|
Guidelines for May-June 1997 |
These guidelines were approved by the governing boards of the following six societies represented in the Intersociety Working Group for Cytology Technologies: American Society for Cytotechnology (ASCT), American Society of Clinical Pathologists (ASCP), American Society of Cytopathology (ASC), College of American Pathologists (CAP), International Academy of Cytology (IAC), and Papanicolaou Society of Cytopathology (PSC). The proposed guidelines as written reflect the current status of technologies in early 1997. These guidelines may evolve over time as newer technologies are developed.
1.0 General Considerations
This document delineates proposed guidelines in evaluating primary screening instruments for gynecological cytology
(cervicovaginal screening) specimens.
The goal of this document is to provide guidance to the FDA and other regulatory agencies
as they evaluate such instruments.
1.1 Intended Use
Primary Screeners are devices which are intended to triage gynecologic cytology slides for identification of malignant
or premalignant disease. Slides are scanned by these devices and are classified, either interactively or independently,
into two categories: No Review Indicated (NRI), and Needs Further Screening (NFS). Slides determined by the Primary
Screener to be excluded from human evaluation should not contain abnormalities from ASCUS/AGUS to invasive cancer
at a rate exceeding that achievable with primary manual screening.
Such devices may or may not Òelectronically commentÓ on specimen adequacy,
endocervical component, or the presence or absence of infectious disease agents. If the devices are not capable
of making these assessments then each slide should be reviewed manually for these components as clinically indicated
or requested.
Discussion
The potential benefit of these devices is that they may increase the overall sensitivity without significant loss
of specificity by identifying an equal or greater number of abnormal slides (again, abnormal is defined as ASCUS/AGUS+)
than a manual screening alone.
The primary criterion for evaluating these devices should be performance in correctly
separating normal slides from those containing neoplastic and preneoplastic conditions. While other functions,
such as evaluation of specimen adequacy, the presence of an endocervical component, etc. are important, they are
not requirements sine qua non. If these devices do not perform these auxiliary functions automatically then these
auxiliary functions would need to be performed manually as clinically indicated or requested. The group of slides
categorized as NRI should not contain slides which are unsatisfactory. While manual evaluation for auxiliary findings
can generally be performed more rapidly than evaluation of a slide for neoplasia, it should be recognized that
any manual evaluation of a slide for any reason reduces the utility and cost-effectiveness of these devices.
These devices do not compensate for smears which are inadequately prepared, are not fully
representative of the ectocervix and endocervix, or are not accompanied by and interpreted in light of appropriate
clinical information.
1.2 Recognized Limitations
Use of these devices should not affect the interval recommended between gynecologic cytology screenings. There
is no substitute for a regular cervicovaginal cytologic screening, particularly because roughly half of all falsely
negative tests are due to conditions unrelated to screening error.1
2.0 Function
Primary screener devices functionally fall into two categories which are not mutually exclusive:
1. Interactive. Interactive devices display potentially abnormal cells or cell
clusters in a computer window-display after they are scanned by a computerized microscope and analyzed by a computer
for features associated with abnormalities. Cytotechnologists review these computerized images or computerized
ÒabstractsÓ of each slide and make a decision whether or not to manually screen each slide based
upon findings on the computer screen. If a cytotechnologist makes a decision not to review a slide further, the
slide is signed out as negative with no further follow-up.
2. Independent. These devices automatically scan slides and assign a score to each
slide based on the potential for abnormalities as ascertained by the computer program. Those slides which are assigned
a score higher than a predetermined threshold are subsequently rescreened by humans. Those slides which are assigned
a score below the threshold are signed out as NRI without human examination.
The result of using either type of device, interactive or independent, or the two in combination,
is the same: The creation of a group of slides which are subjected to one or more human screenings, and a group
of slides which are signed out as NRI and which are never manually screened by a human for the presence of ASCUS/AGUS+.
