A scientific methodology course for advanced medical students: an eight-year perspective

Background: Exponential increases in the development of medical knowledge, the expansion of areas where medicine develops its activities, the emergence of new pathologies ( e.g., COVID-19), novel diagnostic methods and therapeutic strategies, together with the appearance of multiple communication and information technologies, determined that the education of future physicians required targeted training in scientific methodology. Methods: The design and execution of a course in scientific methodology in the curriculum of Facultad de Medicina, Universidad de la República, Uruguay, is described. The course is carried out at an advanced stage of the medical studies for all the students, in which they develop a 10-month research project supervised by the medical school faculty. Students undergo all stages of a research endeavor: generation of hypothesis, elaboration of a research protocol, submission to the Research Ethics and Animal Welfare Committees, data recollection, analysis, interpretation and publication of the results. Results: The course is undertaken at the Facultad de Medicina, Universidad de la República, Uruguay, the main university of the country, with high numbers of students enrolled. The course involves the participation of 600 students and up to 300 professors per year, which implies a huge institutional effort Conclusions: The scientific methodology course resulted in one of the most important incorporations of the current 2008 curriculum. Local students, faculty and international evaluators have qualified this activity as an educational breakthrough, being a gratifying and productive experience. The course represented the first exposure of medical students to the research methodology, scientific literature and publication rules, and emphasized the dynamic nature of medical knowledge within modern medical education. Moreover, for some students it constituted the onset of academic research careers. An additional positive outcome was the reactivation of some faculty research projects, in a way that largely exceeded the boundaries of the course.


Introduction
There is a permanent demand in medical schools to provide a strong background on scientific methodology and research to the future physicians 1 . The exponential increase of information in molecular medicine, genetic engineering and biotechnology, and the continuous evolution of the paradigms of evidence-based and personalized medicine, fosters a focused training of medical students in scientific aspects of the medical sciences. Therefore, innovations in the medical curriculum require the provision of methodological tools and to stimulate a "mindset" for future physicians with the ultimate goal of improving medical practice. The organization of these innovations needs to be adapted, among other factors, to the specific institutional capacities and the number of students.
Universidad de la República in Uruguay, being public and the largest university of the country, has seen a significant increase in students in the last decade, overall representing around 80% of university students in the whole country 2 . The number of active students (those who have presented activity in the last two years), increased from 81,774 in 2008 to 139,830 students in 2019 2 . In 2019, 18,549 students were incorporated to Universidad de la República 2 , of which 2,225 started the medical career at Facultad de Medicina a . Every year, close to 500 medical students graduate (e.g., 483 in 2019) 2 . Thus, in this context, a specific course of "Scientific Methodology in the Medical Sciences" for advanced medical students was conceived and executed, taking into consideration the described conceptual framework and also the numerosity of students. Now, an initial assessment of the organization, evolution and impact of the course over the last eight years will be provided.
In 1910, Abraham Flexner published an extensive report analyzing the situation of 155 medical schools in the United States and Canada 3 , in which he discussed the need to incorporate the basic sciences and a strong scientific component to the training of physicians, believing that this would result in better performance during their clinical practice. From the report arises the need to incorporate training of the scientific method into the medical career, through the formulation of problems, generation of hypothesis and the development of a series of well-designed studies to reject or confirm the hypothesis, with the idea that the skills for problem solving can be applied directly to patient care 4,5 . One hundred years after the publication of the Flexner Report, several authors analyzed how it resulted in a transformative document that generated the foundations for the teaching of 20 th century Medicine 6-9 . At the end of the 90s, the need to generate a change in the study plans of medical careers was raised in the United States, as established in the report generated by the Council on Graduate Medical Education (COGME) 10 . In this context there is a current emphasis, in prestigious schools of medicine at the international level, on explicit scientific training in study plans 11 . Therefore, educational strategies are in full development and are undergoing experimentation, varying in the different academic centers where they are applied.
Although a causal relationship cannot be attributed, recent data suggest that successful early participation in research can influence the long-term scientific activities of clinicians. For instance, Huynh and co-workers described the incorporation of a surgical research program for medical students, and demonstrated that integrating research early in the medical school curriculum provides students with fundamental skills needed for academic achievement, and can help them to establish academic careers 12 . Another recent work published by Waaijer et al., evaluated the scientific activity of medical students, and its effect on scientific activity after graduation 13 . The authors demonstrated that the students who published during their career were more likely to continue publishing after graduation, being more scientifically productive 13 . There is a general consensus that training medical doctors in the 21 st century requires the incorporation of different new skills, including biomedical informatics, information and communication technologies and scientific methodology in addition to clinical skills, in order to cope with exponential increase in medical knowledge 12,14,15 .
In the case of Facultad de Medicina, prior to establishing the Scientific Methodology course described in this work, the past curriculum for medical students had only a minor component of research methodology focusing on (basic principles of) biostatistics at the beginning of the career and an approximation of research design in the first year of clinical training b . It is important to note that Uruguayan medical curriculum resembles that of European universities and therefore differs from the United States. Indeed, right after high school the medical students initiate a seven-year program (three basic, three clinical, and one year internship) ( Figure 1). While in 1995 the Asamblea del Claustro c of Facultad de Medicina already referred specifically to the required scientific quality of medical professionals which must "maintain a critical attitude, based on good scientific training and practice that allows them to analyze, understand and contribute to the resolution of problems related to health in the field in which they operate" 16 , it was not until eight years ago that this requirement could be met with specific course content and adequate strategies to effectively enable good scientific training during undergraduate studies. This incorporation was part of the accreditation process at the regional level d under the MEXA system e a "Facultad de Medicina" will be the term used throughout the manuscript to indicate the School of Medicine of Universidad de la República, Uruguay b The first three years of medical school at Universidad de la República are equivalent to that of undergraduate training in the USA, as Uruguayan students start at the Facultad de Medicina right after high school. The clinical work at the hospitals starts in the 4 th year of training. with the generation of a final report in March 2012 16 which allowed the certification of the medical career in November 2012 by ARCU-SUR f 17 . One important issue mentioned in the report was the need of advancing scientific training of the medical students, indicating the necessity for improvement 16 . It is with that objective that within the current curriculum of the Medical Doctor degree two courses, Scientific Methodology I and II (SMI and SMII), were established. Although this paper will focus on the SMII course, it is important to point out that the SMI course sets theoretical basis for the second course (Table 1).
In addition to the Scientific Methodology courses, a series of activities were incorporated into the 2008 curriculum, where emphasis was placed on the development of activities leading to much needed integration of basic and clinical aspects in various health-disease processes, analyzing scientific approaches to the problem and with a emphasis on the use of medical databases and bibliography accessible through information and communication technologies (ICT). A series of scientific conferences at the Facultad de Medicina were also formalized since 2013, with local and international speakers and the aim of communicating current biomedical research topics.

