The Experts below are selected from a list of 446133 Experts worldwide ranked by ideXlab platform
Aaron S Kesselheim - One of the best experts on this subject based on the ideXlab platform.
-
market Exclusivity length for drugs with new generic or biosimilar competition 2012 2018
Clinical Pharmacology & Therapeutics, 2020Co-Authors: Aaron S Kesselheim, Benjamin N RomeAbstract:Brand-name drugs have periods of market Exclusivity before generic competition begins. Due to high brand-name drug prices charged during this period, market Exclusivity is an important determinant of US prescription drug spending. We used claims data to estimate the market Exclusivity period for 264 small molecule and 4 biologic drugs that faced new generic or biosimilar competition from 2012-2018. Exclusivity periods were longer for biologics compared with new small molecule drugs (median 21.5 vs. 14.4 years, P = 0.02), longer for drugs with annual revenue < $75 million compared with those with revenue ≥ $500 million (16.6 vs. 14.2 years, P = 0.01), and shorter in cases for which the first generic was granted 180 days of Exclusivity, which is an incentive designed to expedite generic competition (14.1 vs. 15.9 years, P < 0.01). Modified versions of existing products had shorter exclusivities than new drugs (9.9 vs. 14.5 years, P < 0.01), with variation by route of administration, therapeutic area, and use of expedited approval pathways. Exclusivity periods for new drugs ranging from 13-17 years are similar to older estimates, but longer Exclusivity among the small number of biologics in the cohort raises concern that overall median Exclusivity may lengthen in the future because biologics represent a larger fraction of new drug approvals over the last decade than they did the previous decade. Unnecessarily long Exclusivity periods delay patient access to lower-priced medications, and policymakers should consider options to encourage timely competition, particularly among biologic drugs.
-
transferrable market Exclusivity extensions to promote antibiotic development an economic analysis
Clinical Infectious Diseases, 2019Co-Authors: Aaron S Kesselheim, Benjamin N RomeAbstract:BACKGROUND: To address the growing threat of multidrug resistant organisms, policymakers are seeking ideas to promote development of novel antibiotics. In 2018, the REVAMP Act was proposed in Congress to reward manufacturers of certain novel antibiotics with transferrable market Exclusivity vouchers. METHODS: We estimated the economic impact of this proposal by identifying antimicrobial drugs approved by the FDA from 2007 - 2016 that would likely have qualified for an Exclusivity voucher and matching each drug to the highest-revenue fast-track drug facing generic entry within 4 years after the antibiotic was approved. Assuming a spending decrease of 75% after generic entry, we calculated the per-drug and total societal costs of these transferrable market Exclusivity extensions over a decade. RESULTS: We identified 10 antimicrobials that would have qualified for an Exclusivity voucher, each of which was matched with one of 17 fast-track drugs facing generic entry through July 2019. These 10 drugs had a median annual revenue prior to generic entry of $249 million (range: $26 million - $2.7 billion). Accounting for a 75% spending reduction after generic entry, the median excess spending associated with 12 months of extended Exclusivity was $187 million, for a total of $4.5 billion over 10 years. CONCLUSIONS: While market Exclusivity extensions are a politically appealing mechanism to encourage novel antibiotic development, this approach would cost public and private payers billions of dollars over the next decade.
-
labeling changes and costs for clinical trials performed under the us food and drug administration pediatric Exclusivity extension 2007 to 2012
JAMA Internal Medicine, 2018Co-Authors: Michael S Sinha, Mehdi Najafzadeh, Elizabeth K Rajasingh, James Love, Aaron S KesselheimAbstract:Importance Pharmaceutical manufacturers can receive 6 additional months of market Exclusivity for performing pediatric clinical trials of brand-name drugs widely used in adults. Congress created this incentive in 1997 because these drugs were being used off-label in children without such trials. Objective To review updates to drug labeling and the cost to consumers of extending market Exclusivity related to the pediatric Exclusivity program. Design From government records, we identified 54 drugs that earned the pediatric Exclusivity incentive between 2007 and 2012. We evaluated labeling changes from the pediatric studies. We then extracted trial details from clinical review documents and used industry estimates of trial costs on a per-patient basis to estimate cost of investment for trials (with a 10% cost of capital). To calculate the net return and cost to consumers during the 6-month Exclusivity period, we estimated additional revenue for the 48 drugs with available information. Main Outcomes and Measures For each drug, we evaluated labeling changes and costs associated with pediatric trials under the Best Pharmaceuticals for Children Act and the cost to consumers of 6-month market Exclusivity extensions. Results The 141 trials in our sample enrolled 20 240 children (interquartile range [IQR], 2-3 trials and 127-556 patients per drug). These trials led to 29 extended indications and 3 new indications, as well as new safety information for 16 drugs. Median cost of investment for trials was $36.4 million (IQR, $16.6 to $100.6 million). Among 48 drugs with available financial information, median net return was $176.0 million (IQR, $47.0 million to $404.1 million), with a median ratio of net return to cost of investment of 680% (IQR, 80% to 1270%). Conclusions and Relevance Clinical trials conducted under the US Food and Drug Administration’s pediatric Exclusivity program have provided important information about the effectiveness and safety of drugs used in children. The costs to consumers have been high, exceeding the estimated costs of investment for conducting the trials. As an alternative, policymakers should consider direct funding of such studies.
