New Drugs Approved by the US FDA in 2008
2. 21 CFR §314.3. Applications for FDA approval to market a new drug: definitions. www.gpo.gov/fdsys /pkg/CFR-2003-title21-vol5/pdf/CFR-2003-title21 -vol5-sec314-3.pdf. Accessed April 22, 2013. 3. US Food and Drug Administration. Speeding access to important new therapies—fast track, accelerated approval and priority review. www.fda .gov/forconsumers/byaudience/forpatientadvocates /speedingaccesstoimportantnewtherapies /ucm128291.htm. Accessed September 20, 2013. 4. International Conference on Harmonization. Guidance for industry: the extent of population exposure to assess clinical safety: for drugs intended for long-term treatment of non-life-threatening conditions. www.fda.gov/downloads/Drugs /GuidanceComplianceRegulatoryInformation /Guidances/UCM073083.pdf. Accessed March 22, 2013.
Original Investigation Research
7. President’s Council of Advisors on Science and Technology. Report to the President on Propelling Innovation in Drug Discovery, Development and Evaluation. Washington, DC: Executive Office of the President of the United States; September 1, 2012. 8. US Food and Drug Administration. Driving Biomedical Innovation: Initiatives to Improve Products for Patients. October 2011. www.fda.gov/AboutFDA/ReportsManualsForms /Reports/ucm274333.htm. Accessed April 22, 2013. 9. Creating an alternative approval pathway for certain drugs intended to address unmet need. Fed Regist. 2013;78(10):3005-3008. www.gpo.gov /fdsys/pkg/FR-2013-01-15/pdf/2013 -00607.pdf. Accessed August 27, 2013.
5. 21 USC §355c. Research into pediatric uses for drugs and biological products. www.gpo.gov/fdsys /pkg/USCODE-2012-title21/pdf/USCODE-2012 -title21-chap9-subchapV-partA-sec355c.pdf. Accessed September 20, 2013.
10. US Food and Drug Administration. Guidance for industry: enrichment strategies for clinical trials to support approval of human drugs and biological products: draft guidance. December 2012. www.fda .gov/downloads/Drugs /GuidanceComplianceRegulatoryInformation /Guidances/UCM332181.pdf. Accessed April 22, 2013.
6. 21 USC §355–1. Risk evaluation and mitigation strategies. www.gpo.gov/fdsys/pkg/USCODE-2012 -title21/pdf/USCODE-2012-title21-chap9 -subchapV-partA-sec355-1.pdf. Accessed September 20, 2013.
11. US Food and Drug Administration. Guidance for industry: Alzheimer’s disease: developing drugs for the treatment of early stage disease: draft guidance. February 2013. www.fda.gov/downloads/Drugs
/GuidanceComplianceRegulatoryInformation /Guidances/UCM338287.pdf. Accessed April 22, 2013. 12. US Food and Drug Administration. Drug approvals and databases. www.fda.gov/Drugs /InformationOnDrugs/default.htm. Accessed April 23, 2013. 13. DailyMed Current Medication Information. US National Library of Medicine website. http://dailymed.nlm.nih.gov/dailymed/about.cfm. Accessed April 23, 2013. 14. 26 USC §45C. Clinical testing expenses for certain drugs for rare diseases or conditions. www .gpo.gov/fdsys/pkg/USCODE-2011-title26/pdf /USCODE-2011-title26-subtitleA-chap1-subchapA -partIV-subpartD-sec45C.pdf. Accessed August 27, 2013. 15. 21 USC §360cc. Protection for drugs for rare diseases or conditions. www.gpo.gov/fdsys/pkg /USCODE-2011-title21/pdf/USCODE-2011-title21 -chap9-subchapV-partB-sec360cc.pdf. Accessed August 27, 2013. 16. Moore TJ, Singh S, Furberg CD. The FDA and new safety warnings. Arch Intern Med. 2012;172(1):78-80. 17. Lester J, Neyarapally GA, Lipowski E, Graham CF, Hall M, Dal Pan G. Evaluation of FDA safety-related drug label changes in 2010. Pharmacoepidemiol Drug Saf. 2013;22(3):302-305.
