Table 3Study design evaluations for PCA3 Research Need 1, Research Questions 1.1–1.3

Study Design ConsiderationsDiagnostic Accuracy StudyProspective-Retrospective StudyCase Control Study
Description of designPCA3 compared to currently used tests (tPSA, free PSA, PSA velocity, externally validated nomograms without PCA3; externally validated nomograms including PCA3); clinical performance (sensitivity, specificity, positive and negative predictive values) assessed and reported in matched comparisons to a biopsy gold standard. Results of PCA3 are blinded and not used in decisionmaking.PCA3 measured in archived samples from patients identified as biopsy-positive or biopsy-negative in a population resembling the intended use population. Not possible because of lack of urine specimen banks, but as noted in the Future Research Needs for Comparative Effectiveness of Treatments of Localized Prostate Cancer,17 such banks are needed.Samples from patients predefined as positive or negative for cancer are selected; testing is performed in these samples.
Advantages of study design for producing a valid resultStudies are usually cross-sectional or involve short-term followup only. Data to support this type of study may already exist, but have been incompletely analyzed and reported.Uses available resources and data, but care must be taken to avoid incorrect handling of samples and incomplete data.Allows use of convenience samples; results may not mimic real world use, and estimates of both sensitivity and specificity must be interpreted with extreme care.
Resource use, size, and durationStudy requires patient recruitment and informed consent with samples collected with active intervention (attentive digital rectal exam), special processing and then testing using PCA3 and correlation of results with standard testing against a biopsy gold standard. Followup or further diagnostic evaluation is not usually required. Currently, no good models exist for addressing verification bias and, therefore, data interpretation may be challenging.Less resource-intensive and shorter than a randomized clinical trial. There may be costs associated with obtaining and using samples and data.Less resource intense than a diagnostic accuracy study or a well performed retrospective study using repository samples reflecting the intended use population.
Ethical, legal and social issuesMinimal; the test is approved for use by FDA, for repeat biopsies. The test is not currently a practice of care standard, and so blinding should pose no dilemma.Minimal; studies must be performed with attention to patient confidentiality and privacy.Minimal; studies must be performed with attention to patient confidentiality and privacy.
Availability of data or ability to recruitThis is a high volume test process and burden of disease is high. Recruitment of subjects should not be difficult although future studies should learn from the comparative effectiveness review and pay more attention to the quality of data being collected.This is currently very problematic in that urine repositories for patients subject to prostate cancer are not available.This is currently problematic in that urine repositories for patients subject to prostate cancer are not available.

Abbreviations: FDA = U.S. Food and Drug Administration; PCA3 = prostate cancer antigen 3 gene; PSA = prostate-specific antigen; tPSA = total prostate-specific antigen

Note:

1.1.

What is the comparative effectiveness of PCA3 compared to the two commonly used add-on tests of fPSA and tPSA velocity/doubling time in predicting prostate biopsy results?

1.2.

What are PCA3’s diagnostic performance characteristics in patients with elevated tPSA levels?

1.3.

What is the comparative effectiveness of PCA3 compared to externally validated nomograms in predicting prostate biopsy results?

From: Results

Cover of PCA3 Testing in the Diagnosis and Management of Prostate Cancer: Future Research Needs
PCA3 Testing in the Diagnosis and Management of Prostate Cancer: Future Research Needs: Identification of Future Research Needs From Comparative Effectiveness Review No. 98 [Internet].
Future Research Needs Papers, No. 24.
Gutman SI, Oliansky DM, Belinson S, et al.

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