Abstract:
BACKGROUND AND OBJECTIVE:Novel cancer therapies are often approved with evidence from a single pivotal trial alone. There are concerns about the credibility of this evidence. Higher validity may be indicated by five methodological and statistical characteristics of pivotal trial evidence that were described by the U.S. Food and Drug Administration (FDA), which may corroborate the reliance on a single trial alone for approval decisions. STUDY DESIGN:We did a metaepidemiologic evaluation of all single pivotal trials supporting FDA approval of novel drugs and therapeutic biologicals for cancers between 2000 and 2016. For each trial, we determined the presence of these five characteristics, which we operationalized as (1) large and multicenter trial (≥200 patients; more than one center); consistent treatment benefits across (2) multiple patient subgroups (in view of FDA reviewers), (3) multiple endpoints (including overall survival, progression-free survival, response rate, health related quality of life), and (4) multiple treatment comparisons (e.g., multi-arm studies); and (5) "statistically very persuasive" results (P-values <0.00125). RESULTS:Thirty-five of 100 approvals were based on evidence from a single pivotal trial without any further supporting evidence on beneficial effects (20 randomized controlled trials and 15 single-arm trials). The number increased substantially from one approval before 2006 to 23 after 2011. Sixty-six percent (23/35) of the trials were large multicenter trials (median 301 patients and 63 centers). Consistent effects were demonstrated across subgroups in 66% (23/35), across endpoints in 43% (15/35), and across multiple comparisons in 3% (1/35). Very low P-values for the primary endpoint were seen in 34% (12/35). At least one of the corroborating characteristics was present in 94% (33/35) of all approvals, two or more were present in 54% (19/35), and none had all characteristics. CONCLUSIONS:Single pivotal trials typically have some of the corroborating characteristics, but often only one or two. These characteristics need to be better operationalized, defined, and reported and whether single trials with such characteristics provide similar evidence about benefits and harms of novel treatments as multiple trials would do needs to be shown.
journal_name
J Clin Epidemioljournal_title
Journal of clinical epidemiologyauthors
Ladanie A,Speich B,Briel M,Sclafani F,Bucher HC,Agarwal A,Ioannidis JPA,Pereira TV,Kasenda B,Hemkens LGdoi
10.1016/j.jclinepi.2019.05.033subject
Has Abstractpub_date
2019-10-01 00:00:00pages
49-59eissn
0895-4356issn
1878-5921pii
S0895-4356(19)30008-3journal_volume
114pub_type
杂志文章abstract:OBJECTIVE:In the course of performing systematic reviews on the prevalence of low back and neck pain, we required a tool to assess the risk of study bias. Our objectives were to (1) modify an existing checklist and (2) test the final tool for interrater agreement. STUDY DESIGN AND SETTING:The final tool consists of 10...
journal_title:Journal of clinical epidemiology
pub_type: 杂志文章
doi:10.1016/j.jclinepi.2011.11.014
更新日期:2012-09-01 00:00:00
abstract::We conducted a retrospective, non-randomized, cost-minimization study, from the perspective of the Ministry of Health, to compare the cost of managing cancer patients who required narcotic infusions, in hospital and at home. Our medical costs averaged $369.72 per inpatient day and $150.24 per outpatient day (saving $2...
journal_title:Journal of clinical epidemiology
pub_type: 杂志文章
doi:10.1016/0895-4356(91)90043-9
更新日期:1991-01-01 00:00:00
abstract:OBJECTIVES:To examine whether the number of early online accesses to medical research articles predicts citations in the scientific literature over time. STUDY DESIGN AND SETTING:Cohort study of research articles published in the BMJ between January and June 1999. The number of online assesses within 1 week of publica...
journal_title:Journal of clinical epidemiology
pub_type: 杂志文章
doi:10.1016/j.jclinepi.2015.01.024
更新日期:2015-12-01 00:00:00
abstract::We performed analyses to examine the structure, validity, and responsiveness to change of the Marks Asthma Quality of Life Questionnaire (AQLQ), originally validated in Australia in a self-administered format, among 539 U.S. subjects with asthma. Subjects were interviewed twice by telephone over an 18-month period. Ba...
