Establishment and application of drug utilization evaluation applying the weighted TOPSIS method: A study based on real-world data of tislelizumab

Abstract

BACKGROUND:

How to comprehensively evaluate the rationality of drug use is a challenging issue.

OBJECTIVE:

To establish the evaluation index of the effective use of tislelizumab, so as to ensure its higher rationality and normalization in clinical application.

METHODS:

Based on the indications, drug instructions, and relevant guidelines of the National Basic Medical Insurance Restriction Catalogue, a retrospective analysis and evaluation of 286 cases of using tislelizumab injection in our hospital from January to December 2022 were conducted using the weighted technique for order of preference by similarity to ideal solution (TOPSIS) method.

RESULTS:

Among the 286 medical records evaluated, the main irrational manifestations were inappropriate indications (90 cases, 31.47%), auxiliary examination and laboratory examination did not meet the minimum requirements of combination chemotherapy drugs (40 cases, 13.99%), the drug course was not standard (39 cases, 13.64%). Among the included cases, 57.34% were reasonable cases ( $C_{i}\geqslant$ 0.8), 10.84% were basic reasonable cases (0.6 $\leqslant$ $C_{i}<$ 0.8), and 31.82% were unreasonable cases ( $C_{i}<$ 0.6).

CONCLUSION:

The TOPSIS method, with its attribute hierarchical model (AHM)-weighted approach, can be employed as the rational assessment technique for the injection of tislelizumab. The clinical application of tislelizumab in our hospital is still insufficient, which needs to be further improved management.

Keywords

Drug use evaluation weighted TOPSIS Tislelizumab attribute hierarchical model

1. Background

Tislelizumab is a Chinese developed IgG4 monoclonal antibody. Unlike traditional programmed death-1 (PD-1) monoclonal antibodies, it possesses a unique antigen-binding receptor. Through recombinant technology targeting the Fc segment of the antigen-binding receptor, it can significantly reduce the inhibitory effects on anti-cancer activity. This further enhances the effectiveness of anti-cancer medications [1]. As of December 2022, this drug has been approved for nine indications in China, and its application scope and usage have been rapidly expanding. However, with the widespread use of the medication, issues related to irrational drug use have gradually surfaced. Irrational drug use not only undermines patients’ economic interests but, more importantly, also affects the efficacy of treatment, increases adverse reactions, and jeopardizes patient health. According to statistics, in developing countries, more than 60% of drugs are subject to irrational use [2]. In the United States, irrational drug use constitutes a significant factor contributing to the onset of diseases and patient mortality [3, 4]. Administrative Measures for the Clinical Application of Antineoplastic Drugs (Trial) [5] and Guidelines for the Clinical Application of New Anti-Tumor Drugs (2021 Edition) [6] emphasize the need to strengthen supervision and management when using Tislelizumab, to ensure its effectiveness and safety.

Drug use evaluation (DUE) was first proposed by the American Pharmaceutical Association in 1987. Its purpose is to conduct a rational assessment of the clinical use of drugs based on predetermined criteria [7]. The technique for order of preference by similarity to ideal solution (TOPSIS) is primarily designed for decision analysis concerning multiple objectives of a certain medication, offering advantages such as convenience and rapidity. This research method can accurately reveal the essential influencing factors of the outcome, providing guidance for subsequent improvement efforts [8, 9]. Thus far, TOPSIS has been widely applied in various disciplines such as environmental science, economics, and human resource management [10, 11]. For this study, patient information was collected from January to December 2022 at our hospital. Through discussions and consultations with experts from diverse fields, standardized criteria for evaluating drug rationality were established. The Attribute Hierarchical Model (AHM) weighting method [12] was employed to assign weights to various indicators of Tislelizumab. Finally, TOPSIS was employed for rationality evaluation. This study establishes the first rational application evaluation criteria for Tislelizumab injection, comprehensively assessing its safety, efficacy, and standardization during clinical use.

2. Data and methods

2.1 Sources

Drug Rational Use Guidance System (DRUGS) was utilized to retrieve relevant clinical data from a tertiary comprehensive hospital in Guangxi (hereinafter referred to as “the hospital”) for a retrospective analysis. The inclusion criteria were archived cases that received Tislelizumab injection from January 2022 to December 2022. Exclusion criteria include: 1) Cases of efficacy could not be assessed; 2) deceased cases; 3) cases that were discharged voluntarily or transferred to another hospital.

