Department of Health and Human Services 
OFFICE OF 
INSPECTOR GENERAL 
M A P
EDICARE  NTIGEN  REPARATION 
JANET REHNQUIST 
Inspector General 
October 2002 
OEI-09-00-00530  Office of Inspector General

http://oig.hhs.gov 
The mission of the Office of Inspector General (OIG), as mandated by Public Law 95-452, as 
amended, is to protect the integrity of the Department of Health and Human Services (HHS) 
programs, as well as the health and welfare of beneficiaries served by those programs.  This 
statutory mission is carried out through a nationwide network of audits, investigations, and 
inspections conducted by the following operating components: 
Office of Audit Services 
The OIG's Office of Audit Services (OAS) provides all auditing services for HHS, either by 
conducting audits with its own audit resources or by overseeing audit work done by others. 
Audits examine the performance of HHS programs and/or its grantees and contractors in 
carrying out their respective responsibilities and are intended to provide independent 
assessments of HHS programs and operations in order to reduce waste, abuse, and 
mismanagement and to promote economy and efficiency throughout the department. 
Office of Evaluation and Inspections 
The OIG's Office of Evaluation and Inspections (OEI) conducts short-term management and 
program evaluations (called inspections) that focus on issues of concern to the department, the 
Congress, and the public.  The findings and recommendations contained in the inspections 
reports generate rapid, accurate, and up-to-date information on the efficiency, vulnerability, and 
effectiveness of departmental programs. 
Office of Investigations 
The OIG's Office of Investigations (OI) conducts criminal, civil, and administrative 
investigations of allegations of wrongdoing in HHS programs or to HHS beneficiaries and of 
unjust enrichment by providers.  The investigative efforts of OI lead to criminal convictions, 
administrative sanctions, or civil monetary penalties.  The OI also oversees state Medicaid fraud 
control units, which investigate and prosecute fraud and patient abuse in the Medicaid program. 
Office of Counsel to the Inspector General 
The Office of Counsel to the Inspector General (OCIG) provides general legal services to OIG, 
rendering advice and opinions on HHS programs and operations and providing all legal support 
in OIG's internal operations.  The OCIG imposes program exclusions and civil monetary 
penalties on health care providers and litigates those actions within the department. The OCIG 
also represents OIG in the global settlement of cases arising under the Civil False Claims Act, 
develops and monitors corporate integrity agreements, develops model compliance plans, 
renders advisory opinions on OIG sanctions to the health care community, and issues fraud 
alerts and other industry guidance.  Department of Health and Human Services 
OFFICE OF 
INSPECTOR GENERAL 
M A P
EDICARE  NTIGEN  REPARATION 
JANET REHNQUIST 
Inspector General 
October 2002 
OEI-09-00-00530  Office of Inspector General

