Improving the reporting of cancer-specific mortality and survival in research using cancer registry data

Population-based registries are increasingly used in cancer research. In such studies, cancer-specific mortality or survival is frequently used as the primary outcome. To determine whether a putative cancer was part of the causal chain of events leading to death, cancer registries primarily rely on death certificates. Hence, they depend on the subjective interpretation of information available to medical examiners at the time of death. Misclassification may occur: studies report misclassification of cancer as a cause of death in 15%–35% of death certificates based on evaluation by expert panels and/or autopsy reports. Further misclassification may occur when coding death causes in the cancer registry. Researchers should be aware of potential misclassification bias when using cancer registry data. Differential misclassification may bias the results towards or away from the null hypothesis, depending on whether there is relative over- or under-reporting of cancer-related deaths in one group. Strategies to improve reporting of cancer-specific survival/mortality include (1) describing the procedure used to identify cancer-specific deaths; (2) considering the use of multiple definitions of cancer-related deaths (strict/liberal definitions of cancer-specific deaths, and/or addition of relative survival as an outcome); and (3) reporting cancer-specific survival/mortality together with the objectively measured parameters overall survival or all-cause mortality.     

Why we should take care of the competing risk bias in survival analysis: A phase II trial on the toxicity profile of radiotherapy for prostate cancer

AimThe aim of the present study is to evaluate and quantify the bias of competing risks in an Italian oncologic cohort comparing results from different statistical analysis methods.BackgroundCompeting risks are very common in randomized clinical trials and observational studies, in particular oncology and radiotherapy ones, and their inappropriate management causes results distortions widely present in clinical scientific articles.Materials and methodsThis is a single-institution phase II trial including 41 patients affected by prostate cancer and undergoing radiotherapy (IMRT-SIB) at the University Hospital of Udine.Different outcomes were considered: late toxicities, relapse, death.Death in the absence of relapse or late toxicity was considered as a competing event.ResultsThe Kaplan Meier method, compared to cumulative incidence function method, overestimated the probability of the event of interest (toxicity and biochemical relapse) and of the competing event (death without toxicity/relapse) by 9.36%. The log-rank test, compared to Gray's test, overestimated the probability of the event of interest by 5.26%.The Hazard Ratio's and cause specific hazard's Cox regression are not directly comparable to subdistribution hazard's Fine and Gray's modified Cox regression; nonetheless, the FG model, the best choice for prognostic studies with competing risks, found significant associations not emerging with Cox regression.ConclusionsThis study confirms that using inappropriate statistical methods produces a 10% overestimation in results, as described in the literature, and highlights the importance of taking into account the competing risks bias.     

Accuracy of industry and occupation on death certificates of electric utility workers: implications for epidemiologic studies of magnetic fields and cancer

A substantial epidemiologic literature has relied on occupation and industry information from death certificates to make inferences about the association of electric and magnetic field exposure with cancer, but the validity of the occupational data on death certificates is questionable. We compared occupation and industry information from death certificates to company work histories for 793 electric utility workers who died from brain cancer (n=143), leukemia (n=156), lung cancer (n=246, randomly sampled), and non-cancer causes (n=248, randomly sampled). Nearly 75% of death certificates correctly indicated utility industry employment and of those, 48% matched the longest held occupation derived from company work histories. Hence, only 36% matched on both industry and occupation. We computed odds ratios relating occupations involving magnetic field exposure to brain cancer and leukemia both for the occupation listed on the death certificate and for the longest-held occupation based on company records in order to examine the impact of exposure misclassification based on reliance on the death certificate information. For brain cancer, the odds ratio was 1.2 based on death certificates and 1.7 based on company work history, suggesting some attenuation due to misclassification. For leukemia, death certificate information yielded an odds ratio of 0.9, whereas company work histories yielded an odds ratio of 1.3. Although work histories are limited to the period of employment in a specific company, these data suggest that there is substantial misclassification in use of death certificate information on industry and occupation of utility workers, as found in other industries. The limited quality of occupation and industry information on death certificates argues against relying on such information to evaluate modest associations with mortality.     

