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Clinical Laboratories and Pathology Groups

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Clinical Laboratories and Pathology Groups

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OPKO Health’s 4Kscore test predicts the rate of high-risk prostate cancer and may become a useful business case study for other labs developing proprietary diagnostic tests

Clinical laboratories and biotech companies with new medical laboratory tests are struggling to win coverage by Medicare and private payers. How big is this problem? There are currently tens of thousands of molecular diagnostic assays and genetic tests offered for clinical use.

Any lab company seeking to obtain an appropriate Current Procedural Terminology (CPT) code, favorable coverage guidelines, and adequate reimbursement from health insurers for its new lab test faces three big challenges, and they are related. First, payers are simply overwhelmed with requests to review new genetic tests. The flood of new test submissions exceeds the capability of payers to respond.

Most Payers May Not Have Right Scientific Expertise to Evaluate Genetic Tests

Second, most health insurance plans lack physicians and medical professionals who have the necessary experience in laboratory medicine, molecular diagnostics, and genetic medicine to evaluate these lab test submissions in a knowledgeable way.

That brings us to the third challenge, which is the need for labs that develop a new diagnostic test to document several things when asking payers to review the data and grant coverage. They are:

1. The new test accurately measures what it is designed to measure and results can be consistently reproduced.

2. The new test has a sensitivity and specificity that makes it acceptable for its targeted purpose, either as a screening test or as a diagnostic test.

3. The new test produces information that is clinically-actionable by the physician, and improves patient care and patient outcomes in a cost-effective manner.

Limited Number of New Molecular Diagnostics Tests Have Enjoyed Success

Over the past decade, only a handful of companies introduced a new genetic test that was reviewed and received a positive coverage determination by Medicare and a significant number of other health insurers, and that was considered a successful launch by clinical labs and the biotech industry. Some examples that are still studied widely took place in the 2000s, when payers looked at genetic tests differently than they do today.

One new molecular diagnostic test currently working its way through the system may represent a useful business case study as to how a lab company can win acceptance by both payers and physicians in today’s tough payer environment. It is a blood test for prostate cancer, called the 4Kscore test.

Moreover, there is another element to the 4Kscore test that has the potential to change how urologists and pathologists collaborate to diagnose, treat, and monitor prostate cancer. For both reasons, should physicians and payers accept this new cancer test on a fast timeline, the 4Kscore test rollout may serve as a useful business case study for other labs introducing proprietary tests.

Prostate Cancer Test Was Given CPT Code

The 4Kscore prostate cancer test was developed by OPKO Health, Inc., based in Miami, Florida. The test has achieved several important milestones essential to the clinical and financial success for any new proprietary molecular or genetic test.

One milestone is a relevant CPT code. The 4Kscore test recently received a Category Level 1 Current Procedural Terminology (CPT) code from the American Medical Association, OPKO stated in a press release. According to OPKO, the 4Kscore test is designed to show a patient’s risk for aggressive prostate cancer.

The second important milestone came last summer, when the National Comprehensive Cancer Network (NCCN) decided “to include 4Kscore as a recommended test in the 2015 NCCN Guidelines for Prostate Cancer Early Detection,” OPKO stated in another press release dated June 26, 2015.

OPKO further stated that “the [NCCN] panel concluded that the 4Kscore, as a blood test with greater specificity over the PSA test, is indicated for use prior to a first prostate biopsy or after a negative biopsy to assist patients and physicians in further defining the probability of high-grade cancer.”

When health insurers assess a new clinical laboratory test to develop coverage guidelines and reimbursement, they look more favorably upon a test that has a CPT code, and which is included in medical guidelines issued by national medical associations. This is why experts, such as Gene Marcial, a noted business writer at Forbes, believe that the 4Kscore prostate cancer test is poised for wide acceptance by payers and broad adoption by urologists and other physicians.

In fact, Marcial is so optimistic about the future of this new lab test that he wrote a story titled: “OPKO’s Prostate Cancer Test a $2 Billion Market Opportunity.” According to Forbes, about 2,000 U.S. urologists have used the test in their practices, and 100 tests per day are being done.

David Okrongly, PhD, President of OPKO Diagnostics, said that the company’s 4Kscore test garnered CPT Editorial Board support partially as a result of the test’s “inclusion in the 2015 National Comprehensive Cancer Network guidelines for Prostate Cancer Early Detection and the growing adoption of the test in the U.S.” (Image copyright: OPKO Health.)

David Okrongly, PhD, President of OPKO Diagnostics, said that the company’s 4Kscore test garnered CPT Editorial Board support partially as a result of the test’s “inclusion in the 2015 National Comprehensive Cancer Network guidelines for Prostate Cancer Early Detection and the growing adoption of the test in the U.S.” (Image copyright: OPKO Health.)

New Pathologist-Urologist Working Relationship

For pathologists and urologists, the 4Kscore test has the potential to be a clinical game-changer by altering how most men are evaluated for prostate cancer. And it’s a game likely to be played soon for at least three reasons:

1. The upgraded code (from a category three) means broader access to the test, according to OPKO.

2. The media continually calls attention to unnecessary biopsies. Forbes reported that more than one million unnecessary biopsies are performed following a prostate-specific antigen (PSA) test each year, costing the U.S. healthcare system about $1.5 billion. So, patients often question them and prefer non-invasive and less stressful ways to diagnose prostate health.