http://oig.hhs.gov 
The mission of the Office of Inspector General (OIG), as mandated by Public Law 95-452, as 
amended, is to protect the integrity of the Department of Health and Human Services (HHS) 
programs, as well as the health and welfare of beneficiaries served by those programs.  This 
statutory mission is carried out through a nationwide network of audits, investigations, and 
inspections conducted by the following operating components: 
Office of Audit Services 
The OIG's Office of Audit Services (OAS) provides all auditing services for HHS, either by 
conducting audits with its own audit resources or by overseeing audit work done by others. 
Audits examine the performance of HHS programs and/or its grantees and contractors in 
carrying out their respective responsibilities and are intended to provide independent 
assessments of HHS programs and operations in order to reduce waste, abuse, and 
mismanagement and to promote economy and efficiency throughout the department. 
Office of Evaluation and Inspections 
The OIG's Office of Evaluation and Inspections (OEI) conducts short-term management and 
program evaluations (called inspections) that focus on issues of concern to the department, the 
Congress, and the public.  The findings and recommendations contained in the inspections 
reports generate rapid, accurate, and up-to-date information on the efficiency, vulnerability, and 
effectiveness of departmental programs. 
Office of Investigations 
The OIG's Office of Investigations (OI) conducts criminal, civil, and administrative 
investigations of allegations of wrongdoing in HHS programs or to HHS beneficiaries and of 
unjust enrichment by providers.  The investigative efforts of OI lead to criminal convictions, 
administrative sanctions, or civil monetary penalties.  The OI also oversees state Medicaid fraud 
control units, which investigate and prosecute fraud and patient abuse in the Medicaid program. 
Office of Counsel to the Inspector General 
The Office of Counsel to the Inspector General (OCIG) provides general legal services to OIG, 
rendering advice and opinions on HHS programs and operations and providing all legal support 
in OIG's internal operations.  The OCIG imposes program exclusions and civil monetary 
penalties on health care providers and litigates those actions within the department. The OCIG 
also represents OIG in the global settlement of cases arising under the Civil False Claims Act, 
develops and monitors corporate integrity agreements, develops model compliance plans, 
renders advisory opinions on OIG sanctions to the health care community, and issues fraud 
alerts and other industry guidance.   E X E C U T I V E  S U M M A R Y  
OBJECTIVE 
To determine if the Centers for Medicare & Medicaid Services (CMS) reimbursement policy 
for the provision of antigens for allergen immunotherapy accurately reflects the resources used 
in a typical physicians practice. 
BACKGROUND 
Allergies, hypersensitive immune reactions to substances that are otherwise harmless, afflict one 
in six Americans. Substances which can trigger allergies are called antigens, and include such 
things as dust, molds, and pet dander.  Symptoms range from mild irritation to life-threatening 
anaphylaxis. Medicare pays for the treatment of allergies through allergen immunotherapy, or 
allergy shots. In this therapy, a physician administers gradually increasing concentrations of an 
antigen in order to desensitize the patient. Treatment generally lasts from 3 to 5 years. 
The preparation of antigens for allergy shots, but not the injection itself, is billed under Current 
Procedural Terminology (CPT) code 95165,  professional services for the provision of 
antigens for allergen immunotherapy; single or multiple antigens, per dose. Traditionally, 
a dose was defined as the amount of serum administered in each allergy shot.  In 1998, the 
CMS revised the definition to be the total amount of serum delivered each treatment session, 
regardless of the number of shots. After receiving many comments from specialty 
organizations, the CMS changed the definition in the November 1, 2000 Federal Register, 
effective January 1, 2001, to a one cc aliquot [part] from a single multidose vial. 
We conducted a survey of a stratified random sample of 306 physicians who provide allergen 
immunotherapy. We received responses from 186 of these for a response rate of 60.8 percent. 
In addition, we conducted follow-up interviews with several sample physicians, interviewed and 
reviewed documentation from 25 of 27 Medicare carriers, and reviewed the Medicare law, 
regulation, and policy related to CPT code 95165. 
1 
Antigen Preparation  OEI-09-00-00530  FINDINGS 
Resources used in allergen immunotherapy differ from CMS assumptions 
Based on our analysis, we found that data used by CMS to calculate practice expense inputs 
for CPT code 95165 are not accurate.  The CMS estimates that in a typical practice, 
physicians provide immunotherapy from 10 cc multidose vials in shots of 1 cc each.  We found 
that the median vial size is 4.9 cc and the median injection volume is 0.47 cc. In addition, while 
the current calculations assume 5 antigens are in each vial of immunotherapy, we found that a 
typical vial contains approximately 8 antigens.  Lastly, while the new definition of a dose 
incorporates 2.2 minutes of clinical staff time, our research indicates that each dose requires 3.0 
to 4.5 minutes to prepare. Practice expense calculations for CPT code 95165 do not factor in 
the dilution boards the typical provider creates, but the allocation per unit for this expense 
would probably be minimal. 
Almost 75 percent of providers are aware of the new definition of a dose 
Nearly three-quarters of immunotherapy providers know about the revision, mainly through 
their specialty society.  However, only 44 percent of all immunotherapy providers have 
changed their billing as a result. In addition, although the revision was intended for practice 
expense calculation and billing purposes only, approximately 14 percent of immunotherapy 
providers have begun giving 1 cc injections or changed other practice patterns. Providers 
generally prefer the traditional definition of a dose as the amount of antigen given in a single 
injection over the current or an alternate definition. 
CONCLUSION 
Based on our analysis of data and information from a random sample of allergists, we conclude 
that CMS did not have accurate data when it calculated the practice expense component for 
CPT code 95615. After consulting with CMS, we conclude that CMS should use this report 
to help refine the practice expense inputs for this code as part of their normal process rather 
than making an immediate change. Since some physicians modified their practice based on the 
changes in reimbursement, CMS should emphasize that physicians need modify only their billing 
to comply with the new definition in any guidance it plans to offer in the future. We also noted 
that most physicians rely on their specialty societies, rather than CMS or its carriers, for 
information about Medicare policy changes.  Therefore, to ensure physicians are getting 
accurate information, CMS and the carriers may want to work directly with the societies to 
explain any policy changes and revisions. 
2 
Antigen Preparation  OEI-09-00-00530  T A B L E  O F  C O N T E N T S  
PAGE

EXECUTIVE SUMMARY ......................................................1

INTRODUCTION

Background .............................................................4

Methodology ............................................................7

FINDINGS 
Typical immunotherapy practices  .............................................9

Practice expense inputs inaccurate  ...........................................11

Providers aware of revision  ................................................13

CONCLUSION  ............................................................. 16

APPENDICES

Appendix A:  Glossary of Terms .............................................17

Appendix B:  Confidence Intervals for Selected Statistics  ..........................18

Appendix C:  P-values for Selected Comparisons ................................21

