Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 35
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
2.
Lancet Infect Dis ; 20(7): e159-e164, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32502431

RESUMO

Antimicrobial resistance is of growing concern. To encourage development of new treatments, some commentators have suggested regulators exercise increased flexibility on the clinical evidence required for approval. We examined all 1065 new drugs and biologics approved by the US Food and Drug Administration between 1984 and 2018 and recorded each drug's use of the Orphan Drug Act, fast-track, priority review, accelerated approval, and breakthrough therapy programmes, as well as dates of investigational new drug application, new drug application, and new drug approval, which were used to calculate clinical development and review times. There were 178 (17%) antimicrobial products, which were more likely than non-antimicrobial products to benefit from priority review (103 [58%] of 178 vs 402 [45%] of 887, p=0·0023), fast-track designation (58 [37%] of 157 vs 151 [19%] of 814], p<0·001), and accelerated approval (23 [18%] of 129 vs 67 [9%] of 711, p=0·0046), and less likely to have Orphan Drug Act designation (25 [14%] of 178 vs 267 [30%] of 887, p<0·0001). Median time from investigational new drug application to approval was shorter for antimicrobial than for non-antimicrobial drugs (5·9 years [IQR 4·6-7·3] vs 7·6 years [IQR 5·7-10·2], p<0·001). Except for Orphan Drug Act status, expedited clinical testing and review programmes have been used at least as frequently for antimicrobial products as for non-antimicrobial drugs. No evidence supported claims that antimicrobial progress through the regulatory approval process in the USA is more time-consuming than non-antimicrobial development.

3.
Healthc Policy ; 15(4): 35-40, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32538347

RESUMO

Lexchin has criticized Health Canada's recently published draft guidance on accelerated drug review, expressing concern over agency conflicts of interest and observing that priority review and notice of compliance with conditions correlate poorly with therapeutic benefit. Although agency operations may be imperfect, perhaps the most important finding of Lexchin's research is that only 11% of newly approved drugs provide meaningful benefit over standard treatments. To improve the expedited review process in light of these findings, we suggest eliminating user fees and fully funding the review process with public monies, reserving the use of expedited approval pathways for when preliminary measures of benefit are so large that traditional approval thresholds can be met earlier in the clinical trial process, improving labelling to quantitatively communicate drug benefits and risks, and avoiding the use of titles such as "priority" review, which could imply a magnitude of clinical superiority that has not been established.

4.
JAMA ; 323(2): 164-176, 2020 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-31935033

RESUMO

Importance: US law requires testing of new drugs before approval to ensure that they provide a well-defined benefit that is commensurate with their risks. A major challenge for the US Food and Drug Administration (FDA) is to achieve an appropriate balance between rigorous testing and the need for timely approval of drugs that have benefits that outweigh their risks. Objective: To describe the evolution of laws and standards affecting drug testing, the use of new approval programs and standards, expansions of the role and authority of the FDA, and changes in the number of drugs approved from the 1980s to 2018. Evidence: Sources of evidence included principal federal laws and FDA regulations (1962-2018) and FDA databases of approved new drugs (1984-2018), generic drugs (1970-2018), biologics (1984-2018), and vaccines (1998-2018); special development and approval programs (Orphan drug [1984-2018], Fast-Track [1988-2018], Priority Review and its predecessors [1984-2018], Accelerated Approval [1992-2018], and Breakthrough Therapy [2012-2018]); expanded access (2010-2017) and Risk Evaluation and Mitigation Strategies (2008-2018); and user fees paid to the FDA by industry (1993-2018). Findings: From 1983 to 2018, legislation and regulatory initiatives have substantially changed drug approval at the FDA. The mean annual number of new drug approvals, including biologics, was 34 from 1990-1999, 25 from 2000-2009, and 41 from 2010-2018. New biologic product approvals increased from a median of 2.5 from 1990-1999, to 5 from 2000-2013, to 12 from 2014-2018. The median annual number of generic drugs approved was 136 from 1970 to the enactment of the Hatch-Waxman Act in 1984; 284 from 1985 to the enactment of the Generic Drug User Fee Act in 2012; and 588 from 2013-2018. Prescription drug user fee funding expanded from new drugs and biologics in 1992 to generic and biosimilar drugs in 2012. The amount of Prescription Drug User Fee Act fees collected from industry increased from an annual mean of $66 million in 1993-1997 to $820 million in 2013-2017, and in 2018, user fees accounted for approximately 80% of the salaries of review personnel responsible for the approval of new drugs. The proportion of drugs approved with an Orphan Drug Act designation increased from 18% (55/304) in 1984-1995, to 22% (82/379) in 1996-2007, to 41% (154/380) in 2008-2018. Use of Accelerated Approval, Fast-Track, and Priority Review for new drugs has increased over time, with 81% (48/59) of new drugs benefiting from at least 1 such expedited program in 2018. The proportion of new approvals supported by at least 2 pivotal trials decreased from 80.6% in 1995-1997 to 52.8% in 2015-2017, based on 124 and 106 approvals, respectively, while the median number of patients studied did not change significantly (774 vs 816). FDA drug review times declined from more than 3 years in 1983 to less than 1 year in 2017, but total time from the authorization of clinical testing to approval has remained at approximately 8 years over that period. Conclusions and Relevance: Over the last 4 decades, the approval and regulation processes for pharmaceutical agents have evolved and increased in complexity as special programs have been added and as the use of surrogate measures has been encouraged. The FDA funding needed to implement and manage these programs has been addressed by expanding industry-paid user fees. The FDA has increasingly accepted less data and more surrogate measures, and has shortened its review times.


