This is the accessible text file for GAO report number GAO-10-201 entitled 'Brand-Name Prescription Drug Pricing: Lack of Therapeutically Equivalent Drugs and Limited Competition May Contribute to Extraordinary Price Increases' which was released on January 11, 2009. This text file was formatted by the U.S. Government Accountability Office (GAO) to be accessible to users with visual impairments, as part of a longer term project to improve GAO products' accessibility. Every attempt has been made to maintain the structural and data integrity of the original printed product. Accessibility features, such as text descriptions of tables, consecutively numbered footnotes placed at the end of the file, and the text of agency comment letters, are provided but may not exactly duplicate the presentation or format of the printed version. The portable document format (PDF) file is an exact electronic replica of the printed version. We welcome your feedback. Please E-mail your comments regarding the contents or accessibility features of this document to Webmaster@gao.gov. This is a work of the U.S. government and is not subject to copyright protection in the United States. It may be reproduced and distributed in its entirety without further permission from GAO. Because this work may contain copyrighted images or other material, permission from the copyright holder may be necessary if you wish to reproduce this material separately. Report to Congressional Requesters: United States Government Accountability Office: GAO: December 2009: Brand-Name Prescription Drug Pricing: Lack of Therapeutically Equivalent Drugs and Limited Competition May Contribute to Extraordinary Price Increases: GAO-10-201: GAO Highlights: Highlights of GAO-10-201, a report to congressional requesters. Why GAO Did This Study: The growing cost of brand-name prescription drugs—FDA-approved drug products that typically have patent protection—is a concern for patients, payers, and providers of health care—particularly when price increases are large and occur suddenly. A 2008 congressional hearing by the Joint Economic Committee drew attention to some small market prescription drugs that had an extraordinary price increase—a price increase of 100 percent or more at a single point in time. GAO was asked to examine extraordinary price increases for brand-name prescription drugs. Specifically, GAO examined the: (1) frequency of extraordinary price increases for brand-name prescription drugs from 2000 to 2008, (2) characteristics of the brand-name prescription drugs that had extraordinary price increases, and (3) factors that contributed to the extraordinary price increases experienced by these brand-name prescription drugs. To determine the frequency and characteristics of the brand-name prescription drugs that experienced an extraordinary price increase, GAO reviewed drug pricing and other data from a pharmaceutical industry compendium. To illustrate the factors that may contribute to extraordinary price increases, GAO developed case studies of six brand-name prescription drugs identified from the analysis of drug pricing data. These brand-name prescription drugs were selected based on factors including price, and the percentage and number of price increases. What GAO Found: From 2000 to 2008, 416 brand-name drug products—different drug strengths and dosage forms of the same drug brands—had extraordinary price increases. These 416 brand-name drug products represented 321 different drug brands. The number of brand-name drug products that had these extraordinary price increases represents half of 1 percent of all brand-name drug products. The number of extraordinary price increases each year more than doubled from 2000 to 2008 and most of the extraordinary price increases ranged between 100 percent and 499 percent. Almost 90 percent of all brand-name drug products that had an extraordinary price increase sustained the new higher price—by either having another increase in price or remaining at the increased price. More than half of the brand-name drug products that had extraordinary price increases were in just three therapeutic classes—central nervous system, anti-infective, and cardiovascular. These therapeutic classes include drugs used to treat conditions such as fungal or viral infections, and heart disease. About half of the extraordinary price increases were for brand-name drug products that were purchased from drug manufacturers or wholesalers, repackaged, and resold in smaller packages to health care providers such as hospitals or physicians. However, some drug repackagers serve a niche in the drug market, and therefore may have a small share of the market in a therapeutic class. The majority of all extraordinary price increases were for drugs priced less than $25 per unit; however, a full course of treatment for some of these drugs could total several thousand dollars. Based on interviews with experts and industry representatives, a lack of therapeutically equivalent drugs—both generics and other brand-name drugs used to treat the same condition—and limited competition may contribute to extraordinary price increases. The limited availability of therapeutically equivalent drugs may result from patent protection and market exclusivity, and the size of the market for a given drug. Patent protection and market exclusivity temporarily limit competition and thereby allow a drug company to recoup research and development costs and earn a return on its financial investment. Two of six case study drugs that had extraordinary price increases were patented at the time of the extraordinary price increase. The transfer of the rights to a drug and corporate consolidations among drug companies may result in fewer drug options and contribute to extraordinary price increases, according to experts. For example, the rights to four of the case-study drugs were obtained by a new drug company, and two of these drugs had an extraordinary price increase shortly after the rights to the drugs were purchased. Finally, experts and industry representatives noted that unusual events—such as disruptions in production due to shortages of raw materials—and other factors, including manufacturing issues, may also contribute to some extraordinary price increases. View [hyperlink, http://www.gao.gov/products/GAO-10-201] or key components. For more information, contact John Dicken at (202) 512-7114 or DickenJ@gao.gov. [End of section] Contents: Letter: Background: More Than 400 Extraordinary Price Increases Occurred for Over 300 Drug Brands from 2000 to 2008: Most Brand-name Drug Products with Extraordinary Price Increases Were in Three Therapeutic Classes, Cost Less Than $25 Per Unit, or Were Repackaged: Lack of Therapeutically Equivalent Drugs and Limited Competition May Contribute to Extraordinary Price Increases for Brand-name Drugs: Expert Comments: Appendix I: Scope and Methodology: Appendix II: Brand-name Prescription Drugs with an Extraordinary Price Increase, 2000 to 2008: Appendix III: Characteristics of Case Study Drugs: Appendix IV: GAO Contact and Staff Acknowledgments: Related GAO Products: Tables: Table 1: Annual Frequency of Extraordinary Price Increases for Brand- name Drugs, 2000 to 2008: Table 2: Annual Frequency of Extraordinary Price Increases for Brand- name Drug Products by Percentage Increase in Price, 2000 to 2008: Table 3: Therapeutic Classes of Brand-name Drug Products That Had Extraordinary Price Increases, 2000 to 2008: Table 4: Frequency of Extraordinary Price Increase by Price Level, by Brand-name Drug Products, 2000 to 2008: Table 5: Annual Frequency of Extraordinary Price Increases for Repackaged and Nonrepackaged Brand-name Drug Products, 2000 to 2008: Table 6: Repackaged Brand-name Drug Products that Had an Extraordinary Price Increase, 2000 to 2008: Table 7: Nonrepackaged Brand-name Drug Products that Had an Extraordinary Price Increase, 2000 to 2008: Table 8: Summary of Characteristics of the Six Case Study Drugs: Abbreviations: AWP: average wholesale price: DOJ: Department of Justice: FDA: Food and Drug Administration: FTC: Federal Trade Commission: NDC: national drug code: [End of section] United States Government Accountability Office: Washington, DC 20548: December 22, 2009: The Honorable Charles E. Schumer: Vice Chairman: Joint Economic Committee: United States Congress: The Honorable Amy Klobuchar: United States Senate: The growing cost of brand-name prescription drugs can be a burden on patients, payers, and providers of health care--particularly when price increases are large and occur suddenly. Controlling rising prescription drug prices helps to ensure that patients can afford medically necessary and sometimes life-saving medications, and to moderate costs for hospitals and third-party payers such as insurance plans and state and federal governments. However, a hearing held in July 2008 by the Joint Economic Committee drew attention to certain prescription drugs that recently had an extraordinary price increase--a price increase equal to 100 percent or more at a single point in time. Drug manufacturers may consider several factors when setting prices for brand-name prescription drugs, including a drug's patent status and market exclusivity. Patents and market exclusivity may provide a limited period of protection from competition, thereby allowing a drug company to recoup research and development costs and earn a return on its financial investment. Drug manufacturers may obtain patents or patent extensions from the U.S. Patent and Trademark Office. In addition, independent of a drug product's patent status, the Federal Food, Drug, and Cosmetic Act authorizes various periods of market exclusivity for drug products. In this report, GAO studied extraordinary price increases for brand- name prescription drugs. Specifically, we examined (1) the frequency of extraordinary price increases for brand-name prescription drugs from 2000 to 2008, (2) the characteristics of the brand-name prescription drugs that had extraordinary price increases, and (3) the factors that contributed to the extraordinary price increases experienced by these brand-name prescription drugs. To determine the frequency of extraordinary price increases, we reviewed the average wholesale price (AWP)[Footnote 1] for all brand- name prescription drugs in Thomson Reuters' Red Book,[Footnote 2] and identified all extraordinary price increases--a unit price[Footnote 3] increase of 100 percent or more at a single point in time--from 2000 to 2008. Red Book includes drug prices for each package size (for example, 30, 60, or 100 tablets) and dosage form (for example, tablet or injection) of a brand-name drug.