Invited Commentary
Can Expedited FDA Drug Approval Without Expedited Follow-up Be Trusted? Daniel Carpenter, PhD
Like blood itself flowing through the human circulatory network, several billion prescriptions and hundreds of billions of drugs course every year through the vast web of factories, wholesale suppliers, hospitals, physicians’ offices, pharmacies, medicine cabinets, and p i l l b oxe s t h at t o ge t h e r Related article page 90 compose the health system in the United States. 1 That network comprises a vast social machine; besides money, the main lubricant is trust premised on evidence. Physicians prescribe drugs in part because they know they have been tested and that their initial safety and efficacy has met the approval c r i t e r i a o f t h e U S Fo o d a n d D r u g A d m i n i s t r a t i o n (FDA). 2 When a generic medication is prescribed, the physician trusts, consciously or unconsciously, that basic conditions of quality manufacturing and bioequivalence have been met. In most instances, the physician does not see the evidence but assumes that someone else,
principally the FDA, has rigorously reviewed the underlying data. The system can fail in many ways, but 2 of the ways are false trust and lack of trust. If regulation fails and unsafe or poor-quality drugs are introduced into the health system, patients are exposed needlessly to risks that could have been avoided by relying on existing treatments. Alternatively, if regulation fails and physicians and the public do not have evidence-based trust in drugs, fewer drugs are prescribed, patients do not receive therapies that might help them, investment drops accordingly, and the social foundations of the health system are weakened.3 In the absence of sound, independent evidence and underlying trust, just about everything can go wrong. In this issue of JAMA Internal Medicine, Moore and Furberg4 report on the development time, clinical testing, and safety risks of new drugs approved by the FDA. Moore and Furberg4 looked back to 2008, the calendar year before President Barack Obama took office. They examined the 20
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Research Original Investigation
New Drugs Approved by the US FDA in 2008
new molecular entities the FDA approved for marketing that year and compared those drugs that received expedited approval with those that underwent standard reviews. They found many differences between the groups; the most noteworthy was that efficacy testing in the drugs with accelerated approvals was performed on less than one-fifth of the median number of patients than for the drugs with standard review (104 patients compared with 580 patients; P = .003). They also report that of the 86 postmarket studies required for the 20 drugs, 26 (31%) had been fulfilled as of January 2013; another 8 (9%) had been submitted to the agency for review. Put differently, more than 4 years after the approval of these drugs, 6 in 10 promises that companies made to the FDA as a condition of approval had yet to be fulfilled. As the authors acknowledge, the number of drugs approved in 2008 was relatively small. The differences in the number of patients studied for each drug relate in part to the various diseases for which the drugs were being studied. And more of the postmarketing commitments are likely to be fulfilled in the years ahead. Yet the findings of Moore and Furberg4 are consistent with other recent evidence. In previous research,5,6 my colleagues and I demonstrated that new molecular entities approved just before the deadline to complete the drug reviews were 3 to 5 times more likely to be subsequently withdrawn from the market for safety reasons or to be subject to a FDA safety alert or a new Black Box warning than drugs approved well in advance of a review deadline. Their findings are also consistent with their previous study showing that it takes, on average, 11 or more years after drug approval for important postmarket safety information to appear in the prescribing information.7 At a time when many investors, lobbyists, and politicians would like to see accelerated approval of new drugs become the norm, the report by Moore and Furberg4 points to emerging troubles in the regulation of pharmaceuticals in applying the standards used for drugs for AIDS, cancer, and other life-threatening diseases to a wide variety of disorders that are either less severe or already have established, welltolerated treatments. In 2004, Avorn1 noted the imbalance between the relative abundance of premarket study of drugs and the relative dearth of postmarket study. Under the Obama Administration, the FDA has proposed to change some of the rules for premarket study without fully addressing the need for more postmarket study, thus perpetuating the imbalance. Earlier in 2013, Fain and colleagues 8 reported that the number of postmarketing studies with delays nearly doubled between 2007 and 2011; 43.5% of the postmarketing commitments agreed to in 2011 had not yet been started by the manufacturer. It is concerning that the FDA may alter the terms of the implicit approval contract with pharmaceutical manufacturers, that is, less clinical testing of drugs before approval with quicker review in exchange for more reliable and rigorous postapproval testing, and not enforce the postapproval requirements as it should. Will the agency accelerate premarket approvals but not postmarket studies? Will follow-up be impoverished, 96