-
Drug Market Exclusivity Periods: Helpful/Harmful?
2018Co-Authors: Amitabh Chandra, Aaron S KesselheimAbstract:What impact do market Exclusivity periods have on the cost of drugs and on incentives for innovation?
-
six month market Exclusivity extensions to promote research offer substantial returns for many drug makers
Health Affairs, 2017Co-Authors: Aaron S Kesselheim, Benjamin N Rome, Ameet Sarpatwari, Jerry AvornAbstract:To incentivize pharmaceutical manufacturers to invest in areas of unmet medical need, policy makers frequently propose extending the market Exclusivity period of desired drugs. Some such proposals are modeled after the pediatric Exclusivity patent extension program, which since 1997 has provided six additional months of market Exclusivity for drugs studied in children. The most recent proposal would encourage rare disease research by providing six months of extended Exclusivity for any existing drug that is granted subsequent FDA approval for a new rare disease indication. Yet the economic impact of such proposals is rarely addressed. We found that for the thirteen FDA-approved drugs that gained supplemental approval for a rare disease indication from 2005 through 2010, the median projected cost of clinical trials leading to approval was $29.8 million. If the Exclusivity extension had been in place, the median discounted financial gain to manufacturers would have been $94.6 million. Median net returns wou...
Jennifer S Li - One of the best experts on this subject based on the ideXlab platform.
-
globalization of pediatric research analysis of clinical trials completed for pediatric Exclusivity
Pediatrics, 2010Co-Authors: Sara K Pasquali, P B Smith, Daniel K Benjamin, Danielle S Burstein, Jennifer S LiAbstract:We evaluated the setting of published studies conducted under the US Pediatric Exclusivity Provision, which provides economic incentives to pharmaceutical companies to conduct drug studies with children. METHODS: Published studies containing the main results of trials con- ducted in 1998 -2007 under the Pediatric Exclusivity Provision were included. Data were extracted from each study and described, includ- ing the therapeutic area of drug studied, number of patients enrolled, number of sites, and location where the study was conducted, if re-
-
Is pediatric Exclusivity working
Pediatric Health, 2007Co-Authors: Jennifer S Li, Robert M Califf, P. Brian Smith, Daniel K BenjaminAbstract:Most drugs prescribed for children have not undergone pediatric testing; therefore, the data on dosing, efficacy and safety that are available for adults are not usually available for children. In 1997, Congress authorized the US FDA to grant extensions of marketing rights known as ‘pediatric Exclusivity’ if FDA-requested pediatric trials are conducted. Although the program has been praised for stimulating an unprecedented number of drug studies in children, it has been criticized as an economic ‘windfall’ to prescription-drug manufacturers. The benefits of pediatric Exclusivity are immeasurable towards improving child health, yet there exist many opportunities to improve the pediatric Exclusivity program.
