Biomedical subjects

J Dik F Habbema

Publications and source records attributed to J Dik F Habbema.

At least 19 recordsLinked to original sources

PubMed2007

Risk-based selection from the general population in a screening trial: selection criteria, recruitment and power for the Dutch-Belgian randomised lung cancer multi-slice CT screening trial (NELSON).

A method to obtain the optimal selection criteria, taking into account available resources and capacity and the impact on power, is presented for the Dutch-Belgian randomised lung cancer screening trial (NELSON). NELSON investigates whether 16-detector multi-slice computed tomography screening will decrease lung cancer mortality compared to no screening. A questionnaire was sent to 335,441 (mainly) men, aged 50-75. Smoking exposure (years smoked, cigarettes/day, years quit) was determined, and expected lung cancer mortality was estimated for different selection scenarios for the 106,931 respondents, using lung cancer mortality data by level of smoking exposure (US Cancer Prevention Study I and II). Selection criteria were chosen so that the required response among eligible subjects to reach sufficient sample size was minimised and the required sample size was within our capacity. Inviting current and former smokers (quit 15 cigarettes/day during >25 years or >10 cigarettes/day during >30 years was most optimal. With a power of 80%, 17,300-27,900 participants are needed to show a 20-25% lung cancer mortality reduction 10 years after randomisation. Until October 18, 2005 11,103 (first recruitment round) and 4,325 (second recruitment round) (total = 15,428) participants have been randomised. Selecting participants for lung cancer screening trials based on risk estimates is feasible and helpful to minimize sample size and costs. When pooling with Danish trial data (n = +/-4,000) NELSON is the only trial without screening in controls that is expected to have 80% power to show a lung cancer mortality reduction of at least 25% 10 years after randomisation.

Aged↗

PubMed2006

Nonattendance is still the main limitation for the effectiveness of screening for cervical cancer in the Netherlands.

Although mass screening for cervical cancer has been operational for more than 2 decades in the Netherlands, 700 women are still diagnosed with this cancer each year (9 per 100,000). We investigated these cases, in order to evaluate opportunities to further increase the effectiveness of the programme. We analyzed the screening history of women diagnosed with cervical cancer between 1994-1997 using the Dutch national pathology file that includes cervical cytology and histological results. More than half of the cases did not have previous preventive cervical smears, and another 30% had never been invited to the programme because of their age. In the future, we estimate that two thirds of all Dutch women with invasive cervical cancer will be unscreened or under-screened, based on current screening participation of more than 70%. We conclude that increasing screening participation has much more potential for further reducing cervical cancer incidence than reducing the screening interval, increasing the age range or having a screening test with higher sensitivity.

Age Factors↗

PubMed2006

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↗

PubMed2006

Value of the HLA-DRB1 shared epitope for predicting radiographic damage in rheumatoid arthritis depends on the individual patient risk profile.

OBJECTIVE: To investigate the influence of individual patient risk profiles on the value of the HLA-DRB1 shared epitope (SE) as a predictor of severe erosive damage in rheumatoid arthritis (RA). METHODS: Patient characteristics, clinical signs and symptoms, rheumatoid factor (RF) status, and HLA-DRB1 genotypes were available for 154 Caucasian women with RA. Risk profiles were defined by non-genetic factors that predict severe erosive disease. The additional value of the SE was defined by the likelihood ratios (LR) of SE presence and absence, which were calculated at the individual patient level. RESULTS: In the total population, the LR of SE presence was 1.42 and the LR of SE absence was 0.37, corresponding to an odds ratio of 3.9, indicating a substantially higher risk of severe erosive disease in those with the SE compared to those without. The LR of SE presence and absence varied depending on the risk profile of the women, from 1.01 to 2.25 for SE presence and 0.22 to 0.49 for SE absence. Considering all the patient characteristics, SE status was most significantly related to RF status. Consequently, the LR of SE presence and absence were higher for RF-negative women compared to RF-positive women (SE presence 1.77 vs 1.40, p < 0.001 and SE absence 0.38 vs 0.30, p < 0.001). CONCLUSION: The additional value of SE testing for predicting severe erosive disease varies according to patient risk profiles. Given the likely availability of genetic and other novel tests in the future, information about the additional value of test results is needed to ensure the optimal use of such testing in the management of RA.

