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ScienceWeek
PUBLIC HEALTH: ON OVER-THE-COUNTER DRUGS
The following points are made by Brian L. Strom (New Engl. J. Med. 2005 352:1403):
1) Approximately 1000 active ingredients are currently in use in more than 100,000 over-the-counter medications in the United States, with combined annual sales exceeding $17 billion. Many drugs have recently been switched from prescription to over-the-counter status; other such switches have been proposed and rejected, in decisions that have sometimes been controversial. Drugs that have been approved by the Food and Drug Administration (FDA) for shifts to over-the-counter status include some nonsteroidal antiinflammatory drugs (such as ibuprofen, naproxen, and ketoprofen), histamine2-receptor blockers (such as cimetidine, ranitidine, and famotidine), topical antifungal agents, and nicotine-based smoking-cessation products. Recent controversial decisions include those regarding nonsedating antihistamines (switched by the FDA despite objections by the manufacturers), hormonal postcoital pregnancy-prevention drugs (i.e., the "morning-after pill," which was denied over-the-counter status), and statins, for which a proposed status change was rejected.
2) Over-the-counter status offers some clear potential advantages over prescription status. The medication becomes easier to obtain, and access to it broadens. The price of the drug often drops, and patients avoid both the cost and the delay of a visit to a prescribing physician. Patients' ability to choose their own medications increases their autonomy, and patients benefit from educating themselves about their options. There are also benefits for the manufacturer, which gains a new opportunity for profits after its patent has expired and competitors have entered the market, since patent protection is frequently extended when such a switch is made.
3) Of course, there are a number of potential disadvantages as well, including risks related to self-treatment by patients --risks of misdiagnosis, delays in obtaining a correct diagnosis, adverse interactions with other medications, reduced opportunities to receive counseling about possible lifestyle therapies (such as exercise and diet), poorer compliance (by patients who view over-the-counter drugs as different from "real" medications), use by patients who are unlikely to benefit from the drug but will nevertheless be exposed to its risks, and patterns of taking medications inappropriately (e.g., "if one is good, two are better"). In addition, patients with insurance that covers medications face the paradox of increased, rather than reduced, costs for their medications, because insurers ordinarily do not cover over-the-counter drugs, prices of which may exceed the amount of patients' copayments for the prescription versions. Finally, over-the-counter use renders it more difficult to study a drug's effects, since prescription databases can no longer be used for that purpose.
4) Generally, drugs are eligible for over-the-counter status if they can be used safely and effectively and have a label that is easily understood by the average person in order to permit self-treatment. Although determining whether a drug meets this standard is ultimately a matter of judgment, there are some generally accepted criteria that may be useful in guiding that judgment. Typically, the condition treated by the medication can be self-diagnosed by consumers, the success of the therapy monitored by patients, and the condition expected to be short-lived, so that consumers can be directed to visit a physician if it continues or worsens. Furthermore, the condition and its other treatments need to be sufficiently understandable to consumers that they can choose whether to initiate treatment, as well as which drug to use and at what dose and frequency to take it. It is also useful if the condition being treated is sufficiently innocuous that symptomatic treatment will not prove counterproductive by delaying definitive treatment.
New Engl. J. Med. http://www.nejm.org
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FROM PRESCRIPTION TO OVER-THE-COUNTER DRUGS
The following points are made by Eric P. Brass (New Engl. J. Med. 2001 345:810):
1) The availability of drugs on an over-the-counter basis, including those drugs previously available only by prescription, in general provides patients with improved access to effective therapies. Removal of the requirement for prescriptions saves time for both the health care professional and the patient.
2) However, the overall effect on health care costs is complex. One such effect may be that costs shift from 3rd party payers to patients. In addition, short-term cost savings may be offset over the long term by problems due to inappropriate use or suboptimal therapy. Optimal therapy with an over-the-counter drug requires that the consumer diagnose the underlying condition correctly and use the drug in a manner that minimizes risk.
3) Assessment of the ability of patients to use drugs in this manner is a critical component of the regulatory review of over-the-counter drugs, and the available data arouse the concern that without the supervision of a health care professional, some patients may not be able to use over-the-counter drugs appropriately for certain diagnoses or chronic conditions or in high-risk situations.
4) On the other hand, the widespread use of over-the-counter aspirin on a long-term basis for cardiovascular-risk reduction illustrates the potential value of increased drug availability for long-term therapy. The future promises increases in the number of drugs available over-the-counter and increases in the variety of indications for their use.
New Engl. J. Med. http://www.nejm.org
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SCIENCE POLICY: ON THE US FOOD AND DRUG ADMINISTRATION
The following points are made by Eve E. Slater (New Engl. J. Med. 2005 352:293):
1) The US Food and Drug Administration (FDA) is responsible for the safety and efficacy of most food products and all human and veterinary drugs, biologic products, medical devices, cosmetics, and products emitting radiation that are sold within US borders -- a list that accounts for an estimated 20 percent of consumer spending, valued at approximately $1.5 trillion.[1,2] Although the FDA is often at the center of controversy, the agency has consistently commanded the respect of more than two thirds of American adults.[3]
2) The author examines the performance of the agency, with particular attention given to the FDA's relationship with its major counterpart, the pharmaceutical industry, especially in the decade since the enactment of the Prescription Drug User Fee Act in 1992. The author is a former senior vice president of Merck Research Laboratories (until 2000) and a former assistant secretary for health at the Department of Health and Human Services.
