关于Highlights and a Hidden Hazard — The FDA's New Labeling Regulations的原因,关于Highlights and a Hidden Hazard — The FDA's New Labeling Regulations的相关知识。 The Food and Drug Administration (FDA) is trying to make the official descriptions of prescription drugs — which are notoriously user-hostile — more helpful. The agency has acknowledged the linguistic toxicity of these documents, known as package inserts or labeling. These are the lengthy listings of drug indications, effects, and associated risks that are routinely included with medications when they are shipped to pharmacies — and just as routinely discarded by pharmacists before any drug is dispensed to patients. Physicians are more likely to see the labeling in tiny print in the voluminous Physicians' Desk Reference (PDR), one of the most commonly consulted sources of information about drugs. The labeling also constitutes the formal, government-approved definition of a drug's benefits and risks. It is written by (and is the property of) the manufacturer but requires FDA approval, and it defines the boundaries of the legal promotion of a product's properties.
The FDA has now admitted what most clinicians have known for decades: the current labeling is poorly organized; it is stuffed with often irrelevant information; it may include an important fact about safety in any of a number of places (categorized as a "warning," a "precaution," or an "adverse effect"); and it often fails to distinguish between a drug's side effects and problems that may not even be causally related to its use.
With some fanfare, the FDA has announced new rules that will go into effect on June 30, 2006.1 It describes them as a breakthrough that will simplify the prescribing process for physicians, decrease medication errors, and improve patient safety. The new rules will require manufacturers to add a "highlights" section at the top of the label that summarizes key information about indications, risks, and doses. Such a summary will be helpful, but this is where the radical innovation ends. The other key provisions are the addition of a table of contents for the rest of the label and some minor modifications of content and format, such as the listing of all risks together, rather than in disparate sections. The revised format will be required for new medications approved after June 30, but the agency is calling for a gradual phase-in for existing products. Drugs already on the market will have three to seven years to implement these modest changes, and most products that were approved before mid-2001 will not have to modify their labels at all.
Even if implementation were universal and instantaneous, though, it would have only a tiny effect on medication use. The highlights section and table of contents will be of some help to prescribers. But any patient who happened to see the package insert would do so outside the context of the clinical encounter during which the prescription was written. These documents are more likely to be seen by physicians who use the PDR, which charges manufacturers a fee to have their labeling documents included. Unfortunately, that compendium is organized by manufacturer and trade name, rather than by therapeutic class — a system that makes it easy for a prescribing physician to look up a specific product, but difficult to compare drugs within a class, and impossible to compare their efficacy or prices (which are not listed).
Even for individual products, there is not much evidence that a revised label format will have much of an effect on patient safety, despite the FDA's claims. Data on risks included in the official label often lag behind the available evidence by as much as several years — a reflection of the FDA's problems with post-marketing surveillance2 and of manufacturers' reluctance to accelerate the inclusion of new data about rates of side effects. Studies of the effects of printed warnings on practice show that physicians frequently prescribe drugs despite important contraindications, even when these are spelled out in the label.3
The new rules will also require manufacturers to provide an electronic version of their package inserts for placement on the FDA Web site. Yet it is unclear whether posting a compendium of drug labels on the Web will influence behavior, especially if the FDA's site remains as difficult to navigate as it is now (try looking up any drug on www.fda.gov). It seems unlikely that such an online compilation will improve clinical decision making as well as other solutions could. By contrast, the British National Formulary (www.bnf.org) is produced by independent physicians and pharmacists and contains even-handed, readable overviews of drugs that are constantly updated by the professional societies that sponsor it.
Ultimately, the most attractive and best-organized labels will not influence behavior if physicians do not read them. As is usually the case in quality improvement, a systems approach will be necessary to achieve better prescribing practices and better outcomes. Evidence-based, comparative decision-support tools, whether online or in print, can provide physicians with current data about drugs' benefits and risks, as well as immediate feedback about appropriate prescribing. But such systems are in their infancy and not in widespread use.
