Comparative Evaluation of the Treatment of COVID-19 with Multicriteria Decision-Making Techniques
Comparative Evaluation of the Treatment of COVID-19 with Multicriteria Decision-Making Techniques
Yildirim, Figen Sarigul;Sayan, Murat;Sanlidag, Tamer;Uzun, Berna;Ozsahin, Dilber Uzun;Ozsahin, Ilker
2021-01-23 00:00:00
Hindawi Journal of Healthcare Engineering Volume 2021, Article ID 8864522, 11 pages https://doi.org/10.1155/2021/8864522 Research Article Comparative Evaluation of the Treatment of COVID-19 with Multicriteria Decision-Making Techniques 1 2,3 3,4 3,5 Figen Sarigul Yildirim , Murat Sayan , Tamer Sanlidag, Berna Uzun, 3,6 3,6 Dilber Uzun Ozsahin , and Ilker Ozsahin Health Science University, Antalya Education and Research Hospital, Department of Infectious Diseases and Clinical Microbiology, Antalya 07050, Turkey Faculty of Medicine, Clinical Laboratory, PCR Unit, Kocaeli University, Kocaeli, Turkey DESAM Institute, Near East University, 99138 Nicosia/TRNC, Mersin 10, Turkey Department of Medical Microbiology, Manisa Celal Bayar University, Manisa, Turkey Department of Mathematics, Near East University, 99138 Nicosia/TRNC, Mersin 10, Turkey Department of Biomedical Engineering, Faculty of Engineering, Near East University, 99138 Nicosia/TRNC, Mersin 10, Turkey Correspondence should be addressed to Ilker Ozsahin; ilker.ozsahin@neu.edu.tr Received 28 August 2020; Revised 25 December 2020; Accepted 9 January 2021; Published 23 January 2021 Academic Editor: Giovanni Improta Copyright © 2021 Figen Sarigul Yildirim et al. -is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Objectives. -e outbreak of coronavirus disease 2019 (COVID-19) was first reported in December 2019. Until now, many drugs and methods have been used in the treatment of the disease. However, no effective treatment option has been found and only case- based successes have been achieved so far. -is study aims to evaluate COVID-19 treatment options using multicriteria decision- making (MCDM) techniques. Methods. In this study, we evaluated the available COVID-19 treatment options by MCDM techniques, namely, fuzzy PROMETHEE and VIKOR. -ese techniques are based on the evaluation and comparison of complex and multiple criteria to evaluate the most appropriate alternative. We evaluated current treatment options including favipiravir (FPV), lopinavir/ritonavir, hydroxychloroquine, interleukin-1 blocker, intravenous immunoglobulin (IVIG), and plasma ex- change. -e criteria used for the analysis include side effects, method of administration of the drug, cost, turnover of plasma, level of fever, age, pregnancy, and kidney function. Results. -e results showed that plasma exchange was the most preferred alternative, followed by FPV and IVIG, while hydroxychloroquine was the least favorable one. New alternatives could be considered once they are available, and weights could be assigned based on the opinions of the decision-makers (physicians/clinicians). -e treatment methods that we evaluated with MCDM methods will be beneficial for both healthcare users and to rapidly end the global pandemic. -e proposed method is applicable for analyzing the alternatives to the selection problem with quantitative and qualitative data. In addition, it allows the decision-maker to define the problem simply under uncertainty. Conclusions. Fuzzy PROMETHEE and VIKOR techniques are applied in aiding decision-makers in choosing the right treatment technique for the management of COVID-19. epidemic [1]. -e virus that causes COVID-19 is called the 1. Introduction severe acute respiratory syndrome coronavirus 2 (SARS- Since December 2019, when coronavirus disease (COVID- CoV-2). As of December 15, 2020, there were around 19) incidents were first reported in Wuhan, China, an in- 71,000,000 confirmed cases and 1,600,000 confirmed deaths creasing number of cases have been reported in all countries all over the world [1]. on all continents except Antarctica. It exceeded the rate of -e virus is released from respiratory secretions when an the number of COVID-19 patients, thus prompting the infected person speaks, sneezes, or coughs. When other World Health Organization to declare COVID-19 as an people come into direct contact with these droplets, they 2 Journal of Healthcare Engineering Decision-making models are the supportive systems that become infected. If those who touch the surface of the virus then touch the mouth, nose, and eyes, the infection can be will give the necessary information to decision-makers about the alternatives and their features. PROMETHEE and transmitted to other people [2–4]. -e exact incubation time is unknown. It is assumed that it is between 2 and 14 days VIKOR techniques are commonly used analytical multi- after exposure, and most cases occur within 5 days after criteria