SUBJECT:

In re CMS LCD COMPLAINT:

Intravenous Immunoglobulin
(LCD) Database ID No. L9245),

Contractor: Blue Cross, Blue Shield of Kansas.

Region VII, Midwest Consortium

DECISION

The record of the local coverage determination (LCD) titled, "Intravenous Immunoglobulin (IVIg)," I.D. No. L9245, issued by the Medicare carrier, Blue Cross Blue Shield of Kansas (the Contractor), is complete and adequate to support the validity of the LCD provisions at issue under the reasonableness standard. Review of the challenged LCD is complete with the issuance of this decision.

I. Background

By an undated document received at the Civil Remedies Division (CRD) of the Departmental Appeals Board (DAB) on July 11, 2005 (the Complaint), the aggrieved parties (Complainants) requested through counsel that the LCD titled "Intravenous Immunoglobulin (IVIg)," I.D. No. L9245, issued by the Contractor, be reviewed. ⁽¹⁾ The case was assigned to me for further proceedings on August 1, 2005.

The regulations provide that an aggrieved party or parties may initiate review of an LCD by filing a "complaint." 42 C.F.R. � 426.400. ⁽²⁾ On September 1, 2005, I issued an "Acknowledgment of Receipt of Acceptable Complaint and Order to File the LCD Record" (Acknowledgment and Order) after evaluating the joint complaint as required by 42 C.F.R. � 426.410(b), (c), and (d) and finding that it was an acceptable joint complaint. I directed the Complainants to serve copies of the joint complaint and supporting documents upon the Contractor and CMS. On September 15, 2005, Complainants certified service of the complaint and supporting documents as directed. I further directed in the Acknowledgment and Order that the Contractor or CMS serve upon the aggrieved parties the LCD record as defined by 42 C.F.R. � 426.418 and serve upon my office the LCD record as defined by 42 C.F.R. � 426.419. Although I have no correspondence or certificate of service from the Contractor or CMS indicating when the LCD record was served, Complainants aver in their "Aggrieved Parties Response to LCD Record" at page 1 that they received the LCD record on October 4, 2005. On November 8, 2005, Complainants' undated Aggrieved Parties Response to LCD Record (AP Response) pursuant to 42 C.F.R. � 426.425(a) with exhibits (AP Ex.) A through G, was received at the CRD. The Contractor filed its "Response of Blue Cross and Blue Shield of Kansas, Inc., to Local Coverage Determination Appeal" (BCBS Response) with exhibits (BCBS Exs.) A through X on November 28, 2005, as authorized by 42 C.F.R. � 426.425(b). On November 28, 2005, the Contractor also filed a document titled "Response of Blue Cross and Blue Shield of Kansas, Inc., to Local Coverage Determination Appeal Contractor's Reply to Aggrieved Parties (sic) Response to LCD Record" (BCBS Reply) with an attached document marked as "Exhibit A," which for purposes of this decision, I have remarked as BCBS Ex. Y.

I advised the Parties in the Acknowledgment and Order that after receiving the LCD record and briefs of the Parties, I would conduct the review specified by 42 C.F.R. � 426.425. I advised that upon completion of my review, I would either issue a decision or issue further orders for discovery and the preparation of this case for hearing. As discussed hereafter, the LCD record is complete and adequate to support the validity of the LCD provisions at issue under the reasonableness standard and no further proceedings or review is required.

II. Discussion

A. Applicable Law

The Act provides at section 1869(f)(2) (42 U.S.C. �1395ff(f)(2)) as follows:

(2) Local Coverage Determination. -
           (A) In General. - Review of any local coverage determination shall be subject to the following   limitations:
                      (i) Upon the filing of a complaint by an aggrieved party, such determination shall be reviewed by an administrative law judge . . . The administrative law judge. --
                                (I) shall review the record and shall permit discovery and the taking of evidence to evaluate the reasonableness of the determination, if the administrative law judge determines that the record is incomplete or lacks adequate information to support the validity of the determination;
                              (II) may, as appropriate, consult with appropriate scientific and clinical
experts; and
                             (III) shall defer only to the reasonable findings of fact, reasonable interpretations of law, and reasonable applications of fact to law by the Secretary.

