Cited by 14,689Statistical Methods in EpidemiologyGlobal Cancer Incidence and ScreeningAdvanced Causal Inference Techniques

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Statistical Aspects of the Analysis of Data From Retrospective Studies of Disease

Nathan Mantel, William M. Haenszel·1959·JNCI: Journal of the National Cancer Institute

DOI 10.1093/jnci/22.4.719

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Abstract

The role and limitations of retrospective investigations of factors possibly associated with the occurrence of a disease are discussed and their relationship to forward-type studies emphasized. Examples of situations in which misleading associations could arise through the use of inappropriate control groups are presented. The possibility of misleading associations may be minimized by controlling or matching on factors which could produce such associations; the statistical analysis will then be modified. Statistical methodology is presented for analyzing retrospective study data, including chi-square measures of statistical significance of the observed association between the disease and the factor under study, and measures for interpreting the association in terms of an increased relative risk of disease. An extension of the chi-square test to the situation where data are subclassified by factors controlled in the analysis is given. A summary relative risk formula, R, is presented and discussed in connection with the problem of weighting the individual subcategory relative risks according to their importance or their precision. Alternative relative-risk formulas, R1, R2, R3, and R4, which require the calculation of subcategory-adjusted proportions of the study factor among diseased persons and controls for the computation of relative risks, are discussed. While these latter formulas may be useful in many instances, they may be biased or inconsistent and are not, in fact, ave…