journal_title:Journal of clinical epidemiology
pub_type: 杂志文章
doi:10.1016/s0895-4356(99)00026-8
更新日期:1999-07-01 00:00:00
abstract::This article (Part II) and the preceding article (Part I) report the development of two clinical staging systems for HIV-infected individuals. The objective of the research reported here (Part II) was to construct a clinical staging system to predict survival in patients with AIDS. We analyzed data from VA Cooperative...
journal_title:Journal of clinical epidemiology
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1016/s0895-4356(97)00182-0
更新日期:1997-11-01 00:00:00
abstract:OBJECTIVES:To assess how trial information reported in conference abstracts differs to their subsequent full publication. METHODS:Randomized trials reported at the American Society of Clinical Oncology conference (1992) were identified. CENTRAL and PubMed (December 2002) were searched to identify corresponding full pu...
journal_title:Journal of clinical epidemiology
pub_type: 杂志文章
doi:10.1016/j.jclinepi.2005.09.016
更新日期:2006-07-01 00:00:00
abstract:OBJECTIVES:To develop the first item bank to measure stress resilience (SR) in clinical populations. STUDY DESIGN AND SETTING:Qualitative item development resulted in an initial pool of 131 items covering a broad theoretical SR concept. These items were tested in n = 521 patients at a psychosomatic outpatient clinic. ...
journal_title:Journal of clinical epidemiology
pub_type: 杂志文章
doi:10.1016/j.jclinepi.2018.04.004
更新日期:2018-08-01 00:00:00
abstract:OBJECTIVES:The aim of article was to assess the risk for random errors in outcomes graded as high certainty of evidence (CoE). STUDY DESIGN AND SETTING:We randomly selected 100 Cochrane reviews with dichotomous outcomes rated as high CoE using Grading of Recommendations Assessment, Development, and Evaluation. To dete...
journal_title:Journal of clinical epidemiology
pub_type: 杂志文章
doi:10.1016/j.jclinepi.2018.10.009
更新日期:2019-02-01 00:00:00
abstract:OBJECTIVE:Hospital mortality outcomes for acute myocardial infarction (AMI) patients are a focus of quality improvement programs conducted by government agencies. AMI mortality risk-adjustment models using administrative data typically adjust for baseline differences in mortality risk with a limited set of common and d...
journal_title:Journal of clinical epidemiology
pub_type: 杂志文章
doi:10.1016/j.jclinepi.2006.05.014
更新日期:2007-02-01 00:00:00
abstract::Toxic Oil Syndrome (TOS) is a previously unreported condition which affected more than 20,000 people in Spain in 1981 and whose natural history is unknown. In 1993-94, a stratified random sample of 1400 survivors was drawn to measure their health status through clinical examination and their self-perception of well-be...
journal_title:Journal of clinical epidemiology
pub_type: 杂志文章
doi:10.1016/s0895-4356(98)00062-6
更新日期:1998-10-01 00:00:00
abstract:OBJECTIVES:Elderly patients are inordinately affected by surgical site infections (SSIs). This study derived and internally validated a model that used routinely collected health administrative data to measure the probability of SSI in elderly patients within 30 days of surgery. STUDY DESIGN AND SETTING:All people exc...
journal_title:Journal of clinical epidemiology
pub_type: 杂志文章
doi:10.1016/j.jclinepi.2016.05.010
更新日期:2016-09-01 00:00:00
abstract:OBJECTIVES:To determine the effectiveness of interventions designed to prevent or reduce publication and related biases. STUDY DESIGN AND SETTING:We searched multiple databases and performed manual searches using terms related to publication bias and known interventions against publication bias. We dually reviewed cit...
journal_title:Journal of clinical epidemiology
pub_type: 杂志文章,评审
doi:10.1016/j.jclinepi.2015.01.008
更新日期:2015-07-01 00:00:00
abstract::Prediction models are developed to aid health care providers in estimating the probability or risk that a specific disease or condition is present (diagnostic models) or that a specific event will occur in the future (prognostic models), to inform their decision making. However, the overwhelming evidence shows that th...