ACKNOWLEDGMENTS ..................................................... 22

3 
Antigen Preparation  OEI-09-00-00530  I N T R O D U C T I O N  
OBJECTIVE 
To determine if the Centers for Medicare & Medicaid Services (CMS) reimbursement policy 
for the provision of antigens for allergen immunotherapy accurately reflects the resources used 
in a typical physicians practice. 
BACKGROUND 
Allergies and Their Treatment 
Allergies afflict one in six Americans. People with allergies experience hypersensitive immune 
system responses to substances, called allergens, which are harmless to non-allergic people. 
Common allergens include pollen, mold, and animal dander. Allergens are a type of antigen, 
which is any foreign substance which triggers an immune response, including substances which 
are universally harmful like pathogenic viruses and bacteria. Allergy symptoms range from mild 
irritation to anaphylaxis, a medical emergency involving an acute systemic allergic reaction. 
The CMS pays for allergy testing of Medicare beneficiaries and for their treatment through 
allergen immunotherapy.  In this treatment, more commonly known as allergy shots, a physician 
administers gradually increasing amounts of an allergen to the patient over a period of several 
weeks. Upon reaching a maintenance level, the patient continues to receive injections on a 
regular basis, generally for at least 3 to 5 years. Allergy shots are normally reserved for those 
patients experiencing intolerable symptoms that do not respond to other therapies. 
Allergists and immunologists, who specialize in the diagnosis and treatment of allergies, provide 
the bulk of allergen immunotherapy services for Medicare beneficiaries. In addition, many 
otolaryngologists (commonly known as ear, nose, and throat doctors, or ENTs) treat allergies, 
especially those affecting the respiratory system.  General internists, family practitioners, and 
other physicians also provide some immunotherapy services.1 
The practice of immunotherapy varies among providers. In one common mode, a physician 
creates a treatment set by first creating a vial containing the specific antigen mix for a given 
patient.  From that vial, the physician then makes multiple diluted vials to 
1
In this report, we will refer to allergists and immunologists as general allergists and otolaryngic allergists 
as otolaryngic allergists or ENT allergists. 
4 
Antigen Preparation  OEI-09-00-00530  provide lower concentration mixes that will be needed to step up the patient to the 
maintenance level. 
Alternatively, a provider may create a treatment or dilution 
Figure 1:  Dilution Board 
board as a first step in administering allergy shots (see 
Figure 1).  As with treatment sets, boards contain multiple 
dilutions of antigens. Rather than dilutions specific to each 
patient, however, the provider creates diluted vials of each 
antigen serum used in his or her practice.  The doctor may 
then draw particular antigens from the board and mix them 
in a multidose vial to be used for a given patient over 
multiple treatment sessions; alternatively, the doctor may 
then treat off the board, meaning he or she mixes and 
delivers each injection individually and directly from the board. 
Instead of using his or her own treatment sets or boards, a provider may choose to order 
treatment vials for each patient from a supplier, and perform only injection and observation 
services. No matter what practice is employed, antigen mixes have a finite shelf life, which is 
inversely proportional to their strength, and must be discarded if not used within a certain time. 
Payment for Physician Services 
Since 1992, Medicare has paid for physician services under a national fee schedule. Under this 
strategy, each medical procedure is assigned a relative value which measures the cost to 
perform the service compared to the cost to perform other covered services.  Three factors 
determine the relative value of a service: physician work, practice expense, and malpractice 
expense. The physician work component, which is a measurement of the time, intensity of 
effort, and skill required for a service, constitutes 55 percent of the total value.  Practice 
expense, which is 42 percent of the total, estimates the costs of doing business for a physician, 
including such expenses as staff salaries, overhead, and supplies.  Malpractice expense, i.e., the 
cost of physician liability insurance, represents the remaining 3 percent.  Payment for a given 
service is a function of its relative value and a geographic index based on the location where the 
service was provided. 
The American Medical Associations Relative Value Update Committee was formed in 1991 to 
provide input on relative value units.  In addition to recommending work inputs, the Committee 
comments on CMS proposed interim relative value units.  The Committee is comprised of 29 
members, most of whom represent major specialty societies, including otolaryngology, but not 
allergy/immunology.  An advisory commission embodying each of the 98 specialties in the 
Associations House of Delegates provides support for the Committee. 
5 
Antigen Preparation  OEI-09-00-00530  The Association plays another important role in fee schedule payments by appointing the panel 
that maintains the list of Current Procedural Terminology (CPT) codes which are used by 
providers to bill Medicare. The CMS adopted CPT codes in 1983 as part of its Common 
Procedure Coding System.  More 
than 7,000 codes appear in the current 
edition of the CPT manual.  Table 1:  Median 95165 billing by specialty 
Per unit 
CPT Code 95165  Allowed 
Specialty  Year  Units  allowed 
amount 
amount 
Medicare allowed approximately 
General  2000  $20.00  2.00  $8.35 
$98 million in charges for allergen 
allergists 
2001  $24.90  3.00  $9.00 
immunotherapy codes in 2000. 
Nearly half of these charges,  ENT  2000  $70.00  10.0  $8.14 
$47 million, were for CPT code  allergists 
2001  $80.00  10.0  $8.65 
95165, professional services for the 
Other  2000  $22.36  2.00  $8.36 
provision of antigens for allergen 
physicians 
immunotherapy; single or multiple  2001  $21.90  2.00  $8.82 