with considerably less statistical power in postmarket studies to detect adverse events and other safety concerns? For creating incentives for truly rigorous research on drug safety and efficacy, there is no more credible or effective guarantee than the FDA’s premarket approval requirement. This requirement is the effective “veto” that the FDA (and by extension, the public) has over a company’s ability to market prescription drugs.2 The findings of Moore and Furberg4 underscore the continuing importance of rigorous premarket studies of ample size. If the critical phrase “serious or life-threatening conditions that would address an unmet medical need” is defined broadly enough (and there are lobbying efforts to define it as broadly as possible), the future of evidence for pharmaceuticals in the United States will look more like 100 patients for efficacy trials instead of 500 patients. The current system of acceleration drug approval in the United States can be described as a growing hodgepodge of exceptions to the rule of rigorous premarket review. Among the exceptions are accelerated approval, priority review, orphan drug designation, separate standards for drugs for AIDS and cancers, and possibly now alternative pathways and “enriched” trials. Alternative pathways include approval based on outcomes assessed by biomarkers, not clinical end points and/or smaller samples for efficacy trials. In an enriched trial, patient selection before randomization is based on the likelihood of response to the experimental agent as estimated by a genomic (BCRA-negative carcinoma), phenotypic (urine expression), or behavioral (previous medication adherence) model of likely response. 9 Under both of these scenarios, the subjects in clinical trials would be progressively limited to those more likely to respond to an experimental agent; however, there is as yet no plan for a corresponding requirement that the drug be marketed only to those patients whose genotypic or phenotypic characteristics were represented in the original study population. The benefits of such changes to the FDA’s standards are uncertain.10 Despite the variety of current drug approval mechanisms, all by and large preserve the core elements of rigorous, randomized and placebo-controlled large-sample trials for efficacy, with exceptions recognized only for clear public health reasons and for conditions without effective treatments. The case is not yet clear, and it is certainly not based on evidence, that the rules for cancer and AIDS should be extended widely to other diseases. If I disagree with Moore and Furberg, it is that they slightly misstate the primary mission of the FDA. The mission is not only to “assure patient safety” but also to ensure the efficacy of drugs on the market and the collective trust of the medical profession and society at large in the efficacy of these drugs. If the FDA’s requirements for new drugs, both premarket and postmarket, are weakened, trust in both the efficacy and safety of prescription drugs is likely to be weakened. The stakes of the current policy debates could not be higher. There is scarcely a feature of the American health care system that does not depend on evidence-based trust in prescription drugs, ratified and enforced by the FDA.
JAMA Internal Medicine January 2014 Volume 174, Number 1
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archinte.jamanetwork.com/ by a University of Georgia User on 06/06/2015
jamainternalmedicine.com
New Drugs Approved by the US FDA in 2008
ARTICLE INFORMATION Author Affiliation: Department of Government and Center for American Political Studies, Radcliffe Institute for Advanced Study, Harvard University, Cambridge, Massachusetts. Corresponding Author: Daniel Carpenter, PhD, Department of Government, Harvard University, 1737 Cambridge St, Cambridge, MA 02138 ([email protected]). Published Online: October 28, 2013. doi:10.1001/jamainternmed.2013.9202. Conflict of Interest Disclosures: None reported. REFERENCES 1. Avorn J. Powerful Medicines: The Benefits, Risks and Costs of Prescription Drugs. New York, NY: Knopf; 2004. 2. Carpenter D. Reputation and Power: Organizational Image and Pharmaceutical Regulation at the FDA. Princeton, NJ: Princeton University Press; 2010. 3. Berenson A. Big drug makers see sales decline with their image. New York Times. November 14,
Original Investigation Research
2005. www.nytimes.com/2005/11/14/business /14pharma.html?pagewanted=all&_r=0. Accessed September 25, 2013. 4. Moore TJ, Furberg CD. Development times, clinical testing, postmarket follow-up, and safety risks for the new drugs approved by the US Food and Drug Administration: the class of 2008 [published online October 28, 2013]. JAMA Intern Med. doi:10.1001/jamainternmed.2013.11813. 5. Carpenter D, Chattopadhyay J, Moffitt S, Nall C. The complications of controlling agency time discretion: FDA review deadlines and postmarket drug safety. Am J Pol Sci. 2012;56(1):98-114. 6. Carpenter D, Zucker EJ, Avorn J. Drug-review deadlines and safety problems. N Engl J Med. 2008;358(13):1354-1361. 7. Moore TJ, Singh S, Furberg CD. The FDA and new safety warnings. Arch Intern Med. 2012;172(1):78-80.
