Overview of clinical data management and statistical analysis of bioequivalence study

Kala N. G., O. Shruti, Aishwarya B. M.


Owing to the demands of both pharmaceutical industry and the regulatory authorities’ clinical data management (CDM) field came into practice. CDM plays a vital role in the study data gathering stage of clinical research. In order to meet this goal, specialized tools i.e. software applications are used to maintain audit trials that offer easy identification and resolution of data discrepancies even in huge and complex clinical trials. Hence a proper and effective clinical data management is required for generating high-quality, accurate, reliable and statistically sound dataset. Such dataset are relatively easy to interpret which is a key step in statistical analysis of a bioequivalence study. Performance of a thorough analysis is dependent on the quality of the trial data. This review highlights how data is processed after it is captured through eCRF, data validation, data cleaning and statistical analysis specially focused on Bioequivalence studies.


Clinical trials, Case report form, Edit checks, Pharmacokinetics, Bioequivalence

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Kwan JL, Lo L, Ferguson J, Goldberg H, Diaz-Martinez JP, Tomlinson G et al. Computerised clinical decision support systems and absolute improvements in care: Meta-analysis of controlled clinical trials. BMJ. 2020;370

Umscheid CA, Margolis DJ, Grossman CE. Key concepts of clinical trials: A narrative review,” Postgraduate medicine. 2011;123(5):194-204.

Bhatt A. Evolution of clinical research: A history before and beyond james lind. Perspectives in clinical research. 2010;1(1):6.

Piantadosi S. Clinical trials: a methodologic perspective. John Wiley & Sons. 2017.

Viergever RF, Li K. Trends in global clinical trial registration: An analysis of numbers of registered clinical trials in different parts of the world from 2004 to 2013. BMJ Open. 2015;5(9).

Califf RM, Zarin DA, Kramer JM, Sherman RE, Aberle LH, Tasneem A. Characteristics of clinical trials registered in clinicaltrials. gov, 2007- 2010. JAMA. 2015;307(17):1838-47.

Chen ML, Shah V, Patnaik R, Adams W, Hussain A, Conner D et al. Bioavailability and bioequivalence: An fda regulatory overview. Pharma Res. 2001;18(12):1645-50.

Meinert CL. Clinical trials, overview. Wiley Handbook of Current and Emerging Drug Therapies. 2006.

Weber B, Hochhaus G. A systematic analysis of the sensitivity of plasma pharmacokinetics to detect differences in the pulmonary performance of inhaled fluticasone propionate products using a model-based simulation approach. AAPS J. 2015;17(4):999-1010.

Sarkar S, Pramanik A, Khatedi N, Maiti J. An investigation of the effects of missing data handling using ‘r’-packages,” in Data Engineering and Communication Technology. Springer. 2020;275-84.

Krishnankutty B, Bellary S, Kumar NB, Moodahadu LS. Data management in clinical research: An overview. Indian J Pharmacol. 2015;44(2):168.

Benedetti MG, Catani F, Leardini A, Pignotti E, Giannini S. Data management in gait analysis for clinical applications. Clin Biomec. 2015;13(3):204-15.

Nourani A, Ayatollahi H, Dodaran MS. A review of clinical data management systems used in clinical trials. Rev Recent Clin Trials. 2015;14(1):10-23.

Nahm M, Shepherd, J Buzenberg A, Rostami R, Corcoran A, McCall J et al. Design and implementation of an institutional case report form library. Clinical Trials. 2011;8(1):94-102.

Bellary S, Krishnankutty B, Latha M. Basics of case report form designing in clinical research. Perspectives Clin Res. 2014;5(4):159.

Fleischmann R, Decker AM, Kraft A, Mai K, Schmidt S. Mobile electronic versus paper case report forms in clinical trials: A randomized controlled trial. BMC Med Res Methodol. 2017;17(1):1-10.

W¨ubbelt P, Fernandez G, Heymer J. Clinical trial management and remote data entry on the internet based on xml case report forms. Medical Infobahn for Europe, IOS Press. 2000;333-7.