Assuntos
Aprovação de Drogas/legislação & jurisprudência , Regulamentação Governamental , Legislação de Medicamentos/tendências , Preparações Farmacêuticas/normas , United States Food and Drug Administration , Aprovação de Drogas/economia , Aprovação de Drogas/estatística & dados numéricos , História do Século XX , Legislação de Medicamentos/história , Estados Unidos
5.
J Glob Oncol ; 5: 1-17, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31860377

RESUMO

PURPOSE: The population of Chile has aged, and in 2017, cancer became the leading cause of death. Since 2005, a national health program has expanded coverage of drugs for 13 types of cancer and related palliative care. We describe the trends in public and private oncology drug expenditures in Chile and consider how increasing expenditures might be addressed. METHODS: We analyzed total quarterly drug expenditures for 131 oncology drugs from quarter (Q)3 2012 until Q1 2017, including public and private insurance payments and patient out-of-pocket spending. The data were analyzed by drug-mix, sources of funding, growth, and intellectual property status. The Laspeyres Price Index was used to analyze expenditure growth. RESULTS: We found 131 oncology drugs associated with 87,129 observations. Spending on drugs rose 120% from the first period, spanning from the first 3 quarters (Q3, Q4, Q1 2012-2013) to the last period (Q3, Q4, Q1 2016-2017), corresponding to an annualized rate of 19.2% and totaling US$398 million (in 2017 dollars). The public sector accounted for 84.2% of spending, which included 50 drugs in the official treatment protocols, whereas private insurance accounted for 7.3% in on-protocol drugs. The remaining 8.5% was paid out of pocket. In the public sector, more than 90% of growth resulted from increased use. Seven drugs, including 3 with nonexpired patents, accounted for 50% of total expenditures. CONCLUSION: Increased use and access enabled by expanded public expenditures drove most of the growth in oncology drug expenditures. However, the rate of public expenditure growth may be fiscally unsustainable. Policies are urgently needed to promote the use of generic drugs, the appropriate mix of on-protocol versus off-protocol drugs, and the curbing of off-label prescribing.

6.
Nat Commun ; 10(1): 3416, 2019 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-31366924

RESUMO

In the face of rising rates of antibacterial resistance, many responses are being pursued in parallel, including 'non-traditional' antibacterial agents (agents that are not small-molecule drugs and/or do not act by directly targeting bacterial components necessary for bacterial growth). In this Perspective, we argue that the distinction between traditional and non-traditional agents has only limited relevance for regulatory purposes. Rather, most agents in both categories can and should be developed using standard measures of clinical efficacy demonstrated with non-inferiority or superiority trial designs according to existing regulatory frameworks. There may, however, be products with non-traditional goals focused on population-level benefits that would benefit from extension of current paradigms. Discussion of such potential paradigms should be undertaken by the development community.