-
economic return of clinical trials performed under the pediatric Exclusivity program
JAMA, 2007Co-Authors: Jennifer S Li, Henry G Grabowski, Eric L Eisenstein, Elizabeth D Reid, Barry Mangum, Kevin A Schulman, John V Goldsmith, Dianne M Murphy, Robert M Califf, Daniel K BenjaminAbstract:ContextIn 1997, Congress authorized the US Food and Drug Administration (FDA) to grant 6-month extensions of marketing rights through the Pediatric Exclusivity Program if industry sponsors complete FDA-requested pediatric trials. The program has been praised for creating incentives for studies in children and has been criticized as a “windfall” to the innovator drug industry. This critique has been a substantial part of congressional debate on the program, which is due to expire in 2007.ObjectiveTo quantify the economic return to industry for completing pediatric Exclusivity trials.Design and SettingA cohort study of programs conducted for pediatric Exclusivity. Nine drugs that were granted pediatric Exclusivity were selected. From the final study reports submitted to the FDA (2002-2004), key elements of the clinical trial design and study operations were obtained, and the cost of performing each study was estimated and converted into estimates of after-tax cash outflows. Three-year market sales were obtained and converted into estimates of after-tax cash inflows based on 6 months of additional market protection. Net economic return (cash inflows minus outflows) and net return-to-costs ratio (net economic return divided by cash outflows) for each product were then calculated.Main Outcome MeasuresNet economic return and net return-to-cost ratio.ResultsThe indications studied reflect a broad representation of the program: asthma, tumors, attention-deficit/hyperactivity disorder, hypertension, depression/generalized anxiety disorder, diabetes mellitus, gastroesophageal reflux, bacterial infection, and bone mineralization. The distribution of net economic return for 6 months of Exclusivity varied substantially among products (net economic return ranged from −$8.9 million to $507.9 million and net return-to-cost ratio ranged from −0.68 to 73.63).ConclusionsThe economic return for pediatric Exclusivity is variable. As an incentive to complete much-needed clinical trials in children, pediatric Exclusivity can generate lucrative returns or produce more modest returns on investment.
-
peer reviewed publication of clinical trials completed for pediatric Exclusivity
JAMA, 2006Co-Authors: Daniel K Benjamin, Dianne M Murphy, Robert M Califf, Debbie Avant, P B Smith, Rosemary Roberts, Lisa Mathis, Jennifer S LiAbstract:ContextMuch of pediatric drug use is off-label because appropriate pediatric studies have not been conducted and the drugs have not been labeled by the US Food and Drug Administration (FDA) for use in children. In 1997, Congress authorized the FDA to grant extensions of marketing rights known as “pediatric Exclusivity” if FDA-requested pediatric trials were conducted. As a result, there have been over 100 product labeling changes. The publication status of studies completed for pediatric Exclusivity has not been evaluated.ObjectiveTo quantify the dissemination of results of studies conducted for pediatric Exclusivity into the peer-review literature.DesignCohort study of all trials conducted for pediatric Exclusivity between 1998 and 2004 as determined by MEDLINE and EMBASE searches through 2005, the subsequent labeling changes, and the publication of those studies in peer-reviewed journals. We categorized any labeling changes resulting from the studies as positive or negative for the drug under study. We then evaluated aspects of the studies and product label changes that were associated with subsequent publication in peer-reviewed medical journals.Main Outcome MeasuresPublication of the trial data in peer-reviewed journals.ResultsBetween 1998 and 2004, 253 studies were submitted to the FDA for pediatric Exclusivity: 125 (50%) evaluated efficacy, 51 (20%) were multi-dose pharmacokinetic, 34 (13%) were single-dose pharmacokinetic, and 43 (17%) were safety studies. Labeling changes were positive for 127/253 (50%) of studies; only 113/253 (45%) were published. Efficacy studies and those with a positive labeling change were more likely to be published.ConclusionsThe pediatric Exclusivity program has been successful in encouraging drug studies in children. However, the dissemination of these results in the peer-reviewed literature is limited. Mechanisms to more widely disperse this information through publication warrant further evaluation.
Adan Cabello - One of the best experts on this subject based on the ideXlab platform.
-
multigraph approach to quantum non locality
Journal of Physics A, 2014Co-Authors: Rafael Rabelo, Cristhiano Duarte, Antonio J Lopeztarrida, Marcelo Terra Cunha, Adan CabelloAbstract:Non-contextuality (NC) and Bell inequalities can be expressed as bounds Ω for positive linear combinations S of probabilities of events, . Exclusive events in S can be represented as adjacent vertices of a graph called the Exclusivity graph of S. In the case that events correspond to the outcomes of quantum projective measurements, quantum probabilities are intimately related to the Grotschel–Lovasz–Schrijver theta body of the Exclusivity graph. Then, one can easily compute an upper bound to the maximum quantum violation of any NC or Bell inequality by optimizing S over the theta body and calculating the Lovasz number of the corresponding Exclusivity graph. In some cases, this upper bound is tight and gives the exact maximum quantum violation. However, in general, this is not the case. The reason is that the Exclusivity graph does not distinguish among the different ways Exclusivity can occur in Bell-inequality (and similar) scenarios. An interesting question is whether there is a graph-theoretical concept which accounts for this problem. Here we show that, for any given N-partite Bell inequality, an edge-coloured multigraph composed of N single-colour graphs can be used to encode the relationships of Exclusivity between each partyʼs parts of the events. Then, the maximum quantum violation of the Bell inequality is exactly given by a refinement of the Lovasz number that applies to these edge-coloured multigraphs. We show how to calculate upper bounds for this number using a hierarchy of semi-definite programs and calculate upper bounds for I3, I3322 and the three bipartite Bell inequalities whose Exclusivity graph is a pentagon. The multigraph-theoretical approach introduced here may remove some obstacles in the program of explaining quantum correlations from first principles.This article is part of a special issue of Journal of Physics A: Mathematical and Theoretical devoted to '50 years of Bell's theorem'.
