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Title XVIII of the
Social Security Act, Section 1862 (a)(1)(A). This section excludes coverage
of items or services that are not reasonable and necessary for the
diagnosis or treatment of illness or injury or to improve the functioning
of a malformed body member.
Title XVIII of the Social Security Act, Section 1833 (e). This section
prohibits Medicare payment for any claim which lacks the necessary
information to process the claim.
Title XVIII of the Social Security Act, Section 1881(b)(1). This section
allows payment for services furnished to individuals who have been
determined to have end stage renal disease.
Title XVIII of the Social Security Act, Section 1881(11)(B)(I). This
section allows payment for erythropoietin provided by a physician.
CMS Pub 100-2, 1-§30; 100-2, 6-§20.4; 100-2, 11-§30.4; 100-4, 8§80.2.1,
27-§80.8; 100-4, 8-§90, 90.1, 90.6, 90.6.1, 90.6.1.1
CMS Pub 100-4, 17-§80.2; 100-4, 8-§60.4
Medicare Provider Reimbursement Manual, Part I, HCFA Pub. 15, Section
2710.3
CMS Pub 100-2, 11-§90
CMS Pub 100-2, 15-§50, 17-§10; 100-4, 8-§60.4; 100-4, 17§20.3.8; 100-4,17
Program Memorandum AB-02-100 Modification of Medicare
Policy for Erythropoietin (EPO)
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Epoetin alfa, FDA approved June 1989, is a recombinant version of
a human protein that stimulates the production of red blood cells and is
used in the treatment of anemia associated with failure of erythropoiesis.
Epogen elevates or maintains the red blood cell level (the hematocrit) to
decrease secondary morbidity and reduce the need for maintenance blood
transfusions in both adult and pediatric patients.
Produced by the normally functioning kidney, erythropoietin signals the
bone marrow to manufacture red blood cells, which are responsible for
transporting energy-producing oxygen to all cells of the body. Endogenous
production of erythropoietin is normally regulated by the level of tissue
oxygenation. Hypoxia and anemia generally increase the production of
erythropoietin, which in turn stimulates erythropoiesis. In normal
subjects, plasma erythropoietin levels range from 0.01 to 0.03 Units/ml,
and increase up to 100- to 1000-fold during hypoxia or anemia. In contrast,
production of erythropoietin in patients with chronic renal failure (CRF)
is impaired, and this erythropoietin deficiency is the primary cause of their
anemia; failure of the kidney to produce this protein leads to anemia in 90
percent of all dialysis patients. Epoetin alfa supplements the failing
kidney’s inadequate supply of erythropoietin and has been shown to
stimulate erythropoiesis in anemic patients with CRF (including both
patients on dialysis and those who do not require regular dialysis) as well
as other hypo-erythropoietic states.
Epogen dosage is initially based on the patient's weight and hematocrit (or
hemoglobin). Hematocrits are checked on a regular basis. Due to the length
of time required for erythroid progenitors to mature and be released into
the circulation, a clinically significant increase in hematocrit is usually
not observed before 2 to 6 weeks. Once the hematocrit reaches the target
range of 30-36% (or Hgb=10-12), the level can be sustained by epoetin
therapy in the absence of iron deficiency and concurrent illnesses. For
this reason an assessment of iron stores prior to initiation of epoetin is
required, and patients who have depleted stores require replacement.
Epoetin alfa may be given either as an intravenous or subcutaneous
injection. In patients on hemodialysis, epoetin alfa usually is often
administered as an IV bolus 3 times weekly with dialysis to obviate the
need for additional injections, although SC administration is generally
considered to be superior and preferable. Patients who have been judged
competent by their physicians to self-administer epoetin alfa without
medical supervision may give themselves SC (or occasionally IV) injections.