antigens, per dose. This code 
describes the preparation of antigen 
serums for use in immunotherapy, but not their injection. General allergists submitted about 
two-thirds of the claims for CPT code 95165, and ENT allergists account for about 20 
Figure 2: 
percent.  Most of the remainder come from internists, general practitioners, family doctors, and 
Vial and 
various group practices.  Although per unit allowed charges are fairly constant across different 
10 cc Syringe 
specialties, ENT allergists bill more units (and receive greater reimbursement) per claim than 
other specialties (see Table 1). 
The interpretation of CPT code 95165 has been controversial.  The code is unlike others in that 
it includes the concept of a dose, which is not defined in the CPT manual. Traditionally, 
providers and payers defined a dose as the amount of antigen given in a single injection. In May 
1998, CMS updated the carrier manual to define a dose as the total amount of antigen to be 
administered to a patient during one treatment session, whether mixed or in separate vials. 
Private payers, however, did not adopt this change; as a result, they paid 590 percent more per 
unit of CPT code 95165 than Medicare in 1999.2 After this change was instituted, the Relative 
Value Scale Update Committee recommended that CMS return to the traditional definition for 
the 1999 fee schedule update.  At the time, though, CMS did not feel a revision was 
appropriate because the Committee failed to comment on the direct practice expense inputs to 
the code.  In November 2000, after receiving many comments from specialty organizations, 
CMS revised the inputs for CPT code 95165. In this revision, effective January 1, 2001, 
CMS defines a dose, for billing and practice expense calculations, as a one cc aliquot [part] 
2
In fact, according to OIG analysis, private payers pay significantly more for nine allergen immunotherapy 
codes than Medicare, and significantly less for the CPT injection codes 95115 and 95117. 
6 
Antigen Preparation  OEI-09-00-00530  from a single multidose vial.3 All practice expense inputs for CPT code 95165 are based on 
this definition, although no allocation is made for resources and work used to create treatment 
or dilution boards. 
METHODOLOGY 
Survey 
We used a mail survey as the primary tool to accomplish the purpose of this study.  The survey 
solicited mainly factual information on physicians practice patterns, including the time and 
resources used in preparing and administering allergy shots. We conducted extensive pre-
testing of the survey instrument to ensure that we were using accurate and understandable 
terminology and to improve the clarity and logical flow of the questions. 
We used a stratified random sample to select physicians to whom we sent the survey.  From 
2001 National Claims History (NCH) data, we defined our universe as physicians appearing on 
claims for CPT code 95165 allowed in an office setting. These physicians were divided into 
three strata: allergists and immunologists in the first stratum, otolaryngologists in the second, 
and general practitioners, family doctors, internists, and group practices and clinics in the third. 
Together, these three strata accounted for 95 percent of the claims submitted for CPT code 
95165 in 2001. 
We randomly selected 102 physicians from each stratum to participate in the survey. To obtain 
names and addresses for these physician, we ran a match against CMS unique provider 
identification number, or UPIN, master file and did our own internet research, which resulted in 
301 valid names and addresses. We sent surveys to each of these addresses and received 
Table 2:  Sample and response rate 
Physicians  Physicians  # of surveys  # of 
Stratum  # usable 
in universe  in sample  mailed  responses 
1 (Allergists)  2348  102  101  69  69 
2 (ENTs)  1974  102  101  65  61 
3 (Others)  1229  102  99  52  47 
Total  5551  306  301  186  177 
responses from 186 (60.8 percent).  Nine of these responses, 
3
Medicare does not accept separate CPT codes for physicians who treat off the board. These physicians 
submit claims based on the same 1 cc standard. 
7 
Antigen Preparation  OEI-09-00-00530  however, did not contain usable information.  Responses were weighted according to each 
stratums representation in the population. Our sample design and response rate were adequate 
to make projections to the universe with a reasonable degree of precision. Table 2 (previous 
page) shows selected information for the three strata. 
Responses to each survey question varied greatly; for instance, respondents reported using 
from 1 to 38 antigens in a multidose vial and injecting from .05 cc to 4.0 cc of serum in each 
allergy shot. Given this variation, we used the median as representative of a typical practice, 
since it is less affected by extreme values than the arithmetic mean. We received a large number 
of zero responses concerning questions about the amount of clinical staff time spent creating 
boards and vials and about the number of boards prepared in a year. For these questions, the 
median may not be an appropriate representation of a typical practice, so we include the mean 
as well. In all such cases, however, we were able to make comparisons among subgroups only 
with mean values. 
Non-respondent analysis. We used chi-square tests and linear regression to compare non-
respondents to respondents in terms of their stratum, year 2001 claims volume (of CPT code 
95165), Medicare patient volume, mean number of services per claim, mean number of 
services per patient, and population and urban/rural characteristics of the county in which they 
practice.  None of these tests was significant at the 95 percent confidence level. 
Other Data 
We interviewed 25 of the 27 Medicare carriers about guidance they received from CMS and 
any instructions they issued to their physician communities. We asked for copies of any written 
guidance distributed to providers, which we evaluated for completeness and clarity. Two 
carriers did not respond to numerous interview requests. 
In addition, we spoke to several representatives of national allergy associations and consulted 