The most troubling aspect of the FDA's new plan, however, has nothing to do with providing information to prescribers. In an unusual move after the end of a five-year period of comments on the initial rule, the agency used the passage of the new labeling regulations to quietly add a new section to its preamble that will make it extremely difficult for anyone to bring legal action against a drug manufacturer for harm caused by one of its products. For years, the pharmaceutical industry had sought to pass legislation that would prohibit litigation over adverse effects as long as the medication was approved by the FDA; Congress has consistently rejected this idea. But after the comment period for the new labeling regulation had closed, language was added to the final rule stating that any FDA-approved label, "whether it be in the old or new format, preempts . . . decisions of a court of law for purposes of product liability litigation."4 Beginning at the end of this month, the new regulations would preempt nearly all action by patients in state courts against drug manufacturers for unanticipated injuries resulting from the use of their products. This immunity would apply even if a company failed to warn prescribers or patients adequately about a known risk, unless a patient could prove that the company intentionally committed fraud — a very hard test to meet.
Several members of the House and Senate have vigorously objected to this provision, as well as to the fact that there was no opportunity to debate it before the regulations were made final; court challenges are likely. Ironically, this low-profile aspect of the new rules could have an effect on the health care system that is much more profound than the small-scale improvements of the new labeling rules themselves. "It will make it impossible to file liability claims," said a former FDA general counsel who is now in private practice.5
In other words, along with the very modest alterations of drug labeling to be phased in over the next seven years, the changes the FDA will begin implementing next month include a regulatory time bomb that could severely limit the accountability of companies that fail to adequately evaluate or report the risks associated with their products.
Yes, the agency is trying — but how effectively, and on whose behalf?
Source Information
Dr. Avorn is a professor of medicine at Harvard Medical School and chief of the Division of Pharmacoepidemiology and Pharmacoeconomics at Brigham and Women's Hospital — both in Boston. Dr. Shrank is an instructor at Harvard Medical School and in the Division of Pharmacoepidemiology and Pharmacoeconomics at Brigham and Women's Hospital.
References
New requirements for prescribing information. Rockville, Md.: Food and Drug Administration, 2006. (Accessed May 18, 2006, at http://www.fda.gov/cder/regulatory/physLabel/default.htm.)
Improvement needed in FDA's postmarket decision-making and oversight process. Washington, D.C.: Government Accountability Office, March 31, 2006. (Accessed May 18, 2006, at http://www.gao.gov/highlights/d06402high.pdf.)
Lasser KE, Seger DL, Yu DT, et al. Adherence to black box warnings for prescription medications in outpatients. Arch Intern Med 2006;166:338-344.
Food and Drug Administration. Requirements on content and format of labeling for human prescription drug and biologic products. Fed Regist 2006;71:3922-3997.www.fda.gov/OHRMS/DOCKETS/98fr/06-545.pdf
Harris G. New drug label rule is intended to reduce medical errors. New York Times. January 19, 2006:A20. (文章出处：《新英格兰医药杂志》)
The FDA has now admitted what most clinicians have known for decades: the current labeling is poorly organized; it is stuffed with often irrelevant information; it may include an important fact about safety in any of a number of places (categorized as a "warning," a "precaution," or an "adverse effect"); and it often fails to distinguish between a drug's side effects and problems that may not even be causally related to its use.
With some fanfare, the FDA has announced new rules that will go into effect on June 30, 2006.1 It describes them as a breakthrough that will simplify the prescribing process for physicians, decrease medication errors, and improve patient safety. The new rules will require manufacturers to add a "highlights" section at the top of the label that summarizes key information about indications, risks, and doses. Such a summary will be helpful, but this is where the radical innovation ends. The other key provisions are the addition of a table of contents for the rest of the label and some minor modifications of content and format, such as the listing of all risks together, rather than in disparate sections. The revised format will be required for new medications approved after June 30, but the agency is calling for a gradual phase-in for existing products. Drugs already on the market will have three to seven years to implement these modest changes, and most products that were approved before mid-2001 will not have to modify their labels at all.
Even if implementation were universal and instantaneous, though, it would have only a tiny effect on medication use. The highlights section and table of contents will be of some help to prescribers. But any patient who happened to see the package insert would do so outside the context of the clinical encounter during which the prescription was written. These documents are more likely to be seen by physicians who use the PDR, which charges manufacturers a fee to have their labeling documents included. Unfortunately, that compendium is organized by manufacturer and trade name, rather than by therapeutic class — a system that makes it easy for a prescribing physician to look up a specific product, but difficult to compare drugs within a class, and impossible to compare their efficacy or prices (which are not listed).
