Table 6Study design evaluations for PCA3 Research Need 3, Research Question 3.1: Does addition of PCA3 testing change long-term health outcomes in prostate screening?

Study Design ConsiderationsRandomized Clinical TrialsProspective Cohort StudyModeling
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. Long-term outcomes, including morbidity, mortality and quality of life followed over 10 to 20 years.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.Estimates of outcomes would be made based on what is known about the natural history of prostate cancer and what is learned through the studies in Research Question 2.1 about likely behavior of cancers diagnosed or treated using information from PCA3 testing.
Advantages of study design for producing a valid resultThe gold standard for understanding health care outcomes occurring as a result of use of PCA3 testing. Clinical characteristics can be carefully balanced.Baseline characteristics can be measured, but may not be balanced. Statistical techniques may be able to partially control potential bias.Modeling allows predictions of outcomes from use of PCA3 based on logical assumptions of tumor behavior and known impact of interventions. However, the strength of the model will depend on the reliability of the assumptions made. While it is possible that informed decisions will be made based on this modeling, the validity will not be well established. Technique has been used by the United States Preventive Services Task Force in developing some recommendations.
Resource use, size, and durationThis is likely to be a resource-intense process of large size, long duration, and high cost. Compliance may be a problem if diagnostic and therapeutic choices change during the duration of the study.Resource use, size, and duration are likely to be similar to that of a randomized clinical trial. Compliance may be a problem if diagnostic and therapeutic choices change during the duration of the study.Likely to be less resource-intense than other approaches.
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.
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 straightforward.This is an area of considerable interest to both physicians and statisticians; this would be a fertile area of collaboration.

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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