"Me-Too" Products — Friend or Foe?
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《新英格兰医药杂志》
To the Editor: The proliferation of "me-too" drugs leads to beneficial cost reductions, as Lee notes in his Perspective article (Jan. 15 issue),1 but it may also put patients at risk. Each me-too drug comes to the market with limited clinical experience as compared with compounds already in use. Five me-too drugs in the statin and quinolone classes have been withdrawn or restricted because of serious adverse effects that were not recognized until months or years after their approval (temafloxacin, grepafloxacin, cerivastatin, sparfloxacin, and trovafloxacin).
The potential for cost savings may induce health systems to use a me-too drug before its safety has been established. Gatifloxacin is a current example. Through competitive bidding, the federal government recently obtained the bargain price of $1.35 for a daily dose of this medication.2 The Department of Defense estimates annual savings of $2 million to $10 million by replacing levofloxacin with gatifloxacin. However, gatifloxacin is associated with higher rates of abnormalities in glucose homeostasis2,3 and torsades de pointes4 than are other popular quinolones. This cost–safety issue has no simple answer. As Lee states, "Physicians have to choose products as if costs matter." We must also be advocates for our patients' safety.
Richard Frothingham, M.D.
Duke University Medical Center
Durham, NC 27710
richard.frothingham@duke.edu
Editor's note: Dr. Frothingham reports having received honoraria from or having served as a consultant for Bayer, Bristol-Myers Squibb, Ortho-McNeil, and Otsuka.
References
Lee TH. "Me-too" products -- friend or foe? N Engl J Med 2004;350:211-212.
Guidance for the new oral fluoroquinolone contract. Fort Sam Houston, Tex.: Pharmacoeconomic Center, Department of Defense, January 2004. (Accessed April 22, 2004, at http://www.pec.ha.osd.mil/national_contracts.htm.)
Hypoglycemia and hyperglycemia with fluoroquinolones. Med Lett Drugs Ther 2003;45:64-64.
Frothingham R. Rates of torsades de pointes associated with ciprofloxacin, ofloxacin, levofloxacin, gatifloxacin, and moxifloxacin. Pharmacotherapy 2001;21:1468-1472.
To the Editor: Dr. Lee's Perspective article on me-too products is puzzling. If, as he claims, me-too drugs promote competition that lowers prices, why has the average wholesale price of brand-name drugs in virtually every therapeutic category continued to rise steadily over the years? And if successive me-too drugs really represent an improvement in quality, why have we not seen head-to-head clinical trials that support such claims? Dr. Lee's discussion of stents coated with sirolimus or paclitaxel does not help to dispel the confusion. We do not know what direct comparisons of their safety and effectiveness would show, and we are told nothing about their relative costs.
Puzzled readers like me would probably be a little less skeptical about Dr. Lee's opinions on me-too products if we knew that he had no financial ties to any pharmaceutical or medical-device companies. This article clearly needed a disclosure statement.
Arnold S. Relman, M.D.
Harvard Medical School
Boston, MA 02115
arelman@rics.bwh.harvard.edu
Dr. Lee replies: Dr. Frothingham is correct in pointing out that me-too drugs often enter the market with less clinical-trial experience and that safety issues may be recognized only after years of use. Concern about the safety of "first-in-class" drugs is also substantial, since they are, after all, the first in their class to be used in large populations for extended periods. We are in agreement that physicians must be advocates for their patients' safety. I add that physicians should also give attention to efficiency, so that we have the resources to provide care to all who need it.
The issues that puzzle Dr. Relman are explained by medical progress and marketplace forces. The rise in the average price of brand-name drugs reflects the introduction of new classes of drugs with clinical advantages for subgroups of patients (e.g., angiotensin-receptor blockers and cyclooxygenase-2 inhibitors). Within these classes, later entrants tend to have lower prices, but these drugs are expensive as compared with older alternatives (angiotensin-converting–enzyme inhibitors and nonselective nonsteroidal antiinflammatory drugs, respectively). The newer, more costly agents are often promoted for use in a wider patient population than that for which their superiority has been proved, and they are therefore bigger drivers of cost increases than they should be.
Manufacturers sponsor head-to-head trials when they have a strong belief that they will demonstrate the clinical superiority of their products, but not surprisingly, they are reluctant to fund such trials when the risk of finding no benefit is moderate or high. When there are no head-to-head data, manufacturers must generally compete on the basis of cost, unless there are other advantages of their products. As I predicted in my Perspective article, the newer, paclitaxel-coated stent is being listed at a price that is $245 less than the price of the sirolimus-coated stent. And that is just the starting point for negotiations. Now that they have more than one option, hospitals are bargaining for and obtaining lower prices by threatening to move their business.
