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<journal-meta>
<journal-id journal-id-type="publisher-id">Front. Med.</journal-id>
<journal-title>Frontiers in Medicine</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Med.</abbrev-journal-title>
<issn pub-type="epub">2296-858X</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.3389/fmed.2024.1395433</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Medicine</subject>
<subj-group>
<subject>Original Research</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>One hundred years of Ecuadorian biomedical scientific output and its association with the main causes of mortality: a bibliometric study</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author" corresp="yes">
<name><surname>Sisa</surname> <given-names>Ivan</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<xref ref-type="corresp" rid="c001"><sup>&#x002A;</sup></xref>
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<contrib contrib-type="author">
<name><surname>Caicedo-Potos&#x00ED;</surname> <given-names>Jhon</given-names></name>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
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<contrib contrib-type="author">
<name><surname>Cordovez</surname> <given-names>Mar&#x00ED;a</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
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<contrib contrib-type="author">
<name><surname>Verdezoto</surname> <given-names>Clara</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
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<contrib contrib-type="author">
<name><surname>Barreno</surname> <given-names>Mishell</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
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<contrib contrib-type="author">
<name><surname>Coral</surname> <given-names>Mart&#x00ED;n</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
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<contrib contrib-type="author">
<name><surname>Herrera-Franco</surname> <given-names>Gricelda</given-names></name>
<xref ref-type="aff" rid="aff3"><sup>3</sup></xref>
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<aff id="aff1"><sup>1</sup><institution>Colegio de Ciencias de la Salud, Escuela de Medicina, Universidad San Francisco de Quito USFQ</institution>, <addr-line>Quito</addr-line>, <country>Ecuador</country></aff>
<aff id="aff2"><sup>2</sup><institution>Centro de Investigaci&#x00F3;n y Proyectos Aplicados a las Ciencias de la Tierra (CIPAT), Escuela Superior Polit&#x00E9;cnica del Litoral (ESPOL)</institution>, <addr-line>Guayaquil</addr-line>, <country>Ecuador</country></aff>
<aff id="aff3"><sup>3</sup><institution>Facultad de Ciencias de la Ingenier&#x00ED;a, Universidad Estatal Pen&#x00ED;nsula de Santa Elena</institution>, <addr-line>La Libertad</addr-line>, <country>Ecuador</country></aff>
<author-notes>
<fn fn-type="edited-by" id="fn0002">
<p>Edited by: Esteban Ortiz-Prado, University of the Americas, Ecuador</p>
</fn>
<fn fn-type="edited-by" id="fn0003">
<p>Reviewed by: Ismael Hoare, University of South Florida, United States</p>
<p>Juan Sebastian Izquierdo-Condoy, University of the Americas, Ecuador</p>
<p>Marco Culqui-S&#x00E1;nchez, Pontificia Universidad Cat&#x00F3;lica del Ecuador, Ecuador</p>
<p>Miguel Angel Garcia Bereguiain, University of the Americas, Ecuador</p>
</fn>
<corresp id="c001">&#x002A;Correspondence: Ivan Sisa, <email>isisa@usfq.edu.ec</email></corresp>
</author-notes>
<pub-date pub-type="epub">
<day>03</day>
<month>07</month>
<year>2024</year>
</pub-date>
<pub-date pub-type="collection">
<year>2024</year>
</pub-date>
<volume>11</volume>
<elocation-id>1395433</elocation-id>
<history>
<date date-type="received">
<day>03</day>
<month>03</month>
<year>2024</year>
</date>
<date date-type="accepted">
<day>12</day>
<month>06</month>
<year>2024</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#x00A9; 2024 Sisa, Caicedo-Potos&#x00ED;, Cordovez, Verdezoto, Barreno, Coral and Herrera-Franco.</copyright-statement>
<copyright-year>2024</copyright-year>
<copyright-holder>Sisa, Caicedo-Potos&#x00ED;, Cordovez, Verdezoto, Barreno, Coral and Herrera-Franco</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/">
<p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</p>
</license>
</permissions>
<abstract>
<sec id="sec1">
<title>Introduction</title>
<p>Historically, low-and middle-income countries have been scarce producers of biomedical research; only 2% of the global scientific output is produced by these countries despite accounting for 92% of the global burden of disease. In addition, few low-and middle-income countries have exhaustively mapped and analyzed their scientific production in health and its association with main local burden of disease.</p>
</sec>
<sec id="sec2">
<title>Objective</title>
<p>To evaluate the evolution of biomedical research in Ecuador over the last 100&#x2009;years and its relationship with the main causes of mortality.</p>
</sec>
<sec id="sec3">
<title>Methods</title>
<p>A bibliometric study embedded in a systematic review design was carried out using biomedical publications indexed in Scopus and Web of Science (WoS) during the period 1920&#x2013;2021. Information from the National Institute of Statistics and Census was used to identify the main causes of mortality.</p>
</sec>
<sec id="sec4">
<title>Results</title>
<p>Our search strategy identified 16,697 publications related to biomedicine in Ecuador. Of these 3,225 articles met the criteria for this study. Since 2010, there has been an exponential increase in scientific production in biomedicine. This increase was predominantly based on cross-sectional observational studies (49.67%). During the period analyzed (1920&#x2013;2021), biomedical production was distributed with 52.43% in clinical research, 37.79% in public health, and 9.77% in basic sciences. The research focus with the highest number of publications was epidemiology and surveillance system of diseases (23.44%). Additionally, private universities are the largest producers of biomedical research compared to public universities, 40.12% vs. 19.60%, respectively. Of the total biomedical research produced, 18.54% is associated with the main causes of mortality, and the Ecuadorian private university is the largest contributor to these studies compared to public universities, 39.97% vs. 16.72%.</p>
</sec>
<sec id="sec5">
<title>Conclusion</title>
<p>In one century, Ecuador produced 3,225 articles in biomedicine, according to our criteria. 18.54% of the total produced is aimed at solving the main causes of mortality in the country. Private universities are the leaders in scientific production related to health in Ecuador.</p>
</sec>
</abstract>
<kwd-group>
<kwd>scientific production</kwd>
<kwd>health research system</kwd>
<kwd>bibliometric</kwd>
<kwd>Ecuador</kwd>
<kwd>burden of disease</kwd>
</kwd-group>
<counts>
<fig-count count="9"/>
<table-count count="3"/>
<equation-count count="0"/>
<ref-count count="42"/>
<page-count count="14"/>
<word-count count="7874"/>
</counts>
<custom-meta-wrap>
<custom-meta>
<meta-name>section-at-acceptance</meta-name>
<meta-value>Regulatory Science</meta-value>
</custom-meta>
</custom-meta-wrap>
</article-meta>
</front>
<body>
<sec sec-type="intro" id="sec6">
<label>1</label>
<title>Introduction</title>
<p>An appropriate and efficient national health research system should address both the health problems of importance to its population and the interventions and outcomes considered important by patients and clinicians (<xref ref-type="bibr" rid="ref1">1</xref>, <xref ref-type="bibr" rid="ref2">2</xref>). However, in reality, there is a tremendous mismatch between the actual health needs and the research conducted, which has been described as one of the factors contributing to the estimated 85% waste in biomedical research globally (<xref ref-type="bibr" rid="ref2">2</xref>). This waste in futile investigations is equivalent to $200 billion of the approximately $240 billion invested in health research and development (R&#x0026;D) in 2010 (<xref ref-type="bibr" rid="ref2">2</xref>, <xref ref-type="bibr" rid="ref3">3</xref>). For example, in the last century cardiovascular disease (e.g., ischemic heart disease and stroke) has become the leading cause of premature mortality and morbidity globally (<xref ref-type="bibr" rid="ref4">4</xref>), and low-and middle-income countries (LMICs) are estimated to contribute to ~80% of the global cardiovascular disease burden (<xref ref-type="bibr" rid="ref5">5</xref>). However, LMICs contributed to only 0.2% of total cardiovascular disease publications, leaving their populations without easily accessible evidence to make informed clinical decisions about their own health (<xref ref-type="bibr" rid="ref2">2</xref>, <xref ref-type="bibr" rid="ref6">6</xref>). Historically, LMICs have been scarce producers of biomedical research; they produce only 2% of global scientific output (<xref ref-type="bibr" rid="ref7">7</xref>). For example, Perel et al. found a poor correlation between burden of disease and research output produced as Randomized Clinical Trials (RCTs) in Latin America (<xref