Simulation modelling to validate the flow method for estimating completeness of case ascertainment by cancer registries

BACKGROUND: To validate estimates of completeness of cancer ascertainment obtained by the flow method. METHODS: We generated a computer simulation of patient-level cancer registration processes, based loosely on the age distribution and survival of colorectal carcinoma patients, and utilizing a mixture of 'cured' and 'killed' subjects with an age-dependent fraction of 'cured' cases. The simulated data were then used in an analysis of completeness using the flow method. Validation of the simulation process was based on similarity of outputs to those obtained using real data, and validation of the flow method on its ability to correctly estimate the known proportion of cases in the simulated data which would never be registered. RESULTS: We successfully generated realistic data and have shown that completeness estimated by the flow method is close to the true value, whereas another method of estimating completeness (Ajiki's) was shown to be strongly biased. We also modelled what happens to completeness estimates when a new registry is set up. CONCLUSIONS: When its assumptions are met (steady state for incidence, survival and stable population structure), the flow method works well but is biased for cancers with good survival. Further research is required to assess the robustness of the method when these conditions are not met.     

An application of capture-recapture methods to the estimation of completeness of cancer registration

Completeness of cancer registration has not been consistently ascertained across different registries. This report describes how capture-recapture methods have been used to estimate completeness at the Ontario Cancer Registry. The method was applied in two fashions; first, using three data sources in a modeling approach: and second, using two data sources and standard, simple capture-recapture methods. The modeling approach is more flexible, since several variables that influence cancer registration can be considered and can be used to identify reporting patterns of different data sources. In the present analysis, estimates of completeness of the registry as a whole were remarkably similar using either two or three data sources, and site-specific comparisons differed by at most 7%. Because of the advantages of capture-recapture methods-estimation of level of completeness, possible comparability of estimates across different registries, and versatility to consider other determinants of cancer registration-a plea for greater use of these methods in cancer registration is made.     

Estimating completeness of cancer registration: an empirical evaluation of the two source capture-recapture approach in Germany.

STUDY OBJECTIVE--In recent years, capture-recapture methods have become increasingly popular in estimating completeness of disease registries. This study aimed to assess the performance of the two source capture-recapture method in estimating the completeness of cancer registration. DESIGN--The study was conducted in the population based cancer registry of Saarland, Germany, for which there are three main sources of notifications: reports by clinicians and pathologists, and death certificates. For groups of cases notified by one of the three sources, known completeness of registration by the other two sources was compared with the corresponding two source capture-recapture estimates. PATIENTS--A total of 16,020 patients notified to the cancer registry in 1970, 1975, 1980, and 1985 were included in the analysis. MAIN RESULTS--There was a tendency towards underestimation of completeness of notifications from pathologists and death certificates for patients notified by clinicians which was essentially confined to the older age groups. In contrast, capture-recapture methods tended to overestimate completeness of notifications from clinicians and death certificates for patients notified by pathologists. This overestimation was observed consistently in all age groups and for all of the most common cancer sites. Nevertheless, deviations of estimated completeness from known completeness were generally small or moderate. Agreement between estimated and known completeness was closest for patients notified by death certificates, although completeness was somewhat underestimated in patients above age 75. The observed patterns are in agreement with knowledge on clinical aspects and clinical management of cancer patients and with the circumstances of cancer registration in Saarland. CONCLUSIONS--Careful application of capture-recapture methods may provide an alternative to traditional approaches for estimating completeness of cancer registration.     

Occupational risk factors for male bladder cancer: results from a population based case cohort study in the Netherlands

OBJECTIVES—This study was conducted to estimate risk of bladder cancer associated with occupational exposures to paint components, polycyclic aromatic hydrocarbons (PAHs), diesel exhausts, and aromatic amines among the general population in The Netherlands.
METHODS—A prospective cohort study was conducted among 58 279 men. In September 1986, the cohort members (55-69 years) completed a self administered questionnaire on risk factors for cancer including job history. Follow up for incident bladder cancer was established by linkage to cancer registries until December 1992. A case-cohort approach was used based on 532 cases and 1630 subcohort members. A case by case expert assessment was carried out to assign to the cases and subcohort members a cumulative probability of occupational exposure for each carcinogenic exposure.
RESULTS—Men in the highest tertiles of occupational exposure to paint components, PAHs, aromatic amines, and diesel exhaust had non-significantly higher age and smoking adjusted incident rate ratios (RRs) of bladder cancer than men with no exposure: 1.29 (95% confidence interval (95% CI) 0.71 to 2.33), 1.24 (95% CI 0.68 to 2.27), 1.32 (95% CI 0.41 to 4.23) and 1.21 (95% CI 0.78 to 1.88), respectively. The associations between paint components and PAHs and risk of bladder cancer were most pronounced for current smokers. Among former smokers it seemed that for cumulative probability of exposure to paint components and PAHs, men who had smoked more than 15 cigarettes a day had RRs below unity compared with men who had smoked less than 15 cigarettes a day, whereas among current smokers the opposite was found. Exposure to diesel exhaust was positively associated with risk of bladder cancer among current and former smokers who had smoked more than 15 cigarettes a day.
CONCLUSIONS—This study provided only marginal evidence for an association between occupational exposure to paint components, PAHs, aromatic amines, and bladder cancer. Despite the small proportion of exposed subjects, an interaction with cigarette smoking was found, specifically for paint components, suggesting that the carcinogenic effect on the bladder might decrease after stopping smoking.