9. US Food and Drug Administration. Guidance for industry: enrichment strategies for clinical trials to support approval of human drugs and biological products: draft guidance. December 2012. www.fda .gov/downloads/Drugs /GuidanceComplianceRegulatoryInformation /Guidances/UCM332181.pdf. Accessed August 19, 2013. 10. Cancer Leadership Council. Letter to Margaret A. Hamburg, MD, re: creating an alternative approval pathway for certain drugs intended to address unmet medical need, FDA-2012-N-1248 -0001. March 1, 2013; www.asco.org/sites/www .asco.org/files/aia/Cancer%20Leadership %20Council%20Comments%20on %20Alternative%20Approval%20Pathway %20March%202013.pdf. Accessed August 19, 2013.
8. Fain K, Daubresse M, Alexander GC. The Food and Drug Administration Amendments Act and postmarketing commitments. JAMA. 2013;310(2):202-204.
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JAMA Internal Medicine January 2014 Volume 174, Number 1
Copyright 2014 American Medical Association. All rights reserved.
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97
2. 21 CFR §314.3. Applications for FDA approval to market a new drug: definitions. www.gpo.gov/fdsys /pkg/CFR-2003-title21-vol5/pdf/CFR-2003-title21 -vol5-sec314-3.pdf. Accessed April 22, 2013. 3. US Food and Drug Administration. Speeding access to important new therapies—fast track, accelerated approval and priority review. www.fda .gov/forconsumers/byaudience/forpatientadvocates /speedingaccesstoimportantnewtherapies /ucm128291.htm. Accessed September 20, 2013. 4. International Conference on Harmonization. Guidance for industry: the extent of population exposure to assess clinical safety: for drugs intended for long-term treatment of non-life-threatening conditions. www.fda.gov/downloads/Drugs /GuidanceComplianceRegulatoryInformation /Guidances/UCM073083.pdf. Accessed March 22, 2013.
Original Investigation Research
7. President’s Council of Advisors on Science and Technology. Report to the President on Propelling Innovation in Drug Discovery, Development and Evaluation. Washington, DC: Executive Office of the President of the United States; September 1, 2012. 8. US Food and Drug Administration. Driving Biomedical Innovation: Initiatives to Improve Products for Patients. October 2011. www.fda.gov/AboutFDA/ReportsManualsForms /Reports/ucm274333.htm. Accessed April 22, 2013. 9. Creating an alternative approval pathway for certain drugs intended to address unmet need. Fed Regist. 2013;78(10):3005-3008. www.gpo.gov /fdsys/pkg/FR-2013-01-15/pdf/2013 -00607.pdf. Accessed August 27, 2013.
5. 21 USC §355c. Research into pediatric uses for drugs and biological products. www.gpo.gov/fdsys /pkg/USCODE-2012-title21/pdf/USCODE-2012 -title21-chap9-subchapV-partA-sec355c.pdf. Accessed September 20, 2013.
10. US Food and Drug Administration. Guidance for industry: enrichment strategies for clinical trials to support approval of human drugs and biological products: draft guidance. December 2012. www.fda .gov/downloads/Drugs /GuidanceComplianceRegulatoryInformation /Guidances/UCM332181.pdf. Accessed April 22, 2013.
