Journal Article
. 2006 Oct; 6:50.
doi: 10.1186/1471-2288-6-50.

Development and validation of MIX: comprehensive free software for meta-analysis of causal research data

Leon Bax 1 Ly-Mee Yu  Noriaki Ikeda  Harukazu Tsuruta  Karel G M Moons  
  • PMID: 17038197
  •     11 References
  •     135 citations


Background: Meta-analysis has become a well-known method for synthesis of quantitative data from previously conducted research in applied health sciences. So far, meta-analysis has been particularly useful in evaluating and comparing therapies and in assessing causes of disease. Consequently, the number of software packages that can perform meta-analysis has increased over the years. Unfortunately, it can take a substantial amount of time to get acquainted with some of these programs and most contain little or no interactive educational material. We set out to create and validate an easy-to-use and comprehensive meta-analysis package that would be simple enough programming-wise to remain available as a free download. We specifically aimed at students and researchers who are new to meta-analysis, with important parts of the development oriented towards creating internal interactive tutoring tools and designing features that would facilitate usage of the software as a companion to existing books on meta-analysis.

Results: We took an unconventional approach and created a program that uses Excel as a calculation and programming platform. The main programming language was Visual Basic, as implemented in Visual Basic 6 and Visual Basic for Applications in Excel 2000 and higher. The development took approximately two years and resulted in the 'MIX' program, which can be downloaded from the program's website free of charge. Next, we set out to validate the MIX output with two major software packages as reference standards, namely STATA (metan, metabias, and metatrim) and Comprehensive Meta-Analysis Version 2. Eight meta-analyses that had been published in major journals were used as data sources. All numerical and graphical results from analyses with MIX were identical to their counterparts in STATA and CMA. The MIX program distinguishes itself from most other programs by the extensive graphical output, the click-and-go (Excel) interface, and the educational features.

Conclusion: The MIX program is a valid tool for performing meta-analysis and may be particularly useful in educational environments. It can be downloaded free of charge via or

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Ann Med Health Sci Res, 2014 Dec 17; 4(6). PMID: 25506474    Free PMC article.
Walking training associated with virtual reality-based training increases walking speed of individuals with chronic stroke: systematic review with meta-analysis.
Juliana M Rodrigues-Baroni, Lucas R Nascimento, Louise Ada, Luci F Teixeira-Salmela.
Braz J Phys Ther, 2015 Jan 16; 18(6). PMID: 25590442    Free PMC article.
Systematic Review.
Meta-analysis of Cognitive Impairment in First-Episode Bipolar Disorder: Comparison With First-Episode Schizophrenia and Healthy Controls.
Emre Bora, Christos Pantelis.
Schizophr Bull, 2015 Jan 27; 41(5). PMID: 25616505    Free PMC article.
Non-steroidal anti-inflammatory drugs as a treatment for Alzheimer's disease: a systematic review and meta-analysis of treatment effect.
Marina Miguel-Álvarez, Alejandro Santos-Lozano, +4 authors, Alejandro Lucia.
Drugs Aging, 2015 Feb 04; 32(2). PMID: 25644018
Systematic Review.
Diastolic dysfunction and mortality in septic patients: a systematic review and meta-analysis.
Filippo Sanfilippo, Carlos Corredor, +4 authors, Maurizio Cecconi.
Intensive Care Med, 2015 Mar 25; 41(6). PMID: 25800584
Systematic Review.
The Optimal Load for Maximal Power Production During Lower-Body Resistance Exercises: A Meta-Analysis.
Marco A Soriano, Pedro Jiménez-Reyes, Matthew R Rhea, Pedro J Marín.
Sports Med, 2015 Jun 13; 45(8). PMID: 26063470
Depression as a predictor of adherence to adjuvant endocrine therapy (AET) in women with breast cancer: a systematic review and meta-analysis.
Brent T Mausbach, Richard B Schwab, Scott A Irwin.
