Introduction Beneficial ownership refers to the natural person or persons who invest in, control, or otherwise reap gains from an asset, such as a bank account, real estate property, company, or trust. In some cases, an asset's beneficial owner may not be listed in public records or disclosed to federal authorities as the legal owner. For some years, the United States has been criticized by international bodies for gaps in the U.S. anti-money laundering (AML) system related to a lack of systematic beneficial ownership disclosure. While beneficial ownership information is relevant to several types of assets, attention has focused on the beneficial ownership of companies, and in particular, the use of so-called "shell companies" to anonymously purchase assets, such as real property, and to store and move money, including through bank accounts and wire transfers. While such companies may be created for a legitimate purpose, there are also concerns that the use of some of these companies can facilitate crimes, such as money laundering. Recent U.S. regulatory steps and legislation have particularly focused on beneficial ownership disclosure related to the use of shell companies with hidden owners that conduct financial transactions or purchase assets. In the context of AML regimes, law enforcement authorities as well as financial institutions and their regulators may seek beneficial ownership information to identify or verify the natural persons who benefit from or control financial assets held in the name of legal entities, such as corporations and limited liability companies. Drug traffickers, terrorist financiers, tax and sanctions evaders, corrupt government officials, and other criminals have been known to obscure their beneficial ownership of legal entities for money laundering purposes. To do so, they may form nominal legal entities, or "shell companies," which have no physical presence and generate little to no economic activity, but are used to anonymously store and transfer illicit proceeds. By relying on third-party nominees to serve as the legal owners of record for such shell companies, criminals can control and enjoy the benefits of the assets held by such companies while shielding their identities from investigators. Although concealing beneficial ownership has long been a central element of many money laundering schemes, many jurisdictions around the world have not established or implemented policy measures that address beneficial ownership disclosure and transparency. According to the Financial Action Task Force (FATF)âan intergovernmental standards-setting body for AML and countering the financing of terrorism (CFT)âfinancial crime investigations are frequently hampered by the absence of adequate, accurate, and timely information on beneficial ownership. FATF has accordingly identified beneficial ownership transparency as an enduring AML/CFT policy challenge. Some U.S. government agencies have also long recognized that the ability to create legal entities without accurate beneficial ownership information is a key vulnerability in the U.S. financial system. Such ongoing vulnerabilities have placed the United States under domestic and international pressure, including from the FATF, to tighten its AML/CFT regime with respect to beneficial ownership disclosure requirements. In recent years, various U.S. regulators have taken actions to address this issue, and congressional interest in this topic has increased. This report first provides selected case studies of high-profile situations where beneficial ownership has been obscured. It then provides an overview of beneficial ownership issues relating to corporate formation and in real estate transactions. Next, it describes the recent history of beneficial ownership policy and legislation. The report then discusses recent U.S. regulatory changes to address aspects of beneficial ownership transparency. Thereafter, the report analyzes selected current policy issues, including sectors not covered by existing Treasury regulations, the status of international efforts to address beneficial ownership, and the evolution of the Global Legal Entity Identifier (LEI) program. Finally, the report analyzes selected legislative proposals in the 116 th Congress. Overview Beneficial Ownership and U.S. Corporate Formation While beneficial ownership information is relevant to a variety of assets, recent policy attention has focused on the beneficial ownership of companies, and in particular, the use of shell companies to anonymously purchase assets, such as real property, and to store and move money, including through bank accounts and wire transfers. FATF has estimated that over 30 million "legal persons" exist in the United States, and about 2 million new such legal persons are created each year in the states and territories owned by the United States. FATF defines legal persons to include entities such as corporations, limited liability companies (LLCs), various forms of partnerships, foundations, and other entities that can own property and are treated as legal persons. FATF considers trusts, which share some of the same characteristics, to be "legal arrangements." FATF recommends that countries mandate some degree of transparency in identifying beneficial owners, at least for law enforcement and regulatory purposes, for legal persons and legal arrangements. There are a range of legitimate reasons for wanting to create such entities, including diversification of risk with joint owners, tax purposes, limiting liability, and other reasons. However, such legal persons and arrangements can also be used to hide the identities of owners of assets, thereby facilitating money laundering, corruption, and financial crime. For this reason, FATF recommends countries take steps to ensure that accurate and updated information on the identities of beneficial owners be maintained and accessible to authorities. In the United States, corporations, LLCs, and partnerships are formed at the state level, not the federal level. Corporation laws vary from state to state, and the "promoter" of the corporation can choose in which state to incorporate or in which to form another legal entity, often paying a "corporate formation agent" within the state to file the required state-level paperwork. Such corporate formation agents may be attorneys, but are not always required to be attorneys. While state laws vary, most states share some basic requirements for forming a corporation or other entity, including the filing of the entity's articles of incorporation with the secretary of state. These articles often include the corporation's name, the business purpose of the corporation, and the corporation's registered agent and address for the purpose of accepting legal service of process if it is sued. While state requirements vary, most states do not collect, verify, or update identifying information on beneficial owners. Because no federal standards currently exist, a promoter of a corporation can choose to incorporate in a state with fewer disclosure requirements if they wish. The FATF evaluation of the United States' AML system found that "measures to prevent or deter the misuse of legal persons and legal arrangements are generally inadequate" in the United States. FATF reported there were no mechanisms in place to record or verify beneficial ownership information in the states during corporate formation. They also warned that "the relative ease with which U.S. corporations can be established, their opaqueness and their perceived global credibility makes them attractive to abuse for money laundering and terrorism financing, domestically as well as internationally." In a Senate Judiciary Committee hearing on June 19, 2019, witness Adam Szubin, former Under Secretary for the Treasury's Office of Terrorism and Financial Intelligence, noted in the question-and-answer portion that the position of the United States as a leader in the financial system at times gave additional credibility to shell companies that had been formed in the United States anonymously by international criminals, enabling them to transact business or open bank accounts outside the United States through these companies with less scrutiny than they might otherwise have received. Beneficial Ownership and U.S. Real Estate Overview of Real Estate Transactions Some argue that land ownership, even more than ownership of other resources, involves both public and private aspectsâsuch as urban planning, resources and environmental planning, and tax consequences. In the United States, however, unlike in many European countries, the federal government has almost no role in the purchase and sale of real estate. Real estate transactions in the United States are largely private contracts, and transfers may or may not be recorded publicly, although many buyers find it advantageous to do so. Most buyers of property finance their purchases with mortgages from banks. Investors or those who do not require such loans may engage in "all-cash" purchases, which simply means that no loans are involved and that the purchasers must come up with the necessary funds on their own. According to the National Association of REALTORSÂ®, approximately 23% of residential real estate sales transactions were all-cash in 2017. Data from real estate data firm CoreLogic for 2016, however, put the figure at 46% for New York state, and similarly higher for some additional states. In addition to realtors, who