[Footnote 4] We report the frequency of extraordinary price increases in two ways--by drug brand (or drug label name as recorded in Red Book) and by brand-name drug product. For the drug brand frequencies, we counted an extraordinary price increase if the price of any version of a brand-name drug increased by 100 percent or more at a single point in time. For brand-name drug products, we counted each extraordinary price increase for each version--drug strength and dosage form--of the brand-name drug separately. For example, if both the 1mg and 5mg tablet versions of a drug had extraordinary price increases, we categorized this as one drug brand increase, and as two brand-name drug product increases (one for each version of the brand-name drug). The frequencies of extraordinary price increases reported include brand-name drug products that were repackaged for resale to health care providers such as hospitals or physicians.[Footnote 5] To identify the characteristics of brand-name drug products that had an extraordinary price increase, we used Red Book data on therapeutic class[Footnote 6] and price. To identify the factors that may contribute to extraordinary price increases, we interviewed drug policy experts; academic researchers; state and federal government officials; consumer advocates; insurance company representatives; and representatives from hospital, health insurance, and retail pharmacy associations. To illustrate the factors that may contribute to extraordinary price increases, we developed case studies of six different brand-name drugs from different drug companies identified from our analysis of Red Book data. Each brand-name drug that was active in the market as of December 31, 2008 and that had an extraordinary price increase was eligible for selection for the case study. To achieve variability in the characteristics of the brand-name drugs reviewed for the case study, our selection was based on several factors, including a drug's price, the level of the percentage increase, whether the drug had more than one extraordinary price increase between 2000 and 2008, availability of the drug from multiple sources, and permanence of the price increase. To gain an understanding of the market and other dynamics leading to the extraordinary price increase experienced by each brand-name drug in our case studies, we interviewed representatives of the companies that manufacture and distribute these brand-name drugs,[Footnote 7] and obtained information about each drug company's business strategy from the companies' Web sites, annual and quarterly reports, and other resources. (See appendix I for a detailed description of our scope and methodology.) We reviewed the Red Book data file to assess its reliability. This review involved an assessment of the variables in Red Book to identify incorrect and erroneous entries or extreme outliers. We compared a random sample of the pricing data reported in Red Book with pricing data in another drug pricing compendium. Based on this review, we determined that the data used in this report were adequate for our purposes. We conducted our work from October 2008 through December 2009 in accordance with all sections of GAO's Quality Assurance Framework that are relevant to our objectives. The framework requires that we plan and perform our engagement to obtain sufficient and appropriate evidence to meet our stated objectives and to discuss any limitations in our work. We believe that the information and data obtained, and the analysis conducted, provide a reasonable basis for any findings and conclusions in this product. Background: Extraordinary price increases for brand-name drugs can lead to substantially higher drug spending for public and private insurance plans, hospitals, and other providers that cover prescription drugs. Patients may also face higher out-of-pocket costs and reduced access to medically necessary and sometimes life-saving drugs. In addition, extraordinary price increases for brand-name drugs may contribute to overall drug spending, which has increased an average of about 10 percent a year since 2000.[Footnote 8] As reported during the Joint Economic Committee hearing, a small but growing subset of drugs have had very large and sudden price increases since 2000, raising questions about the competitiveness of the prescription drug marketplace. Overview of Brand-name Drugs: Brand-name drugs are drug products that have received FDA approval and typically have patent protection.[Footnote 9] After the patent and any applicable period of market exclusivity expires, these drugs are still considered brand-name drugs, but other drug companies may develop a generic equivalent--a similar drug that contains the same active ingredient, strength, dosage form, route of administration, and intended use.[Footnote 10] The FDA reviews and approves both brand-name and generic prescription drugs. Brand-name drugs may be supplied to health care providers from companies other than a drug's manufacturer. For example, brand-name drugs may be repackaged from large drug inventories into smaller packages, and sold by a repackaging company using a unique national drug code (NDC). Repackagers include health maintenance organizations, pharmacies, and private companies. Repackagers are required to follow FDA guidelines, such as registering annually with the FDA and labeling drugs under the same brand name. Repackagers may obtain prescription drugs from wholesalers, and sell the repackaged drugs to health care providers such as hospitals or physicians who then dispense them to patients. Proponents of repackaged drugs believe that they offer convenience to patients and may reduce medication errors.[Footnote 11] However, some experts suggest that repackaging drugs may unnecessarily increase drug prices and profits. Repackagers may assign AWPs for repackaged drugs that differ from the AWP suggested by the drug's manufacturer. Patents, Market Exclusivity, and Orphan Drugs: Patents and market exclusivity protect prescription drugs by limiting competition for a set period of time. A drug manufacturer may seek a 20- year patent on various aspects of its new chemical entity from the U.S. Patent and Trademark Office.[Footnote 12] Once a patent is granted, other drug manufacturers are excluded from making, using, or selling the patented formula during the life of the patent. Companies that develop new brand-name drugs generally obtain a patent on the active ingredient used in the drug. Patents may be granted for other properties of a brand-name drug, such as its formulation and composition, and/or method of use.[Footnote 13] After receiving a patent on a brand-name drug, drug companies typically seek approval from the FDA for use of the drug to treat certain indications. Market exclusivity may be granted for approved drugs and is independent of the rights granted by a patent. The Federal Food, Drug, and Cosmetics Act authorizes various periods of market exclusivity for drug products. Generally, market exclusivities prevent the FDA from approving any application for a competing drug compound for a stated period of time. These exclusivities may relate to new chemical entities (5 years),[Footnote 14] previously approved drugs with a new application that is based on new clinical studies (3 years),[Footnote 15] generic drugs (180 days),[Footnote 16] drugs tested for use in children (6 months),[Footnote 17] and orphan drugs (7 years).[Footnote 18] Market exclusivity and patent protection may run concurrently. The Joint Economic Committee hearing in July 2008 identified certain brand-name drugs which treat rare diseases that experienced extraordinary price increases. Incentives are available for drug companies to develop innovative drugs for rare diseases (orphan drugs). In addition to the 7-year market exclusivity status, these incentives may include tax incentives of up to 50 percent of the cost of clinical research, and a waiver of FDA fees.[Footnote 19] Research grants are also available through the FDA for the development of drugs used to treat rare diseases or conditions. Drug Market Trends: According to experts, the drug industry's traditional business model is changing. In the past, large drug companies conducted research and development on several drugs, with the goal of releasing one or more "blockbuster" drugs that treat a large population and can earn billions of dollars. Recently, drug companies have increasingly focused on specialty drugs that target niche markets, or a smaller population of people with a narrow indication or medical condition. According to experts and industry representatives, the pace of consolidation among drug companies through mergers and acquisitions and transfers of drug ownership rights has increased. Fewer companies producing and marketing drugs can lead to greater market domination among certain companies and less competition. In addition, large drug companies have purchased other drug companies that specialize in manufacturing drugs targeting niche populations or drugs in similar therapeutic classes. Setting Prescription Drug Prices: According to some economists, the usual mechanisms that enforce market discipline may not work in the same manner in the health care market. In most markets--automobiles, for example--consumers are expected to be conscious of the price of goods. If a company raises the price of its goods, consumers would likely purchase fewer goods, causing the company's revenues to decline. However, health care providers influence demand because they typically act on behalf of patients, who may remain unaware of drug costs. If the patient is insured and their medical bills are paid by a third-party payer, then demand may not be significantly influenced by changes in price to the extent that it might be in other markets. Some price restraint may be provided by pharmacy benefit managers and health plans that use drug formularies to negotiate price rebates on brand name prescription drugs. According to industry representatives and experts, drug companies may consider several issues when setting the price of a drug. These include: (1) the perceived value of a drug relative to its competitors, such as its ease of use; (2) the unique characteristics of a drug, such as its novelty, the frequency of administration, and safety; (3) the cost of therapeutically alternative drugs and alternative therapies, such as surgery, medical devices, and existing drugs; (4) the disease treated; (5) the size and characteristics of the patient market; (6) research and development, manufacturing, and marketing costs; (7) the willingness of customers to pay for the drug; and (8) the amount of reimbursement for the drug from third-party payers. To mitigate high drug prices some companies subsidize the price of some of their brand- name drugs through a patient assistance program to low-income uninsured or underinsured patients.