Estimates Of Overdiagnosis Research Articles

Current Controversies in Cardiothoracic Imaging: Overdiagnosis at Lung Cancer Screening-Not So Bad After All-Counterpoint.

Initially introduced into the medical literature in research publications from "Special Project #1" of the Council for Tobacco Research, the concept of overdiagnosed lung cancer (OD LC) has consistently served to misinform and confuse the medical community, contributing to interminable delays in implementation of population lung cancer screening. Estimates of overdiagnosis vary enormously (9.5% to 75%). Careful, judicious application of diagnostic algorithms and clinical practice guidelines prevents overtreatment of potentially OD LC and offers a safe and effective method to prevent tens of thousands of LC-related deaths. Speculative concern over potential OD should not further block availability of computed tomography screening to those at risk.

Estimation of overdiagnosis by detection to incidence ratio in cancer screening.

Objective We aimed to introduce a concept of overdiagnosis with actual formulae. In screening for invasive cancer, the detection proportion to incidence rate (D/I) ratio is used as an intermediate indicator of effect. D is the detection rate (proportion) at screen and I is the background risk (i.e. the expected incidence rate if there were no screening). We sought to determine a proper use of the D/I ratio in the estimation of overdiagnosis in screening. Methods We propose the difference between the D/I ratio per year and incidence-based sensitivity as an estimate of overdiagnosis. As an example to evaluate this, we used screening for colorectal cancer, run as a randomized public health policy in Finland. Conclusion The use of the D/I ratio is inappropriate in predicting effect, and we recommend that the D/I ratio be used as a component in the estimation of overdiagnosis in screening for invasive cancer.

Lifetime risk of prostate cancer overdiagnosis in Australia: quantifying the risk of overdiagnosis associated with prostate cancer screening in Australia using a novel lifetime risk approach

ObjectivesTo quantify the risk of overdiagnosis associated with prostate cancer screening in Australia using a novel lifetime risk approach.DesignModelling and validation of the lifetime risk method using publicly available population...

Overdiagnosis in the population-based organized breast cancer screening program estimated by a non-homogeneous multi-state model: a cohort study using individual data with long-term follow-up

BackgroundOverdiagnosis, defined as the detection of a cancer that would not become clinically apparent in a woman’s lifetime without screening, has become a growing concern. Similar underlying risk of breast cancer in the screened and control groups is a prerequisite for unbiased estimates of overdiagnosis, but a contemporary control group is usually not available in organized screening programs.MethodsWe estimated the frequency of overdiagnosis of breast cancer due to screening in women 50–69 years old by using individual screening data from the population-based organized screening program in Stockholm County 1989–2014. A hidden Markov model with four latent states and three observed states was constructed to estimate the natural progression of breast cancer and the test sensitivity. Piecewise transition rates were used to consider the time-varying transition rates. The expected number of detected non-progressive breast cancer cases was calculated.ResultsDuring the study period, 2,333,153 invitations were sent out; on average, the participation rate in the screening program was 72.7% and the average recall rate was 2.48%. In total, 14,648 invasive breast cancer cases were diagnosed; among the 8305 screen-detected cases, the expected number of non-progressive breast cancer cases was 35.9, which is equivalent to 0.43% (95% confidence interval (CI) 0.10%–2.2%) overdiagnosis. The corresponding estimates for the prevalent and subsequent rounds were 15.6 (0.87%, 95% CI 0.20%–4.3%) and 20.3 (0.31%, 95% CI 0.07%–1.6%), respectively. The likelihood ratio test showed that the non-homogeneous model fitted the data better than an age-homogeneous model (P <0.001).ConclusionsOur findings suggest that overdiagnosis in the organized biennial mammographic screening for women 50–69 in Stockholm County is a minor phenomenon. The frequency of overdiagnosis in the prevalent screening round was higher than that in subsequent rounds. The non-homogeneous model performed better than the simpler, traditional homogeneous model.

Estimation of Overdiagnosis of Lung Cancer in Low-Dose Computed Tomography Screening

This study analyzes data from the Danish Lung Cancer Screening Trial to determine the amount of overdiagnosis of computed tomography–detected lung cancer.