may represent buyers or sellers (but are not required to be involved in transactions), escrow agents and title company agents also play a role in real estate transactions in the United States. Escrow agents essentially act as neutral middlemen in real estate sales, temporarily holding funds for either side. In cases where purchases are made in the name of an LLC, for instance, an escrow agent will look at operating agreements of the LLC to identify the person legally authorized to sign documents, but they generally have no specific duties to locate or identify beneficial owners. Usually, escrow agents are not part of title insurance companies or independent title agencies. After a buyer and seller agree on a sales price and sign a purchase and sales contract, real estate transactions are transferred to a land title company, most likely the American Land Title Association (ALTA). ALTA represents 6,300 title insurance agents and companies, from small, single-county operators to large national title insurers. Title insurance is a form of insurance that protects the holder from financial loss if there are previously undiscovered defects in a title to a property (such as previously undiscovered fraud or forgery, or various other situations). A typical title insurance company, before providing coverage to the buyer of a property, usually investigates prior sales of the property. This process often starts with examining public records tracing the property's history, its owners, sales, and any partial property rights that may have been given away. This title search investigation also normally includes tax and court records to give title companies an understanding of what they might be able to insure in their policies issued to buyers. Title insurers are the only professionals in the real estate community who currently have money laundering requirements, which were imposed through FinCEN's Geographic Targeting Orders (GTOs), as detailed below. As part of this process, when real estate transactions fit the thresholds set in GTOs for certain covered metropolitan areas, title insurance companies work with real estate professionals representing buyers to collect the required beneficial ownership information. Money Laundering Risks Through Real Estate and Shell Companies The FATF 2016 evaluation warned that the lack of AML requirements on real estate professionals constituted a significant vulnerability for the United States' AML system. As detailed below, FinCEN exempted the real estate sector from AML requirements pursuant to the USA PATRIOT Act of 2001 ( P.L. 107-56 ). In a 2015 study of the New York luxury property market, the New York Times found that LLCs with anonymous owners were being increasingly utilized in the New York luxury property market. The Times reported that in 2003, for example, one-third of the units sold in one high-end Manhattan buildingâthe Time Warner buildingâwere purchased by shell companies. By 2014, however, that figure had risen to over 80%, according to the article. And nationwide, the Times reported, nearly half of residential purchases of over $5 million were made by shell companies rather than named people, according to data from property data provider First American Data Tree studied by the Times . According to FinCEN, in 2017, 30% of all high-end purchases in six geographic areas involved a beneficial owner or purchaser representative who was also the subject of a previous suspicious activity report (SAR). A 2017 study by the U.S. Government Accountability Office (GAO) reviewed available information on the ownership of General Services Administration (GSA) leased space that required higher levels of security as of March 2016, and found that GSA was leasing high-security space from foreign owners in 20 buildings. GAO could not obtain the beneficial owners of 36% of those buildings for high-security facilities leased by the federal government, including by the Federal Bureau of Investigation. The Appendix provides an example of how an LLC with hidden owners might be used to purchase real estate in the United States with minimal information as to the natural persons behind the purchase or sale of the property. U.S. Policy Responses History of U.S. Beneficial Ownership Policy and Legislation As previously noted, the U.S. government has long recognized the ability to create legal entities without accurate beneficial ownership information as a key vulnerability of the U.S. financial system. In 2006, GAO published a report entitled Company Formations: Minimal Ownership Information Is Collected and Available , which described the challenges of collecting beneficial owner data at the state level. The U.S. Department of the Treasury's 2015 National Money Laundering Risk Assessment and its 2018 update identify the misuse of legal entities as a key vulnerability in the banking and securities sectors. The 2018 risk assessment additionally clarified that such vulnerability is further compounded by shell companies' ability to transfer funds to other overseas entities. Such ongoing vulnerabilities have placed the United States under domestic and international pressure, including from FATF, to tighten its AML/CFT regime with respect to beneficial ownership disclosure requirements. In its 2016 review of the U.S. government's AML/CFT regime, FATF noted that the "lack of timely access to â¦ beneficial ownership information remains one of the most fundamental gaps in the U.S. context." According to FATF, this gap exacerbates U.S. vulnerability to money laundering by preventing law enforcement from efficiently obtaining such information during the course of investigations. FATF further noted that this gap in the U.S. AML/CFT regime limits U.S. law enforcement's ability to respond to foreign mutual legal assistance requests for beneficial ownership information. By contrast, for instance, the European Union (E.U.), in 2015, enacted the E.U. Fourth Anti-Money Laundering Directive, which required member states to collect and share beneficial ownership information. Since at least the 110 th Congress, legislation has been introduced to address long-standing concerns raised by law enforcement, FATF, and other observers over the lack of beneficial ownership disclosure requirements. For example, in the 110 th Congress, Senator Carl Levin introduced S. 2956 , the Incorporation Transparency and Law Enforcement Assistance Act, on May 1, 2008. In his floor statement introducing the bill, Senator Levin noted that the National Association of Secretaries of State (NASS) had requested that he delay introduction of a bill in order for the NASS to first convene a task force in 2007 to examine state company formation practices. In July 2007, the NASS task force issued a proposal. Rather than cure the problem, however, the proposal was full of deficiencies, leading the Treasury Department to state in a letter that the NASS proposal "falls short" and "does not fully address the problem of legal entities masking the identity of criminals." â¦. That is why we are introducing Federal legislation today. Federal legislation is needed to level the playing field among the States, set minimum standards for obtaining beneficial ownership information, put an end to the practice of States forming millions of legal entities each year without knowing who is behind them, and bring the U.S. into compliance with its international commitments. The 115 th Congress considered a number of bills concerning beneficial ownership reporting, including S. 1454 , the True Incorporation Transparency for Law Enforcement (TITLE) Act and the Corporate Transparency Act of 2017 ( H.R. 3089 and S. 1717 ). In the 116 th Congress, the House Committee on Financial Services on June 11, 2019, passed and ordered to be reported to the House an amendment in the nature of a substitute to H.R. 2513 , the "Corporate Transparency Act of 2019," introduced by Representative Maloney. Also, in the Senate, S. 1889 was introduced on June 19, 2019, by Senator Whitehouse with cosponsors, and a discussion draft bill was circulated June 10, 2019, by Senators Warner and Cotton. This report concludes with an analysis of selected introduced legislative proposals in the 116 th Congress. Current Beneficial Ownership Requirements Several federal tools are available to address money laundering risks posed by entities that obscure beneficial ownership information, including Treasury's Customer Due Diligence (CDD) rule, use of Geographic Targeting Orders (GTOs), and a provision in Section 311 of the USA PATRIOT Act. Treasury also uses various elements of its economic sanctions programs to address such risks. Finally, with regard to international cooperation, the U.S. government may obtain and share beneficial ownership information with foreign governments in the course of law enforcement investigations (see text box below). In other policy contexts that reach beyond money laundering issues, beneficial ownership has emerged as a concern related to entities' disclosure of U.S. ownership for tax purposes and entities that lease high-security government office spaces. Beneficial ownership issues are also relevant in other areas, such as securities, which are beyond the scope of this report. Treasury's Customer Due Diligence (CDD) Rule Pursuant to its regulatory authority under the Bank Secrecy Act (BSA) âthe principal federal AML statuteâFinCEN has long administered regulations requiring various types of financial institutions to