A LCD, as defined by the Act, is "a determination by a fiscal intermediary or a carrier . . . respecting whether or not a particular item or service is covered" within the area covered by the contractor. Act, section 1869(f)(2)(B) (42 U.S.C. �1395ff(f)(2)(B)).

The Secretary promulgated regulations pursuant to sections 1102 and 1871 of the Act (42 U.S.C. �� 1302 and 1395hh), implementing sections 1869(f)(1) and (f)(2) of the Act. 42 C.F.R. � 426.100. The regulations are found at 42 C.F.R. Part 426. The procedures for review of an LCD are in 42 C.F.R. Part 426, Subpart D (42 C.F.R. � 426.400 et. seq.).

The statute provides for a two-level review process by the ALJ. The ALJ reviews the record and if he or she determines that the record is complete with adequate information to support the validity of the LCD, review is complete. If the ALJ reviews the record and determines that the record is incomplete or lacks adequate information to support the validity of the determination, than further process is required, although that process is not specified by the statute. The Secretary's regulations establish a review procedure consistent with that specified by Congress. The regulations provide that after the aggrieved parties file a statement as to why the LCD is not valid and the contractor responds, "the ALJ applies the reasonableness standard to determine whether the LCD record is complete and adequate to support the validity of the LCD." 42 C.F.R. � 426.425(c)(1). "Issuance of a decision finding the record complete and adequate to support the validity of the LCD ends the review process." 42 C.F.R. � 426.425(c)(2). If the ALJ does not determine that the LCD record is complete and adequate to support the validity of the LCD, then the regulation provides for discovery and the taking of additional evidence. No hearing was intended by the drafters or required by the language of the regulation for the first phase review. 68 Fed. Reg. 63,692, 63,700 (Nov. 7, 2003).

The reasonableness standard is defined at 42 C.F.R. � 426.110, as:

[T]he standard that an ALJ or the Board must apply when conducting an LCD or an NCD [national coverage determination] review. In determining whether LCDs or NCDs are valid, the adjudicator must uphold a challenged policy (or a provision or provisions of a challenged policy) if the findings of fact, interpretations of law, and applications of fact to law by the contractor or CMS are reasonable based on the LCD or NCD record and the relevant record developed before the ALJ or the Board.

Further definition of the reasonableness standard is provided by the notice of final rule making at 68 Fed. Reg. 63,692, 63,703-04 (2003). The drafters of the regulation discussed the reasonableness standard adopted as follows:

We are using the statutory language from sections 1869(f)(1)(A)(iii) and (f)(2)(A)(i) of the Act, which instructs adjudicators to defer only to the reasonable findings of fact, reasonable interpretations of law, and reasonable applications of fact to law by the Secretary. The logical corollary is that the ALJs and the Board must accord deference if the contractor's or CMS's findings of fact, interpretations of law, and application of fact to law are reasonable. The concept of deference is one that is generally applied by courts to administrative decisionmaking, in recognition of the expertise of a program agency. Thus, we view the statute as setting out a reasonableness standard that recognizes the expertise of the contractors and CMS in the Medicare program--specifically, in the area of coverage requiring the exercise of clinical or scientific judgment. So long as the outcome is one that could be reached by a rational person, based on the evidence in the record as a whole (including logical inferences drawn from that evidence), the determination must be upheld. This is not simply based on the quantity of the evidence submitted, but also includes an evaluation of the persuasiveness of the material. If the contractor or CMS has a logical reason as to why some evidence is given more weight than other evidence, the ALJs and the Board may not overturn the determination simply because they would have accorded more weight to the evidence in support of coverage. In some situations, different judgments by different contractors may be supportable, especially if explained by differences such as the ready availability of qualified medical professionals in one contractor's area, but not in another. Moreover, an ALJ or the Board may not determine that an LCD is unreasonable solely on the basis that another Medicare contractor has issued an LCD that permits coverage of the service at issue, under the clinical circumstances presented by the complaint. For legal interpretations, the reasonableness standard would not be met if an interpretation is in direct conflict with the plain language of the statute or regulation being interpreted. Moreover, an interpretation in an LCD would not meet the reasonableness standard if it directly conflicts with an NCD or with a CMS Ruling. So long as an interpretation is one of the readings permitted by the plain language of the law and can be reconciled with relevant policy, however, it must be upheld, even if the ALJ or the Board might have reached a different result if interpreting the statute or regulation in the first instance.