The putatively negative group should contain either no or a very small number of slides which are truly high grade
squamous intraepithelial lesions (HSILs) or malignant (these latter situations could have grave consequences for
the patient, especially if a slide of a later stage lesion is incorrectly classified as negative).
| Table I Summary of How Machine Error Compounds Human Error | |||
|
|
|||
| Sort rate (%) |
Machine sensitivity (%) |
Human sensitivity for LSIL+ (%) |
Number of additional missed LSIL+ |
|
|
|||
| 20 30 40 |
99 90 |
75 75 |
7.5 75.0 |
|
|
|||
| *In this population, the prevalence of dysplasia/cancer (LSIL+) lesions is 2.5% and the human false negative rate is 25%. This example illustrates a non-interactive (independent) primary screening instrument. More detailed explanations are also available from member societies or working group members. | |||
Approvability
Approvability items are concerned with the performance of the device as it relates to correctly identifying NRI
and NFS slides. The explicit standard is that the sensitivity of the device plus the cytotechnologist equals or
exceeds the sensitivity of primary manual screening. In addition, the device plus the cytotechnologist should not
cause significant loss of specificity compared to manual screening alone. Sensitivity and specificity obtained
by device plus cytotechnologist and by cytotechnologist alone should be determined in a prospective, two armed
(contemporaneous) adjudicated trial. Performance specifications (defined as sensitivity and positive predictive
value of the instrument alone and in combination with manual screening) should be available to potential users.
While devices need not subclassify, render specific diagnoses, or even separate completely
all the normals from the abnormals, performance (sensitivity and clinical specificity) should be specified for:
ASCUS/AGUS, LSIL, HSIL plus Cancer. Clearly, a missed cancer is more serious than a missed ASCUS. The sensitivity
with respect to cancer and intra-epithelial lesions should equal or exceed primary manual screening, and the results
should be reproducible.
It is recognized that in a properly adjudicated, two-armed study design, it may be difficult
to achieve expert consensus on which slides are truly ASCUS. Therefore, for this category it is important for manufacturers
to report performance results separately and not combine them with intraepithelial lesions and carcinoma. If the
increase in sensitivity is almost exclusively in ASCUS/AGUS without significantly increased sensitivity for LSIL
and above, questions regarding overall clinical value should be raised. Device algorithms may need improvement
or study designs may need reevaluation.
Instruments should be expected to identify for human review the full range of glandular
cell groups in the AGUS designation.
For each category of disease (cancer, intraepithelial lesions, ASCUS and AGUS) the manufacturer
should submit to the FDA contemporaneous data reflecting the Positive Predictive Value of Positive Results (PPVPR)
of performance with and without use of the instrument in each clinical site.
Disclosure items
Potential users should be informed of device performance limitations with respect to: stain variability, identification
of adequate endocervical and squamous components, identification of unsatisfactory slides, identification of endometrial
cells, identification of infectious organisms, acceptance of slides produced by a range of sample preparation devices
(smears versus liquid-based), and slide rejection rate. In addition, any patient-related criteria which would exclude
specimens from device evaluation should be stated. These are all characteristics which may limit the practical
utility of the device in a routine setting and should be disclosed.
Disclosure should include data on sensitivity, specificity and PPVPR separated by diagnostic
categories of ASCUS/AGUS and LSIL+.
It would appear misleading for manufacturers to claim a new Òstandard of practiceÓ
in their product advertising. Professional standards of practice are established over time by the profession.
