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Formulary JournalClinical Pharmacology

Gain a solid understanding of compendia and its impact on patient


access
July 01, 2012
Abstract
The current compendia landscape, though constantly in ux, impacts everything from payer
approval of off-label use to manufacturer patient access initiatives. Drug compendia, dened as
summaries of drug information, affects coverage and reimbursement decisions for pharmaceutical
products, and as a result, it's important for pharmaceutical manufacturers and healthcare providers
to understand the role and impact of compendia off-label uses. Due to the rapid advancement of
drugs and biological agents, especially in oncology, physicians often prescribe drugs for uses other
than what they have been approved for by FDA. In fact, between 50% and 75% of all chemotherapy
agents are prescribed "off-label." As a result, off-label coverage has become an important
component to patient access to medications. Although FDA approval process may not always be a
feasible option for additional indications, guidance is needed to determine which uses are medically
appropriate. Several drug compendia are currently published to outline FDA-approved uses of
medications and evaluations of non-FDA-approved uses. According to the Centers for Medicare and
Medicaid Services (CMS), a compendium should include a summary of pharmacologic
characteristics for each drug/biological that may include dosage and recommended uses. Unlike
disease treatment guidelines that are indexed by disease, these compendia should be indexed by drug
or biologic. Most insurers, including Medicare, refer to compendia when making policy and coverage
decisions, and therefore, a positive or negative listing can have a signicant impact on whether or not
a pharmaceutical product is coveredultimately, affecting prescribing decisions and patient access
to medication treatments. (Formulary. 2012;252256)
The current compendia landscape, though constantly in ux, impacts everything from payer approval of
off-label use to manufacturer patient access initiatives. Drug compendia, dened as summaries of drug
information, affect coverage and reimbursement decisions for pharmaceutical products, and as a result, it's
important for pharmaceutical manufacturers and healthcare providers to understand the role and impact of
compendia off-label listings.
Why the focus on compendia? It all boils down to patient access. Due to the rapid advancement of drugs
and biological agents, especially in oncology, physicians often prescribe drugs for uses other than what
they have been approved for by FDA. In fact, between 50% and 75% of all chemotherapy agents are
prescribed "off-label." As a result, off-label coverage has become an important component to patient access
to medications. Although the FDA approval process may not always be a feasible option for additional
indications, guidance is needed to determine which uses are medically appropriate. Several drug
compendia are currently published to outline FDA-approved uses of medications and evaluations of nonFDA-approved uses. Most insurers, including Medicare, refer to compendia when making policy and
coverage decisions.
In this article, the current compendia landscape and its impact on patient access will be outlined.
Specically, the following will be discussed:
current Medicare and Medicaid coverage criteria,
compendia review process and rating system, and
compendia strategy recommendations.
CURRENT MEDICARE AND MEDICAID COVERAGE CRITERIA
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Drug compendia are dened as summaries of drug information that are compiled by experts who have
reviewed clinical data on drugs. According to the Centers for Medicare and Medicaid Services (CMS), a
compendium should include a summary of pharmacologic characteristics for each drug/biological that may
include dosage and recommended uses. Unlike disease treatment guidelines that are indexed by disease,
these compendia should be indexed by drug or biologic. Through this process, experts may deem certain
off-label uses as "acceptable" as a result of their review of the clinical data. Therefore, a positive or
negative listing can have a signicant impact on whether or not a pharmaceutical product is covered,
ultimately affecting prescribing decisions and patient access to medications.
In the past, many compendia were used, from American Hospital Formulary Service Drug Information
(AHFS-DI) and National Comprehensive Care Network (NCCN) to Clinical Pharmacology, United States
Pharmacopeia Drug Information (USPDI), American Medical Association Drug Evaluations (AMA-DE),
DrugPoints, and DRUGDEX. However, recent reductions and the consolidation of available compendia
have fueled a growing desire for transparency. CMS has even redesigned its process for determining
medically appropriate indications and now allows for submission to be included as its proof compendium.
Before CMS went through the aforementioned process shift, Medicare Parts B and D did not use the same
approved compendia. Now, Medicare (both Parts B and D) relies on data from AHFS-DI, Clinical
Pharmacology, DRUGDEX, and NCCN when making coverage decisions, while Medicaid utilizes only
AHFS-DI and DRUGDEX. In addition, the 2010 Final Medicare Physician Fee Schedule (MPFS) Rule
nalized CMS' proposal requiring recognized and future compendia to have a publicly transparent process
for evaluating therapies and identifying potential conicts of interest, in order to improve regulatory
safeguards.
According to the nal rule, as of January 1, 2010, each compendium must post listings evaluation
processes to their websites, including disclosure of evidence considered and the review of evidence leading
to the development of the recommendation. Compendia are also required to disclose conicts of interest on
each compendium's publicly available website. In these disclosures, compendia must include information
on ownership and investment interests of individuals making recommendations and must list any conicts
of interest regarding decision-makers and their relationships with manufacturers or other interested parties.
Failure to comply with these transparency requirements can result in a compendium's removal from
Medicare policy.
Although Medicare has provided fairly clear instructions on which indications or listings will be covered, it
doesn't necessarily mean the information included in the actual compendium is crystal clear. For example,
compendia can sometimes be vague in their language, often leading to subjective decision-making.
Manufacturers should keep in mind that one negative compendium listing can trump all positive listings, so
as compendia strategies are being developed, it is crucial to determine which compendia to pursue. Sending
submissions to all 4 compendia may not be wise.
Impact on Cancer Care
Cancer care is a therapeutic area undergoing substantial scrutiny regarding how, when, and why certain
drugs are being used. In the 1990s, there was a movement toward the enactment of state Cancer Coverage
Acts, many of which were initiated by the Association of Community Cancer Centers (ACCC) and several
state cancer societies to write legislation that would require commercial payers to honor the compendia
listings for many off-label cancer indications.
After the more recent compendia consolidation efforts, some of these older laws now reference compendia
that are no longer in print or are out of date. This means manufacturers need to work with commercial
payers to ensure that patients have affordable access to their products.
Today, Medicare will cover anti-cancer drugs if one or more of the following is true:
1. the drug is FDA-approved,
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2. the use of the drug is supported by one of the Medicare-approved compendia, and its use is not listed as
"not recommended" in any of the compendia, or
3. the use is supported by clinical research that appears in peer-reviewed medical literature.
The compendia guidelines encompass anti-cancer drugs covered under Medicare Parts A, B, C, and D. For
other types of drugs, contractors may provide coverage for unlabeled uses, taking into consideration the
compendia, literature, and/or other accepted standards of medical practice. Medicare may cover off-label
uses with supportive compendia listings, but only if the FDA has approved the drug for some other use.
Table 1 outlines compendia use for Medicare Part B, Medicare Part D, and Medicaid as of May 2012.
Xcenda, a business unit of AmerisourceBergen Consulting Services,
recently completed a survey with the Managed Care Network on how
payers are using compendia to make off-label coverage decisions. The
survey polled 55 different respondents and found the top compendium used
for oncology products is NCCN.