decision-making techniques that rank the alterna- exposure [5, 6]. Often most infections are self-limited. It may tives under the conflicting criteria successfully applied in cause more serious illness in the elderly population and many fields among the other techniques. VIKOR method those with underlying medical disease [7]. According to ranks alternatives giving the compromise solution, which is current statistics, the most common clinical features at the the closest to the ideal solution. PROMETHEE method gives a comparison to the alternatives based on the pairwise onset of illness are fever in 88%, fatigue in 38%, dry cough in 67%, myalgias in 14.9%, and dyspnea in 18.7% [8]. Pneu- comparison. As opposed to other methods, PROMETHEE gives more choices to the decision-maker for defining the monia is the most common complication. Severe cases have a mortality rate of 2.3 to 5% [7]. preference function for each criterion specifically. -is makes the PROMETHEE method more sensitive in ranking To date, there are no proven specific treatments for patients with the new virus other than supportive care. In the alternatives. China, Italy, France, Spain, Turkey, and now the USA, a large After the fuzzy set theory has been proposed and defined number of patients have received off-label and compas- by Zadeh in 1965, the hybrid models of the classical models, sionate use therapies [1]. -erefore, various options have fuzzy-based models, have been studied by researchers in been used to fight the virus so far. -ree general methods are many fields. Since there is no crisp difference between many used, including current broad-spectrum drugs, immu- objects and cases in the real world, it has been obtained that defining and modeling the problems using fuzzy sets can noenhancement therapy, and viral-specific plasma globulin. Many drugs such as chloroquine, hydroxychloroquine, create a more sensitive model to real-world problems. And fuzzy-based MCDM techniques allow the decision-makers azithromycin, interferon (IFN), favipiravir (FPV), remde- sivir, and lopinavir/ritonavir have been used in patients with to analyze the alternatives even with linguistic data; it is more suitable for many cases where the numerical data are SARS or Middle East respiratory syndrome (MERS), but the effectiveness of some drugs remains controversial [9–15]. not available. Synthetic recombinant interferon α, intravenous immuno- Fuzzy logic has shed light to integrate human opinion globulin (IVIG) (an immunomodulator), tocilizumab, and into decision-making problems [27]. In 2000, Warren et al. interleukin-1 blocker are used in immunoenhancement [28] showed the applicability of the fuzzy logic in modeling therapy [13, 14, 16]. Convalescent plasma therapy was the vagueness of the treatment based on the clinical thought to be an effective way to alleviate the course of the guideline knowledge to support the decision-makers in clinical practices. In 2012, Consenza [29] proposed the fuzzy disease for seriously infected patients, and successful results were obtained in patients on whom this treatment was expert system to provide the optimal amount of the insulin unit that should be taken before the meal for the type-1 attempted [17, 18]. -ese treatment methods have largely been administered diabetes patients corresponding to the characteristic of the in an uncontrolled manner, with the exception of a few food. In 2017, Santini et al. [30] proposed a fuzzy-based tool randomized trials launched in China and recently in the in order to manage and monitor the clinical status of USA [19]. Hence, it is not possible to make the interpretation β-thalassemia patients. -is study has given exemplary re- that if the patient dies, they die from the disease, but if the sults on the online determination of iron overload while patient survives, this is because of the drug given. All monitoring the health conditions of β-thalassemia patients. methods have some advantages and disadvantages. For In 2019, Akram and Adeel [31] discussed the hybrid model example, chloroquine/hydroxychloroquine, azithromycin, of the hesitant m-polar fuzzy sets. -ey provided the ap- plication of the hesitant m-polar fuzzy TOPSIS technique to and lopinavir-ritonavir have several negative effects, in- cluding QT prolongation, hepatitis, acute pancreatitis, rank and select the best alternative under m-polar fuzzy set positive and negative ideal solution for a multicriteria group neutropenia, and anaphylaxis [20, 21]. Agents that have been used less frequently in the past (e.g., remdesivir) can cause decision. In 2020, Akram et al. [32] proposed Dombi ag- serious negative effects that have not been detected previ- gregation operators for decision-making under m-polar ously due to the limited number of exposed patients [22, 23]. fuzzy