Abstract:
BACKGROUND:Tissue micro-arrays (TMAs) are increasingly used to generate data of the molecular phenotype of tumours in clinical epidemiology studies, such as studies of disease prognosis. However, TMA data are particularly prone to missingness. A variety of methods to deal with missing data are available. However, the validity of the various approaches is dependent on the structure of the missing data and there are few empirical studies dealing with missing data from molecular pathology. The purpose of this study was to investigate the results of four commonly used approaches to handling missing data from a large, multi-centre study of the molecular pathological determinants of prognosis in breast cancer. PATIENTS AND METHODS:We pooled data from over 11,000 cases of invasive breast cancer from five studies that collected information on seven prognostic indicators together with survival time data. We compared the results of a multi-variate Cox regression using four approaches to handling missing data - complete case analysis (CCA), mean substitution (MS) and multiple imputation without inclusion of the outcome (MI-) and multiple imputation with inclusion of the outcome (MI+). We also performed an analysis in which missing data were simulated under different assumptions and the results of the four methods were compared. RESULTS:Over half the cases had missing data on at least one of the seven variables and 11 percent had missing data on 4 or more. The multi-variate hazard ratio estimates based on multiple imputation models were very similar to those derived after using MS, with similar standard errors. Hazard ratio estimates based on the CCA were only slightly different, but the estimates were less precise as the standard errors were large. However, in data simulated to be missing completely at random (MCAR) or missing at random (MAR), estimates for MI+ were least biased and most accurate, whereas estimates for CCA were most biased and least accurate. CONCLUSION:In this study, empirical results from analyses using CCA, MS, MI- and MI+ were similar, although results from CCA were less precise. The results from simulations suggest that in general MI+ is likely to be the best. Given the ease of implementing MI in standard statistical software, the results of MI+ and CCA should be compared in any multi-variate analysis where missing data are a problem.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Ali AM,Dawson SJ,Blows FM,Provenzano E,Ellis IO,Baglietto L,Huntsman D,Caldas C,Pharoah PDdoi
10.1038/sj.bjc.6606078subject
Has Abstractpub_date
2011-02-15 00:00:00pages
693-9issue
4eissn
0007-0920issn
1532-1827pii
6606078journal_volume
104pub_type
杂志文章,meta分析abstract::Nine hundred and eighty-four breast cancer patients were interviewed regarding exogenous hormonal use. This represents a random sample of breast cancer patients in Southern Sweden referred to the Department of Oncology at Lund for treatment between 1978 and 1997 (excluding 1980 and 1981) with a 100% follow-up. Ever-us...
journal_title:British journal of cancer
pub_type: 杂志文章
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pub_type: 杂志文章
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更新日期:1980-01-01 00:00:00
abstract::The carcinogenicity of the vegetative tissues of bracken fern (Pteridium) has long been established. More recently, the carcinogenic effects of the spores of bracken have also been recognized. Both vegetative tissues and spores of bracken can induce adducts in DNA in animal tissues, but the possible genotoxic or carci...
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journal_title:British journal of cancer
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journal_title:British journal of cancer
pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章,评审
doi:10.1038/sj.bjc.6603494
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pub_type: 临床试验,杂志文章,随机对照试验
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journal_title:British journal of cancer
pub_type: 杂志文章
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更新日期:1975-09-01 00:00:00
abstract::Accumulating evidence suggests that the p53 gene is a good target for molecular epidemiological studies. We previously reported an association between the presence of p53 mutations and lifetime cigarette consumption. Although over 675 p53 mutations have been reported in lung cancers in the literature thus far, very li...
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pub_type: 杂志文章
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更新日期:1998-05-01 00:00:00
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更新日期:2005-10-17 00:00:00
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abstract::The effect of LiCl on melanoma cell growth and differentiation was studied in mouse and human melanoma cell lines. LiCl markedly inhibited B16 and HT-144 melanoma cell growth in vitro. Clonogenicity in soft agar of the melanoma cells was also markedly inhibited by LiCl. Pretreatment of B16 mouse melanoma cells with Li...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1987.9
更新日期:1987-01-01 00:00:00
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更新日期:2019-04-01 00:00:00