3. The 4Kscore test was reportedly developed based on 10 years of research. Forbes noted that “The four Kallikrein-2 panel of biomarkers used in the 4Kscore test is based on over a decade of research conducted by scientists at Memorial Sloan-Kettering Cancer Center and leading European medical institutions.

A Cancer Network story about the 4Kscore clinical study noted that, currently, about 60% of biopsy patients will have a negative result; another 20% of men will be diagnosed with a 1ow-grade (Gleason Score 6) prostate cancer; and about 20% of biopsies show high-grade cancer.

U.S. Clinical Study Shows Test Predicts Aggressive Prostate Cancer

In a clinical trial of 1,012 men seen at 26 U.S. urology centers the 4Kscore test detected 231 (23%) high-grade prostate cancers. And it better distinguished high-grade versus low-grade cancer as compared to the Prostate Cancer Prevention Trial Risk Calculator developed at by the University of Texas Health Center, the Cancer Network article pointed out.

Men who receive elevated PSA test results can perhaps consider the 4Kscore test as a precursor to a prostate biopsy. Should this begin to happen with increasing frequency, knowledgeable experts are predicting that it would lead to fewer prostate biopsies. In turn, this will reduce the volume of prostate biopsies referred to pathologists for analysis.

“A high-risk 4Kscore test result may be used to select men with a high probability of aggressive prostate cancer who would benefit from a biopsy of the prostate to prevent an adverse and potentially lethal outcome from prostate cancer. Men with a low 4Kscore test result may safely defer biopsy,” explains a paper published in Reviews in Urology.

How Does this Prostate Cancer Test Work?

The 4Kscore test is named for four prostate-specific kallikrein assay results:

1. Total PSA;
2. Free PSA;
3. Intact PSA (proprietary to OPKO); and
4. Human Kallikrein-2 or hK2 (proprietary to OPKO).

The test works by combining the four assays with clinical information and the patient’s age in an algorithm that calculates the risk for aggressive prostate cancer, OPKO reported, adding that its 4Kscore test has a 94% accuracy rate of detecting aggressive cancer.

Big Market Could Mean Big Money

Why is Forbes reporting on the 4Kscore test? Forbes cites data suggesting there are two million abnormal PSAs identified each year that lead to one million biopsy cases. Since the test costs $1,000, the opportunity for OPKO is $2 billion in the U.S., Forbes noted.

“That two million abnormal PSA universe is our market,” said Phillip Frost, MD, CEO of OPKO in the Forbes article.

Creating New Opportunity for Pathologists to Consult with Urologists

Two billion dollars, and two million patients with adverse PSA test results, is a huge market. This is why healthcare professionals are noticing the potential of the 4Kscore test to reduce the number of prostate biopsies (thus saving money for the healthcare system) while contributing to better patient outcomes.

Furthermore, avoiding a 12-core prostate biopsy is a patient-friendly benefit that won’t go unnoticed by men and their wives. In fact, no one should be surprised if men find out about this test before their urologists and arrive at their doctor’s office informed and ready to ask questions about the option of having the 4Kscore test versus an invasive prostate biopsy.

Therefore, this new proprietary clinical laboratory test will probably attract attention from two distinct groups. One group will be medical laboratories and biotech companies that have their own proprietary lab tests to launch. They will be watching to see what lessons can be learned about how OPKO’s 4Kscore test is accepted and reimbursed by Medicare program officials and private health insurance plans.

The other group closely tracking these developments will be anatomic pathologists. If today’s volume of about one million prostate biopsies per year begins to decrease because of wider adoption of the 4Kscore test, then pathologists will not only see a reduction in the volume of prostate biopsies being referred to their group, and the revenue associated with that work, but they will want to become experts on how to use the 4Kscore test results to evaluate patients, help the urologist with the diagnoses, and then stay involved in the multi-year monitoring of those patients who are deemed to not have aggressive prostate cancer.

In closing, it is worth mentioning that many promising diagnostic technologies fail to deliver the expected benefits once they are put into widespread clinical practice. This will be the challenge for OPKO and its 4Kscore prostate cancer test. As more patients undergo testing with this proprietary assay, the company will need to regularly update the clinical performance of the test as evidence that it has acceptable sensitivity and specificity and it is reliable when used over time.

—Donna Marie Pocius

Related Information:

4Kscore test Receives Category 1 CPT Code Approval

OPKO’s Prostate Cancer Test A $2 Billion Market Opportunity

OPKO Health Acquires BioReference Laboratories

Study Confirms 4Kscore Accurately Predicts High-Grade Prostate Cancer

Finding the Wolf in Sheep’s Clothing: The 4Kscore is a Novel Blood Test That Can Accurately Identify the Risk of Aggressive Prostate Cancer

OPKO Health Gets Important Approval for Its Prostate Cancer Test

For Second Time in Three Years, OPKO Health Will Acquire a Clinical Laboratory Company by Spending $1.47 Billion to Acquire Bio-Reference Laboratories