[Footnote 20] Federal Oversight: While prescription drug pricing in the private sector is not subject to federal regulation, drug companies are subject to antitrust enforcement. The Federal Trade Commission (FTC) and the U.S. Department of Justice (DOJ) enforce federal antitrust laws that prohibit activities such as mergers and acquisitions that may substantially reduce competition or create a monopoly.[Footnote 21] Companies are required to notify the FTC and DOJ of certain pending mergers, also known as the pre-merger notification program.[Footnote 22] In addition, the FTC has authority to investigate and take action against unfair methods of competition affecting commerce, including in the drug industry.[Footnote 23] Price fixing agreements between businesses, certain monopolies, and other anticompetitive conduct are subject to review and enforcement action. FTC officials indicated that the FTC has not brought a case against a drug company for charging extraordinarily high prices because such activity is not expressly prohibited by federal law, and because high drug prices in the absence of anticompetitive behavior are not per se illegal. The FTC has challenged anticompetitive patent settlements between brand-name and generic drug manufacturers. For example, FTC officials indicated that the agency has filed cases challenging "pay-to-delay" settlements in which a brand- name manufacturer shares a portion of its future profits with a potential generic competitor in exchange for an agreement to delay marketing the generic prescription drug. Finally, drugs must be manufactured in accordance with FDA regulations called good manufacturing practices, and the FDA inspects manufacturing facilities before a drug can be approved.[Footnote 24] Good manufacturing practices are designed to ensure the safety and quality of drug products and lay out minimum standards for the facilities and equipment used in manufacturing drug products. All drug manufacturers-- including companies that acquire the rights to a drug from another manufacturer--are required to comply with good manufacturing practices. More Than 400 Extraordinary Price Increases Occurred for Over 300 Drug Brands from 2000 to 2008: Between 2000 and 2008, 416 brand-name drug products representing 321 drug brands had extraordinary price increases. Most often, these extraordinary price increases ranged from 100 percent to 499 percent, but in a few cases were 1,000 percent or more. From 2000 to 2008, 416 Extraordinary Price Increases Occurred for 321 Different Drug Brands: From 2000 to 2008, 416 brand-name drug products representing 321 drug brands had an extraordinary price increase. A number of these 321 drug brands had two or more extraordinary price increases between 2000 and 2008. The number of brand-name drug products that had these extraordinary price increases each year trended upwards, more than doubling from 2000 to 2008; however, they represent about half of 1 percent of all brand-name drug products. (See table 1 for the frequency of extraordinary price increases.) Most brand-name drug products that had an extraordinary price increase sustained the new price after the extraordinary price increase occurred.[Footnote 25] For example, following the extraordinary price increase, about 87 percent of the brand-name drug products remained at the increased price, or had another increase in price, and only 13 percent had a decrease in price. [Footnote 26] Table 1: Annual Frequency of Extraordinary Price Increases for Brand- name Drugs, 2000 to 2008: Drug brands[A]: Category: Number of extraordinary price increases for drug brands; 2000: 24; 2001: 21; 2002: 23; 2003: 38; 2004: 38; 2005: 33; 2006: 38; 2007: 52; 2008: 54; Total: 321. Brand-name drug products[B]: Category: Number of extraordinary price increases for brand-name drug products; 2000: 28; 2001: 27; 2002: 31; 2003: 48; 2004: 51; 2005: 39; 2006: 47; 2007: 74; 2008: 71; Total: 416. Total number of all brand-name drug products on the market[C]: 2000: 11,503; 2001: 11,503; 2002: 11,106; 2003: 11,413; 2004: 11,436; 2005: 11,979; 2006: 12,798; 2007: 12,895; 2008: 13,193; Total: N/A[D]. Source: GAO analysis of average wholesale price from Red Book. Note: Drug prices are identified and reported by a unique national drug code (NDC). [A] A drug brand is the drug label name as recorded in Red Book. [B] A brand-name drug product includes the same drug brand with different strengths and dosage forms. The frequencies for brand-name drug products are reported using NDC-9s. [C] Total number of brand-name drugs recorded in the Red Book for each calendar year. As of December 31, 2008, some of these drugs were no longer active on the market. [D] Totals for the period are not provided. Drugs that were recorded in Red Book may appear in multiple years. [End of table] A number of these brand-name drug products had more than one extraordinary price increase. For example, 21 of the 416 brand-name drug products had more than one extraordinary price increase between 2000 and 2008, and 9 of those 21 brand-name drug products had more than one extraordinary price increase in the same year. The 416 brand-name drug products were sold by 91 drug companies, and 12 of these 91 drug companies sold brand-name drug products that had more than one extraordinary price increase between 2000 and 2008. Furthermore, 4 of these 91 drug companies sold brand-name drug products that had more than one extraordinary price increase within the same year. (See appendix II for a list of brand-name drugs that had an extraordinary price increase.) While Most Extraordinary Price Increases Were Less Than 500 Percent, Some Increases Were 1,000 Percent or More: Most extraordinary price increases--for 357 of the 416 brand-name drug products with extraordinary price increases--ranged from 100 percent to 499 percent.[Footnote 27] Overall, the median increase for brand name drug products was about 158 percent. However, some brand-name drug products had very large extraordinary price increases. For example, 26 brand-name drug products had extraordinary price increases greater than 1,000 percent--a tenfold increase. The largest extraordinary price increase for brand-name drug products was about 4,200 percent. (See table 2 for the frequency of extraordinary price increases by percent increase.) In addition, 7 brand-name drug products had extraordinary price increases of 500 percent or more multiple times from 2000 to 2008. Table 2: Annual Frequency of Extraordinary Price Increases for Brand- name Drug Products by Percentage Increase in Price, 2000 to 2008: Brand-name drug products[A]: Category: Total brand-name drug products with extraordinary increase in price; 2000: 28; 2001: 27; 2002: 31; 2003: 48; 2004: 51; 2005: 39; 2006: 47; 2007: 74; 2008: 71; Total: 416. Category: Total brand-name drug products with extraordinary increase in price: 100-499 percent; 2000: 22; 2001: 15; 2002: 23; 2003: 43; 2004: 43; 2005: 37; 2006: 43; 2007: 64; 2008: 67; Total: 357. Category: Total brand-name drug products with extraordinary increase in price: 500-999 percent; 2000: 3; 2001: 3; 2002: 6; 2003: 5; 2004: 6; 2005: 2; 2006: 2; 2007: 3; 2008: 3; Total: 33. Category: Total brand-name drug products with extraordinary increase in price: 1,000-1,499 percent; 2000: 0; 2001: 4; 2002: 0; 2003: 0; 2004: 2; 2005: 0; 2006: 1; 2007: 2; 2008: 1; Total: 10. Category: Total brand-name drug products with extraordinary increase in price: 1,500-1,999 percent; 2000: 1; 2001: 3; 2002: 0; 2003: 0; 2004: 0; 2005: 0; 2006: 0; 2007: 3; 2008: 0; Total: 7. Category: Total brand-name drug products with extraordinary increase in price: More than 2,000 percent; 2000: 2; 2001: 2; 2002: 2; 2003: 0; 2004: 0; 2005: 0; 2006: 1; 2007: 2; 2008: 0; Total: 9. Source: GAO analysis of average wholesale price from Red Book. Note: Drug prices are identified and reported by a unique NDC. [A] A brand-name drug product includes the same drug brand with different strengths and dosage forms. The frequencies for brand-name drug products are reported using NDC-9s. [End of table] Most Brand-name Drug Products with Extraordinary Price Increases Were in Three Therapeutic Classes, Cost Less Than $25 Per Unit, or Were Repackaged: Brand-name drug products that had extraordinary price increases shared similar characteristics including therapeutic class, cost, or packaging. While extraordinary price increases occurred in 20 therapeutic classes, more than half of the increases fell into 3 therapeutic classes--central nervous system agents, anti-infective agents, and cardiovascular agents. Most extraordinary price increases were for brand-name drug products costing less than $25 per unit. Depending on the condition treated and length of treatment, the full cost of treatment for a drug could total several thousand dollars. More than half of all extraordinary price increases were for repackaged brand-name drug products. Three Therapeutic Classes Accounted for More Than Half of the Extraordinary Price Increases: While extraordinary price increases for brand-name drug products occurred in 20 therapeutic classes, the majority of the drugs--52 percent--that had extraordinary price increases fell into 3 therapeutic classes--central nervous system, anti-infective, and cardiovascular drugs.[Footnote 28] * Central nervous system--126 brand-name drug products had extraordinary price increases. Central nervous system drugs include sedatives and antidepressants, and are typically used to treat depression or anxiety. * Anti-infective--55 brand-name drug products had extraordinary price increases. Anti-infective drugs are used to treat infections caused by fungi, bacteria, or viruses. * Cardiovascular drugs--35 brand-name drug products had extraordinary price increases. Cardiovascular drugs such as anti-arrhythmia agents are used to treat the heart. The remaining 17 therapeutic classes comprised 192 brand-name drug products that had extraordinary price increases. (See table 3 for frequency of extraordinary price increases by therapeutic class.) Table 3: Therapeutic Classes of Brand-name Drug Products That Had Extraordinary Price Increases, 2000 to 2008: Brand-name drug products[A]: Therapeutic class: Central nervous system agents; 2000: 9; 2001: 6; 2002: 6; 2003: 16; 2004: 12; 2005: 13; 2006: 20; 2007: 24; 2008: 20; Total: 126. Therapeutic class: Anti-infective agents; 2000: 9; 2001: 2; 2002: 9; 2003: 8; 2004: 8; 2005: 6; 2006: 6; 2007: 2; 2008: 5; Total: 55. Therapeutic class: Cardiovascular agents; 2000: 3; 2001: 2; 2002: 1; 2003: 0; 2004: 4; 2005: 4; 2006: 5; 2007: 5; 2008: 11; Total: 35. Therapeutic class: Other therapeutic classes; 2000: 7; 2001: 15; 2002: 15; 2003: 23; 2004: 27; 2005: 16; 2006: 16; 2007: 42; 2008: 31; Total: 192. Total brand-name drug products that increased in price[B]: 2000: 28; 2001: 27; 2002: 31; 2003: 48; 2004: 51; 2005: 39; 2006: 47; 2007: 74; 2008: 71; Total: 416. Source: GAO analysis of average wholesale price from Red Book. Note: Drug prices are identified and reported by a unique NDC. [A] A brand-name drug product includes the same drug brand with different strengths and dosage forms. The frequencies for brand-name drug products are reported using NDC-9s. [B] Columns do not add up to total because eight records were not classified into a therapeutic class in Red Book. [End of table] Brand-name Drug Products Priced Less Than $25 Per Unit Accounted for Most of the Extraordinary Price Increases: Ninety-six percent of brand-name drug products that had extraordinary price increases cost less than $25 per unit prior to the price increase.