Keywords: bladder cancer; occupation; epidemiology     

A cohort study on cancer incidence in offspring of male printing workers.

We used multistep register linkage to measure the occurrence of cancer in offspring of male members of the Oslo unions of printers. A file of their children was established through linkage with the Central Population Register. Children born 1950-1987 (N = 12,440) were traced for cancer during 1965-1987 in the Cancer Registry of Norway (193,406 person-years). We found 33 cases of cancer. The standardized incidence ratio was near expected for person-years after age 14 (25 cases observed) but lower than expected for person-years in the age group 0-14 years (eight cases observed, standardized incidence ratio 0.58, 95% confidence interval 0.25-1.14). This negative association was stronger when more precise criteria for time of exposure were applied, especially for children 0-14 years with fathers in categories exposed to lead 1 year before the child's birth. Methodologic problems with this approach are nondifferential exposure misclassification and the need for large data sets. The method could serve as an alternative to the case-control design in reproductive epidemiology.     

Liver cancer risk in Japanese male dentists: a long-term retrospective cohort study

It has been speculated that dentists are at high risk for occupational exposure to bloodborne viruses such as hepatitis B and hepatitis C viruses. To assess the risk of the development of liver cancer among Japanese male dentists, we conducted a retrospective cohort study on 3,314 dentists of the Osaka Dental Association who were members between 1964 and 1985, the year before HBV immunization became available. By linking to the Osaka Cancer Registry, we found that during the period of 1964-1997, 36 of the dentists were diagnosed with liver cancer over a mean follow-up of 23.6 yr. The observed number of liver cancer cases was compared with the expected number, which was calculated by multiplying the number of person-years at risk by the corresponding age- and calendar time-specific incidence rate from the Osaka Cancer Registry data. The male dentists had a significantly lower risk of developing liver cancer than the general population of Osaka (O/E=0.71, 95% CI=0.50-0.98). On subcategorical analysis by birth year or duration of follow-up, there was no significantly increased risk of developing liver cancer among the dentists. Contrary to our expectation, our findings indicate that Japanese dentists were not at increased risk of developing liver cancer compared with the general population.     

Assessing the completeness of reporting of human immunodeficiency virus diagnoses in 2002-2003: capture-recapture methods

To determine the completeness of reporting of human immunodeficiency virus (HIV) diagnoses to state surveillance systems, the authors used capture-recapture methods. The numbers of cases diagnosed in the areas were estimated using HIV diagnoses reported to nine surveillance programs by different sources (e.g., laboratories, health-care providers). To account for dependencies between reporting sources, the authors used log-linear models to estimate the number of cases that had been diagnosed but were not identified by any reporting sources. Completeness of reporting (observed cases/expected cases) was determined for two time frames: cases diagnosed within a 1-year period (from October 1, 2002, to September 30, 2003, for most US states) reported up to 6 months after that diagnosis period and cases diagnosed within a 6-month period reported up to 12 months after that diagnosis period. A total of 11,266 HIV diagnoses were reported for the 1-year period with 21,589 report documents. Completeness of reporting of HIV diagnoses was 76% (95% confidence interval: 66, 83) when allowing 6 months of reporting delay (range: 72-95%) and improved to 81% (95% confidence interval: 72, 88) with 12 months' follow-up. When reporting systems retain all relevant documents, capture-recapture is a feasible approach for assessing completeness of reporting of HIV diagnoses. Completeness should be measured by allowing 12-months' reporting delay.     