Table 1 : CMS-recognized
compendia

Respondents were also asked about the use of compendia beyond oncology,
with approximately 50% stating they also use compendia for indications
including the use of IVIG, rheumatoid arthritis, and biologics, with the
most utilized compendia being DRUGDEX.

Though an increased focus on transparency continues to grow, the process for compendium consideration
remains far from standardized. AHFS-DI and Clinical Pharmacology don't have a standard review process,
admission process, or timeline. DRUGDEX and NCCN provide instructions on how to submit for
inclusion, but no formal timeline, which can mean a long wait for review, depending on priority.
COMPENDIA REVIEW PROCESS AND RATING SYSTEM
Each compendium rates and lists products differently. Below is an outline of each compendium and its
requirements.
AHFS-DI
First published in 1959, AHFS-DI is updated annually in hard copy format and provides frequent updates
on its website (www.ahfsdruginformation.com). An annual subscription is required to access this
compendium, which contains the following:
More than 40,000 represented medicines
More than 100,000 represented drug products
Expert medical and pharmaceutical commentary
Off-label and labeled uses
Drug interactions
Cautions and toxicity
Extensive dosage and methods of administration
Chemistry and stability
Well-established, referenced laboratory and test inferences
Pharmacology and pharmacokinetics
More than 70,000 uniquely cited references
In addition, AHFS-DI lists FDA-approved prescribing information, off-label uses, and orphan drug
designations. Originally, off-label indications were identied in the text as a footnote. AHFS-DI has since
adopted the ratings system utilized during the pilot collaboration with the Foundation for Evidenced Based
Medicine (FEBM), and nal determinations are now reported for each drug and published on its website.
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Clinical Pharmacology
Developed by Gold Standard in 1994, Clinical Pharmacology's drug monographs are developed through a
continuous, independent, peer- review process. This process involves reviewing many forms of
drug/medical data from multiple resources and distilling them into usable and concise information.
Throughout the review process, preference is given to peer-reviewed publications that address the impact
of therapy on the disease and patient safety. Off-label data are primarily identied and selected by the
editorial staff for inclusion in the database through regular and comprehensive review of
primary published literature,
new or updated national practice guidelines,
surveillance of other accepted sources of medical information (ie, FDA, Centers for Disease Control
and Prevention [CDC], National Institutes of Health [NIH] communications), and
dialogue with customers or other external reviewers of content.
There is no structured process or timeline for requesting off-label reviews. Manufacturers should provide a
letter outlining the request and should submit with supporting literature.
Clinical Pharmacology is accessible online via a subscription (www.clinicalpharmacology.com) or through
the purchase of a CD-ROM.
DRUGDEX
DRUGDEX uses a three-tiered rating system that assesses each drug's strength of evidence,
recommendation, and efcacy. Evidence-based information covers FDA-approved and investigational
prescription and non-prescription drugs, as well as non-US preparations. Areas discussed include dosage,
pharmacokinetics, cautions, interactions, clinical applications, adverse effects, comparative efcacy, drugof-choice information, and orphan drug status.
Approximately 90 editorial Micromedex staff members, trained in the identication of relevant literature
and accepted literature evaluation techniques, participate in the multistep process to create and update the
content within DRUGDEX. Topics are evaluated based on ongoing review of medical journals, clinical
judgment and recommendations, regulatory standards and compliance, national healthcare trends, FDA
approvals, editorial board suggestions, external requests, and policy changes in health and disease
management from professional health organizations.
Occasionally, external data review requests will be honored. Requestors should submit in writing the
following:
requestor's contact information,
brief explanation of request,
proposed indication, including disease state, patient population, regimen and/or combinations, and
evidence for request, inclusive of positive and negative ndings.
