FDA Approval Does Not Mean What You Think It Does!
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Former Board Member

The Department of Health and Human Services’ (DHHS) Food and Drug Administration (FDA) is well known to Americans, as are their terms “FDA approval” and “off-label usage.” Unfortunately, the inappropriate usage of these terms has created confusion because of misinterpretation, which has damaged the doctor-patient relationship, as well as the incorrect conclusion that FDA approval enabled product use and insurance (Medicare) reimbursement for both the product and physician rendered services. The unintended consequences of misuse of these terms by companies, the media, and individuals have inappropriately interfered with the delivery of health care. Furthermore, FDA approval does not determine product reimbursement, which is solely determined by CMS [Centers for Medicare and Medicaid; formerly, Health Care Financing Administration (HCFA)], which, after FDA product approval, determines whether or not reimbursement should be provided. However, CMS’ non-uniform regional reimbursement policy enables Medicare contractors’ to use selective and indiscriminate reimbursement, which limits patient access to selective FDA approved products, according to their area of domicile. Fortunately, these issues, which have adversely affected patient care, are identifiable:
# The indiscriminate and inappropriate use of these FDA terms has not only confused the public and medical community, but also created doubt about physicians’ motivations, goals and treatments. The disingenuous advancement of these terms by companies, the media, and individuals seductively aggravated the situation because the American people believed that their comprehension of these few simple words revealed that a product’s usage by a physician, other than as described in the FDA-approval, implied wrongdoing and, implicitly, that a physician’s off-label usage was not safe, effective, and beneficial. These conclusions are incorrect. The FDA’s website details that FDA approval is solely for interstate marketing of a company’s product and “off-label usage” is legal and appropriate, within the physician’s discretion and indicates no misconduct; and,
# FDA product approval does not automatically result in reimbursement to the physician or hospital; reimbursement may be limited to only FDA-approved indications, and only occurs after CMS deems a product to be reasonable and necessary. However, CMS’ determinations are not uniform throughout the country.

The following paragraphs will define the FDA’s role and their terms “FDA approval” and “off-label usage”, detail how deceptive misusage of these terms by knowledgeable companies and individuals can adversely affect and limit medical care, and how the CMS’ Medicare contractor’s nonuniform haphazard regional reimbursement policy does not provide all Americans with the same health care.

The FDA’s responsibility is to grant and oversee a company’s interstate medical product marketing. The FDA’s valuable and important role is to conclude whether products are appropriately labeled as determined by risk analysis, assessment, monitoring of approved product clinical studies, evaluation of a company’s safety and efficacy claims, and then to grant interstate marketing licenses. FDA scientists review a company’s proposed claim and determine if marketing the product is appropriate. The Federal Food, Drug, and Cosmetic Act required the FDA to review data derived from adequate and well-controlled tests to establish both safety and effectiveness before a new drug (or device) can be approved for sale (21USC Sections 355, 360c). FDA approval is only for the usage claim(s), and denial of a product claim may occur because of insufficient evidence, unacceptable risks and/or FDA-sponsor disagreement about the scope or wording of the claim. The lack of FDA approval for a different indication, specifically, means that relevant data to establish safety and effectiveness for that indication have not been transmitted to, reviewed and approved by the FDA. This does not mean that the drug or device used for this nonevaluated indication is not safe, effective or beneficial for that particular usage. Since “neither the FDA nor the Federal Government regulate the practice of medicine…any approved product may be used by a licensed practitioner for uses other than those stated in the product label. Off-label use is not illegal, but rather means that data to support that usage have not been independently reviewed by the FDA.” Since the FDA’s appropriate, rigorous regulatory approval pathways are expensive, arduous and time-consuming, companies seek approval for potentially profitable product indications, and not necessarily others. But, a company’s product marketing for unapproved usage claims cannot be condoned because such practices subvert and undermine the product approval processes determinations of safety and benefit, and, in a perverse way, allow a company to practice medicine without a license. In contradistinction, the trained and licensed physician, using best practice guidance and new therapeutic information, can use a product not reviewed by the FDA and not indicated within the product’s usage claims, and, thereby, continue to adhere to his/her paramount obligation of using best efforts in providing care for patients. The FDA has understood this distinct separation between physicians and vendors and has stated such. As an aside, off-label usage accounted for 21% of all prescription medications written (Radley DC et al, Arch Intern Med 2006;166:2554–2555).

While the term “FDA approval” provides comfort to the consumer, its counterpoint, “off-label usage,” is unsettling. Companies advantageously use these unsettling feelings by speciously advancing disinformation. Insurers repeatedly deny claims so as to reduce expenditures; WellPoint, the medical insurer, refused payment for the expensive drug, Avastin, using the off-label usage tact that “insufficient medical evidence” permitted its use against brain tumors (Geeta Anand, “Burden of Proof as Costs Rise, New Medicines Face Pushback: Insurers Limit Coverage to FDA-Approved,” Wall Street Journal, September 18, 2007). The patient’s oncologists used Avastin when all other treatments failed, but the insurer limited coverage of Avastin to only its FDA-approved use, with the innuendo that off-label usage implied ineffectiveness and physician wrongdoing. Mohit Ghose, spokesman for America’s Health Insurance Plans, stated that insurers must limit use of the most expensive drugs or devices to control health-care costs and assure employers of getting the best value of every health-care dollar spent, while avoiding issues of drug efficacy and contracted insurance coverage. After significant commotion, WellPoint paid, despite asserting that patient protection from “unapproved” drug usage was their goal. WellPoint was clearly not acting in the best interests of the patient.