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Indications Summary
Epoetin is a covered service for the treatment of anemia when other
treatable causes have been identified and treated and when the continued
anemia is presumed to be caused by ESRD (on dialysis) OR by CRF
(pre-dialysis with a creatinine clearance of 45 ml/min or less). Prior to
treatment the patient should evidence a hematocrit level that is 30 % or
less (Hgb <= 10) predialysis or a persistent hematocrit less than 33%
(Hgb <11) if on dialysis. Once epoetin is started, the hematocrit
should be maintained in the mid thirties, targeted to a level between 33
and 36 percent (Hgb 11-12). Coverage for epoetin in the setting of CRF
(non-dialysis) only exists when administered "incident to" a
physician's service.
Epoetin is additionally covered for the treatment of significant
symptomatic anemia (e.g. associated with a marked reduction in activities
of daily living) that is secondary to anti-neoplastic drug therapy,
anemia of chronic disease (e.g. non-myeloid malignancies, Rheumatoid
Arthritis), and myelodysplastic syndromes. A serum epoetin level of 200
mu/ml is usually required as noted in the labeled instructions, although
treatment can be covered if medical necessity is otherwise documented for
values between 200 and 500 mu/ml. Epoetin is indicated in the treatment
of anemia for patients with non-myeloid malignancies both when the anemia
is due to the effect of concomitantly administered chemotherapy and when
the anemia is secondary to the malignancy itself. However, there is
insufficient evidence to support the efficacy of epoetin when used to
support hematopoesis during radiation therapy. Epoetin for the treatment
of myeloid malignancies is similarly not covered.
The medical literature does not support the routine maintenance of
hematocrits greater than 37, so a target range higher than 33 to 36
percent (10-12 g/dl) must be justified by documentation of significant
signs, symptoms or progressive medical complications of decreased oxygen
delivery; the selection of target hematocrits greater than 40 is not
anticipated. Dosages in excess of 300 U/kg 3x/week are seldom medically
necessary. Coverage limitations may be applied (typically on a post-pay
basis in accordance with PM AB-02-100) when the 3 month rolling HCT
exceeds 37.5 (or when a peak HCT exceeds 40.5) unless active steps are
being taken to reduce the dosage. However, dialysis facilities that
maintain at least 80 percent of their patients on SC epoetin (as opposed
to IV) will not be held to a 36% maximum target or any utilization
guidelines except a 40.5% rolling limit (see Utilization Guidelines).
Epoetin is covered for the treatment of anemia in patients receiving AZT
for acquired immunodeficiency syndrome (AIDS) or AIDS-related complex
(ARC) when endogenous epoetin levels have been documented at 500Mu/ml or
less, and will continue to be covered up to three months after the
cessation of AZT. It is also covered for correction of anemia in those
patients scheduled for elective hip and knee surgery who are not
candidates for autologous blood transfusion.
Epoetin is not covered for the treatment of other types of anemia,
including iron or folate deficiency, hemolysis, ongoing occult blood
loss, or any other indication not specifically denoted by this policy. Patients
should have at least a three-month life expectancy to qualify for care.
Claims must be submitted with an appropriate anemia ICD-9 code as well as
a diagnosis code that specifies the underlying condition. Value code 49
must be used for reporting the hematocrit. For non-dialysis patients,
administration charges may be billed using procedure code 90782 or 90784
if no other physician service is provided to the beneficiary on the same
day.
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Chronic Renal Failure
1. General
a. Coverage and reimbursement for epoetin in the setting of ESRD is
specified in the Medicare regulations with detailed instructions that do
not apply to other hematinics or other clinical situations.
b. Epoetin is a covered service for treatment of anemia when other
treatable causes of anemia are identified and treated and when the
continued anemia is presumed to be caused by chronic renal failure. This
includes patients on dialysis and those not on dialysis.
c. Coverage for epoetin in the setting of ESRD can be:
- Covered by Part A as an add-on payment to
the composite rate when it is administered in the renal dialysis
facility.
- Covered by Part B when administered
"incident to" a physician's service in a clinic or office
setting. (When administered in a physician office epoetin is billed
to the Carrier.)
- Covered as a DME benefit when
administered to a home dialysis patient. (When administered to a home
dialysis patient using method 1 epoetin is billed to the intermediary
whereas method 2 patients' epoetin is billed to the regional DME
contractor.)
d. Coverage for epoetin in the setting of CRF (non-dialysis) only exists
when administered "incident to" a physician's service in a clinic
or office setting.
