The main responsibility of a Research Ethics Committee (REC) is to guarantee that a biomedical research application meets the standards of scientific, ethical and legal rigor prior to its experimental execution (2). This obligation, in Spain, has been regulated within the framework of the Organic Law (Ley Orgánica, LO) LO 3/2018 (3), both on the protection of personal data; the LO 41/2002, on patient autonomy and obligations regarding information and clinical documentation (4); the SCO/362/2008, on good clinical practice (5); and the Royal Decree (Real Decreto, RD) RD 1090/2015, on clinical trials with drugs (6). Therefore, shortcomings in any aspect related to methods, procedures, ethics or legal frame could lead to a reevaluation, or even rejection by the REC responsible to review a given research application. Nevertheless, reaching this goal implies that the REC must be composed by a robust structure capable to address issues coming from different disciplines (7).

Despite the existence of different national normatives, there are certain coincidences in common aspects of the RECs' activity that could be improved. For example, McNeill (8), Beshir (9), and Wagner and colleagues (10) agree that the REC's administrative work involves a slow bureaucratic process, which has been sometimes criticized as costly or at least making the review process laborious. Others have criticized that inflexible requirements for adherence to narrow literal interpretations of certain normative can lead to a system that is more concerned with “legalism” than the protection of human research participants (2, 11). Furthermore, some authors (12, 13) have highlighted the inconsistencies across different committees, even though they were following the same national normative. In this regard, Edwards and colleagues (14) argue that those inconsistencies are negative only when they derive from a lack of expertise in identifying ethical issues in the research applications that are revised. In addition, Beshir (9) remarks that it is crucial for a REC to ensure that researchers have sufficient research experience and qualifications or alternatively are collaborating with experienced colleagues in the field of their research. This is especially important in two circumstances: when research procedures imply risk for researchers, participants or the environment; and when sensitive aspects related to the privacy and patients' identity can be exposed. In both cases, it is a duty of RECs to minimize the risk of any harm. Finally, some authors have suggested to reassess the role of RECs in order to ensure their purpose is fulfilled to encourage the scientific development maintaining an acceptable ethical framework (7). However, in practice, reaching this goal does not look feasible due to the implicit nature of the ethics and the deliberative methodology followed by the RECs.

The situation above described became more stressful in the last 2 years due to the rapid expansion of the SARS-CoV-2 pandemic and the extremely high number of SARS-CoV-2 infections (COVID-19). The pandemic not only tested the capacity of the scientific community for finding therapeutic and preventive responses to contain and mitigate the disease, but also derived in a greater effort for RECs to guarantee that the increasing number of research applications in different areas were in accordance with scientific, ethical and legal standards. Aware of this situation, the World Commission on the Ethics of Scientific Knowledge and Technology (COMTEST), and the International Bioethics Committee (IBC) signed a joint Ethical Declaration entitled “Ethical considerations from a global perspective”, 2 months after the pandemics was declared (15). The aforementioned document has been received from the research ethics committees as an important exhortation to establish actions in order to facilitate a rapid scientific and technological development, but without neglecting the ethical standards that should always frame any research activity involving human subjects (16). In consonance with this, the Bioethics Committee of Spain (Comité de Bioética de España, CBE) prepared a Report with ethical and legal guidelines that researchers working with health data and biological samples should fulfill during the pandemic (17). In addition, the Spanish Agency of Medicines and Medical Devices (Agencia Española de Medicamentos y Productos Sanitarios, AEMPS) elaborated a special core of guidelines for research activities involving either patients infected with COVID-19 or clinical data from these patients (18). As receptor of these guidelines, each REC was in charge of conciliate practical needs with ethical principles in an extraordinary socio-sanitary context with new research projects increasing rapidly in time.

Evidence of the effect that the pandemic situation has had and in still having on the RECs is scarce. In Spain, there is only one study performed by the REC of the Autonomous Community of Galicia (19). Bugarin-Gonzalez and colleagues, authors of the aforementioned study, reported that the vast majority of research applications submitted to their REC met the ethical requirements necessary for their approval. However, more than a third of them included deficiencies either in methodological aspects or in the informed consent. According to them, these deficiencies could be associated with a lack of knowledge in the normative, training gaps related to management in biomedical research, and a poor communication and interdisciplinary collaboration in the research teams, especially with more experienced professionals. These deficiencies derived not only in delays in the start of research activities, but also implied a work overload in the REC that was forced to dedicate more than one round of revisions for the same application prior to giving a final approval.

Based on the situation described above, this study was designed with the purpose of confirming the following hypothesis: Research group leaders and department heads are usually the most experienced researchers in their groups. In consequence, they play an important role in the success of research applications performed by their teams as first guarantors of a “job well done.” This involvement can be reflected in a favorable opinion of a REC, once those applications are submitted for a first ethical review. With this purpose, four research objectives were pursued:

To collect information of the research applications submitted for an ethical review process based on three areas: profile of the researcher who led the study (principal investigator, PI), aspects related to the study design, and aspects related to the ethical review process.

To identify the ratio of research applications that obtained a favorable opinion in the first ethical review and to confirm whether this ratio was different in the 1st year of pandemic in comparison with the year before the initiation of the pandemic.

To analyse which of the aforementioned variables showed statistical association with a favorable opinion in the first ethical review.

To characterize which of the variables with statistical association appear as predictors of a favorable opinion in the first ethical review.

This study covered the 125 research applications submitted to the Research Ethics Committee of La Rioja (Comité Ético de Investigación con medicamentos de La Rioja, CEImLAR), between January 1st, 2019 and December 31st, 2020. Only applications referred to biomedical research projects were included. Other types of projects, such as clinical trials with previous ethical favorable opinion from another REC (REC of Reference), and informative post-authorization studies, were not included in this study. According to the Royal Decree 1090/2015, which regulates clinical trials with medicines, the Ethics Committees of Drug Research and the Spanish Registry of Clinical Studies, clinical trials following a multicentre study design only require the ethical evaluation of one REC, which will be the REC of Reference.

The CEImLAR was initially established as CEICLAR (Comité Ético de Investigación de La Rioja) in 1995 by Order 10/1995, March 2nd of the Autonomous Community of La Rioja. This Order was updated in 2005 (Order 71/2005, December 2nd). In 2018, the CEICLAR received a certification from the Regional Ministry of Health of La Rioja as a Research Ethics Committee with drugs (CEImLAR). Following the current Spanish normative, the main objective of the CEImLAR is to guarantee the protection of human rights, safety, and well-being of participants and the society as a whole in the framework of activities related to the clinical research, health and scientific advances in La Rioja. Thirteen members, including a permanent secretariat with voice but not vote, currently comprise the CEImLAR. Nine of these members are healthcare professionals (including specialists on clinical and primary care pharmacology, pharmacy, medicine, and nursing), two members are professionals from other disciplines different from medicine (including a lawyer with specialization in data protection, and an economist), a member from a patients' association, and a member with specialization in bioethics. In addition, different regional public health organizations must be represented in the committee's structure. Similar as others RECs, the current activity of the CEImLAR is focused in the evaluation of the methodological, ethical and legal issues of any biomedical research intended to be performed in La Rioja, according to the evaluation criteria stablished by the national normative.

Variables collected were distributed in three groups. Variables composing the first group included information related to the characteristics of the principal investigator (PI), defined as the researcher who led the study and submitted the application. These variables were: identity and academic background of the PI, if the PI was alone or had a research team, if the PI was a professional-in-training (in those cases where the application was part of a post-graduate training program and the PI had a mentor or tutor), and position of the PI in his/her research group, department or unit. The second group of variables referred to different aspects related to the study design. These variables included: the type of study (observational or interventional), the research design (retrospective or prospective), the methodology applied (quantitative, qualitative, or both), participants recruited (minors, adults, or both), and usage of an informed consent form. Finally, aspects related to the ethical review process were collected in a third group of variables. These variables were: dates of first and final ethical revision, time-span (days) between the first and the final opinion of the REC, first and final opinion, number of clarifications required, and type of deficiencies reported in the first ethical review process. Since such deficiencies were not classified in the reports performed by the REC, six categories were created: “informed consent,” “objectives and/or hypotheses,” “methods and/or procedures,” “legal aspects,” “conflict of interests,” and “economic aspects.” Examples of deficiencies reported in the “informed consent” category were applications with informed consent forms in poor writing, with confusing information, or with missing sensitive information. Category “objectives and/or hypotheses” referred to following type of deficiencies: applications with poor writing or confusing research objectives or hypotheses, or applications where those aspects were not connected with the procedures or methodological aspects previously described. Poor writing procedures or procedures missing sensitive aspects related to the process of participants' recruitment, data manipulation, or techniques planned for application in the research protocol, were examples of deficiencies reported in “methods and/or procedures” category. Examples of deficiencies included into the “legal aspects” category were applications not using updated normative or that were not in accordance with the current normative. Applications with financial or other personal considerations that the REC considered could compromise (or had the appearance of compromising) the research purpose and were not reported by the principal investigator, were included in the “conflict of interest” category. Finally, applications requiring clarifications in relation to the sources of financial support, or applications inquired to bring information related to the budget or financial source, were included in the “economic aspects” category.

Data were extracted from the main database of the CEImLAR. This preliminary search covered all research applications presented in 2019 and 2020 based on the inclusion/exclusion criteria and in the pre-defined categories mentioned above. Three researchers, who are members of the CEImLAR (EMM, LGA, and MTAG), extracted the information and created a preliminary dataset. The identity of the PIs was collected in order to search for two indicators of scientific productivity (articles published and h-index) from SCOPUS. Identities of the PIs were extracted in a second dataset after the preliminary dataset was pseudonymized with alphanumeric codes. Another researcher (BBC), who was not a member of the CEImLAR, completed a second dataset with the information collected from SCOPUS. Finally, both datasets were merged. This procedure was performed with the purpose of keeping anonymous the identity of the PIs. The Research Ethics Committee of the Foral Community of Navarra, an independent Research Ethics Committee, approved the aforementioned procedure prior to be executed (Ref. PI 2021/57).

The opinion submitted by the REC after a first ethical review was used as dependent variable. This variable was categorical and included four possible answers: “application rejected,” “application requiring clarifications,” “application approved with minor clarifications,” and “application approved.” For analysis purposes, this variable was recoded into a new binary one with two possible outcomes: zero (“failure”), when the application was rejected or required clarifications after the first ethical review was finished; and one (“successful”), when the application was approved with or without minor clarifications. All the other elements collected were treated as independent variables.

Chi-square test for nominal independent variables and the Mann–Whitney U test for quantitative independent variables were applied in bivariate analyses. Then, in a binary logistic regression model, the magnitude of association of the independent variables that showed a significant relationship in the previous bivariate analysis was determined. In order to measure the power of explanation of the logistic regression model obtained, the Nagelkerke's R squared was calculated. Finally, the weight of association between the dependent variable and its predictors was calculated by the measurement of the Odds ratio.

All analyses were done in the R language and programming environment for statistical and graphical analysis, version 3.6.2 for Windows and with the help of the statistical analysis packages fmsb (20), nortest (21), rstatix (22), and OddsPlotty (23).

This study included a heterogeneous group of studies with different methodologies, study designs, and researchers from different academic and professional backgrounds and profiles. In addition, the study covered only studies submitted to one Research Ethics Committee for an ethical review. Due to the nature of the Autonomous Community of La Rioja, the majority of the studies submitted corresponded to only one healthcare institution, the University Hospital San Pedro of La Rioja. Considering the complexity of the phenomenon analyzed, it is recommended that other two aspects should be included in further studies, such as the age of the PIs or their years of research experience. Unfortunately, both aspects were not collected in this study. However, findings reported in this study bring novel evidence that can help our understanding of elements influencing in a favorable opinion in the review process. Future lines of research could focus in a deep analysis of some of the factors described in this study.

In conclusion, in the wide context of a “job well-done” the aforementioned findings bring new evidence supporting the importance that professionalism plays in biomedical research. In the specific case of biomedical research studies involving human subjects, it implies preparing research applications fulfilling adequate scientific, methodological, legal and ethical standards of quality. In this sense, Research Ethics Committees play an important role as guarantors that such standards are complied before they are executed. Therefore, research applications with deficiencies in some of these aspects are in risk of receiving a non-favorable opinion once they are submitted for a first ethical review or of having delays in obtaining a favorable opinion. Researchers in charge of the preparation of research applications should pay attention to bringing a complete information of the study design, methods and procedures according to the applicable normative in order to ensure a favorable review process. In this frame, more-experienced researchers holding leadership positions in their research groups play a fundamental role during the preparation of new research proposals. Based on the evidence reported in this study, it is recommendable that research group leaders enhance the improvement of lifelong learning and inter-professional collaborative abilities in their teams in order to reduce training gaps.