| Table II Detailed Explanation of Assumptions and Results of 20% Prescreening Sort Rate | ||
|
|
||
| Assumptions: | ||
| Population Assumptions: | ||
| Population | 40,000 | |
| Prevalence of LSIL+ in percent | 2.50% | |
| Prevalence of LSIL+ as a number | 1,000 | |
| Machine Performance Assumptions: | ||
| Percentage of slides reviewed by humans | 80% | |
| Percentage of slides never seen by humans | 20% | If humans review 80%, they never see 20% |
| Sensitivity of machine to LSIL+ slides | 99% | Better than human, on the face of it |
| Percentage of LSIL+ slides never seen by humans (false negative of the machine) | 1% | An inevitable consequence of previous line |
| Number of LSIL+ slides never seen by a human (completely missed!) | 10 | Again, COMPLETELY MISSED. ZERO chance of finding these slides |
| Number of LSIL+ slides which will be part of 80% pool reviewed by humans, and have the potential for being identified | 990 | Only 75% would be ultimately identified (see human sensitivity below) |
| Human Performance Assumptions: | ||
| Human sensitivity | 75% | |
| False negative rate (1-sensitivity) | 25% | |
| Results: | ||
| Human Screening (the way things are done now): | ||
| Truly LSIL+ slides found by humans alone | 750 | False negative rate times number of LSIL+ slides in population |
| Truly LSIL+ slides missed by humans alone | 250 | Sensitivity times number of LSIL+ slides in population |
| Machine Prescreening: | ||
| LSIL+ slides machine fails to bring to attention of humans (therefore never seen by humans) | 10 | These misses occur entirely in the 20% of slides which humans never see. This is a direct consequence of the 99% sensitivity (1% false negative rate of the machine). |
| Slides humans miss among slides humans actually screen | 247.5 | This is product of the human false negative rate (25%) times the number of abnormal slides (990) available for human review. Remember, humans look at only 80% of slides which do contain 99% of abnormals. |
| TOTAL missed slides by machine + human | 257.5 | |
| False negative rate using human + machine | 25.75% | Total missed slides divided by total LSIL+ slides in population |
| The Bottom Line: | ||
| Missed LSIL+ slides by human alone | 250.0 | |
| Missed LSIL+ slides by human/machine combo | 257.5 | |
| Number of additional missed LSIL+ slides by use of machine + human instead of human alone | 7.5 | |
| CONCLUSION: | ||
| Use of Machine which finds 99% of abnormals while reducing total number of slides to be examined by 20% results in 7.5 additional missed slides in a population of 40,000 slides with a 2.5% prevalence rate of LSIL+ | ||
|
|
||
| Table III Detailed Explanation of Assumptions and Results of 30% Prescreening Sort Rate | ||
|
|
||
| Assumptions: | ||
| Population Assumptions: | ||
| Population | 40,000 | |
| Prevalence of LSIL+ in percent | 2.50% | |
| Prevalence of LSIL+ as a number | 1,000 | |
| Machine Performance Assumptions: | ||
| Percentage of slides reviewed by humans | 70% | |
| Percentage of slides never seen by humans | 30% | If humans review 70%, they never see 30% |
| Sensitivity of machine to LSIL+ slides | 95% | Better than human, on the face of it |
| Percentage of LSIL+ slides never seen by humans (false negative of the machine) | 5% | An inevitable consequence of previous line |
| Number of LSIL+ slides never seen by a human (completely missed!) | 50 | Again, COMPLETELY MISSED. ZERO chance of finding these slides |
| Number of LSIL+ slides which will be part of 80% pool reviewed by humans, and have the potential for being identified | 950 | Only 75% would be ultimately identified (see human sensitivity below) |
| Human Performance Assumptions: | ||
| Human sensitivity | 75% | |
| False negative rate (1-sensitivity) | 25% | |
| Results: | ||
| Human Screening (the way things are done now): | ||
| Truly LSIL+ slides found by humans alone | 750 | False negative rate times number of LSIL+ slides in population |
| Truly LSIL+ slides missed by humans alone | 250 | Sensitivity times number of LSIL+ slides in population |
| Machine Prescreening: | ||
| LSIL+ slides machine fails to bring to attention of humans (therefore never seen by humans) | 50 | These misses occur entirely in the 30% of slides which humans never see. This is a direct consequence of the 95% sensitivity (5% false negative rate of the machine). |
| Slides humans miss among slides humans actually screen | 237.5 | This is product of the human false negative rate (25%) times the number of abnormal slides (950) available for human review. Remember, humans look at only 70% of slides which do contain 95% of abnormals. |
| TOTAL missed slides by machine + human | 287.5 | |
| False negative rate using human + machine | 28.75% | Total missed slides divided by total LSIL+ slides in population |
| The Bottom Line: | ||
| Missed LSIL+ slides by human alone | 250.0 | |
| Missed LSIL+ slides by human/machine combo | 287.5 | |