2. Initiation of Therapy
Epoetin is only initially indicated if:
a. The patient carries a diagnosis of ESRD and is on dialysis OR has CRF
(pre-dialysis) with a creatinine clearance of 45 ml/min or less.
b. The patient has a hematocrit level that is 30 % or less (Hgb <= 10)
predialysis or a persistent hematocrit less than 33% (Hgb <11) on
dialysis, unless medical documentation justifies a patient's need for
epoetin with a higher hematocrit in order to prevent complications or
adverse symptoms of:
- severe angina or CHF (coronary
insufficiency syndromes);
- significant persistent and uncorrectable
hypotension;
- severe pulmonary disease
recurrent transfusions, as demonstrated by prior multiple
transfusions
c. Prior evaluation for and exclusion of other treatable causes of anemia
has been performed
d. Therapy for other contributing conditions has been already initiated.
e. If the transferrin saturation is less than 20% and the serum ferritin is
less than 100mg/ml, appropriate iron supplementation has been initiated.
f. Appropriate nutritional intervention has been initiated
3. Maintenance therapy
Based on the 2000 Dialysis Quality Initiative (K/DOQI), the hematocrit
should be maintained in the mid thirties, targeted to a level between 33
and 36 percent (Hgb 11-12). Higher hematocrits may be medically necessary
in certain instances (e.g., high altitudes, above 6000 ft., may require
higher HCT levels to avoid adverse effects); the benefits of higher levels
in typical cases appear promising but unconfirmed. In other situations,
such as the setting of ischemic heart disease or CHF, higher hematocrit
levels, may have some associated increased risk. Supporting medical
documentation to justify average levels greater than 37.5% (12.5gm/dl) must
be present in the record and available upon request.
Follow-up treatment should include an evaluation of both the effectiveness
and continued necessity for epoetin, at the administered dose, including
periodic evaluations of serial hematocrits to confirm that any unusually
high doses remain necessary to sustain a given level of response.
Secondary anemia
1. Initiation of therapy
Epoetin is covered for the treatment of symptomatic anemia that is
secondary to:
- anti-neoplastic/anti-metabolite drug
therapy,
- anemia of chronic disease (e.g.
non-myeloid malignancies, Rheumatoid Arthritis)
- myelodysplastic syndromes.
Epoetin is not covered for the treatment of low laboratory values but only
for significant symptomatic anemia associated with a marked reduction in
activities of daily living; the presence of significant clinical symptoms
is considered at least as important as those abnormal laboratory values.
Typical symptoms include weakness, syncope, tiredness, dyspnea, chest pain,
postural hypotension and tachycardia. It can be also covered for anemia
associated with a significant increased medical risk (e.g. increased risk
of MI) due to comorbid conditions or to decrease the need for transfusions
in patients who have previously required multiple transfusions for
symptomatic anemia.
Epoetin is initially indicated only for anemia with a hematocrit of less
than 30 (Hgb < 10 g/dl). Epoetin can be initiated at higher hematocrits
if the patient has associated severe heart, lung or cerebrovascular disease
or a history of frequent transfusions. Documentation must be submitted with
claims to justify medical necessity. An initial low serum epoetin level
provides critical supporting evidence of medical necessity, and
documentation of the pre-treatment level is required. For an optimal
response, a serum epoetin level of 200 mu/ml or less is suggested and
treatment for an anemia with a level greater than this is not recommended
in the labeled instructions and is therefore not usually covered except in
AZT related anemia. Treatment for patients with levels between 200-500 mu/ml
is occasionally medically necessary; these instances may require a review
of the documentation in the clinical record for evidence that clearly
establishes unique and unusual medical necessity.
2. Maintenance therapy
Most studies of efficacy are based upon target ranges in the mid thirties
or a sufficient hematocrit to alleviate signs and symptoms. Supporting
medical documentation to justify average levels greater than 37.5 must be
present in the record in the unusual instance where higher levels are required.
