April 17, 2006 First public meeting of Southern California Medicare contractor (National Heritage Insurance Company/NHIC) reconsideration of Medicare coverage for culture drug resistance testing

The report dated April 13, 2006 (immediately below) describes the ongoing review process for reconsideration of Medicare coverage for cell culture drug resistance testing (CCDRT). The first of two scheduled public commentary sessions was held today at the downtown Los Angeles headquarters of NHIC.  The second will be held April 19, 2006, at the Hilton Hotel at Los Angeles International Airport (LAX).  I'll be reporting the proceedings of both meetings following the completion of the second meeting.

In preparation for the meeting, I did a last minute review to determine if there were recent developments of relevance. I came across an April 4, 2006 technology review by BlueCross/BlueShield for the Northwestern USA.   As in the case of most Blue Cross/Blue Shield reviews, as well as the ongoing NHIC/Medicare review, this April 4 review relied heavily upon the series of reviews by the National BlueCross/BlueShield TEC review panel, headquartered in Chicago, IL. My general critiques of the entirely inadequate and misleading national BC/BS reviews are contained in my April 13, 2006 response letter (PDF file) to NHIC/Medicare and in my April, 2002 Superior Court testimony in support of a successful lawsuit against Blue Cross of California.

So this most recent BC/BS review simply reiterates the same old inadequate and misleading arguments, and only adds the following new analysis:

"An April 2006 updated search of the literature returned two new studies. Parker and colleagues studied the use of an extreme drug resistance assay in 18 patients with recurrent malignant glioma who were scheduled to receive irinotecan chemotherapy. Of the 15 with evaluable assay results, 4 were classified as extreme drug resistant. The median time to progression was 6 weeks compared to 3 months for those with indeterminate or low drug resistance. However, similar to other studies, results of drug resistance were not used to direct therapy, and there was no control group, both limiting interpretation of this small case series."

COMMENT: Once again, the reviewers fail to realize that they are evaluating a laboratory test and not a treatment. All laboratory tests are evaluated on the basis of test accuracy and no laboratory test in the history of cancer medicine has ever been shown in clinical trials to improve the results of therapy, and this includes estrogen receptor, progesterone receptor, Her2/neu, bacterial culture and sensitivity testing, panels of immunohistochemical stains to subclassify tumors, and on and on.  So this latter small study was simply one more in a long series of studies addressing the accuracy of the CCDRT with respect to predicting for treatment outcomes.  It was clearly a positive study.

The BC/BS review goes on to say:

"Staib and colleagues studied the use of the DISC chemosensitivity index Ci assay to select effective chemotherapy for 226 patients with previously untreated acute myeloid leukemia. (21).  Of the 162 evaluable patients, there were 11 (69%) complete response rates, 34 (21%) blast reduction, no response in 17 (10%), relapse after complete response in 53 (48%), and deaths in 89 (55%).  When compared to a non-randomized comparison group, none of the documented outcomes were statistically significantly different.  Neither study address the limitations noted in the above discussion. Specifically, no studies were identified that provided direct evidence comparing outcomes for patients treated either by assay-guided therapy or contemporaneous empiric therapy.  Therefore, the policy statement is unchanged."

COMMENT: This "expert review" is once again a sad reflection on the incompetence of these closed review panels.  In point of fact, the reviewers completely misunderstood the study.  This study was NOT a comparison of a "comparison group" and an "assay-directed treatment group!"  The DISC assay was NOT used to "select effective chemotherapy!" 