establish AML programs. The centerpiece of FinCEN's response to concerns about beneficial ownership transparency is its Customer Due Diligence Rule (CDD Rule), which went into effect in May 2018. Under the CDD Rule, certain U.S. financial institutions must establish and maintain procedures to identify and verify the beneficial owners of legal entities that open new accounts. The regulation covers financial institutions that are required to develop AML programs, including banks, securities brokers and dealers, mutual funds, futures commission merchants, and commodities brokers. Under the rule, covered financial institutions must now collect certain identifying information on individuals who own 25% or more of legal entities that open new accounts. The CDD Rule also requires covered financial institutions to develop customer risk profiles and to update customer information on a risk basis for the purposes of ongoing monitoring and suspicious transaction reporting. These requirements make explicit what has been an implicit component of BSA and AML compliance programs. Geographic Targeting Orders (GTOs) FinCEN has the authority to impose additional recordkeeping and reporting requirements on domestic financial institutions and nonfinancial businesses in a particular geographic area in order to assist regulators and law enforcement agencies in identifying criminal activity. This authority to impose so-called "Geographic Targeting Orders" (GTOs) dates back to 1988. GTOs may remain in effect for a maximum of 180 days unless extended by FinCEN. Section 274 of the Countering America's Adversaries Through Sanctions Act ( P.L. 115-44 ) replaced statutory language referring to coins and currency with "funds," thereby including a broader range of financial services, such as wire transfers. Several bills in the 116 th Congress seek to address the use of GTOs to disclose the beneficial owners of entities involved in the purchase of all-cash real estate transactions (see text box below). Special Measures Applied to Jurisdictions, Financial Institutions, Classes of Transactions, or Types of Accounts of Primary Money Laundering Concern Section 311 of the USA PATRIOT Act ( P.L. 107-56 ) added a new provision to the Bank Secrecy Act at 31 U.S.C. Â§5318A. This provision, popularly referred to as "Section 311," authorizes the Secretary of the Treasury to impose regulatory restrictions, known as "special measures," upon finding that a foreign jurisdiction, a financial institution outside the United States, a class of transactions involving a foreign jurisdiction, or a type of account, is "of primary money laundering concern." The statute outlines five special measures that Treasury may impose to address money laundering concerns. The second special measure authorizes the Secretary to require domestic financial institutions and agencies to take reasonable and practicable steps to collect beneficial ownership information associated with accounts opened or maintained in the United States by a foreign person (other than a foreign entity whose shares are subject to public reporting requirements or are listed and traded on a regulated exchange or trading market), or a representative of such a foreign person, involving a foreign jurisdiction, a financial institution outside the United States, a class of transactions involving a jurisdiction outside the United States, or a type of account "of primary money laundering concern." Based on a review of Federal Register notices, FinCEN has neither proposed nor imposed the special measure involving the collection of beneficial ownership information. Treasury's Sanctions Programs and the 50% Rule Affecting Entities Owned by Sanctioned Persons Beneficial ownership information is valuable in the context of economic sanctions administered by the Treasury Department's Office of Foreign Assets Control (OFAC). Under economic sanctions programs, assets of designated persons (i.e., individuals or entities) may be blocked (i.e., frozen), thereby prohibiting transfers, transactions, or dealings of any kind, extending to property and interests in property subject to the jurisdiction of the United States as specified in OFAC's specific regulations. As additional persons, including shell and front companies, are discovered to be associated (i.e., owned or controlled by, or acting or purporting to act for or on behalf of, directly or indirectly) with someone already subject to sanctions, OFAC may choose to designate those additional persons to be subject to sanctions. In addition to persons explicitly identified on OFAC's Specially Designated Nationals (SDN) or Sectoral Sanctions Identification (SSI) lists, sanctions also apply to nonlisted entities that are owned, in part, by blocked persons. Current guidance states that sanctions also extend to entities that are at least 50% owned by sanctioned persons. Compliance with this so-called "50% Rule" requires financial institutions and others potentially doing business with designated persons or identified sectoral entities to understand an entity's ownership structure, including its beneficial owners. Disclosure of "Substantial" U.S. Ownership for Tax Purposes The Foreign Account Tax Compliance Act (FATCA; Subtitle A of Title V of the Hiring Incentives to Restore Employment Act; P.L. 111-147 , as amended) is a key U.S. policy tool to combat tax evasion. Pursuant to FATCA, U.S. taxpayers are required to disclose to the Internal Revenue Service (IRS) financial assets held overseas. In addition, FATCA requires certain foreign financial institutions to disclose information directly to the IRS when its customers are U.S. persons or when U.S. persons hold a "substantial" ownership interestâdefined to mean ownership, directly or indirectly, of more than 10% of the stock (by vote or value) of a foreign corporation or of the interests (in terms of profits or capital) of a foreign partnership; or, in the case of a trust, the owner of any portion of it or the holder, directly or indirectly, of more than 10% of its beneficial interest. Foreign financial institutions that do not comply with reporting requirements are subject to a 30% withholding tax rate on U.S.-sourced payments. According to FinCEN, some intergovernmental agreements that the United States negotiated with other governments to facilitate the implementation of FATCA "allow foreign financial institutions to rely on existing AML practices â¦ for the purposes of determining whether certain legal entity customers are controlled by U.S. persons." The U.S. government committed in many of these agreements to pursue "equivalent levels of reciprocal automatic information exchange" on the U.S. financial accounts held by taxpayers of that foreign jurisdiction; there is, however, no reciprocity in FATCA. Various observers have debated whether legal entity ownership disclosure information provided to the IRS could be used by other federal entities for AML purposes. Disclosure of Beneficial Ownership of Office Space Leased by the FederalÂ Government Section 2876 of the National Defense Authorization Act for Fiscal Year 2018 (NDAA; 10 U.S.C. 2661 note) requires the Defense Department to identify each beneficial owner of a covered entity proposing to lease accommodation in a building or other improvement that is intended to be used for high-security office space for a military department or defense agency. Prior to the enactment of Section 2876, in January 2017, the GAO reported that the General Services Administration (GSA) did not keep track of beneficial owners, including foreign owners, of high-security office space it leased for tenants that included the Federal Bureau of Investigation (FBI) and the Drug Enforcement Administration (DEA). According to GAO, GSA began in April 2018 to implement a new lease requirement for prospective lease projects that requires offerors to identify and disclose whether the owner of the leased space, including an entity involved in the financing of the property, is a foreign person or a foreign-owned entity. In the 116 th Congress, H.R. 392 , the Secure Government Buildings from Espionage Act of 2019, seeks to expand the scope of the FY2018 NDAA's provisions. Selected Policy Issues The current policy debate surrounding beneficial ownership disclosure is focused on addressing gaps in the U.S. AML regime and tracking changes made by the international community in its approach to addressing the problem. A key area of congressional activity involves evaluating the risks associated with lack of beneficial ownership information in the corporate formation and real estate sectors. The Treasury's current CDD rule mandates that financial institutions must collect informationâfor beneficial owners who hold more than 25% of an entityâupon opening an account for the entity. Some legislative proposals would mandate that this type of information be collected when such legal entities are formed, and that the information be reported to FinCEN or another central repository that authorities can access. International developments in beneficial ownership disclosure practices, including trends in the adoption of a program known as the Global Legal Entity Identifier System (LEI), also raise issues for U.S. policy consideration. Sectors Not Covered by Treasury's CDD Rule Even following the CDD rule's implementation, some critics argue that gaps remain in U.S. financial transparency requirements The CDD rule, for example, applies only to individuals who own 