Abstract:
:Objective To characterize the prospective controlled clinical studies for all novel drugs that were initially approved by the Food and Drug Administration on the basis of limited evidence.Design Systematic review.Data sources Drugs@FDA database and PubMed.Study inclusion All prospective controlled clinical studies published after approval for all novel drugs initially approved by the FDA between 2005 and 2012 on the basis of a single pivotal trial, pivotal trials that used surrogate markers of disease as primary endpoints, or both. Results Between 2005 and 2012 the FDA approved 117 novel drugs for 123 indications on the basis of a single pivotal trial, pivotal trials that used surrogate markers of disease, or both (single surrogate trials). We identified 758 published controlled studies over a median of 5.5 years (interquartile range 3.4-8.2) after approval, most of which (554 of 758; 73.1%) were studies for indications approved on the basis of surrogate markers of disease. Most postapproval studies used active comparators-67 of 77 (87.0%) indications approved on the basis of single pivotal trials, 365 of 554 (65.9%) approvals based on surrogate marker trials, and 100 of 127 (78.7%) approvals based on single surrogate trials-and examined surrogate markers of efficacy as primary endpoints-51 of 77 (66.2%), 512 of 554 (92.4%), and 110 of 127 (86.6%), respectively. Overall, no postapproval studies were identified for 43 of the 123 (35.0%) approved indications. The median total number of postapproval studies identified was 1 (interquartile range 0-2) for indications approved on the basis of a single pivotal trial, 3 (1-8) for indications approved on the basis of pivotal trials that used surrogate markers of disease as primary endpoints, and 1 (0-2) for single surrogate trial approvals, and the median aggregate number of patients enrolled in postapproval studies was 90 (0-509), 533 (122-3633), and 38 (0-666), respectively. The proportion of approved indications with one or more randomized, controlled, double blind study using a clinical outcome for the primary endpoint that was published after approval and showed superior efficacy was 18.2% (6 of 33), 2.0% (1 of 49), and 4.9% (2 of 41), respectively.Conclusions The quantity and quality of postapproval clinical evidence varied substantially for novel drugs first approved by the FDA on the basis of limited evidence, with few controlled studies published after approval that confirmed efficacy using clinical outcomes for the original FDA approved indication.
journal_name
BMJjournal_title
BMJ (Clinical research ed.)authors
Pease AM,Krumholz HM,Downing NS,Aminawung JA,Shah ND,Ross JSdoi
10.1136/bmj.j1680subject
Has Abstractpub_date
2017-05-03 00:00:00pages
j1680eissn
0959-8138issn
1756-1833journal_volume
357pub_type
杂志文章,评审abstract::An increase in the incidence of cardiovascular disease has generally been observed in postmenopausal women, but there have been few studies of the association between menopausal state and atherosclerosis. In this study 294 premenopausal and 319 postmenopausal women aged 45 to 55 were examined radiographically for calc...
journal_title:BMJ (Clinical research ed.)
pub_type: 杂志文章
doi:10.1136/bmj.298.6674.642
更新日期:1989-03-11 00:00:00
abstract:OBJECTIVE:To investigate whether an important football match increases stress to such an extent that it triggers acute myocardial infarction and stroke. DESIGN:Longitudinal study of mortality around 22 June 1996 (the day the Dutch football team was eliminated from the European football championship). Mortality on 22 J...
journal_title:BMJ (Clinical research ed.)
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abstract:OBJECTIVE:To compare the prevalence of antibody to and proviral DNA of the retrovirus HTLV-I in relatives of 11 British patients with tropical spastic paraparesis who had migrated from Jamaica before they developed symptoms, and to examine factors possibly related to transmission of HTLV-I. DESIGN:Migrant, family stud...
journal_title:BMJ (Clinical research ed.)
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doi:10.1136/bmj.300.6720.300
更新日期:1990-02-03 00:00:00
abstract:OBJECTIVE:To evaluate the cost utility of interferon beta-1b in secondary progressive multiple sclerosis. DESIGN:Population based cost utility model (healthcare perspective). Data on use of health services were obtained from case records and routine morbidity data and utility values from a EuroQol survey. Local and pu...
journal_title:BMJ (Clinical research ed.)
pub_type: 杂志文章
doi:10.1136/bmj.319.7224.1529
更新日期:1999-12-11 00:00:00
abstract:OBJECTIVE:To assess the effectiveness of an antenatal service using community based breastfeeding peer support workers on initiation of breast feeding. DESIGN:Cluster randomised controlled trial. SETTING:Community antenatal clinics in one primary care trust in a multiethnic, deprived population. PARTICIPANTS:66 ante...
journal_title:BMJ (Clinical research ed.)
pub_type: 杂志文章,多中心研究,随机对照试验
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更新日期:2009-01-30 00:00:00
abstract:OBJECTIVE:To assess the impact of teaching general practitioners to carry out structured assessments of their long term mentally ill patients. DESIGN:Randomised controlled trial. SETTING:Sixteen group general practices in South Thames (west) region. SUBJECTS:440 adults disabled by long term mental illness. INTERVEN...
journal_title:BMJ (Clinical research ed.)