Breast Cancer Res Treat, 2015 Jun 17; 152(2). PMID: 26077640    Free PMC article.
Systematic Review.
Do Laboratory Results Concerning High-Viscosity Glass-Ionomers versus Amalgam for Tooth Restorations Indicate Similar Effect Direction and Magnitude than that of Controlled Clinical Trials? - A Meta-Epidemiological Study.
Steffen Mickenautsch, Veerasamy Yengopal.
PLoS One, 2015 Jul 15; 10(7). PMID: 26168274    Free PMC article.
Meta-Analysis of the Effect of Dietary Sodium Restriction with or without Concomitant Renin-Angiotensin-Aldosterone System-Inhibiting Treatment on Albuminuria.
Lanfranco D'Elia, Giovanni Rossi, +3 authors, Pasquale Strazzullo.
Clin J Am Soc Nephrol, 2015 Aug 05; 10(9). PMID: 26240299    Free PMC article.
Methylenetetrahydrofolate reductase gene C677T polymorphism and breast cancer risk: Evidence for genetic susceptibility.
Pradeep Kumar, Upendra Yadav, Vandana Rai.
Meta Gene, 2015 Dec 03; 6. PMID: 26629412    Free PMC article.
Caries-Preventive Effect of High-Viscosity Glass Ionomer and Resin-Based Fissure Sealants on Permanent Teeth: A Systematic Review of Clinical Trials.
Steffen Mickenautsch, Veerasamy Yengopal.
PLoS One, 2016 Jan 23; 11(1). PMID: 26799812    Free PMC article.
Systematic Review.
Insufficient Evidence for Routine Use of Thromboprophylaxis in Ambulatory Patients with an Isolated Lower Leg Injury Requiring Immobilization: Results of a Meta-Analysis.
Roderik Metz, Egbert-Jan M M Verleisdonk, Geert J M G van der Heijden.
Eur J Trauma Emerg Surg, 2009 Apr 01; 35(2). PMID: 26814772
Methylenetetrahydrofolate Reductase (MTHFR) C677T Polymorphism and Alzheimer Disease Risk: a Meta-Analysis.
Vandana Rai.
Mol Neurobiol, 2016 Jan 29; 54(2). PMID: 26820674
Association of methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism with autism: evidence of genetic susceptibility.
Vandana Rai.
Metab Brain Dis, 2016 Mar 10; 31(4). PMID: 26956130
Social Cognition in Multiple Sclerosis: a Meta-Analysis.
Emre Bora, Serkan Özakbaş, Dennis Velakoulis, Mark Walterfang.
Neuropsychol Rev, 2016 Jun 22; 26(2). PMID: 27324894
Folate Pathway Gene Methylenetetrahydrofolate Reductase C677T Polymorphism and Alzheimer Disease Risk in Asian Population.
Vandana Rai.
Indian J Clin Biochem, 2016 Jul 07; 31(3). PMID: 27382194    Free PMC article.
Cardiometabolic Risk Factor Changes Observed in Diabetes Prevention Programs in US Settings: A Systematic Review and Meta-analysis.
Uma Mudaliar, Azadeh Zabetian, +4 authors, Mohammed K Ali.
PLoS Med, 2016 Jul 28; 13(7). PMID: 27459705    Free PMC article.
Systematic Review.
Methylenetetrahydrofolate Reductase C677T Polymorphism and Recurrent Pregnancy Loss Risk in Asian Population: A Meta-analysis.
Vandana Rai.
Indian J Clin Biochem, 2016 Sep 09; 31(4). PMID: 27605737    Free PMC article.
Meta-Analysis of Effect Sizes Reported at Multiple Time Points Using General Linear Mixed Model.
Alfred Musekiwa, Samuel O M Manda, Henry G Mwambi, Ding-Geng Chen.
PLoS One, 2016 Nov 01; 11(10). PMID: 27798661    Free PMC article.
Methylenetetrahydrofolate Reductase C677T Polymorphism and Risk for Male Infertility in Asian Population.
