Pharmacoeconomic evaluation of Pan Long Qi Tablets in the treatment of bone fracture

Pharmacoeconomic evaluation of Pan Long Qi Tablets in the treatment of bone fracture | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Pharmacoeconomic evaluation of Pan Long Qi Tablets in the treatment of bone fracture Liu Bin, Fang Shiyuan, Qin Jian, Zhang Liyong, Wu Zerong, Guo Tuanmao, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6681331/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract OBJECTIVE: To evaluate the economy of Pan Long Qi Tablets compared with Bone-setting Qi Li Tablets in the treatment of fractures. METHODS: A retrospective study was conducted to collect medical records of 6,654 fracture patients from more than 20 hospitals in China from July 2021 to September 2023, which were divided into 3,706 cases in the experimental group (Pan Long Qi tablets combined with the conventional regimen) and 2,948 cases in the control group (Bone-setting Qi Li tablets combined with the conventional regimen) according to the different treatment regimens. Based on the perspective of China's health system, propensity score matching was used to eliminate confounding factors, and a decision tree model was constructed to analyze the cost-effectiveness and cost-utility of the two treatment regimens for treating fractures. Using 0.5 times the per capita GDP of China in 2023 as the willingness-to-pay threshold, one-way sensitivity analysis and probabilistic sensitivity analysis were used to verify the robustness of the results. Results: A total of 6102 samples met the matching requirements for inclusion in the analysis. After matching, the improvement in Visual Analogue Scale(VAS) after treatment in both groups was 0.144 points more in the test group than in the control group, and the improvement in swelling grading score was 0.287 points more in the test group than in the control group. The results of cost-effectiveness analysis showed that the total cost of the trial group regimen was $40.67 higher than that of the control group regimen, and patients in the 60-day recovery period could obtain 0.00442 QALYs more, with an incremental cost-utility ratio(ICER) of $9,213.30/QALY.Univariate sensitivity analyses showed that the incremental QALYs of Pan Long Qi Tablets and the smallest unit median bid price were the main factors influencing the ICER. The probabilistic sensitivity analysis showed that the probability of panax Pan Long Qi tablets combined with conventional treatment being economical was 70.1% when 0.5 times the per capita GDP of China in 2023 was used as the willingness-to-pay threshold. CONCLUSION: Pan Long Qi Tablets are economical compared to Elderberry Qi Li Tablets in the treatment of fractures. pharmacoeconomics Pan Long Qi Tablet Bone-setting Qi Li Tablet propensity score matching Figures Figure 1 Figure 2 Introduction Fractures are a prevalent condition in orthopedic surgery, characterized by the disruption of bone integrity and continuity due to direct or indirect external forces. The primary clinical manifestations include severe pain, swelling, and impaired limb function at the site of injury, imposing significant discomfort on patients [1] and contributing to a substantial economic burden. Data from the Global Health Data Exchange (GHDx) on the official website of the Institute for Health Metrics and Evaluation (IHME) indicate that the incidence of fractures in China rose from 1.06% to 1.496% between 1990 and 2019, marking a notable increase. In this study, fractures were categorized into 12 types, including clavicle, hip, pelvic, skull, and spinal fractures, among others, with the disease burden varying considerably across these categories [2] . The reduced mobility and impaired quality of life experienced by fracture patients increase their dependence on family and heighten the demand for social and medical services. This situation often places patients under prolonged psychological stress, making them vulnerable to negative mental states such as anxiety and depression, thereby exacerbating their mental burden and, to some extent, impeding their recovery [3, 4] . Clinically, non-pharmacological treatments such as manipulative reduction and small splint fixation are usually adopted to promote fracture healing, but they cannot significantly improve the pain and swelling of the affected limbs [5] . Clinical application of conventional analgesic drugs to alleviate the pain of fracture patients, although the effect of pain relief is obvious in a short period of time, but it is easy to produce adverse reactions for a long period of time, so its clinical effect is not ideal [6] . Chinese medicine pays attention to the overall identification and internal and external medication in the treatment of fracture, which has a certain effect on regulating the function of the whole body. At present, Chinese patent medicines commonly used in clinical practice for treating bone fracture include Pan Long Qi Tablet, Bone-setting Qi Li Tablet, Bone-setting Tablet for Injuries, Yunnan Baiyao and so on, and their efficacy has been verified in practical application [7-10] . Among them, Pan Long Qi Tablets have been recommended for rheumatoid bone disease and bone and joint pain treatment by several guidelines, such as Chinese Guidelines for the Treatment of Chronic Musculoskeletal Pain Diseases with Proprietary Chinese Medicines (2023 Edition) [11] , Guidelines for the Combined Western and Traditional Chinese Medicine Diagnosis and Treatment of Osteoarthritis of the Knee [12] , and Guidelines for the Rehabilitation of Pain. Pan Long Qi Tablet is extracted and processed from 29 Chinese medicines, which not only contains danshen, angelica and other products to activate blood circulation and remove blood stasis, but also contains eucommia and other ingredients with the effect of strengthening the muscles and bones, it is a pure traditional Chinese medicine preparation that combines the effects of reducing swelling and relieving pain, activating blood circulation and removing blood stasis, and strengthening the muscles and bones. Pan Long Qi Tablet may be effective in treating rheumatoid arthritis by regulating the signaling pathway related to inflammation and immune response [13] , which is clinically used in rheumatoid arthritis and lumbar muscle strain. And Pan Long Qi tablets can improve the blood rheology index in the evolutionary period of fracture healing, promote the local microcirculation of fracture, provide the material basis for fracture healing, and at the same time accelerate the removal of necrotic tissues and metabolic wastes, and promote the resorption and mechanization of hematoma; it can prevent the production of larger hematoma in the period of primitive bone scab formation, and reduce the cartilage internalization of bone, so as to shorten the time of repair, and speed up the recovery of function. In the current research literature on Pan Long Qi Tablets for the treatment of fractures, most of the studies are simple case-control studies, with data from a single hospital orthopedic department and small sample sizes [14, 15] , and there is a lack of definitive pharmacoeconomic evidence to demonstrate their economics compared to similar products. In this study, we propose to adopt a real-world research design to compare the effects of Pan Long Qi Tablets and Bone-setting Qi Li Tablets in improving pain and swelling in patients with bone fractures through a