ref-type="bibr" rid="ref8">8</xref>). Ecuador, considered by the World Bank as a middle-income country in Latin America, is no exception. Despite being a middle-income country, it struggles with diseases characteristic of low-income countries, such as chronic malnutrition and lower respiratory infections (<xref ref-type="bibr" rid="ref9">9</xref>). Besides, according to the Ecuadorian National Institute of Statistics and Census (INEC), in 2021 the main causes of death were COVID-19-related diseases, ischemic heart disease, and diabetes mellitus (<xref ref-type="bibr" rid="ref10">10</xref>). During the last 15&#x2009;years, Ecuador has undergone important reforms in the areas of health and higher education. In terms of health, a new model (MAIS-FCI, Spanish acronym) of care focused on primary health care was implemented. This model, as well as the National Health Research Policy issued in 2020 by the Ecuadorian Ministry of Public Health (MSP), establishes that all research efforts in the country should be conducted to provide solutions to its main health problems (<xref ref-type="bibr" rid="ref11">11</xref>). In terms of higher education, the Organic Law of Higher Education (LOES) was issued in 2010, which sought to strengthen the research capacity of Ecuadorian universities through multiple regulations and programs. Likewise, the LOES promotes that all research and teaching efforts carried out at the local level should be aligned with the main health, economic, and social needs of Ecuador (<xref ref-type="bibr" rid="ref12">12</xref>, <xref ref-type="bibr" rid="ref13">13</xref>). Academia is the driving force behind research and is naturally called upon to produce knowledge that responds to the particular needs of society (<xref ref-type="bibr" rid="ref14">14</xref>). However, there is little evidence of how academia has contributed to solving the main causes of morbidity and mortality in Ecuador. According to the literature, only two bibliometric analyses have addressed this issue, and their main findings are that during the last decade, scientific production related to health sciences in Ecuador showed an exponential growth. However, this increase has been at the expense of a decrease in the quality of the evidence generated through cohort and randomized clinical trial studies, and with no relation to the main causes of mortality in the Ecuadorian population (<xref ref-type="bibr" rid="ref15">15</xref>, <xref ref-type="bibr" rid="ref16">16</xref>). The weaknesses of these previous studies are the short period of time analyzed and the possibility of missed publications due to the use of a single database (Scopus). The present study seeks to answer the following research questions:</p><list list-type="roman-lower">
<list-item>
<p>How has biomedical research evolved in Ecuador during the last century?</p>
</list-item>
<list-item>
<p>Are Ecuadorian universities contributing to the solution to the main causes of mortality in the country?</p>
</list-item>
</list>
<p>A systematic literature review design embedded in a bibliometric analysis study was used to answer these questions.</p>
</sec>
<sec sec-type="methods" id="sec7">
<label>2</label>
<title>Methods</title>
<p>A bibliometric study embedded in a systematic review design was carried out in three phases: (i) extraction/identification of articles in the Scopus and Web of Science (WoS) databases, (ii) construction of the database and extraction of previously defined variables, and (iii) statistical analysis and generation of results.</p>
<sec id="sec8">
<label>2.1</label>
<title>Phase I: information extraction/identification</title>
<p>In the Scopus and WoS databases, a search equation was applied to identify the largest possible number of articles related to biomedical research produced in Ecuador between 1920 and 2021. Scopus and WoS were selected because of their high quality and coverage of scientific journals. Additionally, WoS is the oldest research and citation database in the world and has the capability to export search results (<xref ref-type="bibr" rid="ref17">17</xref>, <xref ref-type="bibr" rid="ref18">18</xref>). The search equations are available in the <xref ref-type="supplementary-material" rid="SM1">Supplementary material</xref> accompanying this publication (<xref ref-type="supplementary-material" rid="SM1">Supplementary Table S1</xref>). Initially, 11,303 publications were identified in Scopus and 5,394 publications in WoS. The Bibliometrix tool RStudio (<xref ref-type="bibr" rid="ref19">19</xref>) was used to combine both databases and eliminate duplicate documents (<italic>n</italic>&#x2009;=&#x2009;2,626), generating a total of 14,071 articles (<xref ref-type="fig" rid="fig1">Figure 1</xref>).</p>
<fig position="float" id="fig1">
<label>Figure 1</label>
<caption>
<p>PRISMA flowchart.</p>
</caption>
<graphic xlink:href="fmed-11-1395433-g001.tif"/>
</fig>
</sec>
<sec id="sec9">
<label>2.2</label>
<title>Phase II: construction of the database and extraction of variables</title>
<p>During this phase of the study, five members of the research team performed the manual screening of the studies identified in the first phase (<italic>n</italic>&#x2009;=&#x2009;14,071). The following inclusion criteria were applied: (i) studies related to health sciences and with application in humans, (ii) studies carried out by an Ecuadorian institution, and (iii) studies that used data from Ecuador in their analysis. On the other hand, the following exclusion criteria were applied: (i) articles not available in their full version by institutional/library access or on the web as open access and (ii) non-original studies (e.g., letter to the editor, commentary, poster). Thus, the number of studies eligible for the final analysis was 3,225 documents. Additionally, a disambiguation process was carried out to unify the affiliations of the Ecuadorian universities that registered publications in biomedical sciences as described in the literature (<xref ref-type="bibr" rid="ref20">20</xref>). For the extraction of the variables, an electronic form was developed and tested in Microsoft Excel. The following variables were recorded in this form: (i) research focus (basic science, clinical, and public health), (ii) study design (case or series report, case&#x2013;control study, cohort study, cross-sectional/survey study, ecological study, meta-analysis/network meta-analysis, randomized clinical trial study, and other, including laboratory studies, basic science, and modeling, (iii) quartile placement according to SCImago Journal Rank (SJR), as a proxy measure of impact and quality (<xref ref-type="bibr" rid="ref21">21</xref>), (iv) institutional affiliation and type of funding (public, private with state allocation, and private self-financed), (v) line of research, (vi) journal of publication and the number of discontinued journals in Scopus, (vii) geographic location by province, (viii) international collaboration, and (ix) relation with the main causes of mortality in the country. To identify the main causes of mortality, information from the annual reports of the Ecuadorian National Institute of Statistics and Censuses (INEC) was used, and 5 standardized rankings of causes of mortality per decade were constructed. Finally, to assure consistency and accuracy of extracted data, the last author proofread randomly chosen extracted data. Discrepancies in data screening were discussed and resolved by consensus between the first and last authors.</p>
</sec>
<sec id="sec10">
<label>2.3</label>
<title>Phase III: statistical analysis and generation of results</title>
<p>Descriptive statistics were used to summarize the characteristics of the articles analyzed. To explore trends over time in scientific production per institution and mortality, the entire period analyzed was divided into four periods of 25&#x2009;years each and five periods of approximately 10&#x2009;years each (with the exception of 1920&#x2013;1979), respectively. The chi-square test was used to assess differences between categorical variables. To compare university-specific research production, a standardized rate of the number of publications per 1,000 students was calculated. The number of health-related students per university was obtained from the Sistema Integral de Informaci&#x00F3;n de la Educaci&#x00F3;n Superior.<xref ref-type="fn" rid="fn0001"><sup>1</sup></xref> The statistical program used for data processing and analysis was RStudio for Windows, V.4.2.2. To claim statistical significance, we used a <italic>p</italic>-value of &#x003C; 0.05. In addition, ArcGIS Pro V.3.1.2 was used to map the international collaboration of the publications and their geographic distribution at the local level by province.</p>
</sec>
</sec>
<sec sec-type="results" id="sec11">
<label>3</label>
<title>Results</title>
<p>The search strategy used identified 16,697 publications (11,303 from Scopus and 5,394 from WoS) related to biomedicine in Ecuador. A total of 13,472 articles were excluded (duplicate articles <italic>n</italic>&#x2009;=&#x2009;2,626, and articles that did not meet the inclusion criteria <italic>n</italic>&#x2009;=&#x2009;10,846), so the final sample analyzed was 3,225 articles related to biomedicine (<xref ref-type="fig" rid="fig1">Figure 1</xref>).</p>