2.2 Research methods

2.2.1 Establishment of rational evaluation criteria for Tislelizumab

Based on the National Basic Medical Insurance, Work-Related Injury Insurance, and Maternity Insurance Catalog (2021 Edition) [13] and Tislelizumab Injection Drug Information [14] and clinical practice guidelines issued by the Chinese Society of Clinical Oncology (CSCO) [15] along with relevant materials such as the Guidelines for the Clinical Application of Novel Anti-Tumor Drugs (2021 Edition) a joint discussion was conducted involving three hepatobiliary surgeons, three oncology specialists (including one senior physician and two attending physicians), and three clinical pharmacists (including one senior pharmacist and two chief pharmacists) from our hospital. Together, they proposed evaluation criteria for rational drug use, ultimately establishing rational drug use evaluation standards for Tislelizumab, encompassing indications, contraindications, organ function and laboratory indicators, dosing and administration, treatment duration, clinical efficacy, and adverse reactions as key evaluation parameters (Table 1).

Table 1
Rational administration evaluation rules of Tislelizumab for injection

Indicator	Evaluation criteria	Evaluation results
Indications	1. Indications limited by medical insurance: (1) Treatment for relapsed or refractory classical Hodgkin lymphoma that has undergone at least second-line systemic chemotherapy. (2) For locally advanced or metastatic urothelial carcinoma, the use of PD-L1 high expression as a criterion for platinum-based chemotherapy failure, including progression after 12 months of neoadjuvant or adjuvant chemotherapy. (3) Combination of paclitaxel and carboplatin for unresectable locally advanced or metastatic non-small cell lung cancer (squamous cell subtype). (4) Combination of carboplatin and paclitaxel (or albumin-bound paclitaxel) for advanced lung squamous cell carcinoma. (5) Applicable for hepatocellular carcinoma that has received at least one systemic treatment. 2. Indications as per the product insert: (1) Suitable for adult patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) advanced solid tumors. (2) Applicable to other advanced solid tumor patients with disease progression after previous treatments and who are not eligible for alternative treatment options. (3) For advanced colorectal cancer patients who have experienced disease progression after previous treatments with fluoropyrimidines, oxaliplatin, and irinotecan. 3. Off-label use of medication: (1) Combined use of cisplatin and gemcitabine for distant metastatic nasopharyngeal carcinoma. (2) Treatment of locally advanced or metastatic esophageal squamous cell carcinoma that has progressed or is intolerant to first-line standard chemotherapy.	0: conformity (1) 1: conformity (2) or (3)
Organ function and laboratory indicators [21]	Monotherapy: TBIL $<$ 1.5 ULN, GFR $\geqslant$ 30 mlmin^{- 1}/1.73 m², ALT or AST $\leqslant$ 3 ULN Combined treatment: WBC $\geqslant$ 3.5 $\times$ 10⁹ /L, NEU $\geqslant$ 2.0 $\times$ 10⁹/L, PLT $\geqslant$ 100.0 $\times$ 10⁹/L	0: conformity 1: inconformity
Contrain- dications	Patients with hypersensitivity to any component of this product	0: inconformity 1: conformity
Usage	(1) Extract two vials of this injectable solution (total of 20 mg, containing 200 mg), transfer them to an intravenous infusion bag containing 0.9% sodium chloride solution, to prepare a final concentration range of 1 $\sim$ 5 mg/ml, administered once every 3 weeks. (2) When combined with other chemotherapy drugs and administered on the same day, administer this product first. (3) The initial infusion time should not be less than 60 minutes; if well-tolerated, subsequent infusion times should not be less than 30 minutes.	0: conformity (1) and (2) and (3) 1: inconformity (1) or (2) or (3)
Course of treatment	Once every 3 weeks	0: conformity 1: inconformity
Clinical efficacy	The disease improves or stabilizes	0: conformity 1: inconformity
Adverse events	Common adverse reactions: (1) Hypothyroidism, characterized by fatigue, constipation, feeling cold, dry skin, and weight gain. (2) Hyperthyroidism, characterized by tachycardia, sweating, diarrhea, and weight loss. (3) Skin adverse reactions, mainly presenting as rashes, pruritus, and vitiligo, with papules and wheals being the typical skin lesions	0: conformity 1: inconformity

WBC: white blood cell count, NEU: neutrophil, PLT: platelet count, ULN: upper limit of normal, AST: aspartate aminotransferase, ALT: alanine aminotransferase, GFR: glomerular filtration rate, TBIL: total bilirubin.