retrospective, multicenter, case-control study with a large sample size, and to conduct a pharmacoeconomics evaluation, with a view to providing a scientific basis for guiding the rational use of medication for bone fractures. Information and methodology 1.1 Sources In this study, we conducted a retrospective analysis of data from fracture patients across more than 20 hospitals in China, spanning the period from July 2021 to September 2023. The dataset primarily comprised two categories: (1) basic personal information of patients, including gender, age, marital status, and insurance type, and (2) information related to fracture-associated conditions and me-tablets-tabletsn usage. Patients were categorized based on the therapeutic drugs administered. The test group, consisting of 3,706 cases, received Pan Long Qi tablets in addition to conventional treatment, while the control group, comprising 2,948 cases, received Elderberry 7 tablets alongside conventional treatment. Four telephone follow-ups were conducted at key intervals: at the start of enrollment, on the day of fracture surgery or post-displacement (day 1), on the fourth day (day 4), the seventh day (day 7), and the fourteenth day (day 14). During these follow-ups, data pertinent to pharmacoeconomic evaluation, such as pain, swelling, quality of life, and adverse events, were collected through patient self-reports. The study received approval from the Ethics Committee, and a waiver for patient informed consent was obtained. 1.2 Inclusion and exclusion criteria This study employed a real-world observational design, developed in accordance with the relevant guidelines outlined in the Diagnostic and Treatment Guide for Extremity Fractures and the Criteria for Diagnosis and Judgment of Efficacy of Clinical Diseases, to establish specific inclusion and exclusion criteria. The inclusion criteria encompassed patients admitted to the hospital with a confirmed diagnosis of fracture, aged 7 years or older (as of the date of obtaining informed consent), and of any gender. The exclusion criteria comprised individuals who did not satisfy the inclusion criteria, those with incomplete or irregular records on the case report form, cases withdrawn from follow-up visits for reasons other than adverse reactions or lack of efficacy, use of anti-inflammatory and analgesic medications not specified in this study, known allergies to the test medications, excipients, or similar compounds, use of multiple herbal medications, pregnant or lactating women, those planning a pregnancy or unwilling to use contraception, and individuals with suspected or confirmed alcohol or drug abuse, or those who have participated in other clinical trials within the preceding month. 1.3 Treatment The enrolled patients were systematically categorized based on the therapeutic drugs administered. The test group comprised 3,706 cases receiving Pan Long Qi Tablets (State Drug License Z61020050), manufactured by Shaanxi Pan Long Pharmaceutical Group Co. Ltd. The tablets are supplied in boxes containing 48 capsules each, with the primary constituents including 29 flavors of Pan Long Qi , Sheng Chuanwu, Sheng Caowu, Angelica sinensis, Eucommia caryophyllus, Gentiana macrophylla, Tiehlmann's hammer, Safflower, Wugapi, Cow's Knee, Corylus, Dangshen, among others. The prescribed dosage for Pan Long Qi Tablets is oral administration, three times daily, with three tablets per dose, in conjunction with conventional treatment. The control group consisted of 2,948 cases administered Bone-setting Qili Tablets (State Drug License Z20003140), produced by Hunan Jinsha Pharmaceutical Co., Ltd. These tablets are packaged in boxes of 75, with key ingredients including rhubarb, angelica sinensis, boneset, myrrh, borax, frankincense, turkey berry, blood depletion, and natural copper. The recommended dosage for Bone-setting Qili Tablets is oral intake, twice daily, with five tablets per dose, alongside conventional treatment. Follow-up visits were conducted by the researcher, and the collected data were verified for authenticity by quality control personnel. 1.4 Evaluation methodology This study is a non-randomized observational study, and the natural subgroups formed on the basis of doctors' prescriptions are characterized by unbalanced baseline characteristics between groups; for this reason, this study firstly used Logistic regression to estimate the propensity score of each patient to receive Pan Long Qi tablets, and then used the radius matching method (with a radius of 0.01) to match the patients of the two groups, and calculated the corresponding outcome indexes in the samples meeting the matching requirements of the Difference. In this study, were used Cost-Effectiveness Analysis (CEA) method or (Cost-Utility Analysis CUA) method , with Visual Analog Pain Score (VAS) and Swelling Grading Score as the effect indicators, and Quality Adjusted Life Year (QALY) as the utility indicator. A Decision Model (DTM was constructed Tree)to evaluate the economics of the Pan Long Qi tablets regimen compared to the Bone-setting 7-tablet regimen in the treatment of fractures. The threshold was set at 0.5 times the per capita GDP of China in 2023. 1.5 Outcome Indicators 1. 5.1 Effectiveness indicators Pain was evaluated using the visual analog scale (VAS) . The patient drew a point on the horizontal line every day according to his/her self-perception to indicate the degree of pain, and that point was the VAS score. The researcher recorded the VAS score of the patient by telephone call back to the patient 1d, 4d , 7d and 14d after the fracture operation or after the reduction of the fracture. Comparisons were made based on the numerical changes in the VAS score. Swelling assessment was based on the Guiding Principles for Clinical Research of New Chinese Medicines as an indicator of efficacy observation [16] , and swelling scores were based on the Chinese medicine evidence efficacy criteria, and the investigators recorded the swelling scores of the patients by telephone callbacks to the patients 1d, 4d, 7d, and 14d after the patients' fracture surgery or after the dislocation of the fracture. 1. 5.2 Utility indicators Quality-adjusted life years (QALYs) were used as the utility index. The utility values were measured using the universal scale EQ-5D-5L, and the investigators measured the patients by telephone callback four times at 1d, 4d, 7d, and 14d after the patients' fracture surgery or reduction. In a coordinate system with utility value as the vertical axis and survival time as the horizontal axis, QALYs were calculated as the area under the curve of the line connecting the utility values of successive times, and the states of the five EQ-5D dimensions were converted to utility values using the EQ-5D utility value integral system based on the Chinese population [17] . 1. 