| Number of additional missed LSIL+ slides by use of machine + human instead of human alone | 37.5 | |
| CONCLUSION: | ||
| Use of Machine which finds 95% of abnormals while reducing total number of slides to be examined by 30% results in 37.5 additional missed slides in a population of 40,000 slides with a 2.5% prevalence rate of LSIL+ | ||
|
|
||
| Table IV Detailed Explanation of Assumptions and Results of 40% Prescreening Sort Rate | ||
|
|
||
| Assumptions: | ||
| Population Assumptions: | ||
| Population | 40,000 | |
| Prevalence of LSIL+ in percent | 2.50% | |
| Prevalence of LSIL+ as a number | 1,000 | |
| Machine Performance Assumptions: | ||
| Percentage of slides reviewed by humans | 60% | |
| Percentage of slides never seen by humans | 40% | If humans review 60%, they never see 40% |
| Sensitivity of machine to LSIL+ slides | 90% | Better than human, on the face of it |
| Percentage of LSIL+ slides never seen by humans (false negative of the machine) | 10% | An inevitable consequence of previous line |
| Number of LSIL+ slides never seen by a human (completely missed!) | 100 | Again, COMPLETELY MISSED. ZERO chance of finding these slides |
| Number of LSIL+ slides which will be part of 80% pool reviewed by humans, and have the potential for being identified | 900 | Only 75% would be ultimately identified (see human sensitivity below) |
| Human Performance Assumptions: | ||
| Human sensitivity | 75% | |
| False negative rate (1-sensitivity) | 25% | |
| Results: | ||
| Human Screening (the way things are done now): | ||
| Truly LSIL+ slides found by humans alone | 750 | False negative rate times number of LSIL+ slides in population |
| Truly LSIL+ slides missed by humans alone | 250 | Sensitivity times number of LSIL+ slides in population |
| Machine Prescreening: | ||
| LSIL+ slides machine fails to bring to attention of humans (therefore never seen by humans) | 100 | These misses occur entirely in the 40% of slides which humans never see. This is a direct consequence of the 90% sensitivity (10% false negative rate of the machine). |
| Slides humans miss among slides humans actually screen | 225 | This is product of the human false negative rate (25%) times the number of abnormal slides (900) available for human review. Remember, humans look at only 60% of slides which do contain 90% of abnormals. |
| TOTAL missed slides by machine + human | 325 | |
| False negative rate using human + machine | 32.50% | Total missed slides divided by total LSIL+ slides in population |
| The Bottom Line: | ||
| Missed LSIL+ slides by human alone | 250.0 | |
| Missed LSIL+ slides by human/machine combo | 325 | |
| Number of additional missed LSIL+ slides by use of machine + human instead of human alone | 75.0 | |
| CONCLUSION: | ||
| Use of Machine which finds 90% of abnormals while reducing total number of slides to be examined by 40% results in 75 additional missed slides in a population of 40,000 slides with a 2.5% prevalence rate of LSIL+ | ||
|
|
||
4.0 Design Requirements for a Protocol
A study which is used to determine performance should have the following elements:
1. Two-armed prospective design: Device performance in a primary screening modality should
be compared to contemporaneous primary manual screening for the same slide population.
2. Discordant study results from the two study arms should be adjudicated by an independent
panel consisting of experienced cytology professionals. The goal of the adjudication process is to achieve a consensus.
If a consensus is not achieved at the level of cancer or intraepithelial lesions, the slide should be excluded
from the study. For an adjudicated diagnosis of ASCUS, at least two of three panel members should agree in the
consensus phase.
Generally, in determining sensitivity, it is important to use adjudicated cytology as
a gold standard* and not biopsy because:
3. Positive predictive value should also be considered, enabling an approximation of clinical specificity.
This requires use of tissue biopsy (using a consensus diagnoses) of a statistically significant subset of patients
with a positive cytologic diagnosis as the gold standard for this aspect of the study.
4. Using the adjudicated cytology results from 2 (above), or histology from 3 (above),
a comparison of the receiver operator curve (ROC) characteristics of the two study arms is recommended.
5. Bias resulting from differences in cytotechnologist ability in different arms of the
study should be avoided. For example, for interactive devices, cytotechnologists who perform primary manual screening
and cytotechnologists who examine the interactive computer screens should possess comparable experience and abilities.
6. The study arm evaluating the device should replicate intended use conditions in order
to properly assess cytotechnologist and pathologist performance with respect to sensitivity and specificity.
For illustrative examples of the effects of how machine error can compound human error, see Tables IÐIV.