with practicing physicians.  Several local allergists allowed us to observe the preparation of 
antigens and helped us develop our survey instrument.  Lastly, we reviewed laws, regulations, 
policy letters, and other materials related to CPT code 95165. 
This study was conducted in accordance with the Quality Standards for Inspections issued by 
the Presidents Council on Integrity and Efficiency. 
8 
Antigen Preparation  OEI-09-00-00530  F I N D I N G S  
We primarily used a national survey of a random sample of practitioners of allergen 
immunotherapy to develop the findings of this report.  In addition to the survey, we interviewed 
staff and evaluated guidance documents from Medicare carriers. Lastly, we reviewed policy 
and regulations concerning CPT code 95165 and spoke with allergen immunotherapy 
providers. Based on our analysis, we found that current practice expense calculations do not 
accurately reflect typical practices among immunotherapy providers. Also, while most 
providers are aware of the new definition of a dose for CPT code 95165, most say it does not 
correspond with the way they provide allergen immunotherapy. 
Physicians typically use dilution boards to prepare multidose 
vials 
Most physicians create several boards per year 
More than 75 percent of providers indicate that they create boards either for directly treating 
patients or as a first step in creating multidose vials.  Nearly all ENT allergists use boards in 
some fashion, compared to 63 percent of general allergists and 69 percent of other physicians. 
Regardless of specialty or mode of practice, 
Figure 3:  More ENT allergists create boards 
the typical provider prepares 3.6 (median; 
mean=7.6) boards per year.  Physicians in 
counties located entirely in metropolitan areas 
tend to prepare boards more often than their 
less urban counterparts, as do physicians who 
at least sometimes treat off the board.  In 
addition, physicians who provide allergen 
immunotherapy, but do not identify themselves 
as allergists, produce fewer boards than ENT 
or general allergists.4 
Physicians and their staff spend about 
46 minutes (median; mean=93 minutes) 
creating each board.  The greatest amount of 
time is attributed to registered nurses, though 
physicians, licensed vocational 
4
We found no evidence of a relationship at the 95 percent confidence level between the number of boards 
prepared and the number of the physician's patients on allergen immunotherapy. 
9 
Antigen Preparation  OEI-09-00-00530  nurses, medical assistants, and other staff, such as allergy technicians, sometimes contribute.5 
Otolaryngic allergists spend significantly more time (167 minutes) preparing each board than do
general allergists (66 minutes) or other specialties (63 minutes).  We found no evidence,
however, that the amount of staff time needed is associated with treating off the board.  In
addition, physicians who submitted a greater number of claims of CPT code 95165 tend to
take more time preparing boards.  This seems logical in that high-volume practices may require
more antigens or larger volumes of antigen on each board.6
 Fewer than 20 percent of providers treat off the board
Most physicians prepare multidose vials of Figure 4:  Fewer ENT allergists treat off the board
allergen immunotherapy from a treatment or
dilution board rather treat off the board. 
About 81 percent of physicians provide
immunotherapy exclusively from multidose
vials.  Another 14 percent use a combination
of treating off the board and vials, while only
5 percent treat exclusively off the board. 
Treating off the board is much less common
among ENT allergists (5.45 percent) than
either general allergists (26.6 percent) or
other specialties 
(24.8 percent).
Administering shots directly off the board is a
practice quite different from first creating
multidose vials for each patient.  As such,
treating off the board is an important factor in the outcomes of several other survey questions. 
Time spent preparing vials, the number of injections given per treatment session, and a
providers response to the January 2001 change all are influenced by this practice.  Each of
these effects will be discussed later in this report.
5
A single physician rarely uses all of these types of staff, but each type is used by at least one physician in
the sample.
6
This effect is independent of the specialty of the physician.
10
Antigen Preparation                                                         OEI-09-00-00530 More than three-fourths of physicians purchase their allergen immunotherapy 
supplies individually 
An overwhelming proportion (85.5 percent) of practitioners purchase immunotherapy supplies 
individually.  Even in group and clinic settings, more than three-quarters of physicians purchase 
their supplies independently. Physicians who submit a relatively large number of claims for CPT 
code 95615 (more than 50 in the first 6 months of 2001) are more likely to buy supplies on 
their own.  Only one respondent to the survey had a purchasing arrangement with other 
physicians outside his or her group. 
We followed up with nine physicians to determine why they did not enter into group purchasing 
arrangements.  Almost all identified the lack of standardized antigen serum across suppliers as a 
primary reason for maintaining individual arrangements.  They explained that serums differ 
across manufacturers and techniques for mixing antigens and diluent are directly related to type 
of serum obtained from a specific supplier.  Therefore, it would be difficult to get each physician 
in a group purchasing arrangement to agree to the same supplier.  According to our 
interviewees, since most physicians are able to negotiate some discounts on allergen 
immunotherapy supplies purchased individually, the difficulty in designing a group arrangement 
would likely outweigh any potential cost savings.  In fact, nearly half of those interviewed had 
considered group arrangements at some point, but had ultimately decided against them. 
Resources used in allergen immunotherapy differ from CMS 
assumptions 
The one cc aliquot accepted by