The medical literature does not support the routine maintenance of
hematocrits greater than 37, or maintenance of hematocrits greater than 40
in any situation. Dosages in excess of 300 U/kg 3x/week are seldom
medically necessary and would be expected to be supported by a clear and
compelling objective rationale.
After the target hematocrit or the maximal usual dosage has been reached
for a given indication, continued therapy will be considered medically
necessary if the hematocrit remains at least four points above baseline AND
the documentation supports that the initial symptoms were substantially
ameliorated. Alternatively epoetin will remain indicated if the need for
transfusion was substantially reduced.
Once appropriately started, epoetin administration will be presumed to be
necessary during an entire course of chemotherapy even if the above goals
are not met. However, epoetin coverage will stop three months after cancer
chemotherapy is discontinued even if those goals are met. (If the symptomatic
anemia returns with the cessation of the epoetin, it may need to be
reintroduced under the indication for anemia of chronic disease.) A single
weekly administration of epoetin will be allowed as long as it is dose
appropriate for the patient.
Epoetin will not be covered for prophylactic use to prevent the initial
development of anemia or to prevent transfusions entirely; it will be
denied as medically unnecessary in these instances.
Follow-up treatment should include an evaluation of both the effectiveness
and continued necessity for epoetin, at the administered dose, including
periodic evaluations of serial hematocrits to confirm that any unusually
high doses remain necessary to sustain a given level of response.
Evaluation for possible discontinuation of the epoetin is anticipated if
the underlying cause is ameliorated, modified or removed or the patient has
been on chronic therapy for an indication that naturally experiences
exacerbations interspersed with partial remissions.
3. Self administration
Epoetin cannot be reimbursed when self-administered (outside of the setting
of home dialysis) as there is no benefit for self-administered medications.
Coverage for epoetin for indications unrelated to ESRD (dialysis) only
exists when it is administered "incident to" a physician's
service, typically in a clinic or office setting. Note that even this
limited coverage only exists if the medication is determined to be
"not generally self-administered" in accordance with PM AB-02-072.
Note on "Incident To" Coverage: Epoetin, whether
administered sc or iv, is considered not generally self-administered at the
time of publication for this policy. A non self-administered drug is
covered as long as it is administered by a licensed healthcare provider
incident to the services of the physician. "Incident to" services
require the general supervision of the physician in the clinic environment
but require actual physician presence in other outpatient (e.g. Part B SNF)
settings. However, even if epoetin is covered under the "incident
to" provision, its payment may be bundled under a global payment
rather than paid as a separate pass-through payment. The current coverage
status of specific drugs under the "incident to" provision is
posted on the Self-Administered Drugs page of the Riverbend website.
Anemia associated with Malignancy
Epoetin is indicated in the treatment of anemia for patients with
non-myeloid malignancies both when the anemia is due to the effect of
concomitantly administered chemotherapy and when the anemia is secondary to
the malignancy itself. However, there is insufficient evidence to support
the efficacy of epoetin when used to support hematopoesis during radiation
therapy.
a. Anemia related to multiple myeloma is similarly and specifically covered
whether or not chemotherapy is being used.
b. Epoetin is not covered during or within three months of the completion
of a course of radiation therapy.
c. Epoetin for treatment of myeloid malignancies is not covered. The
following diagnoses are considered to be classified as myeloid malignancies
and therefore are non-covered:
- Myeloid leukemia 205.00-205.91;
- Monocytic leukemia 206.00-206.91;
- Other specified and unspecified leukemias
207.00-208.91;
- Personal history of myeloid leukemia
V10.62. (May occasionally be approved with documentation if the
myeloid leukemia is in complete remission AND the indication for
epoetin is unrelated to either the myeloid leukemia or its treatment.)
Ziduvidine Induced Anemia
HIV infected patients taking the antiviral drug AZT (Ziduvidine) generally
develop anemia. This anemia frequently responds to exogenous epoetin
therapy in the individuals who were receiving AZT doses of 4200 mg or
less/week, and whose endogenous levels of epoetin are 500 MU/ml or less.