7. The trial design should allow for separate analyses of sensitivity, specificity and
positive predictive value for three categories of cytologic diagnosis: ASCUS/AGUS, LSIL, and HSIL plus cancer.
By separating ASCUS/AGUS into a class by itself, the increased inter-observer variation in ASCUS/ AGUS can be uncoupled
from the more consistent performance of humans in classifying intraepithelial lesions and cancer.
Working Group Members
Members of the 1996-1997 Intersociety Working Group for Cytology Technologies included Carlos Bedrossian, M.D.
(PSC representative), Thomas Bonfiglio, M.D. (ASCP representative), Denis Coble, EdD, CT (ASCT representative),
Diane Davey, M.D. (Co-Chair, ASC representative), Martha Hutchinson, M.D. (ASC representative), Edward Kaufman,
M.D. (ad hoc), Paul Krieger, M.D. (CAP representative), Dina Mody, M.D. (CAP representative), Stephen Raab, M.D.
(Co-Chair, PSC representative), Ibrahim Ramzy, M.D. (IAC representative), Dorothy Rosenthal, M.D. (IAC representative),
Patricia Saigo, M.D. (ASCP representative), Janet Schumann, CT (ad hoc), Diane Solomon, M.D. (ad hoc), Theresa
Somrak, J.D., CT (ASCP staff), and Sue Zaleski, SCT (ASCT representative).
Reference
Appendix I
Information for Pathologists and Cytotechnologists on New Cytology Technologies
Developed by the Intersociety Working Group for Cytology Technologies
About 15,700 new cases of invasive cervical cancer are diagnosed annually in the United States, and almost 5,000
American women die. About half of the women diagnosed with cervical cancer have never had a Pap screening exam
and another 10% have not had one for at least five years. Still others have had suboptimal frequency of screening.
Therefore, the most important way to decrease cervical cancer morbidity and mortality is to encourage cervical/
vaginal cytology at regular intervals.
False negative Pap smears in patients with cervical cancer can be divided into sampling
and laboratory errors. Many false negative Pap smear results are due to sampling problems, that is, abnormal cells
are not present on the smear when rescreened. In some of the cases, abnormal cells may be obtained by the sampling
device but are obscured on the smear by blood and/or inflammation. Laboratory false negative results may be a result
of screening errors, interpretive errors, or a paucity of well-visualized abnormal cells.
New cytology technologies available or under development aim to decrease false negative
Pap smear results by addressing one or more of the factors responsible. As laboratory errors are the primary ones
addressed, and these account for the minority of all cervical cancers, such technologies cannot be expected to
have a major impact on cancer rates without concurrent emphasis on regular screening of all women at risk.
Factors to consider in evaluation of new technologies include sensitivity, specificity,
reproducibility of diagnoses, how the technology affects the cytologist performance in daily laboratory practice
(vigilance), economics and workload issues, specimen adequacy, and types of specimens appropriate for the new device.
False negative, false positive, and positive predictive value calculations are useful. It is recommended that new
technologies used in an adjunctive mode be documented on the cytology report. Other automated technologies may
be documented in laboratory procedures or records.
A. Specimen Quality and Preparation
Monolayer or thin layer technologies aim to improve specimen adequacy by decreasing obscuring factors and improving
the visualization of any abnormal cells present in the sample. These devices may have an impact on multiple causes
of the false negative Pap smear, including sampling, screening, and interpretation. The sampling (collection) device
is placed in a vial of fixative instead of being smeared onto a slide, and preparations from the liquid specimen
are prepared within the laboratory. The Cytyc ThinPrep 2000 System passes the cell suspension through a polycarbonate
filter until a specified density of cells has been deposited, and then touches the filter to a slide. The AutoCyte
CytoRich uses a density gradient technique to separate the cells of interest, and then allows cells to settle onto
a slide.
Only Cytyc CorporationÕs ThinPrep 2000 has received FDA approval at this date.
Either a ÒbroomÓ type sample collection device or a plastic spatula/endocervical brush combination
must be utilized. Implementation requires a training course for those individuals who will be interpreting the
slides and laboratory validation procedures. Supplies used in the ThinPrep 2000 System must be those designed and
supplied by Cytyc. Only one specimen is processed at a time. A multisample device is being designed and tested.
The FDA trial for the ThinPrep 2000 showed that this system can be used as a replacement
for conventional Pap smear preparation. The FDA also recently approved new labeling for ThinPrep to make the following
claims: 1) ThinPrep is significantly more effective than the conventional Pap smear for the detection of LSIL and
more severe lesions, and 2) Specimen quality with the ThinPrep is significantly improved over that of the conventional
Pap smear preparation. The tables following the references, which were taken from the labeling information, compare
the ThinPrep to the conventional smear.
Costs involved: ThinPrep 2000 device, materials including fixative, filter, slides,
and slide preparation time. Telephone 1-888-THINPREP or 1-800-442-9892 for more information.
The AutoCyte CorporationÕs CytoRich device (formerly Roche) is nearing completion
of its clinical trial and should be submitted for FDA review for use on gynecologic specimens in the near future
(nongynecologic cytology use does not need FDA approval). This instrument prepares and stains a batch of 48 slides
in one run. For further information call 1-800-426-2176.
Finally, the thin layer preparations have not yet received FDA approval for automated
rescreening devices such as PAPNET and AutoPap 300. It might be anticipated that monolayer preparations would facilitate
computerized image analysis, but additional studies and possible software modifications are required prior to FDA
submission and approval.
B. Computer-Assisted Pap Smear Screening Devices
Two automated devices have been approved by the FDA for quality control and/or adjunctive (supplemental) rescreening
of smears. Both devices aim primarily to decrease screening false negative errors, but there may be some impact
on interpretive problems as well.
1.PAPNET (Neuromedical Systems Incorporated [NSI]) is an interactive system approved for
conventionally prepared Pap smears judged negative by initial manual screening. The smear is shipped to an NSI
facility by the clinical laboratory, where it is scanned on an automated computerized microscope which utilizes
algorithms and neural networks, and 128 digitized images of the cells/cell groups scored by the software as most
likely to be abnormal are saved on a digital tape. The slide and tape are returned to the original laboratory which
has been equipped with a computer station video monitor, where the images are viewed. This is done by cytotechnologists
and/or pathologists employed by the original laboratory trained in this technology. The cases which are considered
negative upon viewing the tape are signed out, while potential epithelial cell abnormalities are reviewed and signed
out manually. Recent/future adaptations may allow the microscope which is connected to the computer to go to the
exact location where the cells are located (electronic dotting).
The PAPNET FDA study was a retrospective analysis of previous negative smears in patients
with biopsy-proven HSIL or cancer, and 32% of
patients were found to have abnormalities on
PAPNET-assisted review. Of the control negative slides reviewed by PAPNET, 4.8% were judged abnormal, and 69% of
these revised diagnoses were ASCUS. A new marketing claim recently approved by the FDA involves a comparison between
manual rescreening and PAPNET rescreening. This was a nonparallel historical (retrospective) study at three sites.
Manual rescreen detected errors in 0.6% of 13,761 rescreened cases (years 1985-1992), while PAPNET detected errors
in 6.2% of 2293 specimens (years 1975-1991). The majority of detected errors were ASCUS/AGUS by both methods. NSI
claims that PAPNET-assisted review detects 7.1´ more false negatives when compared with manual rescreening.
Costs involved: Tape viewing computerized station and attachments for microscope,
per slide payment to Neuromedical Systems for off-site screening, additional time for packaging slides as well
as time spent by technologist/pathologist viewing tape and manual rescreening if indicated. Call 1-800-368-3630
or 1-800-PAPNET-4 for more information.
2. The AutoPap 300 QC System (NeoPath Incorporated) is approved for rescreening negative
conventional smears, and if performed on all negative smears, can replace a laboratoryÕs quality control
random rescreening. It is currently a noninteractive system which uses algorithm classifiers to provide a slide
evaluation score of 0 to 1.0 on each slide. Slides receiving scores above a predetermined threshold are to be manually
rescreened. The technology aims to segregate the abnormal cases above the threshold. The FDA study demonstrated
an approximate 5 times improved sensitivity for significant abnormalities compared to those which would be detected
in a 10% random rescreen. Also, 77% of biopsy-confirmed HSIL and cancer cases fell above the threshold in two institutions.
