Medicare Coverage for Oncologic In Vitro Chemoresponse Assay

[gpawelski]

Medicare Contractor Establishes Reimbursement Coverage Policy for Cell Culture Assay Tests

National Heritage Insurance Company (NHIC), the contractor that administers Medicare programs in California, has established a positive coverage policy for Cell Culture Assay Tests known as Chemosensitivity (Resistance) Testing or Oncologic In Vitro Chemoresponse Assays for a tumor specimen from a Medicare patient obtained anywhere within the United States, but submitted for testing by one of the approved laboratories located within Southern California. Medicare bills for this testing are billed through NHIC because the test is conducted by the approved laboratories in California.

This pre-test can help see what treatments have the best opportunity of being successful for "high" risk cancer patients. The test measures the response of "live" tumor cells to drug exposure. Following this exposure, the assays measure both cell metabolism and cell morphology (Functional Profiling). The integrated effect of the drugs on the whole cell, resulting in a cellular response to the drug, measuring the interaction of the entire genome. Assays based on "cell-death" occur in the entire population of tumor cells.

This cell culture assay technology has been clinically validated for the selection of optimal chemotherapy regimens for individual patients. It is a laboratory analysis based on tumor tissue profiling that uses "fresh" human tumor biopsy or surgical specimen to determine which drugs or combinations of chemotherapeutic agents have the highest likelihood of response for individual cancer patients.

Following the collection of "fresh" tumor cells obtained from surgery or tru-cut needle biopsies, a cell culture assay is performed on the tumor sample to measure drug activity (sensitivity and resistance). This will pinpoint which drug(s) are most effective. Tissue, blood, bone marrow, and ascites and pleural effusions are possibilities, providing tumor cells are present. At least one gram of fresh tissue is needed to perform the tests, and a special kit is obtained in advance from the lab. The treatment program developed through this approach is known as assay-directed therapy.

Individualized assay-directed therapy is based on the premise that each patient's cancer cells are unique and therefore will respond differently to a given treatment. This is in stark contrast to standard or empiric therapy, which chemotherapy for a specific patient is based on average population studies from prior clinical trials.

The decision had been made that the assay is a perfectly appropriate medical service, worthy of coverage on a non-investigational basis. What is of particular significance is that they abandoned the artificial distinction between "resistance" testing and "sensitivity" testing and are providing coverage for the whole FDA-approved kit. Drug "sensitivity" testing is merely a point a little farther along on the very same continuum which "resistance" testing resides.

Cell cuture assay tests based on "cell-death" have proven very effective in identifying novel treatment combinations for a variety of cancers. The value of cell-death assays is that they can and do accurately predict clinical outcomes and define novel chemotherapeutic synergies. It can help see what treatments will not have the best opportunity of being successful (resistant) and identify drugs that have the best opportunity of being successful (sensitive).

The current clinical applications of in vitro chemosensitivity testing is ever more important with the influx of new "targeted" therapies. Given the technical and conceptual advantages of "functional profiling" of cell culture assays together with their performance and the modest efficacy for therapy prediction on analysis of genome expression, there is reason for renewed interest in these assays for optimized use of medical treatment of malignant disease.

The payment provided will be sufficiently realistic that all Medicare patients for whom this testing is indicated will be able to get it with only the routine 20% co-payment, as Medi-gap insurance secondaries are mandated to provide payment for co-pays for Medicare-approved services.

The coverage became effective for claims for services performed on or after February 19, 2007. The decision is posted at:

http://www.medicarenhic.com/cal_prov/ar ... t_0107.htm

NHIC Medicare Services reimburses qualified laboratories in Southern California for cell culture assay tests on a Medicare patient anywhere in the United States.

Likewise, Highmark Medicare Services reimburses a qualified laboratory in Pennsylvania for cell culture assay tests on a Medicare patient anywhere in the United States.

NHIC has jurisdiction over Southern California, so that is who gets billed when the laboratory is located in California.

Highmark has jurisdiction over laboratories in Pennsylvania, so that is who gets billed when the laboratory is located in Pennsylvania.

The coverage decision is posted at:

http://www.highmarkmedicareservices.com ... 32007.html

[gpawelski]

Medicare's National Coverage Decision specifically notes noncoverage on two distinct types of assays: a. human tumor stem cell assay, and b. clonogenic assay. These are what most academic oncologists still mistakenly refer to as chemosensitivity testing.

