By Bernadette Toner

Predictive Biosciences has found that adding a real-time PCR assay to its protein-based test for bladder cancer can improve its negative predictive value without reducing its specificity.

The company, which presented this finding at a poster at the 10th Annual Meeting of the Society of Urologic Oncology earlier this month, found that it could improve the negative predictive value of the test — the probability that a patient who has tested negative for cancer is actually free of the disease — from 94 percent with the protein-based assay alone to 97 percent with the combined approach.

The company is seeking CLIA certification for its lab, which it expects to receive by the end of January, and then plans to launch the test commercially "no later than the second quarter of 2010," Ellen Sheets, chief medical officer, told PCR Insider.

Predictive Biosciences, founded in 2006, has for several years been developing a non-invasive diagnostic assay to monitor disease-free status and cancer in high-risk bladder cancer populations. The test is based on matrix metalloproteinases, or MMPs, a family of zinc-dependent endopeptidases that have been associated with certain cancers.

Looking to further increase the negative predictive value of the test, the company recently added a real-time PCR-based assay for detecting mutations in fibroblast growth factor receptor 3 in urine samples. While MMPs are associated with high-grade, invasive tumors, FGFR3 mutations "are particularly associated with low-stage non-invasive tumors where sensitivity reaches approximately 70 percent," the firm said in its poster.

The combined approach, which the company calls Multi-Analyte Diagnostic Readout, or MADR, is an offshoot of its broader diagnostic-development strategy, called Clinical Intervention Determining Diagnostic, or CIDD. CIDD is an algorithmic method that the company has developed to identify biomarker cutoffs that maximize negative predictive value in order to distinguish patients who require no further intervention with very high certainty.

The company believes that with MADR, patients below a certain MMP cutoff would be excluded from unnecessary intervention, while those patients who are positive for an FGFR3 mutation would receive accelerated intervention.

Accentuate the Negative

Tony Shuber, chief technology officer at Predictive Biosciences, told PCR Insider that the company is focused on negative predictive value because it addresses a key issue in cancer treatment. "The reality in a clinical population is that the majority of people at any time will not have cancer. But yet we spend a lot of our healthcare dollars looking for that needle in the haystack," he said.

Predictive's products "are really going to initially focus on negative predictive value — and that is essentially debulking the population of those individuals who absolutely do not have cancer, and allowing the physician to truly triage that population into those that they can wait and see what happens, or not even treat because the result tells them with very high negative predictive value … that the patient doesn't have cancer," Shuber added.

Shuber noted that the company is targeting the test for two particular patient populations: those who have exhibited symptoms of bladder cancer, such as blood in the urine; and bladder cancer survivors. Predictive is currently conducting separate clinical trials for the test in the two high-risk patient populations, which it expects to wrap up next year.

The test currently has a specificity of 38 percent — meaning that 62 percent of true negatives would not be flagged as being cancer-free. Shuber noted that the high negative predictive value means that those patients who are flagged are almost certain to be true negatives, which is of great value in determining which of those high-risk patients will not require further intervention. He stressed that the test would not be of value for screening in a general population, and is not intended for that use.