Adult↗

PubMed2006

Intrauterine insemination with controlled ovarian hyperstimulation versus expectant management for couples with unexplained subfertility and an intermediate prognosis: a randomised clinical trial.

BACKGROUND: Intrauterine insemination with controlled ovarian hyperstimulation is commonly used as first-line treatment for couples with unexplained subfertility. Since such treatment increases the risk of multiple pregnancy, a couple's chances of achieving an ongoing pregnancy without it should be considered to identify those most likely to benefit from treatment. We aimed to assess the incremental effectiveness of intrauterine insemination with controlled ovarian hyperstimulation compared with expectant management in couples with unexplained subfertility and an intermediate prognosis of a spontaneous ongoing pregnancy. METHODS: 253 couples with unexplained subfertility and a 30-40% probability of a spontaneous ongoing pregnancy within 12 months were randomly assigned either intrauterine insemination with controlled ovarian hyperstimulation for 6 months or expectant management for 6 months. The primary endpoint of this hospital-based study was ongoing pregnancy within 6 months. Analysis was by intention to treat. This trial is registered with the Dutch Trial Register and as an International Standard Randomised Clinical Trial, number ISRCTN72675518. FINDINGS: Of the 253 couples enrolled, 127 were assigned intrauterine insemination with controlled ovarian hyperstimulation and 126 expectant management. In the intervention group, 42 (33%) women conceived and 29 (23%) pregnancies were ongoing. In the expectant management group, 40 (32%) women conceived and 34 (27%) pregnancies were ongoing (relative risk 0.85, 95% CI 0.63-1.1). There was one twin pregnancy in each study group, and one woman in the intervention group conceived triplets. INTERPRETATION: A large beneficial effect of intrauterine insemination with controlled ovarian hyperstimulation in couples with unexplained subfertility and an intermediate prognosis can be excluded. Expectant management for 6 months is therefore justified in these couples.

Adult↗

PubMed2006

Predicting retroperitoneal histology in postchemotherapy testicular germ cell cancer: a model update and multicentre validation with more than 1000 patients.

OBJECTIVES: Surgical resection of postchemotherapy retroperitoneal lymph nodes is often performed in patients with advanced nonseminomatous testicular germ cell cancer. We previously developed a model to predict the probability that the lymph nodes contain only necrotic or fibrotic (benign) tissue versus mature teratoma and viable cancer (tumour) to identify patients who actually need resection. The present study used an updated model with new patient data and studied the validity of the updated model across various settings. METHODS: We combined data of 544 patients from the original model with data of 550 new patients and performed a new logistic regression analysis, which included the same six predictors: histology of the primary tumour, prechemotherapy serum levels of alpha-fetoprotein, human chorionic gonadotropin, lactate dehydrogenase, residual mass size measured on computed tomography, and change in mass size. The validity of the updated model was studied in individual centres. Calibration of the predicted probabilities was assessed graphically and with the Hosmer-Lemeshow test. Discrimination was studied with the concordance (c)-statistic. RESULTS: The updated model had slightly different, although more precise, regression coefficients. Statistically nonsignificant Hosmer-Lemeshow tests confirmed good calibration in most centres. The c-statistic for all centres except one exceeded 0.80. The updated model was valid over the complete range of predicted probabilities across a broad spectrum of centres. CONCLUSIONS: This finding gives confidence in the applicability of the model to select patients for resection, particularly patients with small residual masses and low predicted probabilities of benign tissue (i.e., substantial predicted risks of residual tumour).

Humans↗

PubMed2006

Association of SARS susceptibility with single nucleic acid polymorphisms of OAS1 and MxA genes: a case-control study.