Table 3:  Resources used in a typical practice differ from assumptions

CMS as a typical injection of 
CPT code 95165 is much too  Resource  CMS Estimate  Survey Estimate 
large, according to our survey. 
Staff time  2.2 minutes  3.0 minutes 
We found that the median 
Vial size  10 cc  4.90 cc 
volume of an injection is 
about 0.47 cc, less than half the 
Number of antigens in  5  7.95 
figure in the Federal Register  vial 
(FR).7 About 48 percent of 
Antigen volume as  100%  59% 
physicians typically give  percentage of total 
injections of .5 cc, and another

Volume of injection  1.0 cc  0.47 cc 
31 percent inject even smaller

amounts. The specialty of the physician has a strong relationship with the size of injection they

765 FR 65393, November 1, 2000. 
11 
Antigen Preparation  OEI-09-00-00530  administer; 91 percent of ENT
Figure 5:  Vial size varies by specialty
allergists give injections of .5 cc or less,
compared to about 72 percent of other
physicians.  On average, physicians of
all specialties give 1.6 injections per
treatment session.  Physicians who treat
off the board tend to give more
injections, an average of 2.1 compared
to 1.5 for those who do not.
The January 2001 definition of a dose
assumes physicians typically draw
doses from a 10 cc multidose vial.  We
found that about 51 percent of
physicians use a 5 cc multidose vial in
their practice while only 31 percent use
a 10 cc vial.  The remaining 18 percent
of physicians are almost evenly divided between those that use vials of less than 5 cc capacity
and those that use vials of greater than 5 cc, but less than 10 cc.  A few respondents said they
use vials even larger than 10 cc.  The size of vial that is used is strongly correlated with the
specialty of the provider, as shown in Figure 5. Without regard to specialty, the median
capacity of a vial is 4.90 cc.
The Federal Register publication assumes that 5 antigens are present in a typical multidose
vial, without any diluent.  According to our survey, a typical multidose vial contains
approximately 8 antigens.  Providers in a clinic setting use more antigens than others:  11.7 on
average, compared to about 7.8 for solo practitioners or physicians in a single-specialty group. 
In addition, our survey indicates that a typical multidose vial contains only about 59 percent
antigen by volume; the rest is diluent.
According to our respondents, the current rule does not sufficiently account for the time needed
to create multidose vials.  The new definition of a dose incorporates 2.2 minutes of clinical staff
time as a practice expense.  Our survey data suggests that preparing antigens in a multidose vial
requires closer to 3.0 (median) to 4.5 (mean) minutes of staff time per dose.  Our limited visits
to physicians offices, however, suggest that this figure may be inflated; additional direct
observation would be needed to confidently report the amount of time required.  As with
boards, our respondents attribute the greatest portion of time spent creating vials to registered
nurses.  Physicians who sometimes treat off the board in addition to using multidose vials
dedicate less staff time (2.9 minutes per dose) to creating a vial than those that exclusively use
vials (4.8 minutes per dose).
12
Antigen Preparation                                                         OEI-09-00-00530 Almost 75 percent of providers are aware of the new 
definition of a dose 
Providers primarily rely on their specialty society or association for information 
Nearly three-quarters of physicians who provide allergen immunotherapy are aware of the

January 2001 revision. A positive relationship exists between the number of patients for whom

the physician provides immunotherapy and their probability of being aware of the revision. 

Also, general allergists are more likely to know of the revision than ENT allergists, who, in turn,

are more likely than other providers to be aware of the change.

Specialty societies are important sources of information for providers.  Fifty-nine percent of

physicians first learned of the change from their society. In contrast, only 29 percent first

learned of the change from their Medicare carrier. Non-allergists make up a large part of this

group, reflecting their low rate of membership in allergy-related specialty societies.

Although relatively few physicians learned of the revision from their carrier, the

25 carriers we contacted all had received guidance from CMS on the new rule and had issued

a provider bulletin explaining the change. Approximately half of the carriers we interviewed

sent a newsletter to their physicians outlining the change and posted notices on their physician

web site; the remainder only mailed a newsletter or bulletin. The majority of carriers (22 of 25)

issued these instructions between November 2000 and January 2001, though one carrier did

not issue formal instructions until June 2001.

Most of the guidance issued by carriers reiterated the CMS guidance almost verbatim. We

found most of the written notices to be clear and easy to understand, although four notices

failed to adequately highlight information regarding CPT code 95165.  We found that one

notice was particularly confusing because it combined information for CPT code 95165 with

information for CPT code 95115. On the other hand, one carrier offered several clinical

examples in its bulletin to help clarify the new rule.