5.3 Costs In this study, from a health system perspective, the cost indicators include only direct medical costs. This study assumes that the cost of conventional treatment for fracture patients in the two regimens is exactly the same, and because the drugs studied are adjunctive treatment regimens for fractures and have no necessary causal link with postoperative complications, the cost of conventional treatment and the cost of disposing of postoperative complications are not considered in this study. Therefore, the costs included in this study only include the drug costs of Pan Long Qi Tablet and Bone-setting Qi Li Tablet regimens and the costs of dealing with adverse reactions brought about by the drugs, and the drug cost parameters were obtained from the database query of the Pharmaceutical Intelligence Network. With reference to the real-world medication situation and clinical consultation, this study is based on 7d of medication, 14d of efficacy observation, and 2 months after the fracture, the review of X-rays usually shows blurring of the fracture line, the formation of bone scabs, and the local compression and percussion pains are significantly reduced or disappeared. At this time, the fracture enters the stage of bone scab shaping, which is the critical period of healing. The efficacy was extrapolated to 60d for analysis. 1.6 Uncertainty Analysis The effect of changes in each parameter on the results was analyzed by a one-way sensitivity analysis, with each parameter varying by ±10%, and the results were presented in a graph. In addition, probabilistic sensitivity analy sis was carried out using bi-variate Monte Carlo simulation with different distributional assumptions for each parameter, with 10,000 repetitions of sampling, and on the basis of which cost-effectiveness acceptability curves were plotted. The sensitivity analysis was done using Microsoft excel. Results 2.1 Comparison of baseline data before and after matching SPSS22.0 and Stata17.0 software were used to analyze the data.Based on the baseline characteristics combined with the actual clinical situation, the relevant influencing factors were used as covariates, and the propensity score matching with a radius of 0.01 was performed. Intergroup comparisons were performed using the chi-square test for categorical data; continuous data were expressed as mean ± standard deviation (mean ± SD), and comparisons were performed using the paired t-test or chi-square test.. Differences were considered statistically significant at P < 0.05. A total of 3706 patients inthe Pan Long Qi Tablet group and 2948 patients in the group of Bone-setting Qi Li Tablet were included during the study period. As shown in the table, because there were significant differences in the indicators of age, fracture site,hospital level, pre-treatment VAS pain score, pre-treatment swelling score, pre-treatment utility score between patients in the test group and the control group, it indicated that the baseline indicators of the two groups were unbalanced and lacked comparability. In addition, in the context of clinical practice, gender and self-assessed health status indicators may be correlated with outcome measures. To reduce the influence of confounding factors on the results of the clinical study, the above factors that may influence the outcome measures were used as covariates for radius matching. After matching, no significant differences were observed in the above baseline characteristics (see Table 2-1). Table 2-1 Comparison of Pre- and Post-Matching of Baseline Variables norm prematch Treated/Control after matching Treated/Control %reduct[bias] P age 49.174/47.558 49.201/49.332 10.000/-0.800 0.990 sex 0.480/0.448 0.481/0.514 2.480/-2.000 0.009* fracture site tibial fibula 0.117/0.100 0.117/0.141 2.010/-45.700 0.005* ankle 0.079/0.119 0.079/0.083 -5.010/89.100 0.537 femoral 0.114/0.082 0.115/0.104 4.130/65.200 0.153 humerus 0.006/0.074 0.006/0.055 -2.140/66.600 0.427 thoracic and lumbar vertebrae 0.158/0.096 0.159/0.147 7.000/80.800 0.194 foot 0.076/0.079 0.076/0.079 -0.340/-19.600 0.668 else 0.205/0.206 0.204/0.226 -0.100/2014.200 0.039* health status (of an unmarried couple) be close 0.563/0.569 0.561/0.559 -0.510/80.700 0.919 general 0.230/0.200 0.231/0.242 2.720/61.300 0.288 differ from 0.008/0.006 0.008/0.010 0.540/-79.300 0.367 Type of insurance city resident insurance 0.500/0.465 0.497/0.432 2.680/-84.000 0.000* commercial insurance 0.011/0.008 0.011/0.012 0.265/-0.510 0.610 at one's own expense 0.155/0.187 0.156/0.149 -3.180/76.700 0.420 Type of hospital three-tier 0.089/0.319 0.090/0.100 -23.010/95.600 0.174 hospitalization 0.720/0.547 0.716/0.767 13.840/70.500 0.000* Fracture severity Level 1 0.201/0.177 0.201/0.225 2.320/1.200 0.023 Level 2 0.078/0.087 0.077/0.082 -1.310/46.600 0.459 Level 3 0.061/0.071 0.061/0.060 1-.440/84.100 0.805 Level 4 0.122/0.154 0.123/0.158 -3.570/5.700 0.000* Level 5 0.035/0.049 0.034/0.030 -2.710/72.400 0.381 Level 6 0.092/0.092 0.092/0.082 -0.050/-2678.500 0.158 Level 7 0.061/0.108 0.061/0.075 -6.490/69.900 0.027* Level 8 0.148/0.108 0.145/0.129 4.450/59.300 0.066 Types of Fracture Surgery External fixation 0.042/0.016 0.042/0.067 5.790/2.900 0.000* replacement 0.038/0.004 0.038/0.036 8.740/95.700 0.759 molding 0.057/0.019 0.057/0.065 7.410/79.500 0.201 non-operative 0.340/0.466 0.343/0.312 -9.750/75.300 0.010* 2.2 Comparison of output results Based on the cost-effectiveness analysis using matched outcome indicators, the changes in visual analog scale (VAS) and swelling grading scores over 14 days were used as effect measures. The results of these effect measures at 4, 7, and 14 days, as well as the average health utility values of the two groups during different rehabilitation periods after propensity score matching at 1, 4, 7, and 14 days, are presented in Table 2-2. The differences were as follows: for the improvement in the visual analog scale (VAS) after 14 days of treatment, the Pan Long Qi Tablet group showed a 0.144-point greater improvement compared to the Bone-setting Qi Li Tablet group; for the swelling grading score, the Pan Long Qi Tablet group improved by 0.287 points more than the Bone-setting Qi Li Tablet group; and for the utility QALYs after 14 days of treatment, the Pan Long Qi Tablet group had a 0.00063-point higher value than the Bone-setting Qi Li Tablet group (see Table 2-3). In conclusion, the Pan Long Qi Tablet group demonstrated superior effectiveness. Table 2-2 Output results after matching norm treatment plan 1d 4d 7d 14d 4d Improvement 7d Improvements 14d improvement VAS Pain scores test group 7.733 6.308 4.677 2.972 1.425 3.056 4.761** control subjects 7.662 6.263 4.651 3.045 1.399 3.011 4.617 internal bruising marking test group 3.602 2.847 1.598 0.618 0.775 2.004* 2.984** control subjects 3.388 2.584 1.484 0.691 0.804 1.904 2.697 utility value test group 0.313 0.431 0.609 0.743 0.118 0.296** 0.430** control subjects 0.335 0.452 0.618 0.741 0.117 0.283 0.406 efficient test group 9.14%** 56.75%** 87.20%** control subjects 6.16% 52.77% 80.57% 2.3 Pharmacoeconomic analysis Cost-effectiveness analysis and cost-utility analysis were conducted based on the matched outcome indicators. The changes in visual analog scale (VAS) and swelling grading scores over 14 days were used as outcome measures, and the incremental cost-effectiveness ratios (ICERs) were $282.43 per point and $141.71 per point, respectively. This indicates that, compared to the control group, the test group required an additional $282.43 for each point reduction in fracture pain and $141.71 for each point reduction in fracture swelling grading scores. As shown in Table 2-3, the latest bid-winning prices of the two drugs were selected as the drug costs for this specification because both drugs were exclusive products. No adverse reactions requiring intervention were observed in the study; therefore, the adverse reaction management costs for both groups were zero. From the perspective of the health system, the incremental cost-effectiveness ratio (ICER) of the 14-day recovery period Pan Long Qi tablets program