Id.

B. Issue

At this phase in the review process, the issue is whether or not the LCD record is complete and adequate to support the validity of the challenged LCD provisions under the reasonableness standard.

C. Findings Pursuant to 42 C.F.R. �� 426.450 through 426.457

1. The LCD record is complete and adequate to support the validity of the LCD provisions at issue under the reasonableness standard.

Complainants challenge LCD L9245, titled, "Intravenous Immunoglobulin (IVIg)," issued by the contractor carrier Blue Cross Blue Shield of Kansas. ⁽³⁾ More specifically, the Complainants challenge the provisions under the section titled "Indications and Limitations of Coverage and/or Medical Necessity," section 2, titled "Primary Humoral Immunodeficiencies," and the part titled "Limitations: Secondary Immunodeficiencies" which provides "(s)econdary immunodeficiencies or hypogammaglobulinemia, in isolation, will not be covered unless the immunodeficiency is the result of chronic lymphocytic leukemia or childhood Human Immunodeficiency Virus (HIV) Infection." Complaint at 2, 7. Complainants allege that the language of section 2 under the part titled "Limitations: Secondary Immunodeficiencies" "represents the core controversy in this matter in that it explicitly denies off-label immune globulin therapy to persons, like appellants, with illness arising out of secondary humoral immunodeficiencies not the result of chronic lymphocytic leukemis or childhood HIV infection (emphasis omitted)." Complaint at 7. Complainants do not challenge section 7 of the LCD that provides for coverage of IVIg therapy for patients infected with HIV to reduce significant bacterial infection but only when the patient is less than 13 years old, with evidence of either qualitative or quantitative humoral immunologic defects, and current bacterial infections despite appropriate prophylaxis.

The gist of the complaint is that each of the Complainants had been receiving immune globulin (Ig) infusions from their common physician due to hypogammaglobulinemia and recurrent sinusitis or otitis media. ⁽⁴⁾ The Complainants had been notified by their physician, Dr. Patrick M. Nemechek, D.O., P.A., in April 2005, that their treatments would no longer be covered by Medicare. ⁽⁵⁾ Complaint at 2-5; C. Ex. G. Complainants' argue that the provision of the LCD that eliminates Medicare coverage for their treatment and the treatment of others with illnesses arising from secondary humoral immunodeficiencies other than chronic lymphocytic leukemia or childhood HIV infection is invalid. ⁽⁶⁾ Complaint at 5-7. Complainants assert that the "LCD runs contrary to both the best available peer-reviewed literature and the majority of established IVIg LCD's across the country." Id. at 7. Complainants also allege that the Contractor failed to comply with requirements of the CMS Program Integrity Manual (PIM) when promulgating the LCD. Id.

Two issues require comment before proceeding to review the specific LCD provisions challenged under the reasonableness standard.

First, the regulations contemplate that the LCD record served on the ALJ may be different than that served upon the Complainants. The regulation provides that the Contractor must file with the ALJ under seal any proprietary or privileged information; however, such information need not be served upon the Complainants. Compare 42 C.F.R. �� 426.418 and 426.419. Complainants note that the Contractor did not release to them statements from four clinical experts, and they request that the Contractor be compelled to release them or to provide an explanation for why they qualify as proprietary or privileged information. AP Response at 17. The Contractor did file the "excluded documents" with the copy of the LCD record filed with me pursuant to 42 C.F.R. � 426.419, with each document marked "Excluded Document" in the upper right had corner. I have reviewed each of the documents the Contractor marked as "Excluded Document" and conclude that none of the documents are material to a determination that the LCD record is not adequate to support the validity of the LCD provisions challenged by Complainants. Accordingly, I conclude that further development with regard to whether those documents were properly not released to Complainants is unnecessary at this stage of the review process.

Second, I note that the Contractor clarified in its response to the complaint that, on a case-by-case basis, the Contractor will "consider allowing use of IVIg for an adult HIV patient who also has marked hypogammaglobulinemia (total serum immunoglobulin concentrations less than 400 mg/dl) and recurrent infection." BCBS Response at 15. This clarification has no impact upon my decision in this case.