6. 21 USC §355–1. Risk evaluation and mitigation strategies. www.gpo.gov/fdsys/pkg/USCODE-2012 -title21/pdf/USCODE-2012-title21-chap9 -subchapV-partA-sec355-1.pdf. Accessed September 20, 2013.
11. US Food and Drug Administration. Guidance for industry: Alzheimer’s disease: developing drugs for the treatment of early stage disease: draft guidance. February 2013. www.fda.gov/downloads/Drugs
/GuidanceComplianceRegulatoryInformation /Guidances/UCM338287.pdf. Accessed April 22, 2013. 12. US Food and Drug Administration. Drug approvals and databases. www.fda.gov/Drugs /InformationOnDrugs/default.htm. Accessed April 23, 2013. 13. DailyMed Current Medication Information. US National Library of Medicine website. http://dailymed.nlm.nih.gov/dailymed/about.cfm. Accessed April 23, 2013. 14. 26 USC §45C. Clinical testing expenses for certain drugs for rare diseases or conditions. www .gpo.gov/fdsys/pkg/USCODE-2011-title26/pdf /USCODE-2011-title26-subtitleA-chap1-subchapA -partIV-subpartD-sec45C.pdf. Accessed August 27, 2013. 15. 21 USC §360cc. Protection for drugs for rare diseases or conditions. www.gpo.gov/fdsys/pkg /USCODE-2011-title21/pdf/USCODE-2011-title21 -chap9-subchapV-partB-sec360cc.pdf. Accessed August 27, 2013. 16. Moore TJ, Singh S, Furberg CD. The FDA and new safety warnings. Arch Intern Med. 2012;172(1):78-80. 17. Lester J, Neyarapally GA, Lipowski E, Graham CF, Hall M, Dal Pan G. Evaluation of FDA safety-related drug label changes in 2010. Pharmacoepidemiol Drug Saf. 2013;22(3):302-305.
Invited Commentary
Can Expedited FDA Drug Approval Without Expedited Follow-up Be Trusted? Daniel Carpenter, PhD
Like blood itself flowing through the human circulatory network, several billion prescriptions and hundreds of billions of drugs course every year through the vast web of factories, wholesale suppliers, hospitals, physicians’ offices, pharmacies, medicine cabinets, and p i l l b oxe s t h at t o ge t h e r Related article page 90 compose the health system in the United States. 1 That network comprises a vast social machine; besides money, the main lubricant is trust premised on evidence. Physicians prescribe drugs in part because they know they have been tested and that their initial safety and efficacy has met the approval c r i t e r i a o f t h e U S Fo o d a n d D r u g A d m i n i s t r a t i o n (FDA). 2 When a generic medication is prescribed, the physician trusts, consciously or unconsciously, that basic conditions of quality manufacturing and bioequivalence have been met. In most instances, the physician does not see the evidence but assumes that someone else,
principally the FDA, has rigorously reviewed the underlying data. The system can fail in many ways, but 2 of the ways are false trust and lack of trust. If regulation fails and unsafe or poor-quality drugs are introduced into the health system, patients are exposed needlessly to risks that could have been avoided by relying on existing treatments. Alternatively, if regulation fails and physicians and the public do not have evidence-based trust in drugs, fewer drugs are prescribed, patients do not receive therapies that might help them, investment drops accordingly, and the social foundations of the health system are weakened.3 In the absence of sound, independent evidence and underlying trust, just about everything can go wrong. In this issue of JAMA Internal Medicine, Moore and Furberg4 report on the development time, clinical testing, and safety risks of new drugs approved by the FDA. Moore and Furberg4 looked back to 2008, the calendar year before President Barack Obama took office. They examined the 20
jamainternalmedicine.com
JAMA Internal Medicine January 2014 Volume 174, Number 1
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archinte.jamanetwork.com/ by a University of Georgia User on 06/06/2015
95
Research Original Investigation
New Drugs Approved by the US FDA in 2008
new molecular entities the FDA approved for marketing that year and compared those drugs that received expedited approval with those that underwent standard reviews. They found many differences between the groups; the most noteworthy was that efficacy testing in the drugs with accelerated approvals was performed on less than one-fifth of the median number of patients than for the drugs with standard review (104 patients compared with 580 patients; P = .003). They also report that of the 86 postmarket studies required for the 20 drugs, 26 (31%) had been fulfilled as of January 2013; another 8 (9%) had been submitted to the agency for review. Put differently, more than 4 years after the approval of these drugs, 6 in 10 promises that companies made to the FDA as a condition of approval had yet to be fulfilled. As the authors acknowledge, the number of drugs approved in 2008 was relatively small. The differences in the number of patients studied for each drug relate in part to the various diseases for which the drugs were being studied. And more of the postmarketing commitments are likely to be fulfilled in the years ahead. Yet the findings of Moore and Furberg4 are consistent with other recent evidence. In previous research,5,6 my colleagues and I demonstrated that new molecular entities