<sec id="sec12">
<label>3.1</label>
<title>Biomedical production trend over time</title>
<p>According to the period analyzed, there was a linear trend of low production until the beginning of the 2000s and an exponential increase at the end of the same decade (<xref ref-type="fig" rid="fig2">Figure 2</xref>). The most frequently used type of epidemiological design was cross-sectional (49.67%), followed by other (17.11%) and cohort studies (15.63%). There was a downward trend in the production of randomized clinical trial studies (<xref ref-type="fig" rid="fig3">Figure 3</xref>). Additionally, the research area with the highest production was related to clinical areas (52.43%, <italic>n</italic>&#x2009;=&#x2009;1,691/3,225) (<xref ref-type="table" rid="tab1">Table 1</xref>). When analyzing the scientific production by time periods, we found that during periods I and II (1920&#x2013;1969), there was a scarce production of articles (0.09%, <italic>n</italic>&#x2009;=&#x2009;3), mainly in the areas of intestinal parasitosis and tropical diseases such as yellow fever. During period III (1970&#x2013;1994), the production increased to 1.08% (<italic>n</italic>&#x2009;=&#x2009;35) of the total analyzed. In this period, scientific production stood out mainly in the clinical areas (45.71%, <italic>n</italic>&#x2009;=&#x2009;16). Also in this period, the first randomized clinical trial conducted in Ecuador (published in 1989 in the British Journal of Obstetrics and Gynaecology) was recorded. This study assessed whether calcium supplementation reduced the occurrence of pregnancy-induced hypertension. In period IV (1995&#x2013;2021), an exponential production of biomedical research in the country was evidenced, concentrating 98.82% (<italic>n</italic>&#x2009;=&#x2009;3,187) of all that was produced in the last century. In this period, research in the clinical area continued to dominate, with 52.49% (<italic>n</italic>&#x2009;=&#x2009;1,673) of the total produced; however, it is worth mentioning that the production of research at the basic biomedical sciences level was 9.63% (<italic>n</italic>&#x2009;=&#x2009;307) (<xref ref-type="supplementary-material" rid="SM1">Supplementary Tables S2&#x2013;S5</xref>). Overall, the scientific production of the analyzed period was encompassed in 1,157 scientific journals. Currently, 6.57% (76/1,157) of those journals are discontinued in the Scopus database (<xref ref-type="supplementary-material" rid="SM1">Supplementary Table S6</xref>). The scientific journals with the highest number of Ecuadorian publications related to biomedicine in descending order are: Archivos Venezolanos de Farmacolog&#x00ED;a y Terap&#x00E9;utica (2.76%, <italic>n</italic>&#x2009;=&#x2009;89), Revista Ecuatoriana de Neurolog&#x00ED;a (2.36%, <italic>n</italic>&#x2009;=&#x2009;76), and American Journal of Tropical Medicine and Hygiene (2.01%, <italic>n</italic>&#x2009;=&#x2009;65) (<xref ref-type="supplementary-material" rid="SM1">Supplementary Table S7</xref>).</p>
<fig position="float" id="fig2">
<label>Figure 2</label>
<caption>
<p>Ecuadorian trend of biomedical publications from 1920 to 2021. The solid vertical line shows the year of the launching of the Higher Education Law (LOES, Spanish acronym).</p>
</caption>
<graphic xlink:href="fmed-11-1395433-g002.tif"/>
</fig>
<fig position="float" id="fig3">
<label>Figure 3</label>
<caption>
<p>Trend of biomedical production in Ecuador according to the study design used (<italic>n</italic> =&#x2009;3,225). The published studies that did not use a classic epidemiological design were counted in the &#x201C;other&#x201D; category; this category includes mainly basic science studies conducted in a laboratory setting.</p>
</caption>
<graphic xlink:href="fmed-11-1395433-g003.tif"/>
</fig>
<table-wrap position="float" id="tab1">
<label>Table 1</label>
<caption>
<p>Study characteristics and main producers of Ecuadorian biomedical sciences-related publications, 1920&#x2013;2021.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="top">Characteristic</th>
<th align="center" valign="top">Total<break/><italic>n</italic>&#x2009;=&#x2009;3,225</th>
<th align="center" valign="top">Public University<break/><italic>n</italic>&#x2009;=&#x2009;632</th>
<th align="center" valign="top">Private University<break/><italic>n</italic>&#x2009;=&#x2009;1,294</th>
<th align="center" valign="top">Mixed University<break/><italic>n</italic>&#x2009;=&#x2009;331</th>
<th align="center" valign="top">Non-academic Institution<sup>&#x00B6;</sup><break/><italic>n</italic>&#x2009;=&#x2009;968</th>
<th align="center" valign="top"><italic>p</italic>-value<sup>&#x002A;</sup></th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top">SCImago journal rank, <italic>n</italic> (%)</td>
<td/>
<td/>
<td/>
<td/>
<td/>
<td align="char" valign="top" char=".">&#x003C;0.001</td>
</tr>
<tr>
<td align="left" valign="top">Q1</td>
<td align="char" valign="top" char="(">1,397 (43.32)</td>
<td align="char" valign="top" char="(">239 (37.81)</td>
<td align="char" valign="top" char="(">538 (41.57)</td>
<td align="char" valign="top" char="(">119 (35.95)</td>
<td align="char" valign="top" char="(">501 (51.75)</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">Q2</td>
<td align="char" valign="top" char="(">738 (22.88)</td>
<td align="char" valign="top" char="(">134 (21.20)</td>
<td align="char" valign="top" char="(">296 (22.87)</td>
<td align="char" valign="top" char="(">79 (23.87)</td>
<td align="char" valign="top" char="(">229 (23.65)</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">Q3</td>
<td align="char" valign="top" char="(">421 (13.05)</td>
<td align="char" valign="top" char="(">90 (14.24)</td>
<td align="char" valign="top" char="(">174 (13.45)</td>
<td align="char" valign="top" char="(">37 (11.18)</td>
<td align="char" valign="top" char="(">120 (12.40)</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">Q4</td>
<td align="char" valign="top" char="(">579 (17.95)</td>
<td align="char" valign="top" char="(">152 (24.05)</td>
<td align="char" valign="top" char="(">238 (18.39)</td>
<td align="char" valign="top" char="(">87 (26.28)</td>
<td align="char" valign="top" char="(">102 (10.54)</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">None</td>
<td align="char" valign="top" char="(">90 (2.79)</td>
<td align="char" valign="top" char="(">17 (2.69)</td>
<td align="char" valign="top" char="(">48 (3.71)</td>
<td align="char" valign="top" char="(">9 (2.72)</td>
<td align="char" valign="top" char="(">16 (1.65)</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">Study design, <italic>n</italic> (%)</td>
<td/>
<td/>
<td/>
<td/>
<td/>
<td align="char" valign="top" char=".">&#x2013;</td>
</tr>
<tr>
<td align="left" valign="top">Case/series report</td>
<td align="char" valign="top" char="(">18 (0.56)</td>
<td align="char" valign="top" char="(">3 (0.47)</td>
<td align="char" valign="top" char="(">6 (0.46)</td>
<td align="char" valign="top" char="(">3 (0.91)</td>
<td align="char" valign="top" char="(">6 (0.62)</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">Ecological</td>
<td align="char" valign="top" char="(">152 (4.71)</td>
<td align="char" valign="top" char="(">20 (3.16)</td>
<td align="char" valign="top" char="(">23 (1.78)</td>
<td align="char" valign="top" char="(">9 (2.72)</td>
<td align="char" valign="top" char="(">100 (10.33)</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">Cross-sectional/survey</td>
<td align="char" valign="top" char="(">1,602 (49.67)</td>
<td align="char" valign="top" char="(">331 (52.37)</td>
<td align="char" valign="top" char="(">676 (52.24)</td>
<td align="char" valign="top" char="(">187 (56.50)</td>
<td align="char" valign="top" char="(">408 (42.15)</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">Case-control</td>
<td align="char" valign="top" char="(">135 (4.19)</td>
<td align="char" valign="top" char="(">23 (3.64)</td>
<td align="char" valign="top" char="(">80 (6.18)</td>
<td align="char" valign="top" char="(">19 (5.74)</td>
<td align="char" valign="top" char="(">13 (1.34)</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">Cohort</td>
<td align="char" valign="top" char="(">504 (15.63)</td>
<td align="char" valign="top" char="(">51 (8.07)</td>
<td align="char" valign="top" char="(">253 (19.55)</td>
<td align="char" valign="top" char="(">36 (10.88)</td>
<td align="char" valign="top" char="(">164 (16.94)</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">Randomized clinical trial</td>
<td align="char" valign="top" char="(">114 (3.53)</td>
<td align="char" valign="top" char="(">35 (5.54)</td>
<td align="char" valign="top" char="(">27 (2.09)</td>
<td align="char" valign="top" char="(">3 (0.91)</td>
<td align="char" valign="top" char="(">49 (5.06)</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">Systematic review</td>
<td align="char" valign="top" char="(">137 (4.25)</td>
<td align="char" valign="top" char="(">24 (3.79)</td>
<td align="char" valign="top" char="(">40 (3.09)</td>
<td align="char" valign="top" char="(">9 (2.72)</td>
<td align="char" valign="top" char="(">64 (6.61)</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">Meta-analysis</td>