[Footnote 29],[Footnote 30] Overall, brand-name drug products that had an extraordinary price increase ranged in price from $0.01 per unit to $5,400 per unit prior to the price increase. The median price of the brand-name drug products that had an extraordinary price increase rose from $1.66 per unit before the increase to $4.70 per unit after the increase.[Footnote 31] (See table 4 for the frequency of extraordinary price increases by price level.) Table 4: Frequency of Extraordinary Price Increase by Price Level, by Brand-name Drug Products, 2000 to 2008: Brand-name drug products[A]: Price prior to increase: Less than $25.00 per unit; 100-499 percent: 344; 500-999 percent: 31; 1,000-1,499 percent: 8; 1,500-1,999 percent: 7; 2,000 percent or more: 9; Total: 399. Price prior to increase: $25.00 to $49.99 per unit; 100-499 percent: 4; 500-999 percent: 0; 1,000-1,499 percent: 1; 1,500-1,999 percent: 0; 2,000 percent or more: 0; Total: 5. Price prior to increase: $50.00 or more per unit; 100-499 percent: 9; 500-999 percent: 2; 1,000-1,499 percent: 1; 1,500-1,999 percent: 0; 2,000 percent or more: 0; Total: 12. Total number of brand-name drug products that increased in price: 100-499 percent: 357; 500-999 percent: 33; 1,000-1,499 percent: 10; 1,500-1,999 percent: 7; 2,000 percent or more: 9; Total: 416. Source: GAO analysis of average wholesale price from Red Book. Note: Drug prices are identified and reported by a unique NDC. [A] A brand-name drug product includes the same drug brand with different strengths and dosage forms. The frequencies for brand-name drug products are reported using NDC-9s. [End of table] It is important to note that the unit price of a drug is only one factor in determining the cost of a full course of treatment for a medical condition. Other factors affecting cost include the total number of units prescribed and the duration of the treatment. For example, the full cost of treatment for a drug that is priced less than $25 per unit could total several thousand dollars or more. One of the drugs we reviewed that is used to treat a rare cancer cost $390 for a full course of treatment prior to the extraordinary price increase. [Footnote 32] After two extraordinary price increases, the full cost of a course of treatment rose to more than $3,000. Repackaged Drugs Accounted for More Than Half of the Extraordinary Price Increases for Brand-name Drug Products: More than half of the brand-name drug products that had extraordinary price increases were repackaged--that is, purchased from drug manufacturers or wholesalers and resold in smaller packages to health care providers such as hospitals or physicians.[Footnote 33] (See table 5 for frequency of extraordinary price increases for repackaged and nonrepackaged drugs.) Almost all the extraordinary price increases for repackaged drugs appear to have originated from the company that repackaged the drug rather than from the company that manufactured the drug.[Footnote 34] Specifically, 95 percent of repackaged drugs had an extraordinary price increase without a corresponding extraordinary price increase by the drug's manufacturer for the identical nonrepackaged drug. However, some drug repackagers serve a niche in the drug market and therefore may have a small share of the market in a therapeutic class. Table 5: Annual Frequency of Extraordinary Price Increases for Repackaged and Nonrepackaged Brand-name Drug Products, 2000 to 2008: Brand-name drug products[A]: Category: Repackaged drugs that increased in price; 2000: 18; 2001: 10; 2002: 15; 2003: 27; 2004: 19; 2005: 29; 2006: 33; 2007: 31; 2008: 29; Total: 211. Category: Nonrepackaged drugs that increased in price; 2000: 10; 2001: 17; 2002: 16; 2003: 21; 2004: 32; 2005: 10; 2006: 14; 2007: 43; 2008: 42; Total: 205. Category: Total brand-name drugs that increased in price; 2000: 28; 2001: 27; 2002: 31; 2003: 48; 2004: 51; 2005: 39; 2006: 47; 2007: 74; 2008: 71; Total: 416. Total number of all repackaged brand-name drug products on the market[B]: 2000: 3,162; 2001: 3,496; 2002: 3,307; 2003: 3,648; 2004: 3,743; 2005: 4,333; 2006: 5,078; 2007: 5,423; 2008: 5,690; Total: N/A[C]. Source: GAO analysis of average wholesale price from Red Book. Note: Drug prices are identified and reported by a unique NDC. [A] A brand-name drug product includes the same drug brand with different strengths and dosage forms. The frequencies for brand-name drug products are reported using NDC-9s. [B] Total number of brand-name drugs recorded in Red Book for each calendar year. As of December 31, 2008, some of these drugs were no longer active on the market. [C] Totals for the period are not provided. Drugs that were recorded in Red Book may appear in multiple years. [End of table] Almost one-fifth of the 91 companies that sold brand-name drug products that had extraordinary price increases were repackagers. The four companies with the greatest number of brand-name drug products that had an extraordinary price increase were repackagers--ranging from 26 to 51 brand-name drug products per repackaging company.[Footnote 35] About 99 percent of repackaged drugs cost less than $25 per unit.[Footnote 36] The median price of repackaged drugs that had extraordinary price increases rose from $2.14 per unit to $5.39 per unit after the increase.[Footnote 37] Lack of Therapeutically Equivalent Drugs and Limited Competition May Contribute to Extraordinary Price Increases for Brand-name Drugs: Based on interviews with experts and industry representatives, we found that a lack of therapeutically equivalent drugs--generics and other brand-name drugs used to treat the same condition--and limited competition may contribute to extraordinary price increases. According to these experts and industry representatives, the availability of few therapeutically equivalent drugs may result from patent protection and market exclusivity, and the limited size of the market for a given drug. Experts noted that the transfer of drug rights and corporate consolidations may limit competition among drug companies, resulting in few drug options. The experts and industry representatives also noted that unusual events--such as disruptions in production due to shortages of raw materials--and other factors may also contribute to some extraordinary price increases. Limited Availability of Therapeutic Equivalents: Experts we interviewed said that drugs without therapeutic equivalents--in some cases due to patents or a limited market size--may be more likely to have an extraordinary price increase.[Footnote 38] Experts and industry representatives also reported that competition within a therapeutic class of drugs may be limited by (1) patents for a new drug, such as patents for the active ingredient; (2) patents for existing drugs that have been modified by, for example, changing a drug's active ingredient, strength, or delivery mechanism;[Footnote 39] and (3) market exclusivity protections. Patents and market exclusivity may limit the entry of other prescription drugs into the market. An expert also noted that no single factor leads to extraordinary price increases, rather a combination of several factors likely contributes to these extraordinary price increases. Two of our six case study drugs[Footnote 40] had patent protection at the time of the extraordinary price increase. (See appendix III for a summary of the characteristics of the case study drugs.) One drug had a method-of-use patent and was the only FDA-approved drug available to treat an acute illness affecting infants and young children. The other drug was under patent at the time of its extraordinary price increase, and was sold by a licensed repackager that purchased the drug from wholesalers. In addition, experts and industry representatives we interviewed reported that small market drugs, such as orphan drugs or drugs for rare diseases, may lack therapeutically equivalent drugs, and thus may be prone to extraordinary price increases. When the target patient population or market for a drug is relatively small, there may be little financial incentive for potential competitors to enter the market and offer competing drugs. Two of the drugs we examined in our case studies treat rare diseases. These drugs did not have generic equivalents at the time of their extraordinary price increases; however, the drug companies reported the availability of other drugs that treat similar conditions. Both drugs had more than one extraordinary price increase--one of the drugs had two price increases that were each more than 1,000 percent, and the other had extraordinary price increases in 2 consecutive years. Representatives of the manufacturer for one of these drugs reported that their company's business model is based almost solely on sales from the drug that had the extraordinary price increases. This drug is currently approved for several dozen indications, and the company is funding research on other uses for the drug. The second company reported that its business model is structured around facilitating the development of drug products for rare diseases. The company provides financial support to researchers developing new drugs for rare diseases and obtains the rights to the drugs created by these researchers. The company considered their financial support for developing other rare disease drugs when determining the price of their drug. Furthermore, a representative of this company stated that it had obtained other drugs that were discontinued by a prior owner and then reintroduced the drugs onto the market. Both of these drug companies market specialized drugs that treat rare diseases. Transfer of Drug Rights, Corporate Consolidations, Mergers, and Acquisitions: Experts and industry representatives we interviewed reported that transfers of drug ownership rights and consolidations among drug companies have increased.