Getting personal on overdiagnosis: On defining overdiagnosis from the perspective of the individual person

How can overdiagnosis be defined, explained, and estimated on an individual level? The answers to this question are essential for persons to be able to make informed choices and give valid consents for tests. Traditional conceptions of overdiagnosis tend to depend on counterfactual thinking and prophetic abilities as you would have to know what would happen in the future if you did not test now. To avoid this, overdiagnosis can be defined in terms of the chance of diagnosing a person with a disease when this does not avoid or reduce manifest disease. To be able to relate this to 1's own life and deliberation, I argue that we need answers to specific questions such as the following: If I am tested, and the test and subsequent test results are positive, but I am not treated, what is the chance that I would not experience and suffer from manifest disease? A definition of overdiagnosis that aims at providing answers to this question is as follows: Prospectively overdiagnosis (of an individual person) is given by the estimated chance that a person having a positive test result would not experience and suffer from manifest disease if not treated or followed up in any way. Getting personal on overdiagnosis directs the attention of overdiagnosis estimates towards what matters in medicine: the experience of individual persons.

Defining, Estimating, and Communicating Overdiagnosis in Cancer Screening.

The toll of inadequate health care is well-substantiated, but recognition is mounting that "too much" is also possible. Overdiagnosis represents one harm of too much medicine, but the concept can be confusing: It is often conflated with related harms (such as overtreatment, misclassification, false-positive results, and overdetection) and is difficult to measure because it cannot be directly observed. Because the U.S. Preventive Services Task Force (USPSTF) issues screening recommendations aimed largely at healthy persons, it has a particular interest in understanding harms related to screening, especially but not limited to overdiagnosis. In support of the USPSTF, the authors summarize the knowledge and provide guidance on defining, estimating, and communicating overdiagnosis in cancer screening. To improve consistency, thinking, and reporting about overdiagnosis, they suggest a specific definition. The authors articulate how variation in estimates of overdiagnosis can arise, identify approaches to estimating overdiagnosis, and describe best practices for communicating the potential for harm due to overdiagnosis.

As you like it: How the same data can support manifold views of overdiagnosis in breast cancer screening

Overdiagnosis estimates have varied substantially, causing confusion. The discussions have been complicated by the fact that population and study design have varied substantially between studies. To help assess the impact of study design choices on the estimates, we compared them on a single population. A cohort study from Funen County, Denmark, recently suggested little (∼1%) overdiagnosis. It followed previously screened women for up to 14 years after screening had ended. Using publically available data from Funen, we recreated the designs from five high-estimate, highly cited studies from various countries. Selected studies estimated overdiagnosis to be 25-54%. Their designs were adapted only to the extent that they reflect the start of screening in Funen in 1993. The reanalysis of the Funen data resulted in overdiagnosis estimates that were remarkably similar to those from the original high-estimate age-period studies, 21-55%. In additional analyses, undertaken to elucidate the effect of the individual components of the study designs, overdiagnosis estimates were more than halved after the most likely changes in the background risk were accounted for and decreased additionally when never-screened birth cohorts were excluded from the analysis. The same data give both low and high estimates of overdiagnosis, it all depends on the study design. This stresses the need for a careful scrutiny of the validity of the assumptions underpinning the estimates. Age-period analyses of breast cancer overdiagnosis suggesting very high frequencies of overdiagnosis rested on unmet assumptions. This study showed that overdiagnosis estimates should in the future be requested to adequately control for the background risk and include an informative selection of the studied population to achieve valid and comparable estimates of overdiagnosis.

Estimation of overdiagnosis in breast cancer screening using a non-homogeneous multi-state model: A simulation study

Overdiagnosis is regarded as a harm of screening. We aimed to develop a non-homogeneous multi-state model to consider the age-specific transition rates for estimation of overdiagnosis, to validate the model by a simulation study where the true frequency of overdiagnosis can be calculated, and to compare our estimate with the cumulative incidence method. We constructed a four-state model to describe the natural history of breast cancer. The latent disease progression and the observed states for each individual were simulated in a trial with biennial screening of women aged 51-69 and a control group of the same size without screening. We performed 100 repetitions of the simulation with one million women to evaluate the performance of estimates. A sensitivity analysis with reduced number of controls was performed to imitate the data from the service screening programme. Based on the 100 repetitions, the mean value of the true frequency of overdiagnosis was 12.5% and the average estimates by the cumulative incidence method and the multi-state model were 12.9% (interquartile range: 2.46%) and 13.4% (interquartile range: 2.16%), respectively. The multi-state model had a greater bias of overdiagnosis than the cumulative incidence method, but the variation in the estimates was smaller. When the number of unscreened group was reduced, the variation of multi-state model estimates increased. The multi-state model produces a proper estimate of overdiagnosis and the results are comparable with the cumulative incidence method. The multi-state model can be used in the estimation of overdiagnosis, and might be useful for the ongoing service screening programmes.

Quantifying Overdiagnosis in Cancer Screening: A Systematic Review to Evaluate the Methodology.