Assuntos
Antibacterianos/síntese química , Desenho de Fármacos , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Humanos
7.
8.
Drug Discov Today ; 24(4): 949-954, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30711576

RESUMO

In 2017, the US Food and Drug Administration (FDA) approved voretigene neparvovec-rzyl (Luxturna), a gene therapy used to treat a rare form of inherited blindness. Widely described by the media as a curative treatment that 'restores vision', it was priced at US$850000. Although voretigene neparvovec-rzyl represents a substantial therapeutic advance, most reports have failed to adequately describe study outcomes as documented by FDA reviewers. These documents reveal that the drug is not expected to restore normal vision, that only about half of treated patients met the FDA's threshold for minimally meaningful improvement, that improvements might not persist long-term, that the most common measure of visual function was rejected as a primary endpoint after yielding mixed results, and that two patients experienced permanent vision loss. Over US$100 million of additional publicly-funded costs are not evident from the US$850000 figure.


Assuntos
Terapia Genética/economia , Distrofias Retinianas/economia , Transtornos da Visão/economia , Custos e Análise de Custo , Humanos , Distrofias Retinianas/terapia , Estados Unidos , United States Food and Drug Administration , Transtornos da Visão/terapia , cis-trans-Isomerases/deficiência , cis-trans-Isomerases/genética
10.
Appl Health Econ Health Policy ; 17(1): 47-54, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30141133

RESUMO

BACKGROUND: Most new brand-name drugs are protected by patents from generic competition, but these patents are occasionally granted in error. Invalidating such patents has traditionally been accomplished via court litigation by generic manufacturers, which is expensive and time consuming. In 2011, Congress created an administrative alternative to court litigation of patents, called inter partes review, intended to be much faster and less expensive. OBJECTIVE: To evaluate the use of inter partes review to challenge pharmaceutical patents, including the number of challenges, the number of associated drug products, and the extent to which challengers have been successful. METHODS: We obtained data pertaining to inter partes review proceedings, including identity of patent challenger, duration of proceedings, and outcome, from September 16, 2012 through April 24, 2017 from UnifiedPatents.com, and combined it with information about drug products and their associated patents, including patent type, contained in the US Food and Drug Administration's Orange Book. RESULTS: Generic drug manufacturers have embraced the new inter partes review process, succeeding in overturning all challenged claims in 43% of the patents they have targeted since 2011, and some challenged claims in an additional 8%. Inter partes review for drug patents has consistently been completed within 12 months, as required by statute. Successful challenges have been brought most frequently against drug patents covering new formulations or methods of use, rather than drug patents covering active ingredients. CONCLUSION: In the pharmaceutical market, the inter partes review process can meaningfully contribute to ensuring that invalid patents do not block timely availability of generic drugs.


Assuntos
Indústria Farmacêutica/legislação & jurisprudência , Medicamentos Genéricos , Patentes como Assunto/legislação & jurisprudência , Humanos , Legislação de Medicamentos , Estados Unidos
11.
Clin Pharmacol Ther ; 105(1): 92-100, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30415479

RESUMO

In 2010, Congress created an abbreviated application pathway for biosimilars, versions of approved biologics made by different manufacturers. However, as of November 1, 2018, the US Food and Drug Administration (FDA) had approved only 13 biosimilars under this pathway, of which just 6 were available for patients to use. We review the history of US regulation of biologics and identify manufacturing, regulatory, and marketing issues that have limited biosimilar market entry and uptake, concluding with recommendations for reform.


Assuntos
Medicamentos Biossimilares/uso terapêutico , Aprovação de Drogas/métodos , Indústria Farmacêutica/métodos , United States Food and Drug Administration , Medicamentos Biossimilares/química , Indústria Farmacêutica/tendências , Humanos , Medicamentos sob Prescrição/química , Medicamentos sob Prescrição/uso terapêutico , Estados Unidos , United States Food and Drug Administration/tendências
12.
Drug Discov Today ; 24(1): 20-25, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30055271

RESUMO

Patents temporarily protect brand-name drugs from generic competition, but some of the 20-year patent term is used up before marketing approval. To compensate for patent life lost to clinical testing and regulatory review, current law provides patent term restoration (PTR) of up to 5 years. Examining 170 top-selling drugs with a first generic equivalent approved between 2000 and 2012, we found that 49% (83 drugs) received a PTR extension (median extension: 2.75 years) yielding a median total exclusivity period of 13.75 years, compared with 10.0 years for the 87 nonextended drugs. Because PTR substantially prolongs market exclusivity periods, policies that extend non-patent exclusivity periods (which generally run concurrently with patent exclusivity) for less than the extended patent terms of drugs will have little practical impact.


