Clinical Trials: The Role of Regulatory Agencies, Pharmacovigilance Laws, Guidelines, Risk Management, Patenting, and Publicizing Results
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Submitted
9 February 2022
9 February 2022
Published
28 February 2023
28 February 2023
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Abstract
The research carried out to find a better treatment, improve healthcare, and benefit the current medical practice is termed clinical research. Clinical trial includes the pharmacodynamics (mechanisms of action of a new drug), pharmacokinetics (drug metabolism inside the body), therapeutics (efficacy of the drug), and adverse effects (safety of the drug) of the novel medical products. Clinical research is a process that involves human subjects and their biological specimens. The clinical trial is a meticulously planned protocol-based study of a drug/device to discover a new/better way to prevent, diagnose, and treat a disease/illness. Considering the involvement of both healthy and diseased people in clinical trials, the regulatory authorities have a significant role in the processes involving the conduction of clinical research and carefully evaluate their potential implications on humans. Because clinical trials are usually aimed at assessing the safety and efficacy of novel pharmaceutical compounds and medical devices, pharmacovigilance laws and risk management assume increased significance while conducting clinical research/trials. In this review, we attempt to discuss the regulatory authorities' roles in different geographical regions, including the United States of America, The European Union, and India. We also focus on the importance of pharmacovigilance laws and risk management during clinical trials.
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References
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2. Kandi V, Suvvari TK, Vadakedath S, Godishala V. Microbes, Clinical trials, Drug Discovery, and Vaccine Development: The Current Perspectives. Borneo J Pharm. 2021;4(4):311-23. doi:10.33084/bjop.v4i4.2571
3. Tu YF, Chien CS, Yarmishyn AA, Lin YY, Luo YH, Lin YT, et al. A Review of SARS-CoV-2 and the Ongoing Clinical Trials. Int J Mol Sci. 2020;21(7):2657. doi:10.3390/ijms21072657
4. Park JJH, Mogg R, Smith GE, Nakimuli-Mpungu E, Jehan F, Rayner CR, et al. How COVID-19 has fundamentally changed clinical research in global health. Lancet Glob Health. 2021;9(5):e711-20. doi:10.1016/S2214-109X(20)30542-8
5. Bassi A, Arfin S, Joshi R, Bathla N, Hammond NE, Rajbhandari D, et al. Challenges in operationalising clinical trials in India during the COVID-19 pandemic. Lancet Glob Health. 2021;10(3):e317-9. doi:10.1016/s2214-109x(21)00546-5
6. Spigel DR. The value of observational cohort studies for cancer drugs. Biotechnol Healthc. 2010;7(2):18-24.
7. Mamounas EP. NSABP breast cancer clinical trials: recent results and future directions. Clin Med Res. 2003;1(4):309-26. doi:10.3121/cmr.1.4.309
8. Juneja A, Gupta J, Yadav N, Sharma S, Panchal Y, Adhikari T, et al. An overview of primary registries of WHO's international clinical trial registry platform. Ayu. 2019;40(3):141-6. doi:10.4103/ayu.ayu_62_20
9. Kandi V, Vadakedath S. Clinical Research: An Overview of Study Types, Designs, and Their Implications in the Public Health Perspective. Am J Clin Med Res. 2021;9(2):36-42. doi: 10.12691/ajcmr-9-2-1
10. Lim CY, In J. Randomization in clinical studies. Korean J Anesthesiol. 2019;72(3):221-32. doi:10.4097/kja.19049
11. Kang M, Ragan BG, Park JH. Issues in outcomes research: an overview of randomization techniques for clinical trials. J Athl Train. 2008;43(2):215-21. doi:10.4085/1062-6050-43.2.215
12. Lin Y, Zhu M, Su Z. The pursuit of balance: An overview of covariate-adaptive randomization techniques in clinical trials. Contemp Clin Trials. 2015;45(Pt A):21-5. doi:10.1016/j.cct.2015.07.011
13. Selukar S, May S, Law D, Othus M. Stratified randomization for platform trials with differing experimental arm eligibility. Clin Trials. 2021;18(5):562-9. doi:10.1177/17407745211028872
14. Yang HL, Wu XB, Mao C. [Block randomization in clinical trials]. Zhonghua Yu Fang Yi Xue Za Zhi. 2019;53(4):437-40. doi:10.3760/cma.j.issn.0253-9624.2019.04.022
15. Park Y. Challenges and opportunities in biomarker-driven trials: adaptive randomization. Ann Transl Med. 2022;10(18):1035. doi:10.21037/atm-21-6027