2.2.2 Applying the weighted TOPSIS method for rationality evaluation

According to the inclusion criteria, establish a database in Excel and determine the indicator weights. Following the seven indicators in the rational evaluation criteria for Tislelizumab Injection, assess each of the collected 286 archived medical records, assigning a score of 10 for rational indicators and 0 for irrational indicators. Afterward, derive the final results and apply Eqs (2.2.2) and (2) to utilize the AHM for calculating the relative weights of each indicator. By calculating the best and worst solutions for each indicator and applying Eqs (3) and (4) to assess their similarity, the optimal treatment plan ( $C_{i}$ ) can be determined. A $C_{i}$ value closer to 1 indicates a more reasonable treatment plan.

$\displaystyle g\left(x\right)=\left\{{{\begin{array}[]{ll}1,&x>0.5\\ 0,&x\leqslant 0.5\\ \end{array}}}\right.$ $\displaystyle Q_{i}=j:g\left({u_{ij}}\right)=1,1\leqslant j\leqslant n$ $\displaystyle g\left({u_{ij}}\right)=g\left(\mathop{\sum}\nolimits_{i\in i}g% \left({u_{ij}}\right)\right)\geqslant 0,1\leqslant k\leqslant n$ (1) $\displaystyle W_{i}=\frac{2}{n(n-1)}\mathop{\sum}\nolimits_{j=1}^{n}u_{ij}$ (2) $\displaystyle D_{i}^{+}=\sqrt{\mathop{\sum}\nolimits_{j=1}^{n}\left[{W_{J}% \left(Z_{ij}-Z_{j}^{+}\right)}\right]}i=1,2,3\ldots n\ \ j=1,2,3\ldots n$ (3) $\displaystyle D_{i}^{-}=\sqrt{\mathop{\sum}\nolimits_{j=1}^{n}\left[{W_{J}% \left(Z_{j}^{i}-Z_{i}^{-}\right)}\right]}\ i=1,2,3\ldots n\ j=1,2,3\ldots n$ (4) $\displaystyle C_{i}=\frac{D_{i}^{-}}{(D_{i}^{+}+D_{I}^{-})}$ (5)

2.2.3 Statistical analysis

The data analyzed in this study were processed using SPSS 26.0 software and a paired $t$ -test was employed to evaluate the variances between distinct groups. Statistical significance was determined when the $P<$ 0.05.

3. Results

3.1 Basic information

In this study, a total of 286 archived medical records of patients who received Tislelizumab were included. The patients exhibited a mean age of 57 years. Among them, there were 220 male and 66 female patients. 124 cases (43.36%) had a hospital stay of 7 days or more, while 162 cases (56.64%) had a hospital stay of less than 7 days. The predominant tumor types in this study were hepatocellular carcinoma (60.14%), lung cancer (17.83%), and urothelial carcinoma (7.34%) (Table 2).

Table 2
Basic information of the included patients ( $n=$ 286)

Basic information	Classification	Numbers	Percentage (%)
Age	$\geqslant$ 65 yr $<$ 6yr	122 164	42.66 57.34
Sex	Male Female	220 66	76.92 23.08
Length of stay	$\geqslant$ 7 days $<$ 7 days	124 162	43.36 56.64
Tumor types	Hepatocellular carcinoma Lung cancer Urothelium carcinoma Gastric or colorectal cancer Biliary tract neoplasms Pancreatic cancer Head and neck neoplasm Ovarian or cervical cancer Breast cancer Lymphoma Renal cell carcinoma	172 51 21 13 8 7 5 4 2 2 1	60.14 17.83 7.34 4.55 2.80 2.45 1.75 1.40 0.70 0.70 0.35
Primary disease	Hepatitis B Hypertension Diabetes	98 54 25	34.27 18.88 8.74

3.2 Rational evaluation of Tislelizumab using the weighted TOPSIS method

3.2.1 Irrational rate of evaluation index and relevant weight coefficient

Using the AHM weighting method and based on the aforementioned Eqs (2.2.2) and (2), the weight coefficients (W1, W2, $\ldots$ , W7) for the seven evaluation criteria in the Drug Use Evaluation (DUE) standard of Tislelizumab Injection were calculated as follows: W1 $=$ 0.2249, W2 $=$ 0.0536, W3 $=$ 0.2254, W4 $=$ 0.1190, W5 $=$ 0.1121, W6 $=$ 0.1539, and W7 $=$ 0.0771. Among the 286 medical records, the main irrational situations were inappropriate indications (90 cases, 31.47%), organ function and laboratory indicators not meeting requirements (40 cases, 13.99%), and failure to comply with prescribed treatment duration (39 cases, 13.64%), etc. (Table 3).