25% or more of a legal entity. Critics note that the 25% ownership threshold means that if five or more people share ownership, a legal entity may not name or identify any of them (only one management official). Also, the rule applies to new, but not existing, accounts. FATF, for example, has criticized the United States for lacking beneficial ownership requirements for corporate formation agents and real estate transactions. Neither sector is directly affected by the FinCEN rule, but recent legislation has been introduced to address both areas (see section below titled " Selected Legislative Proposals in the 116th Congress "). The following sections discuss potential gaps remaining in U.S. financial transparency requirements after implementation of the CDD rule. Company Formation Agent Transparency Third-party service providers known as "company formation agents" often "play a central role in the creation and ongoing maintenance and support of â¦ shell companies." While these services are not inherently illegitimate, they can help shield the identities of a company's beneficial owners from law enforcement. According to a 2016 FATF report, formation agents handle approximately half of the roughly 2 million new company formations undertaken annually in the United States. As discussed, the regulation of company formation agents is primarily a matter of state law. Formation agents are not subject to the BSA or federal AML regulations. However, observers have argued that states have not served as effective regulators of the company formation industry. These perceived inadequacies with current oversight of the company formation industry have prompted a number of legislative proposals discussed below. Status of the GTO Program A number of policymakers have expressed interest in making FinCEN's GTOs targeting money laundering in high-end real estate permanent or otherwise expanding the scope of the current real estate GTO program. Section 702 of the Defending American Security from Kremlin Aggression Act of 2019 ( S. 482 ) would require the Secretary of the Treasury to prescribe regulations mandating that title insurance companies report on the beneficial owners of entities that engage in certain transactions involving residential real estate. Section 214 of the COUNTER Act of 2019 ( H.R. 2514 ), as amended in a mark-up session of the House Financial Services Committee on May 8, 2019, would require the Secretary of the Treasury to apply the real estate GTOs, which currently cover only residential real estate, to commercial real estate transactions. Section 129 of the Department of the Treasury Appropriations Act, 2019 (Title I of H.R. 264 ) would have required FinCEN to submit a report to Congress on GTOs issued since 2016, but it was not enacted. Establishing AML Requirements for Persons Involved in Real Estate Closings and Settlements Section 352 of the USA PATRIOT Act ( P.L. 107-56 ) requires all financial institutions to establish AML programs. In 2002, however, FinCEN exempted from Section 352 certain financial institutions, including persons involved in real estate closings and settlements, in order to study the impact of AML requirements on the industry. In 2003, FinCEN published an advanced notice of proposed rulemaking (ANPRM) to solicit public comments on how to incorporate persons involved in real estate closings and settlements into the U.S. AML regulatory regime. Although no final rule has been issued, other developments have occurred. In 2017, FinCEN released a public advisory on the money laundering risks in the real estate sector. And in November 2018 a notice in the Federal Register on anticipated regulatory actions contained reference to renewed FinCEN plans to issue an ANPRM to initiate rulemaking that would establish BSA requirements for persons involved in real estate closings and settlements. Disclosure of Beneficial Ownership of U.S.-Registered Aircraft To register an aircraft in the United States with the Federal Aviation Administration (FAA), applicants must certify their U.S. citizenship. Non-U.S. citizens may register aircraft under a trust agreement in which the aircraft's title is transferred to an American trustee (e.g., a U.S. bank). Investigations into the FAA's Civil Aviation Registry have revealed a lack of beneficial ownership transparency among aircraft registered through noncitizen trusts. Reports further indicate that drug traffickers, kleptocrats, and sanctions evaders have been among the operators of aircraft registered with the FAA through noncitizen trusts. Some Members of Congress have sought to address beneficial ownership transparency in the FAA's Civil Aviation Registry through legislation. If enacted, H.R. 393 , the Aircraft Ownership Transparency Act of 2019, would require the FAA to collect identifying information, including nationality, of the beneficial owners of certain entities, including trusts, applying to register aircraft in the United States. Status of International Efforts to Address Beneficial Ownership U.S. policymakers' interest in addressing beneficial ownership transparency has been elevated by a series of leaks to the media regarding the abuse of shell companies by money launderers, corrupt politicians, and other criminals, as well as sustained multilateral attention to the issue. In late 2018, information from such leaks reportedly contributed to a raid by German authorities on Deutsche Bank, one of the world's largest banks. Other major banks have become enmeshed in money laundering scandals involving the abuse of accounts associated with shell companies, including Danske Bank, Denmark's largest bank. The international community has taken steps to acknowledge and address the issue of a lack of beneficial ownership transparency in the context of anti-money laundering efforts. Some countries, including the United Kingdom, have created a public register that provides the beneficial owners of companiesâand more countries have committed or are planning to do so. In April 2018, the European Parliament voted to adopt the European Commission's proposed Fifth Anti-Money Laundering (AML) Directive, which among other measures would require European Union member states to maintain public national-level registers of beneficial ownership information for certain types of legal entities. The European Commission has also sought to identify third-country jurisdictions with "strategic deficiencies" in their national AML/CFT regimes, which pose "significant threats" to the EU's financial system. To this end, the Commission has identified eight criteria or "building blocks" for assessing third countriesâone of which is the "availability of accurate and timely information of the beneficial ownership of legal persons and arrangements to competent authorities." In February 2019, the Commission released a proposed list of third countries with strategic AML/CFT deficiencies that included four U.S. territories: American Samoa, Guam, Puerto Rico, and the U.S. Virgin Islands. A key criticism of the U.S. territories' AML/CFT regime was the lack of beneficial ownership disclosure requirements. Evolution of the Global Legal Entity Identifier (LEI) Program The origins of the LEI system lay in some of the problems highlighted in the 2008 financial crisis. These included excessive opacity as to credit risks, and to potential losses accrued across various affiliates of large financial conglomerates. For example, when Lehman Brothers failed in 2008, financial regulators and market participants found it difficult to gauge their financial trading counterparties' exposure to Lehman's large number of subsidiaries and legal entities, domestically and overseas. Partly to better track such exposures, the Financial Stability Board (FSB) and G-20 helped to design and create the concept of the LEI system, starting in 2009. LEI is a voluntary international program that assigns each separate "legal entity" participating in the program a unique 20-digit identifying number. This number can be used across jurisdictions to identify a legally distinct entity engaged in a financial transaction, including a cross-border financial transaction, making it especially useful in today's globally interconnected financial system. The unique identifying number acts as a reference codeâmuch like a bar code, which can be used globally, across different types of markets and for a wide range of financial purposes. These would include, for example, capital markets and derivatives transactions, commercial lending, and customer ownership, due diligence, and financial transparency purposes; as well as risk management purposes for large conglomerates that may have hundreds or thousands of subsidiaries and affiliates to track. A large international bank, for example, may have an LEI identifying the parent entity plus an LEI for each of its legal entities that buy or sell stocks, bonds, swaps, or engage in other financial market transactions. The LEI was designed to enable risk managers and regulators to identify parties to financial transactions instantly and precisely. Although the origins of the LEI stemmed from concerns over credit risk and safety and soundness that surfaced during the 2008 financial crisis, the LEI may also have benefits for financial transparency. A May 2018 study from the Global Legal Entity Foundation found, based on multiple interviews with financial market companies, that the lack of consistent, reliable automated identifiers was