Vandana Rai, Pradeep Kumar.
Indian J Clin Biochem, 2017 Aug 16; 32(3). PMID: 28811683    Free PMC article.
Methylenetetrahydrofolate reductase A1298C genetic variant& risk of schizophrenia: A meta-analysis.
Vandana Rai, Upendra Yadav, +2 authors, Sanjay Gupta.
Indian J Med Res, 2017 Sep 02; 145(4). PMID: 28862175    Free PMC article.
A systematic meta-analysis of the association of Neuregulin 1 (NRG1), D-amino acid oxidase (DAO), and DAO activator (DAOA)/G72 polymorphisms with schizophrenia.
Vinita Jagannath, Miriam Gerstenberg, +2 authors, Edna Grünblatt.
J Neural Transm (Vienna), 2017 Sep 03; 125(1). PMID: 28864885
Systematic Review.
MetaGenyo: a web tool for meta-analysis of genetic association studies.
Jordi Martorell-Marugan, Daniel Toro-Dominguez, Marta E Alarcon-Riquelme, Pedro Carmona-Saez.
BMC Bioinformatics, 2017 Dec 17; 18(1). PMID: 29246109    Free PMC article.
Effects of physical activity on depressive symptoms during breast cancer survivorship: a meta-analysis of randomised control trials.
Efrossini D Patsou, Georgios D Alexias, Fotios G Anagnostopoulos, Michalis V Karamouzis.
ESMO Open, 2017 Dec 21; 2(5). PMID: 29259819    Free PMC article.
Mutations in the DNA methylation pathway and number of driver mutations predict response to azacitidine in myelodysplastic syndromes.
M Teresa Cedena, Inmaculada Rapado, +11 authors, Joaquin Martínez-López.
Oncotarget, 2018 Jan 02; 8(63). PMID: 29291002    Free PMC article.
Strong Association of C677T Polymorphism of Methylenetetrahydrofolate Reductase Gene With Nosyndromic Cleft Lip/Palate (nsCL/P).
Vandana Rai.
Indian J Clin Biochem, 2018 Jan 27; 33(1). PMID: 29371764    Free PMC article.
Economic Impact of Multisystemic Therapy for Child Abuse and Neglect.
Alex R Dopp, Cindy M Schaeffer, Cynthia Cupit Swenson, Jennifer S Powell.
Adm Policy Ment Health, 2018 Apr 06; 45(6). PMID: 29619643    Free PMC article.
Methylenetetrahydrofolate reductase C677T polymorphism and susceptibility to epilepsy.
Vandana Rai, Pradeep Kumar.
Neurol Sci, 2018 Sep 30; 39(12). PMID: 30267335
Catechol-O-methyltransferase gene Val158Met polymorphism and obsessive compulsive disorder susceptibility: a meta-analysis.
Pradeep Kumar, Vandana Rai.
Metab Brain Dis, 2019 Dec 28; 35(2). PMID: 31879835
Charting the landscape of graphical displays for meta-analysis and systematic reviews: a comprehensive review, taxonomy, and feature analysis.
Michael Kossmeier, Ulrich S Tran, Martin Voracek.
BMC Med Res Methodol, 2020 Feb 08; 20(1). PMID: 32028897    Free PMC article.
Evaluation of COMT Gene rs4680 Polymorphism as a Risk Factor for Endometrial Cancer.
Pradeep Kumar, Garima Singh, Vandana Rai.
Indian J Clin Biochem, 2020 Feb 20; 35(1). PMID: 32071497    Free PMC article.
Prediction of Delayed Cerebral Ischemia with Cerebral Angiography: A Meta-Analysis.
Gyanendra Kumar, Oana M Dumitrascu, +2 authors, Andrei V Alexandrov.
Neurocrit Care, 2018 Jul 13; 30(1). PMID: 29998428
Systematic Review.
Association study and a systematic meta-analysis of the VNTR polymorphism in the 3'-UTR of dopamine transporter gene and attention-deficit hyperactivity disorder.