Turning to the issue of the reasonableness of the LCD provision challenged by Complainants, the focus at this stage is upon the specific provisions or language challenged by the Complainants and whether or not the LCD record is complete and adequate to support the validity of the LCD provisions under the reasonableness standard. My task is to consider the provision in light of the record submitted by the Contractor and determine whether or not the reasonableness standard is satisfied. At this stage of review, the focus is not upon new or additional evidence beyond that in the LCD record. However, I do find relevant and material any evidence submitted to this point that reflects upon the weight of the evidence the Contractor relied upon when promulgating the LCD. In other words, I conclude it is appropriate to consider evidence that Complainants submitted when determining whether the evidence the Contractor relied upon when promulgating the LCD is adequate to support the validity of the LCD provisions under the reasonableness standard.

Complainants argue that the Contractor concedes that the LCD provisions in question are not based upon consideration of a prior shortage of IVIg or that the use of IVIg is unsafe. Rather, Complainants argue that the narrow question is whether IVIg therapy is effective for HIV-infected adults who suffer recurrent bacterial infections. AP Response at 10. In their complaint, Complainants characterize the issue using the formulation from Chapter 13 of the CMS PIM (C. Ex. H), arguing that use of IVIg for secondary immunodeficiencies is "reasonable and necessary" as that phrase is defined by PIM 13.5.1. Complaint at 8. However, in order for a service to be found "reasonable and necessary," PIM 13.5.1 requires that it must be effective. Thus under the "reasonable and necessary" standard, the issue is whether or not IVIg therapy is effective for HIV-infected adults who suffer recurrent bacterial infections. Complainants concede that "(i)t is true that large scale studies involving placebo controlled trials evaluating the effectiveness of IVIg in secondary humoral immunodeficiency have not been performed . . . ." and it is unlikely such studies will be performed in the future. Id. Complainants note the cost of such studies and ethical considerations of denying therapy to a placebo group. Id. at 11. ⁽⁷⁾ Although this case could be resolved solely upon Complainant's concession that effectiveness is unproven, further analysis establishes that the concession is well-founded.

The section of the LCD titled, "Sources of Information and Basis for Decision," lists the seven documents or articles that the Contractor relied upon when promulgating the LCD. LCD Record, LCD at 7; C. Ex. F at 7-8. One of the articles, Thomas A. Ratko, Ph.D. et. al., Recommendations for Off-Label Use of Intravenously Administered Immunoglobulin Preparations, 273 JAMA 1865 (June 21, 1995), had the objective of summarizing the consensus recommendations for off-label uses of IVIg developed by the University Hospital Consortium Expert Panel to guide clinicians in the appropriate and efficient use of IVIg. According to the article, the expert panel was composed of eight physicians who were board certified in critical care, hematology, immunology, neurology, oncology, pediatrics, or rheumatology, and two hospital pharmacists. The panels findings were based upon 201 articles and 1904 original reports, and the reported recommendations were the consensus of the panel. Id. According to the article, IVIg is not supported for HIV or infections in adults. Id. at 1867-69 (table). The article also states:

Finally, for many of the debilitating or fatal off-label conditions in which IVIG has been used, it is highly improbable that randomized comparative trials to evaluate IVIG therapy vs conventional approaches will ever be performed in the United States. This is primarily because of ethical concerns about randomization of seriously ill patients to either placebo treatment or unproven intervention with IVIG, but also because of the high cost of multicenter trial designs necessary to achieve adequate study power. Thus, the therapeutic role of IVIG awaits confirmation for most off-label conditions.

Id. at 1870. Complainants assert that it is important to recognize that most studies involving HIV before this article assessed the impact of IVIg upon HIV and not "sinopulmonary infections from humoral immunodeficiency secondary to HIV Disease (emphasis omitted)." AP Response at 9. I certainly recognize this limitation to the JAMA article as the article itself similarly cautions the reader. However, I note that the absence of studies showing the efficacy of IVIg for the treatment of HIV-infected adults with sinopulmonary infections actually tends to support the Contractor's position rather than that of Complainants.

