Hologic ThinPrep, Operator'S Manual

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MAN-08723-001 Rev. 001 page 23 of 28
Clinical Study Design
This study was a multi–center, split-sample, blinded evaluation of ThinPrep slides generated from the
ThinPrep Genesis processor from the residual cytological specimens. The study was conducted at three (3)
laboratories in the United States. All study specimens were processed on ThinPrep Genesis processor using
“Slide Only” process. All slides were reviewed independently by three (3) cytotechnologists (CT) and three
(3) pathologists at each site. The first review was performed utilizing the ThinPrep Imaging Review Scopes
(TIS) at each site, followed by a manual review arm of the same slides. To minimize reviewer bias, the CTs
and pathologists were blinded to the initially reviewed TIS diagnosis. A two-week interval between the TIS
review arm and the manual review arm minimized the potential for recognition bias. Following TIS and
manual review, all slides were adjudicated by an independent site, the fourth site. All cytological diagnoses
were determined in accordance with the Bethesda System criteria for all slides.
1,260 patients’ ThinPrep Pap Test specimens were enrolled in this study. 1,260 samples were enrolled from
February 2019 through June 2020. Each study site enrolled 420 specimens selected from their residual
inventory (population of gynecological ThinPrep Pap Test specimens sent to the study sites’ cytology
laboratory). The samples for the study included specimens in each of the diagnostic categories being
evaluated A total of 1,260 slides were analyzed for the study. The order in which the slides were processed
was randomized. All slides were stained, coverslipped and read manually following standard laboratory
procedures; all slides prepared at the site were reviewed independently by each of three (3) pairs of
cytotechnologists/pathologists. All cytologic diagnoses were determined in accordance with Bethesda
System 2001 criteria.
Of the 1260 specimens enrolled, 7 specimens were excluded (3 specimens were excluded because of
expiration time and 4 specimens were excluded because there were no adjudication results). In addition, 2
slides were excluded due to no TIS matched pairs. Total number of ThinPrep Genesis slides for an evaluation
of the ThinPrep Genesis processor was 1251.
Table 25: Laboratory Imager-Assisted Review Diagnosis vs. Laboratory Manual Review
Diagnosis by one Pair of Cytotechnologist/Pathologist (Combined Sites)
Combined Review Team 1
Genesis Lab Manual Review Diagnosis
Genesis Lab
Imager- Assisted
Review Diagnosis UNSAT
NILM ASCUS AGUS LSIL ASC-H HSIL Cancer Total
UNSAT 2 2 0 0 0 1 0 0 5
NILM 3 705 41 1 5 9 1 0 765
ASCUS 0 39 53 0 10 3 0 0 105
AGUS 0 0 0 1 0 0 0 1 2
LSIL 0 5 23 0 108 1 5 0 142
ASC-H 0 9 8 1 5 21 6 1 51
HSIL 0 3 3 1 9 13 124 5 158
Cancer 0 0 0 2 0 0 3 18 23
Total 5 763 128 6 137 48 139 25 1251
Reference Diagnosis by Adjudication Review
All slides were subject to an adjudication review. Adjudication was done at a facility that was not
one of the study sites conducting the study. Slides for adjudication were evenly divided between
three (3) adjudication panels each consisting of one (1) Cytotechnologist and three (3) independent
Pathologists. Each adjudication panel was blinded to the original review diagnosis for all slides and
each independent Pathologist within each panel was also blinded to other adjudicator’s diagnoses
for all slides. Adjudication consensus agreement was obtained for each slide reviewed. Consensus
agreement was achieved when at least two (2) of the three (3) Pathologists from a panel rendered an
identical diagnosis. In cases where consensus agreement was not achieved the panel members were
brought together at a multi-head microscope to review the slides together and come to a consensus
diagnosis.
In the study of 1,251 ThinPrep Genesis slides, there were 22 Cancer, 148 HSIL, 32 ASC-H, 200