compared to the Bone-splitting Qilian tablets program was $10,179.445 per QALY, and the ICER of the 60-day recovery period Pan Long Qi tablets program compared to the Bone-splitting Qilian tablets program was $9,213.291 per QALY. According to data published by the National Bureau of Statistics, China’s per capita GDP in 2023 was 89,358 yuan, and the ICER for the 14-day versus 60-day treatment periods in the two groups was below the established threshold (0.5 times per capita GDP). Based on the analysis results, the Pan Long Qi Tablet regimen was relatively more advantageous compared to the Elderberry Qili Tablet regimen. Table 2-3 Cost-Effectiveness Analysis and Cost-Utility Analysis sports event norm test group control subjects difference (the result of subtraction) Incremental Cost-Effectiveness Ratio ($/cents) Incremental cost-utility ratio ($/QALYs) costs Cost of medication (dollars) 63.430 22.760 40.670 - - Adverse reaction disposal costs ($) 0.000 0.000 0.000 - - Total cost (dollars) 63.430 22.760 40.670 - - effect 14-day VAS improvement value (points) 4.761 4.617 0.144 282.430 - 14-day swelling score improvement value (points) 2.984 2.697 0.287 141.710 - QALYs earned in 14 days 0.00894 0.00831 0.00063 - 10179.445 QALYs earned in 60 days 0.08616 0.08174 0.00442 - 9213.291 2.4 Sensitivity analysis The results of the one-way sensitivity analysis are presented in Figure 1. The parameters with the greatest impact on the ICER, ranked by magnitude, are the QALY increment of Bone-setting Qi Li Tablets, the QALY increment of Pan Long, and the unit price of the winning bid for Pan Long Qi Tablets. The results of the base-case analysis demonstrate robustness. The cost-utility plane scatter plot of the probabilistic sensitivity analysis (PSA) is shown in Figure 2. Using 0.5 times the 2023 GDP per capita of our country as the willingness-to-pay threshold, the Pan Long Qi Tablets treatment regimen has a 70.1% probability of being cost-effective. Discussion This study is a pharmacoeconomic evaluation based on real-world observational studies, where the utilization of real-world data (RWD) plays a critical role. Fracture patients are characterized by complexity and individual differences, and the drugs and methods used in actual treatment vary depending on patient conditions, disease progression, and physician choices. Compared with randomized controlled trials, RWD originates from real clinical environments, providing a more comprehensive reflection of the actual efficacy of Pan Long Qi Tablets in diverse populations and offering physicians valuable evidence-based insights. Using fracture patients from real-world clinical settings as the research subjects, we grouped them based on the actual medications prescribed and evaluated the effects of different treatments on pain relief, quality of life, and total cost of ownership. To minimize the impact of confounding factors, this study employed propensity score matching (PSM) to match patients, compared outcome indicators in the matched samples, and conducted cost-effectiveness and cost-utility analyses. After matching, a total of 6102 patients who met the criteria for the common support domain were included in the final sample. The analysis revealed that, for 14 days, the experimental group showed a greater decrease in the visual analog score (VAS) by 0.144 points, a better reduction in the swelling grading score by 0.287 points, and a higher QALY by 0.00063 points compared to the control group. At 60 days, the QALY in the experimental group was also superior by 0.00442 points. According to the WHO recommendations, the incremental cost-utility ratio (ICUR) is considered fully worthwhile when it is lower than the gross domestic product (GDP) per capita; acceptable when it is lower than three times the GDP per capita; and not worthwhile when it exceeds three times the GDP per capita. In 2023, China’s GDP per capita was 89,358 yuan. Based on this threshold, the incremental cost of applying Pan Long Qi Tablets for the treatment of bone fractures is considered acceptable when it is 0.5 times the GDP per capita. Compared to Bone-setting Qi Li Tablet, the increased cost of using Pan Long Qi Tablet for treating bone fractures falls within the acceptable range. In conclusion, Pan Long Qi Tablet demonstrates superior efficacy in reducing pain and swelling, as well as improving the quality of life in patients with bone fractures, compared to Bone-setting Qi Li Tablet. Based on the WHO’s incremental cost-utility criteria, Pan Long Qi Tablet also exhibits a more favorable cost-effectiveness profile. The present study has the following limitations:(1) Although the use of propensity score matching (PSM) can balance observable differences between groups, it cannot eliminate potential biases caused by unobservable differences.(2) In the cost-effectiveness analysis, the worthiness of the costs incurred to reduce the visual analog scale (VAS) for pain or the swelling score cannot be determined due to the lack of comparable studies for reference. Declarations Funding: SHAANXI PANLONG PHARMACEUTICAL GROUP LIMITED BYSHARE LTD Author Contribution L.B. participated in Project administration、Methodology、Writing-original draft、Writing-review&editing;F.S.Y. participated in Resources、Methodology、Writing-review&editing;Q.J. participated in Data curation、Methodology;Z.L.Y. , W.Z.R . , G.T.M. , D.T. , X.W. and Y.J.Z. participated in Investigation、Data curation;M.N.Y. participated in Methodology、Writing-review&editing;All authors reviewed the manuscript. Human Ethics and Informed Consent Statement References Qiao HJ, Hao YK, Li XF. Orthopaedics. [M]. Beijing: Ancient Chinese Medicine; 2009. p. 01. Yu Xinglei C, Daozhang Z, Qun, et al. Analysis of the burden of disease and trend change of hip fracture in China, 1990–2019 [J]. Mod Prev Med. 2022;49(13):2305–11. Zhou Y, Zhu LY, Dai Y, et al. Effects of introducing appreciation intervention on negative psychology and complications in elderly fracture patients [J]. 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Clinical efficacy of Pan Long Qi Tablets in the treatment of bone fracture [J]. Chin J Orthop Traumatol, 2006, (S2): 154–5. Shi-Qin WEI, Gan-Dan GAN. Therapeutic efficacy of Pan Long Qi Tablets in the treatment of traumatic limb fracture [J]. Mod J Integr Med. 2012;21(34):3802–3. Zheng Xiaoyu. Guidelines for Clinical Research of New Chinese Medicines for Trial Implementation [M]. Beijing: China Medical Science and Technology; 2002. LIU G G, WU H, LI M, et al. Chinese time trade-off values for EQ-5D health states [J]. Value Health. 2014;17(5):597–604. Fei XU, Guo-En LIU. Application of propensity value analysis in pharmacoeconomic evaluation [J]. China Pharmacoeconomics. 2015;10(11):14–6. Additional Declarations No competing interests reported. 