Recent decline in the U.S. death rate from myeloproliferative neoplasms, 1999-2006

Background: Myeloproliferative neoplasms (MPNs) are classified as neoplasms of uncertain or unknown behavior in the International Classification of Diseases (ICD) Version 10 and can contribute to risk of death from complications (especially thrombosis). Methods: U.S age-standardized death rates using ICD-Version 10 codes relevant to classical MPN (i.e., polycythemia vera, essential thrombocythemia, and “chronic myeloproliferative disease”) were examined for 1999–2006. The underlying cause of death and also all causes (“multiple causes” or “mentions”) coded on death certificates were considered. Trends were assessed by using percentage change (PC) in rate between 1999 and 2006, and annual percentage change (APC) estimated from linear regression. Results: The decline in death rates was large for MPN, whether based only the underlying cause (PC = ?19.7%, APC = ?3.4%) or on the substantially higher rates based on any cause (PC = ?24.1%, APC = ?3.8%), and was consistent by gender and age group (<65 and 65+ years). For deaths with MPN coded as other than the underlying cause, cardiovascular diseases were the most common underlying cause and the ASR for these deaths declined substantially (PC = ?40.0%). Conclusions: Use of the underlying cause of death in surveillance will considerably underestimate MPN-related mortality rates in the population. Studies are needed on treatment in random samples of MPN patients from population-based cancer registries. Continued surveillance of MPN-related mortality rates in the population is needed in view of recent attempts (including the use of aspirin) to control cardiovascular complications of MPN.     

The validity of cancer information on death certificates in Norway and the impact of death certificate initiated cases on cancer incidence and survival

BackgroundDeath certificates are an important source of information for cancer registries. The aim of this study was to validate the cancer information on death certificates, and to investigate the effect of including death certificate initiated (DCI) cases in the Cancer Registry of Norway when estimating cancer incidence and survival.MethodsAll deaths in Norway in the period 2011–2015 with cancer mentioned on the death certificates were linked to the cancer registry. Notifications not registered from other sources were labelled death certificate notifications (DCNs), and considered as either cancer or not, based on available information in the registry or from trace-back to another source.ResultsFrom the total of 65 091 cancers mentioned on death certificates in the period 2011–2015, 58,425 (89.8%) were already in the registry. Of the remaining 6 666 notifications, 2 636 (2 129 with cancer as underlying cause) were not regarded to be new cancers, which constitutes 4.0% of all cancers mentioned on death certificates and 39.5% of the DCNs. Inclusion of the DCI cases increased the incidence of all cancers combined by 2.6%, with largest differences for cancers with poorer prognosis and for older age groups. Without validation, including the 2 129 disregarded death certificates would over-estimate the incidence by 1.3%. Including DCI cases decreased the five-year relative survival estimate for all cancer sites combined with 0.5% points.ConclusionIn this study, almost 40% of the DCNs were regarded not to be a new cancer case, indicating unreliability of death certificate information for cancers that are not already registered from other sources. The majority of the DCNs where, however, registered as new cases that would have been missed without death certificates. Both including and excluding the DCI cases will potentially bias the survival estimates, but in different directions. This biases were shown to be small in the Cancer Registry of Norway.     

Bayesian sensitivity analysis methods to evaluate bias due to misclassification and missing data using informative priors and external validation data

Background: Recent research suggests that the Bayesian paradigm may be useful for modeling biases in epidemiological studies, such as those due to misclassification and missing data. We used Bayesian methods to perform sensitivity analyses for assessing the robustness of study findings to the potential effect of these two important sources of bias. Methods: We used data from a study of the joint associations of radiotherapy and smoking with primary lung cancer among breast cancer survivors. We used Bayesian methods to provide an operational way to combine both validation data and expert opinion to account for misclassification of the two risk factors and missing data. For comparative purposes we considered a “full model” that allowed for both misclassification and missing data, along with alternative models that considered only misclassification or missing data, and the naïve model that ignored both sources of bias. Results: We identified noticeable differences between the four models with respect to the posterior distributions of the odds ratios that described the joint associations of radiotherapy and smoking with primary lung cancer. Despite those differences we found that the general conclusions regarding the pattern of associations were the same regardless of the model used. Overall our results indicate a nonsignificantly decreased lung cancer risk due to radiotherapy among nonsmokers, and a mildly increased risk among smokers. Conclusions: We described easy to implement Bayesian methods to perform sensitivity analyses for assessing the robustness of study findings to misclassification and missing data.     