Patients with AZT induced anemia whose endogenous serum epoetin levels are
more than 500 MU/ml do not appear to respond to this therapy.
Epoetin is covered for the treatment of anemia in patients receiving AZT
for acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC)
when endogenous epoetin levels have been documented at 500Mu/ml or less.
Although starting doses may be higher for this indication, target values
and maximal dosages are not significantly different from other secondary
anemias.
Epoetin therapy is covered not for the laboratory diagnosis of anemia but
only for symptomatic anemia. Symptomatology must be particularly well
documented to validate medical necessity of higher Hgb/Hct levels than those
noted above.
Epoetin therapy is covered up to three months after cessation of the AZT.
Anemia of Chronic Disease
Chronic disease for this purpose is defined as one that is persistent and
inflammatory in nature. This includes rheumatoid arthritis, ulcerative
colitis and other autoimmune diseases, but may also include chronic
infections that have been refractory to treatment.
These anemias are usually characterized by low serum iron, low iron-binding
capacity, increased tissue iron stores, and a reduced rate of red cell
production. However they are usually not severe and are only rarely
symptomatic or require therapy.
Medicare will cover the use of epoetin for symptomatic anemia associated
with chronic disease when the pretreatment HCT level is 30 percent or less
and when the pretreatment epoetin level is 200 MU/ml or less (or between
200 and 500 with supporting evidence of unusual medical necessity), or if
the patient has been transfusion dependent for at least three months and
the anemia is showing no signs of spontaneous improvement.
Myelodysplastic Syndrome
Myelodysplastic syndromes are a heterogeneous group of hematological
malignancies characterized by dysplastic (abnormal) and ineffective
hematopoiesis (blood cell production) and a variable risk of transformation
to acute leukemia. This creates a refractory anemia, i.e. a deficiency of
RBC production that cannot be assigned to a specific vitamin or mineral
deficiency.
For clarification, terminology that may be used on the bone marrow biopsy report
to define myelodysplastic conditions are as follows:
- Myelodysplastic disease, disorder, or
syndrome
- Myelodysplasia
- Refractory anemia
- Refractory anemia with ringed
sideroblasts; Sideroblastic anemia
- Increased stainable iron stores with
ringed sideroblasts
- Refractory anemia with excess blasts
- Refractory anemia with excess blasts in
transition (to acute leukemia)
- Pre-leukemia, pre-leukemic syndrome
- Erythroid hyperplasia with
dyserythropoiesis
- Chronic myelodysplastic leukemia
- Dysmyelopoietic syndrome
- Refractory dysmyelopoietic anemia
- Myeloid dysplasia
- Subacute myeloid leukemia
Epoetin is covered for treatment of refractory anemia in patients with
Myelodysplastic Syndrome who meet the following criteria:
1. There is a pathologic diagnosis of a myelodysplastia associated with a
refractory anemia. When this is further classified as "in
transformation to leukemia" there must be a medical contraindication
to active treatment of the acute leukemia.
2. Hemoglobin (Hgb) less than 10 g/d1 or Hematocrit < 30% and a
endogenous erythropoietin serum level less than 200 mu/ml (or between 200
and 500 with supporting evidence of unusual medical necessity).
3. Patients who have a reasonable expectancy of at least 3 month survival.
4. Patients who exhibited significant symptoms of anemia or have required
frequent transfusions.
Therapy should commence with a 6-week trial period as treatment with
erythropoietin increases the hematocrit in only 25% of treated patients. If
the patient responds to treatment, as evidenced by a statistically
significant rise in Hgb and HCT levels, the patient may continue therapy
until the Hgb is 12 or higher or the HCT is 36% or higher. If, after 6
weeks, the patient's Hgb has not risen by greater than 1 Gm or the HCT has
not risen by greater than 3 points, it would be determined that the anemia
is unresponsive to epoetin therapy and further treatment with epoetin would
not be medically indicated. However, the ultimate determinant of
therapeutic response is the amelioration of symptoms and/or a reduction in
the need for transfusions.