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Hospital of USTC, University of Science and Technology of China","correspondingAuthor":false,"prefix":"","firstName":"Fang","middleName":"","lastName":"Shiyuan","suffix":""},{"id":463771188,"identity":"9cf46b8d-4073-41d6-af70-3fe10e1cf17e","order_by":2,"name":"Qin Jian","email":"","orcid":"","institution":"Nanjing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Qin","middleName":"","lastName":"Jian","suffix":""},{"id":463771189,"identity":"00c961f1-dd94-438c-b31a-704ada066bcd","order_by":3,"name":"Zhang Liyong","email":"","orcid":"","institution":"Yangzhou Hospital of TCM","correspondingAuthor":false,"prefix":"","firstName":"Zhang","middleName":"","lastName":"Liyong","suffix":""},{"id":463771190,"identity":"f4e5ae4c-5861-4d2f-a553-c3f78bd4e7d1","order_by":4,"name":"Wu Zerong","email":"","orcid":"","institution":"Shenzhen Baoan Traditional Chinese Medicine Hospital","correspondingAuthor":false,"prefix":"","firstName":"Wu","middleName":"","lastName":"Zerong","suffix":""},{"id":463771191,"identity":"6f810ea0-ebbd-4197-b443-4de7242ad8f8","order_by":5,"name":"Guo Tuanmao","email":"","orcid":"","institution":"Xianyang Central Hospital","correspondingAuthor":false,"prefix":"","firstName":"Guo","middleName":"","lastName":"Tuanmao","suffix":""},{"id":463771192,"identity":"d4c32f7b-36fc-4360-b54a-3632dddd914b","order_by":6,"name":"Dong Ting","email":"","orcid":"","institution":"Hangzhou Fuyang Traditional Chinese Medicine Bone and Joint Hospita","correspondingAuthor":false,"prefix":"","firstName":"Dong","middleName":"","lastName":"Ting","suffix":""},{"id":463771193,"identity":"2e28b42c-6c15-4557-ae96-c161b8fe9dda","order_by":7,"name":"Xu Wei","email":"","orcid":"","institution":"The First Affiliated Hospital of USTC, University of Science and Technology of China","correspondingAuthor":false,"prefix":"","firstName":"Xu","middleName":"","lastName":"Wei","suffix":""},{"id":463771194,"identity":"84a0d939-6cae-47f2-b9f5-29a2f1ea174e","order_by":8,"name":"Yang Jiazhao","email":"","orcid":"","institution":"The First Affiliated Hospital of USTC, University of Science and Technology of China","correspondingAuthor":false,"prefix":"","firstName":"Yang","middleName":"","lastName":"Jiazhao","suffix":""},{"id":463771195,"identity":"ed9a0702-7e5e-4c7d-aaa3-73c09980157b","order_by":9,"name":"Mao Ningying","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAsklEQVRIiWNgGAWjYHAC9g8fftjw8LM3EK+FjXFmT5qMZM8BErQw87AdtjG44UCket3ZPWYPeHjO8zDcYGD88DGHCC1md86YG0hY3OZhnN3ALDlzGzFabuQYSBjw3OZhljnAxsxLtJYEtnM8bECSaC1mEgfYDvDwkKAlrdiwsSeZR4LnYDOxfkne+PjPDzt7++PNBz98JEYLAwOHAZTB2ECUeiBgf0CsylEwCkbBKBipAACpoDWai3GSBAAAAABJRU5ErkJggg==","orcid":"","institution":"China Pharmaceutical University","correspondingAuthor":true,"prefix":"","firstName":"Mao","middleName":"","lastName":"Ningying","suffix":""}],"badges":[],"createdAt":"2025-05-16 13:53:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6681331/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6681331/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":83837788,"identity":"c579f94b-2cd1-4b83-b406-89f25e1f086d","added_by":"auto","created_at":"2025-06-03 13:27:08","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":57789,"visible":true,"origin":"","legend":"\u003cp\u003eCyclorama of one-factor sensitivity analysis\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6681331/v1/eeb450e9b1e8a97435ccb085.png"},{"id":83836658,"identity":"0bdb9417-c9c2-4c66-bf6d-60f38f316c3b","added_by":"auto","created_at":"2025-06-03 13:19:08","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":60395,"visible":true,"origin":"","legend":"\u003cp\u003eScatterplot of cost-utility plane\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-6681331/v1/ea05c5460f574106fd54f332.png"},{"id":92811640,"identity":"16f4ff39-9a69-4cbd-8c01-4f4cba6cc4ea","added_by":"auto","created_at":"2025-10-05 16:17:12","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":787215,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6681331/v1/b5ea3344-ab67-42db-92cc-52c448e877f5.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Pharmacoeconomic evaluation of Pan Long Qi Tablets in the treatment of bone fracture","fulltext":[{"header":"Introduction","content":"\u003cp\u003eFractures are a prevalent condition in orthopedic surgery, characterized by the disruption of bone integrity and continuity due to direct or indirect external forces. The primary clinical manifestations include severe pain, swelling, and impaired limb function at the site of injury, imposing significant discomfort on patients \u003csup\u003e[1]\u003c/sup\u003e and contributing to a substantial economic burden. Data from the Global Health Data Exchange (GHDx) on the official website of the Institute for Health Metrics and Evaluation (IHME) indicate that the incidence of fractures in China rose from 1.06% to 1.496% between 1990 and 2019, marking a notable increase. In this study, fractures were categorized into 12 types, including clavicle, hip, pelvic, skull, and spinal fractures, among others, with the disease burden varying considerably across these categories\u003csup\u003e[2]\u003c/sup\u003e. The reduced mobility and impaired quality of life experienced by fracture patients increase their dependence on family and heighten the demand for social and medical services. This situation often places patients under prolonged psychological stress, making them vulnerable to negative mental states such as anxiety and depression, thereby exacerbating their mental burden and, to some extent, impeding their recovery\u003csup\u003e[3, 4]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eClinically, non-pharmacological treatments such as manipulative reduction and small splint fixation are usually adopted to promote fracture healing, but they cannot significantly improve the pain and swelling of the affected limbs\u003csup\u003e\u0026nbsp;[5]\u003c/sup\u003e . Clinical application of conventional analgesic drugs to alleviate the pain of fracture patients, although the effect of pain relief is obvious in a short period of time, but it is easy to produce adverse reactions for a long period of time, so its clinical effect is not ideal\u003csup\u003e\u0026nbsp;[6]\u003c/sup\u003e . Chinese medicine pays attention to the overall identification and internal and external medication in the treatment of fracture, which has a certain effect on regulating the function of the whole body. At present, Chinese patent medicines commonly used in clinical practice for treating bone fracture include Pan Long Qi Tablet, Bone-setting Qi Li Tablet, Bone-setting Tablet for Injuries, Yunnan Baiyao and so on, and their efficacy has been verified in practical application\u003csup\u003e\u0026nbsp;[7-10]\u003c/sup\u003e . Among them, Pan Long Qi \u0026nbsp;Tablets have been recommended for rheumatoid bone disease and bone and joint pain treatment by several guidelines, such as Chinese Guidelines for the Treatment of Chronic Musculoskeletal Pain Diseases with Proprietary Chinese Medicines (2023 Edition)\u003csup\u003e\u0026nbsp;[11]\u003c/sup\u003e , Guidelines for the Combined Western and Traditional Chinese Medicine Diagnosis and Treatment of Osteoarthritis of the Knee\u003csup\u003e\u0026nbsp;[12]\u003c/sup\u003e , and Guidelines for the Rehabilitation of Pain.\u003c/p\u003e\n\u003cp\u003ePan Long Qi Tablet is extracted and processed from 29 Chinese medicines, which not only contains danshen, angelica and other products to activate blood circulation and remove blood stasis, but also contains eucommia and other ingredients with the effect of strengthening the muscles and bones, it is a pure traditional Chinese medicine preparation that combines the effects of reducing swelling and relieving pain, activating blood circulation and removing blood stasis, and strengthening the muscles and bones. Pan Long Qi Tablet may be effective in treating rheumatoid arthritis by regulating the signaling pathway related to inflammation and immune response\u003csup\u003e\u0026nbsp;[13]\u003c/sup\u003e , which is clinically used in rheumatoid arthritis and lumbar muscle strain. And Pan Long Qi tablets can improve the blood rheology index in the evolutionary period of fracture healing, promote the local microcirculation of fracture, provide the material basis for fracture healing, and at the same time accelerate the removal of necrotic tissues and metabolic wastes, and promote the resorption and mechanization of hematoma; it can prevent the production of larger hematoma in the period of primitive bone scab formation, and reduce the cartilage internalization of bone, so as to shorten the time of repair, and speed up the recovery of function.