Table 5Study design evaluations for PCA3 Research Need 1, Research Question 2.2: Does the addition of PCA3, either alone or in combination with other markers, change prostate cancer biopsy or treatment decisionmaking for the patient or physician?

Study Design ConsiderationsRandomized Clinical TrialsProspective Cohort StudyPhysician/Patient Survey
Description of designPatients at risk for prostate cancer (initial or repeat biopsy) based on elevated tPSA and/or abnormal DRE or with positive biopsies are randomized to receive PCA3 in addition to standard testing or standard testing alone. Biopsies performed versus deferred and the yield of positive and negative results in the two arms are compared, and evidence of patients with aggressive versus indolent disease in the two arms is also compared. Features of aggressiveness can be enhanced by including studies that use standardized criteria linking results to clinical outcomes using published or unpublished, but public, information as available. In order to assess impact on patients choosing active surveillance versus aggressive therapy, experiments could be designed to add PCA3 to on-going studies of active surveillance. In addition, different PCA3 values could be compared to grading changes between biopsy and prostatectomy.Patients with and without prostate cancer identified in an intended use population and tracked according to PCA3 status --tested or not tested, positive or negative test results). Patients followed prospectively to determine choices about biopsy and treatment.Hypothetical scenarios for test use can be developed and evaluated in physicians or patients to determine how they might use information in comparison to current standard of care. To develop a meaningful survey, it is necessary to have good information on test performance and to consider how decision aids might be used to maximize use of testing information provided in such a survey.
Advantages of study design for producing a valid resultWith proper inclusion and exclusion criteria and careful recording of results, this should provide a clear indication of how results will be used in decisionmaking and will also provide information on the outcomes of testing—how many cancers identified and what type (indolent or aggressive).Baseline characteristics can be measured, but may not be balanced. Statistical techniques may be able to partially control potential bias.There is a growing interest in the use of conjoint analysis to determine how medical information is used to affect management choices. Although the approach is new, it appears able to provide valuable information toward understanding how information might be used.
Resource use, size, and durationThis is likely to be a resource-intense process. Since the study is focused only on immediate decisionmaking and biopsy results, long -term followup would be interesting, but not essential, to answer the questions raised.Resource use, size, and duration are likely to be similar to that of a randomized clinical trial.Less resource intensive and shorter than a prospective study.
Ethical, legal and social issuesMinimal; although the test has been approved by FDA for repeat biopsy (previous negative biopsy patients), there is no information on health care outcomes, hence the need for study.Minimal; although the test has been approved by FDA for repeat biopsy (previous negative biopsy patients), there is no information on health care outcomes, hence the need for study.None. This type of survey presents no ethical, legal, or social issues.
Availability of data or ability to recruitBiopsy or treatment choice is commonly encountered in urological practice; the area is one of considerable physician and patient interest; recruitment would be expected to be relatively straightforward.Biopsy or treatment choice is commonly encountered in urological practice; the area is one of considerable physician and patient interest; recruitment would be expected to be relatively straight forward.This is an area of considerable interest to both physicians and patients; recruitment should be relatively straightforward.

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

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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