Methodology for clinical research


Study design
Clinical research
Observational studies
Experimental studies


A clinical research requires a systematic approach with diligent planning, execution and sampling in order to obtain reliable and validated results, as well as an understanding of each research methodology is essential for researchers. Indeed, selecting an inappropriate study type, an error that cannot be corrected after the beginning of a study, results in flawed methodology. The results of clinical research studies enhance the repertoire of knowledge regarding a disease pathogenicity, an existing or newly discovered medication, surgical or diagnostic procedure or medical device. Medical research can be divided into primary and secondary research, where primary research involves conducting studies and collecting raw data, which is then analysed and evaluated in secondary research. The successful deployment of clinical research methodology depends upon several factors. These include the type of study, the objectives, the population, study design, methodology/techniques and the sampling and statistical procedures used. Among the different types of clinical studies, we can recognize descriptive or analytical studies, which can be further categorized in observational and experimental. Finally, also pre-clinical studies are of outmost importance, representing the steppingstone of clinical trials. It is therefore important to understand the types of method for clinical research. Thus, this review focused on various aspects of the methodology and describes the crucial steps of the conceptual and executive stages.


[1] Pepperell Montague W. The ways of knowing; or, The methods of philosophy. London: G. Allen & Unwin Ltd. 1st ed. New York: The Macmillan Company 1925.
[2] Goldstein M, Goldstein IF. How we know: an exploration of the scientific process. 1st ed. New York: Plenum Press 1979.
[3] Hepburn B, Hanne A. Scientific Method. In: Zalta EN, ed. The Stanford Encyclopedia of Philosophy. Available at: Accessed on: 30/02/2022.
[4] Popper K. The Logic of Scientific Discovery. 2nd ed. London: Routledge 2002.
[5] Hugh G. Gauch Jr. Scientific method in practice, 1st ed. Cambridge: Cambridge University Press 2003.
[6] Achinstein P. Science rules: a historical introduction to scientific methods. 1st ed. Baltimore: The Johns Hopkins University Press 2004.
[7] Gower B. Scientific Method. 1st ed. London: Routledge 1996.
[8] Carey SS. A beginner’s guide to scientific method. 4th ed. Belmont: Wadsworth Cengage Learning 2011.
[9] Garg R. Methodology for research I. Indian J Anaesth 2016;60:640.
[10] Prasad K. Fundamentals of evidence based medicine. 1st ed. New Delhi: Springer India 2014.
[11] Lewsey J. Medical Statistics: a guide to data analysis and critical appraisal. Ann R Coll Surg Eng 2006;88:600-3.
[12] Ozhan Caparlar C, Donmez A. What is scientific research and how can it be done? Turk J Anaesthesiol Reanim 2016;44:212-8.
[13] Röhrig B, du Prel JB, Wachtlin D, Blettner M. Types of study in medical research. Dtsch Arztebl Int 2009;106:262-8.
[14] Frérot M, Lefebvre A, Aho S, Callier P, Astruc K, Aho Glélé LS. What is epidemiology? Changing definitions of epidemiology 1978-2017. PLoS One 2018;13:e0208442.
[15] Schröder W, Nickel S. Research Data Management as an Integral part of the research process of empirical disciplines using landscape ecology as an example. Data Sci J 2020;19. 10.5334/dsj-2020-026
[16] Chew BH. Planning and conducting clinical research: the whole process. Cureus 2019.
[17] del Mar C, Hoffmann TC. A guide to performing a peer review of randomised controlled trials. BMC Med 2015;13:248.
[18] Sessler DI, Imrey PB. Clinical Research Methodology 2. Anesth Analg 2015;121:1043-51.
[19] Stanley K. Design of randomized controlled trials. Circulation 2007;115:1164-9.
[20] Levin KA. Study design VII. Randomised controlled trials. Evid Based Dent 2007;8:22-3.
[21] NIS Definitions. Available at: Accessed on: 26/06/2022.
[22] Elfil M, Negida A. Sampling methods in clinical research; an educational review. Emerg (Tehran) 2017;5:e52.
[23] Bray F, Colombet M, Mery L, Piñeros M, Znaor A, Zanetti R, Ferlay J. Cancer Incidence in five continents, Volume XI. IARC Scientific Publication 2021. Available at: https://publications. Accessed on: 26/06/2022.
[24] Pheby DF, Etherington DJ. Improving the comparability of cancer registry treatment data and proposals for a new national minimum dataset. J Public Health Med 1994;16:331-40.
[25] Sedgwick P. Retrospective cohort studies: advantages and disadvantages, BMJ 2014;348:g1072-g1072.
[26] Gandhi P. Clinical research methodology, Ind J Pharm Edu Res 2011;45:199-209.
[27] Sedgwick P. What is recall bias? BMJ 2012;344:e3519-e3519.
[28] Pieterse H, Diamant Z. Good clinical practice in clinical interventional studies. Eur Clin Respir J 2014;1:26422.
[29] Nair B. Clinical trial designs. Indian Dermatol Online J 2019;10:193.
[30] Patino CM, Ferreira JC. Inclusion and exclusion criteria in research studies: definitions and why they matter. J Bras Pneumol 2018;44:84.
[31] Lim CY, In J. Randomization in clinical studies. Korean J Anesthesiol 2019;72:221-32.
[32] Suresh G, Suresh K, Thomas S. Design, data analysis and sampling techniques for clinical research. Ann Indian Acad Neurol 2011;14:287.
[33] Smith DH, Neutel JM, Lacourcière Y, Kempthorne-Rawson J. Prospective, randomized, open-label, blinded-endpoint (PROBE) designed trials yield the same results as double-blind, placebo-controlled trials with respect to ABPM measurements. J Hypertens 2003;21:1291-8.
[34] Mann H, Djulbegovic B. Choosing a control intervention for a randomised clinical trial. BMC Med Res Methodol 2003;3:7.
[35] Misra S. Randomized double blind placebo control studies, the ‘Gold Standard’ in intervention based studies. Indian J Sex Transm Dis AIDS 2012;33:131.
[36] Sedgwick P. External and internal validity in clinical trials. BMJ 2012;344:e1004-e1004.
[37] Arjmand B, Payab M, Goodarzi P. Biomedical Product Development: Bench to Bedside. 1st ed. Cham: Springer International Publishing 2020.
[38] Honek J. Preclinical research in drug development. Medical Writing 2017;26:5-8.
[39] Sarzotti-Kelsoe M, Cox J, Cleland N, Denny T, Hural J, Needham L, Ozaki D, Rodriguez-Chavez IR, Stevens G, Stiles T, Tarragona-Fiol T, Simkins A. Evaluation and recommendations on good clinical laboratory practice guidelines for phase I-III clinical trials. PLoS Med 2009;6:e1000067.
[40] Declaration of Helsinki Medical Research Involving Human Subjects, 1964. Available at: Accessed on: 26/06/2022.
[41] Medical ethics Deontology, Codes of Practice, Guidelines, Professionalism. Available at: Accessed on: 26/06/ 2022.