[Footnote 41] These transfers and consolidations may limit competition as companies that may offer competing prescription drugs in a therapeutic class merge or sell their rights to a drug, potentially leading to extraordinary price increases for drugs. Fewer drug companies competing in a therapeutic class may lead to fewer prescription drugs being developed and sold within that class. Industry representatives and experts reported that larger drug companies are acquiring drugs from smaller drug companies that conduct drug research. Notwithstanding potential FTC or DOJ review, drug companies may still acquire competitors that offer similar drugs, potentially leading to market domination in a therapeutic class. [Footnote 42] The rights to four of our case study drugs were obtained by a new drug company, and two of these drugs had an extraordinary price increase shortly after the rights to the drugs were purchased. Unusual Events: Extraordinary price increases were also attributed by industry representatives and experts to the occurrence of unusual events, such as disruptions in the production of a drug due to shortages of necessary raw materials or the added costs to renovate outdated drug production plants. For example, a drug in our case study was purchased from a drug company that was suspending production of the drug. The company that purchased this drug reported investing millions of dollars transferring and upgrading the manufacturing equipment, processes, and testing methods required to make the drug. The drug's manufacturer attributed the first of two extraordinary price increases to compensating for the drug's production expenses and other costs. Prior to the company's purchase of the drug, it was sold only in limited quantities through a patient advocacy group.[Footnote 43] Another drug from our case study was purchased by a company that spent several years trying to identify a technical partner capable of processing the drug's active ingredient, which was difficult to manufacture because of its cytotoxic nature and the limited quantity of drugs produced. The company's representative stated that due to the unique challenges of producing the active ingredient of the drug, two companies were involved in manufacturing and packaging the drug. As a result of changes made in manufacturing the drug, the company reported investing several million dollars upgrading its manufacturing equipment and processes in order to meet updated FDA regulations.[Footnote 44] This company considered its investment to produce a stable supply of the drug when pricing the product. Other Factors: Representatives of the drug companies we reviewed for our case studies reported that they considered other factors when determining the price of their drugs. For example, one expert noted that extraordinary price increases may occur because a drug manufacturer updates the price of a drug after obtaining new information about certain demand and supply factors affecting the drug. Three of the drug companies reported that their products were difficult to manufacture. These companies employ third-party manufacturers that produce the drugs. One of these companies said that its drug was very toxic, and since its manufacturing equipment was used to make other drug products, the equipment must be decontaminated after each batch is produced. These drug companies factored in these additional costs when they raised the price of their products. Some of the drug companies we reviewed revised the price of their brand- name drugs to bring them in line with the prices of what they regarded as similar drugs. One company reviewed the estimated annual cost of several orphan drugs when determining the price for its drug, which treats a rare disease. Three companies reviewed various drug products and priced their drugs in line with these drugs. This pricing strategy led, in part, to these drugs experiencing an extraordinary price increase. An official from one of these companies reported that the drug was underpriced, and the company increased the price of the drug based on the prices of competing drug products used for similar medical conditions. Some of the drug companies considered the financial solvency of their drug product and company, and their fiduciary responsibility to their shareholders when determining the price of their drug. In some cases, representatives of drug companies cited the quantity of free or low-cost drugs donated through their patient assistance program and the level of rebates paid to the Medicaid program as factors that they considered when raising the price of their brand-name drugs. [Footnote 45] Two drug companies said that the level of rebates paid to the Medicaid program was a factor for their drugs' extraordinary price increases.[Footnote 46] The companies reported that they charged a higher retail price for their drugs, in part, to account for the large financial outlays to patient assistance and government programs. One company said that Medicaid beneficiaries represent a large portion of the patient population that uses their drug product. This company's representatives stated that over half of its drug sales were targeted to their patient assistance program for low-income, underinsured, or uninsured individuals or were reimbursed under Medicaid and therefore subject to rebates. These companies reported that they offered patient assistance programs that provide a large volume of free prescription drugs to patients who meet established criteria. The programs also provide financial assistance to insured patients who face financial hardship from paying copayments or coinsurance. Expert Comments: We provided a draft of this report to drug policy experts, who provided technical comments that we incorporated as appropriate. As agreed with your offices, unless you publicly announce the contents of this report earlier, we plan no further distribution until 30 days from the report date. At that time, we will send copies of this report to other interested parties. We will also provide copies to others upon request. In addition, the report is available at no charge on the GAO Web site at [hyperlink, http://www.gao.gov]. If you or your staff have any questions about this report, please contact me at (202) 512-7114 or at dickenj@gao.gov. Contact points for our Offices of Congressional Relations and Public Affairs can be found on the last page of this report. GAO staff members who made major contributions to this report are listed in appendix IV. Signed by: John E. Dicken Director, Health Care: [End of section] Appendix I: Scope and Methodology: In this report we address the following objectives: (1) the frequency of extraordinary price increases for brand-name prescription[Footnote 47] drugs from 2000 to 2008, (2) the characteristics of the brand-name drugs that had extraordinary price increases, and (3) the factors that contributed to the extraordinary price increases experienced by these brand-name drugs. To determine the frequency of extraordinary price increases, we reviewed the average wholesale price (AWP)[Footnote 48] for all brand- name drugs in Thomson Reuters' Red Book,[Footnote 49] and identified all extraordinary price increases--a unit price increase[Footnote 50] equal to 100 percent or more at a single point in time from 2000 to 2008. We calculated the percent change in unit AWP recorded in the Red Book for each 11-digit national drug code (NDC-11).[Footnote 51] For example, where a NDC-11 had three unit prices reported in Red Book from 2000 to 2008 (unit price at point 1, unit price at point 2, and unit price at point 3), two data records were created. One record contained the percent change in unit price from point 1 to point 2, and the other record contained the percent change from point 2 to point 3. We identified extraordinary price increases by selecting only records (NDC- 11s) with a percent change of 100 percent or more. Drugs sold in different package sizes--for example, 30, 60, or 100 tablets--have different NDC-11 codes. Each NDC-11 record captures the label name of the drug which includes the dosage form of the drug. Because a brand-name drug may have several NDC-11 codes for different package sizes, we identified the number of brand-name drug products that had an extraordinary price increase by their NDC-9 code, which represents the manufacturer and drug name, and strength. Where more than one package size of the same brand-name drug had an extraordinary price increase, we selected the package size with the highest extraordinary price increase.[Footnote 52] We counted an NDC-9 with different package sizes that had an extraordinary price increase on the same date only once. In this report, we use three terms to refer to the brand-name prescription drugs recorded in the Red Book. Drug brand refers to the label name of a brand-name prescription drug; brand-name drug product refers to the different products of the same drug brand. Otherwise we use the term brand-name drug or drug when we do not need to distinguish between drug brand and brand-name drug product. We report the frequency of brand-name drugs that had extraordinary price increases by (1) drug brand (drug label name as recorded in Red Book), and (2) brand-name drug product (NDC-9 code). The frequencies of extraordinary price increases reported by brand-name drug products (NDC- 9) include the same drug brand sold in different strengths and dosage forms (e.g., a 1mg or a 5mg tablet). The frequency of extraordinary price increases reported includes brand-name drug products that were repackaged by a distributor for resale to health care providers. [Footnote 53],[Footnote 54] (See appendix II for a list of the brand- name drugs that had extraordinary price increases.) To identify the characteristics of brand-name drugs that had an extraordinary price increase, we used Red Book data on therapeutic class and price. To identify the factors that may contribute to extraordinary price increases we interviewed drug policy experts; academic researchers; state and federal government officials; consumer advocates; insurance company representatives; and hospital, health insurance, and retail pharmacy associations representatives. To illustrate the factors that may contribute to extraordinary price increases, we developed case studies of six drugs from different companies identified from our analysis of Red Book data. Each brand-name drug (NDC-11) was eligible for inclusion as a case study if it was active in the market as of December 31, 2008, and had an extraordinary price increase. To achieve variability in the characteristics of the drugs reviewed for the case study, selection was based on several factors, such as the (1) unit price, (2) percentage increase in price, (3) year of increase, (4) number of increases, (5) availability from multiple sources, (6) orphan drug status, and (7) permanence of the price increase. We also interviewed representatives of the companies that manufactured and distributed the case study drugs about the market dynamics leading to the drugs' extraordinary price increases. We gathered information on: (1) the characteristics of each drug, such as its patent and market exclusivity status, indication, volume, and utilization; (2) corporate business and marketing strategy for each drug; (3) factors that influenced the extraordinary price increase; and (4) agreements with the makers of drugs in the same therapeutic class. Some information provided by the representatives during these interviews is considered proprietary. As a result, the names of the participating companies and brand-name drugs are not identified. (See appendix III for information on each of the drugs from the case studies.) Information was also obtained from drug companies' Web sites, annual and quarterly reports, and other resources. We systematically reviewed Red Book to assess its reliability. The review involved an assessment of the frequencies of all numeric and date variables in Red Book to identify incorrect and erroneous entries or extreme outliers.