<td align="char" valign="top" char="(">11 (0.34)</td>
<td align="char" valign="top" char="(">1 (0.15)</td>
<td align="char" valign="top" char="(">2 (0.15)</td>
<td align="char" valign="top" char="(">&#x2013;</td>
<td align="char" valign="top" char="(">8 (0.82)</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">Other<sup>&#x00B6;&#x00B6;</sup></td>
<td align="char" valign="top" char="(">552 (17.12)</td>
<td align="char" valign="top" char="(">144 (22.78)</td>
<td align="char" valign="top" char="(">187 (14.45)</td>
<td align="char" valign="top" char="(">65 (19.64)</td>
<td align="char" valign="top" char="(">156 (16.11)</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">Research focus, <italic>n</italic> (%)</td>
<td/>
<td/>
<td/>
<td/>
<td/>
<td align="char" valign="top" char=".">&#x003C;0.001</td>
</tr>
<tr>
<td align="left" valign="top">Basic science</td>
<td align="char" valign="top" char="(">315 (9.77)</td>
<td align="char" valign="top" char="(">71 (11.23)</td>
<td align="char" valign="top" char="(">140 (10.82)</td>
<td align="char" valign="top" char="(">38 (11.48)</td>
<td align="char" valign="top" char="(">66 (6.82)</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">Clinical</td>
<td align="char" valign="top" char="(">1,691 (52.43)</td>
<td align="char" valign="top" char="(">297 (46.99)</td>
<td align="char" valign="top" char="(">719 (55.56)</td>
<td align="char" valign="top" char="(">171 (51.66)</td>
<td align="char" valign="top" char="(">504 (52.07)</td>
<td/>
</tr>
<tr>
<td align="left" valign="top">Public health</td>
<td align="char" valign="top" char="(">1,219 (37.79)</td>
<td align="char" valign="top" char="(">264 (41.77)</td>
<td align="char" valign="top" char="(">435 (33.62)</td>
<td align="char" valign="top" char="(">122 (36.86)</td>
<td align="char" valign="top" char="(">398 (41.12)</td>
<td/>
</tr>
</tbody>
</table>
<table-wrap-foot>
<p><sup>&#x002A;</sup>Categorical data was analyzed using chi-square test.</p>
<p><sup>&#x00B6;</sup>Non-academic institutions encompass hospitals/clinics, governmental agencies, and NGOs.</p>
<p><sup>&#x00B6;&#x00B6;</sup>This category refers to research conducted in a laboratory setting (traditional medicine, genetic/molecular analysis) or any kind of computational modeling research.</p>
</table-wrap-foot>
</table-wrap>
</sec>
<sec id="sec13">
<label>3.2</label>
<title>Main producers of biomedical research</title>
<p>Overall (1920&#x2013;2021), private universities were the largest producer of biomedical research at the local level, followed by non-academic institutions (hospitals/clinics, ministry of public health, and non-governmental organizations), 40.12% (<italic>n</italic>&#x2009;=&#x2009;1,294) vs. 30.01% (<italic>n</italic>&#x2009;=&#x2009;968), respectively (<xref ref-type="table" rid="tab1">Table 1</xref>). Regarding the impact and quality of publications, non-academic institutions had the highest percentage of publications in Q1 journals, followed by private universities, 51.75% vs. 41.57%, respectively; <italic>p</italic>-value &#x003C; 0.001 (<xref ref-type="table" rid="tab1">Table 1</xref>). When analyzing the data by Higher Education Institutions (HEIs) only, we found that the three universities with the highest production were: Pontificia Universidad Cat&#x00F3;lica del Ecuador (11.06%, <italic>n</italic>&#x2009;=&#x2009;357), Universidad San Francisco de Quito USFQ (10.97%, <italic>n</italic>&#x2009;=&#x2009;354), and Universidad Central del Ecuador (10.60%, <italic>n</italic>&#x2009;=&#x2009;342) (<xref ref-type="fig" rid="fig4">Figure 4</xref>). This trend varied after standardizing research output by number of health-related students; thus, Universidad San Francisco de Quito USFQ and Universidad Esp&#x00ED;ritu Santo had the highest production per 1,000 students&#x2014;295 and 239 publications, respectively (<xref ref-type="supplementary-material" rid="SM1">Supplementary Table S8</xref>). It is worth mentioning that Pontificia Universidad Cat&#x00F3;lica del Ecuador, Universidad San Francisco de Quito USFQ, and Universidad Central del Ecuador have undergraduate and graduate programs in health sciences, with Universidad Central del Ecuador in operation for more than 180&#x2009;years (<xref ref-type="supplementary-material" rid="SM1">Supplementary Table S8</xref>). However, other higher education institutions without a faculty or academic college for the study of medicine/health sciences also registered biomedical publications, as was the case of the Escuela Superior Polit&#x00E9;cnica del Litoral (ESPOL) (<xref ref-type="fig" rid="fig4">Figure 4</xref>). The cross-sectional design was the most used by both researchers and universities, with a predominance of research carried out in collaboration between private and public universities (56.50%) (Mixed University) (<xref ref-type="table" rid="tab1">Table 1</xref>; <xref ref-type="fig" rid="fig5">Figure 5</xref>). Studies with greater methodological complexity, such as cohort studies and randomized clinical trials, were carried out in a higher percentage by private and public universities, 19.55% vs. 5.54%, respectively. It is worth mentioning that public universities in the country registered a higher percentage of research classified as &#x201C;other&#x201D; (22.78%, <italic>n</italic>&#x2009;=&#x2009;144). This category encompasses research conducted in a laboratory facility to study traditional medicine, genetic/molecular analysis, or studies of any kind of computational modeling research. This finding was aligned with the data by research focus, where public universities and mixed collaboration (public and private) had a high percentage of publications in basic sciences (22.71%). In contrast, private universities had a higher contribution in the area of clinical sciences, with 55.56%. Finally, public universities together with non-academic institutions registered the highest contributions in the area of public health at the local level, 41.77% vs. 41.12%, respectively (<xref ref-type="table" rid="tab1">Table 1</xref>).</p>
<fig position="float" id="fig4">
<label>Figure 4</label>
<caption>
<p>Distribution of Ecuadorian biomedical publications by university and SCImago ranking quartile.</p>
</caption>
<graphic xlink:href="fmed-11-1395433-g004.tif"/>
</fig>
<fig position="float" id="fig5">
<label>Figure 5</label>
<caption>
<p>Distribution of Ecuadorian biomedical publications by type of design study used and university.</p>
</caption>
<graphic xlink:href="fmed-11-1395433-g005.tif"/>
</fig>
</sec>
<sec id="sec14">
<label>3.3</label>
<title>Lines of research and focus on the main causes of mortality</title>
<p>The analysis of the lines of research shows that 23.44% of the publications focus on epidemiology and surveillance system of diseases, followed by diagnosis and treatment research (17.21%) and research on causes of diseases (16.62%) (<xref ref-type="table" rid="tab2">Table 2</xref>). Public universities in Ecuador, compared to private universities and non-academic institutions, publish more in the lines of research related to early detection and prevention research (5.85%), psychosocial aspects of diseases (15.66%), and other (4.43%). On the other hand, private universities focus on research related to research on causes of diseases (21.33%), and non-academic institutions focus mainly on epidemiology and surveillance system of diseases (26.55%) (<xref ref-type="table" rid="tab2">Table 2</xref>). According to INEC, 18.54% (<italic>n</italic>&#x2009;=&#x2009;598) of the total research produced during the century 1920&#x2013;2021 was associated with the main causes of mortality. Sixty-two percent of these publications had clinical areas as their main research focus (<xref ref-type="supplementary-material" rid="SM1">Supplementary Figure S1</xref>). The private university (self-and co-financed) in Ecuador contributed the most to this research compared to public universities, 39.97% (<italic>n</italic>&#x2009;=&#x2009;239/598) vs. 16.72% (<italic>n</italic>&#x2009;=&#x2009;100/598), respectively. For example, the three universities with the highest contributions were Universidad Esp&#x00ED;ritu Santo (UEES), Universidad de las Am&#x00E9;ricas (UDLA), and Universidad Central del Ecuador (UCE) (<xref ref-type="fig" rid="fig6">Figure 6</xref>). When removing the publications related to COVID-19 (<italic>n</italic>&#x2009;=&#x2009;194), the trend of the four largest producers of studies related to the main causes of mortality maintained their trend, two private universities with one public university (UESS, UCE, and USFQ in order of frequency) as the largest producers of studies related to the main causes of mortality was maintained (<xref ref-type="supplementary-material" rid="SM1">Supplementary Figure S2</xref>). Thus, only 15.59% (63/404) of public university production is on track to resolve main local causes of mortality compared to private universities at 38.61% (156/404) (<xref ref-type="supplementary-material" rid="SM1">Supplementary Figure S3</xref>). <xref ref-type="table" rid="tab3">Table 3</xref> shows the percentage of biomedical research output dedicated to addressing the leading causes of mortality per decade in Ecuador. Hence, before the 80s, 