approved just before the deadline to complete the drug reviews were 3 to 5 times more likely to be subsequently withdrawn from the market for safety reasons or to be subject to a FDA safety alert or a new Black Box warning than drugs approved well in advance of a review deadline. Their findings are also consistent with their previous study showing that it takes, on average, 11 or more years after drug approval for important postmarket safety information to appear in the prescribing information.7 At a time when many investors, lobbyists, and politicians would like to see accelerated approval of new drugs become the norm, the report by Moore and Furberg4 points to emerging troubles in the regulation of pharmaceuticals in applying the standards used for drugs for AIDS, cancer, and other life-threatening diseases to a wide variety of disorders that are either less severe or already have established, welltolerated treatments. In 2004, Avorn1 noted the imbalance between the relative abundance of premarket study of drugs and the relative dearth of postmarket study. Under the Obama Administration, the FDA has proposed to change some of the rules for premarket study without fully addressing the need for more postmarket study, thus perpetuating the imbalance. Earlier in 2013, Fain and colleagues 8 reported that the number of postmarketing studies with delays nearly doubled between 2007 and 2011; 43.5% of the postmarketing commitments agreed to in 2011 had not yet been started by the manufacturer. It is concerning that the FDA may alter the terms of the implicit approval contract with pharmaceutical manufacturers, that is, less clinical testing of drugs before approval with quicker review in exchange for more reliable and rigorous postapproval testing, and not enforce the postapproval requirements as it should. Will the agency accelerate premarket approvals but not postmarket studies? Will follow-up be impoverished, 96
with considerably less statistical power in postmarket studies to detect adverse events and other safety concerns? For creating incentives for truly rigorous research on drug safety and efficacy, there is no more credible or effective guarantee than the FDA’s premarket approval requirement. This requirement is the effective “veto” that the FDA (and by extension, the public) has over a company’s ability to market prescription drugs.2 The findings of Moore and Furberg4 underscore the continuing importance of rigorous premarket studies of ample size. If the critical phrase “serious or life-threatening conditions that would address an unmet medical need” is defined broadly enough (and there are lobbying efforts to define it as broadly as possible), the future of evidence for pharmaceuticals in the United States will look more like 100 patients for efficacy trials instead of 500 patients. The current system of acceleration drug approval in the United States can be described as a growing hodgepodge of exceptions to the rule of rigorous premarket review. Among the exceptions are accelerated approval, priority review, orphan drug designation, separate standards for drugs for AIDS and cancers, and possibly now alternative pathways and “enriched” trials. Alternative pathways include approval based on outcomes assessed by biomarkers, not clinical end points and/or smaller samples for efficacy trials. In an enriched trial, patient selection before randomization is based on the likelihood of response to the experimental agent as estimated by a genomic (BCRA-negative carcinoma), phenotypic (urine expression), or behavioral (previous medication adherence) model of likely response. 9 Under both of these scenarios, the subjects in clinical trials would be progressively limited to those more likely to respond to an experimental agent; however, there is as yet no plan for a corresponding requirement that the drug be marketed only to those patients whose genotypic or phenotypic characteristics were represented in the original study population. The benefits of such changes to the FDA’s standards are uncertain.10 Despite the variety of current drug approval mechanisms, all by and large preserve the core elements of rigorous, randomized and placebo-controlled large-sample trials for efficacy, with exceptions recognized only for clear public health reasons and for conditions without effective treatments. The case is not yet clear, and it is certainly not based on evidence, that the rules for cancer and AIDS should be extended widely to other diseases. If I disagree with Moore and Furberg, it is that they slightly misstate the primary mission of the FDA. The mission is not only to “assure patient safety” but also to ensure the efficacy of drugs on the market and the collective trust of the medical profession and society at large in the efficacy of these drugs. If the FDA’s requirements for new drugs, both premarket and postmarket, are weakened, trust in both the efficacy and safety of prescription drugs is likely to be weakened. The stakes of the current policy debates could not be higher. There is scarcely a feature of the American health care system that does not depend on evidence-based trust in prescription drugs, ratified and enforced by the FDA.