Methods
The current curriculum for the Facultad de Medicina was designed and approved by the Council in 2008 and started to be progressively applied in March 2009 ( Figure 2).
According to the 2008 curriculum, the career has a duration of seven years, organized in three different modules: two initial modules of three years each, and the internship in the last year. Both modules finish with the Scientific Methodology I and II courses, respectively ( Figure 1).
Taking into consideration the Accreditation Report 16 , a formal training process in scientific research throughout the career f By its initials in Spanish: Sistema de Acreditación Regional de Carreras Universitarias del MERCOSUR; translated as Regional Accreditation System of University Careers of MERCOSUR. ARCU-SUR includes educational agreements between MERCOSUR member countries (Uruguay, Brazil, Argentina and Paraguay) and associated member countries (Chile and Bolivia).
was incorporated into the new study plan; to this end, specific courses and activities for the incorporation of research skills and current medical and ICTs which are available were designed. The Scientific Methodology course I (SMI) for the first-time presents theoretical elements related to the design, methodological and ethical aspects of research, medical literature searches and biostatistics ( Table 1). The Scientific Methodology II course (SMII) in practical terms aims to complete the scientific training of future physicians at an advanced stage of their medical studies while working on specific research projects. The most significant contribution of SMII is that builds on top of the theoretical contents offered in the SMI course with the experience of an actual investigation. The research project covers all the stages from the conception of the hypothesis and design of the investigation to the final communication of the results, with the support of extensive literature searches and the power of current ICT.
The SMII Course has an initial section of two months, that includes biostatistics, ICT and exploration of biomedical databases, where students learn to search in medical databases for scientific literature and are trained in the critical analysis of papers (Table 1). This section runs in parallel with the design and execution of a research project over ten months under the supervision of Facultad de Medicina faculty ( Figure 3).
It is noteworthy that the course is mandatory and involves the participation of 600 students and up to 300 professors per year. The overall course is managed and supervised by a coordinator who is a faculty member of the Facultad de Medicina and an active biomedical investigator.
The course began its activities for the first time in March 2014 ( Figure 2) and has as its main goal the design and execution of a research project in groups of six students mentored by faculty (both junior and senior). Professors are recruited each year by an open call to the faculty members to voluntarily propose a research topic in which the students will perform their investigations, depending on their own interests. The selection process is performed in the virtual campus platform where all the available topics proposed by the faculty are displayed and selected on a first-come and first-serve basis by one student delegate per group.  The ten-month research process starts with the project that involves setting a hypothesis and establishing the research design and corresponding protocols which must be formally presented to the corresponding ethics or animal welfare committees.
Once the project is approved, the groups start to collect and analyze data followed by data interpretation, discussion and conclusions. The group and faculty members meet periodically at least twice per month over the year for guidance and evaluation of the process (Figure 3).
The project finishes with the generation of: a) a monographic work by each group, with a predefined format of an original paper or review article, g and b) a two-day poster presentation in the Annual Meeting of the course, with the participation of the students and professors of Facultad de Medicina ( Figure 3). Topics proposed cover all the aspects of the medical sciences related to the different departments of the school (e.g., basic, epidemiological and clinical areas), with several projects in translational medicine.
The completed research project carried out by the students is evaluated by an external evaluating committee that selects a set of works to be published in the official journal of Facultad de Medicina, Anales de la Facultad de Medicina. The evaluation of all the projects is first performed using a guideline to standardize criteria, followed by a meeting of the whole committee to perform an extensive analysis of the different projects and select the best ones. The publication process allows the students to become familiar with the editorial process and represents an important aspect for the diffusion and promotion of some of the research performed in the different departments of the Facultad de Medicina.
The SMII course Annual Meeting allows the presentation of the results of all the participating groups (100 groups per year) and a vivid collegial exchange between students and professors. g A guideline is provided so that all monographs have preestablished sections, format and length and must include a given number of tables, figures and references.
Next, the evolution of the eight-year experience in the implementation of the SMII course will be described.