Overdiagnosis is the main harm of cancer screening programs but is difficult to quantify. This review aims to evaluate existing approaches to estimate the magnitude of overdiagnosis in cancer screening in order to gain insight into the strengths and limitations of these approaches and to provide researchers with guidance to obtain reliable estimates of overdiagnosis in cancer screening. A systematic review was done of primary research studies in PubMed that were published before January 1, 2016, and quantified overdiagnosis in breast cancer screening. The studies meeting inclusion criteria were then categorized by their methods to adjust for lead time and to obtain an unscreened reference population. For each approach, we provide an overview of the data required, assumptions made, limitations, and strengths. A total of 442 studies were identified in the initial search. Forty studies met the inclusion criteria for the qualitative review. We grouped the approaches to adjust for lead time in two main categories: the lead time approach and the excess incidence approach. The lead time approach was further subdivided into the mean lead time approach, lead time distribution approach, and natural history modeling. The excess incidence approach was subdivided into the cumulative incidence approach and early vs late-stage cancer approach. The approaches used to obtain an unscreened reference population were grouped into the following categories: control group of a randomized controlled trial, nonattenders, control region, extrapolation of a prescreening trend, uninvited groups, adjustment for the effect of screening, and natural history modeling. Each approach to adjust for lead time and obtain an unscreened reference population has its own strengths and limitations, which should be taken into consideration when estimating overdiagnosis.

Overdiagnosis in breast cancer screening: The impact of study design and calculations

Overdiagnosis in breast cancer screening is an important issue. A recent study from Denmark concluded that one in three breast cancers diagnosed in screening areas in women aged 50–69 years were overdiagnosed. The purpose of this short communication was to disentangle the study's methodology in order to evaluate the soundness of this conclusion. We found that both the use of absolute differences as opposed to ratios; the sole focus on non-advanced tumours and the crude allocation of tumours and person-years by screening history for women aged 70–84 years, all contributed to the very high estimate of overdiagnosis. Screening affects cohorts of screened women. Danish registers allow very accurate mapping of the fate of every woman. We should be past the phase where studies of overdiagnosis are based on the fixed age groups from routine statistics.

Benefit-to-harm ratio of the Danish breast cancer screening programme.

The primary aim of breast cancer screening is to reduce breast cancer mortality, but screening also has negative side‐effects as overdiagnosis. To evaluate a screening programme, both benefits and harms should be considered. Published estimates of the benefit‐to‐harm ratio, the number of breast cancer deaths prevented divided by the number of overdiagnosed breast cancer cases, varied considerably. The objective of the study was to estimate the benefit‐to‐harm ratio of breast cancer screening in Denmark. The numbers of breast cancer deaths prevented and overdiagnosed cases [invasive and ductal carcinoma in situ (DCIS)] were estimated per 1,000 women aged 50–79, using national published estimates for breast cancer mortality and overdiagnosis, and national incidence and mortality rates. Estimations were made for both invited and screened women. Among 1,000 women invited to screening from age 50 to age 69 and followed until age 79, we estimated that 5.4 breast cancer deaths would be prevented and 2.1 cases overdiagnosed, under the observed scenario in Denmark of a breast cancer mortality reduction of 23.4% and 2.3% of the breast cancer cases being overdiagnosed. The estimated benefit‐to‐harm ratio was 2.6 for invited women and 2.5 for screened women. Hence, 2–3 women would be prevented from dying from breast cancer for every woman overdiagnosed with invasive breast cancer or DCIS. The difference between the previous published ratios and 2.6 for Denmark is probably more a reflection of the accuracy of the underlying estimates than of the actual screening programmes. Therefore, benefit‐to‐harm ratios should be used cautiously.

Detecting cancer in primary care: Where does early diagnosis stop and overdiagnosis begin?

Detecting cancer in primary care: Where does early diagnosis stop and overdiagnosis begin?

Overdiagnosis of gastric cancer by endoscopic screening.

Gastric cancer screening using endoscopy has recently spread in Eastern Asian countries showing increasing evidence of its effectiveness. However, despite the benefits of endoscopic screening for gastric cancer, its major harms include infection, complications, false-negative results, false-positive results, and overdiagnosis. The most serious harm of endoscopic screening is overdiagnosis and this can occur in any cancer screening programs. Overdiagnosis is defined as the detection of cancers that would never have been found if there is no cancer screening. Overdiagnosis has been estimated from randomized controlled trials, observational studies, and modeling. It can be calculated on the basis of a comparison of the incidence of cancer between screened and unscreened individuals after the follow-up. Although the estimation method for overdiagnosis has not yet been standardized, estimation of overdiagnosis is needed in endoscopic screening for gastric cancer. To minimize overdiagnosis, the target age group and screening interval should be appropriately defined. Moreover, the balance of benefits and harms must be carefully considered to effectively introduce endoscopic screening in communities. Further research regarding overdiagnosis is warranted when evaluating the effectiveness of endoscopic screening.