[Footnote 55] We compared a sample of the pricing data for brand-name drugs that had extraordinary price increases reported in Red Book with pricing data contained in another drug pricing compendium and found a high degree of concurrence between the prices recorded in both data sources. Based on this review, we determined that the data used in our report were adequate for our purposes. We conducted our work from October 2008 through December 2009 in accordance with all sections of GAO's Quality Assurance Framework that are relevant to our objectives. The framework requires that we plan and perform our engagement to obtain sufficient and appropriate evidence to meet our stated objectives and to discuss any limitations in our work. We believe that the information and data obtained, and the analysis conducted, provide a reasonable basis for any findings and conclusions in this product. [End of section] Appendix II: Brand-name Prescription Drugs with an Extraordinary Price Increase, 2000 to 2008: Using Thomson Reuters' Red Book,[Footnote 56] we calculated the change in average wholesale price (AWP) and identified all unit price increases equal to 100 percent or more at a single point in time from 2000 to 2008. (See appendix I for more information.) Based on this analysis, we identified the label names of drugs that had extraordinary price increases by their NDC-9 code.[Footnote 57] AWP records in Red Book are reported by the drug manufacturer and published in Red Book. In some cases, when drug manufacturers do not report AWP, Red Book calculates AWP from other drug pricing benchmarks provided by drug manufacturers. GAO did not audit the drug pricing information reported to Red Book by drug manufacturers nor the calculations performed by Red Book to fill nonreported AWP data. Some of the drugs on this list were repackaged, or nonrepackaged, while other drugs were both repackaged and nonrepackaged. In a few cases, drugs were removed from the list because changes in the recorded package size led to errors in the calculated change in unit prices. See table 6 below for the label names of brand-name prescription drugs that had an extraordinary price increase between 2000 and 2008. Table 6: Repackaged Brand-name Drug Products that Had an Extraordinary Price Increase, 2000 to 2008: Repackaged brand name drugs (Pricing for these drugs is typically set by the repackager and not the drug's manufacturer): Name and strength of drug: Abilify Tab 5MG; Actos Tab 15MG; Actos Tab 30MG; Adderall Tab 5MG; Ambien Tab 5MG; Ambien Tab 10MG; Amoxil Cap 250MG; Amoxil Cap 500MG; Anaprox Tab 275MG; Anaprox-DS Tab 550MG; Ansaid Tab 100MG; Antabuse Tab 250MG; Aricept Tab 10MG; Arthrotec Tab 75MG-0.2MG; Avandia Tab 4MG; Axert Tab 12.5MG; Bayhep B Inj; Bextra Tab 20MG; Biaxin Sus 250MG/5ML; Bontril Cap ER 105MG; Bontril Slow Cap 105MG; Brevital Sodium Inj 500MG; Bromfed Tab; Cataflam Tab 50MG; Ceftin Tab 125MG; Ceftin Tab 250MG; Ceftin Tab 500MG; Celebrex Cap 200MG; Celebrex Cap 100MG; Cerumenex Otic Sol 10%; Cipro Tab 500MG; Cipro Tab 750MG; Claritin Tab 10MG; Codiclear DH Syr; Combivir Tab; Compazine Sup 25MG; Compazine Tab 10MG; Coumadin Tab 2.5MG; Cutivate Cre 0.05%; Cytotec Tab 200mcg; Dalmane Cap 30MG; Daypro Tab 600MG; Depo-Estradio Inj 5MG/ML; Desowen CRE 0.05%; Diovan Tab 160MG; Dovonex Cre 0.005%; Dovonex Oin 0.005%; Duricef Cap 500MG; E.E.S.-400 Film Tab 400MG; Econopred Plus OP Sus 1%; Effexor Tab 100MG; Effexor XR Cap ER 75MG; Effexor-XR Cap 75MG; Effexor-XR Cap 37.5MG; Eryc Cap 250MG; Estrace Tab 1MG; Flexeril Tab 5MG; Flovent Inh 0.22/Act; Floxin Tab 200MG; Floxin Tab 300MG; Floxin Tab 400MG; Fulvicin P/G Tab 330MG; Glyset Tab 25MG; Ionamin Cap 15MG; Ismo Tab 20MG; Lamictal Tab 25MG; Lamictal Tab 200MG; Lanoxin Tab 0.25MG; Levaquin Tab 250MG; Levaquin Tab 500MG; Levaquin Leva-pak 750MG; Levoxyl Tab 0.088MG; Lidoderm Patch 5%; Lipitor Tab 80MG; Locoid Cre 0.1%; Lomotil Tab 0.025MG-2.5MG; Lotensin Tab 40MG; Lunesta Tab 1MG; Lunesta Tab 2MG; Lunesta Tab 3MG; Lyrica Cap 100MG; Lyrica Cap 200MG; Lyrica Cap 50MG; Lyrica Cap 75MG; Marcaine Inj 0.5%; Maxitrol Opth Sus; Mephyton Tab 5MG; Methergine Tab 0.2MG; Mevacor Tab 20MG; Miacalcin Spr 200iu/Act; Miralax Pwd for Soln; Mobic Tab 15MG; Mobic Tab 7.5MG; Motrin Tab 800MG; Niferex-150 Forte Cap; Nitrolingu Spr 0.4/Spray; Nitrostat SL Tab 0.4MG; Norco Tab; Norflex Tab 100MG; Norvasc Tab 10MG; Norvir Cap 100MG; Ovral Tab; Paxil CR Tab 25MG; Paxil CR Tab 12.5MG; Paxil CR Tab 37.5MG; Pediazole Sus; Pepcid Tab 40MG; Peridex Liq 0.12%; Phenergan Tab 25MG; Phenergan Sup 12.5MG; Phenergan Sup 50MG; Phenhist Expectorant Liq; Phoslo Tab 667MG; Plendil Tab 5MG; Plendil Tab 10MG; Ponstel Cap 250MG; Premarin Tab 0.625MG; Prilosec Cap 20MG; Provera Tab 2.5MG; Prozac Cap 20MG; Restoril Cap 30MG; Risperdal Tab 1MG; Risperdal Tab 0.5MG; Risperdal Tab 0.25MG; Robinul Inj 0.2MG/ML; Septra DS Tab; Seroquel Tab 25MG; Seroquel Tab 100MG; Seroquel Tab 50MG; Silvadene Cre 1%; Singulair Tab 10MG; Skelaxin Tab 400MG; Skelaxin Tab 800MG; Soma Compound w/Code Tab; Sumycin Cap 250MG; Synalgos-DC Cap; Synthroid Tab 0.1MG; Synthroid Tab 0.088MG; Terazol 3 Vag Cre 0.8%; Tigan Inj 100MG/ML; Tobradex Opth Sus; Tobrex Opth Sol 0.3%; Topamax Tab 25MG; Topamax Tab 100MG; Toprol XL Tab 50MG; Transderm Scop Patch; Ultram Tab 50MG; Ultram ER Tab ER 200MG; Valium Tab 5MG; Valtrex Tab 1GM; Vicodin Tab; Vicoprofen Tab; Vioxx Tab 25MG; Viracept Tab 250MG; Viramune Tab 200MG; Vivelle-Dot 0.1MG/24hrs; Voltaren Tab 75MG; Zebeta Tab 5mg; Ziagen Tab 300MG; Zithromax Tab 250MG; Zithromax Z-Pak Tab 250MG; Zocor Tab 10MG; Zocor Tab 20MG; Zocor Tab 40MG; Zoloft Tab 25MG; Zyprexa Tab 10MG; Zyprexa Tab 2.5MG; Zyprexa Tab 7.5MG; Zyprexa Tab 5MG; Source: GAO analysis of Red Book data. Note: Following the extraordinary price increase, some drugs may have become discontinued or transferred from one manufacturer to another. In some cases, an extraordinary price increase for a drug may not be attributed to the manufacturer that currently owns the drug. [End of table] Table 7: Nonrepackaged Brand-name Drug Products that Had an Extraordinary Price Increase, 2000 to 2008: Nonrepackaged brand name drugs: Name and strength of drug: Adderall Tab 5MG; Ala-Scalp HP Lot 2%; Amytal Sodium Inj 0.5GM; Ancobon Cap 250MG; Ancobon Cap 500MG; Bensal HP 60MG-30MG/1GM; Bontril PDM Tab 35MG; Bontril Slow Cap ER 105MG; Brethine Inj 1MG/ML; Brevital Sodium 2.5GM; Brevital Sodium Inj 2.5GM; Buprenex Inj 0.3MG/ML; Capital w/Codeine Sus; Cefazolin 1GM/50ML; Cefotan Inj 1GM; Cefotan Inj 2GM; Cellcept Cap 250MG; Cenolate Inj 500MG/ML; Ceretec Kit; Cogentin Inj Soln 1MG/1ML; Cognex Cap 10MG; Cognex Cap 20MG; Cognex Cap 30MG; Cognex Cap 40MG; Combipatch 0.05MG-0.14MG; Combipatch 0.05MG-0.25MG; Cortrosyn Inj 0.25MG; Cosmegen IV 0.5MG; Cuprimine Cap 250MG; Cystadane 1GM/1Scoopful; D.H.E. 45 Inj 1MG/ML; Dantrium IV 20MG; Demser Cap 250MG; Dermagraft Sheet; Digoxin Soln 0.05MG/1ML; Diprivan IV Emul 10MG/1ML; Diuril Sodium IV 0.5GM; Dopram IV Soln 20MG/1ML; Duramorph Inj 0.5MG/1ML; Duramorph Inj 1MG/1ML; Duramorph PF Inj 1MG/ML; Dynex Tab; Edecrin Sodium Inj 50MG; Edecrin Tab 25MG; Elliotts B Inj; Ergotrate Tab 0.2MG; Erythrocin Lac Inj 500MG; EtheDent Chew Tab 0.25MG; EtheDent Chew Tab 0.5MG; EtheDent Chew Tab 1MG; Fareston Tab 60MG; FazaClo Dis Tab 100MG; FazaClo Dis Tab 25MG; Formalyde-10 Spr 10%; Fosrenol Chew Tab 500MG; Geref Inj 50mcg; NovaPlus H.P. Acthar Gel 80U/1ML; Hectorol Cap 2.5MCG; Hectorol Liq Cap 2.5MCG; Hep-Lock Inj 10U/ML; Histatrol Inj 0.275/ML; Histatrol Soln 2.75MG/ML; Histussin HC 2.5-5-1/5; Hypaque-76 Inj; Inderal LA Cap 60MG; Inderal LA Cap 80MG; Inderal LA Cap 120MG; Inderal LA Cap 160MG; Inderal LA Cap ER 120MG; Inderal LA Cap ER 160MG; Inderal LA Cap ER 60MG; Inderal LA Cap ER 80MG; Indocin IV Pwd for Soln; Indocin Susp 25MG/5ML; Infumorph 200 Inj; Infumorph 500 Inj; Inversine Tab 2.5MG; Iodopen Inj 118MCG/1ML; Isuprel Inj 0.2MG/ML; Kenalog Spr 0.147/GM; Lacrisert Opth Dev 5MG; Levo-Dromoran Tab 2MG; Liposyn III Inj 10%; Liposyn III Inj 20%; Liposyn III IV Emul 10%; Liposyn III IV Emul 20%; Locoid Oin 0.1%; Locoid Sol 0.1%; Locoid Crm 0.1%; Locoid Lipocrem 0.1%; Lymphazurin Inj 10MG/ML; Matulane Cap 50MG; Maxipime Inj 1GM; Maxipime Inj 2GM; MD-Gastroview 66%-10%; Mephyton Tab 5MG; Methylin Chew Tab 10MG; Methylin Chew Tab 2.5MG; Methylin Chew Tab 5MG; Methylin Soln 10MG/5ML; Methylin Soln 5MG/5ML; Minocin Cap 50MG; Minocin Cap 100MG; Muri-Lube Oil; Mustargen IV Pwd for Soln; Nascobal Gel 500mcg/0.1ML; Nembutal Sod Inj 50MG/ML; Nicomide Tab; Nitropress Inj 50MG; Norvir Cap 100MG; Norvir Sol 80MG/ML; Novahistine DH 7.25-2-5/5; NovaPlus Diprivan IV 10/1; Nydrazid Inj 100MG/ML; Omnipaque 300 Inj 64.7%; Oncoscint CR/OV Inj 1MG; Optison IV Susp; Oracit Sol; Ortho-Prefest Tab; Pamelor Cap 10MG; Pamelor Cap 25MG; Panhematin IV 313MG; Phrenilin Forte 50-650; Prefest Tab; Prevacid SoluTab 15MG; Prevacid SoluTab 30MG; Prevpac Kit; Promit IV 150MG/1ML; Quelicin Inj 100MG/ML; Quelicin Inj 20MG/1ML; Regonol Inj Soln 5MG/1ML; Rejuvesol Inj; Rescon-MX Tab ER; Robaxin Inj Soln 100MG/ML; Robinul Inj Soln 0.2MG/ML; Roxicet Tab 500MG-5MG; Ryna-12 S Sus; Seconal Sodium Cap 100MG; Septra DS Tab; Sucraid Sol 8500 IU/ML; Sulfoxyl Regular Lot; Sulfoxyl Strong Lot; Sumycin Tab 250MG; Sumycin Tab 500MG; Syprine Cap 250MG; Syrex Inj 0.9%; Tenormin Inj 0.5MG/ML; Testopel Pellets 