Comparative Effectiveness of Biomarkers to Target Cancer Treatment: Modeling Implications for Survival and Costs.

BACKGROUND: Biomarkers used at the time of diagnosis to tailor treatment decisions may diffuse into clinical practice before data become available on whether biomarker testing reduces cancer mortality. In the interim, quantitative estimates of the mortality impact of testing are needed to assess the value of these diagnostic biomarkers. These estimates are typically generated by customized models that are resource intensive to build and apply. METHODS: We developed a user-friendly system of models for Cancer Translation of Comparative Effectiveness Research (CANTRANce) to model the mortality impact of cancer interventions. The Diagnostic Biomarker module of this system projects the mortality impact of testing for a diagnostic biomarker, given data on how testing affects treatment recommendations. Costs and quality-of-life outcomes may also be modeled. We applied the Diagnostic Biomarker module to 2 case studies to demonstrate its capabilities. RESULTS: The user interface (http://www.fhcrc.org/cantrance) allows comparative effectiveness researchers to use the Diagnostic Biomarker module of CANTRANce. Our case studies indicate that the model produces estimates on par with those generated by customized models and is a strong tool for quickly generating novel projections. LIMITATIONS: The simple structure that makes CANTRANce user-friendly also constrains the complexity with which cancer progression can be modeled. The quality of the results rests on the quality of the input data, which may pertain to small or dissimilar populations or suffer from informative censoring. CONCLUSIONS: The Diagnostic Biomarker module of CANTRANce is a novel public resource that can provide timely insights into the expected mortality impact of testing for diagnostic biomarkers. The model projections should be useful for understanding the long-term potential of emerging diagnostic biomarkers.

Overdetection of recurrence after radical prostatectomy: estimates based on patient and tumor characteristics.

PURPOSE: Prostate-specific antigen recurrence (PSA-R) after radical prostatectomy (RP) can occur years before metastasis. This study estimates the chance that an untreated PSA-R would not progress to clinical metastasis within the patient's lifetime, that is, that recurrence is overdetected. EXPERIMENTAL DESIGN: Times from PSA-R to metastasis were estimated from patients with RP treated at Johns Hopkins University (Baltimore, MD) who did not receive salvage treatment (n = 441) at PSA-R. Times to other-cause death were based on U.S. life tables adjusted to reflect other-cause survival among RP cases in the Surveillance, Epidemiology, and End Results (SEER) registry. We used competing risks simulation to estimate lower bounds on the chance that other-cause death would precede clinical metastasis for patients with disease characteristics at diagnosis based on the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) database (n = 4,455). RESULTS: Cumulative incidence of PSA-R in CaPSURE was 13.6% at 5 years and 19.9% at 10 years. The risk of other-cause death among patients with RP in SEER was 60% lower than the age-matched U.S. population. At least 9.1% of patients with PSA-R <5 years after RP and at least 15.6% of patients with PSA-R 5 to 10 years after RP were overdetected. At least 31.4% of patients over the age of 70 years at diagnosis, who recurred <10 years of diagnosis, were overdetected. CONCLUSIONS: This analysis indicates that PSA-R after RP may be overdetected, with risk depending on patient age and tumor characteristics. The potential for overdetection of recurrence confirms the need for approaches to determine whether and when to initiate salvage therapies.

Influence of study features and methods on overdiagnosis estimates in breast and prostate cancer screening.

Knowledge of the likelihood that a screening-detected case of cancer has been overdiagnosed is vitally important to make treatment decisions and develop screening policy. An overdiagnosed case is an excess case detected by screening. Estimates of the frequency of overdiagnosis in breast and prostate cancer screening vary greatly across studies. This article identifies features of overdiagnosis studies that influence results and shows their effect by using published research. First, different ways to define and measure overdiagnosis are considered. Second, contextual features and how they affect overdiagnosis estimates are examined. Third, the effect of estimation approach is discussed. Many studies use excess incidence under screening as a proxy for overdiagnosis. Others use statistical models to make inferences about lead time or natural history and then derive the corresponding fraction of cases that are overdiagnosed. This article concludes with questions that readers of overdiagnosis studies can use to evaluate the validity and relevance of published estimates and recommends that authors of studies quantifying overdiagnosis provide information about these features.

Management of diabetes and associated cardiovascular risk factors in seven countries: a comparison of data from national health examination surveys.

OBJECTIVE: To examine the effectiveness of the health system response to the challenge of diabetes across different settings and explore the inequalities in diabetes care that are attributable to socioeconomic factors. METHODS: We used nationally representative health examination surveys from Colombia, England, the Islamic Republic of Iran, Mexico, Scotland, Thailand and the United States of America to obtain data on diagnosis, treatment and control of hyperglycaemia, arterial hypertension and hypercholesterolaemia among individuals with diabetes. Using logistic regression, we explored the socioeconomic determinants of diagnosis and effective case management. FINDINGS: A substantial proportion of individuals with diabetes remain undiagnosed and untreated, both in developed and developing countries. The figures range from 24% of the women in Scotland and the USA to 62% of the men in Thailand. The proportion of individuals with diabetes reaching treatment targets for blood glucose, arterial blood pressure and serum cholesterol was very low, ranging from 1% of male patients in Mexico to about 12% in the United States. Income and education were not found to be significantly related to the rates of diagnosis and treatment anywhere except in Thailand, but in the three countries with available data insurance status was a strong predictor of diagnosis and effective management, especially in the United States. CONCLUSION: There are many missed opportunities to reduce the burden of diabetes through improved control of blood glucose levels and improved diagnosis and treatment of arterial hypertension and hypercholesterolaemia. While no large socioeconomic inequalities were noted in the management of individuals with diabetes, financial access to care was a strong predictor of diagnosis and management.