JAMA Internal Medicine January 2014 Volume 174, Number 1
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://archinte.jamanetwork.com/ by a University of Georgia User on 06/06/2015
jamainternalmedicine.com
New Drugs Approved by the US FDA in 2008
ARTICLE INFORMATION Author Affiliation: Department of Government and Center for American Political Studies, Radcliffe Institute for Advanced Study, Harvard University, Cambridge, Massachusetts. Corresponding Author: Daniel Carpenter, PhD, Department of Government, Harvard University, 1737 Cambridge St, Cambridge, MA 02138 ([email protected]). Published Online: October 28, 2013. doi:10.1001/jamainternmed.2013.9202. Conflict of Interest Disclosures: None reported. REFERENCES 1. Avorn J. Powerful Medicines: The Benefits, Risks and Costs of Prescription Drugs. New York, NY: Knopf; 2004. 2. Carpenter D. Reputation and Power: Organizational Image and Pharmaceutical Regulation at the FDA. Princeton, NJ: Princeton University Press; 2010. 3. Berenson A. Big drug makers see sales decline with their image. New York Times. November 14,
Original Investigation Research
2005. www.nytimes.com/2005/11/14/business /14pharma.html?pagewanted=all&_r=0. Accessed September 25, 2013. 4. Moore TJ, Furberg CD. Development times, clinical testing, postmarket follow-up, and safety risks for the new drugs approved by the US Food and Drug Administration: the class of 2008 [published online October 28, 2013]. JAMA Intern Med. doi:10.1001/jamainternmed.2013.11813. 5. Carpenter D, Chattopadhyay J, Moffitt S, Nall C. The complications of controlling agency time discretion: FDA review deadlines and postmarket drug safety. Am J Pol Sci. 2012;56(1):98-114. 6. Carpenter D, Zucker EJ, Avorn J. Drug-review deadlines and safety problems. N Engl J Med. 2008;358(13):1354-1361. 7. Moore TJ, Singh S, Furberg CD. The FDA and new safety warnings. Arch Intern Med. 2012;172(1):78-80.
9. US Food and Drug Administration. Guidance for industry: enrichment strategies for clinical trials to support approval of human drugs and biological products: draft guidance. December 2012. www.fda .gov/downloads/Drugs /GuidanceComplianceRegulatoryInformation /Guidances/UCM332181.pdf. Accessed August 19, 2013. 10. Cancer Leadership Council. Letter to Margaret A. Hamburg, MD, re: creating an alternative approval pathway for certain drugs intended to address unmet medical need, FDA-2012-N-1248 -0001. March 1, 2013; www.asco.org/sites/www .asco.org/files/aia/Cancer%20Leadership %20Council%20Comments%20on %20Alternative%20Approval%20Pathway %20March%202013.pdf. Accessed August 19, 2013.
8. Fain K, Daubresse M, Alexander GC. The Food and Drug Administration Amendments Act and postmarketing commitments. JAMA. 2013;310(2):202-204.
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JAMA Internal Medicine January 2014 Volume 174, Number 1
Copyright 2014 American Medical Association. All rights reserved.
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97