creating a great burden on the financial industry; that most in the industry believed the "Know Your Customer" process of onboarding new clients would likely become more automated; and that "there is clearly an opportunity to align on one identifier to generate efficiencies." Similar conclusions were reached in a 2017 study by McKinsey & Co. The current LEI system is aimed more at tracking financial transactions of various affiliates, but creating a unified global identifier could be considered a natural first step toward more easily tracking ownership of affiliates as well. Worldwide, more than 700,000 LEIs have been issued to entities in over 180 countries as of November 2017; however, use of the LEI remains largely voluntary as opposed to legally mandatory. In the United States and abroad, some aspects of financial reporting require use of the LEI and these, in substantial part, rely on voluntary implementation. Some have called the lack of broader adoption of a common legal identifier a collective action problem. In a collective action problem, all participants in a system benefit if everyone participates; if only a few participate, those few bear high costs, as early adopters, with little benefit. Collective action problems are classic examples of situations where a government-organized solution may improve outcomes. Similarly, some argue that all parties would benefit if such LEIs were uniformly assigned, but there is no incentive to be a sole or early adopter. Academics have urged regulators to mandate the use of the LEI in regulatory reporting as a means of solving this collective action problem. Treasury's Office of Financial Research noted, "Universal adoption is necessary to bring efficiencies to reporting entities and useful information to the Financial Stability Oversight Council, its member agencies, and other policymakers." Selected Legislative Proposals in the 116th Congress112 In response to some of the issues discussed above, a number of lawmakers have introduced legislation that would require the collection of beneficial ownership information for both newly formed and existing legal entities. The subsections below discuss two of these proposals in the 116 th Congress. H.R. 2513, Corporate Transparency Act of 2019 In June 2019, the House Committee on Financial Services approved legislation that would require many small corporations and LLCs to report their beneficial owners to the federal government. Under H.R. 2513 , the Corporate Transparency Act of 2019, newly formed corporations and LLCs would be required to report certain identifying information concerning their beneficial owners to FinCEN and annually update that information. The bill would also impose these reporting requirements on existing corporations and LLCs two years after FinCEN adopts final regulations to implement the legislation. Subject to certain exceptions, the bill defines the term beneficial owner to mean natural persons who "directly or indirectly" exercise "substantial control" over a corporation or LLC; own 25% or more of the equity of a corporation or LLC; or receive "substantial economic benefits" from a corporation or LLC. H.R. 2513 's reporting requirements are limited to small corporations and LLCs. Specifically, the bill exempts a variety of regulated entities from its reporting requirements, in addition to any company that (1) employs more than 20 full-time employees, (2) files income tax returns reflecting more than $5 million in gross receipts, and (3) has an operating presence at a physical office within the United States. The bill would also authorize FinCEN to promulgate a number of rules. First, H.R. 2513 would allow FinCEN to adopt a rule requiring covered corporations and LLCs to report changes in their beneficial ownership sooner than the annual update required by the legislation itself. Second, the bill would direct the Treasury Secretary to promulgate a rule clarifying the circumstances in which an individual receives "substantial economic benefits" from a corporation or LLC for purposes of its definition of beneficial owner . Third, the legislation would require FinCEN to revise the CDD Rule within one year of the bill's enactment in order to bring the rule "into conformance" with the bill's requirements and reduce any "unnecessary" burdens on financial institutions. Finally, H.R. 2513 would impose civil and criminal penalties on persons who knowingly provide FinCEN with false beneficial ownership information or willfully fail to provide complete or updated information. S. 1889, True Incorporation Transparency for Law Enforcement (TITLE) Act In June 2019, Senator Sheldon Whitehouse introduced legislation that would require states receiving funds under the Omnibus Crime Control and Safe Streets Act of 1968 to adopt transparent incorporation systems within three years of the bill's enactment. Specifically, S. 1889 , the True Incorporation Transparency for Law Enforcement (TITLE) Act, would mandate that transparent incorporation systems require newly formed corporations and LLCs to report certain identifying information concerning their beneficial owners to their states of incorporation. Under the bill, a compliant formation system would also require corporations and LLCs to report changes in their beneficial ownership within 60 days. These requirements would apply to existing corporations and LLCs two years after a state's adoption of a compliant formation system. Subject to certain exceptions, S. 1889 defines the term beneficial owner to mean natural persons who "directly or indirectly" (1) exercise "substantial control" over a corporation or LLC, or (2) have a "substantial interest" in or receive "substantial economic benefits" from a corporation or LLC. Like H.R. 2513 , S. 1889 's requirements would be limited to small corporations and LLCs. Specifically, S. 1889 would allow states to exempt various regulated entities, in addition to any company that (1) employs more than 20 full-time employees, (2) files income tax returns reflecting more than $5 million in gross receipts, (3) has an operating presence at a physical office within the United States, and (4) has more than 100 shareholders. The bill would also impose civil and criminal penalties on persons who knowingly provide states with false beneficial ownership information or willfully fail to provide complete or updated information. Finally, S. 1889 would amend the BSA to include "any person engaged in the business of forming corporations or [LLCs]" in its definition of a regulated "financial institution," and would direct FinCEN to issue a proposed rule requiring such persons to establish AML programs. Appendix. Hypothetical Example of Shell Companies Obscuring U.S. Property Sale Figure A-1 demonstrates hypothetically how hidden foreign or U.S. buyers might purchase real estate in the United States with minimal disclosure of their identities as hidden beneficial owners. First, foreign or U.S. individuals might establish a foreign-incorporated LLC, subject to that foreign jurisdiction's laws, which could present particular challenges to a U.S. law enforcement agency seeking to investigate the purchase. Alternately, foreign or U.S. individuals could create a U.S. LLC incorporated in a U.S. state with only a "registered agent" required to be disclosed under various states' laws. A foreign LLC might pay for the property through a wire transfer from a foreign bank account. If the foreign LLC or the U.S. LLC were to open a U.S. bank account to pay for the purchase, then, if this were a new account opened since May 2018, the U.S.-regulated bank would look for beneficial owners owning more than 25% of the LLC, and keep records of that information. Currently, however, that information would not be reported to FinCEN automatically, and law enforcement would most likely require a subpoena to procure that information from the bank's records. To create additional layers that could obscure the actual buyers of the property, the LLC, whether U.S. or foreign, could route the payment to the title company, which handles the real estate closing, through a law firm. Payments and wire transfers routed through law firms present an extra layer of information a prosecutor or law enforcement agent must go through to try to obtain details of individuals who own the LLC and are purchasing a property. Often the U.S. attorney-client privilege can make it more difficult to exercise this subpoena authority, without at least the possibility that a legal challenge may arise. Finally, the payment is routed to the title company, which processes the property sale and distributes payment, normally to the seller's account. If the seller obscures his or her identity through an LLC as well, natural persons involved on both sides of the transfer may be hidden.