Edna Grünblatt, Anna Maria Werling, +2 authors, Susanne Walitza.
J Neural Transm (Vienna), 2019 Mar 30; 126(4). PMID: 30923918    Free PMC article.
Systematic Review.
Meta-analysis and systematic review for the treatment of perpetrators of intimate partner violence.
Günnur Karakurt, Esin Koç, +2 authors, Shari Bolen.
Neurosci Biobehav Rev, 2019 Aug 16; 105. PMID: 31415863    Free PMC article.
Systematic Review.
Glucagon-like Peptide-1 Receptor Agonists versus Sodium-Glucose Cotransporter Inhibitors for Treatment of T2DM.
Alexis McKee, Ali Al-Khazaali, Stewart G Albert.
J Endocr Soc, 2020 Apr 29; 4(5). PMID: 32342023    Free PMC article.
WITHDRAWN: Preoperative statin therapy for patients undergoing cardiac surgery.
Elmar W Kuhn, Ingo Slottosch, Thorsten Wahlers, Oliver J Liakopoulos.
Cochrane Database Syst Rev, 2016 May 25; (5). PMID: 27219528    Free PMC article.
Systematic Review.
Medication-related osteonecrosis of the jaws (MRONJ) in cancer patients treated with denosumab VS. zoledronic acid: A systematic review and meta-analysis.
A Limones, L-M Sáez-Alcaide, +3 authors, P Molinero-Mourelle.
Med Oral Patol Oral Cir Bucal, 2020 Apr 10; 25(3). PMID: 32271321    Free PMC article.
Systematic Review.
Craniocervical and Cervical Spine Features of Patients with Temporomandibular Disorders: A Systematic Review and Meta-Analysis of Observational Studies.
Ferran Cuenca-Martínez, Aida Herranz-Gómez, +6 authors, Ibai López-de-Uralde-Villanueva.
J Clin Med, 2020 Sep 03; 9(9). PMID: 32872670    Free PMC article.
Association of Allelic Variants of the Reelin Gene with Autistic Spectrum Disorder: A Systematic Review and Meta-Analysis of Candidate Gene Association Studies.
Ignacio Hernández-García, Antonio-Javier Chamorro, +3 authors, José-Antonio Mirón-Canelo.
Int J Environ Res Public Health, 2020 Nov 05; 17(21). PMID: 33143244    Free PMC article.
Systematic Review.
Quantitative phenotype analysis to identify, validate and compare rat disease models.
Yiqing Zhao, Jennifer R Smith, +2 authors, Mary Shimoyama.
Database (Oxford), 2019 Apr 03; 2019. PMID: 30938777    Free PMC article.
Methylenetetrahydrofolate reductase (MTHFR) gene C677T (rs1801133) polymorphism and risk of alcohol dependence: a meta-analysis.
Vandana Rai, Pradeep Kumar.
AIMS Neurosci, 2021 Mar 13; 8(2). PMID: 33709025    Free PMC article.
Subfascial Breast Augmentation: A Systematic Review and Meta-Analysis of Capsular Contracture.
Daniel J Gould, Orr Shauly, Levonti Ohanissian, W Grant Stevens.
Aesthet Surg J Open Forum, 2020 Feb 05; 2(1). PMID: 33791626    Free PMC article.
Risk of recurrence among patients with HR-positive, HER2-negative, early breast cancer receiving adjuvant endocrine therapy: A systematic review and meta-analysis.
Elizabeth M Salvo, Abril Oliva Ramirez, +4 authors, Imtiaz A Samjoo.
Breast, 2021 Mar 08; 57. PMID: 33677313    Free PMC article.
Catechol-O-methyltransferase (COMT) Val158Met Polymorphism and Susceptibility to Alcohol Dependence.
Amrita Chaudhary, Pradeep Kumar, Vandana Rai.
Indian J Clin Biochem, 2021 Jul 06; 36(3). PMID: 34220001    Free PMC article.