42.85% of research production was aligned with the main burden of disease for that period of time, and the main producer was non-academic institutions (<italic>n</italic>&#x2009;=&#x2009;5) like International Health Board. Meanwhile, the lowest research output (10.73%) was seen at the beginning of the year 2000, and the main producers during this period were non-academic institutions (<italic>n</italic>&#x2009;=&#x2009;217) and private universities (<italic>n</italic>&#x2009;=&#x2009;116) (<xref ref-type="supplementary-material" rid="SM1">Supplementary Table S9</xref>). It is worth mentioning that during the years 2011&#x2013;2021, the scientific production related to the main and historical causes of mortality (e.g., cardiovascular disease, diabetes, cancer, etc.) was over-represented due to the COVID-19 effect. Thus, after removing COVID-19 related publications, the percentage of scientific output dedicated to addressing classical main causes of mortality during 2011&#x2013;2021 decreased to 12.43%. The following causes of mortality were the highest researched per decade: infectious and parasitic disease (<italic>n</italic>&#x2009;=&#x2009;3, 42.85% [years &#x003C;1980]), other protein-energy malnutrition (<italic>n</italic>&#x2009;=&#x2009;3, 17.6% [years 1980&#x2013;1989]), malnutrition (<italic>n</italic>&#x2009;=&#x2009;6, 12.8% [years 1990&#x2013;1999]), certain conditions originating in the prenatal and perinatal period (<italic>n</italic>&#x2009;=&#x2009;10, 2.4% [years 2000&#x2013;2010]), and diabetes mellitus (<italic>n</italic>&#x2009;=&#x2009;59, 2.1% [years 2011&#x2013;2021]). Regarding which institutions were the main scientific drivers of publications aligned with the principal causes of mortality, we found that non-academic and public institutions led the production at the beginning of the analysis period. However, after the decade 2000, private universities took the lead as the main scientific producers in the country, and this trend is consistent after analyzing overall production and only INEC-related publications (<xref ref-type="fig" rid="fig7">Figure 7</xref>; <xref ref-type="supplementary-material" rid="SM1">Supplementary Figure S4</xref>).</p>
<table-wrap position="float" id="tab2">
<label>Table 2</label>
<caption>
<p>Distribution of Ecuadorian biomedical sciences-related publications by research line and type of university.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="top">Research lines, <italic>n</italic> (%)</th>
<th align="center" valign="top">Total<break/><italic>n</italic>&#x2009;=&#x2009;3,225</th>
<th align="center" valign="top">Public University<break/><italic>n</italic>&#x2009;=&#x2009;632</th>
<th align="center" valign="top">Private University<break/><italic>n</italic>&#x2009;=&#x2009;1,294</th>
<th align="center" valign="top">Mixed University<break/><italic>n</italic>&#x2009;=&#x2009;331</th>
<th align="center" valign="top">Non-academic Institution<break/><italic>n</italic>&#x2009;=&#x2009;968</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top">Epidemiology and surveillance system of diseases</td>
<td align="char" valign="top" char="(">756 (23.44)</td>
<td align="char" valign="top" char="(">135 (21.36)</td>
<td align="char" valign="top" char="(">268 (20.71)</td>
<td align="char" valign="top" char="(">96 (29.00)</td>
<td align="char" valign="top" char="(">257 (26.55)</td>
</tr>
<tr>
<td align="left" valign="top">Research on causes of diseases</td>
<td align="char" valign="top" char="(">536 (16.62)</td>
<td align="char" valign="top" char="(">93 (14.71)</td>
<td align="char" valign="top" char="(">276 (21.33)</td>
<td align="char" valign="top" char="(">54 (16.31)</td>
<td align="char" valign="top" char="(">113 (11.67)</td>
</tr>
<tr>
<td align="left" valign="top">Biology research of diseases (molecular and cellular mechanisms)</td>
<td align="char" valign="top" char="(">387 (12)</td>
<td align="char" valign="top" char="(">81 (12.81)</td>
<td align="char" valign="top" char="(">173 (13.37)</td>
<td align="char" valign="top" char="(">45 (13.60)</td>
<td align="char" valign="top" char="(">88 (9.09)</td>
</tr>
<tr>
<td align="left" valign="top">Early detection and prevention research</td>
<td align="char" valign="top" char="(">176 (5.46)</td>
<td align="char" valign="top" char="(">37 (5.85)</td>
<td align="char" valign="top" char="(">69 (5.33)</td>
<td align="char" valign="top" char="(">18 (5.44)</td>
<td align="char" valign="top" char="(">52 (5.37)</td>
</tr>
<tr>
<td align="left" valign="top">Diagnosis and treatment research</td>
<td align="char" valign="top" char="(">555 (17.21)</td>
<td align="char" valign="top" char="(">99 (15.66)</td>
<td align="char" valign="top" char="(">178 (13.76)</td>
<td align="char" valign="top" char="(">47 (14.20)</td>
<td align="char" valign="top" char="(">231 (23.86)</td>
</tr>
<tr>
<td align="left" valign="top">Provision of health services</td>
<td align="char" valign="top" char="(">177 (5.48)</td>
<td align="char" valign="top" char="(">36 (5.70)</td>
<td align="char" valign="top" char="(">57 (4.40)</td>
<td align="char" valign="top" char="(">12 (3.63)</td>
<td align="char" valign="top" char="(">72 (7.44)</td>
</tr>
<tr>
<td align="left" valign="top">Psychosocial aspects of diseases</td>
<td align="char" valign="top" char="(">384 (11.90)</td>
<td align="char" valign="top" char="(">99 (15.66)</td>
<td align="char" valign="top" char="(">194 (14.99)</td>
<td align="char" valign="top" char="(">43 (12.99)</td>
<td align="char" valign="top" char="(">48 (4.96)</td>
</tr>
<tr>
<td align="left" valign="top">Public policy</td>
<td align="char" valign="top" char="(">151 (4.68)</td>
<td align="char" valign="top" char="(">24 (3.80)</td>
<td align="char" valign="top" char="(">44 (3.40)</td>
<td align="char" valign="top" char="(">8 (2.42)</td>
<td align="char" valign="top" char="(">75 (7.75)</td>
</tr>
<tr>
<td align="left" valign="top">Other</td>
<td align="char" valign="top" char="(">103 (3.19)</td>
<td align="char" valign="top" char="(">28 (4.43)</td>
<td align="char" valign="top" char="(">35 (2.70)</td>
<td align="char" valign="top" char="(">8 (2.42)</td>
<td align="char" valign="top" char="(">32 (3.31)</td>
</tr>
</tbody>
</table>
</table-wrap>
<fig position="float" id="fig6">
<label>Figure 6</label>
<caption>
<p>Distribution of biomedical production related to the main causes of mortality by higher education institutions.</p>
</caption>
<graphic xlink:href="fmed-11-1395433-g006.tif"/>
</fig>
<table-wrap position="float" id="tab3">
<label>Table 3</label>
<caption>
<p>Distribution of Ecuadorian biomedical research output and leading causes of mortality per decade, 1920&#x2013;2021.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="top">Ranking</th>
<th align="left" valign="top">&#x003C;1980<break/><italic>n</italic>&#x2009;=&#x2009;7</th>
<th align="center" valign="top"><italic>n</italic> (%)</th>
<th align="left" valign="top">1980&#x2013;1989<break/><italic>n</italic>&#x2009;=&#x2009;17</th>
<th align="center" valign="top"><italic>n</italic> (%)</th>
<th align="left" valign="top">1990&#x2013;1999<break/><italic>n</italic>&#x2009;=&#x2009;47</th>
<th align="center" valign="top"><italic>n</italic> (%)</th>
<th align="left" valign="top">2000&#x2013;2010<break/><italic>n</italic>&#x2009;=&#x2009;410</th>
<th align="center" valign="top"><italic>n</italic> (%)</th>
<th align="left" valign="top">2011&#x2013;2021<break/><italic>n</italic>&#x2009;=&#x2009;2,744</th>
<th align="center" valign="top"><italic>n</italic> (%)</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top">1</td>
<td align="left" valign="top">Infectious and parasitic diseases</td>
<td align="center" valign="top">3 (42.85)</td>
<td align="left" valign="top">Intestinal infectious diseases</td>
<td align="center" valign="top">1 (5.9)</td>
<td align="left" valign="top">Cerebrovascular disease</td>
<td align="center" valign="top">2 (4.3)</td>
<td align="left" valign="top">Cerebrovascular disease</td>
<td align="center" valign="top">3 (0.73)</td>
<td align="left" valign="top">Diabetes mellitus</td>
<td align="center" valign="top">59 (2.1)</td>
</tr>
<tr>
<td align="left" valign="top">2</td>
<td align="left" valign="top">Tuberculosis</td>
<td align="center" valign="top">&#x2013;</td>
<td align="left" valign="top">Pneumonia</td>
<td align="center" valign="top">&#x2013;</td>
<td align="left" valign="top">Pneumonia</td>
<td align="center" valign="top">1 (2.1)</td>
<td align="left" valign="top">Diabetes mellitus</td>
<td align="center" valign="top">5 (1.21)</td>
<td align="left" valign="top">Hypertension</td>
<td align="center" valign="top">48 (1.7)</td>
</tr>
<tr>
<td align="left" valign="top">3</td>
<td align="left" valign="top">Intestinal infectious diseases</td>
<td align="center" valign="top">&#x2013;</td>
<td align="left" valign="top">Cerebrovascular disease</td>
<td align="center" valign="top">&#x2013;</td>
<td align="left" valign="top">Intestinal infectious diseases</td>
<td align="center" valign="top">2 (4.3)</td>
<td align="left" valign="top">Hypertension</td>
<td align="center" valign="top">5 (1.21)</td>
<td align="left" valign="top">Cerebrovascular disease</td>
<td align="center" valign="top">54 (1.4)</td>
</tr>
<tr>
<td align="left" valign="top">4</td>