BACKGROUND: Host genetic factors may play a role in susceptibility and resistance to SARS associated coronavirus (SARS-CoV) infection. The study was carried out to investigate the association between the genetic polymorphisms of 2',5'-oligoadenylate synthetase 1 (OAS1) gene as well as myxovirus resistance 1 (MxA) gene and susceptibility to SARS in Chinese Han population. METHODS: A hospital-based case-control study was conducted. A collective of 66 SARS cases and 64 close contact uninfected controls were enrolled in this study. End point real time polymerase chain reaction (PCR) and PCR-based Restriction Fragment Length Polymorphism (RFLP) analysis were used to detect the single nucleic polymorphisms (SNPs) in OAS1 and MxA genes. Information on other factors associated with SARS infection was collected using a pre-tested questionnaire. Univariate and multivariate logistic analyses were conducted. RESULTS: One polymorphism in the 3'-untranslated region (3'-UTR) of the OAS1 gene was associated with SARS infection. Compared to AA genotype, AG and GG genotypes were found associated with a protective effect on SARS infection with ORs (95% CI) of 0.42 (0.20-0.89) and 0.30 (0.09-0.97), respectively. Also, a GT genotype at position 88 in the MxA gene promoter was associated with increased susceptibility to SARS infection compared to a GG genotype (OR = 3.06, 95% CI: 1.25-7.50). The associations of AG genotype in OAS1 and GT genotype in MxA remained significant in multivariate analyses after adjusting for SARS protective measures (OR = 0.38, 95% CI: 0.14-0.98 and OR = 3.22, 95% CI: 1.13-9.18, respectively). CONCLUSION: SNPs in the OAS1 3'-UTR and MxA promoter region appear associated with host susceptibility to SARS in Chinese Han population.

2',5'-Oligoadenylate Synthetase↗

PubMed2006

Survival of non-seminomatous germ cell cancer patients according to the IGCC classification: An update based on meta-analysis.

The International Germ Cell Consensus (IGCC) Classification distinguishes patients with non-seminomatous germ cell tumours (NSGCT) with a good, intermediate or poor prognosis, with a reported 5-year overall survival of 92%, 80% and 48%, respectively. Since the IGCC classification was based on patients treated between 1975 and 1990, we aimed to investigate whether survival has improved for more recently treated patients. We did a systematic search of the literature and included studies on survival of patients with NSGCT, treated after 1989 and classified according to the IGCC classification. Survival estimates of selected studies were pooled using meta-analytic techniques. We included 10 papers, describing 1775 patients with NSGCT with good (n = 1087), intermediate (n = 232), or poor (n = 456) prognosis. Pooled 5-year survival estimates were 94%, 83% and 71%, respectively. Since the publication of the IGCC classification, there was a small increase in survival for good and intermediate prognosis patients, and a large increase in survival for patients with a poor prognosis. This increase is most likely due to both more effective treatment strategies and more experience in treating NSGCT patients.

Adult↗

PubMed2006

Advances and challenges in predicting the impact of lymphatic filariasis elimination programmes by mathematical modelling.

Mathematical simulation models for transmission and control of lymphatic filariasis are useful tools for studying the prospects of lymphatic filariasis elimination. Two simulation models are currently being used. The first, EPIFIL, is a population-based, deterministic model that simulates average trends in infection intensity over time. The second, LYMFASIM, is an individual-based, stochastic model that simulates acquisition and loss of infection for each individual in the simulated population, taking account of individual characteristics. For settings like Pondicherry (India), where Wuchereria bancrofti infection is transmitted by Culex quinquefasciatus, the models give similar predictions of the coverage and number of treatment rounds required to bring microfilaraemia prevalence below a level of 0.5%. Nevertheless, published estimates of the duration of mass treatment required for elimination differed, due to the use of different indicators for elimination (EPIFIL: microfilaraemia prevalence < 0.5% after the last treatment; LYMFASIM: reduction of microfilaraemia prevalence to zero, within 40 years after the start of mass treatment). The two main challenges for future modelling work are: 1) quantification and validation of the models for other regions, for investigation of elimination prospects in situations with other vector-parasite combinations and endemicity levels than in Pondicherry; 2) application of the models to address a range of programmatic issues related to the monitoring and evaluation of ongoing control programmes. The models' usefulness could be enhanced by several extensions; inclusion of different diagnostic tests and natural history of disease in the models is of particular relevance.

