Overview of Phase IV Clinical Trials Targeting COVID-19: Status Report of Studies Registered on the ClinicalTrials.gov Platform
PDF

Keywords

COVID-19
Pharmacovigilance
Pharmacoepidemiology
Clinical Trials
Phase IV as Topic
Registries

How to Cite

da-Silva, R. F.-., & Alves, J. M. . (2022). Overview of Phase IV Clinical Trials Targeting COVID-19: Status Report of Studies Registered on the ClinicalTrials.gov Platform . Current Medicine, 1. Retrieved from https://mediterraneanjournals.com/index.php/cm/article/view/610

Abstract

Introduction: Phase IV trials evaluate drugs' efficacy, safety, and tolerability in a real-world setting, which may provide evidence related to the safety of approved drugs. This study aimed to characterize the phase IV clinical trials registered at ClinicalTrials.gov targeting COVID-19 and reflect on future needs for post-marketing clinical trials.
Methods: A descriptive cross-sectional study was performed in the ClinitalTrials.gov database with phase IV clinical trials addressed to COVID-19. The search was carried out on March 23rd, 2021, considering search filters for this disease.
Results: A total of 146 protocols were retrieved through a structured search. The results showed the need to promote new, blinded, and larger sample-size phase IV clinical trials. 93.9% of the clinical trials were funded by individuals, universities, and organizations (category "other" funders), and 56.8% were open-label. America and Europe played a more critical role in phase IV clinical trials, with the former leading with 58 trials spread across five countries and the latter with 38 trials in 17 countries. More than two-thirds of the trials (69.8%) included 500 participants.
Conclusions: For the observed period, phase IV clinical trials registered in the ClinicalTrials.gov were dominated by short-term follow-up, open-label designs, small sample sizes, funded mainly by individuals, universities, and organizations, and centered mainly in America and Europe. The methodological features of future studies should be emphasized, namely adequate sample sizes, for which appropriate funding for the implementation of these studies is paramount.

PDF

References

Englev E, Petersen K. [ICH-GCP guideline: quality assurance of clinical trials. Status and perspectives]. Ugeskr Laeger. 2003 Apr 14; 165(16):1659–62.

Dixon JR. The international conference on harmonisation good clinical practice guideline. Qual Assur. Apr-Jun 1999; 6(2):65–74. https://doi.org/10.1080/105294199277860

Gale EAM. Post-marketing studies of new insulins: sales or science? BMJ. 2012 Jun 12; 344: e3974. https://doi.org/10.1136/bmj.e3974

Hulley SB, Cummings SR, Browner WS, Grady DG, Newman TB. Designing Clinical Research. Wolters Kluwer Health; 2013.

Lazarou J, Pomeranz BH, Corey PN. Incidence of adverse drug reactions in hospitalised patients: a meta-analysis of prospective studies. JAMA. 1998 Apr 15; 279(15):1200-5. https://doi.org/10.1001/jama.279.15.1200

Bakke OM, Manocchia M, de Abajo F, Kaitin KI, Lasagna L. Drug safety discontinuations in the United Kingdom, the United States, and Spain from 1974 through 1993—a regulatory perspective. Clin Pharmacol Ther. 1995 Jul; 58(1):108–17. https://doi.org/10.1016/0009-9236(95)90078-0

Hartzema A. Pharmacoepidemiology. Vol 41, 3rd ed. Cincinnati:Harvey Whitney Books; 1998.

Glasser SP, Salas M, Delzell E. Importance and challenges of studying marketed drugs: what is a phase IV study? Common clinical research designs, registries, and self-reporting systems. J Clin Pharmacol. 2007 Sep;47(9):1074–86. https://doi.org/10.1177/0091270007304776

Schmidt LG, Grohmann R, Helmchen H, Langscheid-Schmidt K, Müller-Oerlinghausen B, Poser W, et al. Adverse drug-reactions—an epidemiological study at psychiatric hospitals. Acta Psychiatr Scand. 1984 Jul; 70(1):77–89. https://doi.org/10.1111/j.1600-0447.1984.tb01185.x

Wells KB. Treatment research at the crossroads: the scientific interface of clinical trials and effectiveness research. Am J Psychiatry. 1999 Jan; 156(1):5-10. https://doi.org/10.1176/ajp.156.1.5

Medicine USNLo. ClinicalTrials.gov. [Accessed 2022 Jan 19]. Available from: https://clinicaltrials.gov/ct2/home

Health NIo. Coronavirus Disease 2019 (COVID-19): Treatment Guidelines. [Accessed 2022 Jan 19]. Available from: https://www.covid19treatmentguidelines.nih.gov/whats-new/

Dhanda S, Osborne V, Lynn E, Shakir S. Postmarketing studies: can they provide a safety net for COVID-19 vaccines in the UK? BMJ Evid Based Med. 2020 Oct 21:bmjebm-2020-111507. https://doi.org/10.1136/bmjebm-2020-111507

Cihoric N, Tsikkinis A, van Rhoon G, Crezee H, Aebersold DM, Bodis S, et al. Hyperthermia-related clinical trials on cancer treatment within the ClinicalTrials.gov registry. Int J Hyperthermia. 2015; 31:609–14. https://doi.org/10.3109/02656736.2015.1040471