Causes of death in men with prostate cancer: Results from the Danish Prostate Cancer Registry (DAPROCAdata)

BackgroundCurrent knowledge of the validity of registry data on prostate cancer-specific death is limited. We aimed to determine the underlying cause of death among Danish men with prostate cancer, to estimate the level of misattribution of prostate cancer death, and to examine the risk of death from prostate cancer when accounting for competing risk of death.Material and methodsWe investigated a nationwide cohort of 15,878 prostate cancer patients diagnosed in 2010–2014; with 3343 deaths occurring through 2016. Blinded medical chart review was carried out for 670 deaths and compared to the national cause of death registry. Five death categories were defined: 1) prostate cancer-specific death, 2) other unspecified urological cancer death, 3) other cancer death 4) cardiovascular disease death, and 5) other causes of death. Competing risk analyses compared Cox cause-specific and Fine-Gray regression models.ResultsChart review attributed 51.2% of deaths to prostate cancer, 17.0% to cardiovascular disease, and 16.7% to other causes. The Danish Register of Causes of Death attributed 71.7% of deaths to prostate cancer when including all registered contributing causes of death, and 57.0% of deaths when including only the primary registered cause of death. The probability of death by prostate cancer was 10% at 2-year survival.ConclusionsMore than half of the deceased men in our study cohort died of their prostate cancer disease within a mean of 2.4 years of follow up. Data from the death registry is prone to misclassification, potentially overestimating the proportion of deaths from prostate cancer.     

Impact of and Correction for Outcome Misclassification in Cumulative Incidence Estimation

Cohort studies and clinical trials may involve multiple events. When occurrence of one of these events prevents the observance of another, the situation is called “competing risks”. A useful measure in such studies is the cumulative incidence of an event, which is useful in evaluating interventions or assessing disease prognosis. When outcomes in such studies are subject to misclassification, the resulting cumulative incidence estimates may be biased. In this work, we study the mechanism of bias in cumulative incidence estimation due to outcome misclassification. We show that even moderate levels of misclassification can lead to seriously biased estimates in a frequently unpredictable manner. We propose an easy to use estimator for correcting this bias that is uniformly consistent. Extensive simulations suggest that this method leads to unbiased estimates in practical settings. The proposed method is useful, both in settings where misclassification probabilities are known by historical data or can be estimated by other means, and for performing sensitivity analyses when the misclassification probabilities are not precisely known.     

Impact of using multiple causes of death codes to compute site-specific, death certificate-based cancer mortality statistics in the United States

Background: Cancer mortality statistics, an important indicator for monitoring cancer burden, are traditionally restricted to instances when cancer is determined to be the underlying cause of death (UCD) based on information recorded on standard certificates of death. This study's objective was to determine the impact of using multiple causes of death codes to compute site-specific cancer mortality statistics. Methods: The state cancer registries of California, Colorado and Idaho provided linked cancer registry and death certificate data for individuals who died between 2002 and 2004, had at least one cancer listed on their death certificate and were diagnosed with cancer between 1993 and 2004. These linked data were used to calculate the site-specific proportion of cancers not selected as the UCD (non-UCD) among all cancer-related deaths (any mention on the death certificate). In addition, the retrospective concordance between the death certificate and the population-based cancer registry, measured as confirmations rates, was calculated for deaths with cancer as the UCD, as a non-UCD, and for any mention. Results: Overall, non-UCD deaths comprised 9.5 percent of total deaths; 11 of the 79 cancer sites had proportions greater than 3 standard deviations from 9.5 percent. The confirmation rates for UCD and for any mention did not differ significantly for any of the cancer sites. Conclusion and impact: The site-specific variation in proportions and rates suggests that for a few cancer sites, death rates might be computed for both UCD and any mention of the cancer site on the death certificate. Nevertheless, this study provides evidence that, in general, restricting to UCD deaths will not under report cancer mortality statistics.     

Cause‐specific mortality among older African‐Americans: Correlates and consequences of age misreporting

Abstract

This paper examines the quality of age reporting on death certificates of elderly African‐Americans by major causes of death. We utilize a sample of death certificates linked to early census records and to Social Security Administration records to establish a “true” age at death. We then examine the patterns, predictors, and consequences of age misreporting for major causes of death. We find a pattern of greater age misreporting among females, identify educational background as a key predictor of accurate age reporting, and show that mortality crossovers are eliminated for most causes of death when more accurate age data are used.     