3) The pressure to approve drugs more or less rapidly ebbs and flows, largely as a consequence of external events. The publication of THE JUNGLE, Upton Sinclair's expose of the meatpacking industry, helped to create the FDA in 1906.[4] The crisis over the elixir sulfanilamide in the 1930s and the thalidomide tragedy in the 1960s prompted legislation to expand the FDA's authority. In the 1980s, the AIDS epidemic focused attention on the need for faster approval of drugs, especially for potentially lifesaving therapies. For the most part, current convention has demanded rapid review coupled with scientifically sound judgment by a strong agency. The Prescription Drug User Fee Act was passed primarily to improve the efficiency of the FDA, specifying that sponsors pay user fees to provide resources to allow the FDA to be more efficient in reviewing applications. The act's subsequent extension, the FDA Modernization Act of 1997, facilitated certain evidentiary standards for priority drugs. Amendments to the Prescription Drug User Fee Act that are contained in the Public Health Security and Bioterrorism Preparedness and Response Act of 2002 renewed prior provisions, added several more efficiency measures, and provided modest funding for post-marketing surveillance.[5]
4) The FDA currently employs approximately 10,000 people, an increase of 85 percent in the decade since the Prescription Drug User Fee Act was enacted, and commands a budget of $1.7 billion, of which $300 million (18 percent) is projected to derive from user fees that are charged to companies when they submit applications.[1,2] By comparison, the FDA budget is less than 1/50 that of the Department of Agriculture, which has 10 times the workforce of the FDA. The FDA's budget did not increase in tandem with the recent doubling of the annual budget of the National Institutes of Health to more than $27 billion. However, as a consequence of the terrorist attacks of September 11, 2001, additional money (more than $500 million) has been earmarked primarily for food-safety surveillance.[1,2]
5) Under the Prescription Drug User Fee Act, the FDA has made appreciable progress in the efficiency of its review process, especially for drugs that are granted priority status, and has enhanced the scientific quality of its actions. This improvement is largely attributable to the growth in the number of its employees, as well as to the maturing of regulatory science. In 2003, the FDA's Center for Drug Evaluation and Research approved 21 new molecular entities, defined as drugs that differ from others on the market, with a total median time for approval of 16.6 months (6.7 months for priority drugs and 23.1 months for standard review, as compared with 14.9 months and 27.2 months, respectively, a decade ago).[1]
6) Since 1992, the average time that is required for clinical development and regulatory review has been reduced by 25 percent, from 9.2 to 6.9 years, and since 1997, the average time for clinical development of fast-track drugs (as compared with standard drugs) has been shortened by 2.0 to 2.5 years. On the other hand, response times for requests that remain outside tracking mandated by the Prescription Drug User Fee Act have continued to suffer from inefficiencies that are extraneous to science. In important progress that is largely attributable to the Food and Drug Administration Modernization Act, the agency has adopted a more streamlined approach to clinical development -- for example, through the use of surrogate markers for accelerated approval or approval on the basis of a single multicenter clinical trial. Among the provisions of the 2002 amendments to the Prescription Drug User Fee Act are pilot programs involving continuous marketing applications, in which data are submitted and reviewed in continuous fashion, as was done for the first protease inhibitors to treat AIDS, and retrospective performance reviews.
7) It should be noted that the failure rate for compounds during development has remained fairly constant; however, the overall time from the discovery of a drug to its commercialization has increased from approximately 10 years to 12 years. The reasons are that the time that is required for preclinical development has been increasing in some cases and that although priority drugs are coming to market sooner, the review time for standard agents has changed less dramatically. Presumably, the Prescription Drug User Fee Act has not resulted in a reduction in the cost of the development of drugs, a figure that has been increasing rather briskly, according to industry statistics. Furthermore, the sequential legislative actions have placed certain pressures on the agency. According to the Government Accountability Office, performance goals have created overwork for many reviewers. This observation, coupled with the fact that more than 30 percent of the FDA's workforce is eligible for retirement within five years, is cause for concern.[2]
References (abridged):
1. McClellan MB. The Food and Drug Administration's strategic action plan: protecting and advancing America's health: responding to new challenges and opportunities. August 2003. Accessed December 30, 2004, at http://www.fda.gov/oc/mcclellan/strategic.html
2. FY 2004 Justification of Estimates for Appropriations Committees. Promoting public health through patient, food, and consumer safety. Rockville, Md.: Food and Drug Administration, 2003. Accessed December 30, 2004, at http://www.fda.gov/oc/oms/ofm/budget/2004/bib1.htm
3. Taylor H. CDC, NIH, FAA, FDA get highest ratings of eleven federal government agencies. Harris Poll no. 73. Accessed December 30, 2004, at http://www.harrisinteractive.com/harris_poll/index.asp?PID=422
4. Sinclair U. The jungle. New York: Doubleday, Page, 1906:102. 5. Prescription Drug User Fee Act of 1992, Pub. L. No. 102-571, 21 U.S.C. 379, 106 Stat. 4491 (Oct. 29, 1992)
6. Food and Drug Administration Modernization Act of 1997, Pub. L. No. 105-115, 21 U.S.C. 355a, 111 Stat. 2296 (Nov. 21, 1997)
New Engl. J. Med. http://www.nejm.org
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