The article by Elizabeth F. Jaffe, M.D., Ph.D., cited in the LCD, does not recommend for or against the use of IVIg for adults with HIV and recurrent sinus or other infections but does recommend use for HIV-infected children. Elizabeth F. Jaffe, M.D., Ph.D., Humoral Immunodeficiencies, Secondary Hypogammaglobulinemia, 21 Immunology and Allergy Clinics of North America 141 (February 2001) (C. Ex. 12); LCD Record at 15 (as printed). Complainants offer a January 3, 2005 letter from Dr. Jaffe in which she advises that it has come to her attention that her article "is being used as a resource to deny IVIg treatment to some patients with a demonstrated secondary humoral immunodeficiency." C. Ex. L. Dr. Jaffe indicates that her article focused on situations where a low immunoglobulin G level may not represent a true state of immunodeficiency. She advises that patients, with secondary immunodeficiency that cannot make functional antibodies, would likely benefit greatly from IVIg. She suggests that "(a)t least a trial use of IVIG is warranted if the clinical and laboratory evidence of immune deficiency is evident." Id. The problem with Dr. Jaffe's letter for Complainants is that she points to no study or publication that supports the assertion that IVIg is an effective therapy for an HIV-infected adult with recurrent sinusitis or otitis media.

The article titled, "Availability of Immune Globulin Intravenous for Treatment of Immune Deficient Patients - United States, 1997-1998, Centers for Disease Control, 48 Morbidity and Mortality Weekly Report 159-62 (March 1999), Table 1, indicates that IVIg is not useful for adult HIV infections. LCD Record.

None of the other publications cited in the LCD specifically address whether or not IVIg is effective for adults with HIV and recurrent sinus or other infections. The LCD refers to the article by Mark Ballow, M.D., Primary Immunodeficiency Disorders: Antibody Deficiency, 10 Journal of Allergy and Clinical Immunology 581-91 (April 2002) (C. Ex. M). The article discusses, as its title implies, primary immunodeficiency disorders not secondary immunodeficiencies in an HIV-infected adult with hypogammaglobulinemia and recurrent sinusitis or otitis media. Complainants argue that Dr. Ballow's article is "a basis for denying IVIg to patients like appellants (sic) with secondary immune deficiency disorders." Complaint at 12. My review clearly indicates that the Ballow article neither speaks for or against IVIg therapy for secondary immunodeficiencies in an HIV-infected adult with recurrent sinusitis or otitis media. Complainants provided me a copy of a memorandum or letter dated January 12, 2005, from Dr. Ballow. He indicates that he has "been asked to comment on the use of IGIV therapy in HIV infected patients who demonstrate a deficiency in antibody formation and have recurrent infections." C. Ex. N. Dr. Ballow acknowledges that well-controlled studies are not available to show the efficacy of IVIg therapy for the treatment of HIV/AIDS adults with infectious complications. He nevertheless argues that such patients may benefit from IVIg therapy based on "information and data from other clinical trials not only reducing mortality and morbidity from these diseases, but also increasing the quality of life of patients." Id. Dr. Ballow points to an article by Kiehl, which I will discuss further along in this decision, and he suggests extrapolating from controlled trials in children. He recommends that the LCD guidelines for IVIg in persons with secondary immune deficiency disorders permit patients with such disorders who have recurrent bacterial infections, and for whom a deficiency of specific antibodies can be demonstrated, to receive IVIg therapy. While it is clear to me that Dr. Ballow believes that IVIg therapy might be helpful, like Dr. Jaffe, he points to no specific studies to support his opinion and acknowledges that no such studies exist, except the Kiehl study.