Introduction Both legislators and regulators have expressed concern about the safety and effectiveness of prescription drugs prescribed for "off-label uses"âpurposes other than those for which the Food and Drug Administration (FDA) has approved their sale. Two recent incidents illustrate the bases for those concerns. The first involves a drug already on the market. Safety experts raised concerns about ketamine, a drug available as an injectable anesthetic. They noted that physicians have created outpatient clinics to administer intravenous ketamine in an off-label use to treat depression and migraines. FDA has not reviewed clinical data that could support the clinics' promotional claims of safety and effectiveness. In August 2018, a second incident occurred in a Texas courtroom. Astra Zeneca settled a case concerning its alleged promotion of Seroquel for uses other than those for which it had sought and obtained FDA approval for sale in the United States. The core of the complaint by the state of Texas was that the company promoted the drug's use in children, although the FDA-approved labeling of the drug was for adult use. It was one of a number of settlements since 2000 resulting in payments by drug companies for the promotion of off-label uses. To help understand the issues involving off-label use, and how these issues might concern Congress, this report addresses five questions: What is drug labeling? What is off-label use? How are off-label prescriptions used in medicine today? What are the risks and benefits associated with off-label prescriptions? What concerns, if any, does Congress have about such prescriptions? If Congress wanted to do something about off-label prescriptions, what would be some of the options? Drug Labeling and Off-Label Use To market a prescription drug in the United States, a manufacturer needs FDA approval. To obtain that approval, the manufacturer must demonstrate the drug's safety and effectiveness according to criteria specified in law and agency regulations. It must also ensure that its manufacturing plant passes FDA inspection. Finally, it must obtain FDA approval for the drug's labelingâa term that covers all written material about the drug, including, for example, packaging, prescribing information for physicians, and patient brochures. FDA, thus, approves the drug and its labeling for a specific use. That use specifies the disease or condition, the population, and the way the drug is packaged and administered. When a physician prescribes a drug for reasons other than those specified in the FDA approval and labeling, the medical profession considers this to be off-label use . FDA regulates the drug and the manufacturer. Each state regulates clinicians and pharmacies. A licensed physician mayâexcept in highly restricted circumstances âprescribe the approved drug without limitation. A prescription to an individual whose demographic or medical characteristics differ from those indicated in a drug's FDA-approved labeling is accepted medical practice. In a 2006 study of drug prescribing by office-based physicians, 21% of prescriptions were written for off-label uses. Of those off-label prescriptions, the study's authors found that 27% were backed by strong scientific support. A 2016 Canadian study of primary care clinics found an overall rate of 12% of prescriptions for off-label uses. The percentage varied, however, by therapeutic class, ranging from 5% for ear, nose, and throat medications to 25% for central nervous system medications. An econometric model from the National Ambulatory Medical Care Survey estimated a 38% rate of off-label use. Research has shown that more than half of oncology drug use is off-label. A 2018 study examined 43 FDA-approved cancer drugs and compared their 99 labeled uses with the acceptable uses published by a national compendium Medicare relies on to make coverage decisions. Of the 451 compendium-accepted uses, 56% were off-label. Of the off-label uses, the authors deemed 91% as "well-accepted off-label use." Labeling: History, Requirements, and Value History. Drug labeling has been central to FDA's role as a protector of the public's health since 1906. That year, Congress (1) required that sellers state on a drug's label the "quantity or proportion of any alcohol [or] opium" contained, and (2) considered as "misbranded" any drug whose label was "false or misleading." Requirements that drugs be safe were not established until 1938. Congress did not require they be effective until 1962. Requirements. Today, a drug's labeling is more than the sticker the pharmacy places on the amber vial it dispenses to a customer. The Federal Food, Drug, and Cosmetics Act (FFDCA) and associated FDA regulations require and describe a product's labeling as "a compilation of information about the product, approved by FDA, based on the agency's thorough analysis of the new drug application (NDA) or biologics license application (BLA) submitted by the applicant. This labeling contains information necessary for safe and effective use." FDA requires that labeling begin with a highlights section that includes, if appropriate, black-box warnings, so called because their black borders signify importance. The regulations list the required elements of labeling: Value. Labeling plays a major role in the presentation of safety and effectiveness information. For clinicians, it is a primary source of prescribing information. The manufacturer submits the approved labeling for publication in the widely used Physician's Desk Reference . That labeling also serves as the basis for several patient-focused information sheets that manufacturers, pharmacy vendors, and many web-based drug information sites produce. Off-Label Use: Description and Examples Off-label prescribing can reflect cutting-edge clinical expertise. It can also be a response to price: a physician may choose to prescribe a lower-priced drug instead of a specifically labeled higher-priced one. Or a physician may prescribe off-label in an attempt to try a different treatment approach when other options have failed. Sometimes an off-label use becomes so widespread that it becomes accepted practice. However, without the backing of carefully designed clinical trials and expert analysis, it remains unknown whether the drug is, in fact, safe and effective for the off-label use. Also unknown are dosing details and systematically evaluated associated adverse events. Examples of off-label use include a drug tested for the treatment of one disease prescribed in an attempt to prevent or treat another; a drug tested at one dose used at higher or lower doses; a drug tested in adults prescribed to children; and a drug tested in an eight-week trial prescribed for long-term use. Table 1 lists several examples of FDA-approved drugs widely prescribed for off-label uses. Although FDA materials do not list off-label uses, several drug compendia include both labeled and off-label uses. For Medicare coverage, for example, the Social Security Act defines "medically accepted indication" as those, in addition to uses approved by FDA, that have been evaluated and supported and listed in one of several compendia, or for which there is "supportive clinical evidence in peer reviewed medical literature." Benefits and Risks of Off-Label Use Why has Congress given FDA the authority to regulate whether a drug may be on the U.S. market? Two key reasons: to protect patients and to encourage research in a competitive pharmaceutical industry. By statute and regulation, FDA now approves a drug for a specific use once its sponsor (usually the manufacturer) has provided sufficient evidence that the drug is safe and effective for that use. FDA has developed procedures for the review of that evidence. The FDA-approved labeling, which informs the clinician about dosing and likely and unlikely adverse events, helps protect the individuals for whom the drug is prescribed. Labeling also helps protect the interests of the manufacturers who invest in the clinical trials that demonstrate safety and effectiveness. For new drugs and new uses of already approved drugs, the sponsor receives a period of market protection, in the form of regulatory exclusivity for the sale of the drug for those uses. Payorsâsuch as private health insurers or Medicareâbenefit from FDA-approved labeling in their evaluation of whether to pay for a drug's use. But use of a drug evolves as clinicians (and the manufacturer) share their experiences regarding off-label uses, which, by definition, were not part of the premarket clinical studies used to obtain FDA approval. Off-label use can benefit patients. In some instances, such as in the treatment of rare diseases, clinical practice may use drugs approved for other indications. A manufacturer may choose not to invest in trials for such a small patient group. A patient whose physician is already prescribing the drug off-label may not want to enroll in a clinical trial where there is a chance he or she may be assigned to the placebo group. Once drugs are well-established in off-label uses, manufacturers rarely design studies to determine or verify the safety and effectiveness of such uses. Individuals and groups wanting to conduct such studies may find it hard to obtain funding. Examples of adverse events (AEs) associated with the use of drugs for specific off-label uses include heart valve damage from the use of fenfluramine and phentermine (fen-phen) for weight loss, and seizures from the use of tiagabine hydrochloride for depression. Using a Canadian primary care database that captured all prescriptions, the reason for each prescription, and adverse events, researchers looked at the rate of AEs for on-label use, off-label use associated with "strong scientific evidence," and off-label use without such evidence. They found more AEs for off-label prescriptions than for on-label prescriptions. However, off-label use associated with strong scientific evidence had similar rates of AEs as did on-label uses. The increased risk of AEs for off-label use was concentrated in those uses without strong scientific evidence. Manufacturers benefit from sales