DRUGDEX is accessible by subscription only (www.micromedex.com/products/drugdex/).
NCCN
Based directly on NCCN Clinical Practice Guidelines in Oncology, the NCCN compendium contains
authoritative, scientically derived information to support decision-making about appropriate use of drugs
and biologics in patients with cancer. NCCN guidelines are developed and updated by 44 individual panels,
comprising more than 800 clinicians and oncology researchers from the 21 NCCN member institutions and
their afliates. The uses identied in the compendium are based upon evaluation of evidence from
scientic literature integrated with expert judgment in an evidence-based process.
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Indicated uses are categorized in a systematic approach that describes the type of evidence available and
the degree of consensus for each recommendation. The level of evidence and degree of panel consensus
determine the rating of the drug (or combination of drugs) for a specic indication. Upon development or
update of a tumor-specic guideline, the data and ratings are converted into the compendium.
Other Compendia
Facts & Comparisons, published by Wolters Kluwer Health, provides up-to-date, comprehensive drug
information, including off-label uses. It is not, however, a Medicare- or Medicaid-approved compendium.
DrugPoints is a summary of Thomson Micromedex DRUGDEX and a successor publication to USPDI. It
is not accepted by CMS as a Medicare-approved compendium, although, it may be utilized by private
payers. DrugPoints does not utilize its own ratings system, but, rather, references the DRUGDEX ratings.
DrugPoints uses three distinct evidence-based rating types for FDA-labeled and off-label indications. All
indications are assigned one rating for each three rating types: 1) efcacy, 2) strength of recommendation,
and 3) strength of evidence.
Recent changes in health policy as a result of healthcare reform do not currently impact Medicare and
Medicaid's approach and use of compendia for off-label indications. This is a uid environment, however,
and there exists the potential for changes in both the public and private payer settings as healthcare reform
progresses. With CMS' increased focus on comparative effectiveness determinations, the coverage
landscape may shift, including the way in which compendia are utilized.
COMPENDIA STRATEGY RECOMMENDATIONS
In today's healthcare landscape, regulatory and legislative changes constantly shift the dynamics of patient
access to drug therapies. Regulatory agencies, such as CMS, continually implement changes to Medicare
and Medicaid programs, including the appropriate use of compendia for drug coverage determinations.
During the past several years, CMS has reviewed and analyzed the various compendia utilized by
Medicare, Medicaid, and other payers to determine which sources are best suited for utilization by
government agencies that provide healthcare to its beneciaries. As a result of this review, a few years ago,
CMS changed the criteria for recognition of compendia and indicated that other regulatory and legislative
changes impacting compendia are also likely to occur in the future.
Such a dynamic environment requires detailed monitoring and analysis to anticipate, assess, and react to
the impact of ongoing health policy changes on coverage, especially through the appropriate use of
compendia in therapeutic areas where few treatment options exist and as patients and healthcare providers
seek greater access to needed drugs and therapies.
Given the importance of compendia and the increase in off-label uses of medications, it's important for
manufacturers to have a proper strategy in place to help ensure appropriate listings within the most
commonly referenced compendia. Strategies should be centered around disease states or be product
specic. This is important, as the end points considered for one indication may be vastly different from
another.
It's also important to decide when to pursue compendia submissions. If conducted before the product
comes to market, manufacturers can use information gleaned to help design the next round of clinical trials.
If performed in the midst of clinical trials, the manufacturer will learn if evidence needs to be stronger to
garner a positive listing. Regardless of timing, manufacturers should keep a nger on the pulse of the
market and watch how payers respond to industry leaders. This will provide key insights into how payers
are using compendia to make coverage decisions and how compendia may be inuencing treatment
guidelines (and vice versa).
Strategy Development

