COVID-19 Research Comparative Outcome looking through Real-World Evidence Vs. Clinical Trials
DOI:
https://doi.org/10.14738/jbemi.91.11762Keywords:
RCTs, RWD, COVID-19, regulatory decisionAbstract
Randomized controlled trials (RCTs) are considered the gold standard because of their conventional study design, accurately defined endpoints, and high-quality evidence to define any cause-effect relationships. On the other hand, Real-world Data (RWD) relates to the collection of data pertaining to health status of the patient and/or delivery of routine health care. As the sources of RWD are becoming vast, Real-World Evidence (RWE) studies are gaining increasing attention. RWE can emerge as the backbone for regulatory decision-making in clinical research by providing adequate scientific evidence. A lot of RWE studies have been conducted in COVID-19, where a variety of repurposed drugs have been tested in real-world settings for the treatment and management of COVID-19. The current need is to work on a Hybrid trial methodology combining the most important parts of traditional RCTs and observational study designs to infer the RWE.
References
Villines TC, Cziraky MJ, Amin AN. Awareness, Knowledge, and Utility of RCT Data vs RWE: Results From a Survey of US Cardiologists: Real-world Evidence in Clinical Decision Making. Clin Med Insights Cardiol. 2020 Sep 2;14:1179546820953410. doi: 10.1177/1179546820953410. PMID: 32952404; PMCID: PMC7476349.
Bhide A, Shah PS, Acharya G. A simplified guide to randomized controlled trials. Acta Obstet Gynecol Scand. 2018 Apr;97(4):380-387. doi: 10.1111/aogs.13309. Epub 2018 Feb 27. PMID: 29377058.
Karanicolas PJ, Farrokhyar F, Bhandari M. Practical tips for surgical research: blinding: who, what, when, why, how?. Can J Surg. 2010;53(5):345-348.
Sil A, Kumar P, Kumar R, Das NK. Selection of Control, Randomization, Blinding, and Allocation Concealment. Indian Dermatol Online J. 2019;10(5):601-605. Published 2019 Aug 28. doi:10.4103/idoj.IDOJ_149_19
Hariton E, Locascio JJ. Randomised controlled trials - the gold standard for effectiveness research: Study design: randomised controlled trials. BJOG. 2018;125(13):1716. doi:10.1111/1471-0528.15199
Haidich AB, Ioannidis JP. Patterns of patient enrollment in randomized controlled trials. J Clin Epidemiol. 2001 Sep;54(9):877-83. doi: 10.1016/s0895-4356(01)00353-5. PMID: 11520646.
Booth CM, Tannock IF. Randomised controlled trials and population-based observational research: partners in the evolution of medical evidence. Br J Cancer. 2014;110(3):551-555. doi:10.1038/bjc.2013.725.
Blonde L, Khunti K, Harris SB, Meizinger C, Skolnik NS. Interpretation and impact of real-world clinical data for the practicing clinician. Adv Ther. 2018; 35:1763-1774.
Nicholls SG, Carroll K, Brehaut J, et al. Stakeholder views regarding ethical issues in the design and conduct of pragmatic trials: study protocol. BMC Med Ethics. 2018; 19:90.
Jarow JP, LaVange L, Woodcock J. Multidimensional evidence generation and FDA regulatory decision making defining and using “real-world” data. JAMA. 2017; 318:703-704.
Ozair, FF, N Jamshed, A Sharma, and P Aggarwal. 2015. “Ethical Issues in Electronic Health Records: A General Overview.” Perspect Clin Res 6 (2): 73–76.
https://www.itu.int/net4/wsis/archive/stocktaking/Project/Details?projectId=1515593078. Mantri, Manisha. 2016. “Electronic Health Record (EHR) Standards for India (2016),” 57. Ministry of Health & Family Welfare, and Government of India. 2018. “Digital Information Security in Healthcare, Act [Draft for Public Consultation].
Data sharing and the future of science. Nat Commun. 2018; 9:2817.
National Academy of Sciences. Sharing Clinical Trial Data. Available at: http://www.nationalacademies.org/hmd/Activities/Research/DrugForum/Sharing-Clinical-Trial-Data .aspx. Accessed February 20, 2019.