My article carried no disclosure statement because there is nothing to disclose. Like all editors of the New England Journal of Medicine, I have no equity in or consulting or advisory-board relationships with pharmaceutical or medical-device companies, and I accept no honoraria. My Perspective article reflects data and experience.
Thomas H. Lee, M.D.
Partners Healthcare System
Boston, MA 02199
The potential for cost savings may induce health systems to use a me-too drug before its safety has been established. Gatifloxacin is a current example. Through competitive bidding, the federal government recently obtained the bargain price of $1.35 for a daily dose of this medication.2 The Department of Defense estimates annual savings of $2 million to $10 million by replacing levofloxacin with gatifloxacin. However, gatifloxacin is associated with higher rates of abnormalities in glucose homeostasis2,3 and torsades de pointes4 than are other popular quinolones. This cost–safety issue has no simple answer. As Lee states, "Physicians have to choose products as if costs matter." We must also be advocates for our patients' safety.
Richard Frothingham, M.D.
Duke University Medical Center
Durham, NC 27710
richard.frothingham@duke.edu
Editor's note: Dr. Frothingham reports having received honoraria from or having served as a consultant for Bayer, Bristol-Myers Squibb, Ortho-McNeil, and Otsuka.
References
Lee TH. "Me-too" products -- friend or foe? N Engl J Med 2004;350:211-212.
Guidance for the new oral fluoroquinolone contract. Fort Sam Houston, Tex.: Pharmacoeconomic Center, Department of Defense, January 2004. (Accessed April 22, 2004, at http://www.pec.ha.osd.mil/national_contracts.htm.)
Hypoglycemia and hyperglycemia with fluoroquinolones. Med Lett Drugs Ther 2003;45:64-64.
Frothingham R. Rates of torsades de pointes associated with ciprofloxacin, ofloxacin, levofloxacin, gatifloxacin, and moxifloxacin. Pharmacotherapy 2001;21:1468-1472.
To the Editor: Dr. Lee's Perspective article on me-too products is puzzling. If, as he claims, me-too drugs promote competition that lowers prices, why has the average wholesale price of brand-name drugs in virtually every therapeutic category continued to rise steadily over the years? And if successive me-too drugs really represent an improvement in quality, why have we not seen head-to-head clinical trials that support such claims? Dr. Lee's discussion of stents coated with sirolimus or paclitaxel does not help to dispel the confusion. We do not know what direct comparisons of their safety and effectiveness would show, and we are told nothing about their relative costs.
Puzzled readers like me would probably be a little less skeptical about Dr. Lee's opinions on me-too products if we knew that he had no financial ties to any pharmaceutical or medical-device companies. This article clearly needed a disclosure statement.
Arnold S. Relman, M.D.
Harvard Medical School
Boston, MA 02115
arelman@rics.bwh.harvard.edu
Dr. Lee replies: Dr. Frothingham is correct in pointing out that me-too drugs often enter the market with less clinical-trial experience and that safety issues may be recognized only after years of use. Concern about the safety of "first-in-class" drugs is also substantial, since they are, after all, the first in their class to be used in large populations for extended periods. We are in agreement that physicians must be advocates for their patients' safety. I add that physicians should also give attention to efficiency, so that we have the resources to provide care to all who need it.
The issues that puzzle Dr. Relman are explained by medical progress and marketplace forces. The rise in the average price of brand-name drugs reflects the introduction of new classes of drugs with clinical advantages for subgroups of patients (e.g., angiotensin-receptor blockers and cyclooxygenase-2 inhibitors). Within these classes, later entrants tend to have lower prices, but these drugs are expensive as compared with older alternatives (angiotensin-converting–enzyme inhibitors and nonselective nonsteroidal antiinflammatory drugs, respectively). The newer, more costly agents are often promoted for use in a wider patient population than that for which their superiority has been proved, and they are therefore bigger drivers of cost increases than they should be.
Manufacturers sponsor head-to-head trials when they have a strong belief that they will demonstrate the clinical superiority of their products, but not surprisingly, they are reluctant to fund such trials when the risk of finding no benefit is moderate or high. When there are no head-to-head data, manufacturers must generally compete on the basis of cost, unless there are other advantages of their products. As I predicted in my Perspective article, the newer, paclitaxel-coated stent is being listed at a price that is $245 less than the price of the sirolimus-coated stent. And that is just the starting point for negotiations. Now that they have more than one option, hospitals are bargaining for and obtaining lower prices by threatening to move their business.
My article carried no disclosure statement because there is nothing to disclose. Like all editors of the New England Journal of Medicine, I have no equity in or consulting or advisory-board relationships with pharmaceutical or medical-device companies, and I accept no honoraria. My Perspective article reflects data and experience.
Thomas H. Lee, M.D.
Partners Healthcare System
Boston, MA 02199