scholarly journals We need to talk about reliability: Making better use of test-retest studies for study design and interpretation

2018 ◽  
Author(s):  
Granville J. Matheson
Keyword(s):  
Positron Emission Tomography ◽  
Validation Studies ◽  
R Package ◽  
Experimental Designs ◽  
Emission Tomography ◽  
Summary Statistics ◽  
Positron Emission ◽  
Different Populations ◽  
Scientific Questions ◽  
Healthy Participants

ABSTRACTPositron emission tomography (PET), along with many other fields of clinical research, is both timeconsuming and expensive, and recruitable patients can be scarce. These constraints limit the possibility of large-sample experimental designs, and often lead to statistically underpowered studies. This problem is exacerbated by the use of outcome measures whose accuracy is sometimes insufficient to answer the scientific questions posed. Reliability is usually assessed in validation studies using healthy participants, however these results are often not easily applicable to clinical studies examining different populations. I present a new method and tools for using summary statistics from previously published test-retest studies to approximate the reliability of outcomes in new samples. In this way, the feasibility of a new study can be assessed during planning stages, and before collecting any new data. An R package called relfeas also accompanies this article for performing these calculations. In summary, these methods and tools will allow researchers to avoid performing costly studies which are, by virtue of their design, unlikely to yield informative conclusions.

scholarly journals We need to talk about reliability: making better use of test-retest studies for study design and interpretation

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e6918 ◽  
Author(s):  
Granville J. Matheson
Keyword(s):  
Clinical Research ◽  
Study Design ◽  
Validation Studies ◽  
Clinical Studies ◽  
R Package ◽  
Experimental Designs ◽  
Summary Statistics ◽  
Different Populations ◽  
Scientific Questions ◽  
Healthy Participants

Neuroimaging, in addition to many other fields of clinical research, is both time-consuming and expensive, and recruitable patients can be scarce. These constraints limit the possibility of large-sample experimental designs, and often lead to statistically underpowered studies. This problem is exacerbated by the use of outcome measures whose accuracy is sometimes insufficient to answer the scientific questions posed. Reliability is usually assessed in validation studies using healthy participants, however these results are often not easily applicable to clinical studies examining different populations. I present a new method and tools for using summary statistics from previously published test-retest studies to approximate the reliability of outcomes in new samples. In this way, the feasibility of a new study can be assessed during planning stages, and before collecting any new data. An R package called relfeas also accompanies this article for performing these calculations. In summary, these methods and tools will allow researchers to avoid performing costly studies which are, by virtue of their design, unlikely to yield informative conclusions.

scholarly journals An open-label, positron emission tomography study of the striatal D2/D3 receptor occupancy and pharmacokinetics of single-dose oral brexpiprazole in healthy participants

2020 ◽  
Author(s):  
Dean F. Wong ◽  
Arash Raoufinia ◽  
Patricia Bricmont ◽  
James R. Brašić ◽  
Robert D. McQuade ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Single Dose ◽  
Caudate Nucleus ◽  
Receptor Occupancy ◽  
Emission Tomography ◽  
Maximum Plasma ◽  
Open Label ◽  
Post Dose ◽  
Positron Emission ◽  
Healthy Participants

Abstract Purpose The aim of this Phase 1, open-label, positron emission tomography (PET) study was to determine the degree of striatal D2/D3 receptor occupancy induced by the serotonin–dopamine activity modulator, brexpiprazole, at different single dose levels in the range 0.25–6 mg. Methods Occupancy was measured at 4 and 23.5 h post-dose using the D2/D3 receptor antagonist [11C]raclopride. The pharmacokinetics, safety and tolerability of brexpiprazole were assessed in parallel. Results Fifteen healthy participants were enrolled (mean age 33.9 years; 93.3% male). Mean D2/D3 receptor occupancy in the putamen and caudate nucleus increased with brexpiprazole dose, leveled out at 77–88% with brexpiprazole 5 mg and 6 mg at 4 h post-dose, and remained at a similar level at 23.5 h post-dose (74–83%). Estimates of maximum obtainable receptor occupancy (Omax) were 89.2% for the putamen and 95.4% for the caudate nucleus; plasma concentrations predicted to provide 50% of Omax (EC50) were 8.13 ng/mL and 7.75 ng/mL, respectively. Brexpiprazole area under the concentration–time curve (AUC∞) and maximum plasma concentration (Cmax) increased approximately proportional to dose. No notable subjective or objective adverse effects were observed in this cohort. Conclusion By extrapolating the observed single-dose D2/D3 receptor occupancy data in healthy participants, multiple doses of brexpiprazole 2 mg/day and above are expected to result in an efficacious brexpiprazole concentration, consistent with clinically active doses in schizophrenia and major depressive disorder. Trial registration ClinicalTrials.gov NCT00805454 December 9, 2008.

scholarly journals False positive rates in positron emission tomography (PET) voxelwise analyses

2020 ◽  
pp. 0271678X2097496
Author(s):  
Melanie Ganz ◽  
Martin Nørgaard ◽  
Vincent Beliveau ◽  
Claus Svarer ◽  
Gitte M Knudsen ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
False Positive ◽  
Multiple Comparisons ◽  
Emission Tomography ◽  
Permutation Testing ◽  
Brain Pet ◽  
Positron Emission ◽  
Healthy Participants ◽  
Significant Attention ◽  
Non Parametric

Issues with inflated false positive rates (FPRs) in brain imaging have recently received significant attention. However, to what extent FPRs present a problem for voxelwise analyses of Positron Emission Tomography (PET) data remains unknown. In this work, we evaluate the FPR using real PET data under group assignments that should yield no significant results after correcting for multiple comparisons. We used data from 159 healthy participants, imaged with the serotonin transporter ([11C]DASB; N = 100) or the 5-HT4 receptor ([11C]SB207145; N = 59). Using this null data, we estimated the FPR by performing 1,000 group analyses with randomly assigned groups of either 10 or 20, for each tracer, and corrected for multiple comparisons using parametric Monte Carlo simulations (MCZ) or non-parametric permutation testing. Our analyses show that for group sizes of 10 or 20, the FPR for both tracers was 5-99% using MCZ, much higher than the expected 5%. This was caused by a heavier-than-Gaussian spatial autocorrelation, violating the parametric assumptions. Permutation correctly controlled the FPR in all cases. In conclusion, either a conservative cluster forming threshold and high smoothing levels, or a non-parametric correction for multiple comparisons should be performed in voxelwise analyses of brain PET data.

Positron Emission Tomography of Cocaine Binding Sites on the Dopamine Transporter

1994 ◽  
Author(s):  
Bertha K. Madras ◽  
◽  
David R. Elmaleh ◽  
Peter C. Meltzer ◽  
Anna Y. Liung ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Dopamine Transporter ◽  
Binding Sites ◽  
Emission Tomography ◽  
Positron Emission
Sign in / Sign up

Export Citation Format

Share Document