PM10 and pregnancy outcomes: a hospital-based cohort study of pregnant women in Seoul

OBJECTIVE:: The aim of this study was to evaluate the effects of PM10 on birth outcomes using a prospective cohort of pregnant women. METHODS:: The multicenter prospective study was conducted in Korea from 2001 to 2004. To estimate the effects of PM10 exposure on birth outcomes, the logistic and linear regression model and the generalized additive model for nonlinear relationships were used. RESULTS:: Stillbirths were affected by PM10 level during the third trimesters (OR = 1.10, 95% CI = 1.02-1.14), and birth defects were influenced by the PM10 exposure during the second trimesters (OR = 1.16, 95% CI = 1.00-1.34). Intrauterine growth retardation was affected by the first trimester's PM10 exposure. On the other hand, premature birth was affected by the PM10 exposure during the third trimester, and low-birth-weight births were affected by the PM10 level during entire trimesters of pregnancy. CONCLUSIONS:: PM10 exposure during pregnancy may result in adverse birth outcomes with different critical periods.     

Completeness of case ascertainment in a Scottish regional cancer registry for the year 1992

To assess completeness of case ascertainment by the Scottish Cancer Registry for the year 1992, we assembled a collection of databases containing potential registrations (excluding non-melanoma skin tumours and non-invasive neoplasms) from 14 separate sources relating to the population covered by one of the five regional registries. Apparently missed registrations were identified by linkage of these databases to cancer registration records. Their eligibility for registration was determined by reference to medical records, or when these were unavailable, by reference to the local Community Health Index (to establish residency at the time of diagnosis) in conjunction with the text of the original pathology report and/or the original death certificate. Misclassifications of site or incidence year were not regarded as missed cases.Of 517 apparently missed cancer registrations, 66 cases (3.5% of the revised total number of registrations of malignant neoplasms other than non-melanoma skin tumours for the study area in 1992) should have been registered as new independent primary malignant neoplasms, giving an overall estimate of completeness of 96.5%. The fact that so many apparently missed registrations were not eligible for registration illustrates the limitations of passive registration. Ascertainment of cases by the Scottish Cancer Registry appears to be high for most sites and compares favourably to the figures reported by registries outside Scotland.     

Item non-responses in mailed food frequency questionnaires in a Korean male cancer cohort study

Item non-responses are frequently encountered in mailed food frequency questionnaires (FFQs) in epidemiological studies. The effects of item non-responses in a FFQ on presumed nutrient intake and subject classifications were examined in this study of a male cancer cohort in Korea. A semi-quantitative FFQ was developed and mailed to adult males aged between 40 and 59 in Seoul. Among the 14,533 cohort participants, 7,647 subjects who fully completed the FFQ initially and 216 subjects who completed the frequency missing items at resurvey were compared. When item non-responses were treated as not eaten, the average nutrient intakes of this group were significantly lower than both the average intake of subjects who fully completed at the initial survey and the average intake of those who completed at the resurvey. Increases in nutrient intakes during resurvey were substantively proportional to the number of items originally omitted. Cross classifications of item non-response subjects by nutrient intake after the initial survey and after resurvey showed misclassification towards lower quantile. Moreover, distribution of 'never or seldom' answer of resurvey group was similar to initial complete group. These results indicate that treating item non-responses as not eaten introduces bias when estimating nutrient intakes or when classifying subjects on the basis of nutrient intakes. More study is required to determine how best to treat non-response items in FFQ.     

Lung cancer risk in male dentists: a retrospective cohort study in Japan, 1964-1997

It is reported that dentists are exposed to heavy metals in their clinics. To assess the risk of developing lung cancer among male Japanese dentists, we conducted a retrospective cohort study of 3,314 members of Osaka Dental Association (Osakafu-Shikaishikai). During 1964-1997, 39 were diagnosed with lung cancer, which figure was obtained from the file of the Osaka Cancer Registry. The observed number of lung cancers was compared with the expected number calculated by multiplying the number of person-years at risk by the corresponding age- and calendar time-specific incidence rate from the Osaka Cancer Registry data. The male dentists had no significantly different risk than general population.(O/E=1.01, 95%CI=0.72-1.39). Contrary to expectation, these findings indicate that Japanese dentists had almost the same overall risk of developing lung cancer as the general population.     