information. -ey tested their operation validity for Interleukin blockers may cause immunosuppression, in- obtaining the bestagricultural land and thebest bankwithits creasing the risk of sepsis, bacterial pneumonia, and hep- performance. -ey also compared their technique with the atotoxicity [24, 25]. ELECTRE-I method and they found that the optimal al- ternative is the same by applying the ELECTRE-I method. -e rapid and simultaneous combination of supportive care and randomized control studies is the only way to find Garg et al. [27] proposed a new fuzzy operation compared with the Yager operation for Fermatean fuzzy numbers, and effective and safe treatments for COVID-19 and other future outbreaks. In one open-label nonrandomized control study, they applied this technique to obtain a ranking result for the COVID-19 testing facilities. In 2020, Akram et al. [33] FPV had significantly better outcomes for disease pro- gression and viral clearance; these results should provide an presented new aggregation operators such as Fermatean important advance in creating standard treatment guidelines fuzzy Einstein weighted averaging, Fermatean fuzzy Einstein for combating SARS-CoV-2 infection [26]. ordered weighted averaging, generalized Fermatean fuzzy Journal of Healthcare Engineering 3 Einstein weighted averaging, and generalized Fermatean pathogenicity and the phase in which the host inflammatory fuzzy Einstein ordered weighted averaging to cumulate the response is predominant in terms of the timing of the agent Fermatean fuzzy data in decision-making environments to be used in the treatment. In this case, different methods which has more flexible structure than the intuitionistic and have been used to treat COVID-19 at different stages of the Pythagoreanfuzzy sets. -ey applied thesetechniques forthe disease. However, scientists and real-life data have dem- COVID-19 sanitizer selection problem. onstrated that it is more beneficial to start many treatments -us far, we have used a multicriteria decision-making early [12]. (MCDM) technique called fuzzy PROMETHEE to compare the confusion regarding the choice of effective treatment practices using the following guidelines, to make a mutual 2.1. Treatment Techniques. We have chosen the methods comparison between selected treatment methods, and to that have been most frequently used since the beginning of determine the strongest one [34–38]. -e PROMETHEE the COVID-19 pandemic. Chloroquine, an antimalaria technique was developed by Brans and Vincle in 1985 [39]. drug, is the first agent used against the COVID-19 disease. It Since then, it has been used successfully as an MCDM both has an immune-modulating activity and can inhibit technique in many fields [40], and recently, it has been this virus with an in vitro effect [10]. It has been proven in a applied in the field of material selection, medicine, and clinically controlled study that chloroquine, an antimalarial healthcare [41–50], as well as it was selected as a proper drug, is effective in the treatment of patients with COVID-19 COVID-19 diagnosis tool [51]. VIKOR is another com- [59]. Since the side effects of hydroxychloroquine are lower monly used MCDM technique that determines the order of than chloroquine, the use of hydroxychloroquine has been alternatives under conflicting criteria based on the closeness preferred in the treatment of COVID-19 [60]. In COVID-19 to the ideal solution [52]. It provides the maximum group patients, hydroxychloroquine allows the viral nasopharyn- utility and the minimum individual regret for determining geal carriage of SARS-CoV-2 to be cleared in just three to six the compromise solution of the decision-making problem. days [61]. Its effect is reinforced by azithromycin, an anti- Fuzzy logic was first presented in 1965 by Zadeh in order to bacterial agent [61]. Azithromycin is used to treat or prevent define vague conditions or linguistic data mathematically certain bacterial infections, predominantly those causing [53]. A fuzzy logic-based clinical decision support system for middle ear infections, throat, pneumonia, typhoid, bron- the evaluation of renal function in posttransplant patients chitis, and sinusitis [62]. Azithromycin and hydroxy- has been implemented successfully [54]. -e analytic hier- chloroquine have the side effect of QTprolongation (that can archy process (AHP), which is another methodology based cause sudden death). on both mathematical and psychological approaches with a Remdesivir, a terminate of viral RNA transcription, has similar purpose as PROMETHEE and VIKOR, is exploited in vitro activity against SARS-CoV-2 [63]. It was originally to analyze and solve complex problems, in order to make the used for the treatment of the Ebola virus disease and best decision. Some examples