for off-label uses. However, they risk losing that market should a competitor complete studies to obtain FDA approval and labeling for those uses. Researchers who are not supported by the manufacturer who try to assess the safety and effectiveness of off-label uses are hampered by the inexact nature of secondary data sources: the standard clinical trial data collection in preparation for an FDA application is not available for off-label uses. What may begin as hopeful and intermittent off-label use may gain momentum and offer opportunities for planned studies. Drug and device companies argue that current regulations prevent them from distributing important information to physicians and payors about unapproved, off-label uses of their products. In November 2016, FDA held a two-day public meeting to hear from various groups regarding off-label uses of approved or cleared medical products. In June 2018, FDA issued final guidances explaining the agency's policy about medical product communications that include data and information not contained in FDA-approved labeling. One FDA guidance document, in particular, described the types of information that a manufacturer could provide payors and formulary committees about unapproved uses of approved products. FDA made two points especially relevant to off-label uses. First, FDA differentiates among its audiences in its presentation of information. The material it allows in product labeling is directed to a clinical audience. FDA staff have reviewed the information and require that it be presented in a way that is understandable by individual clinicians, who often do not have the statistical sophistication or data analysis skills or resources to fully evaluate the claims of manufacturers. This guidance notes, though, that payors and formulary committees do have such expertise and resources. FDA also acknowledges that it is useful for payors to have information in their decisions on coverage, but it wants to ensure that the information manufacturers provide is not misleading. Second, the FDA guidance describes what harm could come from allowing more sharing of information about off-label use. Some firm communications regarding unapproved products or unapproved uses of approved/cleared/licensed medical products may potentially undermine substantial government interests related to health and safety. These interests include motivating the development of robust scientific data on safety and efficacy; maintaining the premarket review process for safety and efficacy of each intended use in order to prevent harm, to protect against fraud, misrepresentation, and bias, and to develop appropriate instructions for use for medical products; protecting the integrity and reliability of promotional information regarding medical product uses; and preventing the diversion of health care resources toward ineffective treatments. The concerns FDA raised in the June 2018 final guidance documents might explain why Congress may be interested in exploring the issue of off-label use further. History of Congressional Interest and Action Congress has developed a system to protect the public by ensuring that drugs sold in the United States have met clinical and manufacturing standards of safety and effectiveness. Labeling is the mechanism that bridges the regulated drug and the use of that drug in clinical practice. The labeling establishes the uses for which the manufacturer has demonstrated safety and effectiveness to FDA's satisfaction. Congress and the FDA have tried several approaches, using labeling as a tool, to reduce the risk to patients. Table A-1 includes examples of congressional and FDA actions to expand the information provided in a drug's labeling. The actions have addressed topics such as content labeling, directions for use, permissible and prohibited advertising, research incentives to support labeling specific to population subgroups (e.g., children), criteria for Medicare coverage, required and permissible labeling changes, and balance of benefit and risk information in labeling and advertising. Manufacturers, meanwhile, want to be able to provide information to insurers and other entities (such as the Centers for Medicare and Medicaid Services [CMS] and hospital pharmacy and therapeutics committees) that decide whether to cover a drug in a policy and whether to limit reimbursement for specific uses. Congress has provided some leeway relative to its earlier prohibition on promotional activities. For example, in 2016, it broadened the types of health care economic information drug and device manufacturers could provide to payors (e.g., insurance companies). Although the underlying FFDCA section continues to exclude information related only to an off-label use, it now requires "a conspicuous and prominent statement describing any material differences between the health care economic information and the labeling approved for the drug." Several bills concerning off-label use have been introduced that would have expanded the information that manufacturers could provide about off-label uses. For example, the Subcommittee on Health of the House Committee on Energy and Commerce marked up H.R. 2026 (115 th Congress), the Pharmaceutical Information Exchange Act, in January 2018, which would have allowed the provision of scientific information to payors, in addition to health care economic information. Then-Subcommittee Chair Michael Burgess, in commenting on the bill's effort to clarify how manufacturers can share "if it is based on competent and reliable evidence," expressed strong support for the bill. He noted "the importance of cutting edge information in medicine and science to optimize patient care and outcomes â¦ and [how the bill] could have the potential to save patients' lives." Then-Ranking Member (now, Chair) Frank Pallone, Jr., though, argued that the ability to communicate about off-label use "had great potential to undermine" FDA's approval process and to "hamstring" its enforcement efforts. H.R. 2026 passed the subcommittee, although it did not reach the floor in the 115 th Congress. Possible Avenues of Future Congressional Interest Off-label use presents both opportunities and risks to clinicians, patients, manufacturers, and researchers. At times, those interests clash. Academics, public health organizations, and journals have suggested what actions Congress might take based on their particular concerns regarding off-label prescriptions. These actions include both direct legislation and oversight activities to encourage action by other entities. The 116 th Congress might consider some of these varied approaches, summarized in the issues described below. Disclosure to patients. Most individuals, unaware of the nuances of FDA regulation, may not know that physicians may prescribe drugs for uses that FDA has not reviewed for safety and effectiveness. Several potential opportunities for providing this information exist. Congress could require or work with the states to require that the prescriber inform the patient about the off-label use and describe the meaning of off-label use; the prescriber note in the prescription why the drug is being prescribed; or the pharmacist inform the patient that the use is off-label. Data collection and availability. FDA, under federal law, determines whether a drug requires a prescription. The states, under their individual laws, determine what information the prescription order contains. Because clinicians do not need to note on the prescription order why they are prescribing a drug (e.g., simvastatin for high cholesterol or citalopram for depression), the information in pharmacy, administrative, and clinical databases often cannot directly identify off-label uses. Therefore, as Congress and other public policy groups consider whether and how to address off-label drug prescribing, they do not have adequate information on the scope and details of the practice. Congress could require or work with the states to encourage clinicians to note on prescriptions the reason for medication use (e.g., the specific condition, disease, or symptom), thereby allowing that information to appear in pharmacy databases, which would enable focused analysis of off-label uses; the establishment of confidential registries of off-label prescribing and follow-up information that FDA (or other designated scientifically appropriate agencies) could use in its electronic surveillance systems to identify associated adverse events and other drug use problems; or FDA to increase its surveillance of available data sources, such as registries and administrative and clinical databases, to identify patterns of off-label use and evidence suggesting effectiveness and associated adverse events. Dissemination. Because some information may be valuable to clinicians and entities that influence prescribing decisions (such as insurers and pharmacy and therapeutics committees), Congress could allow manufacturers to disseminate information about off-label uses that they have developed or of which they are aware, perhaps subject to certain limitations or accompanying reporting requirements. Possibilities include broader sharing of clinical analyses of off-label use with coverage deciders (e.g., CMS, insurers, pharmacy and therapeutics committees) to support requests that they cover a particular use of the drug; and dissemination of clinical analyses of off-label use at clinical and pharmaceutical conferences. Oversight. With