Staining and coverslipping of slides need to be optimized for the instrument to score the slides. Future enhancements
may include electronic dotting.
Costs involved: Lease/purchase of instrument or per slide charge, time spent to
load machine and manually rescreen slides, time spent to optimize stain/preparation. Call 1-800-NEOPATH for more
information.
3. Cytology support/assistance devices: These automated devices aid the cytotechnologist/
pathologist in screening the entire slide and automatically recording information. They include a microscope and
computer, and some include a complete workstation with the following: automated stage, specimen identification,
slide loading, automatic dotting, data management. Two companies marketing such devices are AccuMed International
(AcCell Series 2000, phone 1-800-650-2228), and CompuCyte Corporation (Pathfinder System, phone 1-800-840-1303).
References
Appendix II
Evaluation of Automated Systems
|
||||||||||
|
||||||||||
| Broken down by severity of lesion | ||||||||||
| What is the gold standard? Expert review, consensus, rescreening, biopsy, HPV |
Evaluation of Automated Systems
ASC Position Statement
ASC Position Statement
ThinPrep 3 Category Analysis
|
Conventional smear |
||||
|
|
||||
| ThinPrep |
Neg |
Atypical |
LSIL+ |
Total |
|
|
||||
| Neg Atypical LSIL+ Total |
5224 125 5680 |
298 99 529 |
71 413 538 |
5593 637 6747 |
|
|
||||
| Atypical=ASCUS/AGUS | ||||
ThinPrep Specimen Adequacy
|
Conventional smear |
||||
|
|
||||
| ThinPrep |
SAT |
SBLB |
Unsat |
Total |
|
|
||||
| SAT SBLB Unsat Total |
4316 63 5101 |
1302 41 2008 |
38 32 114 |
5656 136 7223 |
|
|
||||
ThinPrep Clinical Trial
PAPNET study (Neuromedical)
PAPNET QC Claim
PAPNET (Neuromedical)
AutoPap 300 (Neopath)
AutoPap Study (Neopath)
Appendix III
Intersociety Working Group for Cytology Technologies
| Name | Organization | Address | Telephone | FAX | E-mail Address |
|
|
|||||
| Diane Davey, M.D. Co-Chair | American Society of Cytopathology | Univ. of Kentucky 800 Rose Street MS117 Lexington, KY 40536-0084 |
606-257-5357 | 606-323-2094 | ddavey@pop.uky.edu |
| Martha Hutchinson, M.D. | American Society of Cytopathology | Dept of Path/Lab Med Women & Infants Hosp. 101 Dudley St., Providence, RI 02906 |
401-453-7939 | 401-453-7689 | 75321.3156@compuserve.com |
| Paul Krieger, M.D. | College of American Pathologists |
Corning Clin. Labs. 1 Malcolm Ave. Teterboro, NJ 07608 |
201-393-5436 | 201-393-6127 | |
| Dina Mody, M.D. | College of American Pathologists |
Baylor College of Med. One Baylor Plaza Houston, TX 77030 |
713-790-5903 | 713-793-1473 | dinam@path.bcm.tmc.edu |
| Carlos Bedrossian, M.D. | Papanicolaou Society of Cytopathology |
Detroit Med Ctr. 4707 St. Antoine Blvd. Detroit, MI 48201 |
313-745-0834 | 313-993-8894 | Bedrosian2@aol.com |
| Stephen S. Raab, M.D. Co-Chair |
Papanicolaou Society of Cytopathology |
Univ. of Iowa Hospitals & Clinics Iowa City, IA 52242 |
319-356-4164 | 319-356-8470 | Stephen-Raab@UIOWA.edu |
| Thomas Bonfiglio, M.D. | American Society of Clinical Pahtologists |
Univ. of Rochester Medical Center Rochester, NY 14642 |
716-275-3184 | 716-273-1027 | tbonfiglio@pathology.rochester.edu |
| Patricia Saigo, M.D. | American Society of Clinical Pathologists |
Memorial Sloan- Kettering Cancer Ctr. 1275 York Ave. New York, NY 10021 |
212-639-5902 | 212-639-6318 | saigop@mskcc.org |
| Theresa Somrak, JD, CT(ASCP) |
American Society of Clinical Pathologists (Staff) |
Cytopath. Education Consortium, 2100 W. Harrison Street Chicago, IL 60612 |
312-738-4851 | 312-738-9798 | theresas@ascp.org |
| Sue Zaleski SCT(ASCP) |