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Method
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Method
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“Another way to account for complexity is stratified analysis [24].”
Background
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Method
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“In a meta-analysis using the Mantel–Haenszel method (Mantel & Haenszel, 1959 for calculating the weighted pooled odds ratio with a fixed effects model, using the combined samples from these two papers, with a total sample of 923, ASD was a significant risk factor for suicide attempt: pooled OR =…”
Method
Selected birth defects in relation to caffeine-containing beverages
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1α,25(OH)2-Vitamin D and a Nongenomic Vitamin D Analogue Inhibit Ultraviolet Radiation–Induced Skin Carcinogenesis
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“Statistical analyses The Mantel–Haenszel log-rank test (39) was used to analyze incidence data—as the progressive probability of acquiring a tumor, comparing all treatments with control over the entire time course of the study.”
Method
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Risk factors for genital prolapse in non-hysterectomized women around menopause
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“In the absence of significant heterogeneity, the pooled estimate was calculated using the fixed effect model [16].”
Method
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“1) (DerSimonian and Laird, 1986), and a fixed-effect analysis was conducted when no significant heterogeneity was observed (Mantel and Haenszel, 2004).”
BackgroundMethodInfluential
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Meta-analysis of genome-wide association scans for genetic susceptibility to endometriosis in Japanese population
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“The random effects model was used as the pooling method if an obvious between-study heterogeneity (I(2) N 50%) was found [10]; otherwise, the fixed effects model was used [11].”
Method
Antenatal exposure to indomethacin increases the risk of severe intraventricular hemorrhage, necrotizing enterocolitis, and periventricular leukomalacia: a systematic review with metaanalysis
Hammers, A. L., Sanchez-Ramos, L., & Kaunitz, A. M. (2015) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2014.10.1091 · Cited by 101
“Estimates of RR were calculated with fixed-effects (Mantel-Haenszel) and random-effects (DerSimonian and Laird) models.(70,71)”
Method
Effectiveness of short message services and voice call interventions for antiretroviral therapy adherence and other outcomes: A systematic review and meta-analysis
Amankwaa, I., Boateng, D., Quansah, D. Y., Akuoko, C. P., & Evans, C. (2018) · PLOS ONE · doi:10.1371/journal.pone.0204091 · Cited by 98
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“(Mantel–Haenszel method) [17] and a random-effects model”
Behavioral Responses of Aedes aegypti (Diptera: Culicidae) Exposed to Deltamethrin and Possible Implications for Disease Control
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Meta-analysis of studies using metformin as a reducer for liver cancer risk in diabetic patients
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“An inverse variance fixed-effects model was used to calculate when the test for heterogeneity was not statistically significant, otherwise the DerSimonian–Laird random-effects model was employed.([17]) Sensitivity analyses were performed to assess the robustness of results.”
Method
Meta-Analysis of Proportions
Schwarzer, G., & Rücker, G. (2022) · Methods in Molecular Biology · doi:10.1007/978-1-0716-1566-9_10 · Cited by 90
Hypothyroidism in patients with multiple myeloma following treatment with thalidomide
Badros, A. Z., Siegel, E., Bodenner, D., Zangari, M., Zeldis, J., Barlogie, B., & Tricot, G. (2002) · The American Journal of Medicine · doi:10.1016/s0002-9343(01)01137-8 · Cited by 83
Digital training for building resilience: systematic review, meta-analysis, and meta-regression
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“Dichotomous outcomes were expressed as relative measures, and the Mantel–Haenszel method (Mantel & Haenszel, 1959) was used to obtain the pooled intervention effect.”
Method
Role of Calcineurin in Stress Resistance, Morphogenesis, and Virulence of a Candida albicans Wild-Type Strain
Bader, T., Schröppel, K., Bentink, S., Agabian, N., Köhler, G., & Morschhäuser, J. (2006) · Infection and Immunity · doi:10.1128/iai.00142-06 · Cited by 81
Diabetes mellitus is associated with elevated risk of mortality amongst patients with prostate cancer: A meta-analysis of 11 cohort studies
Cai, H., Xu, Z., Xu, T., Yu, B., & Zou, Q. (2015) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.2582 · Cited by 80
“When there was no heterogeneity amongst studies, the fixed-effects model (the Mantel–Haenszel method) was used to calculate the pooled HRs [24].”
Method
Continuation and maintenance therapy with antidepressive agents: Meta-analysis of research
Loonen, A. J. M., Peer, P. G. M., & Zwanikken, G. J. (1991) · Pharmaceutisch Weekblad Scientific Edition · doi:10.1007/bf01957741 · Cited by 79
The efficacy of staple line reinforcement during laparoscopic sleeve gastrectomy: A meta-analysis of randomized controlled trials
Wang, Z., Dai, X., Xie, H., Feng, J., Li, Z., & Lu, Q. (2016) · International Journal of Surgery · doi:10.1016/j.ijsu.2015.12.007 · Cited by 74
Meta-analysis of the relationship between homocysteine, vitamin B12, folate, and multiple sclerosis
Zhu, Y., He, Z.-Y., & Liu, H.-N. (2011) · Journal of Clinical Neuroscience · doi:10.1016/j.jocn.2010.12.022 · Cited by 75
Association between adverse maternal and embryo-fetal effects in norfloxacin-treated and food-deprived rabbits
CLARK, R. (1986) · Fundamental and Applied Toxicology · doi:10.1016/0272-0590(86)90157-0 · Cited by 73
Dose effect of psilocybin on primary and secondary depression: a preliminary systematic review and meta-analysis
Li, N.-X., Hu, Y.-R., Chen, W.-N., & Zhang, B. (2022) · Journal of Affective Disorders · doi:10.1016/j.jad.2021.09.041 · Cited by 72
Genome-wide association study identifies novel susceptible loci and highlights Wnt/beta-catenin pathway in the development of adolescent idiopathic scoliosis
Zhu, Z., Xu, L., Leung-Sang Tang, N., Qin, X., Feng, Z., Sun, W., Zhu, W., Shi, B., Liu, P., Mao, S., et al. (2017) · Human Molecular Genetics · doi:10.1093/hmg/ddx045 · Cited by 69
“cate the heterogeneity among the three stages (39).”
Pelvic endometriosis: Reproductive and menstrual risk factors at different stages in Lombardy, northern Italy
Parazzini, F., Ferraroni, M., Fedele, L., Bocciolone, L., Rubessa, S., & Riccardi, A. (1995) · Journal of Epidemiology and Community Health · doi:10.1136/jech.49.1.61 · Cited by 68
Short versus long duration of antibiotic therapy for bacterial meningitis: a meta-analysis of randomised controlled trials in children
Karageorgopoulos, D. E., Valkimadi, P. E., Kapaskelis, A., Rafailidis, P. I., & Falagas, M. E. (2009) · Archives of Disease in Childhood · doi:10.1136/adc.2008.151563 · Cited by 68
