The current compendia landscape, through constantly in flux, impacts everything from payer approval of off-label use to manufacturer patient access initiatives. Drug compendia, defined as summaries of drug information, affects coverage and reimbursement decisions for pharmaceuticals products, and as a result, it's important for pharmaceitucal manufacturers and healthcare providers to understand the role and impact of compendia off-label uses.
The current compendia landscape, though constantly in flux, impacts everything from payer approval of off-label use to manufacturer patient access initiatives. Drug compendia, defined 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 significant impact on whether or not a pharmaceutical product is covered-ultimately, affecting prescribing decisions and patient access to medication treatments. (Formulary. 2012;252–256)
The current compendia landscape, though constantly in flux, impacts everything from payer approval of off-label use to manufacturer patient access initiatives. Drug compendia, defined 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.
In this article, the current compendia landscape and its impact on patient access will be outlined. Specifically, the following will be discussed:
CURRENT MEDICARE AND MEDICAID COVERAGE CRITERIA
Drug compendia are defined 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 significant 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 finalized CMS' proposal requiring recognized and future compendia to have a publicly transparent process for evaluating therapies and identifying potential conflicts of interest, in order to improve regulatory safeguards.
According to the final 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 conflicts 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 conflicts 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,
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.
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.
First published in 1959, AHFS-DI is updated annually in hard copy format and provides frequent updates on its website ( http://www.ahfsdruginformation.com/). An annual subscription is required to access this compendium, which contains the following:
In addition, AHFS-DI lists FDA-approved prescribing information, off-label uses, and orphan drug designations. Originally, off-label indications were identified 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 final determinations are now reported for each drug and published on its website.
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 identified and selected by the editorial staff for inclusion in the database through regular and comprehensive review of
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 ( http://www.clinicalpharmacology.com/) or through the purchase of a CD-ROM.
DRUGDEX uses a three-tiered rating system that assesses each drug's strength of evidence, recommendation, and efficacy. 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 efficacy, drug-of-choice information, and orphan drug status.
Approximately 90 editorial Micromedex staff members, trained in the identification 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:
DRUGDEX is accessible by subscription only ( http://www.micromedex.com/products/drugdex/).
Based directly on NCCN Clinical Practice Guidelines in Oncology, the NCCN compendium contains authoritative, scientifically 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 affiliates. The uses identified in the compendium are based upon evaluation of evidence from scientific literature integrated with expert judgment in an evidence-based process.
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 specific indication. Upon development or update of a tumor-specific guideline, the data and ratings are converted into the compendium.
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) efficacy, 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 fluid 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 beneficiaries. 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 specific. 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 finger 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 influencing treatment guidelines (and vice versa).
When developing a compendia strategy, manufacturers must first thoroughly understand the components of the Medicare-recognized compendia:
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
Addressing Payer-Specific 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 qualified 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 field promotion of off-label indications is not allowed, most physicians stay on top of the latest data to support therapies available for a particular indication. As such, manufacturers often provide resources regarding access coverage for both labeled and unlabeled uses.
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:
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 financial disclosures as related to products discussed in this article.