<td align="left" valign="top">Heart diseases</td>
<td align="center" valign="top">&#x2013;</td>
<td align="left" valign="top">Bronchitis, emphysema, and asthma</td>
<td align="center" valign="top">&#x2013;</td>
<td align="left" valign="top">Ischemic heart disease</td>
<td align="center" valign="top">&#x2013;</td>
<td align="left" valign="top">Influenza and pneumonia</td>
<td align="center" valign="top">9 (2.2)</td>
<td align="left" valign="top">Dementia and Alzheimer&#x2019;s disease</td>
<td align="center" valign="top">9 (0.32)</td>
</tr>
<tr>
<td align="left" valign="top">5</td>
<td align="left" valign="top">Cancer</td>
<td align="center" valign="top">&#x2013;</td>
<td align="left" valign="top">Road traffic injuries</td>
<td align="center" valign="top">&#x2013;</td>
<td align="left" valign="top">Road traffic injuries</td>
<td align="center" valign="top">&#x2013;</td>
<td align="left" valign="top">Ischemic heart disease</td>
<td align="center" valign="top">1 (0.24)</td>
<td align="left" valign="top">Road traffic injuries</td>
<td align="center" valign="top">16 (0.5)</td>
</tr>
<tr>
<td align="left" valign="top">6</td>
<td align="left" valign="top">Vascular diseases of the central nervous system</td>
<td align="center" valign="top">&#x2013;</td>
<td align="left" valign="top">Ischemic heart disease</td>
<td align="center" valign="top">&#x2013;</td>
<td align="left" valign="top">Violence/homicide</td>
<td align="center" valign="top">&#x2013;</td>
<td align="left" valign="top">Violence/homicide</td>
<td align="center" valign="top">1 (0.24)</td>
<td align="left" valign="top">Influenza and pneumonia</td>
<td align="center" valign="top">37 (1.3)</td>
</tr>
<tr>
<td align="left" valign="top">7</td>
<td align="left" valign="top">Violence/homicide</td>
<td align="center" valign="top">&#x2013;</td>
<td align="left" valign="top">Other protein-energy malnutrition</td>
<td align="center" valign="top">3 (17.6)</td>
<td align="left" valign="top">Bronchitis, emphysema, and asthma</td>
<td align="center" valign="top">&#x2013;</td>
<td align="left" valign="top">Road traffic injuries</td>
<td align="center" valign="top">3 (0.73)</td>
<td align="left" valign="top">Violence/homicide</td>
<td align="center" valign="top">10 (0.3)</td>
</tr>
<tr>
<td align="left" valign="top">8</td>
<td/>
<td/>
<td align="left" valign="top">Tuberculosis</td>
<td align="center" valign="top">&#x2013;</td>
<td align="left" valign="top">Diabetes mellitus</td>
<td align="center" valign="top">1 (2.1)</td>
<td align="left" valign="top">Liver diseases</td>
<td align="center" valign="top">&#x2013;</td>
<td align="left" valign="top">Ischemic heart disease</td>
<td align="center" valign="top">20 (0.7)</td>
</tr>
<tr>
<td align="left" valign="top">9</td>
<td/>
<td/>
<td align="left" valign="top">Stomach cancer</td>
<td align="center" valign="top">&#x2013;</td>
<td align="left" valign="top">Stomach cancer</td>
<td align="center" valign="top">&#x2013;</td>
<td align="left" valign="top">Stomach cancer</td>
<td align="center" valign="top">&#x2013;</td>
<td align="left" valign="top">Cirrhosis and other chronic liver diseases</td>
<td align="center" valign="top">8 (0.29)</td>
</tr>
<tr>
<td align="left" valign="top">10</td>
<td/>
<td/>
<td align="left" valign="top">Measles</td>
<td align="center" valign="top">&#x2013;</td>
<td align="left" valign="top">Tuberculosis</td>
<td align="center" valign="top">&#x2013;</td>
<td align="left" valign="top">Malnutrition</td>
<td align="center" valign="top">5 (1.22)</td>
<td align="left" valign="top">Immuno-preventable diseases</td>
<td align="center" valign="top">22 (0.8)</td>
</tr>
<tr>
<td align="left" valign="top">11</td>
<td/>
<td/>
<td align="left" valign="top">Violence/homicide</td>
<td align="center" valign="top">&#x2013;</td>
<td align="left" valign="top">Hypertension</td>
<td align="center" valign="top">&#x2013;</td>
<td align="left" valign="top">Other heart diseases (heart failure and arrest)</td>
<td align="center" valign="top">1 (0.24)</td>
<td align="left" valign="top">Heart failure, complications and ill-defined diseases</td>
<td align="center" valign="top">5 (0.18)</td>
</tr>
<tr>
<td align="left" valign="top">12</td>
<td/>
<td/>
<td/>
<td/>
<td align="left" valign="top">Nephritis, nephrotic syndrome, and nephrosis</td>
<td align="center" valign="top">&#x2013;</td>
<td align="left" valign="top">Certain conditions originating in the prenatal and perinatal period</td>
<td align="center" valign="top">10 (2.4)</td>
<td align="left" valign="top">Urinary system diseases</td>
<td align="center" valign="top">10 (0.3)</td>
</tr>
<tr>
<td align="left" valign="top">13</td>
<td/>
<td/>
<td/>
<td/>
<td align="left" valign="top">Cirrhosis and other chronic liver diseases</td>
<td align="center" valign="top">&#x2013;</td>
<td align="left" valign="top">Urinary system diseases</td>
<td align="center" valign="top">1 (0.24)</td>
<td align="left" valign="top">Stomach cancer</td>
<td align="center" valign="top">4 (0.14)</td>
</tr>
<tr>
<td align="left" valign="top">14</td>
<td/>
<td/>
<td/>
<td/>
<td align="left" valign="top">Malnutrition</td>
<td align="center" valign="top">6 (12.8)</td>
<td/>
<td/>
<td align="left" valign="top">Chronic diseases of the lower respiratory tract</td>
<td align="center" valign="top">15 (0.5)</td>
</tr>
<tr>
<td align="left" valign="top">15</td>
<td/>
<td/>
<td/>
<td/>
<td/>
<td/>
<td/>
<td/>
<td align="left" valign="top">Certain conditions originating in the prenatal period</td>
<td align="center" valign="top">24 (0.8)</td>
</tr>
<tr>
<td align="left" valign="top">16</td>
<td/>
<td/>
<td/>
<td/>
<td/>
<td/>
<td/>
<td/>
<td align="left" valign="top">COVID-19</td>
<td align="center" valign="top">194 (7.0)</td>
</tr>
<tr>
<td align="left" valign="top">n (%)</td>
<td/>
<td align="center" valign="top">3 (42.85)</td>
<td/>
<td align="center" valign="top">4 (23.53)</td>
<td/>
<td align="center" valign="top">12 (25.53)</td>
<td/>
<td align="center" valign="top">44 (10.73)</td>
<td/>
<td align="center" valign="top">535 (19.50)</td>
</tr>
</tbody>
</table>
</table-wrap>
<fig position="float" id="fig7">
<label>Figure 7</label>
<caption>
<p>Time trend of Ecuadorian biomedical publications by institution producer (<italic>n</italic>&#x2009;=&#x2009;3,225).</p>
</caption>
<graphic xlink:href="fmed-11-1395433-g007.tif"/>
</fig>
</sec>
<sec id="sec15">
<label>3.4</label>
<title>International collaboration and distribution by geographic area</title>
<p>Overall, foreign universities/institutions contributed to 70.97% (2,289/3,225) of the scientific output. Ecuadorian researchers collaborated mostly with the following countries: (i) United States (32.77%, <italic>n</italic>&#x2009;=&#x2009;1,057), (ii) Spain (9.52%, <italic>n</italic>&#x2009;=&#x2009;307), Brazil (7.63%, <italic>n</italic>&#x2009;=&#x2009;246), United Kingdom (6.48%, <italic>n</italic>&#x2009;=&#x2009;209), and Colombia (4.28%, <italic>n</italic>&#x2009;=&#x2009;138) (<xref ref-type="fig" rid="fig8">Figure 8</xref>). The Ecuadorian institutions with the highest number of jointly publications with the United States in descending order are: Universidad San Francisco de Quito USFQ (<italic>n</italic>&#x2009;=&#x2009;166), MSP (<italic>n</italic>&#x2009;=&#x2009;160), Universidad Esp&#x00ED;ritu Santo (<italic>n</italic>&#x2009;=&#x2009;129), Pontificia Universidad Cat&#x00F3;lica del Ecuador (<italic>n</italic>&#x2009;=&#x2009;116). This international collaboration has catalyzed research projects in several areas including environmental health due to exposure to pesticides, vector-borne zoonotic diseases, and gastrointestinal pathologies (<xref ref-type="supplementary-material" rid="SM1">Supplementary Table S10</xref>). Regarding the local distribution of scientific production in biomedicine, we found that the provinces of Pichincha (<italic>n</italic>&#x2009;=&#x2009;1,686), Guayas (<italic>n</italic>&#x2009;=&#x2009;822), and Azuay (<italic>n</italic>&#x2009;=&#x2009;319) are the largest producers of scientific articles, together contributing 87.66% (<italic>n</italic>&#x2009;=&#x2009;2,827) of the total produced during the period of analysis (<xref ref-type="supplementary-material" rid="SM1">Supplementary Figure S5</xref>). The focus of research in clinical areas is predominant in the great majority of the 24 provinces of the country, with the exception of Napo province, which registers more research in the area of basic sciences (<xref ref-type="supplementary-material" rid="SM1">Supplementary Figure S6</xref>). Similarly, the lines of research related to epidemiology and surveillance system of diseases, diagnosis and treatment research, and research on causes of diseases are the most studied at the provincial level (<xref ref-type="fig" rid="fig9">Figure 9</xref>).</p>
<fig position="float" id="fig8">
<label>Figure 8</label>
<caption>
<p>International collaboration according to number of biomedical publications.</p>
</caption>
<graphic xlink:href="fmed-11-1395433-g008.tif"/>
</fig>
<fig position="float" id="fig9">
<label>Figure 9</label>
<caption>
<p>Distribution of Ecuadorian biomedical production by research lines and per province (<italic>n</italic>&#x2009;=&#x2009;3,225).</p>
</caption>