of the application of AHP in Marburg virus infections. One of the side effects of healthcare and health technologies can be found in [55–57]. remdesivir is hepatotoxicity. -e data of the COVID-19 treatment techniques contain FPV selectively inhibits RNA-bound RNA polymerase of quantitative and qualitative data of multicriteria with dif- RNA viruses and has been approved for new influenza ferent importance weights which cannot be simply evaluated therapy since 2014 [64]. It is also hepatotoxic. by the decision-makers. -erefore, we have applied two of Lopinavir and ritonavir are antiretroviral protease in- the successfully used analytical MCDM techniques. Both of hibitors that have been used in combination for the treat- the techniques give consistent ranking results as expected. ment of human immunodeficiency virus infection since Besides, by applying the PROMETHEE method, we are able 2000 [65]. -is has reduced the replication by 50% in the to see the positive and negative sides of each alternative. MERS coronavirus in vitro [66]. -e most common side In this study, the use of fuzzy scale based on fuzzy logic effects are gastrointestinal problems such as nausea, vom- has enabled the experts to express qualitative data such as iting, and diarrhea. side effects, applicability, and compliance of COVID-19 Oseltamivir is a neuraminidase enzyme inhibitor used treatment techniques meaningfully to be included in the for influenza. In fact, many patients with COVID-19 model. It is also used to express the degrees of importance symptoms might have influenza. -erefore, it is better to assigned to the criteria more easily and with the common give this medicine to prevent the patient from getting worse sense of the experts. [66]. Interferon is a broad-spectrum antiviral agent that acts by interacting with toll-like receptors and inhibits viral 2. Methods replication [67] and anti-SARS-CoV-1 activity in vitro [68]. SARS-CoV-2 is an enveloped, positive, single-strand RNA Tocilizumab is a recombinant humanized monoclonal beta-coronavirus and is structurally similar to SARS-CoV-1 antibody that acts as an IL-6 receptor antagonist and is used and MERS [58]. -ere are two overlapping hypotheses in the for the treatment of rheumatoid arthritis. Interleukin-6 was pathogenesis of the disease: triggered by the virus itself and reported to be released considerably in SARS and MERS the host response. -ere is significant confusion regarding patients and might play a role in the pathogenesis of these diseases [69]. In COVID-19 patients, higher plasma levels of the therapeutic approaches used in COVID-19. Currently, it is imperative to distinguish between the phase of viral cytokines have also been found [69]. 4 Journal of Healthcare Engineering have used different fuzzy models most probably, we will IVIG might be the safest immunomodulator for long- term use in patients of all ages and could help to inhibit the obtain the same ranking results. production of proinflammatory cytokines and increase the production of anti-inflammatory mediators [13]. 2.3. Fuzzy PROMETHEE. In real-world problems, one of the While evaluating these methods, we used different cri- major challenges involves the collection of crisp data to teria that were selected based on the doctors, the treatment analyze systems. In 1965, Zadeh laid the foundations for the methods, and the host. Regime cost, side effects, number of idea of establishing a rule functioning and then transferring tablets, dose frequency, treatment duration, plasma stability, it to a machine by making use of human life experiences and plasma turnover, time of suppression, practicability, intra- various kinds of knowledge. Fuzzy logic can be defined as a venous form, oral form, and drug-drug interaction were decision mechanism design in its simplest form. It allows chosen as the treatment method-related criteria. Age, decision-makers to identify vague conditions and analyze pregnancy, glomerular filtration rate (GFR), compliance, the systems using linguistic data if it is needed [53]. fever, pneumonia, intensive care, organ failure, macrophage MCDM is a research area that involves the analysis of activation syndrome, and the hemophagocytic syndrome various available choices in a situation or research area, were chosen as the host-related criteria. -ese are symptoms which spans daily life, social sciences, engineering, medicine, and phases of diseases in COVID patients. False prescription and many other areas. and inefficient drug combination were chosen as the doctor- MCDM analyzes the alternatives (qualitatively or related criteria. All of these factors are important when quantitatively) involved in a criterion that makes the al- selecting treatment methods for COVID-19 patients. ternatives a favorable or unfavorable choice for