Journal Article↗

PubMed2006

Mobility and HIV in Tanzanian couples: both mobile persons and their partners show increased risk.

OBJECTIVE: To investigate how mobility is related to sexual risk behavior and HIV infection, with special reference to the partners who stay behind in mobile couples. METHODS: HIV status, sexual behavior and demographic data of 2800 couples were collected in a longitudinal study in Kisesa, rural Tanzania. People were considered short-term mobile if they had slept outside the household at least once on the night before one of the five demographic interviews, and long-term mobile if they were living elsewhere at least once at the time of a demographic round. RESULTS: Overall, whereas long-term mobile men did not report more risk behavior than resident men, short-term mobile men reported having multiple sex partners in the last year significantly more often. In contrast, long-term mobile women reported having multiple sex partners more often than resident women (6.8 versus 2.4%; P = 0.001), and also had a higher HIV prevalence (7.7 versus 2.7%; P = 0.02). In couples, men and women who were resident and had a long-term mobile partner both reported more sexual risk behavior and also showed higher HIV prevalence than people with resident/short-term mobile partners. Remarkably, risk behavior of men increased more when their wives moved than when they were mobile themselves. CONCLUSIONS: More sexual risk behavior and an increased risk of HIV infection were seen not only in mobile persons, but also in partners staying behind. Interventions aiming at reducing risk behavior due to mobility should therefore include partners staying behind.

Adolescent↗

PubMed2006

Comparison of Carpentier-Edwards pericardial and supraannular bioprostheses in aortic valve replacement.

OBJECTIVE: This study aimed at calculating and comparing the long-term outcomes of patients after aortic valve replacement with the Carpentier-Edwards bovine pericardial and porcine supraannular bioprostheses using microsimulation. METHODS: We conducted a meta-analysis of eight studies on the Carpentier-Edwards pericardial valves (2,685 patients, 12,250 patient-years) and five studies on the supraannular valves (3,796 patients, 20,127 patient-years) to estimate the occurrence rates of valve-related events. Eighteen-year follow-up data sets were used to construct age-dependent Weibull curves that described their structural valvular deterioration. The estimates were entered into a microsimulation model, which was used to calculate the outcomes of patients after aortic valve replacement. RESULTS: The annual hazard rates for thrombo-embolism after aortic valve replacement were 1.35% and 1.76% for the pericardial and supraannular valves, respectively. For a 65-year-old male, median time to structural valvular deterioration was 20.1 and 22.2 years while the lifetime risk of reoperation due to structural valvular deterioration was 18.3% and 14.0%, respectively. The life expectancy of the patient was 10.8 and 10.9 years and event-free life expectancy 9.0 and 8.8 years, respectively. CONCLUSIONS: The microsimulation methodology provides insight into the prognosis of a patient after aortic valve replacement with any given valve type. Both the Carpentier-Edwards pericardial and supraannular valve types perform satisfactorily, especially in elderly patients, and show no appreciable difference in long-term outcomes when implanted in the aortic position.

Aged↗

PubMed2006

Subgroup analyses in therapeutic cardiovascular clinical trials: are most of them misleading?