journal_title:Journal of clinical epidemiology
pub_type: 杂志文章
doi:10.1016/j.jclinepi.2014.11.010
更新日期:2015-02-01 00:00:00
abstract:OBJECTIVES:Meta-analyses inform clinical practice by summarizing treatment effect estimates based on results from several trials. However, the statistical significance of a meta-analysis (i.e., whether the pooled treatment effect is statistically significant or not) may rely on the outcome of only a few patients from s...
journal_title:Journal of clinical epidemiology
pub_type: 杂志文章
doi:10.1016/j.jclinepi.2019.03.012
更新日期:2019-07-01 00:00:00
abstract:OBJECTIVE:To evaluate a self-report version of the Home Falls and Accidents Screening Tool (HOME FAST-SR). STUDY DESIGN AND SETTING:The HOME FAST-SR was designed using expert review, pretesting and piloting. Agreement of self-reported home hazard ratings and ratings by health professionals was evaluated using the kapp...
journal_title:Journal of clinical epidemiology
pub_type: 杂志文章
doi:10.1016/j.jclinepi.2010.02.013
更新日期:2011-02-01 00:00:00
abstract:OBJECTIVES:The Osteoarthritis Questionnaire (OA-Quest) is a new measure of individual burden of osteoarthritis, composing seven brief (4-11 items; total 42 items), independent scales. This study describes the psychometric evaluation of the OA-Quest. Specifically, temporal stability, convergent and discriminant validity...
journal_title:Journal of clinical epidemiology
pub_type: 杂志文章
doi:10.1016/j.jclinepi.2019.06.001
更新日期:2019-10-01 00:00:00
abstract::A 110-item food frequency questionnaire was tested among 152 community controls of the Kuopio Breast Cancer Study. They completed the questionnaire twice and kept two 7-day diet records at 3-month intervals. The intraclass correlations for nutrients varied from 0.49 (thiamine with supplements) to 0.81 (lactose), and f...
journal_title:Journal of clinical epidemiology
pub_type: 杂志文章
doi:10.1016/0895-4356(95)00551-x
更新日期:1996-04-01 00:00:00
abstract:OBJECTIVES:Calibration is often thought to assess the bias of a clinical prediction rule. In particular, if the rule is based on a linear logistic model, it is often assumed that an overestimation of all coefficients results in a calibration slope less than 1 and an underestimation in a slope larger than 1. STUDY DESI...
journal_title:Journal of clinical epidemiology
pub_type: 杂志文章
doi:10.1016/j.jclinepi.2013.06.003
更新日期:2013-11-01 00:00:00
abstract:OBJECTIVES:The objective of this study was to determine whether disagreements among multiple data sources affect systematic reviews of randomized clinical trials (RCTs). STUDY DESIGN AND SETTING:Eligible RCTs examined gabapentin for neuropathic pain and quetiapine for bipolar depression, reported in public (e.g., jour...
journal_title:Journal of clinical epidemiology
pub_type: 杂志文章,评审
doi:10.1016/j.jclinepi.2017.07.014
更新日期:2017-11-01 00:00:00
abstract:OBJECTIVE:Adding risk factors to a prediction model often increases the area under the receiver operating characteristic curve (AUC) only slightly, particularly when the AUC of the model was already high. We investigated whether a risk factor that minimally improves the AUC may nevertheless improve the predictive abili...
journal_title:Journal of clinical epidemiology
pub_type: 杂志文章
doi:10.1016/j.jclinepi.2016.07.002
更新日期:2016-11-01 00:00:00
abstract::Measuring the effectiveness of cognitive rehabilitation programs poses both conceptual and practical challenges. We compared several standardized outcome measures with goal attainment scaling (GAS) to assess their sensitivity to changes in health status in patients undergoing cognitive rehabilitation. GAS is a measure...