U.S. Food and Drug Administration, “Use of Real-World Evidence to Support Regulatory Decision-Making for Medical Devices,” August 31, 2017, https://www.fda.gov/downloads/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm513027.pdf
Ziemssen T, Hillert J, Butzkueven H. The importance of collecting structured clinical information on multiple sclerosis. BMC Med 2016; 14:81.
Association of the British Pharmaceutical Industry. Demonstrating Value with Real World Data: A Practical Guide. Association of the British Pharmaceutical Industry; 2011. Available from: http://www. abpi.org.uk/ourwork/library/guidelines/Pages/real-world-data. Aspx.
Sherman RE, Anderson SA, Dal Pan GJ, Gray GW, Gross T, Hunter NL, et al. Real-world evidence – What is it and what can it tell us? N Engl J Med 2016; 375:2293-7.
Mentz RJ, Hernandez AF, Berdan LG, Rorick T, O’Brien EC, Ibarra JC, et al. Good clinical practice guidance and pragmatic clinical trials: Balancing the best of both worlds. Circulation 2016; 133:872-80.
Klonoff DC. The Expanding Role of Real-World Evidence Trials in Health Care Decision Making. J Diabetes Sci Technol. 2020 Jan;14(1):174-179. doi: 10.1177/1932296819832653. Epub 2019 Mar 6. PMID: 30841738.
Lyman GH, Kuderer NM. Randomized Controlled Trials Versus Real-World Data in the COVID-19 Era: A False Narrative. Cancer Invest. 2020 Nov;38(10):537-542.
Kim HS, Lee S, Kim JH. Real-world Evidence versus Randomized Controlled Trial: Clinical Research Based on Electronic Medical Records. J Korean Med Sci. 2018 Aug;33(34):e213. https://doi.org/10.3346/jkms.2018.33.e213
Baumfeld Andre E, Reynolds R, Caubel P, Azoulay L, Dreyer NA. Trial designs using real-world data: The changing landscape of the regulatory approval process. Pharmacoepidemiol Drug Saf. 2020 Oct;29(10):1201-1212. doi: 10.1002/pds.4932. Epub 2019 Dec 10. PMID: 31823482; PMCID: PMC7687110.
Klonoff DC. The New FDA Real-World Evidence Program to Support Development of Drugs and Biologics. J Diabetes Sci Technol. 2020 Mar;14(2):345-349. doi: 10.1177/1932296819832661. Epub 2019 Mar 12. PMID: 30862182; PMCID: PMC7196856.
Zhu M, Sridhar S, Hollingsworth R, Chit A, Kimball T, Murmello K, Greenberg M, Gurunathan S, Chen J. Hybrid clinical trials to generate real-world evidence: design considerations from a sponsor's perspective. Contemp Clin Trials. 2020 Jul;94:105856. doi: 10.1016/j.cct.2019.105856. Epub 2019 Oct 24. PMID: 31669449.
Patsopoulos NA. A pragmatic view on pragmatic trials. Dialogues Clin Neurosci. 2011;13(2):217-24. doi: 10.31887/DCNS.2011.13.2/npatsopoulos. PMID: 21842619; PMCID: PMC3181997.
Martina R, Jenkins D, Bujkiewicz S, Dequen P, Abrams K; GetReal Workpackage 1. The inclusion of real world evidence in clinical development planning. Trials. 2018 Aug 29;19(1):468. doi: 10.1186/s13063-018-2769-2. PMID: 30157904; PMCID: PMC6116448.
Jahanshahi, M., Gregg, K., Davis, G. et al. The Use of External Controls in FDA Regulatory Decision Making. Ther Innov Regul Sci 55, 1019–1035 (2021). https://doi.org/10.1007/s43441-021-00302-y
Fang Y, Zhang H, Xie J, Lin M, Ying L, Pang P, Ji W. Sensitivity of chest CT for COVID-19: comparison to RT-PCR. Radiology. 2020 Aug;296(2):E115-7.
Raptis CA, Hammer MM, Short RG, Shah A, Bhalla S, Bierhals AJ, Filev PD, Hope MD, Jeudy J, Kligerman SJ, Henry TS. Chest CT and coronavirus disease (COVID-19): a critical review of the literature to date. American Journal of Roentgenology. 2020 Oct;215(4):839-42.