a particular application and attempts to compare this criterion based on the selected criteria against every other available option in an 2.2. Fuzzy-Based MCDM Models. Ranking the fuzzy num- attempt to support the decision-maker when selecting an bers contains the main problematic part of the decision- option with maximum advantages without negotiation. making problems under the fuzzy environment. -is process PROMETHEE is an MCDM tool that allows a user to is also the most important stage of the decision-making analyze and rank accessible alternatives according to the process since it simplifies the complexity of the problem. criteria of each alternative. It compares the available alter- Comparison of the fuzzy numbers has practical applications natives based on the selected criteria [39]. -e PROM- in optimization, forecasting, decision-making, and ap- ETHEE technique is a valuable and sensitive MCDM proximate reasoning. Real-world decision problems often technique for reasons that include the following: involve uncertain conditions of the properties of alterna- tives, and fuzzy numbers allow the decision-maker to be (i) PROMETHEE can be used to handle qualitative and used in the analysis by taking these uncertain conditions into quantitative criteria simultaneously account. -ere are many types of fuzzy-based MCDM (ii) PROMETHEE deals with fuzzy relations, vagueness, models available for different aims, and there are many and uncertainties studies that present different techniques for the comparison (iii) PROMETHEE is easy to handle and provides the of the fuzzy numbers [70–72]. Although the centroid con- user with maximum control over the preference of cept has been applied in many fields and has been known for the alternatives with regard to the criteria hundreds of years, first in 1980, Yager proposed the centroid method for the comparison of the fuzzy numbers [73]. After When using PROMETHEE, only two types of infor- Yager, there have been many studies that used this method mation are required from the decision-maker: information for the construction of the individually defined ranking regarding the importance weights of the selected criteria and index [74–76]. Some of these researchers have used the value the preference function to be used in comparing the al- of x alone, while some of them used a combination of x and y ternatives’ contribution with regard to each criterion. values to obtain their own ranking index that depends on the Different preference functions (P ) are available on centroid concept. -ere are also some research studies that PROMETHEE for the definition of different criteria. -e aim to produce the most suitable or correct centroid value preference function defines assigning values to the ranking formula [77, 78] for the usage of the ranking index. -ese of two alternatives (a and a ) in relation to specific criteria research studies provide valuable information for comparing and a preference degree of the limit between 0 and 1 [39]. the fuzzy numbers that depend on the centroid approaches. -e preference functions for practical purposes that can be However, some studies found that the Yager index has great used at the discretion of the decision-maker include the potential in fuzzy optimization [79]. In our study, some of usual function, V-shape function, level function, u-shape the criteria, such as side effects, were defined by the experts function, linear function, and Gaussian function [39]. A using the linguistic fuzzy scale since no crisp values are complete explanation of the preference functions used, their available for those criteria. Furthermore, fuzzy data of the ranking, and how to make a decision on which function best defined parameters have been compared using the centroid suits a scenario was presented by Brans et al. [39]. concept, defined by the Yager index, which is successfully In the PROMETHEE analysis, after collecting the criteria applied and confirmed by many researchers. If we could of the alternatives, the preference function p (d) for each j Journal of Healthcare Engineering 5 net criterion j should be defined, and the importance weight of -e better alternative is the one with the higher Φ (a ) each criterion w �(w , w , . . ., w ) should be determined. value (32). t 1 2 k Normalization of the weights or equality of weights can be In this study, we proposed the use of the fuzzy-based chosen by the decision-maker based on the application. PROMETHEE technique for the evaluation of the available -en, for every alternative pair (a , a ∈A), the outranking treatment options for COVID-19. -e selected treatment t t’ relation π(a , a ) should be determined as seen in options are favipiravir (FPV), remdesivir, “lopinavir/ritonavir,” t t′ “hydroxychloroquine,” “oseltamivir+hydroxychloroquine,” π