\u003c/p\u003e\n\u003cp\u003eIn the current research literature on Pan Long Qi Tablets for the treatment of fractures, most of the studies are simple case-control studies, with data from a single hospital orthopedic department and small sample sizes\u003csup\u003e\u0026nbsp;[14, 15]\u003c/sup\u003e , and there is a lack of definitive pharmacoeconomic evidence to demonstrate their economics compared to similar products. In this study, we propose to adopt a real-world research design to compare the effects of Pan Long Qi Tablets and Bone-setting Qi Li Tablets in improving pain and swelling in patients with bone fractures through a retrospective, multicenter, case-control study with a large sample size, and to conduct a pharmacoeconomics evaluation, with a view to providing a scientific basis for guiding the rational use of medication for bone fractures.\u003c/p\u003e"},{"header":"Information and methodology","content":"\u003cp\u003e1.1 Sources\u003c/p\u003e\n\u003cp\u003eIn this study, we conducted a retrospective analysis of data from fracture patients across more than 20 hospitals in China, spanning the period from July 2021 to September 2023. The dataset primarily comprised two categories: (1) basic personal information of patients, including gender, age, marital status, and insurance type, and (2) information related to fracture-associated conditions and me-tablets-tabletsn usage. Patients were categorized based on the therapeutic drugs administered. The test group, consisting of 3,706 cases, received Pan Long Qi \u0026nbsp; tablets in addition to conventional treatment, while the control group, comprising 2,948 cases, received Elderberry 7 tablets alongside conventional treatment. Four telephone follow-ups were conducted at key intervals: at the start of enrollment, on the day of fracture surgery or post-displacement (day 1), on the fourth day (day 4), the seventh day (day 7), and the fourteenth day (day 14). During these follow-ups, data pertinent to pharmacoeconomic evaluation, such as pain, swelling, quality of life, and adverse events, were collected through patient self-reports. The study received approval from the Ethics Committee, and a waiver for patient informed consent was obtained.\u003c/p\u003e\n\u003cp\u003e1.2 Inclusion and exclusion criteria\u003c/p\u003e\n\u003cp\u003eThis study employed a real-world observational design, developed in accordance with the relevant guidelines outlined in the Diagnostic and Treatment Guide for Extremity Fractures and the Criteria for Diagnosis and Judgment of Efficacy of Clinical Diseases, to establish specific inclusion and exclusion criteria. The inclusion criteria encompassed patients admitted to the hospital with a confirmed diagnosis of fracture, aged 7 years or older (as of the date of obtaining informed consent), and of any gender. The exclusion criteria comprised individuals who did not satisfy the inclusion criteria, those with incomplete or irregular records on the case report form, cases withdrawn from follow-up visits for reasons other than adverse reactions or lack of efficacy, use of anti-inflammatory and analgesic medications not specified in this study, known allergies to the test medications, excipients, or similar compounds, use of multiple herbal medications, pregnant or lactating women, those planning a pregnancy or unwilling to use contraception, and individuals with suspected or confirmed alcohol or drug abuse, or those who have participated in other clinical trials within the preceding month.\u003c/p\u003e\n\u003cp\u003e1.3 Treatment\u003c/p\u003e\n\u003cp\u003eThe enrolled patients were systematically categorized based on the therapeutic drugs administered. The test group comprised 3,706 cases receiving Pan Long Qi Tablets (State Drug License Z61020050), manufactured by Shaanxi Pan Long Pharmaceutical Group Co. Ltd. The tablets are supplied in boxes containing 48 capsules each, with the primary constituents including 29 flavors of Pan Long Qi , Sheng Chuanwu, Sheng Caowu, Angelica sinensis, Eucommia caryophyllus, Gentiana macrophylla, Tiehlmann's hammer, Safflower, Wugapi, Cow's Knee, Corylus, Dangshen, among others. The prescribed dosage for Pan Long Qi Tablets is oral administration, three times daily, with three tablets per dose, in conjunction with conventional treatment. The control group consisted of 2,948 cases administered Bone-setting Qili Tablets (State Drug License Z20003140), produced by Hunan Jinsha Pharmaceutical Co., Ltd. These tablets are packaged in boxes of 75, with key ingredients including rhubarb, angelica sinensis, boneset, myrrh, borax, frankincense, turkey berry, blood depletion, and natural copper. The recommended dosage for Bone-setting Qili Tablets is oral intake, twice daily, with five tablets per dose, alongside conventional treatment. Follow-up visits were conducted by the researcher, and the collected data were verified for authenticity by quality control personnel.\u003c/p\u003e\n\u003cp\u003e1.4 Evaluation methodology\u003c/p\u003e\n\u003cp\u003eThis study is a non-randomized observational study, and the natural subgroups formed on the basis of doctors' prescriptions are characterized by unbalanced baseline characteristics between groups; for this reason, this study firstly used Logistic regression to estimate the propensity score of each patient to receive Pan Long Qi \u0026nbsp; tablets, and then used the radius matching method (with a radius of 0.01) to match the patients of the two groups, and calculated the corresponding outcome indexes in the samples meeting the matching requirements of the Difference.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;In this study, were used Cost-Effectiveness Analysis (CEA) method or (Cost-Utility Analysis CUA) method , with Visual Analog Pain Score (VAS) and Swelling Grading Score as the effect indicators, and Quality Adjusted Life Year (QALY) as the utility indicator. A Decision \u0026nbsp;Model (DTM was constructed Tree)to evaluate the economics of the Pan Long Qi tablets regimen compared to the Bone-setting 7-tablet regimen in the treatment of fractures. The threshold was set at 0.5 times the per capita GDP of China in 2023.\u003c/p\u003e\n\u003cp\u003e1.5 Outcome Indicators\u003c/p\u003e\n\u003cp\u003e1. 5.1 Effectiveness indicators\u003c/p\u003e\n\u003cp\u003ePain was evaluated using the visual analog scale (VAS) . The patient drew a point on the horizontal line every day according to his/her self-perception to indicate the degree of pain, and that point was the VAS score. The researcher recorded the VAS score of the patient by telephone call back to the patient 1d, 4d , 7d and 14d after the fracture operation or after the reduction of the fracture. Comparisons were made based on the numerical changes in the VAS score.