journal_title:Journal of clinical epidemiology
pub_type: 杂志文章
doi:10.1016/s0895-4356(97)00014-0
更新日期:1997-05-01 00:00:00
abstract:OBJECTIVES:The methodology for the critical assessment of medical interventions is well established. Regulatory agencies and institutions adhere, in principle, to the same standards. This consistency, however, is not always the case in practice. STUDY DESIGN AND SETTING:Using the evaluation of the CAPRIE (Clopidogrel ...
journal_title:Journal of clinical epidemiology
pub_type: 杂志文章
doi:10.1016/j.jclinepi.2009.10.009
更新日期:2010-12-01 00:00:00
abstract::Since the demonstration in the 1940s of foreign body induction of sarcomas in rodents, the safety of artificial implants in humans has been a matter of concern. In this study, we assess the risk for the development of breast sarcomas in women with silicone breast implants. Our analysis is based on the National Cancer ...
journal_title:Journal of clinical epidemiology
pub_type: 杂志文章
doi:10.1016/0895-4356(94)00210-h
更新日期:1995-04-01 00:00:00
abstract::We have evaluated the reproducibility and relative validity of a semiquantitative food frequency questionnaire (FFQ) used in a prospective study of risk factors for cervical neoplasia. The questionnaire is a modified version of one developed and evaluated in a middle-aged Danish population. In the present study, 122 w...
journal_title:Journal of clinical epidemiology
pub_type: 杂志文章
doi:10.1016/s0895-4356(96)00379-4
更新日期:1997-03-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:A large number of trials remain difficult to locate or unpublished for systematic reviews. The objective of this article was to determine the usefulness of making e-mail contact with authors of clinical trials and literature reviews found in MEDLINE to identify unpublished or difficult to locat...
journal_title:Journal of clinical epidemiology
pub_type: 杂志文章
doi:10.1016/j.jclinepi.2005.11.022
更新日期:2006-07-01 00:00:00
abstract::We studied the relationship between age at natural menopause and total mortality as well as mortality from ischemic heart disease in a cohort of 6182 California Seventh-Day Adventist women who reported a natural menopause. During follow-up from 1976 through 1988, there were 1831 deaths. A total of 308 deaths due to is...
journal_title:Journal of clinical epidemiology
pub_type: 杂志文章
doi:10.1016/s0895-4356(98)00170-x
更新日期:1999-04-01 00:00:00
abstract:OBJECTIVES:Our study aimed to systematically assess and report the methodological quality used in epidemiological systematic reviews (SRs) and meta-analysis (MA) of pathogen genotypes/genogroups. STUDY DESIGN AND SETTING:Nine electronic databases and manual search of reference lists were used to identify relevant stud...
journal_title:Journal of clinical epidemiology
pub_type: 杂志文章,评审
doi:10.1016/j.jclinepi.2019.11.009
更新日期:2020-03-01 00:00:00
abstract:OBJECTIVES:The aim of the present study was to obtain a cross-cultural adaptation and evaluation of a Simplified Chinese (SC) version of the Tampa Scale for Kinesiophobia (TSK) for use in patients with low back pain (LBP). STUDY DESIGN AND SETTING:The TSK was translated and adapted cross-culturally following internati...
journal_title:Journal of clinical epidemiology
pub_type: 杂志文章
doi:10.1016/j.jclinepi.2015.07.003
更新日期:2015-10-01 00:00:00
abstract::This study aims to estimate the prevalence of Helicobacter pylori in Glasgow, and to provide a systematic analysis of factors associated with this prevalence. The data used are from a random population sample of 793 men and 838 women aged 25-64 years conducted in 1995. The prevalence is estimated to be 66% (95% confid...
journal_title:Journal of clinical epidemiology
pub_type: 杂志文章
doi:10.1016/s0895-4356(99)00171-7
更新日期:2000-02-01 00:00:00
abstract:BACKGROUND:The impact of disease on population health is most commonly estimated by the population attributable fraction (PAF), or less commonly by the excess risk, an alternative measure that estimates the absolute risk of disease in the population that can be ascribed to the exposure. Using chronic airflow obstructio...
journal_title:Journal of clinical epidemiology
pub_type: 杂志文章
doi:10.1016/j.jclinepi.2017.10.020
更新日期:2018-01-01 00:00:00