-
Exclusivity principle forbids sets of correlations larger than the quantum set
Physical Review A, 2014Co-Authors: Barbara Amaral, Marcelo Terra Cunha, Adan CabelloAbstract:We show that the Exclusivity (E) principle singles out the set of quantum correlations associated with any Exclusivity graph assuming the set of quantum correlations for the complementary graph. Moreover, we prove that, for self-complementary graphs, the E principle, by itself (i.e., without further assumptions), excludes any set of correlations strictly larger than the quantum set. Finally, we prove that, for vertex-transitive graphs, the E principle singles out the maximum value for the quantum correlations assuming only the quantum maximum for the complementary graph. This opens the door for testing the impossibility of higher-than-quantum correlations in experiments.
-
basic Exclusivity graphs in quantum correlations
Physical Review A, 2013Co-Authors: Adan Cabello, Antonio J Lopeztarrida, Lars Eirik Danielsen, Jose R PortilloAbstract:A fundamental problem is to understand why quantum theory only violates some noncontextuality (NC) inequalities and identify the physical principles that prevent higher-than-quantum violations. We prove that quantum theory only violates those NC inequalities whose Exclusivity graphs contain, as induced subgraphs, odd cycles of length five or more, and/or their complements. In addition, we show that odd cycles are the Exclusivity graphs of a well-known family of NC inequalities and that there is also a family of NC inequalities whose Exclusivity graphs are the complements of odd cycles. We characterize the maximum noncontextual and quantum values of these inequalities, and provide evidence supporting the conjecture that the maximum quantum violation of these inequalities is exactly singled out by the Exclusivity principle.
Daniel K Benjamin - One of the best experts on this subject based on the ideXlab platform.
-
globalization of pediatric research analysis of clinical trials completed for pediatric Exclusivity
Pediatrics, 2010Co-Authors: Sara K Pasquali, P B Smith, Daniel K Benjamin, Danielle S Burstein, Jennifer S LiAbstract:We evaluated the setting of published studies conducted under the US Pediatric Exclusivity Provision, which provides economic incentives to pharmaceutical companies to conduct drug studies with children. METHODS: Published studies containing the main results of trials con- ducted in 1998 -2007 under the Pediatric Exclusivity Provision were included. Data were extracted from each study and described, includ- ing the therapeutic area of drug studied, number of patients enrolled, number of sites, and location where the study was conducted, if re-
-
Is pediatric Exclusivity working
Pediatric Health, 2007Co-Authors: Jennifer S Li, Robert M Califf, P. Brian Smith, Daniel K BenjaminAbstract:Most drugs prescribed for children have not undergone pediatric testing; therefore, the data on dosing, efficacy and safety that are available for adults are not usually available for children. In 1997, Congress authorized the US FDA to grant extensions of marketing rights known as ‘pediatric Exclusivity’ if FDA-requested pediatric trials are conducted. Although the program has been praised for stimulating an unprecedented number of drug studies in children, it has been criticized as an economic ‘windfall’ to prescription-drug manufacturers. The benefits of pediatric Exclusivity are immeasurable towards improving child health, yet there exist many opportunities to improve the pediatric Exclusivity program.
