Revisiting the concept of Innovative Developing Countries (IDCs) for its relevance to health innovation and neglected tropical diseases and for the prevention and control of epidemics

<div><p>Introduction</p><p>Countries have traditionally been split into two major groups: developed or industrialized (“the North”) and developing or underdeveloped (“the South”). Several authors and organizations have challenged this classification to recognize countries that have reached an intermediate stage of social and economic development. As proposed by Morel and collaborators in 2005, the concept of Innovative Developing Countries (IDCs) defines a group of nations with impactful scientific programs. Here, IDCs are reexamined by a variety of metrics to highlight their role in health innovation through research and development (R&D) programs on neglected tropical diseases (NTDs) that also positively impact epidemic preparedness.</p><p>Results</p><p>To address the global changes due to expanding globalization we updated the original indicator of the number of USPTO patents deposited by individual countries per GDP and per capita to the number of international patents applications, related to applicant residence and deposited under the Patent Cooperation Treaty (PCT) per GNI (or GDP) and per capita. A comparison of the originally described ranking of top innovative countries to those in the present study revealed new members that updated the list of IDCs and showed a prominent role now played by China.</p><p>Analyzing scientific publications in international journals since the introduction of the IDC concept in 2005 we found that IDCs do prioritize Neglected Tropical Diseases (NTDs) as an area of research.</p><p>Finally we investigated the role of IDCs in two major public health emergencies between 2012 and 2016, the outbreaks of Ebola in West Africa and Zika in South America. An analysis of the co-authorship country networks demonstrated an important role for IDC infrastructure and personnel in the prevention and control of these epidemics.</p><p>Discussion and conclusions</p><p>Different techniques can be used to evaluate and measure innovative performance of countries. Country rankings published by traditional indexes, such as the Bloomberg Innovation Index (BII) and the Global Innovation Index (GII), only include high income economies among the top 20 performers. This is in sharp contrast to our approach, which identified 8-9 IDCs among the first 25 with China occupying the top position. Through an analysis of the pros and cons of the different methodologies, the IDC concept challenges more conventional approaches to address and estimate the innovative capacity of countries.</p></div

Top 25 innovative countries.

<p>Comparison of the 2005 original country ranking with those of the present study.</p

Coauthorship networks, Ebola 2015 and Zika 2016.

<p>Top 5 relevant countries and institutions, number of publications and betweenness centralities.</p

Evolution of publications on Ebola and Zika, 2012-2016.

<p>Publications on Ebola were already non negligible before the epidemics and peaked in 2015 while the Zika virus was not really in the global radar screen of researchers or institutions before the epidemics spread in Brazil in 2015.</p

Distribution of countries according to % publications addressing NTDs.

<p>The red line spans from 0.07% (Ukraine) up to 2.17% (Brazil).</p

Distribution of total patent applications in the world, 2004/2015.

<p>The top 4 country patent offices are indicated. Source: WIPO Statistics (World 2004: 1.574.200 patent applications; World 2015: 2.888.800 patent applications). Available in: <a href="https://www3.wipo.int/ipstats/keysearch.htm?keyId=221" target="_blank">https://www3.wipo.int/ipstats/keysearch.htm?keyId=221</a>. Access in: August 18, 2017.</p

Distribution of countries according to R. A. Mashelkar.

<p>Developed, industrialized nations occupy the top-right quadrant; less developed countries the bottom-left quadrant. Countries of high economic strength due to abundant natural resources (such as the oil-exporters rich countries of the Middle East) occupy the top-left position. The lower-right quadrant was regarded by Mashelkar as the most interesting as it was home of countries with high S&T capacity but at the turn of the century relatively weak from an economic point of view. Reproduced from [<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0006469#pntd.0006469.ref001" target="_blank">1</a>] with permission.</p

Coauthorship country networks addressing epidemics.