Overdiagnosis of breast cancer in population screening: does it make breast screening worthless?

The risk of breast cancer (BC) overdiagnosis attributed to mammography screening is an unresolved issue, complicated by heterogeneity in the methodology of quantifying its magnitude, and both political and scientific elements surrounding interpretation of the evidence on this phenomenon. Evidence from randomized trials and also from observational studies shows that mammography screening reduces the risk of BC death; similarly, these studies provide sufficient evidence that overdiagnosis represents a serious harm from population breast screening. For both these outcomes of screening, BC mortality reduction and overdiagnosis, estimates of magnitude vary between studies however overdiagnosis estimates are associated with substantial uncertainty. The trade-off between the benefit and the collective harms of BC screening, including false-positives and overdiagnosis, is more finely balanced than initially recognized, however the snapshot of evidence presented on overdiagnosis does not mean that breast screening is worthless. Future efforts should be directed towards (a) ensuring that any changes in the implementation of BC screening optimize the balance between benefit and harms, including assessing how planned or actual changes modify the risk of overdiagnosis; (b) informing women of all the outcomes that may affect them when they participate in screening using well-crafted and balanced information; and (c) investing in research that will help define and reduce the ensuing overtreatment of screen-detected BC.

Breast cancer incidence trends in Norway and estimates of overdiagnosis

Objective Fluctuations in the incidence of breast cancer in Norway in the last three decades are partly explained by the use of hormone replacement therapy and mammography screening, but overdiagnosis has also been suggested as a cause. We assessed the trends in breast cancer incidence and overdiagnosis in Norway. Methods We calibrated our microsimulation model to Norwegian Cancer Registration data. The model takes into account the use of mammography (both within and outside the Norwegian Breast Cancer Screening Programme) and of hormone replacement therapy. We obtained a proper fit of breast cancer incidence in recent years, when assuming an increase in the background risk for breast cancer, and estimated overdiagnosis. Results We estimated a 2% overdiagnosis rate as a fraction of all cancers diagnosed in women aged 50-100, and a 3% overdiagnosis rate as a fraction of all cancers diagnosed in women aged 50-70 (i.e. screening age). If all of the increased incidence would be the result of the detection of slow growing tumours, these estimates were 7% and 11%, respectively. Conclusion Besides mammography and hormone replacement therapy use, additional risk factors contributed to the sudden increase in breast cancer incidence in Norway. Overdiagnosis estimates due to screening were within the range of international plausible estimates.

Estimation of overdiagnosis using short-term trends and lead time estimates uncontaminated by overdiagnosed cases: Results from the Norwegian Breast Screening Programme.

BackgroundEstimating overdiagnosis in cancer screening is complicated. Using observational data, estimation of the expected incidence in the screening period and taking account of lead time are two major problems.MethodsUsing data from the Cancer Registry of Norway and the Norwegian Breast Cancer Screening Programme, we estimated incidence trends, using age-specific trends by year in the pre-screening period (1985–95). We also estimated sojourn time and sensitivity using interval cancers only. Thus, lead time estimates were uncontaminated by overdiagnosed cases. Finally, we derived estimates of overdiagnosis separately for all cancers, and for invasive cancers only, correcting for lead time, using two different methods.ResultsOur results indicate that overdiagnosis of all cancers, invasive and in situ, constituted 15–17% of all screen-detected cancers in 1996–2009. For invasive cancers only, the corresponding figures were -2 to 7% in the same period, suggesting that a substantial proportion of the overdiagnosis in the Norwegian Programme was due to ductal carcinoma in situ.ConclusionUsing short-term trends, instead of long, prior to screening was more effective in predicting incidence in the screening epoch. In addition, sojourn time estimation using symptomatic cancers only avoids over-correction for lead time and consequently underestimation of overdiagnosis. Longer follow-up will provide more precise estimates of overdiagnosis.

Population-Based Breast Cancer Screening With Risk-Based and Universal Mammography Screening Compared With Clinical Breast Examination: A Propensity Score Analysis of 1 429 890 Taiwanese Women.