Results
The Scientific Methodology II course implies the participation of a large number of faculty members either in their role of project directors or evaluators. Since the course was established in 2014, the number of faculty and departments involved has steadily increased, with the important participation of most of the basic, epidemiological and clinical services. In 2021, over 300 professors were involved in the direction of research projects, and around 60 departments in all basic and clinical areas, from a total of 80, participated (Figure 4) 18 . It is important to note that in the initial years (e.g., 2014) there was one professor allocated to each group, while now there is an average of three professors per group, in many cases from different departments (e.g., 100 in 2014, and 300 in 2021) which helps to foster interdisciplinarity.
An important issue to mention is that initially there was the significant participation of professors from the basic areas, who had considerable expertise in research activities (28% from basic medicine, 41% from all clinical areas in 2014). This changed significantly over the years and actually there is a significant involvement of the general and specialized areas which is an important goal of these courses (3% from basic medicine, 81% from all clinical areas in 2021) ( Figure 5) 18 .
If a closer analysis of the distribution of areas of Facultad de Medicina that are participating since 2014 is done it can be observed that, since 2015, general and specialized clinical departments increased the number of mentors and projects, notably for the surgical areas, which had no participation at all in 2014, and are now participating in several groups ( Figure 5). Indeed, the SMII course nurtures novel research development in surgical areas.
Each year a diversity of topics from all departments are presented which allow students to work in different areas of their interest, since they will choose their topics at the beginning of the year, and usually are related to their future specialization.     To exemplify, selected topics from the past eight years are shown in Table 2 and Table 3, underscoring the high diversity on research themes and areas 18 .
In 2020, the coronavirus disease (COVID-19) pandemic imposed an additional challenge on all the faculty staff and on the students themselves. Despite the fact that the health situation in Uruguay was for the most part of the evolution of the pandemic significantly better than other countries of the region and the world 19,20 , we also had to adapt part of the course to virtual activities, and there were some periods of the year when access to the university and hospitals was restricted or even forbidden. However, this context was used by many of the groups to carry out work related to SARS-CoV-2 and COVID-19, which ended up generating a wealth of relevant local information in the 2020-2021 courses. Table 3 summarizes some of the topics related to the COVID-19 pandemic, showing the adaptation to these particular circumstances 18 .
Last year, at the end of the 2020 course and due to the pandemic, the Annual Meeting was restructured, and the presentation of posters could not be done as usual because the university was closed at that time of the year. Instead, the 100 groups presented their work orally through a virtual platform, Table 3. constituting an unprecedented and unique experience in Facultad de Medicina, which will be incorporated in future editions of the course.

Department Research Topic
In the pandemic context, it is noteworthy to note the creation of an honorary scientific advisory group (GACH) i that worked during 2020 and until July 2021 advising the national government in making decisions based on the best available scientific evidence 19 . This group was assembled with recognized scientists and physicians, many of whom are faculty of the School of Medicine, who at the same time worked in SMII either in the mentoring of the groups or in the evaluation of the projects. For our medical students, this was a compelling and "live" example of how appropriate scientific training can directly impact in the management and the resolution of health problems in our society.