After an initial response therapy may be restarted when the Hgb drops to 10
or the HCT to 30 or may be restarted sooner if significant symptoms recur.
Pre-operative Hyperstimulation
The Canadian Orthopedic Perioperative Study Group clinical trial on
effectiveness of perioperative recombinant human erythropoietin in elective
hip replacement demonstrated that erythropoietin therapy resulted in a greater
reduction in exposure to allogeneic blood during orthopedic surgery in
patients who received erythropoietin than those who received placebo.
Goodnough, et. al., demonstrated that the equivalent of one unit of blood
is produced by day seven, and the equivalent of five units is produced by
day 28. Since the equivalent of three-five units of blood in patients
undergoing complex procedures such as orthopedic joint-replacement surgery,
the preoperative interval necessary for erythropoietin-stimulated erythropoiesis
can be estimated to be two to four weeks.
Goodnough, Monk, Andrioli "suggest that erythropoietin therapy is
indicated in patients scheduled for surgery with estimated blood losses of
1000 to 3000 ml and initial hematocrits of 33-39%…". At this time,
coverage is being extended for only for correction of anemia in those
patients scheduled for elective hip and knee surgery who meet coverage
criteria as defined in this policy.
The record must reflect:
1. A prior work-up establishing a diagnosis of an anemia of chronic
disease, as broadly defined, and excluding causes that are either
epoetin-unresponsive or treatable by more
conventional means. Excludable causes include:
- correctable nutritional deficiencies
(e.g. Iron, B12, etc.)
- blood loss
- hereditary anemia or hemoglobinopathy
- hemolytic disease
2. The hemoglobin must be between 10-13 gm/dl (Hct = 30% to 39%).
3. The proposed surgical procedure (hip or knee) must be expected to
produce a blood loss of more than two units.
4. The patient is not a candidate for autologous blood transfusion.
5. At least three weeks of lead time are available for treatment prior to
surgery.
6. The dose of erythropoietin should be:
- calculated based on the volume of blood
that is expected to be lost (and therefore replaced)
- targeted to a final goal of Hgb15 gm/dl
(Hct 45%)
- administered subcutaneously in weekly
doses prior to surgery (e.g., days 21, -14, -7). An additional (4th)
dose on the day of surgery will also be covered.
General exclusions
Epoetin is indicated only in the treatment of anemia as detailed above. It
will not be covered to treat other types of anemia, including iron or
folate deficiency, hemolysis, ongoing occult blood loss, or any other
indication not specifically by this policy. Patients should have at least a
three-month life expectancy to qualify for care.
Reasons for Denial:
- Non-FDA approved uses and off-label uses not supported by
peer-reviewed literature (Investigational).
- Failure to comply with the indications and limitations of the
policy.
- Utilization (dosages, frequency and target hematocrits) that
is inconsistent with standard care as detailed in this policy (not
medically necessary).
- Failure to provide documentation as requested.
- Continued non-ESRD use after failure to respond to an
adequate trial.
- Usage to prevent anemia is preventative care and not covered.
- Treatment with epoetin prior to addressing
correctable deficiency states is not medically necessary.
- Use as an alternative to transfusion for patients who refuse
transfusions for religious or other reasons.
- Epoetin use is not medically necessary
when used as a pre-surgical procedure:
1. to increase the amount of blood which can be drawn for auto-donation
prior to surgery
2. to prime a patient prior to surgery in anticipation of postoperative
anemia
3. when the time between initiation of epoetin and the surgery is less than
3 weeks, or the surgery is not elective
4. for any surgical procedure other than hip or knee surgery
Medicare will consider changing its coverage when additional supportive
data and peer-reviewed literature support the safety and effectiveness of
epoetin injections for the treatment of radiation oncology with or without
chemotherapy. Other coverage changes, such as higher target hematocrits for
ESRD patients, will similarly be entertained as new evidence-based medical
literature accumulates. New literature to support coverage changes are
encouraged; physicians should submit these to the Contractor Medical
Director along with their own clinical insight.
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