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Assessing the probability that a positive report is false: an approach for molecular epidemiology studies.

ABSTRACT: Too many reports of associations between genetic variants and common cancer sites and other complex diseases are false positives. A major reason for this unfortunate situation is the strategy of declaring statistical significance based on a P value alone, particularly, any P value below.05. The false positive report probability (FPRP), the probability of no true association between a genetic variant and disease given a statistically significant finding, depends not only on the observed P value but also on both the prior probability that the association between the genetic variant and the disease is real and the statistical power of the test. In this commentary, we show how to assess the FPRP and how to use it to decide whether a finding is deserving of attention or "noteworthy." We show how this approach can lead to improvements in the design, analysis, and interpretation of molecular epidemiology studies. Our proposal can help investigators, editors, and readers of research articles to protect themselves from overinterpreting statistically significant findings that are not likely to signify a true association. An FPRP-based criterion for deciding whether to call a finding noteworthy formalizes the process already used informally by investigators--that is, tempering enthusiasm for remarkable study findings with considerations of plausibility.

SUBMITTER: Wacholder S

PROVIDER: S-EPMC7713993 | biostudies-literature | 2004 Mar

REPOSITORIES: biostudies-literature

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Assessing the probability that a positive report is false: an approach for molecular epidemiology studies.

Wacholder Sholom S Chanock Stephen S Garcia-Closas Montserrat M El Ghormli Laure L Rothman Nathaniel N

Journal of the National Cancer Institute 20040301 6

Too many reports of associations between genetic variants and common cancer sites and other complex diseases are false positives. A major reason for this unfortunate situation is the strategy of declaring statistical significance based on a P value alone, particularly, any P value below.05. The false positive report probability (FPRP), the probability of no true association between a genetic variant and disease given a statistically significant finding, depends not only on the observed P value b ...[more]

PMID: 15026468

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Project description:False-positive mammography results are common. Biennial screening may decrease the cumulative probability of false-positive results across many years of repeated screening but could also delay cancer diagnosis.To compare the cumulative probability of false-positive results and the stage distribution of incident breast cancer after 10 years of annual or biennial screening mammography.Prospective cohort study.7 mammography registries in the National Cancer Institute-funded Breast Cancer Surveillance Consortium.169,456 women who underwent first screening mammography at age 40 to 59 years between 1994 and 2006 and 4492 women with incident invasive breast cancer diagnosed between 1996 and 2006.False-positive recalls and biopsy recommendations stage distribution of incident breast cancer.False-positive recall probability was 16.3% at first and 9.6% at subsequent mammography. Probability of false-positive biopsy recommendation was 2.5% at first and 1.0% at subsequent examinations. Availability of comparison mammograms halved the odds of a false-positive recall (adjusted odds ratio, 0.50 [95% CI, 0.45 to 0.56]). When screening began at age 40 years, the cumulative probability of a woman receiving at least 1 false-positive recall after 10 years was 61.3% (CI, 59.4% to 63.1%) with annual and 41.6% (CI, 40.6% to 42.5%) with biennial screening. Cumulative probability of false-positive biopsy recommendation was 7.0% (CI, 6.1% to 7.8%) with annual and 4.8% (CI, 4.4% to 5.2%) with biennial screening. Estimates were similar when screening began at age 50 years. A non-statistically significant increase in the proportion of late-stage cancers was observed with biennial compared with annual screening (absolute increases, 3.3 percentage points [CI, -1.1 to 7.8 percentage points] for women age 40 to 49 years and 2.3 percentage points [CI, -1.0 to 5.7 percentage points] for women age 50 to 59 years) among women with incident breast cancer.Few women underwent screening over the entire 10-year period. Radiologist characteristics influence recall rates and were unavailable. Most mammograms were film rather than digital. Incident cancer was analyzed in a small sample of women who developed cancer.After 10 years of annual screening, more than half of women will receive at least 1 false-positive recall, and 7% to 9% will receive a false-positive biopsy recommendation. Biennial screening appears to reduce the cumulative probability of false-positive results after 10 years but may be associated with a small absolute increase in the probability of late-stage cancer diagnosis.National Cancer Institute.

Dataset Information

Assessing the probability that a positive report is false: an approach for molecular epidemiology studies.

Publications

Assessing the probability that a positive report is false: an approach for molecular epidemiology studies.

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