Cozzi A, Schiaffino S, Arpaia F, Della Pepa G, Tritella S, Bertolotti P, Menicagli L, Monaco CG, Carbonaro LA, Spairani R, Paskeh BB. Chest x-ray in the COVID-19 pandemic: Radiologists’ real-world reader performance. European journal of radiology. 2020 Nov 1;132:109272.
Wang Z, Deng H, Ou C, Liang J, Wang Y, Jiang M, Li S. Clinical symptoms, comorbidities and complications in severe and non-severe patients with COVID-19: A systematic review and meta-analysis without cases duplication. Medicine (Baltimore). 2020 Nov 25;99(48):e23327.
G. Lippi, J. Wong, B.M. Henry, Hypertension and its severity or mortality in Coronavirus Disease 2019 (COVID-19): a pooled analysis, Pol Arch Intern Med (2020), https://doi.org/10.20452/pamw.15272.
W.J. Guan, Z.Y. Ni, Y. Hu, W.H. Liang, C.Q. Ou, J.X. He, L. Liu, H. Shan, C.L. Lei, D.S.C. Hui, B. Du, L.J. Li, G. Zeng, K.Y. Yuen, R.C. Chen, C.L. Tang, T. Wang, P. Y. Chen, J. Xiang, S.Y. Li, J.L. Wang, Z.J. Liang, Y.X. Peng, L. Wei, Y. Liu, Y.H. Hu, P. Peng, J.M. Wang, J.Y. Liu, Z. Chen, G. Li, Z.J. Zheng, S.Q. Qiu, J. Luo, C.J. Ye, S.Y. Zhu, N.S. Zhong, Clinical Characteristics of Coronavirus Disease 2019 in China, N Engl J Med 382 (2020) 1708–1720, https://doi.org/10.1056/ NEJMoa2002032.
Group TR. Dexamethasone in hospitalized patients with Covid-19—preliminary report. The New England journal of medicine. 2020 Jul 17.
Zhou P, Yang X-L, Wang X-G, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579(7798):270–273.
Tao Y, Tang LV, Hu Y. Treatments in the COVID-19 pandemic: an update on clinical trials. Expert Opinion on Emerging Drugs. 2020 Apr 2;25(2):81-8.
Mancilla-Galindo J, García-Méndez JÓ, Márquez-Sánchez J, Reyes-Casarrubias RE, Aguirre-Aguilar E, Rocha-González HI, Kammar-García A. All-cause mortality among patients treated with repurposed antivirals and antibiotics for COVID-19 in Mexico City: A real-world observational study. EXCLI journal. 2021;20:199.
Zhu Z, Lu Z, Xu T, et al. Arbidol monotherapy is superior to lopinavir/ritonavir in treating COVID-19. J Infect. 2020. DOI:10.1016/j.jinf.2020.03.060
Deng L, Li C, Zeng Q, et al. Arbidol combined with LPV/r versus LPV/r alone against corona virus disease 2019: a retrospective cohort study. J Infect. 2020. DOI:10.1016/j.jinf.2020.03.002.
Million M, Gautret P, Colson P, Roussel Y, Dubourg G, Chabriere E, Honore S, Rolain JM, Fenollar F, Fournier PE, Lagier JC. Clinical efficacy of chloroquine derivatives in COVID-19 infection: comparative meta-analysis between the big data and the real world. New microbes and new infections. 2020 Nov 1;38:100709.
Singh S, Khan A, Chowdhry M, Chatterjee A. Outcomes of hydroxychloroquine treatment among hospitalized COVID-19 patients in the United States-real-world evidence from a federated electronic medical record network. MedRxiv. 2020 Jan 1.
Annie FH, Sirbu C, Frazier KR, Broce M, Lucas Jr BD. Hydroxychloroquine in Hospitalized Patients with COVID-19: Real-World Experience Assessing Mortality. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy. 2020 Nov;40(11):1072-81.
Soto-Becerra P, Culquichicón C, Hurtado-Roca Y, Araujo-Castillo RV. Real-world effectiveness of hydroxychloroquine, azithromycin, and ivermectin among hospitalized COVID-19 patients: results of a target trial emulation using observational data from a nationwide healthcare system in Peru. Azithromycin, and Ivermectin Among Hospitalized COVID-19 Patients: Results of a Target Trial Emulation Using Observational Data from a Nationwide Healthcare System in Peru. 2020 Jan 1.