<graphic xlink:href="fmed-11-1395433-g009.tif"/>
</fig>
</sec>
</sec>
<sec sec-type="discussion" id="sec16">
<label>4</label>
<title>Discussion</title>
<p>This research provides an overview of biomedical research in the last century in Ecuador, highlighting the following findings: (i) Exponential increase in scientific production during the last decade, (ii) Predominance of cross-sectional observational studies and studies related to basic biomedical sciences, (iii) Private universities as the largest producers of biomedical research in the country (40.12%), and (iv) Mismatch between the main causes of mortality and local scientific production.</p>
<sec id="sec17">
<label>4.1</label>
<title>Comparison with other studies</title>
<p>Biomedical research in Ecuador has traditionally been scarce and mostly of a descriptive observational type, until the last decade where an exponential increase in scientific production is evident (<xref ref-type="bibr" rid="ref16">16</xref>, <xref ref-type="bibr" rid="ref22">22</xref>, <xref ref-type="bibr" rid="ref23">23</xref>). This increase, we believe, is mainly due to the effect that the LOES has had on the country&#x2019;s higher education system through the creation of The Council for the Evaluation, Accreditation, and Quality Assurance of Higher Education (CEAACES) in 2011 (<xref ref-type="bibr" rid="ref16">16</xref>, <xref ref-type="bibr" rid="ref22">22</xref>). The CEAACES designed an evaluation model for both public and private universities, one of the parameters being &#x201C;research&#x201D; with a weight of 21% of the overall evaluation. Thus, HEIs that had publications indexed in SCImago, Scopus, or WoS received a better evaluation and ranking within the Ecuadorian higher education system (<xref ref-type="bibr" rid="ref22">22</xref>). This generated a pressure effect on Ecuadorian HEIs and their researchers to increase publication of scientific papers. Among the positive effects of this pressure, local HEIs incorporated mechanisms to stimulate and strengthen research such as hiring research professors with terminal academic degrees (e.g., PhD), reducing teaching hours to dedicate them to research activities, investing in infrastructure such as laboratories, creating internal seed funds, internationalizing policies to attract foreign funds and expertise, and establishing a research culture (<xref ref-type="bibr" rid="ref23">23</xref>, <xref ref-type="bibr" rid="ref24">24</xref>). Additionally, at the government level, funding for research production initially came through the implementation of two programs. The first consisted of a study-abroad grant program for students and faculty members to obtain bachelor and terminal (MS/PhD) degrees in foreign universities. Until 2016 this program benefited about 5,715 Ecuadorian citizens, 21.9% of whom received scholarships in the area of health and wellbeing (<xref ref-type="bibr" rid="ref25">25</xref>). The second program, called &#x201C;Prometeo-Viejos Sabios,&#x201D; was designed to bring foreign researcher expertise to Ecuador to strengthen local research capacity (<xref ref-type="bibr" rid="ref12">12</xref>). &#x201C;Prometeo-Viejos Sabios&#x201D; ended in 2017, but during its execution, it was able to bring 1,046 foreign researchers to Ecuador (8% belonging to health areas) and produced more than 400 documents indexed in Scopus (<xref ref-type="bibr" rid="ref15">15</xref>). Both programs were available for public and private HEIs. In 2018 the Secretary of Higher Education, Science, Technology, and Innovation (SENESCYT) of Ecuador created a national program for funding research initiatives called &#x201C;IN&#x00C9;DITA.&#x201D; This program grants $50,000 USD for individual projects and up to $200,000 USD for collaborative research projects (<xref ref-type="bibr" rid="ref26">26</xref>). However, despite the positive effects of the LOES/CEAACES to catalyze biomedical research in Ecuador, we also identify negative effects such as a decrease in the performance of studies with higher level of evidence, such as prospective cohorts or randomized clinical trials to inform health policy-making. Several factors could explain this observation including that these types of studies demand greater financial, logistical, and time resources (<xref ref-type="bibr" rid="ref16">16</xref>). Other contributing factors include inadequate financial investment by the local governments, unstable political environments, ethical and regulatory system obstacles, and the lack of highly/appropriately qualified researchers (<xref ref-type="bibr" rid="ref4">4</xref>, <xref ref-type="bibr" rid="ref16">16</xref>). This decrease in the generation of studies with higher level of evidence has also been documented elsewhere (<xref ref-type="bibr" rid="ref16">16</xref>, <xref ref-type="bibr" rid="ref27">27</xref>). Also, what is surprising is that the same pressure effect exercised by LOES/CEAACES upon local HEIs for publishing has not contributed to addressing the main causes of mortality and morbidity in Ecuador. One example of this finding is that chronic malnutrition in children under 5&#x2009;years of age continues to be a major public health concern with catastrophic and permanent effects on Ecuadorian children (<xref ref-type="bibr" rid="ref9">9</xref>). On the other hand, it is important to highlight the high production (17.12%) of local research not related to classic epidemiological designs, which mainly reflects the publication of research at the level of basic sciences in biomedicine. However, compared with neighboring countries such as Colombia, which reported 47.9% of research in the basic sciences during the period 1993&#x2013;2003, the Ecuadorian production is lower (<xref ref-type="bibr" rid="ref28">28</xref>). In Ecuador, private universities produce more biomedical research (40.12%) than public universities (19.59%). Also, Ecuadorian private universities produce more research aligned to resolving main causes of local mortality compared to public universities, 38.61% vs. 15.59%, respectively. This lower biomedical production by public universities could be explained by several factors, including: (i) Politicization of public universities. Currently, university authorities (e.g., Chancellors) are appointed through internal elections where even high school graduates are required to vote. This has undermined and interfered with the autonomy, independence, and governance of local public universities. Ultimately, this politicization of the Ecuadorian public higher education system weakens its research endeavors and contributions to national human capital formation and societal development as described in other LMICs (<xref ref-type="bibr" rid="ref29">29</xref>). (ii) Incapacity to use research funding due to an inefficient, rigid, and highly bureaucratic management system that causes long wait times to acquire basic laboratory supplies or hire well-qualified human resources. For example, Jan Feyen in his publication entitled &#x201C;WAKE-UP CALL for Ecuador&#x2019;s universities&#x201D; describes an administrative hierarchy within public universities through which all activities must pass, resulting in a huge loss of time. He also observes that contracted staff are required to complete activity reports, which are seldom if ever read in the first place (<xref ref-type="bibr" rid="ref30">30</xref>). (iii) Strong preference for immediate outcomes, which has precluded the realization of long-term and impactful research projects/interventions that assure sustainable funding beyond specific project life cycle. In addition to all this, there are other factors such as the lack of a research culture, overregulation by the state, and lack of funding (<xref ref-type="bibr" rid="ref31">31</xref>). This has resulted in the fact that, in most cases, private universities in Ecuador are better positioned to conduct research and ranked locally and internationally, according to international rankings such as QS World University Ranking and SCImago Institution Rankings (<xref ref-type="bibr" rid="ref32">32</xref>, <xref ref-type="bibr" rid="ref33">33</xref>). It is important to mention that there are public universities that, despite not having health majors, contribute to local health research, as is the case of ESPOL and YACHAY Tech. This could be explained because ESPOL has undergraduate and graduate programs for the study of biology, nutrition, and biotechnology, and YACHAY Tech has undergraduate programs in biology and biotechnology (<xref ref-type="bibr" rid="ref34">34</xref>, <xref ref-type="bibr" rid="ref35">35</xref>). In general, 18.54% (<italic>n</italic>&#x2009;=&#x2009;598) of the total produced during the last 100&#x2009;years in Ecuador is aimed at providing solutions to the main causes of mortality, despite the fact that the MAIS-FCI model, the National Health Research Policy, and the LOES establish that all health research efforts in the country should be aimed at providing solutions to the main causes of mortality (<xref ref-type="bibr" rid="ref11 ref12 ref13">11&#x2013;13</xref>). This percentage decreases to 12.53% when removing publications related to COVID-19, and the mismatch between disease burden and scientific production is more pronounced from the 2000s onwards. This discordance coincides with a local study published in 2021 revealing that only 9% of the scientific production in health sciences was aligned with the main causes of mortality (<xref ref-type="bibr" rid="ref16">16</xref>). Possible causes for this include a weak national policy and unclear agenda on the country&#x2019;s health research priorities, weak role of the Ministry of Public Health of Ecuador in monitoring and supporting the articulation of a national health research system, lack of specific competitive funds for these health priorities, lack of appropriately trained researchers, and the absence of cooperation and communication between researchers and key decision makers. In practice, Ecuadorian researchers prioritize other areas and topics that are not aligned with the main health needs of the population, generating a waste of research efforts carried out locally (<xref ref-type="bibr" rid="ref2">2</xref>, <xref ref-type="bibr" rid="ref36">36</xref>).</p>