Public officials intimately involved with public health-care policy and their legislative underpinnings speak and act in ways that do not have the needs of their constituents as a primary focus. Congressman Henry Waxman, a lawyer and leader on health issues, railed against the FDA’s policy change that allowed pharmaceutical companies to provide physicians peer-reviewed articles that detailed off-label drug use (www. Waxman argued passionately that this “would allow drug and device companies to short-circuit FDA review and approval by sponsoring drug trials that are carefully constructed to deliver positive results and then [use] the results to influence prescribing patterns…While there may need to be a balance between First Amendment and protection of public health, the answer is not to open the door to unrestricted dissemination of potentially questionable information about drug safety and effectiveness,…allowing marketing through journal articles can reduce the incentive for drug and device companies to conduct rigorous studies needed to win full FDA review and approval.” Waxman knew that off-label usage of drugs was appropriate and legal, but said that such a policy puts too much reliance on peer-reviewed journals to disseminate medical information and provide balance. Waxman’s remarks directly attacked physician integrity, medical research and researchers, peer-reviewed publications and physician motivation. Perhaps, Waxman wanted to be the ultimate peer reviewer, without credentials. In reality, Waxman attempted to prevent physicians from getting timely, peer-reviewed information from an additional source, the pharmaceutical representative, which would facilely allow physician assessment as to its place in patients’ therapy.

The FDA’s regulatory approval of a product’s safety and effectiveness influences patient care, as does the misuse of the FDA terms by companies and individuals. However, for a product to be widely employed, reimbursement is mandatory. The CMS, administrators of Medicare and Medicaid, is tasked with the mission to ensure effective, up-to-date and quality health-care coverage for beneficiaries, and their reimbursement decisions concern a product being reasonable and necessary. “Both CMS and the FDA review scientific evidence, and may review the same evidence, to make purchasing and regulatory decisions, respectively. (Federal Registry: DeterminationProcess/Downloads/FR09262003.pdf)… [But] CMS and its contractors make coverage determinations (67 FR 66755, November 1, 2002) … [by assessing whether] the product is reasonable and necessary as a condition of coverage under section 1862(a)(1)(A) of the Act. CMS adopts FDA determinations of safety and effectiveness, and CMS evaluates whether or not the product is reasonable and necessary for the Medicare population. Although an FDA-regulated product must receive FDA approval or clearance (unless exempt from the FDA premarket review process) for at least one indication to be eligible for Medicare coverage, except for Category B devices under an IDE clinical trial (see 60 FR 48417, September 19, 1995), FDA approval/clearance alone does not generally entitle that device to coverage.” However, all Medicare-covered Americans do not receive the same insurance coverage from their local Medicare contractor, and, thereby, the same care. “We [DHHS] contract with private insurance companies, referred to as carriers … to process Medicare claims; that is, claims-payment contractors…Medicare contractors review and adjudicate claims to ensure that Medicare payments are made only for those items or services covered under Medicare Part A or Part B. In the absence of a specific NCD [national coverage determination], coverage determinations are made locally by the Medicare contractors within the boundaries established by the law. Sometimes these determinations are made on a claim-by-claim basis.” Thus, no uniform payment policy exists, and people from different parts of the country can receive different care because of different local reimbursement decisions, i.e., some patients will receive care for a product, while others not. The lack of a uniform policy allows these Medicare contractors to make nonuniform determinations, using a variety of unregulated reasons, concerning American’s health care, which is inappropriate.

Medicine’s rapid evolution demands facile physician adaptation and adoption of new therapies, and many patients cannot wait for governmental imprimaturs or published outdated guidelines to receive therapy. This concept underscores the physician’s awesome responsibility. The dilemma of new therapies supplanting another therapeutic alternative raises a myriad of specters including unethical clinical investigations, experimentation and inappropriate financial inducements for product usage. The medical community has taken these issues seriously, and the physician’s paramount obligation has unwaveringly remained, to use the best medical skills to heal the sick. The overwhelming majority of physicians have neither abandoned this credo, nor postured they are immune or opposed to criticism or critique. The deceptive and disingenuous use of FDA terms damages the doctor-patient relationship of trust, and improperly creates public fear and uncertainty about physicians and therapies. The FDA should not remain silent when these situations occur. The nonuniformity of Medicare contractors’ indiscriminate and selective reimbursement policies results in the unintended consequence of their practicing medicine by limiting the use of FDA-approved products for some physicians and not others, as well as inappropriate (tortious) interference with the contractual doctor-patient relationship by limiting access to particular FDA-approved products. A uniform policy of reimbursement procedures should be instituted. The inappropriate advancement of disinformation and the nonuniformity of reimbursement by Medicare contractors have damaged the doctor-patient relationship of trust, impugned physician integrity and limited the physician’s therapeutic armamentarium, all of which can adversely affect patient care. These issues can be facilely corrected.

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From the Dorros-Feuer Interventional Cardiovascular Disease Foundation, Ltd., Wilson, Wyoming.

The author reports no conflicts of interest regarding the content herein.

Manuscript submitted April 20, 2010, provisional acceptance given May 26, 2010, final version accepted June 23, 2010.

Address for correspondence: Gerald Dorros, MD, P.O. Box 1654, 1120 South Thunder Road, Wilson, WY 83014. E-mail: