Letter to Editor

Challenges of the Data Monitoring Committee in the clinical trial of the first Cuban vaccine for COVID-19

Sonia Pérez-Rodríguez^{1  *} 
http://orcid.org/0000-0002-0755-6373

¹Centro Nacional de Toxicología, La Habana, Cuba.

With the development of the chemical pharmaceutical and biotechnological industry, the sponsor in charge of the commencement, management and financing of a clinical trial, looks for the support of external experts who guarantee the quality of both its studies and the reliability of the results. The heterogeneous team appointed by the sponsor for these aims is the Data Monitoring Committee (DMC), also known as the independent, external or safety committee.

The sponsors of clinical trials has several responsibilities, according to the norms of good clinical practices of Cuba, the Americas and the International Conference for Harmonization (ICH).^1,2,3) The sponsor can or should consider the establishment of an independent DMC in clinical trials to provide advice, at intervals, on the progress of the research, and based on its considerations, to recommend the sponsor to continue, modify or halt the study.

The implementation of the DMC in the clinical trials guarantees the quality of the research and brings a healthy component of independence and objectivity to unplanned decisions in the study. In addition, it provides it an additional value for its external monitoring role, under the principles of confidentiality, responsibility and no conflicts of interest, which contributes with a progressive recognition of its scientific value worldwide.^4,5

The clinical trial of the first Cuban vaccine against COVID-19 is registered in the public record of clinical trials in Cuba (RPCEC 00000332). The sponsor appointed the DMC during the planning of the study. It was made up by a multidisciplinary group of experts, trained and experienced in good clinical practices, biostatistics, bioethics and the disease under study. Moreover, the members show teamwork skills, autonomy, sound judgement and training in the operation of the committee.

The requirements to establish a DMC in a clinical trial are broad. There is a tendency to extend its implementation in other researches because of its benefits.^4,5 The committees are particularly important in confirmatory, large, multicenter, double-blind studies, aimed at improving survival or reducing the risk of major morbidity, in emergency situations, high-mortality diseases, in vulnerable populations and an intermediate analysis of the collected data if required. According to its design, the clinical trial of the first Cuban vaccine against Covid-19, sponsored by the Finlay Vaccine Institute (IFV), fulfills the requirements, hence its appointment is considered a strength for the study.

The DMC has important and numerous tasks to fulfill and responsibilities to take over.^6,7) In general, it periodically reviews the efficacy and safety data collected in the trial. It analyzes risk/benefit profile of the intervention (vaccine) under test and any adverse event that may happen with analysis and definition of its causal relationship, issues periodic reports to the National Regulatory Authority and advices the sponsor on the progress of the research.

The DMC is not routinely necessary in the exploratory studies.^4,5) Nevertheless, the strategy of its appointment in this trial is paramount in order to shorten the times in research and development of the product and to make it available to the population in a timely manner, as a tool in the prevention of the disease.

The DMC closely analyzes the progress and management of the trial and assesses whether the study protocol is being followed or not. This includes reviewing the volunteer recruitment, selection and inclusion process; the integrity of the data declared by the sites and safety of the individuals enrolled. As it is a clinical trial with adaptive design and several treatment arms, the committee, with authority to unveil codes, advices the sponsor about the best options with which to advance to the next phase of research.^4,8

It is necessary to lay the foundations to encourage the systematic use of DMCs in Cuba in the clinical trials linked to Covid-19 prevention and treatment, which guarantees the safety of the participating individuals, the validity and integrity of the data as well as reliability of the results. This enables the early introduction of the new product in regular medical practice.

Referencias/References

1. Organización Panamericana para la Salud. BPC: documento de las Américas. Washington: OPS; 2005. Disponible en: https://apps.who.int/medicinedocs/documents/s18627es/s18627es.pdf.

2. Centro para el Control Estatal de Medicamentos, Equipos y Dispositivos Médicos. Directrices sobre Buenas Prácticas Clínicas en Cuba. La Habana: CECMED; 2000. Disponible en: https://www.cecmed.cu/sites/default/files/adjuntos/Reglamentacion/Dir_BPC.pdf.

3. United States Department of Health and Human Services Food and Drug Administration. E6 (R2) Good Clinical Practice: Integrated Addendum to ICH E6 (R1) Guidance for Industry. Washington: FDA; 2018. Disponible en: https://www.fda.gov/downloads/Drugs/Guidances/UCM464506.pdf.

4. Ellenberg SS, Fleming TR, DeMets DL. Data Monitoring Committees in clinical trials: a practical perspective. 2nd ed. Southern Gate (UK): John Wiley & Sons; 2019. Disponible en: http://93.174.95.29/_ads/B8971AC4CE00890D8EDD1CA1CF98DAFD.

5. Food and Drug Administration. Guidance for clinical trial sponsors: establishment and operation of clinical trial Data Monitoring Committees. Washington: FDA; 2006. Disponible en: http://www.gmp-compliace.org/guidemgr/files/clindatmon.pdf.

6. Acevedo L, Jaramillo D, Donado JH. Análisis interino en ensayos clínicos: un estudio meta-epidemiológico. Med U.P.B. 2017;36(2):134-7. doi: https://10.18566/medupb.v36n2.a05.

7. Gates A, Caldwell P, Curtis S, Dans L, Fernandez RM, Hartling L, et al. Reporting of data monitoring committees and adverse events in pediatric trials: a descriptive analysis. BMJ; 2019;3:1-8. Disponible en: https://bmjpaedsopen.bmj.com/content/bmjpo/3/1/e000426.full.pdf.

8. Viada-González CE, Fors-López MM, Robaina-García M, Lorenzo-Luaces P, Crombet-Ramos T, Macías-Abraham A, et al. Diseños adaptativos fase II - III para pacientes con cáncer en Cuba. Rev Investigación operacional. 2009;28(3):205-13. doi: https://10.1136/bmjpo-2018-000426.

Received: October 02, 2020; Accepted: November 03, 2020