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When developing a compendia strategy, manufacturers must rst thoroughly understand the components of
the Medicare-recognized compendia:
Editorial review processes by compendium
Submission procedures and timeline guidelines by compendium
Rating nomenclature and systems by compendium
Coverage and use by rating and payer type
Compendia utilization data
Recent compendia trends, such as the type, size, and number of studies each compendium is likely to
require
State Cancer Coverage Act legislation to understand where compendia are covered
Medicaid compendia coverage summaries
Listing of compendia sources
After manufacturers have a full understanding of the key elements and current market challenges, they
must conduct a clinical evidence review for the indication. This includes researching proxy product
benchmarking in order to assess the likelihood of successful submission for the product by each
compendium. The analysis should evaluate compendia listings for the indication and listings that mention
biomarkers or diagnostic testing. Wherever possible, manufacturers should compare listings for a product
across two or more compendia.
Conducting Gap Analysis
In addition to evaluating proxy products, it's important to review clinical trial literature to identify
informational gaps for data or evidentiary support that may be needed for the compendia submission. This
includes a thorough review of the product's published data, trials currently under way, and trials planned for
the future. In addition, manufacturers should evaluate the evidence level, strength of end points, and
outcomes (if available) for the product. These data points then should be compared to the compendia
benchmarks for the competitor proxy products. Once the gap analysis is complete, a summary should be
developed that includes
the likelihood of compendia listing by line of therapy and compendium,
any identied information gaps, and
differences in clinical data and supporting information.
Addressing Payer-Specic Populations
Manufacturers should also prioritize a product's payer population and determine the compendia/guidelines
used by those payers to make coverage decisions. Manufacturers must work to determine the type and level
of evidence, including end points and outcomes, needed for favorable listings. It might also be wise to
consider which individuals on the manufacturer side are interfacing with the payers. Medical science
liaisons, which work directly with payers, rather than account managers are most qualied to understand
the payers' needs and have the ability to address off-label questions. This team can help payers recognize
which additional indications have data to support appropriate utilization and coverage.
In addition, manufacturers may want to consider surveying the payer and provider community on an
ongoing basis to determine which compendia and guidelines are considered well-established and which are
most respected in the industry.
Integrating Compendia Strategy with Patient Access Strategy
Generally, compendia strategy dovetails with patient access strategies. For example, many manufacturers
have a reimbursement hotline to help providers and patients access therapies more affordably. These
hotlines could also be utilized to assist physicians should they need support with off-label indications.
While eld promotion of off-label indications is not allowed, most physicians stay on top of the latest data
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to support therapies available for a particular indication. As such, manufacturers often provide resources
regarding access coverage for both labeled and unlabeled uses.
CONCLUSION
Manufacturer strategies and tactical plans will continue to integrate and be incorporated earlier in the
clinical trial phase to maximize the greatest patient access prior to launch. Movements around comparative
effectiveness and healthcare reform are driving this process, while also, hopefully, simultaneously reducing
healthcare costs. Considering the high use of off-label indications in the oncology space (as well as other
orphan diseases), payers will likely increasingly include off-label products in their coverage decisions.
In summary, manufacturers should consider the following as part of their compendia strategy development
process:
Gaining a solid understanding of compendia and their processes
Conducting Medicare, Medicaid, and private payer compendia surveillance
Engaging in private payer compendia education
Analyzing each compendium by drug and diagnosis
Engaging in advocacy groups
Conducting ongoing compendia and payer surveillance (monthly or quarterly)
Monitor compendia recognition (annually)
In-depth market research on how Medicare, Medicaid, and private payers use compendia may be helpful to
better segment the marketplace.
Ms Brown is senior vice president, Xcenda, a business unit of AmerisourceBergen Consulting Services.
Disclosure Information: The author reports no nancial disclosures as related to products discussed in this
article.

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