New Methods for Clinical Trials: AML as an Example
Gertjan J. L. Kaspers, Bertrand Coiffier, Michael C. Heinrich, Elihu Estey in Innovative Leukemia and Lymphoma Therapy, 2019
The stipulation of a 5% significance (i.e., false positive) rate and a 10% to 20% false negative rate is also relevant in this regard. This formulation is used for phase 3 trials in many different diseases that, however, are medically quite different. Thus, while the desire to provide more protection against a false positive result than a false negative one is appropriate in diseases for which there is already reasonably effective treatment, the same desire appears less appropriate in a disease such as AML for which treatment is less effective and, accordingly in which replacement of a standard treatment by a (falsely positive) new treatment is less consequential. Accordingly, I think that phase 3 studies might be designed to provide the same protection say 10% to 15% against both false positive and false negative conclusions. This proposal would also make possible smaller sample sizes and allow more timely completion of studies.
Breast Cancer
Andrew Stevens, James Raftery in Breast Cancer Health Care Needs Assessment, 2018
Acceptability of screening There is no evidence that the screening programme increases psychological morbidity among women invited for screening.159,160 90% of screened women will re-attend for further screening; women who do not are more likely to view the previous experience of screening negatively.161 The majority of women with screen-detected abnormalities will have a benign diagnosis (false-positive). These healthy women undergo unnecessary investigation and occasionally treatment with the possibility of resultant physical and psychological morbidity.162 Therefore it is important to keep the false-positive rate low. Concerns have been expressed about uptake among ethnic minorities. A RCT of pre-screening visits from linkworkers failed to demonstrate a beneficial effect on subsequent uptake of invitation.163
Principles of cancer diagnosis and staging
Peter Hoskin, Peter Ostler in Clinical Oncology, 2020
A small specimen of body fluid (e.g. sputum, ascitic fluid, pleural fluid, urine, cerebrospinal fluid) may be spun down and the cells in it stained and examined under the microscope within minutes of its collection. An experienced cytologist can then give an immediate and accurate diagnosis. The false-positive rate is very low, although false negatives occur owing to errors in interpretation or sampling. This analysis has the advantage that the specimen can often be collected as an outpatient procedure with minimal discomfort and it gives a result quickly so that treatment can be started as soon as possible. Of course, the cellular material obtained may be insufficient for immunohistochemical analysis unless a centrifuge is used to produce a cellular pellet, which can be fixed in wax and sectioned/stained in the usual way.
Fecal immunochemical test in cancer screening – colonoscopy outcome in FIT positives and negatives
Published in Scandinavian Journal of Gastroenterology, 2019
Hanna Ribbing Wilén, Johannes Blom, Jonas Höijer, Gaya Andersson, Christian Löwbeer, Rolf Hultcrantz
Findings at colonoscopy were evaluated at cut off levels 10, 20, 40, 60 and 80 µg hemoglobin (Hb)/g for the first FIT sample, any of the two samples and mean of two samples. Confidence intervals for positivity, sensitivity and specificity were calculated using the Clopper–Pearson method. Associations between binary variables were assessed by Chi2-test and McNemar’s test, and Mann–Whitney’s U test was used for continuous variables (total number of adenomas). The positive predictive value (PPV) for AN was defined as the proportion of participants with AN among FIT positives, and the negative predictive value (NPV) as the proportion of FIT-negatives among participants without AN. The false negative rate was defined as the proportion of negatives among participants with AN (1 – sensitivity). The false positive rate was defined as the proportion of positives among those without AN (1 – specificity).
Cincinnati Prehospital Stroke Scale Can Identify Large Vessel Occlusion Stroke
Published in Prehospital Emergency Care, 2018
Christopher T. Richards, Ryan Huebinger, Katie L. Tataris, Joseph M. Weber, Laura Eggers, Eddie Markul, Leslee Stein-Spencer, Kenneth S. Pearlman, Jane L. Holl, Shyam Prabhakaran
The Spearman's rank test was performed for correlation after skewness and kurtosis tests were performed to evaluate for the presence of non-normally distributed data. Descriptive statistics were performed for the demographic data, Student's t-test was used to compare proportions, and the Wilcoxon rank-sum test was used to compare medians. The Youden index was performed to identify the optimal cut-off scores for the CPSS (41, 42). A receiver operating characteristic (ROC) analysis was also performed for each cut-off score. The Youden index seeks to identify the point on the ROC curve that maximizes the equation “J = sensitivity + specificity – 1.” A test with perfect sensitivity and specificity has a Youden index of 1, and, therefore, a screening test's cut-off score with the highest Youden index optimally balances sensitivity and specificity (43). Multivariate logistic regression, controlling for age, sex, and race, was performed to determine the odds ratio (OR) for LVO. An upper limit cut-off of last known well time of 270 minutes was applied for analyses involving revascularization because IV tPA was not routinely given to AIS patients with symptom onset greater than 270 minutes at the study hospital. The false positive rate was defined as 100 x number of false positive / (number of false positive + number of true negatives). Cohen's kappa was calculated to determine inter-rater reliability for CPSS abstraction with a Cohen's kappa ≥ 0.75 considered “excellent” interrater agreement (44). STATA 12.1 (StataCorp, College Station, TX) was used for statistical analysis.
Point of care molecular and antigen detection tests for COVID-19: current status and future prospects
Published in Expert Review of Molecular Diagnostics, 2022
William Stokes, Byron M. Berenger, Allison A. Venner, Vincent Deslandes, Julie L. V. Shaw
The validation of RATs for asymptomatic screening requires large studies that must consider the prevalence of disease in the population tested. A lower PPV is expected when prevalence is low. One study found a RAT PPV of 0.12% in a low prevalence population [41]. A large Canadian study (71,849 RAT) looked at the performance of two RATs (Abbott Panbio and BD Veritor (Becton Dickinson, NJ, USA)) for asymptomatic screening of healthcare workers at continuing care sites and found a high false-positive rate (30% or 70% positives were false, respectively) [42] . A high false positive rate can have several negative impacts, such as anxiety, loss of income or staff shortages. False-positive results can be minimized by following the manufacturer’s instructions for use, and by minimizing cross-contamination by working in a clean environment [43]. The PPV will also be higher in populations with higher disease prevalence [44]. Another Canadian study assessed the performance of the Abbott Panbio RAT for asymptomatic screening of ~3000 healthcare workers in long-term care homes, and found an NPV of 99.8%, which was a minimal improvement over the NPV based on pretest probability alone (99.6%) [45]. Only 14 positive individuals were identified in this study by PCR, with no false positives by RAT. All tests were performed by trained lab technologists or by healthcare professionals trained by the laboratory.
Related Knowledge Centers
- False Discovery Rate
- Null Hypothesis
- Sensitivity & Specificity
- Statistical Hypothesis Testing
- Type I & Type II Errors
- Multiple Comparisons Problem
- Family-Wise Error Rate
- Type I & Type II Errors
- Statistical Significance
- False Positives & False Negatives
- False Coverage Rate
- Sensitivity & Specificity