Different screening strategies for breast cancer are available but have not been researched in quantitative detail. To assess the benefits and the harms of risk-based and universal mammography screening in comparison with annual clinical breast examination (CBE). Population-based cohort study comparing incidences of stage II+ disease and death from breast cancer across 3 breast cancer screening strategies, with adjustment for a propensity score for participation based on risk factors for breast cancer and comparing the 3 strategies for overdetection between January 1999 and December 2009. Asymptomatic women attending outreach screening in the community or undergoing mammography in hospitals were enrolled in the 3 screening programs. Risk-based biennial mammography, universal biennial mammography, and annual CBE. Detection rates, stage II+ disease incidence, mortality from breast cancer, and overdiagnosis were compared using a time-dependent Cox proportional hazards regression model. A total of 1 429 890 asymptomatic women attending outreach screening in the community or undergoing mammography in hospitals were enrolled in the 3 screening programs. Detection rates (prevalent screen and subsequent screens per 1000) were the highest for universal biennial mammography (4.86 and 2.98, respectively), followed by risk-based mammography (2.80 and 2.77, respectively), and lowest for annual CBE (0.97 and 0.70, respectively). Universal biennial mammography screening, compared with annual CBE, was associated with a 41% mortality reduction (risk ratio, 0.59; 95% CI, 0.48-0.73) and a 30% reduction of stage II+ breast cancer (RR, 0.70; 95% CI, 0.66-0.74). Risk-based mammography screening was associated with an 8% reduction of stage II+ breast cancer (RR, 0.92; 95% CI, 0.86-0.99) but was not associated with a statistically significant mortality reduction (risk ratio [RR], 0.86; 95% CI, 0.73-1.02). Estimates of overdiagnosis were no different from CBE for risk-based screening and 13% higher than CBE for universal mammography. Compared with population-based screening for breast cancer with annual CBE, universal biennial mammography resulted in a substantial reduction in breast cancer deaths, whereas risk-based biennial mammography resulted in only a modest benefit. Compared with annual CBE, risk-based and universal mammography screening did not result in significant overdiagnosis of breast cancer.

Conditions for Valid Empirical Estimates of Cancer Overdiagnosis in Randomized Trials and Population Studies.

Cancer overdiagnosis is frequently estimated using the excess incidence in a screened group relative to that in an unscreened group. However, conditions for unbiased estimation are poorly understood. We developed a mathematical framework to project the effects of screening on the incidence of relevant cancers-that is, cancers that would present clinically without screening. Screening advances the date of diagnosis for a fraction of preclinical relevant cancers. Which diagnoses are advanced and by how much depends on the preclinical detectable period, test sensitivity, and screening patterns. Using the model, we projected incidence in common trial designs and population settings and compared excess incidence with true overdiagnosis. In trials with no control arm screening, unbiased estimates are available using cumulative incidence if the screen arm stops screening and using annual incidence if the screen arm continues screening. In both designs, unbiased estimation requires waiting until screening stabilizes plus the maximum preclinical period. In continued-screen trials and population settings, excess cumulative incidence is persistently biased. We investigated this bias in published estimates from the European Randomized Study of Screening for Prostate Cancer after 9-13 years. In conclusion, no trial or population setting automatically permits unbiased estimation of overdiagnosis; sufficient follow-up and appropriate analysis remain crucial.

Revised estimates of overdiagnosis from the Canadian National Breast Screening Study

We have re-estimated overdiagnosis of breast cancer from mammography screening by age group in the Canadian National Breast Screening Study (CNBSS), a randomized screening trial. In the CNBSS, participants were recruited in 15 centers. 89,835 women were randomized with informed consent, 50,430 age 40–49 and 39,405 age 50–59. Women aged 40–49 received annual mammography and physical examination (MA+PX) versus a single physical examination and usual care in the community (UC). Women aged 50–59 received (MA+PX) versus (PX-alone) annually. Individual randomization resulted in 44 almost identically distributed demographic and risk factors. Annual compliance over the five or four scheduled screens was 86–95%. The cumulative numbers of invasive and in situ breast cancers ascertained by year during screening and subsequent follow-up to 25 years post entry to the CNBSS in the mammography arm have been compared to those in the control arm. Estimates of overdiagnosis were derived using post-screening cessation cut-off points from 1 to 20years.⋯Overdiagnosis of invasive breast cancer at five years post cessation of screening for women aged 40–49 was estimated to be 32%, and 16% for women aged 50–59; 20years post cessation of screening 48% for women 40–49 and 5% for those 50–59. Including ductal carcinoma in situ with invasive cancer, estimates were 41%, 25%, 55% and 16%, respectively. We conclude that approximately 30% of invasive screen-detected breast cancers in women age 40–49 were overdiagnosed, and 20% of those screen-detected in women age 50–59. Including ductal carcinoma in situ, the estimates are 40% and 30%, respectively.