In support of their position that IVIg is effective, Complainants point to several sources of information. A 1991 letter to the editor of Vox Sang indicates that a pilot open study was done at the Blood Transfusion Centre and Department of Genitourinary Medicine, Royal Infirmary, and Infectious Disease Unit, City Hospital, Edinburgh, UK. ⁽⁸⁾ The letter stated that while it has been suggested that IgG replacement therapy may be beneficial to HIV-infected adults with frequent infections of the respiratory tract, studies evaluating the efficacy of IVIg replacement are difficult because only a minority suffer recurrent infections and it is difficult to control other factors. In fact, the writers acknowledged that at the time, there were no published reports of any trials of intravenous IVIg treatment in HIV-infected adults with recurrent bacterial infections only one anecdotal report of a single HIV-infected adult who benefitted significantly from IVIg therapy. Thus, the writers undertook to conduct the pilot study. The study involved six HIV-infected adults with recurrent bacterial infections. The participants were selected on the basis of recurrent infections that did not respond to antibiotic therapy. Each participant acted as his or her own control. The six subjects were infused every three weeks. The occurrence of need for antibiotics and hospitalization during the period of infusions was compared with each subject's history for the six months preceding the infusions. The writers concluded that for five of the six, while IVIg did not completely prevent the occurrence of infections, there was a reduction in antibiotics required. The sixth subject experienced no change. Four of the six experienced a reduction in hospitalizations. The writers concluded that "(f)urther studies, preferably of randomised placebo-controlled cross-over design, are required to determine the place of this therapy in the management of the HIV-infected patient with recurrent bacterial infections." P.E. Williams, et. al. Controlled Study of Intravenous IgG Therapy for HIV-Infected Adults with Recurrent Bacterial Infections, 60 Vox Sang 126-27 (1991). The authors clearly did not suggest that their pilot study was sufficient to determine that IVIg therapy was appropriate for the management of HIV-infected adults with recurrent bacterial infections.

Complainants also rely upon a study reported in the article by Michael G. Kiehl, M.D., et. al., A Controlled Trial of Intravenous Immune Globulin for the Prevention of Serious Infections in Adults with Advanced Human Immunodeficiency Virus Infection, 156 Archives of Internal Medicine 2545-50 (December 1996) (C. Ex. Q) (the Kiehl study). The authors state that studies on HIV-infected children suggest that high-dose Ig therapy might be beneficial in reducing recurrent infections. However, they point-out that comparable adult studies are not available. Id. at 2545. The authors objective in the study they undertook was to determine the efficacy of IVIg therapy in "preventing infections and reducing days with fever, as well as the duration and frequency of hospitalization" for HIV-infected adults. Id. Study design and treatment Protocol for the study are set forth in the article and were approved by the Ethics Committee of the University of Münster, Münster, Germany. Id. at 2546. The study was an open, randomized outpatient clinical trial, involving persons older than 18 who had evidence of HIV disease. Between August 1991 and June 1994, 175 patients enrolled in the study and 48 of those were excluded from statistical analysis. The study permitted statistical analysis of the remaining 127 patients (57 in a control group and 70 in a treatment group) with a median observation time of 31 weeks. The authors report as results that IVIg "significantly" increased time during which patients were free of serious infection; there was a reduction in the number and duration of hospitalizations for short-term care; a reduction in days with fever; and a reduction in frequency of diarrhea. Id. The authors further report that, due to the favorable results, the local ethics board stopped the study. Nevertheless, the authors of the study conclude their article as follows:

In summary, our data suggest that prophylactic IV immune globulin therapy reduces the frequency of serious infections and the frequency as well as duration of hospitalization. . . . Furthermore, IV immune globulin treatment may increase the quality of life by reducing the number of days with fever and the frequency of diarrhea. The obvious benefits of IV immune globulin treatment in this randomized open study argue for a double-blinded, placebo-controlled study to substantiate the role of IV immune globulin treatment of HIV-infected adults.

Id. at 2550. The concluding comments clearly signal that the authors did not believe their study conclusive or the basis upon which to recommend the use of IVIg therapy for HIV-infected adults with recurrent infections. Rather, the authors recognized that their study supported the need for more study to determine the efficacy of such therapy. The Contractor submitted as BCBS Ex. H an article, L. Mouthon & O. Lortholary, 9 Clinical Microbiology and Infectious Diseases, 333-38 (2003), that questions the Kiehl study because the data were not corrected for another prophylactic treatment modality and roughly 25 percent of the patients were excluded from the study. Id. at 334-35. This article was not cited by the Contractor as a basis for the LCD provision in issue, but rather it was submitted by the Contractor to negatively reflect upon the credibility and probative value of the Kiehl study and article. The Contractor also highlights the authors' conclusion that at the time of the article in 2002, "prophylactic use of IVIg to prevent the occurrence of recurrent bacterial infections in HIV-infected adults cannot be recommended." BCBS Response at 11-12.