Even for individual products, there is not much evidence that a revised label format will have much of an effect on patient safety, despite the FDA's claims. Data on risks included in the official label often lag behind the available evidence by as much as several years — a reflection of the FDA's problems with post-marketing surveillance2 and of manufacturers' reluctance to accelerate the inclusion of new data about rates of side effects. Studies of the effects of printed warnings on practice show that physicians frequently prescribe drugs despite important contraindications, even when these are spelled out in the label.3
The new rules will also require manufacturers to provide an electronic version of their package inserts for placement on the FDA Web site. Yet it is unclear whether posting a compendium of drug labels on the Web will influence behavior, especially if the FDA's site remains as difficult to navigate as it is now (try looking up any drug on www.fda.gov). It seems unlikely that such an online compilation will improve clinical decision making as well as other solutions could. By contrast, the British National Formulary (www.bnf.org) is produced by independent physicians and pharmacists and contains even-handed, readable overviews of drugs that are constantly updated by the professional societies that sponsor it.
Ultimately, the most attractive and best-organized labels will not influence behavior if physicians do not read them. As is usually the case in quality improvement, a systems approach will be necessary to achieve better prescribing practices and better outcomes. Evidence-based, comparative decision-support tools, whether online or in print, can provide physicians with current data about drugs' benefits and risks, as well as immediate feedback about appropriate prescribing. But such systems are in their infancy and not in widespread use.
The most troubling aspect of the FDA's new plan, however, has nothing to do with providing information to prescribers. In an unusual move after the end of a five-year period of comments on the initial rule, the agency used the passage of the new labeling regulations to quietly add a new section to its preamble that will make it extremely difficult for anyone to bring legal action against a drug manufacturer for harm caused by one of its products. For years, the pharmaceutical industry had sought to pass legislation that would prohibit litigation over adverse effects as long as the medication was approved by the FDA; Congress has consistently rejected this idea. But after the comment period for the new labeling regulation had closed, language was added to the final rule stating that any FDA-approved label, "whether it be in the old or new format, preempts . . . decisions of a court of law for purposes of product liability litigation."4 Beginning at the end of this month, the new regulations would preempt nearly all action by patients in state courts against drug manufacturers for unanticipated injuries resulting from the use of their products. This immunity would apply even if a company failed to warn prescribers or patients adequately about a known risk, unless a patient could prove that the company intentionally committed fraud — a very hard test to meet.
Several members of the House and Senate have vigorously objected to this provision, as well as to the fact that there was no opportunity to debate it before the regulations were made final; court challenges are likely. Ironically, this low-profile aspect of the new rules could have an effect on the health care system that is much more profound than the small-scale improvements of the new labeling rules themselves. "It will make it impossible to file liability claims," said a former FDA general counsel who is now in private practice.5
In other words, along with the very modest alterations of drug labeling to be phased in over the next seven years, the changes the FDA will begin implementing next month include a regulatory time bomb that could severely limit the accountability of companies that fail to adequately evaluate or report the risks associated with their products.
Yes, the agency is trying — but how effectively, and on whose behalf?
Source Information
Dr. Avorn is a professor of medicine at Harvard Medical School and chief of the Division of Pharmacoepidemiology and Pharmacoeconomics at Brigham and Women's Hospital — both in Boston. Dr. Shrank is an instructor at Harvard Medical School and in the Division of Pharmacoepidemiology and Pharmacoeconomics at Brigham and Women's Hospital.
References
New requirements for prescribing information. Rockville, Md.: Food and Drug Administration, 2006. (Accessed May 18, 2006, at http://www.fda.gov/cder/regulatory/physLabel/default.htm.)
Improvement needed in FDA's postmarket decision-making and oversight process. Washington, D.C.: Government Accountability Office, March 31, 2006. (Accessed May 18, 2006, at http://www.gao.gov/highlights/d06402high.pdf.)
Lasser KE, Seger DL, Yu DT, et al. Adherence to black box warnings for prescription medications in outpatients. Arch Intern Med 2006;166:338-344.
Food and Drug Administration. Requirements on content and format of labeling for human prescription drug and biologic products. Fed Regist 2006;71:3922-3997.www.fda.gov/OHRMS/DOCKETS/98fr/06-545.pdf
Harris G. New drug label rule is intended to reduce medical errors. New York Times. January 19, 2006:A20. (文章出处：《新英格兰医药杂志》)