75MG; Tetanus To Inj 10LF/0.5ML; Trasylol Inj 10,000kiu/ML; Tricitrasol Cnt 46.7%; Tridesilon Cre 0.05%; Tridesilon Oin 0.05%; Trisenox IV Soln 1MG/1ML; Tuinal Cap 50MG; Uretron D/S Tab; Utira-C Tab; Virazole Sus 6GM; Vitrasert Imp 4.5MG; Westhroid Tab 130MG; Westhroid Tab 32.5MG; Westhroid Tab 65MG. Source: GAO analysis of Red Book data. Note: Following the extraordinary price increase, some drugs may have become discontinued or transferred from one manufacturer to another. In some cases, an extraordinary price increase for a drug may not be attributed to the manufacturer that currently owns the drug. [End of table] [End of section] Appendix III: Characteristics of Case Study Drugs: To gain an understanding of the market dynamics leading to extraordinary price increases for brand-name drugs, we developed case studies of six brand-name drugs identified from our analysis of Red Book data. Selection for inclusion as a case study was based on several factors including price, the level of the percentage increase, whether the drug had more than one extraordinary price increase between 2000 and 2008, availability of the drug from multiple sources, and the permanence of the price increase. See table 8 for characteristics of the drugs selected for the case studies. Table 8: Summary of Characteristics of the Six Case Study Drugs: Drug characteristics: Year of FDA approval; Drug A: 1987; Drug B: 1952; Drug C: 1969; Drug D: 1960; Drug E: 1985; Drug F: 1991. Drug characteristics: Year of unit price increase; Drug A: 2007; Drug B: 2001 and 2007; Drug C: 2004 and 2005; Drug D: 2004; Drug E: 2008; Drug F: 2001. Drug characteristics: Percent unit price increase[A]; Drug A: 1,100; Drug B: 1,800 and 1,300; Drug C: 900 and 700; Drug D: 100; Drug E: 100; Drug F: 1,400. Drug characteristics: Patent status at time of price increase; Drug A: No patent; Drug B: No patent; Drug C: No patent; Drug D: No patent; Drug E: Under patent[B]; Drug F: Under patent. Drug characteristics: Market exclusivity status at time of price increase[C]; Drug A: None; Drug B: None; Drug C: None; Drug D: None; Drug E: None; Drug F: None. Drug characteristics: Repackaged drug; Drug A: No; Drug B: No; Drug C: No; Drug D: No; Drug E: No; Drug F: Yes[D]. Drug characteristics: Year of drug acquisition[E]; Drug A: 2007; Drug B: 2001; Drug C: 1998; Drug D: 2000; Drug E: N/A[F]; Drug F: N/A[G]. Drug characteristics: Generic equivalent available on the market at time of price increase[H]; Drug A: Yes; Drug B: No; Drug C: No; Drug D: No; Drug E: No[I]; Drug F: No. Drug characteristics: Drug available through patient assistance program[J]; Drug A: No; Drug B: Yes; Drug C: Yes; Drug D: No; Drug E: No; Drug F: Yes[K]. Drug characteristics: Drug is considered low volume or high volume[L]; Drug A: Low volume; Drug B: Low volume; Drug C: Low volume; Drug D: Low volume; Drug E: Low volume; Drug F: High volume[M]. Source: GAO analysis of Red Book and interviews with drug company representatives. Note: Changes in unit prices are calculated using average wholesale price (AWP) in Thomson Reuters' Red Book. An extraordinary price increase is a unit price increase equal to 100 percent or more at a single point in time from 2000 to 2008. Patent status is reported as of the date the extraordinary price increase occurred. [A] Percent increase is rounded to the nearest hundred percent. [B] This drug had a method-of-use patent. [C] The Federal Food, Drug, and Cosmetics Act authorizes various periods of market exclusivity for new drug products. Generally, market exclusivities prevent the Food and Drug Administration (FDA) from approving any application for a competing drug compound for a stated period of time. [D] This drug was sold by a repackager. The price of the drug was set by the repackager and not the manufacturer. [E] Indicates the year that the rights to the drug were acquired from the previous manufacturer. [F] This company owns the original rights to the drug. [G] This drug was sold by a repackager. [H] This information was obtained from the companies and publicly available information from the FDA. [I] This drug's active ingredient is available as a generic in other dosage forms. [J] Patient assistance programs are typically established to offer a company's drug products at low or no cost to low-income, underinsured, or uninsured individuals. [K] This drug was sold by a repackager. At the time of its extraordinary price increase, the drug was available through the manufacturer's patient assistance program. [L] Drug companies were asked to identify their drug as either low volume or high volume, depending on the amount manufactured annually. [M] The manufacturer of the drug said that this drug was a high-volume product at the time of its extraordinary price increase. The repackager told us it sold a small amount of the drug at the time of its extraordinary price increase. [End of table] [End of section] Appendix IV: GAO Contact and Staff Acknowledgments: GAO Contact: John E. Dicken at (202) 512-7114 or Dickenj@gao.gov. Acknowledgments: In addition to the contact named above, Martin T. Gahart, Assistant Director; N. Rotimi Adebonojo; Rashmi Agarwal; George Bogart; Kristin Helfer Koester; Martha Kelly; Yesook Merrill; Giao N. Nguyen; Daniel Ries; and Timothy Walker made major contributions to this report. [End of section] Related GAO Products: Medicaid Outpatient Prescription Drugs: Second Quarter 2008 Federal Upper Limits for Reimbursement Compared with Average Retail Pharmacy Acquisition Costs. [hyperlink, http://www.gao.gov/products/GAO-10-118R]. Washington, D.C.: November 30, 2009. Prescription Drugs: Overview of Approaches to Control Prescription Drug Spending in Federal Programs. [hyperlink, http://www.gao.gov/products/GAO-09-819T]. Washington, D.C.: June 24, 2009. Medicare Part D Prescription Drug Coverage: Federal Oversight of Reported Price Concessions Data. [hyperlink, http://www.gao.gov/products/GAO-08-1074R]. Washington, D.C.: September 30, 2008. Prescription Drugs: Trends in Usual and Customary Prices for Drugs Frequently Used by Medicare and Non-Medicare Health Insurance Enrollees. [hyperlink, http://www.gao.gov/products/GAO-07-1201R]. Washington, D.C.: September 7, 2007. Prescription Drugs: Oversight of Drug Pricing in Federal Programs. [hyperlink, http://www.gao.gov/products/GAO-07-481T]. Washington, D.C.: February 9, 2007. Prescription Drugs: An Overview of Approaches to Negotiate Drug Prices Used by Other Countries and U.S. Private Payers and Federal Programs. [hyperlink, http://www.gao.gov/products/GAO-07-358T]. Washington, D.C.: January 11, 2007. Medicaid Outpatient Prescription Drugs: Estimated 2007 Federal Upper Limits for Reimbursement Compared with Retail Pharmacy Acquisition Costs. [hyperlink, http://www.gao.gov/products/GAO-07-239R]. Washington, D.C.: December 22, 2006. Prescription Drugs: Price Trends for Frequently Used Brand and Generic Drugs from 2000 through 2004. [hyperlink, http://www.gao.gov/products/GAO-05-779]. Washington, D.C.: August 15, 2005. Medicaid Drug Rebate Program: Inadequate Oversight Raises Concerns about Rebates Paid to States. [hyperlink, http://www.gao.gov/products/GAO-05-102]. Washington, D.C.: February 4, 2005. Medicaid: States' Payments for Outpatient Prescription Drugs. [hyperlink, http://www.gao.gov/products/GAO-06-69R]. Washington, D.C.: October 31, 2005. Federal Employees' Health Benefits: Effects of Using Pharmacy Benefit Managers on Health Plans, Enrollees, and Pharmacies. [hyperlink, http://www.gao.gov/products/GAO-03-196]. Washington, D.C.: January 10, 2003. Prescription Drugs: Expanding Access to Federal Prices Could Cause Other Price Changes. [hyperlink, http://www.gao.gov/products/GAO/HEHS-00-118]. Washington, D.C.: August 7, 2000. [End of section] Footnotes: [1] In this report, drug prices are measured by the AWP, a drug pricing benchmark that is commonly used in the pharmaceutical industry. AWP is in most cases the manufacturer's suggested list price and does not necessarily reflect the actual price charged by a wholesaler. [2] Red Book is a drug pricing compendium with information about prices and other characteristics of drug products, published by Thomson Reuters. [3] A unit price is the (1) price per gram; (2) price per milliliter; or (3) price for each piece, such as for products sold in tablets. The unit price and other characteristics of the brand-name drugs cited in this report were those recorded in the Red Book as of December 31, 2008. [4] The name of a drug and its manufacturer, the strength of the drug, and the package size or number of units (such as tablets) in the package are represented by a 11-digit national drug code (NDC-11). [5] Prescription drugs may be repackaged from bulk drug purchases into smaller packages and identified by the repackaging company's unique NDC. Repackaged drugs are typically sold to health care providers, who then resell them to patients. [6] Drugs that possess a similar chemical structure and similar therapeutic effects are grouped into therapeutic classes. Most drugs within a therapeutic class produce similar benefits, side effects, adverse reactions, and interactions with other drugs and substances. [7] For this report, companies that manufacture and/or sell brand-name drugs are referred to as drug companies. [8] While prescription drug spending and prices continue to rise, the rate of growth in spending and prices for prescription drugs declined in 2007. In 2000, national spending for retail prescription drugs was $120.6 billion, compared to $227.5 billion in 2007--an average increase of 10 percent a year. In 2007, retail prescription drug spending grew 4.9 percent, and prescription drug prices increased 1.4 percent. M. Hartman, A. Martin, P. McDonnell, A. Catlin, and the National Health Expenditure Accounts Team, "National Health Spending in 2007: Slower Drug Spending Contributes to Lowest Rate of Overall Growth Since 1998," Health Affairs, vol. 28, no. 1 (2009). However, there is preliminary indication of higher drug price increases from 2008 to 2009. [9] To obtain FDA approval for a drug, a drug company must conduct clinical studies showing that the drug is safe and effective for its intended use, or indication. [10] While a brand-name drug is patented, therapeutically similar brand- name drugs not containing the same active chemical ingredient, also known as "me-too" drugs, may be developed and marketed by a drug company. Also, the FDA may not approve generic therapeutic equivalents to a brand-name drug prior to the expiration of the drug's patent unless the applicant certifies that the patent is invalid or that the generic drug does not infringe the patent. [11] Drugs obtained directly from health care providers may eliminate travel to