Incidence and completeness of notification of Legionnaires' disease in The Netherlands: covariate capture-recapture analysis acknowledging regional differences

To estimate incidence and completeness of notification of Legionnaires' disease (LD) in The Netherlands in 2000 and 2001, we performed a capture-recapture analysis using three registers: Notifications, Laboratory results and Hospital admissions. After record-linkage, 373 of the 780 LD patients identified were notified. Ascertained under-notification was 52.2%. Because of expected and observed regional differences in the incidence rate of LD, alternatively to conventional log-linear capture-recapture models, a covariate (region) capture-recapture model, not previously used for estimating infectious disease incidence, was specified and estimated 886 LD patients (95% confidence interval 827-1022). Estimated under-notification was 57.9%. Notified, ascertained and estimated average annual incidence rates of LD were 1.15, 2.42 and 2.77/100 000 inhabitants respectively, with the highest incidence in the southern region of The Netherlands. Covariate capture-recapture analysis acknowledging regional differences of LD incidence appears to reduce bias in the estimated national incidence rate.     

腰围与男性肺癌发病关系的前瞻性队列研究

目的 探讨腰围与男性肺癌发病风险的关系。方法 以开滦集团全体在职及离退休男性职工为调查对象,自2006年5月建立开滦集团男性动态队列并随访。基线调查时收集研究对象身高、体重、腰围等信息,并在随访时收集结局事件信息。腰围按五分位数进行分组：<80、80~、85~、90~、≥95 cm,并以腰围80~cm组为参比组,采用多因素Cox比例风险回归模型分析腰围与男性肺癌发病的风险比（HR）和95%CI。结果 截止2014年12月31日,共有105 386名研究对象进入队列,共随访739 651.13人年,平均随访7.00年,共收集肺癌新发病例707例。以80~cm组为参比组,调整年龄、文化程度、吸烟状态、累计吸烟量、饮酒情况、体育锻炼、工作环境、糖尿病史后,腰围<80及85~、90~、≥95 cm组发生肺癌的HR值（95%CI）分别为1.17（0.90~1.52）及0.96（0.74~1.23）、0.94（0.72~1.21）、0.80（0.63~1.03）,趋势检验P=0.005。按吸烟、饮酒状态分层分析显示,腰围与肺癌发病风险在吸烟（腰围≥95 cm组与80~cm组相比：HR=0.69,95%CI：0.48~0.99）、饮酒（腰围≥95 cm组与80~cm组相比：HR=0.65,95%CI：0.45~0.94）者中呈负相关。结论 腰围可能与男性肺癌的发病风险之间有负相关关系。     

Hazardous waste site frequency: use of the capture-recapture method

This investigation used a two-source capture-recapture method (CRM) for determining ascertainment and undercounts of non-national priority listed hazardous waste sites in the states of Arizona, Maine and Pennsylvania. These findings suggest that ascertainment of hazardous waste sites vary greatly, with some more accurate (i.e., Maine) than others (i.e., Pennsylvania). These data suggest that nontraditional manufacturing states (e.g., Maine) have a higher ascertainment rate than traditional manufacturing states (e.g., Pennsylvania). These results indicate that resources for locating hazardous waste sites should be more heavily allotted to industrialized areas. We suggest that the CRM is a convenient, low cost and effective method for determining (1) the accuracy of previous estimates, and (2) the number of sites in a locale with 95% confidence intervals along with an estimate of the undercount. Findings suggest that estimates of hazardous waste sites should use the CRM to determine and improve accuracy.     

Cerebral palsy registers and high-quality data: an evaluation of completeness of the 4Child register using capture-recapture techniques

Background As the survival of very preterm and low‐birthweight infants increases, so does the importance of monitoring the birth prevalence of childhood impairments; disease registers provide a means to do so for these rare conditions. High levels of ascertainment for disease research registers have become increasingly difficult to achieve in the face of additional challenges posed by consent and confidentiality issues. 4Child – Four Counties Database of Cerebral Palsy, Vision Loss and Hearing Loss in Children has been collecting data and monitoring these three major childhood impairments since 1984. Methods This study used capture–recapture and related techniques to identify areas which are particularly affected by low ascertainment, to estimate the magnitude of missing cases on the 4Child register and to provide birth prevalence estimates of cerebral palsy which allow for these missing cases. Results Estimates suggest that while overall around 27% of cerebral palsy cases were not reported to 4Child, ascertainment for severely motor‐impaired children (93% complete) and those born in two of the four counties was good (Oxfordshire: 90%, Northamptonshire: 94%). After allowing for missing cases, adjusted estimates of cerebral palsy birth prevalence for 1984–1993 were 3.0 per 1000 live births versus 2.5 per 1000 live births in 1994–2003. Conclusions Capture–recapture techniques can identify areas of poor ascertainment and add to information around the provision of cerebral palsy birth prevalence estimates. Despite variation in ascertainment over time, capture–recapture estimates supported a decline in cerebral palsy birth prevalence between the earlier and later study periods in the four English counties of the geographical area covered by 4Child.     