BACKGROUND: Treatment decisions in clinical cardiology are directed by results from randomized clinical trials (RCTs). We studied the appropriateness of the use and interpretation of subgroup analysis in current therapeutic cardiovascular RCTs. METHODS: We reviewed main reports of phase 3 cardiovascular RCTs with at least 100 patients, published in 2002 and 2004, and from major journals (Circulation, J Am Coll Cardiol, Am Heart J, Am J Cardiol, N Engl J Med, Lancet, JAMA, BMJ, Ann Intern Med). Information on subgroups included prespecification, number, interaction test use, significant subgroups found, and emphasis on findings. We examined appropriateness of reporting and differences according to sample size, overall trial result, and CONSORT adoption. RESULTS: We selected 63 RCTs, with a median of 496 (range 100-15,245) patients. Thirty-nine RCTs were reported with subgroup analyses and 26 with > 5 subgroups. No trial was specifically powered to detect subgroup effects, and only 14 RCTs were reported with fully prespecified subgroups. Only 11 RCTs were reported with interaction tests. Furthermore, 21 RCTs were reported with claims of significant subgroups and 15 with equal or more emphasis to subgroups than to the overall results. Subgroup analyses in large RCTs (> 500 patients) were reported more often than in small ones (24/30 vs 15/33, P = .005). No differences were found according to overall result (positive/negative) or CONSORT adoption. CONCLUSIONS: Subgroup analyses in recent cardiovascular RCTs were reported with several shortcomings, including a lack of prespecification and testing of a large number of subgroups without the use of the statistically appropriate test for interaction. Reporting of subgroup analysis needs to be substantially improved because emphasis on these secondary results may mislead treatment decisions.

Cardiovascular Diseases↗

PubMed2006

Some prognostic models for traumatic brain injury were not valid.

OBJECTIVE: Various prognostic models have been developed to predict outcome after traumatic brain injury (TBI). We aimed to determine the validity of six models that used baseline clinical and computed tomographic characteristics to predict mortality or unfavorable outcome at 6 months or later after severe or moderate TBI. STUDY DESIGN AND SETTING: The validity was studied in two selected series of TBI patients enrolled in clinical trials (Tirilazad trials; n = 2,269; International Selfotel Trial; n = 409) and in two unselected series of patients consecutively admitted to participating centers (European Brain Injury Consortium [EBIC] survey; n = 796; Traumatic Coma Data Bank; n = 746). Validity was indicated by discriminative ability (AUC) and calibration (Hosmer-Lemeshow goodness-of-fit test). RESULTS: The models varied in number of predictors (four to seven) and in development technique (two prediction trees and four logistic regression models). Discriminative ability varied widely (AUC: .61-.89), but calibration was poor for most models. Better discrimination was observed for logistic regression models compared with trees, and for models including more predictors. Further, discrimination was better when tested on unselected series that contained more heterogeneous populations. CONCLUSION: Our findings emphasize the need for external validation of prognostic models. The satisfactory discrimination indicates that logistic regression models, developed on large samples, can be used for classifying TBI patients according to prognostic risk.

Area Under Curve↗

PubMed2006

Survival estimates of a prognostic classification depended more on year of treatment than on imputation of missing values.

BACKGROUND AND OBJECTIVE: The International Germ Cell Consensus (IGCC) classification defines good, intermediate, and poor prognosis groups among patients with nonseminomatous germ cell cancer. In the database used to develop the IGCC classification (n = 5,202), >40% of patients were excluded because of missing values (n = 2,154). We looked for effects of this exclusion on survival estimates in the three IGCC prognosis groups. STUDY DESIGN AND SETTING: We imputed missing values using a multiple imputation procedure. The IGCC classification was applied to patients with complete data (n = 3,048) and with imputed data (n = 2,154), and 5-year survival was calculated for each prognosis group. RESULTS: Patients with missing values had a lower 5-year survival than those without missing values: 76% vs. 82%. Five-year survival in the complete and imputed data samples was 92% and 87% for the good prognosis groups and 80% and 70% for the intermediate prognosis groups, whereas 5-year survival for the poor prognosis groups in both samples was similar (50% and 47%, respectively). This difference in survival was largely explained by a higher proportion of missing values among patients treated before 1985, who had a worse survival than patients treated after 1985. CONCLUSION: Multiple imputation of the missing values led to lower survival estimates across the IGCC prognosis groups, compared with estimates based on the complete data. Although imputation of missing values gives statistically better survival estimates, adjustments for year of treatment are necessary to make the estimates applicable to currently diagnosed patients with testicular cancer.