Assuntos
Patentes como Assunto , Preparações Farmacêuticas , Estados Unidos
13.
Value Health ; 21(12): 1382-1389, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30502781

RESUMO

OBJECTIVES: To develop and test a method for approximating generic entry of top-selling drugs. METHODS: The procedure involved 1) identifying products' key patents as those with a patent term restoration extension (whenever relevant) or otherwise as the first expiring patent listed in the US Food and Drug Administration's patent register, 2) determining whether the key patent had been extended through an associated pediatric extension, 3) identifying other regulatory exclusivities associated with the drug, and 4) categorizing key patents as active ingredient (or extended) patents versus secondary patents. The accuracy and precision of the procedure's predictions were then tested against a database containing the timing of generic entry for 170 top-selling drugs that lost market exclusivity between 2000 and 2012, on the basis of Medicaid data. RESULTS: Overall, the procedure predicted a median market exclusivity period of 12.5 years (interquartile range [IQR] 7.25-14.5) compared with the median actual period of 12.5 years (IQR 8.5-14.75 years). Among the 131 drugs (77%) with active ingredient patents, the median predicted market exclusivity was 12.25 years (IQR 7.5-14.5) compared with a median actual period of 13.0 years (IQR 10.0-14.75). Among the 38 (22%) drugs protected only by secondary patents, the median predicted market exclusivity was 16.0 years (IQR 6.75-19.5), but the median actual market exclusivity was only 8.25 years (IQR 6.25-13.5). CONCLUSIONS: The procedure approximated median actual exclusivity with reasonable accuracy and precision for drugs with active ingredient patents, but substantially overestimated exclusivity for drugs with only secondary patents.


Assuntos
Indústria Farmacêutica/economia , Controle de Medicamentos e Entorpecentes , Medicamentos Genéricos/economia , Competição Econômica , Modelos Teóricos , Patentes como Assunto , Bases de Dados Factuais , Medicamentos Genéricos/química , Humanos , Medicaid , Preparações Farmacêuticas/química , Preparações Farmacêuticas/economia , Sistema de Registros , Reprodutibilidade dos Testes , Estados Unidos , United States Food and Drug Administration
14.
Health Aff (Millwood) ; 37(5): 724-731, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29733717

RESUMO

Precision medicines can benefit patients by increasing the probability of a successful treatment response in selected patient populations. The potential for more immediate signals of efficacy during clinical trials suggests such medicines will reach the market more rapidly than traditional drugs will. Using data from the Food and Drug Administration (FDA), we examined the regulatory review and pivotal trial characteristics of precision medicines. We found that in the period January 2013-June 2017, precision medicines were developed and reviewed almost two years faster than nonprecision medicines. In addition, approximately 48 percent of the precision medicines in our study qualified for the FDA's breakthrough therapy designation. Precision medicines were also approved based on fewer pivotal trials with fewer patients, and the trials were less likely to be randomized, blinded, or controlled with either an active or placebo comparator.


Assuntos
Produtos Biológicos/administração & dosagem , Aprovação de Drogas , Medicina de Precisão/estatística & dados numéricos , United States Food and Drug Administration , Ensaios Clínicos como Assunto , Estudos Transversais , Bases de Dados Factuais , Feminino , Humanos , Masculino , Terapia de Alvo Molecular , Preparações Farmacêuticas , Medicina de Precisão/métodos , Estatísticas não Paramétricas , Estados Unidos
15.
J Clin Oncol ; 36(18): 1805-1812, 2018 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-29688832

