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Tauvid ™ (flortaucipir F18 injection)
300-3700 MBq/mL
This information is provided in response to your request. Resources may contain information about doses, uses, formulations and populations different from product labeling. See Prescribing Information above, if applicable.
What is the test accuracy of Tauvid™ (flortaucipir F 18)?
Flortaucipir F 18 PET provides an in vivo estimate of neurofibrillary tangle stage that has high sensitivity (92% to 100%) and specificity (52% to 92%) for B3 tau pathology.
Indication and Usage
Flortaucipir F 18 is indicated for use with positron emission tomography (PET) imaging of the brain to estimate the density and distribution of aggregated tau neurofibrillary tangles (NFTs) in adult patients with cognitive impairment who are being evaluated for Alzheimer’s disease (AD).1
A positive scan
- shows increased neocortical activity in posterolateral temporal, occipital, or parietal/precuneus region(s) with or without frontal activity, and
- supports the presence of widely distributed tau neuropathology (B3 tau pathology).1
A negative scan shows
- no increased neocortical activity, or
- increased neocortical activity isolated to the mesial temporal, anterolateral temporal, and/or frontal regions.1
Limitations of Use
Flortaucipir F 18 is not indicated for use in the evaluation of patients for chronic traumatic encephalopathy.1
Measures of Test Accuracy
The statistical measures of accuracy applied to diagnostic tests include
- sensitivity and specificity
- accuracy
- positive and negative predictive values (PPVs and NPVs), and
- likelihood ratios (LRs).2-4
Additional information about these measures is available in the Appendix.
The performance of flortaucipir F 18 to estimate the density and distribution of aggregated tau NFTs was evaluated in 2 clinical studies.1,5,6
The first study examined flortaucipir F 18 images from 156 individuals who had a terminal illness and cognitive disorders ranging from clinically normal through dementia and had agreed to participate in a postmortem brain donation program. Five independent readers who were blinded to clinical and neuropathological results visually interpreted flortaucipir F 18 PET scans as having or not having a pattern of flortaucipir F 18 retention consistent with AD (moderate or advanced AD tau pattern or negative AD tau pattern).1,5 Flortaucipir F 18 is intended for use in adult patients with cognitive impairment who are being evaluated for AD.1 The patients in this study differ from the intended use population, but were selected in order to compare the detection of AD-type tau pathology in the brain using flortaucipir F 18 with brain autopsy results.5
The second study, a validation study, utilized 5 new readers who assessed the original flortaucipir F 18 PET images for comparison to autopsy in addition to 159 patients with cognitive impairment being evaluated for AD (the indicated population).1,5,6
Because PPV and NPV depend in part on the prevalence of disease or condition in the population that is tested,4 the PPV and NPV for individual patients undergoing evaluation for cognitive decline may be different from those observed in the clinical studies because the patients in these studies differ from the intended use population.5
Reader interpretation of the flortaucipir F 18 scans was compared to tau pathology based on scoring provided by independent pathologists, who evaluated the density and distribution of NFTs in the postmortem brain. Tau pathology scoring included
- B0 = no NFTs (negative)
- B1 = NFTs limited to transentorhinal brain region (negative)
- B2 = B1 + NFTs limited to limbic brain regions (negative), and
- B3 = B2 + NFTs distributed throughout the neocortex (positive).1
The accuracy characteristics of flortaucipir F 18 from the clinical studies, using autopsy as the truth standard, are summarized in Flortaucipir F 18 Test Characteristics From Clinical Studies.
The findings from study 1 demonstrated statistically significant sensitivity and specificity of flortaucipir F 18 PET imaging for detecting tau neurofibrillary pathology which were confirmed by a second set of independent readers of the PET scans in the validation study.5
|
Study 1a |
Study 2a |
Sensitivity |
92.3%-100.0% |
87.2%-97.4% |
Specificity |
52.0%-92.0% |
52.0%-91.4% |
Accuracy |
81.3%-92.2% |
79.7%-92.2% |
PPV |
76.5%-94.7% |
76.0%-92.5% |
NPV |
86.4%-100.0% |
85.7%-92.9% |
LR+ |
2.08-11.54 |
2.5-10.4 |
LR- |
0.00-0.10 |
0.1 |
Abbreviations: LR+ = likelihood ratio of a positive test result; LR- = likelihood ratio of a negative test result; NFT = neurofibrillary tangle; NPV = negative predictive value; PET = positron emission tomography; PPV = positive predictive value.
aFlortaucipir F 18 PET visual reads for all 5 individual readers, compared with pathology findings for identifying standards of B3 NFT scores (a score of B3 was considered positive).
Exploratory analysis evaluated interreader agreement in two subgroups. In this analysis, Fleiss’ kappa (95% CI) was 0.82 (0.75, 0.88) in the terminally ill patients and 0.90 (0.85, 0.95) in the indicated population.1
Enclosed Prescribing Information
References
The published references below are available by contacting 1-800-LillyRx (1-800-545-5979).
1Tauvid [package insert]. Indianapolis, IN: Eli Lilly and Company; 2024.
2Jaeschke R, Guyatt GH, Sackett DL, et al. Users’ guides to the medical literature. III. How to use an article about a diagnostic test B. What are the results and will they help me in caring for my patients? JAMA. 1994;271(9):703-707. http://dx.doi.org/10.1001/jama.1994.03510330081039
3Pewsner D, Battaglia M, Minder C, et al. Ruling a diagnosis in or out with “SpPIn” and “SnNOut”: a note of caution. BMJ. 2004;329(7459):209-213. http://dx.doi.org/10.1136%2Fbmj.329.7459.209
4Mandrekar JN. Simple statistical measures for diagnostic accuracy assessment. J Thorac Oncol. 2010;5(6):763-764. http://dx.doi.org/10.1097/JTO.0b013e3181dab122
5Fleisher AS, Pontecorvo MJ, Devous MD, et al; A16 Study Investigators. Positron emission tomography imaging with [18F]flortaucipir and postmortem assessment of Alzheimer disease neuropathologic changes. JAMA Neurol. 2020;77(7):829-839. http://dx.doi.org/10.1001/jamaneurol.2020.0528
6A reader study to assess accuracy and reliability of flortaucipir F 18 positron emission tomography (PET) scan interpretation. ClinicalTrials.gov identifier: NCT03901092. Updated September 9, 2020. Accessed October 18, 2024. https://clinicaltrials.gov/ct2/show/NCT03901092
7Hyman BT, Phelps CH, Beach TG, et al. National Institute on Aging-Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease. Alzheimers Dement. 2012;8(1):1-13. http://dx.doi.org/10.1016/j.jalz.2011.10.007
8Braak H, Alafuzoff I, Arzberger T, et al. Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry. Acta Neuropathol. 2006;112(4):389-404. https://doi.org/10.1007/s00401-006-0127-z
9Data on file, Eli Lilly and Company and/or one of its subsidiaries.
10Galvin JE, Sadowsky CH. Practical guidelines for the recognition and diagnosis of dementia. J Am Board Fam Med. 2012;25(3):367-382. http://dx.doi.org/10.3122/jabfm.2012.03.100181
11Rajan KB, Weuve J, Barnes LL, et al. Population estimate of people with clinical Alzheimer's disease and mild cognitive impairment in the United States (2020-2060). Alzheimers Dement. 2021;17(12):1966-1975. http://dx.doi.org/10.1002/alz.12362
12Alzheimer's Association. 2023 Alzheimer's disease facts and figures. Alzheimers Dement. 2023;19(4):1598-1695. https://doi.org/10.1002/alz.13016
13Fleisher AS, Chen K, Liu X, et al. Apolipoprotein E ε4 and age effects on florbetapir positron emission tomography in healthy aging and Alzheimer disease. Neurobiol Aging. 2013;34(1):1-12. http://dx.doi.org/10.1016/j.neurobiolaging.2012.04.017
Appendix
Statistical Concepts Applied to the Evaluation of the Accuracy of a Diagnostic Test
Sensitivity and Specificity
Sensitivity is defined as the proportion of people with the target disorder in whom the test result is positive.2
Specificity is the proportion of people without the target disorder in whom the test result is negative.2
The measures of sensitivity and specificity are not explicitly dependent on disease prevalence, but are properties of the test itself.4
Accuracy
Accuracy is measured by comparing the results from a diagnostic test (positive or negative) with the true disease using a gold standard (presence or absence).4
Positive and Negative Predictive Values
PPV is the proportion of people with a positive test result who have the target disorder.3 This is equal to the posttest probability for a positive test result.
NPV is the proportion of people with a negative test result who do not have the target disorder.3 This is equal to 1 minus the posttest probability for a negative test result.
Likelihood Ratios
Likelihood ratios are another measure of accuracy and are independent of disease prevalence; their magnitude is a measure of the certainty of a positive or negative diagnosis.2-4
A LR is the probability of that finding in patients with disease divided by the probability of the same finding in patients without disease.2-4
- The LR of a positive test result (LR+) = sensitivity/(1–specificity).
- The LR of a negative test result (LR–) = (1–sensitivity)/specificity.3
- A LR >1 increases the probability that the target disorder is present, while an LR <1 decreases the probability that the target disorder is present. A LR = 1 does not change the pretest probability that target disorder is present.2
Factors That Can Impact Measures of Test Accuracy
Factors that can impact measures of test accuracy in AD should be taken into consideration when evaluating the value or applicability of a diagnostic test.10
The prevalence of AD in the United States increases with age with approximately
- 5% in those 65-74 years of age
- 13% in those 75-84 years of age, and
- 33% in those ≥85 years of age.11,12
In the evaluation of patients with dementia, AD accounts for 60% to 80% of all cases, representing a high pretest probability in this population.12 Furthermore, age and apolipoprotein E ε4 carrier status have also been shown to impact β-amyloid plaque burden, such that apolipoprotein E ε4 positivity and increased age were associated with increased β-amyloid plaque burden.13
Date of Last Review: October 18, 2024