Complainants offer letters from two physicians who report that they have had success in using IVIg in patients with secondary humoral immunodeficiency. C. Exs. O, P. Anecdotal reports of success are not adequate to support an LCD (see PIM 13.7.1, C. Ex. H) and I do not find them sufficiently weighty to provide a basis for finding the LCD provision at issue here invalid.

Complainants allege that other provisions of section 2 of the LCD titled, "Primary Humoral Immunodeficiencies," provide an independent basis for finding the LCD invalid. Complaint at 16-23. However, the evidence does not show that any of the four Complainants suffer from a Primary Humoral Immunodeficiencies or that the other provisions of section 2 of the LCD related thereto have any application to them. In fact, Complainants allege that language of section 2 under the part titled "Limitations: Secondary Immunodeficiencies" "represents the core controversy in this matter in that it explicitly denies off-label immune globulin therapy to persons, like appellants, with illness arising out of secondary humoral immunodeficiencies . . . (emphasis omitted)." Complaint at 7. "Appellants' use of IVIg is for secondary antibody deficiency." Complaint at 6. As Complainants state in their response, "(t)he relevant scope of inquiry for this appeal is the effect of IVIg on recurrent bacterial infections secondary to HIV." AP Response at 3. Thus, Complainants have not shown that they are aggrieved parties within the meaning of 42 C.F.R. � 426.110 with respect to the other provisions of section 2 of the LCD they challenge or that they may initiate review of those provisions under 42 C.F.R. � 426.320(a).

Complainants also undertook to review 67 LCDs they located on the CMS website. Based upon their review Complainants allege that the majority of contractors allow off-label IVIg therapy for diagnosis of hypogammaglobulinemia (non-specified), qualitative or quantitative evidence of humoral immunodeficiency, or simply a diagnosis of Acquired Immunodeficiency Syndrome alone. They also allege that no other carriers or fiscal intermediaries limit secondary immunodeficiencies to just HIV-infected children or Chronic Lympohocytic Leukemia. Complaint at 13, 23-26. Complainants conclude their analysis with the assertion: "(t)his analysis clearly demonstrates that the overwhelming majority of Medicare LRMP/LCD policies allow use of immune globulin for immunodeficiency states which cannot be accurately classified as a primary immunodeficiency and are therefore classified as secondary regardless of the originating cause of the immune deficiency." Complaint at 26. The Contractor also reviewed LCDs and characterizes the results of its review differently. The Contractor alleges that many of the LCDs Complainants reviewed were not current policies. The Contractor further alleges that of those reviewed initially by Complainants, only 29 of 71 would allow off-label use of IVIg for secondary hypogammaglobulinemia, IgG subclass deficiency or functional antibody deficiency, and then only for a severe or significant deficiency. BCBS Response at 21. The Contractor points out that the Complainants' reliance upon listings of codes in the LCDs analyzed is not particularly helpful as one must consider what is specifically provided under the Indications and Limitations of Coverage and/or Medical Necessity section of each LCD as well as any other limiting language. Based on its analysis, the Contractor found 48 current Medicare Part B IVIg LCDs, 4 of which allow no coverage for HIV regardless of age, 5 allow coverage of adult HIV, and the remaining 39 limit coverage to HIV patients under the age of 13. BCBS Response at 21-23. I conclude that it is unnecessary to resolve the parties inconsistent conclusions. The issue before me is whether or not the LCD record is complete and adequate to support the validity of the challenged LCD provisions under the reasonableness standard. I can resolve that issue without the benefit of the parties studies of other LCDs. The studies do not help me resolve the key factual issue of whether or not IVIg therapy is effective for HIV-infected adults who suffer recurrent bacterial infections. Furthermore, I may not decide that an LCD that denies coverage is unreasonable on the basis that another Medicare contractor would permit coverage. 68 Fed. Reg. 63,692, 63,704. I do note that Complainants do not specifically point to any one of the LCDs they studied and assert that their IVIg therapy for recurrent bacterial infections would be considered covered by the contractor that issued the LCD.