Conclusions
The described Scientific Methodology course (SMII) has successfully evolved after eight years of execution, resulting in one of the most important incorporations of the current 2008 curriculum. The students finished the course with knowledge on how to use, navigate and gather information from databases such as Pubmed, Cochrane and Lilacs, among others, understand how to formulate and progress through a small research project, consider aspects of bioethical and animal i GACH from its initials in Spanish, Grupo Asesor Científico Honorario; the General Coordinator of the group was one of the coauthors, Rafael Radi, MD, PhD.
welfare and go through the approval process, get trained in scientific reading and English language, collect and interpret data, generate a complete written document, and communicate in public their work in poster format. All of the participating parts and international faculty have qualified this activity as an educational breakthrough in our institution. Students and professors consider this course as a highly gratifying and productive experience. An additional positive outcome was the "reactivation" of some research topics in the departments, in a way that largely exceeded the boundaries of the course. Also, some departments which were not significantly involved in research activities started to participate actively in the course, and generate new research lines in their areas. In addition, some of the students were integrated in research groups and communicated their work at local and international meetings, publishing their investigations in national and international journals in an early stage of their career. This action is now synergizing with other courses of the curriculum with the final aim to incorporate the scientific methodology approach as a continuous process through the medical career. Another outcome of the course is the participation of professors as co-directors from other faculties (e.g., Sciences, Psychology and Engineering), generating interdisciplinary projects around the university.
In addition, Uruguayan scientific and medical societies have included presentations from the SMII course students in their meetings, and many research projects have resulted in original publications both in national and international journals.
In spite of the great number of students of each generation, an innovative and successful program was instated in our institution. The course impacted positively on the scientific background of advanced medical students, and renovated the research activities in many clinical Departments.
Recently, a similar experience was published by Uebel et al. at New South Wales University, Australia, however, the number of students involved is much lower than the one of Facultad de Medicina, Universidad de la República. They reported the implementation of an independent learning project (ILP), to promote research skills within the medical students in the whole cohort of the last year of the career where students performed a 34-week research project. Similar to what is reported in this paper, they conducted a long evaluation process (14 years), concluding that students gained valuable experience in research methodology 21 .
Though similar experiences are incorporated in different medical schools around the world, it is remarkable that Facultad de Medicina has a quite large number of students at this stage of their medical studies (i.e., 600 students). This condition represents an additional challenge since the proposal intends to allow the students to undergo all the stages of a research project in a short period of time (10 months).
While this manuscript describes the background, design, execution and direct outcomes of the course, a quantitative study of its impact in the incorporation of research skills and scientific performance of graduate medical students in different cohorts of Facultad de Medicina (2010-2021) is now being conducted. These data will allow to provide further objective elements on the influence that incorporation of formal scientific training in the curriculum of medical students has on continuous education and professional performance. In line with Flexner's original views on the role of research training in medical education, the SMII course experience is providing us with positivity and hope in the context of the future medical practice and also on how medical research is perceived by physicians as an integral part of the health system.

Data availability
Zenodo This project contains the following underlying data: according their impact factor, assuming a strong correlation between IF and clinical performance. Unproven and dangerous assumption -I think! I also wonder if requiring research for clinical promotion have contributed to the 85% waste of research investment. 1 Furthermore, what proportion of publications have any value to improve clinical practice?] Please consider diminishing overlapping of the second paragraph methods with previous wording.
Page 6, first paragraph. You require students to start stating their "hypothesis". I'm overwhelmed by the extensive use of the word "hypothesis" and I wonder if this will remain in the future, after the criticisms to the P-value and the abuse of "significant" 2 . As an example, your own paper, had any concrete hypothesis? Might you describe your aim without using the term 'hypothesis'? In addition, please consider deleting the term 'significant'.
You use "fashion" terms such as personalized and translational Medicine. I wonder if they are needed to your report. [Personally, I think each intervention is already "personalized" with the definition of the eligibility criteria. 3 ] Please, consider starting your results with a demographical description of your subjects, both students and trainers.
Please, consider reporting frequencies including their numerator and denominator. For example, "X out of n (28%) departments from basic medicine" instead of "28% from basic medicine".
I also wonder if the statistical principles used in pharmacology (such as a constant effect) apply to surgery, because a different effect can be assumed to each interventionist -see the consort extension to non-pharmacological interventions. So, although I like the implication of surgeons and other non-pharmacological experts in this project, I wonder if they have to learn the same statistical methods.
You start the conclusions section stating the "success" of your training. I think you can be proud, but I have been trained to strictly define the rules of a "success" before starting. Please, consider describing in the previous results section the indicators that would allow you this statementspecifying you have done this once you have viewed the results and your paper is not free of the risk of bias for selective reporting.
Other comments I liked your proposal in footnote 'a' to call "Facultad de Medicina" your school. Please review you use this term throughout the text, figures and footnotes.
program and the success through successful dissemination, including publication, of student projects. Overall, the manuscript is well written and addresses an important topic in medical education.
Is the rationale for developing the new method (or application) clearly explained? Yes

Is the description of the method technically sound? Yes
Are sufficient details provided to allow replication of the method development and its use by others? Yes If any results are presented, are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions about the method and its performance adequately supported by the findings presented in the article? Yes