Estimating bias in causes of death ascertainment in the Finnish Randomized Study of Screening for Prostate Cancer

BackgroundPrecise cause of death (CoD) ascertainment is crucial in any cancer screening trial to avoid bias from misclassification due to excessive recording of diagnosed cancer as a CoD in death certificates instead of non-cancer disease that actually caused death. We estimated whether there was bias in CoD determination between screening (SA) and control arms (CA) in a population-based prostate cancer (PCa) screening trial.MethodsOur trial is the largest component of the European Randomized Study of Screening for Prostate Cancer with more than 80,000 men. Randomly selected deaths in men with PCa (N = 442/2568 cases, 17.2%) were reviewed by an independent CoD committee. Median follow-up was 16.8 years in both arms.ResultsOverdiagnosis of PCa was present in the SA as the risk ratio for PCa incidence was 1.19 (95% confidence interval (CI) 1.14–1.24). The hazard ratio (HR) for PCa mortality was 0.94 (95%CI 0.82–1.08) in favor of the SA. Agreement with official CoD registry was 94.6% (κ = 0.88) in the SA and 95.4% (κ = 0.91) in the CA. Altogether 14 PCa deaths were estimated as false-positive in both arms and exclusion of these resulted in HR 0.92 (95% CI 0.80–1.06).ConclusionsA small differential misclassification bias in ascertainment of CoD was present, most likely due to attribution bias (overdiagnosis in the SA). Maximum precision in CoD ascertainment can only be achieved with independent review of all deaths in the diseased population. However, this is cumbersome and expensive and may provide little benefit compared to random sampling.     

Partner status and survival after cancer: A competing risks analysis

ObjectiveThe survival benefits of having a partner for all cancers combined is well recognized, however its prognostic importance for individual cancer types, including competing mortality causes, is less clear. This study was undertaken to quantify the impact of partner status on survival due to cancer-specific and competing mortality causes.MethodsData were obtained from the population-based Queensland Cancer Registry on 176,050 incident cases of ten leading cancers diagnosed in Queensland (Australia) from 1996 to 2012. Flexible parametric competing-risks models were used to estimate cause-specific hazards and cumulative probabilities of death, adjusting for age, stage (breast, colorectal and melanoma only) and stratifying by sex.ResultsBoth unpartnered males and females had higher total cumulative probability of death than their partnered counterparts for each site. For example, the survival disadvantage for unpartnered males ranged from 3% to 30% with higher mortality burden from both the primary cancer and competing mortality causes. The cause-specific age-adjusted hazard ratios were also consistent with patients without a partner having increased mortality risk although the specific effect varied by site, sex and cause of death. For all combined sites, unpartnered males had a 46%, 18% and 44% higher risk of cancer-specific, other cancer and non-cancer mortality respectively with similar patterns for females. The higher mortality risk persisted after adjustment for stage.ConclusionsIt is important to better understand the mechanisms by which having a partner is beneficial following a cancer diagnosis, so that this can inform improvements in cancer management for all people with cancer.     

Probabilities of dying from cancer and other causes in French cancer patients based on an unbiased estimator of net survival: A study of five common cancers

BackgroundNet survival is the survival that would be observed if cancer were the only possible cause of death. Although it is an important epidemiological tool allowing temporal or geographical comparisons, it cannot inform on the “crude” probability of death of cancer patients; i.e., when taking into account other possible causes of deaths.MethodsIn this work, we provide estimates of the crude probabilities of death from cancer and from other causes as well as the probability of being alive up to ten years after cancer diagnosis according to the age and year of diagnosis. Based on a flexible excess hazard model providing unbiased estimates of net survival, our methodology avoids the pitfalls associated with the use of the cause of death. We used data from FRANCIM, the French network of cancer registries, and studied five common cancer sites: head and neck, breast, prostate, lung, and colorectal cancers.ResultsFor breast, prostate, and colorectal cancers, the impact of the other causes on the total probability of death increased with the age at diagnosis whereas it remained negligible for lung and head and neck cancers whatever the age. For breast, prostate, and colorectal cancer, the more recently was the cancer diagnosed, the less was the probability of death from cancer.ConclusionThe crude probability of death is an intuitive concept that may prove particularly useful in choosing an appropriate treatment, or refining the indication of a screening strategy by allowing the clinician to estimate the proportion of cancer patients who will die specifically from cancer.     