Finally, Complainants argue that the LCD under consideration was promulgated in violation of the PIM. Complainants' lengthy review of the history of their treating physician with the Contractor and his repeated audits by the Contractor lead to their conclusion that the LCD was promulgated due to a vendetta against their physician. Complaint at 26-35. The PIM is not a statute or a regulation and one may question that Complainants enjoy any enforceable rights based on that policy document. However, even if one concludes that they may enforce the PIM against the Contractor and CMS, the legal issue before me is whether or not the LCD meets the reasonableness standard and, factually, the issue is whether there has been a showing that IVIg therapy is efficacious for HIV-infected adults who suffer recurrent bacterial infections.

Based upon the foregoing analysis, I conclude that Complainants have not shown that IVIg is efficacious for HIV-infected adults who suffer recurrent bacterial infections as they allegedly do. The LCD record shows that IVIg therapy for HIV-infected adults with recurrent bacterial infections has not been determined to be effective. It is not unreasonable for the Contractor to reject anecdotal evidence of some beneficial effect of IVIg therapy in one patient or a small group of patients or reports of studies that conclude with a recommendation for more study to determine the effectiveness of such therapy. Complainants have provided me no evidence that is more persuasive than that included in the LCD or record or that would support a conclusion that the Contractor's findings and conclusions were not reasonable.

2. The review process is complete upon issuance of this decision.

The LCD record is complete and adequate to support the validity of the challenged LCD provisions under the reasonableness standard. "Issuance of a decision finding the record complete and adequate to support the validity of the LCD ends the review process." 42 C.F.R. � 426.425(c)(2).

III. Conclusion

The LCD record is complete and adequate to support the validity of the LCD provisions at issue under the reasonableness standard and review of the challenged LCD is complete.

Keith W. Sickendick

Administrative Law Judge

1. On November 7, 2003, the Centers for Medicare & Medicaid Services (CMS) published regulations governing review of LCDs. The regulations are codified at 42 C.F.R. Part 426 and the regulations and applicable provisions of the Social Security Act (the Act) discussed hereafter, control in this case.

2. In this case, the aggrieved parties filed with their complaint supporting documents marked as exhibits (C. Ex.) A through BB with LCD's numbered 1 through 67 from other contractors. I treat the 67 LCDs as C. Ex. CC 1 through 67 for purposes of this decision.

3. The copy of the LCD submitted as C. Ex. F reflects an original policy effective date of September 16, 1999 and a revision effective date of April 13, 2005. The copy of the LCD submitted as part of the LCD record reflects the same original policy effective date but a revision effective date of August 17, 2005. Complainants have raised no objection and I note that the challenged provisions appear to be identical in both versions.

4. Treatments for one of the Complainants began in 1997, for one in 1999, and for the other two in 2001 and 2002, respectively. IVIg was initiated for three due to hypogammaglobulinemia and recurrent sinusitis and for the fourth due to hypogammaglobulinemia and recurrent otitis media. Complaint at 3-5.

5. I do not have evidence that the Complainants applied for but were denied benefits.

6. The identity of the individual Complainants and their medical histories are important to establish their standing as aggrieved parties but is not relevant or material on the issue of the validity of the LCD provisions in issue.

7. Complainants also argue that the argument of the Contractor that current antiretroviral agents may improve humoral immune function, or pneumococcal vaccine response, is unsupported by any study. AP Response at 11-17. Of course, the effectiveness of antiretroviral agents is not the issue before me. The issue, as characterized by Complainants, is the effectiveness of IVIg. However, I note that two articles submitted by Complainants indicate that it is reasonable to infer that highly-active antiretroviral therapy (HAART) is "positively affecting humoral responses to pneumococcal antigens," i.e., HAART seems to reduce the incidence of pneumonia in HIV-infected adults. Maria C. Rodriguez-Barradas, et. al., Response of Human Immunodeficiency Virus-Infected Patients Receiving Highly Active Antiretroviral Therapy to Vaccination with 23-Valent Pneumococcal Polysaccharide Vaccine, 37 Clinical Infectious Diseases 438, at 442 (August 2003) (AP Ex. D); Mark S. Dworkin, et. al., Pneumococcal Disease among Human Immunodeficiency Virus-Infected Persons: Incidence, Risk Factors, and Impact of Vaccination, 32 Clinical Infectious Diseases 794, at 796-797 (March 2001) (AP Ex. E).

8. AP Response at 2, AP Ex. A.