Prevalência de mortes e exclusões antecipadas de participantes de estudos clínicos em decorrência de eventos adversos sérios relacionados à COVID-19 / Prevalence of deaths and early terminations of clinical trial subjects as a result of COVID-19 related serious adverse events

Abstract

Prevalence of Deaths and Early Terminations of Clinical Trial subjects as a result of COVID.19-related Serious Adverse Events

Background: The COVID-19 disease had its initial outbreak in Wuhan, China around December 2019, rapidly spreading over several countries in the world and being classified by the World Health Organization (WHO) as a global pandemic in early March 2020. In November 2021, WHO official numbers counted nearly 255 million confirmed cases and approximately 5.2 million deaths as a result of COVID-19 worldwide. In addition to its terrible impact on the world public health, the COVID-19 pandemic affected multiple economic, social, educational and academic sectors, including the clinical research for the development of new drugs for the pharmaceutical industry. Objective: Assessing the impact of the COVID-19 pandemic on the clinical research of new drugs in terms of the prevalence of Serious Adverse Events (SAEs) related to the COVID-19 (COVID-19 SAEs) in clinical trial subjects as well as the prevalence of deaths and early terminations of subjects as a result of such Serious Adverse Events. Methods: An Observational, transversal, descriptive and prevalence study utilizing a sample of 155 ongoing clinical trials from a Contract Research Organization (CRO) database in order to analyze the prevalence of SAEs related to COVID-19 (COVID-19 SAEs) occurred in clinical trial subjects during the period of March, 01^st 2020 through February, 28^th 2021. Results: During the analyzed period, there were 307 COVID-19 SAEs and 60 deaths of clinical trial subjects as result of such COVID-19 SAEs. This number represents 14.3% of all SAEs reported in the 155 clinical trials within the same period and a prevalence of 1.98 COVID-19 SAE per clinical trial and 0.0065 COVID-19 SAE per clinical trial subject. There was a higher prevalence of COVID-19 SAEs in the United States (USA), followed by China, India, Spain, Brazil and Poland, whereas there was a higher prevalence of deaths as a result of COVID-19 SAEs in Spain, followed by USA, China and South Africa. The prevalence of COVID-19 SAEs was higher in Oncology, Cardiology and Nephrology trials respectively, whereas the prevalence of deaths from COVID-19 SAEs was higher in Endocrinology, Nephrology and Oncology trials respectively. 46.5% (n = 143) of the COVID-19 SAEs had a direct impact on the recruitment/maintenance of clinical trial subjects in the sample studies, where 19.5% of the COVID-19 SAEs (n = 60) caused the subject to die and 27% (n = 83) resulted in the early termination of the subject, giving us an average of 5 subject deaths per month and 6.9 early terminations per month during the analyzed period. Our results were generally compatible with the global epidemiological situation of the COVID-19 pandemic, nevertheless, due to its method limitations, the results from this current study are to be considered suggestive only as they are not sufficient to establish a defined cause-effect relationship with the global pandemic scenario. Conclusion: The considerable prevalence of deaths and early terminations of clinical trial subjects as a result of the COVID-19 SAEs represented an extremely significant impact on the sample clinical trials, not only due to the deaths of the clinical trial subjects and/or the serious hazard to their health, but also due to the extreme difficulty in replacing those subjects given the serious limitations in patient recruitment during the most critical moments of the COVID-19 pandemic.

Keywords: Covid-19; Pharmacovigilance; Serious Adverse Events; Clinical Trials; Clinicial Research.