The impact of Kaposi sarcoma and non-Hodgkin lymphoma on mortality of people with AIDS in the highly active antiretroviral therapies era

Background: Kaposi sarcoma (KS) and non-Hodgkin lymphoma (NHL) have strongly diminished in the HAART era, but their impact on life expectancy of people with AIDS (PWA) needs to be monitored. We aimed at quantifying the burden of KS and NHL on mortality of PWA in the HAART period in Italy. Methods: Death certificates of 3209 PWA diagnosed in 1999–2006 who died as of December 2006 were reviewed to identify those deaths in which KS or NHL was the underlying cause. Standardized mortality ratios (SMR) were computed. Results: KS or NHL appeared in 4.3% and 14.6% death certificates, respectively; they were the underlying cause of death in 3.1% and 13.4% of cases. SMR were 8698-fold higher for KS and 349-fold higher for NHL, and tended to decline over the study period. Conclusion: KS and NHL caused about 16% of deaths of PWA in the HAART era, with 100-fold higher risks of death compared to the Italian general population also in recent years. Clinicians and public health officials should be aware of the persisting negative impact of these cancers on life expectancy of PWA.     

The effect of diagnostic misclassification on non-cancer and cancer mortality dose response in A-bomb survivors.

We used the EM algorithm in the context of a joint Poisson regression analysis of cancer and non-cancer mortality in the Radiation Effects Research Foundation (RERF) Life Span Study (LSS) to assess whether the observed increased risk of non-cancer death due to radiation exposure (Shimizu et al., RERF Technical Report 02-91, 1991) can be attributed solely to misclassification of cancer as non-cancer on death certificates. We show that greater levels of dose-independent misclassification than are indicated by a series of autopsies conducted on a subset of LSS members would be required to explain the non-cancer dose response, but that a relatively small amount of dose-dependence in the misclassification of cancer would explain the result. The adjustment for misclassification also results in higher risk estimates for cancer mortality. We review applications of similar statistical methods in other contexts and discuss extensions of the methods to more than two causes of death.     

Programmed Cell Death–Ligand 1 Overexpression in Thyroid Cancer

Objective: Programmed cell death–ligand 1 (PD-L1) expression on tumor tissue has been associated with favorable response to anti–programmed cell death–receptor 1/PD-L1 therapy in many human cancers. Studies have reported that PD-L1 is also expressed in thyroid cancer. The objective of this paper is to introduce the potential predictive and therapeutic values of PD-L1 in thyroid cancer.Methods: A literature search was conducted in the PubMed database using the terms “PD-L1,” “B7-H1,” and “thyroid cancer.” PD-L1 positivity was determined by immunohistochemical assay.Results: The frequency of PD-L1 positivity in different studies ranged from 6.1 to 82.5% in papillary thyroid cancer (PTC) patients and 22.2 to 81.2% in anaplastic thyroid cancer (ATC) patients. PD-L1 positivity rate was higher in ATC than in PTC within the same studies, and its expression intensity was significantly higher in tumor tissue than in the corresponding nontumor thyroid tissues. Moreover, PD-L1 expression was positively associated with the aggressiveness and recurrence of thyroid cancers and negatively associated with the differentiation status and outcomes. PD-L1 checkpoint pathway blockade may emerge as a promising therapeutic target in the treatment of thyroid cancers.Conclusion: PD-L1 is a potential biomarker to predict the recurrence and prognosis of thyroid cancers. It is also a novel immunotherapy target for optimizing the management landscape of radioiodine-refractory and ATCs.Abbreviations: ATC = anaplastic thyroid cancer; DTC = differentiated thyroid cancer; IHC = immunohistochemical; OS = overall survival; PD-1 = programmed cell death–receptor 1; PD-L1 = programmed cell death–ligand 1; PD-L2 = programmed cell death–ligand 2; PTC = papillary thyroid cancer; TNM = tumor-node-metastasis; Treg = regulatory T cell     

Excess Long-Term Mortality following Non-Variceal Upper Gastrointestinal Bleeding: A Population-Based Cohort Study

Background

It is unclear whether an upper gastrointestinal bleed is an isolated gastrointestinal event or an indicator of a deterioration in a patient''s overall health status. Therefore, we investigated the excess causes of death in individuals after a non-variceal bleed compared with deaths in a matched sample of the general population.

Methods and Findings

Linked longitudinal data from the English Hospital Episodes Statistics (HES) data, General Practice Research Database (GPRD), and Office of National Statistics death register were used to define a cohort of non-variceal bleeds between 1997 and 2010. Controls were matched at the start of the study by age, sex, practice, and year. The excess risk of each cause of death in the 5 years subsequent to a bleed was then calculated whilst adjusting for competing risks using cumulative incidence functions.16,355 patients with a non-variceal upper gastrointestinal bleed were matched to 81,523 controls. The total 5-year risk of death due to gastrointestinal causes (malignant or non-malignant) ranged from 3.6% (≤50 years, 95% CI 3.0%–4.3%) to 15.2% (≥80 years, 14.2%–16.3%), representing an excess over controls of between 3.6% (3.0%–4.2%) and 13.4% (12.4%–14.5%), respectively. In contrast the total 5-year risk of death due to non-gastrointestinal causes ranged from 4.1% (≤50 years, 3.4%–4.8%) to 46.6% (≥80 years, 45.2%–48.1%), representing an excess over controls of between 3.8% (3.1%–4.5%) and 19.0% (17.5%–20.6%), respectively. The main limitation of this study was potential misclassification of the exposure and outcome; however, we sought to minimise this by using information derived across multiple linked datasets.