-
economic return of clinical trials performed under the pediatric Exclusivity program
JAMA, 2007Co-Authors: Jennifer S Li, Henry G Grabowski, Eric L Eisenstein, Elizabeth D Reid, Barry Mangum, Kevin A Schulman, John V Goldsmith, Dianne M Murphy, Robert M Califf, Daniel K BenjaminAbstract:ContextIn 1997, Congress authorized the US Food and Drug Administration (FDA) to grant 6-month extensions of marketing rights through the Pediatric Exclusivity Program if industry sponsors complete FDA-requested pediatric trials. The program has been praised for creating incentives for studies in children and has been criticized as a “windfall” to the innovator drug industry. This critique has been a substantial part of congressional debate on the program, which is due to expire in 2007.ObjectiveTo quantify the economic return to industry for completing pediatric Exclusivity trials.Design and SettingA cohort study of programs conducted for pediatric Exclusivity. Nine drugs that were granted pediatric Exclusivity were selected. From the final study reports submitted to the FDA (2002-2004), key elements of the clinical trial design and study operations were obtained, and the cost of performing each study was estimated and converted into estimates of after-tax cash outflows. Three-year market sales were obtained and converted into estimates of after-tax cash inflows based on 6 months of additional market protection. Net economic return (cash inflows minus outflows) and net return-to-costs ratio (net economic return divided by cash outflows) for each product were then calculated.Main Outcome MeasuresNet economic return and net return-to-cost ratio.ResultsThe indications studied reflect a broad representation of the program: asthma, tumors, attention-deficit/hyperactivity disorder, hypertension, depression/generalized anxiety disorder, diabetes mellitus, gastroesophageal reflux, bacterial infection, and bone mineralization. The distribution of net economic return for 6 months of Exclusivity varied substantially among products (net economic return ranged from −$8.9 million to $507.9 million and net return-to-cost ratio ranged from −0.68 to 73.63).ConclusionsThe economic return for pediatric Exclusivity is variable. As an incentive to complete much-needed clinical trials in children, pediatric Exclusivity can generate lucrative returns or produce more modest returns on investment.
-
peer reviewed publication of clinical trials completed for pediatric Exclusivity
JAMA, 2006Co-Authors: Daniel K Benjamin, Dianne M Murphy, Robert M Califf, Debbie Avant, P B Smith, Rosemary Roberts, Lisa Mathis, Jennifer S LiAbstract:ContextMuch of pediatric drug use is off-label because appropriate pediatric studies have not been conducted and the drugs have not been labeled by the US Food and Drug Administration (FDA) for use in children. In 1997, Congress authorized the FDA to grant extensions of marketing rights known as “pediatric Exclusivity” if FDA-requested pediatric trials were conducted. As a result, there have been over 100 product labeling changes. The publication status of studies completed for pediatric Exclusivity has not been evaluated.ObjectiveTo quantify the dissemination of results of studies conducted for pediatric Exclusivity into the peer-review literature.DesignCohort study of all trials conducted for pediatric Exclusivity between 1998 and 2004 as determined by MEDLINE and EMBASE searches through 2005, the subsequent labeling changes, and the publication of those studies in peer-reviewed journals. We categorized any labeling changes resulting from the studies as positive or negative for the drug under study. We then evaluated aspects of the studies and product label changes that were associated with subsequent publication in peer-reviewed medical journals.Main Outcome MeasuresPublication of the trial data in peer-reviewed journals.ResultsBetween 1998 and 2004, 253 studies were submitted to the FDA for pediatric Exclusivity: 125 (50%) evaluated efficacy, 51 (20%) were multi-dose pharmacokinetic, 34 (13%) were single-dose pharmacokinetic, and 43 (17%) were safety studies. Labeling changes were positive for 127/253 (50%) of studies; only 113/253 (45%) were published. Efficacy studies and those with a positive labeling change were more likely to be published.ConclusionsThe pediatric Exclusivity program has been successful in encouraging drug studies in children. However, the dissemination of these results in the peer-reviewed literature is limited. Mechanisms to more widely disperse this information through publication warrant further evaluation.
Chen Jing - One of the best experts on this subject based on the ideXlab platform.
-
Research on the pediatric Exclusivity system
Chinese Journal of New Drugs, 2020Co-Authors: Chen JingAbstract:A sound system of pediatric Exclusivity has been established in U.S.and Euroupean.This paper comprehensively studied the background of pediatric Exclusivity system,the content of the U.S.and European pediatric Exclusivity systems and its active roles and shortcomings.The necessity and the problems of establishment of pediatric Exclusivity system in China were also analyzed.China should view the existing problems of the current pediatric use,learn from the successful experience of foreign countries,and establish the corresponding system.
-
Pediatric Exclusivity system (I)
Chinese Journal of New Drugs, 2020Co-Authors: Chen JingAbstract:The U.S.and the EU have established a sound system of pediatric Exclusivity,which has played a prominent role or will play a role.This paper comprehensively studied the background of pediatric Exclusivity system,the EU and the U.S.pediatric Exclusivity systems,and its active roles and shortcomings.We also analyzed the necessity and the problems in the establishment of pediatric Exclusivity system in China.In China,clinicians should view the existed problems of the current pediatric medication,learn from the successful experience of foreign countries,and establish the corresponding system.