Shields KE, Lyerly AD. Exclusion of pregnant women from industry-sponsored clinical trials. Obstet Gynecol. 2013 Nov;122(5):1077–81. https://doi.org/10.1097/aog.0b013e3182a9ca67

Califf RM, Zarin DA, Kramer JM, Sherman RE, Aberle LH, Tasneem A. Characteristics of Clinical Trials Registered in ClinicalTrials.gov, 2007–2010. JAMA. 2012 May 2; 307(17):1838–47. https://doi.org/10.1001/jama.2012.3424

Meinert CL, Tonascia S, Higgins K. Content of reports on clinical trials: a critical review. Control Clin Trials. 1984 Dec; 5(4):328-47. https://doi.org/10.1016/s0197-2456(84)80013-6

Chan AW, Altman DG. Epidemiology and reporting of randomised trials published in PubMed journals. Lancet. 2005 Mar 26-Apr 1; 365(9465):1159-1162. https://doi.org/10.1016/s0140-6736(05)71879-1

Ioannidis JP. The mass production of redundant, misleading, and conflicted systematic reviews and meta-analyses. Milbank Q. 2016 Sep; 94(3):485–514. https://doi.org/10.1111/1468-0009.12210

Moher D, Goodman SN, Ioannidis J. Academic criteria for appointment, promotion and rewards in medical research: where's the evidence? Eur J Clin Investig. 2016 May;46(5):383-5. https://doi.org/10.1111/eci.12612

Canevelli M, Remoli G, Trentin F, Riccardi G, Tariciotti L, Risoleo G, et al. The Pipeline of Therapeutics Testing During the Emergency Phase of the COVID-19 Outbreak. Front Med (Lausanne). 2020 Sep 24; 2020; 7: 552991. https://doi.org/10.3389/fmed.2020.552991

Gale EAM. Post-marketing studies of new insulins: sales or science? BMJ. 2012 Jun 12; 344:e3974. https://doi.org/10.1136/bmj.e3974

Glasser SP, Salas M, Delzell E. Importance and challenges of studying marketed drugs: what is a phase IV study? Common clinical research designs, registries, and self-reporting systems. J Clin Pharmacol. 2007 Sep; 47(9):1074-86. https://doi.org/10.1177/0091270007304776

COVID-19 Clinical Research Coalition. Global coalition to accelerate COVID-19 clinical research in resource-limited settings. Lancet. 2020 Apr 25; 395(10233):1322-1325. https://doi.org/10.1016/s0140-6736(20)30798-4

Global Data Healthcare. The UK leads Covid-19 clinical investigations in Europe. Clin trial sarena. [Accessed 2022 Jan 19]. Available from: https://www.clinicaltrialsarena.com/comment/europe-clinical-trials-covid-19/

Yusuf S, Collins R, Peto R. Why do we need some large, simple randomised trials? Stat Med. Oct-Dec 1984; 3(4):409-22. https://doi.org/10.1002/sim.4780030421

Peto R, Collins R, Gray R. Large-scale randomised evidence: large, simple trials and overviews of trials. J Clin Epidemiol. 1995 Jan;48(1):23-40. https://doi.org/10.1016/0895-4356(94)00150-o

Califf RM, DeMets DL. Principles from clinical trials relevant to clinical practice: part I. Circulation. 2002 Aug 20; 106(8):1015-21. https://doi.org/10.1161/01.cir.0000023260.78078.bb

Suresh K, Chandrashekara S. Sample size estimation and power analysis for clinical research studies. J Hum Reprod Sci. 2012 Jan; 5(1):7-13. https://doi.org/10.4103/0974-1208.97779

McEvoy JP, Freudenreich O. CHAPTER 3 - Issues in the Design and Conductance of Clinical Trials. In: McArthur RA, Borsini F, eds. Animal and Translational Models for CNS Drug Discovery. Academic Press; 2008:75-95.

Nikfar S. Safety Testing, Clinical Studies. In: Wexler P, ed. Encyclopedia of Toxicology (Third Edition). Academic Press; 2014:203-204.

Glickman SW, McHutchison JG, Peterson ED, Cairns CB, Harrington RA, Califf RM, et al. Ethical and scientific implications of the globalisation of clinical research. N Engl J Med. 2009 Feb 19; 360(8): 816-823.https://doi.org/10.1056/nejmsb0803929

Pasquali SK, Burstein DS, Benjamin DK Jr, Smith PB, Li JS. Globalisation of pediatric research: analysis of clinical trials completed for pediatric exclusivity. Pediatrics. 2010 Sep; 126(3):e687-e692. https://doi.org/10.1542/peds.2010-0098

Califf RM, Harrington RA. American industry and the U.S. Cardiovascular Clinical Research Enterprise an appropriate analogy? J Am Coll Cardiol. 2011 Aug; 58(7):677-80. https://doi.org/10.1016/j.jacc.2011.03.048

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Copyright (c) 2022 Ferreira- da-Silva R et al.