American Society for Cytotechnology |
Univ. of Iowa Hospitals and Clinics 220 Hawkins Dr. 5222 RCP Iowa City, IA 52242 |
319-356-3976 | 319-356-8470 | sue-zaleski@uiowa.edu |
| Janet Schumann, CT (ASCP) |
American Society for Cytotechnology (Alternate) |
4101 Lake Boone Trail, Suite 201 Raleigh, NC 27607 |
919-787-5181 203-452-7811 203-459-2532 |
919-787-4916 203-459-2532 |
|
| Denis A. Coble, EdD, CT (ASCP) |
American Society for Cytotechnology |
Univ. of Conn. Allied Health U-101 358 Mansfield Road Storrs, CT 06269-2101 |
860-486-0014 | 860-486-4191 | |
| Dorothy Rosenthal, M.D. | International Academy of Cytology |
Johns Hopkins Hosp. 600 N. Wolfe St. Baltimore, MD 21287 |
410-955-1180 | 410-614-9556 | drosenth@pathlan.path.jhu.edu |
| Ibrahim Ramzy, M.D. | International Academy of Cytology |
Baylor College of Medicine One Baylor Plaza Houston, TX 77030 |
713-790-4508 | 713-793-1473 | iramzy@bcm.tmc.edu |
| Kenneth Noller, M.D. | ACOG | Univ. of Massachusetts Medical Center 119 Belmont Street, Worcester, MA 01605-2903 |
508-793-6266 | 508-793-6063 | |
| Edward Kaufman, M.D. |
Ad Hoc | SmithKline Beecham 1201 South Collegeville Road, Collegeville, PA 19426 |
610-454-6182 | 610-983-2010 | edward.kaufman@sb.com |
| Lee Hilborne, M.D. | Ad Hoc | 11116 Montana Ave. Los Angeles, CA 90049 |
310-825-5656 | 310-794-9218 | Lhilborn@UCLA.Edu LEEH@Rand.Org |
| Diane Solomon, M.D. | Ad Hoc | NCI EPN Room 233 301-402-6211 6130 Executive Blvd. Rockville, MD 20852 |
301-496-6355 | 301-480-9939 | dianesol@box-d.nih.gov |
|
|
|||||
Editorial Comment
The Committee on Cytology Automation of the International Academy of Cytology published guidelines for designers
of automated systems1 that are worthy of repetition upon this occasion. The standards are divided into two major
groups: (I) Mandatory Conditions and (II) Highly Desirable Features:
I. Mandatory Conditions (Conditio sine qua non)
I.1. The system shall not be designed or constructed so as to pass as negative any sample
that contains malignant tumor cells;
I.2. The system shall not flag more Òfalse alarmsÓ on normal cells than
could be readily handled by visual manual review;
I.3. The system shall not use up the entire sample or render the sample unusable for classic
microscopic review; the pathologist must be able to examine the sample after routine staining;
I.4. The system shall yield reproducible results on repeated scannings of the same sample
(within appropriate confidence limits);
I.5. The system shall have an internal calibration standard for quality control; and
I.6. The system shall identify the inadequate (or empty) slide.
II. Highly Desirable Features (Required for Clinical Application)
II.1. The system should be able to clearly demonstrate the item that led to an ÒalarmÓ
for subsequent review by a human observer;
II.2. The system should include dysplastic cells in the alarm group and should not restrict
itself to the identification of frankly malignant tumor cells;
II.3. The system should detect and identify contamination and artifacts as such to avoid
unnecessary human review;
II.4. The preprocessing of the sample required by a given system should be convenient
and inexpensive for the clinician and laboratory (worst case: a system requiring specific preprocessing that is
more expensive than the entire routine classic workup and evaluation while not offering improved diagnostic quality);
II.5. Infectious organisms, such as trichomonads and fungi, as well as Òfootprints,Ó
as in herpes
inclusions and koilocytosis, should be identified; and
II.6. The system should operate cost-effectively.
Reference