Table 3
The unreasonable rate and relative weight coefficient of evaluation indicators

Indicator	Relative weight coefficient	Reasonable case (%)	Unreasonable case (%)	Score
Indications	0.2249	196 (68.53)	90 (31.47)	1960
Organ function and laboratory indicators	0.0536	246 (86.01)	40 (13.99)	2470
Contraindications	0.2254	286 (100)	0 (0)	2860
Usage	0.1190	279 (97.55)	7 (2.45)	2790
Course of treatment	0.1121	247 (86.36)	39 (13.64)	2470
Clinical efficacy	0.1539	279 (97.55)	7 (2.45)	2790
Adverse events	0.0771	267 (93.35)	19 (6.65)	2670

3.2.2 Degree of relative closeness

The higher the value of the “degree of relative closeness” ( $C_{i}$ ), the more optimal the rationality evaluation result of the included medical records [16]. By using Eqs (3) and (4), the optimal and worst solutions for each indicator were calculated, and Eq. (5) was utilized to Ci for each indicator’s best solution. The results indicate that there are 91 cases (31.82%) with $C_{i}$ values $<$ 0.6, 5 cases (1.75%) with 0.6 $\leqslant$ $C_{i}<$ 0.7, 26 cases (9.09%) with 0.7 $\leqslant$ $C_{i}<$ 0.8, 27 cases (9.79%) with 0.8 $\leqslant$ $C_{i}<$ 1.0, and a total of 136 cases (47.55%) with $C_{i}=$ 1.0. The proportion of rational medical records is 57.34%, the proportion of basically rational medical records is 10.84%, and the proportion of irrational medical records is 31.82% (Table 4).

Table 4
Ci of tislelizumab and evaluation results of the rationality of medication ( $n=$ 286)

	Relative distance	Numbers	Percentage (%)
Reasonable case	Ci $=$ 1.0 0.9 $\leqslant$ Ci $<$ 1.0 0.8 $\leqslant$ Ci $<$ 1.0	136 1 27	47.55 0.35 9.44
Basically reasonable case	0.7 $\leqslant$ Ci $<$ 0.8 0.6 $\leqslant$ Ci $<$ 0.7	26 5	9.09 1.75
Unreasonable case	0.5 $\leqslant$ Ci $<$ 0.6 Ci $<$ 0.5	91 0	31.82 0

4. Discussion

By establishing a rational application evaluation criterion for Tislelizumab Injection, the weighted TOPSIS method was used to analyze the drug utilization. The evaluation results revealed that the clinical irrationality rate of Tislelizumab in our hospital ( $C_{i}<$ 0.6) reached 31.82%, indicating significant room for improvement. Further analysis showed that the irrational drug use was primarily concentrated in inappropriate indications, failure to meet organ function and laboratory testing requirements, and non-compliance with prescribed treatment courses. Based on these highlighted issues, we provided a targeted set of recommendations after conducting a thorough analysis and discussion.

4.1 Strictly adhere to the indications for drug use

In the 286 included archived medical records of Tislelizumab Injection, there were a total of 90 cases (31.47%) with inappropriate indications. It is well known that cancer treatment is characterized by its long-term and complex nature, and off-label drug use may occur during the treatment process. For example, in the endocrine treatment of breast cancer, the aromatase inhibitor drug exemestane is indicated in the product label for postmenopausal patients. However, in clinical practice, it is also frequently used for premenopausal patients, similar to its counterpart tamoxifen. Off-label drug use has always been a barrier in cancer treatment. In April 2015, the Chinese Pharmacological Society issued the first nationwide “Expert Consensus on Off-label Drug Use” [17]. It provides protection for off-label use of drugs at the legal level. During the clinical treatment process, when facing necessary and evidence-based off-label drug use, it is recommended that doctors strictly follow the corresponding record-filing procedures and develop appropriate emergency plans based on the drug’s characteristics. This ensures the maximization of patient benefits while also guaranteeing professional safety. Furthermore, the study found that in some cases, clinical physicians may choose to use Tislelizumab as a substitute for Sintilimab in immunotherapy. However, after consulting relevant literature and guidelines, there have been no reports explicitly stating that such substitution is acceptable. Therefore, it is advised to avoid the interchange of similar drugs without evidence-based support whenever possible. In situations necessitating substitution, clinical guidelines should form the basis. One must consider high-quality clinical research evidence while taking into account the patient’s specific condition for drug usage. Additionally, detailed drug analysis and records should be kept throughout the course of treatment. Clinical pharmacists can play a role by monitoring drug use through prescription review systems, promptly correcting irrational drug use, and actively providing drug guidance to assist clinical physicians in better understanding the appropriate use of Tislelizumab.