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1136/bmj.311.6997.93
更新日期:1995-07-08 00:00:00
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journal_title:BMJ (Clinical research ed.)
pub_type: 杂志文章,meta分析,评审
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更新日期:2010-08-18 00:00:00
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journal_title:BMJ (Clinical research ed.)
pub_type: 杂志文章
doi:10.1136/bmj.323.7306.199
更新日期:2001-07-28 00:00:00
abstract:OBJECTIVES:To elucidate current trends and geographical patterns in the sex ratio at birth and in the population aged under 20 in China and to determine the roles played by sex selective abortion and the one child policy. DESIGN:Analysis of household based cross sectional population survey done in November 2005. SETT...
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pub_type: 杂志文章,多中心研究
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更新日期:2009-04-09 00:00:00
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pub_type: 杂志文章
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更新日期:1990-06-16 00:00:00
abstract:OBJECTIVE:To assess the effect of weight loss induced by a very low energy diet on moderate and severe obstructive sleep apnoea in obese men. Design Single centre, two arm, parallel, randomised, controlled, open label trial. Blocked randomisation procedure used for treatment allocation. Setting Outpatient obesity clini...
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pub_type: 杂志文章,随机对照试验
doi:10.1136/bmj.b4609
更新日期:2009-12-03 00:00:00
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journal_title:BMJ (Clinical research ed.)
pub_type: 杂志文章,评审
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更新日期:1997-01-18 00:00:00
abstract:OBJECTIVE:To examine whether the decline in child injury death rates between 1981 and 1991 varied by social class. DESIGN:Comparison of class specific child injury death rates for 1979, 1980, 1982, and 1983, with those for the four years 1989-92. SETTING:England and Wales. SUBJECTS:Children aged 0-15 years. MAIN OU...
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pub_type: 杂志文章
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更新日期:1996-09-28 00:00:00
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journal_title:BMJ (Clinical research ed.)
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1994-01-29 00:00:00
abstract:OBJECTIVES:To investigate current practice of screening children from abroad for infections after coming to the United Kingdom, and to make recommendations for future practice. DESIGN:A review of literature and a questionnaire sent to all health authorities and boards in the United Kingdom. SETTING:All health authori...
journal_title:BMJ (Clinical research ed.)
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更新日期:1990-10-06 00:00:00
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journal_title:BMJ (Clinical research ed.)
pub_type: 杂志文章
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journal_title:BMJ (Clinical research ed.)
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更新日期:2014-12-16 00:00:00
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pub_type: 杂志文章
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更新日期:1996-01-27 00:00:00
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pub_type: 杂志文章,meta分析,评审
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更新日期:2012-03-15 00:00:00
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pub_type: 杂志文章,多中心研究,随机对照试验
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更新日期:2010-03-09 00:00:00
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journal_title:BMJ (Clinical research ed.)
pub_type: 杂志文章,meta分析,评审
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更新日期:2002-10-26 00:00:00
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pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:1989-07-01 00:00:00
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更新日期:2012-12-17 00:00:00
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journal_title:BMJ (Clinical research ed.)
pub_type: 杂志文章,meta分析,评审
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更新日期:2012-08-07 00:00:00
abstract::Cancer control encompasses the whole spectrum from prevention and early diagnosis to treatment and palliation. The key to the future of cancer control will be to establish multidisciplinary approaches to each type of cancer across this spectrum. For primary prevention this requires some understanding of the causes of ...
journal_title:BMJ (Clinical research ed.)
pub_type: 杂志文章,评审
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更新日期:1994-08-13 00:00:00
abstract:OBJECTIVE:To assess the safety and effectiveness of eflornithine as first line treatment for human African trypanosomiasis. DESIGN:Cohort study. SETTING:Control programme in Ibba, southern Sudan. PARTICIPANTS:1055 adults and children newly diagnosed with second stage disease in a 16 month period. MAIN OUTCOME MEASU...
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更新日期:2008-03-29 00:00:00