Rattanaumpawan P, Jirajariyavej S, Lerdlamyong K, Palavutitotai N, Saiyarin J. Real-world experience with favipiravir for treatment of COVID-19 in Thailand: Results from a multi-center observational study. MedRxiv. 2020 Jan 1.
Wang Y, Zhang D, Du G, et al. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebocontrolled, multicentre trial. Lancet. 2020. 395(10236):1569–1578.
Flisiak R, Zarebska-Michaluk D, Berkan-Kawinska A, Tudrujek-Zdunek M, Rogalska M, Piekarska A, Kozielewicz D, Klos K, Rorat M, Bolewska B, Szymanek-Pasternak A. Remdesivir-based therapy improved recovery of patients with COVID-19 in the SARSTer multicentre, real-world study. medRxiv. 2020 Jan 1.
Yao TT, Qian J-D, Zhu W-Y, et al. A systematic review of lopinavir therapy for SARS coronavirus and MERS coronavirus-A possible reference for coronavirus disease-19 treatment option. J Med Virol. 2020;92(6):556–563.
Shen C, Wang Z, Zhao F, et al. Treatment of 5 critically Ill patients with COVID-19 with convalescent plasma. JAMA. 2020;323(16):1582–1589.
Duan K, Liu B, Li C, et al. Effectiveness of convalescent plasma therapy in severe COVID-19 patients. Proc Nat Acad Sci. 2020;117 (17):9490–9496.
Kumar RN, Wu EL, Stosor V, Moore WJ, Achenbach C, Ison MG, Angarone MP. Real-World Experience of Bamlanivimab for COVID-19: A Case-Control Study. Clinical Infectious Diseases: an Official Publication of the Infectious Diseases Society of America. 2021 Apr 13.
Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395 (10223):507–513.
Ramaswamy M, Mannam P, Comer R, Sinclair E, McQuaid DB, Schmidt ML. Off-label real world experience using tocilizumab for patients hospitalized with COVID-19 disease in a regional community health system: a case-control study. medrxiv. 2020 Jan 1.
Vikse J, Henry BM. Tocilizumab in COVID-19: beware of risk of intestinal perforation. Int J Antimicrob Agents. 2020. DOI:10.1016/ j.ijantimicag.2020.10.6009.
Antinori S, Bonazzetti C, Gubertini G, et al. Tocilizumab for cytokine storm syndrome in COVID-19 pneumonia: an increased risk for candidemia? Autoimmun Rev. 2020. DOI:10.1016/j. autrev.2020.102564. Epub ahead of print.
Tritschler T, Mathieu ME, Skeith L, Rodger M, Middeldorp S, Brighton T, Sandset PM, Kahn SR, Angus DC, Blondon M, Bonten MJ. Anticoagulant interventions in hospitalized patients with COVID-19: A scoping review of randomized controlled trials and call for international collaboration. Journal of thrombosis and haemostasis. 2020 Nov;18(11):2958-67.
Baden LR, El Sahly HM, Essink B, Kotloff K, Frey S, Novak R, et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 Vaccine. N Engl J Med. 2021;384(5):403-416.
Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, et al. Safety and efficacy of the BNT162b2 mRNA COVID-19 Vaccine. N Engl J Med. 2020;383(27):2603-2615.
Pawlowski C, Lenehan P, Puranik A, Agarwal V, Venkatakrishnan AJ, Niesen MJ, Horo JC, Badley AD, Halamka J, Soundararajan V. FDA-authorized COVID-19 vaccines are effective per real-world evidence synthesized across a multi-state health system. MedRxiv. 2021 Jan 1.
Chodcik G, Tene L, Patalon T, Gazit S, Ben-Tov A, Cohen D, Muhsen K. The effectiveness of the first dose of BNT162 b 2 vaccine in reducing SARS-CoV-2 infection 13-24 days after immunization: real-world evidence. Medrxiv. 2021 Jan 1.
Jabal KA, Ben-Amram H, Beiruti K, Batheesh Y, Sussan C, Zarka S, Edelstein M. Impact of age, ethnicity, sex and prior infection status on immunogenicity following a single dose of the BNT162b2 mRNA COVID-19 vaccine: realworld evidence from healthcare workers, Israel, December 2020 to January 2021. Eurosurveillance. 2021 Feb 11;26(6):2100096.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2022 Niveditha Hariharan
This work is licensed under a Creative Commons Attribution 4.0 International License.