16. Tavana B, Chen A. Determination of Drugs in Clinical Trials: Current Status and Outlook. Sensors. 2022;22(4):1592. doi:10.3390/s22041592
17. Yan F, Thall PF, Lu KH, Gilbert MR, Yuan Y. Phase I-II clinical trial design: a state-of-the-art paradigm for dose finding. Ann Oncol. 2018;29(3):694-9. doi:10.1093/annonc/mdx795
18. Sramek JJ, Murphy MF, Adcock S, Stark JG, Cutler NR. Phase 1 Clinical Trials of Small Molecules: Evolution and State of the Art. Rev Recent Clin Trials. 2021;16(3):232-41. doi:10.2174/1574887116666210204125844
19. Pascual CD. Clinical Drug Trials: The Path to the Patient. Methods Mol Biol. 2021;2296:411-21. doi:10.1007/978-1-0716-1358-0_24
20. Torres-Saavedra PA, Winter KA. An Overview of Phase 2 Clinical Trial Designs. Int J Radiat Oncol Biol Phys. 2022;112(1):22-9. doi:10.1016/j.ijrobp.2021.07.1700
21. Vadakedath S, Godishala V, Suvvari TK, Kandi V. Pharmacology and Pharmacotherapeutics: Finding New Avenues of Research. Am J Pharmacol Sci. 2021;9(2):46-55. doi:10.12691/ajps-9-2-1
22. Bhatt A. Clinical trials during the COVID-19 pandemic: Challenges of putting scientific and ethical principles into practice. Perspect Clin Res. 2020;11:59-63. doi:10.4103/picr.PICR_77_20
23. Pal M, Berhanu G, Desalegn C, Kandi V. Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2): An Update. Cureus. 2020;12(3):e7423. doi:10.7759/cureus.7423
24. Bhatt A. Evolution of clinical research: a history before and beyond james lind. Perspect Clin Res. 2010;1(1):6‐10.
25. Fogel DB. Factors associated with clinical trials that fail and opportunities for improving the likelihood of success: A review. Contemp Clin Trials Commun. 2018;11:156-64. doi:10.1016/j.conctc.2018.08.001
26. Annas GJ. Beyond Nazi War Crimes Experiments: The Voluntary Consent Requirement of the Nuremberg Code at 70. Am J Public Health. 2018;108(1):42-6. doi:10.2105/ajph.2017.304103
27. Muthuswamy V. Ethical issues in clinical research. Perspect Clin Res. 2013;4(1):9-13. doi:10.4103/2229-3485.106369
28. Williamson AE, Burns N. The safety of researchers and participants in primary care qualitative research. Br J Gen Pract. 2014;64(621):198-200. doi:10.3399/bjgp14x679480
29. Collins JF, Sather MR. Regulatory Issues for Clinical Trials in Humans. Epidemiol Rev 2002; 24(1):59-66. doi:10.1093/epirev/24.1.59
30. Bierer BE, White SA, Barnes JM, Gelinas L. Ethical Challenges in Clinical Research During the COVID-19 Pandemic. J Bioeth Inq. 2020;17(4):717-22. doi:10.1007/s11673-020-10045-4
31. Viajayanathan A, Nawawi O. The importance of Good Clinical Practice guidelines and its role in clinical trials. Biomed Imaging Interv J. 2008;4(1):e5. doi:10.2349/biij.4.1.e5
32. Devine S, Dagher RN, Weiss KD, Santana VM. Good clinical practice and the conduct of clinical studies in pediatric oncology. Pediatr Clin North Am. 2008;55(1):187-209. doi:10.1016/j.pcl.2007.10.008
33. Castelino LJ, Narayanan AV, Fernandes SD, Kumar P, Sandeep DS. Good Clinical Practices: An Indian Perspective. Res J Pharm Technol. 2018;11(7):3209-15. doi:10.5958/0974-360X.2018.00590.5
34. Arango J, Chuck T, Ellenberg SS, Foltz B, Gorman C, Hinrichs H, et al. Good Clinical Practice Training: Identifying Key Elements and Strategies for Increasing Training Efficiency. Ther Innov Regul Sci. 2016;50(4):480-6. doi:10.1177/2168479016635220
35. Barkan H. Statistics in clinical research: Important considerations. Ann Card Anaesth. 2015;18(1):74‐82. doi:10.4103/0971-9784.148325
36. Ganasegeran K, Ch'ng ASH, Jamil MFA, Looi I. Clinicians' Perceived Understanding of Biostatistical Results in the Medical Literature: A Cross-Sectional Study. Medicina. 2019;55(6):227. doi:10.3390/medicina55060227
37. Feehan AK, Garcia-Diaz J. Investigator Responsibilities in Clinical Research. Ochsner J. 2020;20(1):44-9. doi:10.31486/toj.19.0085
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Authors
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Kandi V, Vadakedath S, Addanki PS, Godishala V, Pinnelli VB. Clinical Trials: The Role of Regulatory Agencies, Pharmacovigilance Laws, Guidelines, Risk Management, Patenting, and Publicizing Results. Borneo J Pharm [Internet]. 2023Feb.28 [cited 2025Apr.6];6(1):93-109. Available from: https://journal.umpr.ac.id/index.php/bjop/article/view/3263
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