The brain‐derived neurotrophic‐factor ( BDNF ) val66met polymorphism is associated with geriatric depression: A meta‐analysis
Pei, Y., Smith, A. K., Wang, Y., Pan, Y., Yang, J., Chen, Q., Pan, W., Bao, F., Zhao, L., Tie, C., et al. (2012) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32062 · Cited by 67
“1) [Mantel and Haenszel, 1959] or a random-effects model (if P <0.”
Background
Effects of fenofibrate on plasma lipoproteins in hypercholesterolemia and combined hyperlipidemia
Knopp, R. H., Brown, W. V., Dujovne, C. A., Farquhar, J. W., Feldman, E. B., Goldberg, A. C., Grundy, S. M., Lasser, N. L., Mellies, M. J., Palmer, R. H., et al. (1987) · The American Journal of Medicine · doi:10.1016/0002-9343(87)90871-0 · Cited by 65
Human performance in detecting deepfakes: A systematic review and meta-analysis of 56 papers
Diel, A., Lalgi, T., Schröter, I. C., MacDorman, K. F., Teufel, M., & Bäuerle, A. (2024) · Computers in Human Behavior Reports · doi:10.1016/j.chbr.2024.100538 · Cited by 64
“The meta-analysis on ORs was calculated by the Mantel-Haenszel method (Mantel & Haenszel, 1959).”
Meta-analysis of FKBP5 gene polymorphisms association with treatment response in patients with mood disorders
Zou, Y.-F., Wang, F., Feng, X.-L., Li, W.-F., Tao, J.-H., Pan, F.-M., Huang, F., & Su, H. (2010) · Neuroscience Letters · doi:10.1016/j.neulet.2010.08.019 · Cited by 61
Fibrates in the prevention of cardiovascular disease in patients with type 2 diabetes mellitus--a pooled meta-analysis of randomized placebo-controlled clinical trials
Saha, S. A., & Arora, R. R. (2010) · International Journal of Cardiology · doi:10.1016/j.ijcard.2008.11.211 · Cited by 61
The efficacy and safety of probiotics for patients with constipation-predominant irritable bowel syndrome: A systematic review and meta-analysis based on seventeen randomized controlled trials
Wen, Y., Li, J., Long, Q., Yue, C.-C., He, B., & Tang, X.-G. (2020) · International Journal of Surgery · doi:10.1016/j.ijsu.2020.04.063 · Cited by 62
Antipsychotics and the risk of cerebrovascular accident: a systematic review and meta-analysis of observational studies
Hsu, W.-T., Esmaily-Fard, A., Lai, C.-C., Zala, D., Lee, S.-H., Chang, S.-S., & Lee, C.-C. (2017) · Journal of the American Medical Directors Association · doi:10.1016/j.jamda.2017.02.020 · Cited by 59
Risk of Obstructive Sleep Apnea in Parkinson’s Disease: A Meta-Analysis
Zeng, J., Wei, M., Li, T., Chen, W., Feng, Y., Shi, R., Song, Y., Zheng, W., & Ma, W. (2013) · PLoS ONE · doi:10.1371/journal.pone.0082091 · Cited by 60
Case Fatality Rates of Recurrent Thromboembolism and Bleeding in Patients Receiving Direct Oral Anticoagulants for the Initial and Extended Treatment of Venous Thromboembolism: A Systematic Review
Gómez-Outes, A., Lecumberri, R., Suárez-Gea, M. L., Terleira-Fernández, A.-I., Monreal, M., & Vargas-Castrillón, E. (2015) · Journal of Cardiovascular Pharmacology and Therapeutics · doi:10.1177/1074248415575154 · Cited by 57
“10 Case fatality VTE rate (95%CI), % 16 (7-28) 4 (0.”
Utilization of the evidence from studies with no events in meta-analyses of adverse events: an empirical investigation
Xu, C., Zhou, X., Zorzela, L., Ju, K., Furuya-Kanamori, L., Lin, L., Lu, C., Musa, O. A. H., & Vohra, S. (2021) · BMC Medicine · doi:10.1186/s12916-021-02008-2 · Cited by 43
Fetal safety of nicotine replacement therapy in pregnancy: systematic review and meta-analysis.
Taylor, L., Claire, R., Campbell, K., Coleman‐Haynes, T., Leonardi‐Bee, J., Chamberlain, C., Berlin, I., Davey, M., Cooper, S., & Coleman, T. (2021) · Addiction · doi:10.1111/add.15185 · Cited by 53
“Review Manager version 5 software generated pooled risk ratios (RR) using a random‐effects model and an estimate of heterogeneity using the I(2) statistic from the Mantel–Haenszel model [21].”
Association of the glycogen synthase locus on 19q13 with NIDDM in Pima Indians
Majer, M., Mott, D. M., Mochizuki, H., Rowles, J. C., Pedersen, O., Knowler, W. C., Bogardus, C., & Prochazka, M. (1996) · Diabetologia · doi:10.1007/s001250050447 · Cited by 53
The need of health policy perspective to protect Healthcare Workers during COVID-19 pandemic. A GRADE rapid review on the N95 respirators effectiveness
Iannone, P., Castellini, G., Coclite, D., Napoletano, A., Fauci, A. J., Iacorossi, L., D’Angelo, D., Renzi, C., La Torre, G., Mastroianni, C. M., et al. (2020) · PLOS ONE · doi:10.1371/journal.pone.0234025 · Cited by 52
“We then calculated the pooled estimates by using both the fixed-effects and the DerSimonian and Laird random-effects model [28, 29].”
Method
Assessing the Effectiveness of Problem-Based Learning of Preventive Medicine Education in China
Ding, X., Zhao, L., Chu, H., Tong, N., Ni, C., Hu, Z., Zhang, Z., & Wang, M. (2014) · Scientific Reports · doi:10.1038/srep05126 · Cited by 49
The effect of sleep impairment on gestational diabetes mellitus: a systematic review and meta-analysis of cohort studies
Zhang, X., Zhang, R., Cheng, L., Wang, Y., Ding, X., Fu, J., Dang, J., Moore, J., & Li, R. (2020) · Sleep Medicine · doi:10.1016/j.sleep.2020.05.014 · Cited by 50
Common variants upstream of KDR encoding VEGFR2 and in TTC39B associate with endometriosis
Steinthorsdottir, V., Thorleifsson, G., Aradottir, K., Feenstra, B., Sigurdsson, A., Stefansdottir, L., Kristinsdottir, A. M., Zink, F., Halldorsson, G. H., Munk Nielsen, N., et al. (2016) · Nature Communications · doi:10.1038/ncomms12350 · Cited by 48
Carbohydrate Intake, Glycemic Index, Glycemic Load, and Stroke: A Meta-analysis of Prospective Cohort Studies
Cai, X., Wang, C., Wang, S., Cao, G., Jin, C., Yu, J., Li, X., Yan, J., Wang, F., Yu, W., et al. (2015) · Asia Pacific Journal of Public Health · doi:10.1177/1010539514566742 · Cited by 47
Lack of Association of P2RX7 Gene rs2230912 Polymorphism with Mood Disorders: A Meta-Analysis
Feng, W.-P., Zhang, B., Li, W., & Liu, J. (2014) · PLoS ONE · doi:10.1371/journal.pone.0088575 · Cited by 48
“Dependent on the results of heterogeneity test among individual studies, the fixed effect model (Mantel–Haenszel) or random effect model (DerSimonian–Laird) was selected to summarize the pooled OR [30,31].”
Method
Irritancy and Repellency Behavioral Responses of Three Strains of Aedes aegypti Exposed to DDT and α-Cypermethrin
Thanispong, K., Achee, N. L., Bangs, M. J., Grieco, J. P., Suwonkerd, W., Prabaripai, A., & Chareonviriyaphap, T. (2009) · Journal of Medical Entomology · doi:10.1603/033.046.0622 · Cited by 42
Sun exposure and malignant melanoma among susceptible individuals
Dubin, N., Moseson, M., & Pasternack, B. S. (1989) · Environmental Health Perspectives · doi:10.1289/ehp.8981139 · Cited by 43
Apo A5 −1131T/C, FgB −455G/A, −148C/T, and CETP TaqIB gene polymorphisms and coronary artery disease in the Chinese population: a meta-analysis of 15,055 subjects
Li, Y.-Y., Wu, X.-Y., Xu, J., Qian, Y., Zhou, C.-W., & Wang, B. (2013) · Molecular Biology Reports · doi:10.1007/s11033-012-2257-9 · Cited by 41
“Otherwise, the fixedeffects model was adopted (the Mantel–Haenszel method) [30].”
Method