13 
Antigen Preparation  OEI-09-00-00530  The revised definition has led some physicians to change billing and medical 
practices 
Most physicians did not change their billing  Figure 6:  Physicians' response to revision 
or medical practice because of the new 
definition. Approximately 
57 percent of physicians were either 
unaware of the revision or did not make any 
changes in response to it.  Several of the 
latter group explained that they had already 
been billing Medicare according to the 
January 2001 definition before it went into 
effect. 
Fifty-four percent of physicians who were 
aware of the new definition changed their 
billing as a result.  About one-quarter of 
these physicians say they now bill 1 cc as a 
dose, as outlined in the Federal Register. 
Another 16 percent report that they no longer bill for dilutions. The remainder either did not 
specify the particular change or indicated a change other than the two listed above. 
Some experts expressed concern that the revision as published in the Federal Register would 
cause physicians to alter their medical practice as well as their billing. This concern is borne out 
somewhat by our data:  almost 20 percent of physicians who were aware of the new definition 
say they have changed how they administer allergen immunotherapy in response.  Some of these 
explained that they now administered 1 cc as a dose for each Medicare patient, while others 
altered other aspects of their practices.  The CMS, however, did not intend to dictate the 
practice of medicine and, in fact, issued an update to the carrier manual in September 2001 to 
clarify this point. 
Only 11 percent of practitioners prefer the new definition of a dose 
According to our survey, more practitioners (46.7 percent) prefer the traditional definition of a 
dose, the amount of antigen administered in a single injection, than any other. Only about 11 
percent feel that the definition should be based on a particular volume of antigen, as it is 
currently.  Seventeen percent of practitioners said that the definition of a dose should revert to 
the 1998 guidance of the total amount of antigen administered in an office visit. 
Many respondents, as well as physicians to whom we spoke in preinspection, offered specific 
recommendations for an improved definition. Several believe one of the main problems with 
both the past and current definitions is they do not account for time and 
14 
Antigen Preparation  OEI-09-00-00530  resources used to create treatment and dilution boards.  Others suggest that the definition lacks 
consideration for the different strength dilutions used in creating vials. Still others say that it is 
more appropriate to base the definition on the number and strengths of allergenic extracts used 
rather than a volume of serum, which could contain any number of allergens. Several providers 
expressed sympathy for CMS dilemma in defining a dose amid a wide variety of practices. 
15 
Antigen Preparation  OEI-09-00-00530  C O N C L U S I O N  
The CMS commented on the working draft of this report and concurred with our findings.  They 
indicated, however, that CMS will take no action at this time to address CPT code 95165. The 
CMS believes that using a 10 cc vial and 1 cc aliquots as the basis for practice expense 
calculations are not significantly different from using a 5 cc vial and 0.5 cc aliquots. Also, 
according to CMS, allocating the time and resources spent creating a dilution board to each 
individual dose would result in a minuscule, if any, change in payment.  The clinical staff time 
required per dose, as stated in the report, requires more study before it could be used as a basis 
for changing reimbursement.  The amount of antigen in a vial, however, is a practice expense 
issue that CMS has indicated they may address in the future. 
With CMS comments in mind, we conclude that although the agency did not have accurate data 
when it calculated the practice expense component for CPT code 95615, there is no compelling 
need for immediate change. Therefore, CMS could use the information in this report to help 
refine the practice expense inputs for CPT code 95165 as they see fit, perhaps in conjunction 
with the next meeting of the Practice Expense Advisory Committee.  Since some physicians 
modified their practice based on the changes in reimbursement, CMS could continue to 
emphasize that physicians need modify only their billing to comply with the new definition in any 
guidance it plans to offer in the future.  We also noted that most physicians rely on their specialty 
societies, rather than CMS or its carriers, for information about Medicare policy changes. 
Therefore, to ensure physicians are getting accurate information, CMS and the carriers may 
want to work directly with the societies to explain any policy changes and revisions. 
16 
Antigen Preparation  OEI-09-00-00530  A P P E N D I X  A  
Glossary of Terms 
Aliquot - A part of a whole which is a proper divisor of that whole [Websters]; used in the Federal 
Register definition of a dose to mean an extract from a multidose vial. 
Allergy - Reactions of the immune system to substances that, in most people, cause no symptoms. 
[AAAAI website] 
Allergen - A foreign substance that leads to allergies by starting an immune response. [AAAAI 
wesbite] 
Anaphylaxis -A medical emergency which involves an acute systemic allergic reaction. [AAAAI 
website] 
Antigen -A substance that can trigger an immune response. [AAAAI website] 
Diluent - A liquid used to dilute the strength of an antigen serum. 
Immunotherapy - (allergy shots) A form of preventive and anti-inflammatory treatment of allergy. 
Immunotherapy involved gradually increasing doses of allergen(s), causing a decrease in immune 
sensitivity to the allergen. [AAAAI website] 
Maintenance level - The maximum antigen concentration and volume tolerated by a patient and at 
which they will be given immunotherapy over a period of time. 
Multidose vial - A vial containing antigen serum intended to be used for multiple injections of a 
particular patient. 
Treatment or dilution board - A board used to store multiple vials of antigen serums at various 
concentrations, for use either in directly treating patients or in creating multidose treatment vials which 
are then used to treat patients. 
Treat off the board - Mix and inject shots directly from a treatment board rather than first creating 
multidose vials. 
Treatment set - A set of multidose vials, prepared for a single patient, which is made up of vials at 
various concentrations and used to step up the patient to a maintenance level. 
17 
Antigen Preparation  OEI-09-00-00530  A P P E N D I X  B 
Confidence Intervals for Selected Statistics