</sec>
<sec id="sec18">
<label>4.2</label>
<title>Strengths and weaknesses</title>
<p>Among the strengths of this research are: (i) Use of well-known and extensive databases such as Scopus and WoS, widely used in bibliometric studies for their quality (<xref ref-type="bibr" rid="ref17">17</xref>). (ii) The analysis time of 100&#x2009;years. Previous bibliometric studies conducted in the country have only analyzed up to a maximum of 18&#x2009;years (<xref ref-type="bibr" rid="ref16">16</xref>). (iii) Provision of disaggregated information by universities and regions of the country, and international collaboration that was not available in previous studies (<xref ref-type="bibr" rid="ref16">16</xref>, <xref ref-type="bibr" rid="ref27">27</xref>). Limitations of the current work must also be considered. First, we did not consider the regional database Latindex or Redalyc, so publications written in Spanish could have been omitted, which may explain the lack of scientific publications by some universities with health sciences majors. However, due to the broad period analyzed and the use of two comprehensive databases (Scopus and WoS) (<xref ref-type="bibr" rid="ref17">17</xref>, <xref ref-type="bibr" rid="ref18">18</xref>), we anticipate a minimal effect on the final findings. Second, we did not use other metrics or indices besides mortality to assess the impact of local scientific output besides mortality. In future investigations, it might be possible to use other indices such as disability-adjusted life years (<xref ref-type="bibr" rid="ref36">36</xref>). Third, attributable mortality especially for neglected and/or tropical diseases might be underreported due to errors in national cause-of-death data sets (e.g., INEC), as described elsewhere (<xref ref-type="bibr" rid="ref37">37</xref>).</p>
</sec>
<sec id="sec19">
<label>4.3</label>
<title>Implications of the results</title>
<p>This study provides valuable information for institutions and local decision-makers in charge of formulating and monitoring research and development, higher education, and health policy in Ecuador. One of the findings that was not evident until this study and that calls attention is the low contribution of public universities to research aimed at finding solutions to the main causes of mortality in the country, compared to private universities, 15.59% vs. 38.61%, respectively. Traditionally, public higher education has been considered a central societal resource and public good. In most countries, state-sponsored universities occupy the higher ranks in terms of quality, scientific production, and innovation (<xref ref-type="bibr" rid="ref38">38</xref>). Public universities are called to use tax money in an efficient, responsible, and ethical manner, and therefore, scientific research produced by public universities should be impactful and of high quality in order to improve population health and health equity (<xref ref-type="bibr" rid="ref1">1</xref>). However, this is not the case in Ecuador, where, between 1920 and 2021, only 19.59% (632/3,225) of the overall biomedical production was led by public universities, with only 16.72% (100/598) of production aligned to resolving main causes of mortality, compared to 39.97% (239/598) of production by private universities. The Ecuadorian public university should learn from the good practices of its private counterparts in terms of administrative management and research policies (<xref ref-type="bibr" rid="ref30">30</xref>). On the other hand, the slowdown in the country&#x2019;s production of intervention studies like clinical trials in the country should call us to reflect and identify its potential causes in addition to those previously mentioned. In Ecuador, there is capacity for high-quality and impactful research; an example of this is the country&#x2019;s participation in a clinical trial of COVID-19 vaccine published in The New England Journal of Medicine (<xref ref-type="bibr" rid="ref39">39</xref>). A positive finding that should be supported at all levels is the generation of basic science research in the country; this type of research is essential because the information it provides allows its application in new ways of diagnosing, treating, and preventing diseases (<xref ref-type="bibr" rid="ref40">40</xref>). In 2010, there was evidence of a consultative effort to define health research priorities in Ecuador; however, there are no evaluation and impact reports available for this activity (<xref ref-type="bibr" rid="ref41">41</xref>). Future efforts to prioritize what to research in health at the local level should not only focus on the technical and procedural aspects, but also on ethical values such as transparency, inclusion, and accountability (<xref ref-type="bibr" rid="ref42">42</xref>).</p>
</sec>
</sec>
<sec sec-type="conclusions" id="sec20">
<label>5</label>
<title>Conclusion</title>
<p>Biomedical research in Ecuador was first recorded in 1920. Since then, it has been scarce and mainly focused on parasitic infectious diseases and malnutrition. Since 2010 there has been an exponential growth in biomedical publications, which could be due to the effect that the LOES has had on the Ecuadorian higher education system; however, further analysis is needed to evaluate this trend. During the period analyzed (1920&#x2013;2021), biomedical production was distributed with 52.43% in clinical research, 37.79% in public health, and 9.77% in basic sciences. Private universities are the main generators of biomedical research in the country, and their research efforts are aimed at solving the main causes of local mortality in a higher percentage than their public counterparts. Despite this, there is still a significant mismatch between the burden of disease and local scientific production. Thus, in Ecuador, 18.54% of research produced in a century is destined to solve the main causes of mortality in the country.</p>
</sec>
<sec sec-type="data-availability" id="sec21">
<title>Data availability statement</title>
<p>The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.</p>
</sec>
<sec sec-type="author-contributions" id="sec22">
<title>Author contributions</title>
<p>IS: Writing &#x2013; review &#x0026; editing, Writing &#x2013; original draft, Supervision, Project administration, Methodology, Investigation, Formal analysis, Conceptualization. JC-P: Writing &#x2013; review &#x0026; editing, Visualization, Software, Investigation, Formal analysis, Data curation. MCord: Writing &#x2013; review &#x0026; editing, Methodology, Investigation, Data curation. CV: Writing &#x2013; review &#x0026; editing, Methodology, Investigation, Data curation. MB: Writing &#x2013; review &#x0026; editing, Methodology, Investigation, Data curation. MCora: Writing &#x2013; review &#x0026; editing, Methodology, Investigation, Data curation. GH-F: Writing &#x2013; original draft, Formal analysis, Writing &#x2013; review &#x0026; editing, Supervision, Methodology, Investigation, Conceptualization.</p>
</sec>
</body>
<back>
<sec sec-type="funding-information" id="sec23">
<title>Funding</title>
<p>The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.</p>
</sec>
<ack>
<p>The authors thank Carlos Mora-Frank from Centro de Investigaci&#x00F3;n y Proyectos Aplicados a las Ciencias de la Tierra (CIPAT), Escuela Superior Polit&#x00E9;cnica del Litoral (ESPOL), for his technical support at the beginning of the present research project.</p>
</ack>
<sec sec-type="COI-statement" id="sec24">
<title>Conflict of interest</title>
<p>The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p>
</sec>
<sec sec-type="disclaimer" id="sec25">
<title>Publisher&#x2019;s note</title>
<p>All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.</p>
</sec>
<sec sec-type="supplementary-material" id="sec26">
<title>Supplementary material</title>
<p>The Supplementary material for this article can be found online at: <ext-link xlink:href="https://www.frontiersin.org/articles/10.3389/fmed.2024.1395433/full#supplementary-material" ext-link-type="uri">https://www.frontiersin.org/articles/10.3389/fmed.2024.1395433/full#supplementary-material</ext-link></p>
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