an estimated 12% to 38% of all prescriptions' (and 56% of oncology prescriptions') being written for uses not listed on FDA-approved labeling, valid information on the extent of off-label use and the effect of such use on manufacturer, insurer, and clinician behavior could potentially better inform debate on how to best protect the public's health. Congress could direct the Government Accountability Office (GAO) to study the extent of off-label use in government-provided care (e.g., Department of Veterans Affairs, Bureau of Prisons, and Indian Health Service) and in government-funded care (e.g., Medicare and Medicaid); the Secretary of Health and Human Services (HHS) to contract with the National Academy of Medicine or a similar organization to assemble management or industrial policy experts to study the costs and rewards to industry of off-label prescriptions; or FDA and the Federal Trade Commission to investigate drugs whose off-label prescriptions account for a particularly high percentage of all prescriptions or that generate a particularly high percentage or high dollar value of sales. Pricing. The decision to use a drug off-label based solely or primarily on price introduces a new element to study. For example, the pricing difference between Avastin and Lucentis, both made by the same manufacturer with the same active ingredient, is so large that many ophthalmologists use the lower priced Avastin in their treatment of macular degeneration, despite its being an off-label use. The manufacturer included the treatment of macular degeneration in its application to FDA for Lucentis. To explore the ramifications of a traditionally nonclinical element in prescribing decisions, Congress could require the HHS Secretary to study the relationship among pricing, access, and prescribing and its effect on patient safety. Reimbursement. Although FDA approval of a drugânot for each use of a drugâis a requirement for sale in the United States, the decision to reimburse a physician or patient for a drug is made by entities such as the CMS and private insurers. Such decisions, therefore, influence what drugs are prescribed and, in part, for what uses drugs are prescribed. Congress could direct the HHS Secretary to study such coverage decisions or to contract with the National Academy of Medicine or a similarly equipped entity to do so; or HHS to form a task force to include CMS and FDA, along with private insurers and others involved in coverage decisions, and patient and clinician groups representing those affected by coverage decisions, to identify areas in need of action and to recommend steps in those directions. Congress also could encourage payors to require safety and effectiveness evidence before covering off-label uses. Research. The traditional path toward adding an indication (reason for use) to the labeling of a drug already approved for other uses has been for the sponsor of the drug to conduct clinical trials and submit a supplemental new drug application (NDA) to FDA. The widespread extent of off-label use suggests that relying on that model is not helping prescribers get better information. Congress could consider assigning responsibility (and funding) to the National Institutes of Health and the Patient-Centered Outcomes Research Institute for safety and effectiveness evaluations of off-label uses; or requiring, for a drug that has substantial (to be defined) off-label sales, that the manufacturer fund studies, such as clinical trials, to assess the safety and effectiveness of the drug for the off-label use and submit evidence to the HHS Secretary. Depending on the Secretary's assessment of the evidence, the Secretary could request that the manufacturer amend the drug's labeling either to add the off-label use to the label as an approved use or to add a statement that clinical evidence does not support the safety and effectiveness of the drug for the off-label use. Research transparency. FDA regulations describe standards for the design and analysis of clinical trials that a sponsor uses in an NDA. Studies done by or for the manufacturer or by other groups or individuals are not always made public, in which case their findings cannot be reviewed and evaluated. Because the results of such studies may be used in support of off-label uses, by providing positive and negative incentives, Congress could consider requiring or encouraging prospective posting of the designs and statistical plans of studies of off-label uses; or public reporting of studies of off-label use. Clinical guidance. Professional societies and other clinical groups often supplement the information available to prescribers from FDA-approved labeling, medical journals, and information from manufacturers. They can issue guidelines and recommend best practices. Congress could engage such groups and encourage professional societies to develop evidence-based clinical guidelines and training regarding off-label use. Precedents from other countries. The United States is not alone in facing the health care and economic implications of off-label use. For example, the member countries of the European Union have addressed measures involving reimbursement, guidance for prescribers, professional standards, and informed consent. Congress could require HHS to contract with the National Academy of Medicine or a similarly equipped entity to review measures taken by the European Union and other regulatory bodies and recommend legislative or administrative actions as appropriate. Concluding Comments Concerns over off-label use overlap with questions raised by some legislators and regulators in other contexts. In addition to clearly related issues such as what is allowable information in direct-to-consumer advertising, promotion to clinicians, and material shared with payors and insurers, off-label use also affects the entire basis of FDA regulation of drugs through its authority to approve drugs. That means it directly or indirectly affects research, clinical innovation, transparency, patents and exclusivities, pricing, and access. Changes in law or regulation in any one area may have benefits in some areas and drawbacks in others. For example, FDA's initiative to encourage research in drugs used traditionally but never reviewed and approved by FDAâso-called legacy drugsâstems from its desire for evidence of safety and effectiveness. Such evidence helps protect patients from possible use of ineffective, unsafe, or misdosed drugs. That initiative, in turn, helps enable sponsors to conduct the clinical trials, submit new drug applications, obtain regulatory exclusivity with the new drug approvalâand then raise the price of the new branded product while expecting FDA to honor the exclusivity and block the sale of the drug by others. For example, clinicians had been prescribing a compounded version of progestin for use in preventing preterm delivery. Such use had never been adequately tested in clinical trials. One company conducted those trials, and FDA approved its new drug application. The initial price for the new drug, Makena, was $30,000 for a 20-week course; patients had been paying pharmacists $200-$400 for the same course. Unanticipated price increases can also arise from the apparent following of FDA procedures. For example, a new owner of the FDA-approval of an old antiparasitic generic drug raised the price from $14 per tablet to $750, Daraprim's initial price. Such sudden and large price increases become a barrier to patient access and, therefore, a potential threat to health. In the case of off-label prescribing, actions in any directionâwhether by Congress, FDA, or the courtsâcould have both intended and unanticipated effects. Actions to limit off-label prescribing could have the intended effects of reducing safety risks and the economic cost of using drugs ineffective for their prescribed purposes. Such limits, however, could also stifle informed clinical exploration. Similarly, incentives to mount clinical trials needed to add an indication to the label could help identify and disseminate information on dosing and contradictions. Such incentives, however, could also hurt. For example, a brand drug that added a new indication to its labeling could prevent, through exclusivities, generics from similarly modifying their labeling. Patients could need to pay more. The recent debates over the right-to-try movement regarding use of investigational drugs by terminally ill patients may preview discussion about any proposed restrictions on off-label use. The Goldwater Institute, considered a key impetus to development and passage of the 2018 enactment of a right-to-try act, looks to diminish government's role in an individual's choice and has supported dissemination of off-label information. Congress has built a process in which a robust FDA can regulate drugs to protect the public's health. Is there cause for concern that perhaps a third of prescriptions are for off-label uses and that, in at least one study, three-quarters of those had minimal or no accepted scientific evidence to support their use? Policy tension exists over the line between wanting to ensure individuals' freedom to take drugs for off-label uses and wanting to protect the public from the risk of unsafe or ineffective drugs. Where to draw that lineâand how to know when it may be time to move the lineâis of continuing interest to regulators and legislators. Appendix. Selected Actions to Expand Information in Drug Labeling