4.2 Improve the detection of laboratory indicators, according to the prescribed course of medication

As a new type of anti-tumor drug, there is currently no unified reference for organ function and laboratory indicator requirements for Tislelizumab. In this study, we based the requirements on similar drugs as a reference. For single-agent therapy, the following criteria should be met: TBIL $<$ 1.5 ULN, GFR $\geqslant$ 30 mlmin^{- 1}/1.73 m², ALT or AST $\leqslant$ 3 ULN. When used in combination with chemotherapy drugs, patients’ blood routine indicators should meet the following requirements: WBC $\geqslant$ 3.5 $\times$ 10⁹ /L, NEU $\geqslant$ 2.0 $\times$ 10⁹/L, PLT $\geqslant$ 100.0 $\times$ 10⁹/L. In addition, when Tislelizumab is used in combination with chemotherapy drugs, it is essential to closely monitor the patients’ liver and kidney functions, among other indicators. Regular assessment of the patient’s overall condition is necessary for timely intervention to minimize the toxic side effects of the treatment drugs. Among the included medical records, a total of 40 cases (13.99%) did not meet the requirements for organ function and laboratory tests, and no relevant measures were taken to address the abnormal indicators before treatment. Tislelizumab has a relatively large molecular weight and is primarily metabolized and eliminated through the protein hydrolysis enzymes. Population pharmacokinetic data show that patients with mild to moderate renal impairment do not require dosage adjustments, similar to patients with mild hepatic impairment. However, the impact of moderate to severe hepatic impairment and severe renal impairment on pharmacokinetics is still unknown. However, for patients with moderate to severe hepatic and severe renal insufficiency, definitive conclusions cannot yet be drawn from existing studies [18]. Based on this, patients with moderate to severe liver insufficiency and severe renal insufficiency are not recommended to use this medication. Clinical physicians should pay close attention to patients’ laboratory indicators before and during treatment, fully evaluate their condition, and closely monitor their blood and liver and kidney function. This ensures that patients with cancer receive the maximum benefit from the treatment. Strict adherence to the prescribed treatment course is a crucial prerequisite for the therapeutic benefits in cancer patients. Tislelizumab requires an injection every 3 weeks, and clinical practitioners should explain the detailed treatment plan and the timing of the next treatment cycle to the patients. This will help patients understand the importance of adhering to the prescribed treatment course and encourage them to receive treatment within the specified treatment duration.

4.3 Ensure drug safety

Compared to traditional chemotherapy drugs, Tislelizumab targets the body’s immune response system rather than tumor cells. While it may lead to favorable treatment outcomes, it can also result in adverse drug reactions in multiple organs of the body. In this study, a total of 19 patients experienced drug-related adverse reactions, primarily presenting as skin itching and thyroid dysfunction. Based on the U.S. Common Terminology Criteria for Adverse Events (CTCAE), all adverse reactions were graded as 1–2, indicating mild to moderate severity. These reactions were effectively managed with oral prednisone or symptomatic treatment, and there were no cases of severe adverse reactions observed. In a large-scale study involving 1,183 participants, Tislelizumab monotherapy showed a relatively high incidence of adverse reactions, primarily immune-related thyroid dysfunction and immune-related skin adverse reactions. However, the majority of these adverse reactions could be managed and improved with treatment using corticosteroids or supportive care, which aligns with the results of our study [19]. Indeed, immune-related adverse reactions can occur over a wide span of time and affect multiple organs, making their identification and diagnosis relatively challenging. Therefore, healthcare professionals should closely monitor patients during the treatment process with Tislelizumab, aiming for early detection and timely diagnosis and intervention to prevent the occurrence of severe adverse reactions.