The following table shows the point estimates and 95 percent confidence intervals for selected 
statistics, in the order they appear in the findings.  In addition, the table shows point estimates 
and confidence intervals for both the median and mean, where applicable. These calculations are 
weighted according to the stratification described in the methodology. 
Point  95 Percent 
Statistic  N 
Estimate  Confidence Interval 
FINDING I 
Percent of physicians who use boards  177  75.37%  69.24% - 81.49% 
Mean number of boards prepared per year  146  7.56  4.46 - 10.66 
Median number of boards prepared per year  146  3.57  2.87 - 3.73 
Mean time (minutes) spent preparing each  154  92.50  75.34 - 109.67 
board 
Median time (minutes) spent preparing each  154  45.71  28.37 - 67.49 
board 
Percent of physicians who treat exclusively using  166  80.66%  74.81% - 86.50% 
multidose vials 
Percent of physicians who mix using vials and  166  14.12%  8.98% - 19.26% 
boards 
Percent of physicians who treat exclusively off  166  5.22%  1.87% - 8.58% 
the board 
Percent of physicians who purchase supplies  176  85.53%  80.57% - 90.48% 
independently 
Percent of physicians in group/clinic settings  91  78.16%  69.79% - 86.53% 
who purchase supplies independently 
FINDING II 
Mean volume (cc) of injection  172  .578  .505 - .651 
18 
Antigen Preparation  OEI-09-00-00530  A P P E N D I X  B 
Median volume (cc) of injection  172  .470  .463 - .477 
Percent of physicians who inject .5 cc  172  47.57%  40.18% - 54.96% 
Percent of physicians who inject < .5 cc  172  30.80%  23.93% - 37.66% 
Mean number of injections per session  172  2.36  1.99 - 2.73 
Median number of injections per session  172  1.59  1.50 - 1.69 
Percent of physicians who use a 5 cc vial  155  50.84%  43.22% - 58.47% 
Percent of physicians who use a 10 cc vial  155  31.13%  24.09% - 38.18% 
Percent of physicians who use a <5 cc vial  155  9.54%  4.85% - 14.24% 
Percent of physicians who use between a 5 and  155  7.03%  3.14% - 10.92% 
10 cc vial 
Percent of physicians who use a >10 cc vial  155  1.45%  <= 3.07% 
Mean vial capacity (cc)  155  6.91  6.33 - 7.49 
Median vial capacity (cc)  155  4.90  4.83 - 4.97 
Mean number of antigens per vial  155  9.84  8.84 - 10.83 
Median number of antigens per vial  155  7.95  7.61 - 9.91 
Antigen as a proportion of vial volume  151  58.9%  55.55% - 61.78% 
Mean time (minutes) to create a dose  147  4.45  3.69 - 5.22 
Median time (minutes) to create a dose  147  2.98  2.91 - 4.05 
FINDING III 
Percent of physicians aware of revision  177  73.84%  67.81% - 79.88% 
Percent of physicians who learned of revision  122  58.93%  50.50% - 67.35% 
from their specialty society 
Percent of physicians who learned of revision  122  29.03%  21.26% - 36.80% 
from their carrier 
Percent of physicians who were unaware of  177  56.53%  49.33% - 63.72% 
revision or did nothing in response 
19 
Antigen Preparation  OEI-09-00-00530  A P P E N D I X  B 
Percent of physicians who were unaware of  177  26.16%  20.12% - 32.19% 
revision 
Percent of physicians who did nothing in  177  30.37%  23.53% - 37.21% 
response 
Percent of physicians who changed practice  177  14.12%  8.87% - 19.37% 
Percent of physicians who changed billing  177  39.52%  32.39% - 46.65% 
Percent of aware physicians who changed  122  54.21%  45.45% - 62.97% 
billing 
 percent of above who now bill 1 cc as dose  71  23.39%  13.46% - 33.32% 
 percent of above who no longer bill dilutions  71  16.26%  7.37% - 25.09% 
 percent of above who made some other  71  63.63%  52.48% - 74.78% 
change 
Percent of aware physicians who changed  122  19.37%  12.33% - 26.41% 
practice 
Percent of physicians who prefer traditional  173  46.75%  39.40% - 54.09% 
definition 
Percent of physicians who prefer volume-based  173  11.15%  6.41% - 15.90% 
definition 
Percent of physicians who prefer 1998 definition  173  17.31%  11.59% - 23.03% 
20 
Antigen Preparation  OEI-09-00-00530  A P P E N D I X  C
P-values for Selected Comparisons
The following table 1 shows the results t-tests for selected comparisons.  Where we conducted
pairwise tests of multiple groups, the particular groups tested are displayed, as is the threshold
for determining significance (calculated using the Bonferroni method.)  We used "=0.05 for all
tests.
Comparison Group Statistic Threshold Result
Mean number of Rural counties 2.93 n/a
boards by
significant
urban/rural
Urban counties 8.82
character of county
Mean number of (1) General allergists  9.51 0.0167 vs.(3) - significant
boards by specialty,
pairwise (2) ENT allergists 6.96 vs.(3) - significant
(3) Non-allergists 2.43 -
Median number of Not off the board 1.51 n/a
injections by
significant
treating off the
Off the board 2.06
board
Number of antigens (1) Solo practitioner 7.81 0.00833 vs.(3) - significant
by type of practice
(2) Group practice 7.80 vs.(3) - significant
(3) Clinic 11.74 -
The next table shows a sample chi-square for the comparison between physicians specialty and
treating off the board.
Number of respondents
Specialty
Not off the board Off the board
General Allergist 60 (weighted=1278.77) 23 (weighted=463.63)
ENT Allergist 52 (weighted=1006.35) 3 (weighted=58.06)
Non-allergist 20 (weighted=292.14) 8 (weighted=96.39)
  Chi-square for treating off the board by specialty = 0.0004895 - significant
21
Antigen Preparation                                                         OEI-09-00-00530 ACKNOWLEDGMENTS 
This report was prepared under the direction of Paul A. Gottlober, Regional Inspector General for 
Evaluation and Inspections in the San Francisco Regional Office. Other principal Office of Evaluation 
and Inspections staff who contributed include: 
Scott Hutchison, Project Leader 
Pamela Minniear, Program Analyst 
Camille Harper, Program Analyst 
Thomas Purvis, Program Analyst 
Chris Tarbell, Program Analyst 
Stephanie Lattin Program Specialist 
This inspection team would like to thank all the respondents to the survey. We would like to particularly 
thank the physicians who assisted us in designing the survey instruments and reviewing the background 
section of the report. 
For information or copies of this report, please contact the Office of Inspector Generals Public Affairs 
office at (202) 619-1343.