RESUMO

Purpose The breakthrough therapy program was established in 2012 to expedite the development and review of new medicines. We evaluated the times to approval, efficacy, and safety of breakthrough-designated versus non-breakthrough-designated cancer drugs approved by the US Food and Drug Administration (FDA). Methods We studied all new cancer drugs approved by the FDA between January 2012 and December 2017. Regulatory and therapeutic characteristics (time to FDA approval, pivotal trial efficacy end point, novelty of mechanism of action) were compared between breakthrough-designated and non-breakthrough-designated cancer drugs. Random-effects meta-regression was used to assess the association between breakthrough therapy designation and hazard ratios for progression-free survival (PFS), response rates (RRs) for solid tumors, serious adverse events, and deaths not attributed to disease progression. Results Between 2012 and 2017, the FDA approved 58 new cancer drugs, 25 (43%) of which received breakthrough therapy designation. The median time to first FDA approval was 5.2 years for breakthrough-designated drugs versus 7.1 years for non-breakthrough-designated drugs (difference, 1.9 years; P = .01). There were no statistically significant differences between breakthrough-designated and non-breakthrough-designated drugs in median PFS gains (8.6 v 4.0 months; P = .11), hazard ratios for PFS (0.43 v 0.51; P = .28), or RRs for solid tumors (37% v 39%; P = .74). Breakthrough therapy-designated drugs were not more likely to act via a novel mechanism of action (36% v 39%; P = 1.00). Rates of deaths (6% v 4%; P = .99) and serious adverse events (38% v 36%; P = 0.93) were also similar in breakthrough-designated and non-breakthrough-designated drugs. Conclusion Breakthrough-designated cancer drugs were associated with faster times to approval, but there was no evidence that these drugs provide improvements in safety or novelty; nor was there a statistically significant efficacy advantage when compared with non-breakthrough-designated drugs.


Assuntos
Antineoplásicos/administração & dosagem , Aprovação de Drogas/métodos , Neoplasias/tratamento farmacológico , Antineoplásicos/efeitos adversos , Estudos de Coortes , Drogas em Investigação/administração & dosagem , Drogas em Investigação/efeitos adversos , Humanos , Intervalo Livre de Progressão , Análise de Regressão , Estados Unidos , United States Food and Drug Administration
20.
Cornell J Law Public Policy ; 27(1): 189-206, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29239595

RESUMO

Each year in the United States, surgeons perform approximately 64 million surgical procedures, ranging from tooth extraction to open heart surgery. Yet, notwithstanding the frequency of surgical procedures and their often critical importance to patient health, no state or federal agency either approves the use of new surgical procedures or directly regulates existing procedures. The absence of surgical procedure regulation differs from the regulation of new pharmaceutical products, which can be introduced into interstate commerce only after the Food and Drug Administration (FDA) has reviewed "adequate and well-controlled [clinical] investigations" and concluded the data from those studies sufficiently establish the drug's safety and efficacy. Surgical procedures, by contrast, are more often conveyed from professor to student, the result being that surgical approaches may vary considerably from one geographic region to another. Whether different techniques produce different outcomes is not always clear, in part because the absence of regulation means that evidence often has not been systematically generated or may be in a form not suitable for comparison. Commentators have noted the differing treatment that persists between surgery and pharmaceuticals and have offered a number of justifications. For example, they have suggested that the surgical profession should self-regulate, that excessive regulation could deter surgeries of unproven benefit even when the surgery may be in the best interest of the patient, and that surgical trials could disrupt the doctor-patient relationship, such as by emphasizing uncertainty in a context where patient trust is important. In the context of innovative (as opposed to established) surgical procedures, controlled trials might be disfavored due to concern that desperate patients might unwisely submit themselves to risky experimental treatments undertaken by overzealous researchers. When commentators advocate for increased surgical regulation, they generally limit their calls for reform to innovative surgical procedures. The absence of direct regulation, however, has implications for the quality of evidence available to support an optimal choice from among all of the alternatives in the surgeon's armamentarium, whether innovative or standard, and whether surgical or non-surgical. This Article first examines the current framework of indirect regulation surrounding surgical procedures and then offers potential explanations as to why surgical procedures themselves are not already subject to direct federal regulation. Finally, it considers possible contributions of increased surgical regulation, including the identification of evidence gaps, the generation or collection of evidence to fill those gaps, and the impact on surgeon decision-making and patient consent.


Assuntos
Cirurgia Geral/normas , Regulamentação Governamental , Procedimentos Cirúrgicos Operatórios/legislação & jurisprudência , Credenciamento , Humanos , Privilégios do Corpo Clínico , Ensaios Clínicos Controlados Aleatórios como Assunto , Procedimentos Cirúrgicos Operatórios/normas , Terminologia como Assunto , Estados Unidos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA