The many weak instruments problem and Mendelian randomization.

Abstract:

:Instrumental variable estimates of causal effects can be biased when using many instruments that are only weakly associated with the exposure. We describe several techniques to reduce this bias and estimate corrected standard errors. We present our findings using a simulation study and an empirical application. For the latter, we estimate the effect of height on lung function, using genetic variants as instruments for height. Our simulation study demonstrates that, using many weak individual variants, two-stage least squares (2SLS) is biased, whereas the limited information maximum likelihood (LIML) and the continuously updating estimator (CUE) are unbiased and have accurate rejection frequencies when standard errors are corrected for the presence of many weak instruments. Our illustrative empirical example uses data on 3631 children from England. We used 180 genetic variants as instruments and compared conventional ordinary least squares estimates with results for the 2SLS, LIML, and CUE instrumental variable estimators using the individual height variants. We further compare these with instrumental variable estimates using an unweighted or weighted allele score as single instruments. In conclusion, the allele scores and CUE gave consistent estimates of the causal effect. In our empirical example, estimates using the allele score were more efficient. CUE with corrected standard errors, however, provides a useful additional statistical tool in applications with many weak instruments. The CUE may be preferred over an allele score if the population weights for the allele score are unknown or when the causal effects of multiple risk factors are estimated jointly.

journal_name

Stat Med

journal_title

Statistics in medicine

authors

Davies NM,von Hinke Kessler Scholder S,Farbmacher H,Burgess S,Windmeijer F,Smith GD

doi

10.1002/sim.6358

subject

Has Abstract

pub_date

2015-02-10 00:00:00

pages

454-68

issue

3

eissn

0277-6715

issn

1097-0258

journal_volume

34

pub_type

杂志文章
  • Statistical estimation of parameters in a disease transmission model: analysis of a Cryptosporidium outbreak.

    abstract::Population dynamic models, commonly used tools in the study of epidemics and other complex population processes, are implicit non-linear mathematical equations. Inference based on such models can be difficult due to the problems associated with high dimensional parameters that may be non-identified and complex likelih...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.1258

    authors: Brookhart MA,Hubbard AE,van der Laan MJ,Colford JM Jr,Eisenberg JN

    更新日期:2002-12-15 00:00:00

  • A semi-parametric Bayesian approach to average bioequivalence.

    abstract::Bioequivalence assessment is an issue of great interest. Development of statistical methods for assessing bioequivalence is an important area of research for statisticians. Bioequivalence is usually determined based on the normal distribution. We relax this assumption and develop a semi-parametric mixed model for bioe...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.2620

    authors: Ghosh P,Rosner GL

    更新日期:2007-03-15 00:00:00

  • Quantifying the bias due to observed individual confounders in causal treatment effect estimates.

    abstract::It is often of interest to use observational data to estimate the causal effect of a target exposure or treatment on an outcome. When estimating the treatment effect, it is essential to appropriately adjust for selection bias due to observed confounders using, for example, propensity score weighting. Selection bias du...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.8549

    authors: Parast L,Griffin BA

    更新日期:2020-08-15 00:00:00

  • Utility-based optimization of phase II/III programs.

    abstract::Phase II and phase III trials play a crucial role in drug development programs. They are costly and time consuming and, because of high failure rates in late development stages, at the same time risky investments. Commonly, sample size calculation of phase III is based on the treatment effect observed in phase II. The...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.6624

    authors: Kirchner M,Kieser M,Götte H,Schüler A

    更新日期:2016-01-30 00:00:00

  • Discriminant analysis when all variables are ordered.

    abstract::Determination of the equation that relates an ordered dependent variable to ordered independent variables is sought. One solution, non-parametric discriminant analysis (NPD), involves obtaining the best monotonic step function by means of a computer search procedure. Although one can use alternative selection criteria...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.4780110804

    authors: Johnston B,Seshia SS

    更新日期:1992-06-15 00:00:00

  • The effect of non-differential outcome misclassification on estimates of the attributable and prevented fraction.

    abstract::This paper considers the effect of non-differential outcome misclassification on the population attributable fraction and the population prevented fraction. I examine the bias in the attributable and the prevented fraction derived from a risk ratio estimate as a function of the sensitivity and specificity of the outco...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.4780100308

    authors: Hsieh CC

    更新日期:1991-03-01 00:00:00

  • Nonparametric regression of state occupation, entry, exit, and waiting times with multistate right-censored data.

    abstract::We construct nonparametric regression estimators of a number of temporal functions in a multistate system based on a continuous univariate baseline covariate. These estimators include state occupation probabilities, state entry, exit, and waiting (sojourn) time distribution functions of a general progressive (e.g., ac...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.5703

    authors: Mostajabi F,Datta S

    更新日期:2013-07-30 00:00:00

  • Descriptive statistical analyses of serial dilution data.

    abstract::The serial dilution assay (for example, an in vitro antimicrobic susceptibility test or a serum antibody titer assay) is an important technique in biomedical research. The structure of the experiment forces grouping of the threshold concentrations into intervals. Statistical methods to analyse threshold concentrations...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.4780070410

    authors: Hamilton MA,Rinaldi MG

    更新日期:1988-04-01 00:00:00

  • A refined method for the meta-analysis of controlled clinical trials with binary outcome.

    abstract::For the meta-analysis of controlled clinical trials with binary outcome a test statistic for testing an overall treatment effect is proposed, which is based on a refined estimator for the variance of the treatment effect estimator usually used in the random-effects model of meta-analysis. In simulation studies it is s...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.1009

    authors: Hartung J,Knapp G

    更新日期:2001-12-30 00:00:00

  • Smoothing across time in repeated cross-sectional data.

    abstract::Repeated cross-sectional samples are common in national surveys of health like the National Health Interview Survey (NHIS). Because population health outcomes generally evolve slowly, pooling data across years can improve the precision of current-year annual estimates of disease prevalence and other health outcomes. P...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.3897

    authors: Lockwood JR,McCaffrey DF,Setodji CM,Elliott MN

    更新日期:2011-02-28 00:00:00

  • Correlation analysis for longitudinal data: applications to HIV and psychosocial research.

    abstract::Correlation analysis is widely used in biomedical and psychosocial research for assessing rater reliability, precision of diagnosis and accuracy of proxy outcomes. The popularity of longitudinal study designs has propelled the proliferation in recent years of new methods for longitudinal and other multi-level clustere...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.2857

    authors: Tu XM,Feng C,Kowalski J,Tang W,Wang H,Wan C,Ma Y

    更新日期:2007-09-30 00:00:00

  • A new approach to designing phase I-II cancer trials for cytotoxic chemotherapies.

    abstract::Recently, there has been much work on early phase cancer designs that incorporate both toxicity and efficacy data, called phase I-II designs because they combine elements of both phases. However, they do not explicitly address the phase II hypothesis test of H0 : p ≤ p0 , where p is the probability of efficacy at the ...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.6124

    authors: Bartroff J,Lai TL,Narasimhan B

    更新日期:2014-07-20 00:00:00

  • On the statistical analysis of allelic-loss data.

    abstract::This paper concerns the statistical analysis of certain binary data arising in molecular studies of cancer. In allelic-loss experiments, tumour cell genomes are analysed at informative molecular marker loci to identify deleted chromosomal regions. The resulting binary data are used to infer properties of putative supp...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/(sici)1097-0258(19980715)17:13<1425::aid-s

    authors: Newton MA,Gould MN,Reznikoff CA,Haag JD

    更新日期:1998-07-15 00:00:00

  • A semi-Markov model for multistate and interval-censored data with multiple terminal events. Application in renal transplantation.

    abstract::The semi-Markov assumption emphasizes the importance of time spent in a state. In order to compute this type of multistate model, most transition times are always considered to be exactly identified or right censored. However, in the longitudinal analysis of chronic diseases, investigators are often confronted with in...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.3100

    authors: Foucher Y,Giral M,Soulillou JP,Daures JP

    更新日期:2007-12-30 00:00:00

  • Estimating treated prevalence and service utilization rates: assessing disparities in mental health.

    abstract::There is considerable public concern about health disparities among different cultural/racial/ethnic groups. Important process measures that might reflect inequities are treated prevalence and the service utilization rate in a defined period of time. We have previously described a method for estimating N, the distinct...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.3904

    authors: Laska EM,Meisner M,Wanderling J,Siegel C

    更新日期:2010-07-20 00:00:00

  • Bayesian joint ordinal and survival modeling for breast cancer risk assessment.

    abstract::We propose a joint model to analyze the structure and intensity of the association between longitudinal measurements of an ordinal marker and time to a relevant event. The longitudinal process is defined in terms of a proportional-odds cumulative logit model. Time-to-event is modeled through a left-truncated proportio...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.7065

    authors: Armero C,Forné C,Rué M,Forte A,Perpiñán H,Gómez G,Baré M

    更新日期:2016-12-10 00:00:00

  • A nonparametric smoothing method for assessing GEE models with longitudinal binary data.

    abstract::Studies involving longitudinal binary responses are widely applied in the health and biomedical sciences research and frequently analyzed by generalized estimating equations (GEE) method. This article proposes an alternative goodness-of-fit test based on the nonparametric smoothing approach for assessing the adequacy ...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.3315

    authors: Lin KC,Chen YJ,Shyr Y

    更新日期:2008-09-30 00:00:00

  • A note on sample size calculations for cluster randomised crossover trials with a fixed number of clusters.

    abstract::Girardeau, Ravaud and Donner in 2008 presented a formula for sample size calculations for cluster randomised crossover trials, when the intracluster correlation coefficient, interperiod correlation coefficient and mean cluster size are specified in advance. However, in many randomised trials, the number of clusters is...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.8191

    authors: Kelly TL,Pratt N

    更新日期:2019-08-15 00:00:00

  • Mixtures of proportional hazards regression models.

    abstract::This paper presents a mixture model which combines features of the usual Cox proportional hazards model with those of a class of models, known as mixtures-of-experts. The resulting model is more flexible than the usual Cox model in the sense that the log hazard ratio is allowed to vary non-linearly as a function of th...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/(sici)1097-0258(19990515)18:9<1119::aid-si

    authors: Rosen O,Tanner M

    更新日期:1999-05-15 00:00:00

  • Group sequential designs for cure rate models with early stopping in favour of the null hypothesis.

    abstract::Ewell and Ibrahim derived the large sample distribution of the logrank statistic under general local alternatives. Their asymptotic results enable us to extend several group sequential designs which allow for early stopping in favour of the null hypothesis to the setting in which the cure rate model is appropriate. In...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/1097-0258(20001130)19:22<3023::aid-sim638>

    authors: Patricia Bernardo MV,Ibrahim JG

    更新日期:2000-11-30 00:00:00

  • Formulae and tables for the determination of sample sizes and power in clinical trials for testing differences in proportions for the two-sample design: a review.

    abstract::This paper is a compendium of exact and asymptotic formulae and tables for estimating the sample size in a clinical trial with two treatment groups and a dichotomous outcome. The paper provides separate formulae for equal and unequal treatment group sizes, formulae for the calculation of power given the sample size, a...

    journal_title:Statistics in medicine

    pub_type: 杂志文章,评审

    doi:10.1002/(SICI)1097-0258(19960115)15:1<1::AID-SIM13

    authors: Sahai H,Khurshid A

    更新日期:1996-01-15 00:00:00

  • Nonparametric collective spectral density estimation with an application to clustering the brain signals.

    abstract::In this paper, we develop a method for the simultaneous estimation of spectral density functions (SDFs) for a collection of stationary time series that share some common features. Due to the similarities among the SDFs, the log-SDF can be represented using a common set of basis functions. The basis shared by the colle...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.7972

    authors: Maadooliat M,Sun Y,Chen T

    更新日期:2018-12-30 00:00:00

  • Application of a two-stage random effects model to longitudinal pulmonary function data from sarcoidosis patients.

    abstract::We applied a two-stage random effects model to pulmonary function data from 31 sarcoidosis patients to illustrate its usefulness in analysing unbalanced longitudinal data. For the first stage, repeated measurements of percentage of predicted forced vital capacity (FVC%) from an individual were modelled as a function o...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.4780080206

    authors: Vacek PM,Mickey RM,Bell DY

    更新日期:1989-02-01 00:00:00

  • Non-parametric methods for recurrent event data with informative and non-informative censorings.

    abstract::Recurrent event data are commonly encountered in health-related longitudinal studies. In this paper time-to-events models for recurrent event data are studied with non-informative and informative censorings. In statistical literature, the risk set methods have been confirmed to serve as an appropriate and efficient ap...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.1029

    authors: Wang MC,Chiang CT

    更新日期:2002-02-15 00:00:00

  • A threshold-free summary index of prediction accuracy for censored time to event data.

    abstract::Prediction performance of a risk scoring system needs to be carefully assessed before its adoption in clinical practice. Clinical preventive care often uses risk scores to screen asymptomatic population. The primary clinical interest is to predict the risk of having an event by a prespecified future time t0 . Accuracy...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.7606

    authors: Yuan Y,Zhou QM,Li B,Cai H,Chow EJ,Armstrong GT

    更新日期:2018-05-10 00:00:00

  • Estimation of infection prevalence and sensitivity in a stratified two-stage sampling design employing highly specific diagnostic tests when there is no gold standard.

    abstract::In this work, we describe a two-stage sampling design to estimate the infection prevalence in a population. In the first stage, an imperfect diagnostic test was performed on a random sample of the population. In the second stage, a different imperfect test was performed in a stratified random sample of the first sampl...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.6545

    authors: Miller E,Huppert A,Novikov I,Warburg A,Hailu A,Abbasi I,Freedman LS

    更新日期:2015-11-10 00:00:00

  • On the estimation of total variability in assay validation.

    abstract::In the pharmaceutical industry, an assay method is considered validated if the accuracy and precision for an assay meet some acceptable limits. This paper discusses the assessment of assay precision in terms of the estimation of total variability of an assay from a one-way random effects model which is often considere...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.4780101006

    authors: Chow SC,Tse SK

    更新日期:1991-10-01 00:00:00

  • Sensitivity of Fisher's exact test to minor perturbations in 2 x 2 contingency tables.

    abstract::The two tailed Fisher's exact P value is extremely sensitive to small perturbations in 2 x 2 contingency tables. An example indicates that a 1 per cent increase in the denominator of one treatment group results in a 32 per cent drop in the exact P value, but a mere 0.1 per cent decrease in the treatment success rate. ...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.4780050610

    authors: Dupont WD

    更新日期:1986-11-01 00:00:00

  • Dunnett-type inference in the frailty Cox model with covariates.

    abstract::A frequent objective in medical research is the investigation of differences in patient survival between several experimental treatments and one standard treatment. In order to assess these differences statistically, we have to apply adjustments for multiple comparisons to prevent an increased number of false-positive...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.4403

    authors: Herberich E,Hothorn T

    更新日期:2012-01-13 00:00:00

  • Discrimination and other statistical intervals for the interpretation of in vivo patient monitoring data.

    abstract::A calibration line is used to define the relationship between a new clinical technique and a standard in vitro laboratory methodology. Discrimination intervals quantify the reliability of inverse estimates obtained from the calibration line. Applied to transcutaneous PCO2 monitoring, a new in vivo measurement, discrim...

    journal_title:Statistics in medicine

    pub_type: 杂志文章

    doi:10.1002/sim.4780050407

    authors: Kost GJ

    更新日期:1986-07-01 00:00:00