Authors: Mantel, N., & Haenszel, W. M.
Affiliations: National Cancer Institute (US)
Venue: JNCI: Journal of the National Cancer Institute
Publisher: Oxford University Press (OUP)
Published: 1959-04
Volume: 22
Issue: 4
Pages: 719-48
ISSN: 0027-8874 (ISSN-L)
1460-2105
DOI: 10.1093/jnci/22.4.719
OpenAlex: W2150000105
Cited by: 14,689
References: 41
Citations by year: 2026: 35 · 2025: 180 · 2024: 268 · 2023: 297 · 2022: 326 · 2021: 467 · 2020: 479 · 2019: 451 · 2018: 499 · 2017: 551 · 2016: 517 · 2015: 749 · 2014: 815 · 2013: 823 · 2012: 635
FWCI: 6.70
Type: journal article
Language: en
Open access: closed
Locations: JNCI Journal of the National Cancer Institute (publishedVersion)
PubMed (publishedVersion)
Topics: Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Epidemiology
Health Sciences › Medicine › Oncology › Global Cancer Incidence and Screening
Physical Sciences › Mathematics › Statistics and Probability › Advanced Causal Inference Techniques
Keywords: retrospective analysis, case-control study, control group selection, confounding, relative risk, chi-square test, subclassification, women
MeSH terms: Humans, Neoplasms, Retrospective Studies, Statistics as Topic

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Statistical Aspects of the Analysis of Data From Retrospective Studies of Disease

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