Classification↗

PubMed2006

Which factors play a role in clinical decision-making in subfertility?

Sixteen vignettes of subfertile couples were constructed by varying fertility history, post-coital test, sperm motility, FSH concentration and Chlamydia antibody titre (CAT). Thirty-five gynaecologists estimated probabilities of treatment-independent pregnancy, intrauterine insemination (IUI) and IVF. Thereafter, they chose IUI, IVF or no treatment. The relative contribution of each factor to probability estimates and to subsequent treatment decisions was calculated. Duration of subfertility and maternal age were the most important contributors for gynaecologists' estimates of treatment-independent pregnancy [relative contribution (RC) 41, 26%]. Maternal age and FSH concentration were the most important contributors in the estimates for IUI (RC: 51, 25%) and for IVF (RC: 64, 31%). The decision to start IVF was mainly determined by maternal age, duration of subfertility, FSH concentration and CAT. The relative contribution of maternal age and duration of subfertility was in concordance with existing prediction models, whereas previous pregnancy and FSH concentration were under- and overestimated respectively. In conclusion, maternal age, duration of subfertility and FSH concentration are the main factors in clinical decision-making in subfertility. Gynaecologists overestimate the importance of FSH concentration, but underestimate that of a previous pregnancy, as compared with their importance reported in prediction models and guidelines.

Adult↗

PubMed2006

Adjustment for strong predictors of outcome in traumatic brain injury trials: 25% reduction in sample size requirements in the IMPACT study.

The aim of this study was to quantify the potential reduction in sample size that can be achieved by adjustment for predictors of outcome in traumatic brain injury (TBI) trials. We used individual patient data from seven therapeutic phase III randomized clinical trials (RCTs; n = 6166) in moderate or severe TBI, and three TBI surveys (n = 2238). The primary outcome was the dichotomized Glasgow Outcome Scale at 6 months (favorable/unfavorable). Baseline predictors of outcome considered were age, motor score, pupillary reactivity, computed tomography (CT) classification, traumatic subarachnoid hemorrhage, hypoxia, hypotension, glycemia, and hemoglobin. We calculated the potential sample size reduction obtained by adjustment of a hypothetical treatment effect for one to seven predictors with logistic regression models. The distribution of predictors was more heterogeneous in surveys than in trials. Adjustment of the treatment effect for the strongest predictors (age, motor score, and pupillary reactivity) yielded a reduction in sample size of 16-23% in RCTs and 28-35% in surveys. Adjustment for seven predictors yielded a reduction of about 25% in most studies: 20-28% in RCTs and 32-39% in surveys. A major reduction in sample size can be obtained with covariate adjustment in TBI trials. Covariate adjustment for strong predictors should be incorporated in the analysis of future TBI trials.

Age Factors↗

PubMed2006

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↗

PubMed2006

Impact of mammography on U.S. breast cancer mortality, 1975-2000: are intermediate outcome measures informative?

Seven models have estimated the contribution of screening to the decrease in U.S. breast cancer mortality between 1975 and 2000. We will investigate whether the model estimates of the mortality reduction due to screening are associated with intermediate outcome measures (IOMs). Detection rates at screening, 1- and 2-year sensitivity, program sensitivity, and incidence of advanced tumors are used as IOMs. Moreover, the model parameters preclinical duration and sensitivity are analyzed. The correlation of IOMs with mortality is assessed for actual U.S. screening and for an intensive screening scenario, with annual screening at ages 40-79 years with 100% participation. Also, 12 alternative screening scenarios are run for one of the models, and within-model correlation between IOMs and mortality reduction is described. Resulting correlations between IOMs and mortality reduction are mostly weak. For 2-year sensitivity and the incidence of advanced tumors, correlations are high in the intensive screening scenario. Within-model correlations are strong for incidence of advanced tumors and program sensitivity. Intermediate outcome measures have limited potential in predicting the impact of mammographic screening on mortality. Incidence of advanced tumors and program sensitivity are measures that merit further consideration as surrogates for mortality reduction.

Adult↗