In October 2003, CMS notified all contractors that the NCD was very specific to those tests and does not include tumor cell sensitivity or resistance testing on any other class of cells other than tumor stem cells. In 2006, Medicare officially recognized cancer chemosensitivity tests as a special test category in Federal Regulations (42 CFR 414.510((3), 71 FR 69705, 12/01/2006).

Two Medicare contractors (NHIC Medicare Services and Highmark Medicare Services) established reimbursement coverage policies for cell culture assay tests, the same way that the Oncotype DX assay is being covered. Medicare bills for Chemosensitivity (Resistance) Testing, from any Medicare patients, anywhere in the United States, are billed through NHIC and Highmark Medicare Services because the test is conducted by approved laboratories in Southern California and one in Pennsylvania. As far as payments for this test, it is just as good as having a NCD. Numerous private payors pay for the tests also.

As with any other laboratory tests in cancer medicine, the determination of the efficacy of cell culture assays is based on clinical correlations (comparisions of laboratory results with patient response). The "standard" of retrospective correlations between treatment outcomes and laboratory results is sufficient in the case of ALL laboratory tests. It is what established FDA-approval for the test kit.

[gpawelski]

It amazes me not only that some private insurance carriers don't like to pay for cell culture assay tests but that they don't emphatically mandate it as a requirement for obtaining chemotherapy reimbursement against ill-directed treatments.

The validation standard that private insurance companies is accepting from "molecular" profiling tests is "accuracy" and not "efficacy." The "bar" has been instantly lowered. No longer will it be essential to prove that the use of a diagnostic test improves clinical outcomes, all they have to do for these "molecular" profiling tests is prove that the test has a useful degree of "accuracy." However, at the same time, the validation standard they want for "cell-based" profiling tests is "efficacy."

The "cell-based" profiling tests have the same entitlement to be judged by the same validation standard as "molecular" profiling tests. The combination of measuring morphologic (structural) effects and metabolic (cell metabolism) effects constitutes measuring the "profile" at the whole cell level. It must be noted that both types of dignostic tests are just that, "tests" and not treatment.

Profit, as we have seen, is a powerful motivating force. Among the private payors, at least, the profit motive is entirely consistent with the goal of the test, which is to identify efficacious therapies irrespective of drug mark-up rates.

The evidence in support of these assays is more than sufficient to justify the funding of validation trials, if any more truly are needed, as claimed - speciously and self-servingly - by the medical establishment.

Everyone is scared to death - and rightly so - at what is going to happen to the healthcare economic system with the introduction of increasingly expensive new drugs that benefit only a small percentage of patients who receive them, hence the headlong rush to develop tests to identify molecular predisposing mechanisms whose presence still does not guarantee that a drug will be effective for an individual patient.

Nor can they, for any patient or even large group of patients, discriminate the potential for clinical activity among different agents of the same class, such as Sutent, Tarceva, Iressa, and Nexavar.

The FDA could benefit too, as they find themselves under increasing pressure to allow new drugs into marketplace while at the same time protecting the safety of potential recipients of those drugs as well as the financial interests of those who will have to pay for them.

It explains the new paradigm of requiring a companion diagnostic as a condition for approval of new targeted therapies. The pressure, in fact, is so great that the companion diagnostics they've approved often have been mostly or totally ineffective at identifying clinical responders (durable and otherwise) to the various therapies.

I think that in both of these areas - private insurance carriers and the FDA - there is a very real opportunity to make a substantial impact and contribution, an interest in saving the healthcare system perhaps billions of dollars a year (and thereby the healthcare system itself) by ensuring that expensive treatments are used appropriately.

Committee chairpersons, committee members and persons in congress who may have personal interests not only in discovering new cancer treatments - everybody wants that - but also, in the "here and now," using currently-available cell culture assay technologies to improve the effectiveness of existing drugs and save lives today by administering the right drug to the right patient at the right time.

[gpawelski]

Scott Gottlieb, a doctor who is a former FDA official, in a June 24th WSJ op-ed article pointed out that Medicare has only about 20 doctors and 40 total clinicians working in its coverage office, and fewer than a dozen in the office that sets doctors' reimbursement rates.