4.4 Application of weighted TOPSIS method

This study established the rational evaluation criteria for the clinical application of Tislelizumab based on drug instructions and relevant guidelines. The AHM weighting method was used, with guidance from experts in various fields, to assign corresponding weight coefficients to each evaluation index. Mathematical and statistical analysis were then employed to construct a mathematical statistical analysis model for the seven evaluation indices. The data were normalized, and the ideal solution $C_{i}$ for each case was calculated to assess the rationality of Tislelizumab use in our hospital. The weighted TOPSIS method was primarily used for evaluating the rationality of a single drug, enabling a better assessment of the importance of the evaluation indices and efficient utilization of data resources. It has the advantages of simplicity in computation and flexibility in application. The weighted TOPSIS not only allows for a more accurate assessment of the importance of the evaluation criteria but also enables better utilization of data resources. It possesses the advantages of simplicity in computation and flexibility in application [20]. The key challenge of this study lies in establishing the criteria for evaluation indicators. Due to the relatively short time Tislelizumab has been on the market and its limited therapeutic references, unified standards for certain indicators are unavailable. Ambiguous indicators require special attention. After extensive literature review and repeated validation discussions with experts, the most rational standards for these indicators were ultimately formulated. Among the 286 included cases, 164 cases (57.34%) were considered rational ( $C_{i}\geqslant$ 0.8), 31 cases (10.84%) were deemed basically rational (0.6 $\leqslant$ $C_{i}<$ 0.8), and 91 cases (31.82%) were considered irrational ( $C_{i}<$ 0.6). The number of irrational cases was close to that of patients with inappropriate indications, indicating that inappropriate indications were the main issue in the irrational use of Tislelizumab in our hospital. It also showed that by assigning weights to the DUE indicators and quantifying the evaluation results, the subjectivity of the assessment was reduced. This allowed for a rapid and accurate identification of the major influencing factors for the rational use of Tislelizumab. Healthcare professionals can use these results to quickly implement improvement measures, strengthen drug management, and intervene in drug use effectively, thereby reducing manpower and resources while ensuring medication safety.

5. Conclusion

With the increasing use of novel anti-tumor drugs like Tislelizumab, drug utilization evaluation will become a key focus of clinical pharmacists’ work. In this study, we successfully evaluated the rationality of drug usage using the weighted TOPSIS method and identified the main issues in the medication process. In future work, we will focus on targeted improvements based on the medication issues identified in this study. We will intervene promptly through the prescription system before medication, addressing prescriptions that do not comply with indications and laboratory test requirements. After medication, we will conduct focused medication reviews, provide feedback to clinicians, propose improvement solutions, and continuously monitor the situation. Additionally, pharmacists need to enhance their monitoring of adverse drug reactions, provide education on adverse reactions to both doctors and patients, ensuring that the content of the education avoids causing unnecessary patient anxiety about the medication. Implementing comprehensive improvements in the workflow can effectively reduce the incidence of irrational drug usage events.

Funding

The study was supported by the 2022 Pharmaceutical Research Project of Guangxi Pharmaceutical Association Hospital, Grant/Award Number: GXYXH1-202209 and the 2022 Bethune $\cdot$ Quest Pharmaceutical Research Capacity Building Project, Grant/Award Number: YLSY-ZH-KY-202208(035).

Author contributions

XFW and GYM conceived and designed the study. YL drafted the manuscript. QXC contributed to manuscript revisions. TZ and SHL supervised data collection. CHL and GZW conducted data analysis. All authors critically reviewed the manuscript and approved the final version.

Ethics statement

All methods were performed in accordance with the pertinent guidelines and regulations. This study was approved by the Research Ethics Committee of the Sixth Affiliated Hospital of Guangxi Medical University Review Board (YLSY-IRB-RP-202300). The requirement for written informed consent was exempted by the Research Ethics Committee of the Sixth Affiliated Hospital of Guangxi Medical University because of the retrospective design of the study.

Availability of data and materials

The datasets used and/or analysed during the current study available from the corresponding author on reasonable request.

Competing interests

The authors declare that they have no competing interests.

Footnotes

Acknowledgments

The authors express their gratitude to the staff of the Pharmacy Department for their invaluable support during the course of this study.

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