harms and benefits. RESULTS: Nations or terrorists possessing a smallpox weapon could feasibly mount attacks that vary with respect to tactical complexity and target size, and patterns of spread can be expected to vary according to whether index patients are hospitalized early. For acceptable results, vaccination of contacts must be accompanied by effective isolation. Vaccination of contacts plus isolation is expected to result in 7 deaths (from vaccine or smallpox) in a scenario involving the release of variola virus from a laboratory, 19 deaths in a human-vector scenario, 300 deaths in a building-attack scenario, 2735 deaths in a scenario involving a low-impact airport attack, and 54,729 deaths in a scenario involving a high-impact airport attack. Immediate vaccination of the public in an attacked region would provide little additional benefit. Prior vaccination of health care workers, who would be disproportionately affected, would save lives in large local or national attacks but would cause 25 deaths nationally. Prior vaccination of health care workers and the public would save lives in a national attack but would cause 482 deaths nationally. The expected net benefits of vaccination depend on the assessed probability of an attack. Prior vaccination of health care workers would be expected to save lives if the probability of a building attack exceeded 0.22 or if the probability of a high-impact airport attack exceeded 0.002. The probability would have to be much higher to make vaccination of the public life-saving. CONCLUSIONS: The analysis favors prior vaccination of health care workers unless the likelihood of any attack is very low, but it favors vaccination of the public only if the likelihood of a national attack or of multiple attacks is high.
Bioterrorism↗
Overdiagnosis due to prostate-specific antigen screening: lessons from U.S. prostate cancer incidence trends.
BACKGROUND: Overdiagnosis of clinically insignificant prostate cancer is considered a major potential drawback of prostate-specific antigen (PSA) screening. Quantitative estimates of the magnitude of this problem are, however, lacking. We estimated rates of prostate cancer overdiagnosis due to PSA testing that are consistent with the observed incidence of prostate cancer in the United States from 1988 through 1998. Overdiagnosis was defined as the detection of prostate cancer through PSA testing that otherwise would not have been diagnosed within the patient's lifetime. METHODS: We developed a computer simulation model of PSA testing and subsequent prostate cancer diagnosis and death from prostate cancer among a hypothetical cohort of two million men who were 60-84 years old in 1988. Given values for the expected lead time--that is, the time by which the test advanced diagnosis--and the expected incidence of prostate cancer in the absence of PSA testing, the model projected the increase in population incidence of prostate cancer associated with PSA testing. By comparing the model-projected incidence with the observed incidence derived from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) registry data, we determined the lead times and corresponding overdiagnosis rates that were consistent with the observed data. RESULTS: SEER data on prostate cancer incidence from 1988 through 1998 were consistent with overdiagnosis rates of approximately 29% for whites and 44% for blacks among men with prostate cancers detected by PSA screening. CONCLUSIONS: Among men with prostate cancer that would be detected only at autopsy, these rates correspond to overdiagnosis rates of, at most, 15% in whites and 37% in blacks. The observed trends in prostate cancer incidence are consistent with considerable overdiagnosis among PSA-detected cases. However, the results suggest that the majority of screen-detected cancers diagnosed between 1988 and 1998 would have presented clinically and that only a minority of cases found at autopsy would have been detected by PSA testing.
Aged↗
Prostate cancer mortality reduction by screening: power and time frame with complete enrollment in the European Randomised Screening for Prostate Cancer (ERSPC) trial.
From 1992-2001, 7 countries in Europe gradually recruited men for the European Randomised Screening for Prostate Cancer (ERSPC) trial. Centres recruit different age groups and have different designs for recruiting and countries have different underlying risks for prostate cancer. Recruitment has reached 163,126 men aged 55-69 at entry now. Our purpose was to calculate the power of the trial and at what point in time can statistically significant differences in prostate cancer mortality be expected. Recruitment data were collected from the screening centres. We calculated the expected number of prostate cancer deaths in each follow-up year, based on national statistics and expected rate in trial entrants. The power was calculated using different assumptions on intervention effect and contamination rate and also if the ERSPC trial would cooperate with other trials. With an assumed 25% intervention effect in men actually screened and a 20% contamination rate, the trial will reach a power of 0.86 in 2008. With an assumed intervention effect of 40%, the power reaches 0.90 in 2003-2004. Pooling data with those of the Prostate, Lung, Colorectal and Ovary (PLCO) trial early is expected to improve the power to 79% (20% intervention effect) to 92% (40% intervention effect PLCO). Adding more centres with compliance rates lower than 45% decreases the power of the trial. The ERSPC trial has sufficient power to detect a significant difference in prostate cancer mortality between the 2 arms if the true reduction in mortality by screening is 25% or more or if contamination remains limited to 10% if the true effect is 20% or more. If early detection and treatment turns out to have a stronger effect as may be suggested by observational data, the ERSPC trial is likely to conclusively show that within the next 5 years.
Aged↗
Cost-effectiveness of cervical cancer screening: comparison of screening policies.
BACKGROUND: Recommended screening policies for cervical cancer differ widely among countries with respect to targeted age range, screening interval, and total number of scheduled screening examinations (i.e., Pap smears). We compared the efficiency of cervical cancer-screening programs by performing a cost-effectiveness analysis of cervical cancer-screening policies from high-income countries. METHODS: We used the microsimulation screening analysis (MISCAN) program to model and determine the costs and effects of almost 500 screening policies, some fictitious and some actual (i.e., recommended by national guidelines). The costs (in U.S. dollars) and effects (in years of life gained) were compared for each policy to identify the most efficient policies. RESULTS: There were 15 efficient screening policies (i.e., no alternative policy exists that results in more life-years gained for lower costs). For these policies, which considered two to 40 total scheduled examinations, the age range expanded gradually from 40-52 years to 20-80 years as the screening interval decreased from 12 to 1.5 years. For the efficient policies, the predicted gain in life expectancy ranged from 11.6 to 32.4 days, compared with a gain of 46 days if cervical cancer mortality were eliminated entirely. The average cost-effectiveness ratios increased from $6700 (for the longest screening interval) to $23 900 per life-year gained. For some countries, the recommended screening policies were close to efficient, but the cost-effectiveness could be improved by reducing the number of scheduled examinations, starting them at later ages, or lengthening the screening interval. CONCLUSIONS: The basis for the diversity in the screening policies among high-income countries does not appear to relate to the screening policies' cost-effectiveness ratios, which are highly sensitive to the number of Pap smears offered during a lifetime.
Adult↗