This is how the study worked:

The authors first studied 76 patients between 1994 and 1997. They used the assay results in these patients to establish retrospective cut-off definitions between sensitivity and resistance for the various drugs used in treatment.  Then they prospectively applied these definitions to a subsequent group of 86 patients treated between 1997 and 2000.  No patients in either cohort received assay directed therapy.  All were treated with standard cooperative group acute leukemia protocols. The purpose of the study was to see how well the assay predicted for treatment outcomes. The "expert" BlueCross/BlueShield reviewers were apparently confused by the authors' Table II, the point of which was simply to show that the 1994-1997 patient cohort was similar to the 1997-2000 patient cohort.  The table showed that there were no significant differences between the "training set" and "test set" groups (which is a strength and not weakness of the study), yet the inept BlueCross/BlueShield reviewers thought that the table represented a comparison between outcomes of control and assay treated groups!  This is an embarrassing mistake representative of many such mistakes in the present and prior reviews, all of which could have been avoided had the review been an open process (inviting input and commentary from all interested parties, including true experts in the field) rather than an entirely closed and opaque process, as all of these so called "expert technology reviews" have been.

The results as described by the study authors were as follows (Staib,P. et al. Br J Haematol 128:783-781, 2005):

"We found an overall predictive accuracy of 98.2% concerning treatment response, which compares favorably with previously published data ranging from 75% to 92%. Moreover the [assay results] proved to be the strongest prognostic factor for overall survival in a multivariate Cox regression analysis... (P<0.001)...and enabled the evaluation of response to combination therapies and selection of possible treatment alternatives. Our data suggest that [the assay] could serve as a powerful tool for assay-directed therapy strategies in [acute leukemia]."

These authors identified a population of patients, who, if treated with standard cooperative group protocols, had a 100% mortality within 12 months.  These results are precisely analogous to those of Bosanquet, et al, who identified a population of patients who, if treated with the most popular form of "standard" therapy, had a median survival of 8 months and were all dead within 18 months, but, if treated with something other than the most popular form of standard therapy, survived substantially longer.

Now, these are precisely the sorts of studies which are used to validate other types of laboratory tests used as an aid in the selection of patient treatment.  I'd like to ask any readers of this to ask themselves if they (the readers) had acute leukemia or chronic lymphocytic leukemia (two diseases where the National Cancer Institute currently identifies a number of different drug regimens as being equally likely to be active if chosen by coin flip), would they not want to avail themselves of a simple laboratory test (which could be performed on a simple blood or bone marrow specimen) which could help them avoid receiving a treatment which was likely to be a death sentence (when a large number of otherwise equal by coin flip regimens could be chosen instead)? 

But BlueCross/BlueShield and ASCO think that studies such as this are irrelevant and ASCO specifically EXCLUDED all such studies from its negative technology assessment review published in the September, 2004 edition of the Journal of Clinical Oncology (discussed in my April 13, 2004 letter to NHIC/Medicare [PDF file]).  Despite the fact that, if they applied the same criteria to evaluate all laboratory tests as they apply to review cell culture drug resistance testing, there would be absolutely zero laboratory or radiographic tests available to assist physicians in the management of cancer patients.

More later, as the NHIC/Medicare re-review process continues.

April 13, 2006 Southern California Medicare contractor (National Heritage Insurance Company) reconsidering previously-approved coverage for cell culture drug resistance testing

Background: Medicare has no national coverage decisions regarding the types of cell culture drug resistance testing which have been available in the USA since the early 1990s.  It has an earlier (circa early 1980s) coverage decision denying payment for two specific forms of cell culture testing which were available at the time. The first of these was the "human tumor stem cell" assay and the second was the "fluorescent cytoprint assay." The first was based on measuring tumor cell "clones," while the second was based on measuring "tumor microorgans."  Neither of these tests has been available for general clinical application in more than a decade (more than two decades for the latter). The new Southern California Medicare contractor has confused the distinction between the specifically non-covered technologies (the above, long-abandoned technologies) and the current technologies, which have been available for the past 15 years, as will be seen and discussed below and in my response letter (link provided below).