\u003c/p\u003e\n\u003cp\u003eSwelling assessment was based on the Guiding Principles for Clinical Research of New Chinese Medicines as an indicator of efficacy observation\u003csup\u003e\u0026nbsp;[16]\u003c/sup\u003e , and swelling scores were based on the Chinese medicine evidence efficacy criteria, and the investigators recorded the swelling scores of the patients by telephone callbacks to the patients 1d, 4d, 7d, and 14d after the patients' fracture surgery or after the dislocation of the fracture.\u003c/p\u003e\n\u003cp\u003e1. 5.2 Utility indicators\u003c/p\u003e\n\u003cp\u003eQuality-adjusted life years (QALYs) were used as the utility index. The utility values were measured using the universal scale EQ-5D-5L, and the investigators measured the patients by telephone callback four times at 1d, 4d, 7d, and 14d after the patients' fracture surgery or reduction. In a coordinate system with utility value as the vertical axis and survival time as the horizontal axis, QALYs were calculated as the area under the curve of the line connecting the utility values of successive times, and the states of the five EQ-5D dimensions were converted to utility values using the EQ-5D utility value integral system based on the Chinese population\u003csup\u003e\u0026nbsp;[17]\u003c/sup\u003e .\u003c/p\u003e\n\u003cp\u003e1. 5.3 Costs\u003c/p\u003e\n\u003cp\u003eIn this study, from a health system perspective, the cost indicators include only direct medical costs. This study assumes that the cost of conventional treatment for fracture patients in the two regimens is exactly the same, and because the drugs studied are adjunctive treatment regimens for fractures and\u0026nbsp;have no necessary causal link with postoperative complications, the cost of conventional treatment and the cost of disposing of postoperative complications are not considered in this study. Therefore, the costs included in this study only include the drug costs of Pan Long Qi Tablet and Bone-setting Qi Li Tablet regimens and the costs of dealing with adverse reactions brought about by the drugs, and\u0026nbsp;the drug cost parameters were obtained from the database query of the Pharmaceutical Intelligence Network. With reference to the real-world medication situation and clinical consultation, this study is based on 7d of medication, 14d of efficacy observation, and 2 months after the fracture, the review of X-rays usually shows blurring of the fracture line, the formation of bone scabs, and the local compression and percussion pains are significantly reduced or disappeared. At this time, the fracture enters the stage of bone scab shaping, which is the critical period of healing. The efficacy was extrapolated to 60d for analysis.\u003c/p\u003e\n\u003cp\u003e1.6 Uncertainty Analysis\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe effect of changes in each parameter on the results was analyzed by a one-way sensitivity analysis, with each parameter varying by ±10%, and the results were presented in a graph. In addition, probabilistic sensitivity analy \u0026nbsp; sis was carried out using bi-variate Monte Carlo simulation with different distributional assumptions for each parameter, with 10,000 repetitions of sampling, and on the basis of which cost-effectiveness acceptability curves were plotted. The sensitivity analysis was done using Microsoft excel.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e2.1 Comparison of baseline data before and after matching\u003c/p\u003e\n\u003cp\u003eSPSS22.0 and Stata17.0 software were used to analyze the data.Based on the baseline characteristics combined with the actual clinical situation, the relevant influencing factors were used as covariates, and the propensity score matching with a radius of 0.01 was performed. Intergroup comparisons were performed using the chi-square test for categorical data; continuous data were expressed as mean\u0026nbsp;±\u0026nbsp;standard deviation (mean\u0026nbsp;±\u0026nbsp;SD), and comparisons were performed using the paired t-test or chi-square test.. Differences were considered statistically significant at P \u0026lt; 0.05.\u003c/p\u003e\n\u003cp\u003eA total of 3706 patients inthe Pan Long Qi Tablet group and 2948 patients in the group of Bone-setting Qi Li Tablet were included during the study period. As shown in the table, because there were significant differences in the indicators of age, fracture site,hospital level, pre-treatment VAS pain score, pre-treatment swelling score, pre-treatment utility score between patients in the test group and the control group, it indicated that the baseline indicators of the two groups were unbalanced and lacked comparability. In addition, in the context of clinical practice, gender and self-assessed health status indicators may be correlated with outcome measures. To reduce the influence of confounding factors on the results of the clinical study, the above factors that may influence the outcome measures were used as covariates for radius matching. After matching, no significant differences were observed in the above baseline characteristics (see Table 2-1).\u003c/p\u003e\n\u003cp\u003eTable 2-1 Comparison of Pre- and Post-Matching of Baseline Variables\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"99%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003enorm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eprematch\u003c/p\u003e\n \u003cp\u003eTreated/Control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eafter matching\u003c/p\u003e\n \u003cp\u003eTreated/Control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e%reduct[bias]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e49.174/47.558\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e49.201/49.332\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e10.000/-0.800\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.990\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003esex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.480/0.448\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.481/0.514\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.480/-2.000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.009*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003efracture site\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003etibial fibula\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.117/0.100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.117/0.141\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.010/-45.700\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.005*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eankle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.079/0.119\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.079/0.083\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-5.010/89.100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.537\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003efemoral\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.114/0.082\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.115/0.104\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e4.130/65.200\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.153\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ehumerus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.006/0.074\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.006/0.055\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-2.140/66.600\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.427\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ethoracic and lumbar