Conclusions

Deaths from all causes were increased following an upper gastrointestinal bleed compared to matched controls, and over half the excess risk of death was due to seemingly unrelated co-morbidity. A non-variceal bleed may therefore warrant a careful assessment of co-morbid illness seemingly unrelated to the bleed. Please see later in the article for the Editors'' Summary     

Death certification in cancer of the breast.

The cause of death entered on the death certificates of 193 patients originally diagnosed as having cancer of the breast was compared with information obtained from clinical records, cancer registry records, and necropsy findings to determine the accuracy of death certification and the proportion of patients who, though dying from another cause, still had overt signs of cancer of the breast. It was found that the overall error in certifying cause of death as breast cancer was small, being an underestimate of about 4%. About a third of patients with breast cancer dying from other causes had overt signs of breast cancer at the time of death.     

Circulating levels of 25-hydroxyvitamin D and prostate cancer prognosis

Objectives: Ecological, in vitro, and in vivo studies demonstrate a link between vitamin D and prostate tumor growth and aggressiveness. The goal of this study was to investigate whether plasma concentration of vitamin D is associated with survivorship and disease progression in men diagnosed with prostate cancer. Materials and methods: We conducted a population-based cohort study of 1476 prostate cancer patients to assess disease recurrence/progression and prostate cancer-specific mortality (PCSM) risks associated with serum levels of 25(OH) vitamin D [25(OH)D]. Results: There were 325 recurrence/progression and 95 PCSM events during an average of 10.8 years of follow-up. Serum levels of 25(OH)D were not associated with risk of recurrence/progression or mortality. Clinically deficient vitamin D levels were associated with an increased risk of death from other causes. Conclusions: We did not find evidence that serum vitamin D levels measured after diagnosis affect prostate cancer prognosis. Lower levels of vitamin D were associated with risk of non-prostate cancer mortality.     

Assessing the impact of misclassification error on an epidemiological association between two helminthic infections

Background

Polyparasitism can lead to severe disability in endemic populations. Yet, the association between soil-transmitted helminth (STH) and the cumulative incidence of Schistosoma japonicum infection has not been described. The aim of this work was to quantify the effect of misclassification error, which occurs when less than 100% accurate tests are used, in STH and S. japonicum infection status on the estimation of this association.

Methodology/Principal Findings

Longitudinal data from 2276 participants in 50 villages in Samar province, Philippines treated at baseline for S. japonicum infection and followed for one year, served as the basis for this analysis. Participants provided 1–3 stool samples at baseline and 12 months later (2004–2005) to detect infections with STH and S. japonicum using the Kato-Katz technique. Variation from day-to-day in the excretion of eggs in feces introduces individual variations in the sensitivity and specificity of the Kato-Katz to detect infection. Bayesian logit models were used to take this variation into account and to investigate the impact of misclassification error on the association between these infections. Uniform priors for sensitivity and specificity of the diagnostic test to detect the three STH and S. japonicum were used. All results were adjusted for age, sex, occupation, and village-level clustering. Without correction for misclassification error, the odds ratios (ORs) between hookworm, Ascaris lumbricoides, and Trichuris trichiura, and S. japonicum infections were 1.28 (95% Bayesian credible intervals: 0.93, 1.76), 0.91 (95% BCI: 0.66, 1.26), and 1.11 (95% BCI: 0.80, 1.55), respectively, and 2.13 (95% BCI: 1.16, 4.08), 0.74 (95% BCI: 0.43, 1.25), and 1.32 (95% BCI: 0.80, 2.27), respectively, after correction for misclassification error for both exposure and outcome.

Conclusions/Significance

The misclassification bias increased with decreasing test accuracy. Hookworm infection was found to be associated with increased 12-month cumulative incidence of S. japonicum infection after correction for misclassification error. Such important associations might be missed in analyses which do not adjust for misclassification errors.