In November, 1999, Medicare convened a national coverage advisory committee meeting, where the issue was intensely reviewed, as described in detail in my letter of April 13, 2006 (PDF file). Although the conclusions of this national coverage advisory committee review were generally favorable, no national coverage decision was made, and coverage decisions were left to the local/regional Medicare contractors.  Subsequently, TransAmerica, the previous contractor for the Southern California region (where most of the laboratories providing this service are located), officially granted partial coverage for cell culture drug resistance testing (also described in detail in my letter, same PDF file as above).

As a direct result of two unfavorable reviews published in the September, 2004 issue of the Journal of Clinical Oncology (discussed also in the April 13, 2006 letter, same PDF file), the new Southern California Medicare contractor (National Heritage Insurance) has proposed to rescind previously-approved (by TransAmerica) coverage for this testing, as described on the National Heritage website and reproduced directly below. As described in my April 13 letter (same PDF file as above), this proposed rescinding of coverage cannot be justified by any rational consideration of the issues and data.  This proposed change will be discussed at open meetings in Los Angeles, to be held April 17 and 19, as also described on the National Heritage website (on their website, above, click Southern California/April agenda).

The following is currently posted on the National Heritage website, relating to the proposed rescinding of coverage:

"DL22566   Oncologic in Vitro Chemoresponse Assays - Noncoverage 

"06-02.5   Primary Geographic Jurisdiction California - Southern, Oversight Region Region IX 

"Medicare has a National Coverage Decision (NCD) on human tumor stem cell sensitivity assays which states:

"Human tumor drug sensitivity assays are considered experimental, and therefore, not covered under Medicare at this time.

"The clinical application of the assay, based on testing in tumor microorgans rather than in clones derived from single cells, is considered experimental, and therefore, not covered under Medicare at this time.

"A provider was granted a CMS review for reversal of this noncoverage on 8/4/1999, but the request was withdrawn during CMS’s review of the data (4/13/2000). CMS declined to issue any form of coverage for chemoresponse testing in 2000. [nb. This characterization is entirely incorrect, as described in my April 13, 2006 response letter PDF file  ].

"In 2004, reports were published by the American Society of Clinical Oncology (ASCO) and the Blue Cross “TEC” technology evaluation committee. The ASCO report concluded flatly that,

'The use of chemotherapy sensitivity and resistance assays to select chemotherapeutic agents for individual patients is not recommended outside of the clinical trial setting. Oncologists should make chemotherapy treatment recommendations on the basis of published reports of clinical trials and a patient’s health status and treatment preferences.'

"NHIC was unable to identity major national published protocols (e.g. www.nccn.org, for ovarian cancer) which utilize in vitro chemoresponse testing as a necessary step in therapy selection.

"Indications and Limitations of Coverage

"CMS gives several specific instructions to contractors regarding criteria for coverage evaluations.

"1. Criteria are similar for LCD and NCD determinations; both follow the same language at Section 1862(a) of the Social Security Act (care must be “reasonable and necessary; see Federal Register, 5/16/2000).

"2. Positions of national associations and/or the Blue Cross TEC committee are explicitly called out as appropriate criteria for medical necessity decisions (HCFA Ruling 95-1, Section 5).

"3. Contractors are specifically guided to weight consensus medical statements and association statements over individual providers (Program Integrity Manual, Chapter 13, Section 13.7.1).

"Accordingly, NHIC does not cover oncologic in vitro chemosensitivity tests per Medicare’s NCD (190.17). The reciprocal tests (chemoresistance or extreme resistance tests), are not covered per this LCD.

"Important note: Jurisdiction issue with Part A may supercede this LCD where current specimen dating rules place the date of service within a Part A hospital stay. See Claims Processing Manual, Chapter 16, Section 120.1 (minor updates by CR 4156, 4/3/2006) and also Section 40.3 and guidance on Part A, Part B billing and bundling issues."

Once again, my responses and rejoinders to the above statements and proposed rescinding of coverage are presented in my April 13 letter sent to the Southern California Medicare contractor (click here for PDF file of this letter). I shall also be attending both meetings, where I will offer oral commentary, and I shall report  the results of these meetings later next week on this website.