Respiratory cancer in Danish bakers: a 10 year cohort study.

A national cohort based on the census at 9 November 1970 and the death registration files from 1970 to 1980 was analysed to see if skilled Danish bakers had an excess of respiratory cancer. The group of skilled bakers was divided into occupational subgroups to try to narrow down the possible causes of cancer. Significant excess mortality was found among skilled bakers in retail bakeries, skilled bakers in hotels and restaurants, and independent bakers. To adjust for confounding factors, the SMR was calculated with control groups of equal social status and smoking habits. With all skilled workers as the reference group, skilled bakers in retail bakeries still had an excess, but now insignificant, risk but skilled bakers in hotels and restaurants had a significant excess risk. Compared with all self employed people in urban occupations in which an average of six or fewer workers were employed as a referent group, independent bakers had an insignificant excess risk. Suspected carcinogens in bakeries include polycyclic aromatic hydrocarbons (PAH), reaction products of PAH, free radicals, n-nitrosodimethylamine, aflatoxin, sterigmatocystin, and zeralenone.     

Arsenic concentrations in prediagnostic toenails and the risk of bladder cancer in a cohort study of male smokers

At high concentrations, inorganic arsenic can cause bladder cancer in humans. However, it is unclear whether low exposure to inorganic arsenic in drinking water (<100 microg/liter) is related to bladder cancer risk. No study has been known to use biomarkers to assess the relation between individual arsenic exposure and bladder cancer risk. Toenail samples provide an integrated measure of internal arsenic exposure and reflect long-term exposure. The authors examined the relation between toenail arsenic levels and bladder cancer risk among participants in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, a cohort of Finnish male smokers aged 50-69 years. Data for 280 incident bladder cancer cases, identified between baseline (1985-1988) and April 1999, were available for analysis. One control was matched to each case on the basis of age, toenail collection date, intervention group, and smoking duration. Arsenic levels in toenail samples were determined by using neutron activation analysis. Logistic regression analyses were performed to estimate odds ratios. Arsenic toenail concentrations in this Finnish study were similar to those reported in US studies (range: 0.02-17.5 microg/g). The authors observed no association between inorganic arsenic concentration and bladder cancer risk (odds ratio = 1.13, 95% confidence interval: 0.70, 1.81 for the highest vs. lowest quartile). These findings suggest that low-level arsenic exposure is unlikely to explain a substantial excess risk of bladder cancer.     

Application of the capture-recapture method for estimating number of mobile male sex workers in a port city of Bangladesh

Male sex workers (MSWs) and sex trades are not new in Bangladesh. Current HIV interventions for MSWs need to be expanded in the major cities, but the number of MSWs needs to be scientifically estimated. Although two-sample capture-recapture surveys are suitable for closed populations, this method was here applied to indirectly estimate the number of mobile MSWs in a conservative social setting, a port city of Bangladesh. Use of the method resulted in an estimation of 248 MSWs (95% confidence interval, 246-250) who picked up clients only at open and known contact venues. This estimate does not, however, reflect the total number as MSWs who worked in unknown hidden venues and could not be reached. Experience suggests that the two-sample capture-recapture method is a simple technique for reliably estimating an unrecognized population. The limitation of this method can be minimized by shortening the time gap between surveys, creating an enabling environment to encounter harassment of MSWs, and offering safety to peer-staff.     

Estimating the prevalence of drug misuse in Dundee, Scotland: an application of capture-recapture methods.

STUDY OBJECTIVES: To apply capture-recapture methods to provide an estimate of the prevalence of opiate and benzodiazepine misuse in Dundee, Scotland. DESIGN: A four sample capture-recapture method using data from both statutory and non-statutory data sources to estimate drug misuse prevalence in Dundee between January 1990 and December 1994. PARTICIPANTS: Users of benzodiazepines or opiates residing within Dundee. RESULTS: Altogether 855 drug misusers were identified from various sources within Dundee; many were identified from more than one source. Using this data, the estimated unknown population was 1702, giving a total population of 2557 (95% confidence interval (CI) 1974, 3458) who misuse benzodiazepines or opiates. This represents a prevalence of 28.8 (95% CI 22.3, 39.0) per thousand. CONCLUSIONS: Capture-recapture techniques can be applied to statutory and non-statutory agency data to produce an estimate of at least certain sections of the drug misusing population. However, it is important to recognise the limitations of this methodology and in future to seek to combine a range of approaches to the problem of estimating prevalence rather than sticking rigidly to any single approach.