Also, Medicare doesn't have a single oncologist on staff, yet since the year 2000, the program issued 165 restrictions and directives on the use of cancer drugs and diagnostic tools. Private insurers, on the other hand, employ thousands of doctors and nurses to do this.

I guess that would explain why there wasn’t a National Coverage Decision for the Cell Culture Assays (known officially as Oncologic In Vitro Chemorespone Assays) in 2006, but a Local Coverage Decision? That’s not enough staff to do a thorough analysis of these valuable tests.

On the other hand, private insurers employ thousands of doctors, nurses and pharmacists to do tech assessments, which would include cancer diagnostic tests. National Heritage Insurance Company and Highmark Medicare Services, contractors that administer Medicare programs, had established a positive coverage policy; a bio-marker assay that is perfectly appropriate medical service, worthy of coverage on a non-investigational basis.

However, in regards to cancer drugs, Medicare has radically expanded its authorization for use of cancer drugs by putting off-label decision making in the hands of compendia writers in the private sector, many of whom are on the payrolls of the companies that make the drugs.

[CaroleHammett]

Greg:

Thank you so much for posting this series. As always, I have to read it repeatedly before it begins sinking in (I majored in English Lit, not Pre-Med!), but it seems to me that overall this is very good news, initially for those of us on Medicare, but ultimately because it's not only opening at least one door, but is also paving the way for more doors to open?

On another note, I have to add that I was stunned to learn that Medicare doesn't have a single oncologist on staff? How can that be? It is utterly and totally illogical given the number of Medicare cancer patients.

I will be doing another re-read tomorrow (still trying to assimilate the technical terms), but again, thanks so much for posting this info.

Carole

[gpawelski]

I am speechless Carole that Medicare does not have a single oncologist on staff!!!

No wonder the Medicare contractor (National Heritage Insurance Company) had to complete an extensive review of all available information, including the antiquated ASCO tech assessment/position statements, and finalized an official Local Coverage Decision providing Medicare payment for this bio-marker assay for any Medicare patient anywhere in the U.S.

In November, 1999, Medicare convened a national coverage advisory committee meeting, where the testing was intensely reviewed. Although the conclusions of the national coverage advisory committee review were favorable, no national coverage decision was made, and coverage decisions were left to the local/regional Medicare contractors. Subsequently, the previous Medicare contractor for Southern California, officially granted partial coverage (resistance testing) for this test in 2000.

However, it wasn't until December, 2006 that they abandoned the artifical distinction between "resistance" testing and "sensitivity" testing and provided coverage for the whole FDA-approved kit. Drug "sensitivity" testing is merely a point a little farther along on the very same continuum which "resistance" testing resides.

To add insult to injury, the validation standard that some private insurance companies are accepting today from "molecular" profiling tests is "accuracy" and not "efficacy." The "bar" had been instantly lowered. No longer will it be essential to prove that the use of a diagnostic test improves clinical outcomes, all they have to do for these "molecular" profiling (genetic) tests is prove that the test has a useful degree of "accuracy." However, the validation standard the American Society of Clinical Oncology (ASCO) wants for cell-based profiling tests is "efficacy." Perhaps ASCO needs to update their tech assessments on cell-based profiling assays? Transparently of course!

And now, Medicare wants to put off-label drug decision making in the hands of compendia writers in the private sector, many of whom are on the payrolls of the companies that make the drugs!

[CaroleHammett]

Greg:

Thanks again for helping me understand (at least partially, I'm still on the downside of this latest learning curve) the issues here.

As to the compendia, Barb and I have already voiced our concerns about these and your comments serve to validate them.

As to efficacy vs. accuracy, I'm still confused, but will go back and re-read and re-read later today (Sorry... I'm just incredibly slow when it comes to this technical stuff!).

Carole

Life is not measured by the number of breaths we take, but by the moments that take our breath away.--the late, great George Carlin

[CaroleHammett]

gpawelski: And now, Medicare wants to put off-label drug decision making in the hands of compendia writers in the private sector, many of whom are on the payrolls of the companies that make the drugs!