<p>Each node represents one country and two countries were considered connected if their authors shared the authorship of a paper. The thickness of links indicates the frequency of collaboration between two nodes. Bigger sizes and warmer colors indicate high betweenness centrality. Upper part: countries publishing on Ebola, 2015. Lower part: countries publishing on Zika, 2016.</p

Restrictive or liberal red-cell transfusion for cardiac surgery

Background: The effect of a restrictive versus liberal red-cell transfusion strategy on clinical outcomes in patients undergoing cardiac surgery remains unclear. Methods: In this multicenter, open-label, noninferiority trial, we randomly assigned 5243 adults undergoing cardiac surgery who had a European System for Cardiac Operative Risk Evaluation (EuroSCORE) I of 6 or more (on a scale from 0 to 47, with higher scores indicating a higher risk of death after cardiac surgery) to a restrictive red-cell transfusion threshold (transfuse if hemoglobin level was <7.5 g per deciliter, starting from induction of anesthesia) or a liberal red-cell transfusion threshold (transfuse if hemoglobin level was <9.5 g per deciliter in the operating room or intensive care unit [ICU] or was <8.5 g per deciliter in the non-ICU ward). The primary composite outcome was death from any cause, myocardial infarction, stroke, or new-onset renal failure with dialysis by hospital discharge or by day 28, whichever came first. Secondary outcomes included red-cell transfusion and other clinical outcomes. Results: The primary outcome occurred in 11.4% of the patients in the restrictive-threshold group, as compared with 12.5% of those in the liberal-threshold group (absolute risk difference, −1.11 percentage points; 95% confidence interval [CI], −2.93 to 0.72; odds ratio, 0.90; 95% CI, 0.76 to 1.07; P<0.001 for noninferiority). Mortality was 3.0% in the restrictive-threshold group and 3.6% in the liberal-threshold group (odds ratio, 0.85; 95% CI, 0.62 to 1.16). Red-cell transfusion occurred in 52.3% of the patients in the restrictive-threshold group, as compared with 72.6% of those in the liberal-threshold group (odds ratio, 0.41; 95% CI, 0.37 to 0.47). There were no significant between-group differences with regard to the other secondary outcomes. Conclusions: In patients undergoing cardiac surgery who were at moderate-to-high risk for death, a restrictive strategy regarding red-cell transfusion was noninferior to a liberal strategy with respect to the composite outcome of death from any cause, myocardial infarction, stroke, or new-onset renal failure with dialysis, with less blood transfused. (Funded by the Canadian Institutes of Health Research and others; TRICS III ClinicalTrials.gov number, NCT02042898.)C. David Mazer, M.D., Richard P. Whitlock, M.D., Ph.D., Dean A. Fergusson, Ph.D., M.H.A., Judith Hall, M.Sc., Emilie Belley-Cote, M.D., Katherine Connolly, M.D., Boris Khanykin, M.D., Alexander J. Gregory, M.D., Étienne de Médicis, M.D., Shay McGuinness, M.B., Ch.B., Alistair Royse, M.B., B.S., M.D., François M. Carrier, M.D., Paul J. Young, F.C.I.C.M., Ph.D., Juan C. Villar, M.D., Ph.D., Hilary P. Grocott, M.D., Manfred D. Seeberger, M.D., Stephen Fremes, M.D., François Lellouche, M.D., Ph.D., Summer Syed, M.D., Kelly Byrne, M.B., Ch.B., Sean M. Bagshaw, M.D., Nian C. Hwang, M.B., B.S., G.D.Acu., Chirag Mehta, M.D., Thomas W. Painter, M.B., Ch.B., Colin Royse, M.B., B.S., M.D., Subodh Verma, M.D., Ph.D., Gregory M.T. Hare, M.D., Ph.D., Ashley Cohen, M.Sc., Kevin E. Thorpe, M.Math., Peter Jüni, M.D. and Nadine Shehata, M.D. for the TRICS Investigators and Perioperative Anesthesia Clinical Trials Grou