a pharmacy to obtain a prescribed drug. In addition, the availability of repackaged drugs from the health care provider may reduce medication errors caused by poor handwriting--such as administering the wrong medication or an incorrect dosing. [12] See 35 U.S.C. §§ 111, 154. [13] Patents may be granted for several properties of a drug. For example, a drug company may obtain a patent on the active ingredient used in the drug. Companies may also obtain patents on the use of a drug, and a drug's formula and composition. Although a patent may be granted for a drug product long before its approval for marketing by the FDA, a company may obtain a patent term extension in certain circumstances. [14] 21 U.S.C. § 355(c)(3)(D)(ii). [15] 21 U.S.C. § 355(c)(3)(D)(iii). [16] 21 U.S.C. § 355(j)(2)(D)(iv). Exclusivity pertains to the first applicant of an abbreviated new drug application based on a previously approved brand-name drug. [17] 21 U.S.C. § 355a. [18] 21 U.S.C. § 360cc. An orphan drug is a drug that treats a rare disease or condition which is generally defined as affecting fewer than 200,000 people in the United States. [19] The FDA is responsible for designating drugs as orphan drugs. [20] Underinsured patients typically face limited covered benefits and high out-of-pocket costs such as deductibles, coinsurance, or copayments. [21] See 15 U.S.C. §§ 18, 1. In addition, states investigate and litigate potential violations of state as well as federal antitrust law. See 15 U.S.C. § 15c. [22] 15 U.S.C. § 18a. Companies involved in transactions that do not meet certain criteria are not required to notify the FTC and DOJ. The FTC and DOJ may seek an injunction to halt the acquisition or require that companies divest certain drugs if they determine that the merger is likely to be anticompetitive. [23] See 15 U.S.C. § 45 (prohibiting unfair methods of competition). [24] See 21 C.F.R. part 211 (2009). [25] About 90 percent of the extraordinary price increases--380 brand- name drug products--remained at the increased price for more than 90 days after experiencing the price increase, and more than four-fifths remained at the increased price for 180 days or more. [26] We compared the price of the drug immediately after the extraordinary price increase to the last recorded price of the drug as of December 31, 2008. For 361 drugs that had extraordinary price increases, the final price recorded for these drugs was the same price or higher than the price immediately after the extraordinary price increase. [27] The NDC-9 code represents the name of the drug and its manufacturer, and strength of the drug. The price increases for brand- name drug products that had an extraordinary price increase were reported using unit price data recorded at the NDC-9 level. [28] These three therapeutic classes represented 40 percent of all brand-name drugs recorded in Red Book. [29] The unit price for brand-name drug products that had an extraordinary price increase were reported using unit price data at the NDC-9 level. We report the unit price of a drug prior to the extraordinary price increase. A unit price is denoted by Thompson Reuters in Red Book as (1) price per gram; (2) price per milliliter; and (3) price for each piece, such as products sold by the item, such as tablets or capsules. [30] Of the brand-name drug products priced less than $25 per unit prior to the extraordinary price increase, 40 percent were priced less than a dollar, 54 percent between $1 and $9.99, and 6 percent between $10 and $24.99. After the extraordinary price increase, 18 percent of these drugs were priced less than a dollar, 63 percent between $1 and $9.99, and 19 percent between $10 and $24.99. [31] The median price after the increase is calculated using the price recorded in Red Book as of December 31, 2008, because the price of these drugs may have increased or decreased following the extraordinary price increase. [32] The calculation of treatment cost is based on two courses of treatment lasting up to 28 days. In some cases, patients on this drug may receive only one course of treatment. The out-of-pocket cost for a patient varies depending on insurance coverage. [33] The price increases for drugs that had an extraordinary price increase are reported using unit price data recorded at the NDC-9 level. Less than half of all brand-name drug products recorded in Red Book were repackaged drugs. [34] To determine whether an extraordinary price increase was initiated by a drug's manufacturer or by the repackager of the drug, we matched all repackaged drugs that had an extraordinary price increase to the nonrepackaged equivalent drug brand sold by the manufacturer. To account for increases initiated by manufacturers of nonrepackaged drugs that had an increase of less than 100 percent and therefore were not captured from Red Book, we counted only repackaged drugs that had an increase of at least 200 percent for this analysis. [35] These four repackaging companies accounted for about three quarters of all repackaged drugs that had an extraordinary price increase. [36] As discussed earlier, the price of a course of treatment depends on the nature of the condition treated, how long the condition should be treated, and the number of units of a drug used to treat the condition. [37] The median price after the increase is calculated using the price recorded in Red Book as of December 31, 2008, because the price of these drugs may have increased or decreased following the extraordinary price increase. [38] For this report, we use the term therapeutically equivalent drugs to include both generic versions of a brand-name drug and other brand- name drugs used to treat the same condition. Generally, according to the FDA a therapeutically equivalent drug refers only to the generic version of a brand-name drug. [39] Drug companies may also receive a patent for minor alterations to the formulation of a drug such as reversing only the structure of the chemical used in the active ingredient. [40] See Apps. I and III for more details on the case study drugs. [41] A drug's patent(s) may be acquired through grant, sale, or other type of transfer. [42] Two companies in our case studies have acquired another drug company and its drug products. Also, some of the companies in our case studies have acquired the rights to drugs manufactured by other companies. [43] According to the company, the previous owner sold the rights to the drug because of difficulty manufacturing the drug and its financial losses from low sales of the drug. [44] These changes included upgrades to manufacturing equipment used to detect and reduce impurities and revalidation of the entire manufacturing process. [45] Drug manufacturers that wish to have their drugs available for Medicaid enrollees are required to enter into rebate agreements with the federal government on behalf of states. These rebate agreements are intended to ensure that Medicaid pays the lowest price that the manufacturer offers for the drug. Rebates are computed and paid by the drug manufacturer each quarter based on drug utilization data supplied by Medicaid. [46] The basic Medicaid rebate is 15.1 percent of a drug's average manufacturer price (AMP) per unit, or the difference between AMP and a drug's best price, whichever is greater. If a brand-name drug's AMP rises faster than inflation, as measured by the consumer price index, an additional unit rebate may be calculated. See U.S.C. § 1396r-8(c). The two companies indicated that due to the application of additional unit rebates caused by increases in their drug prices, their Medicaid rebates actually exceeded their drugs' AMPs. [47] Unless otherwise noted, in this report "brand-name drugs" refers to brand-name prescription drugs. [48] In this report, drug prices are measured by AWP. AWP is in most cases the manufacturer's suggested price and does not necessarily reflect the actual price charged by a wholesaler. AWP is a drug pricing benchmark that is commonly used in the pharmaceutical industry. [49] Red Book is a proprietary database containing drug pricing and other drug-related information published by Thomson Reuters. Drug manufacturers and companies report the price of their drug--in AWP or other pricing benchmarks--to Thomson Reuters for publication in the Red Book. In some cases, Red Book calculates AWP values using other pricing benchmarks. [50] A unit price is the (1) price per gram; (2) price per milliliter; or (3) price for each piece, such as for products sold in tablets. The unit price and other characteristics of the brand-name drugs cited in this report were those recorded in Red Book as of December 31, 2008. [51] Drug prices are identified and reported in Red Book by an 11-digit number called the NDC-11 code. The NDC-11 code represents the name of the drug and its manufacturer, the strength of the drug, and the package size--or number of units (such as tablets) in the package. [52] As a result, for these brand-name drugs we do not capture this variation in extraordinary price increase by package size. [53] Prescription drugs may be repackaged from bulk drug purchases into individual dose packages and identified by the repackaging company's unique NDC. Repackaged drugs may be sold to health care providers, who then dispense them to their patients. [54] To determine whether an extraordinary price increase was initiated by a drug's manufacturer or by the repackager of the drug, we matched all repackaged drugs that had an extraordinary price increase to the nonrepackaged equivalent drug brand sold by the manufacturer. Whenever a match between the repackaged and nonrepackaged drug was not found, we concluded that the repackaged drug had an extraordinary price increase without a corresponding increase by the drug's manufacturer for the identical nonrepackaged drug. To account for increases initiated by manufacturers of nonrepackaged drugs that had an increase of less than 100 percent and therefore were not captured from Red Book, we counted only repackaged drugs that had an increase of at least 200 percent for this analysis. [55] We deleted records from our data files in a few cases where a drug company provided evidence showing that an extraordinary price increase had not occurred. In one case, data entry errors recording an incorrect package size was the reason for an extraordinary price increase. We also deleted one record that showed an extraordinary price increase after December 31, 2008. [56] Red Book is a database containing drug pricing and other drug- related information published by Thomson Reuters. [57] The NDC-9 code represents the name of the drug and its manufacturer, and strength of the drug. 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