Greg:

I had missed your postings in the "Activism/Advocacy" forum regarding the compendia and wanted to add the link here for those of us who have been following this subject in this ("Lung Cancer in the News") forum:

http://lungevity.org/l_community/viewtopic.php?t=37588

Thanks as always for your very informative postings.

Carole

[gpawelski]

What is the appropriate standard to judge medical tests?

1. Efficacy (use of tests improves clinical outcomes)

2. Accuracy (the test accurately measures what they are purported to measure)

Laboratory tests are judged by accuracy and reproducibility and never by their effect upon treatment outcomes. Most tests used today in oncology have comparable "sensitivities" and "specificities."

For instance, Pet Scans were not approved because they saved lives in a controlled clinical trial that compared the outcome of patients who received care with or without the benefit of a Pet Scan. They were approved because their performance characteristics (sensitivity/specificity) are reproducible, favorable and provide information to treating physicians. That is exactly what cell-based assays do.

No test in oncology has ever been shown in prospective randomized clinical trials to improve patient outcomes. The existing standard has always been the "accuracy" of the test. This is true for every single test used in cancer medicine, from estrogen receptors to panels of immunohistochemical stains (IHC) to diagnosing and classifying tumor to Her2/neu and CA-125 to cell culture assay to MRI's, CT Scans, Pet Scans and so on.

Medicare (through individual Medicare contractors) established that cell-based assay technology has been clinically validated for the selection of optimal chemotherapy regimens for individual patients. The test is reimbursed for a specimen from a Medicare patient obtained anywhere within the United States, but submitted for testing by one of the approved laboratories. Medicare bills for this testing are billed through Medicare contractors because the test is conducted by the approved laboratories in their jurisdictions.

Some private insurance companies pay for the test, if indicated. However, some do not pay for the tests because of a previous ASCO tech assessment which looked at "efficacy" and not "accuracy" standards. ASCO reviews of this testing specifically excluded from consideration all publications relating to assay "accuracy" and only considered publications relating to assay "efficacy." The authors of these reviews were attempting to impose an entirely new standard for the evaluation of laboratory tests.

It was interesting seeing which standard would be applied to the new laboratory tests associated with the prediction of drug resistance, such as tests based on gene expression patterns (genetic-based tests). As I stated above, the validation standard that some private insurance companies are accepting today for these genetic-based tests is "accuracy" and not "efficacy." All they have to do for these tests is prove that the test has a useful degree of "accuracy."

The cell-based profiling tests have the same entitlement to be judged by the same validation standard as molecular profiling tests. It must be noted that both types of diagnostic tests are just that, "tests" and not treatment. That's why ASCO needs to update their tech assessments on cell-based profiling assays. And do it transparently this time!

[CaroleHammett]

Thank you, thank you, thank you!

(Translation: I understand now, and it only took one reading this time! )

Seriously, Greg. You have no idea how much I appreciate your "walking me through" all this. I used to consider myself half-a**ed bright, but trying to understand the technological has definitely humbled me.

Carole

Life is not measured by the number of breaths we take, but by the moments that take our breath away.--the late, great George Carlin

[gpawelski]

The situation with Medicare (CMS) understaffing has very similar parallels with the nursing home crisis.

Medicare (CMS) having only about 20 doctors and 40 total clinicians working in its coverage office versus private insurers employing thousands of doctors, nurses and pharmacists.

Medicare (CMS) has passed on the off-label decision making process in the hands of compendia writers in the private sector, many on the payrolls of the companies that make the drugs.

Medicare (CMS) has passed off coverage decisions to the local/regional Medicare contractors, who are private insurers.

Medicare (CMS) contracts out the oversight of each nursing home to each state's health department. And there are a number of cancer patients in our nation's nursing centers.

Just for your perusal: http://www.baltimoresun2.com/talk/showt ... p?t=147677

[CaroleHammett]

Thanks for the nursing home links, Greg.

As a retired union rep whose work included representing nursing home employees, I have been long aware of the dangers posed to patients by staff shortages, particularly in facililties owned by national for-profits whose only bottom line is the almighty dollar--into their own pockets, of course.

As to Medicare, what your postings show clearly is that Medicare has already been "privatized" (controlled by the for-profits)--via the back door.

Carole

Life is not measured by the number of breaths we take, but by the moments that take our breath away.--the late, great George Carlin