Powell G, Bonnett L, Tudur-Smith C, Hughes D, Marson T, Williamson. Using routinely recorded data in a clinical trial: The feasibility, agreement and additional benefits compared to standard prospective data collection methods. Biomed Central. 2017;8.

Richesson RL, Nadkarni P. Data standards for clinical research data collection forms: Current status and challenges. Journal of the American Medical Informatics Association. 2011;18(3):341-6.

Coons SJ, Eremenco S, Lundy JJ, O’Donohoe P, O’Gorman H, Malizia W. Capturing patient-reported outcome (pro) data electronically: The past, present, and promise of epro measurement in clinical trials. The Patient-PatientCentered Outcomes Research. 2015;8(4):301-9.

Thriemer K, Ley B, Ame SM, Puri MK, Hashim R, Chang NY et al. Replacing paper data collection forms with electronic data entry in the field: Findings from a study of community acquired bloodstream infections in pemba, Zanzibar. BMC Res Notes. 2012;5(1):1-7.

Deepa M, Ranganath B, Gopa R. Clinical Data Management Importance. Clinical Research. Asian J Pharm Clin Res. 2016;9(2):59-62.

Al-Jundi A, Sakka S. Protocol writing in clinical research. J Clin Diagnos Res. 2016;10(11):ZE10.

Cipriani A, Barbui C. What is a clinical trial protocol? Epidemiol Psychiatric Sci. 2016;19(2):116-7.

Chan AW, Tetzlaff JM, Altman DG, Laupacis A, Gøtzsche PC, KrleˇzaJeri´c K et al. Spirit 2013 statement: Defining standard protocol items for clinical trials. Revista Panamericana de Salud P´ublica. 2015;38:506-14.

Li G, Taljaard M, Van den Heuvel ER, Levine MA, Cook DJ et al. An introduction to multiplicity issues in clinical trials: The what, why, when and how. Int J Epidemiol. 2017.

Moon KK. Techniques for designing case report forms in clinical trials. ScianNews. 2006.

Le Jeannic A, Quelen C, Alberti C, Durand-Zaleski I. Comparison of two data collection processes in clinical studies: Electronic and paper case report forms. BMC Med Res Methodol. 2015;14(1):1-10.

Vijayananthan A, Nawawi O. The importance of good clinical practice guidelines and its role in clinical trials. Biomedical Imaging Intervention J. 2008;4(1).

Matkar S, Gangawane A. An outline of data management in clinical research. Int J Clin Trials. 2011;4(1):1-6.

Vijayananthan A, Nawawi O. The importance of Good Clinical Practice guidelines and its role in clinical trials. Biomedical imaging and intervention J. 2008;4(1):e5.

Koppula M. Clinical Data Management. 2016.

Anderson S, Hauck WW. A new procedure for testing equivalence in comparative bioavailability and other clinical trials. Communications in Statistics-Theory and Methods. 1983;12(23):2663-92.

Patterson SD, Jones B. Bioequivalence and statistics in clinical pharmacology. Chapman and Hall/CRC; 2005.

Alloway RR, Vinks AA, Fukuda T, Mizuno T, King EC, Zou Y et al. Bioequivalence between innovator and generic tacrolimus in liver and kidney transplant recipients: A randomized, crossover clinical trial. PLoS medicine. 2016;14(11):e1002428.

Ott RL, Longnecker MT. An introduction to statistical methods and data analysis. Cengage Learning. 2015.

Meinert CL. Clinical trials, overview. Wiley Handbook of Current and Emerging Drug Therapies. 2006.

Knief U, Forstmeier W. Violating the normality assumption may be the lesser of two evils. Behavior Research Methods. 2021;1-15.

Kaur P, Jiang X, Duan J, Stier E. Applications of in vitro–in vivo correlations in generic drug development: Case studies. The AAPS journal. 2015;17(4):1035-9.

Wang J, Zhang H, Wang R, Cai Y. Pharmacokinetics, bioequivalence and safety evaluation of two ticagrelor tablets under fasting and fed conditions in healthy chinese subjects. Drug Design, Development and Therapy. 2015;15:1181.

Lu C, Chim C. Generic medications: A primer for pharmacists and patients. US Pharm. 2015;43(6):6-8