vertebrae\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.158/0.096\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.159/0.147\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e7.000/80.800\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.194\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003efoot\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.076/0.079\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.076/0.079\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-0.340/-19.600\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.668\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eelse\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.205/0.206\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.204/0.226\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-0.100/2014.200\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.039*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ehealth status\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e(of an unmarried couple) be close\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.563/0.569\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.561/0.559\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-0.510/80.700\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.919\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003egeneral\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.230/0.200\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.231/0.242\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.720/61.300\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.288\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ediffer from\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.008/0.006\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.008/0.010\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.540/-79.300\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.367\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eType of insurance\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ecity resident insurance\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.500/0.465\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.497/0.432\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.680/-84.000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.000*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ecommercial insurance\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.011/0.008\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.011/0.012\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.265/-0.510\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.610\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eat one's own expense\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.155/0.187\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.156/0.149\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-3.180/76.700\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.420\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eType of hospital\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ethree-tier\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.089/0.319\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.090/0.100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-23.010/95.600\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.174\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ehospitalization\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.720/0.547\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.716/0.767\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e13.840/70.500\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.000*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eFracture severity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eLevel 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.201/0.177\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.201/0.225\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.320/1.200\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.023\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eLevel 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.078/0.087\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.077/0.082\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-1.310/46.600\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.459\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eLevel 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.061/0.071\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.061/0.060\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;1-.440/84.100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.805\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eLevel 4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.122/0.154\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.123/0.158\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-3.570/5.700\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.000*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eLevel 5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.035/0.049\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.034/0.030\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-2.710/72.400\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.381\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eLevel 6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.092/0.092\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.092/0.082\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-0.050/-2678.500\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.158\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eLevel 7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.061/0.108\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.061/0.075\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-6.490/69.900\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.027*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eLevel 8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.148/0.108\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.145/0.129\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e4.450/59.300\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.066\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eTypes of Fracture Surgery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eExternal fixation\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.042/0.016\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.042/0.067\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e5.790/2.900\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.000*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003ereplacement\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.038/0.004\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.038/0.036\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e8.740/95.700\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.759\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003emolding\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.057/0.019\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.057/0.065\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e7.410/79.500\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.201\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003enon-operative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.340/0.466\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.343/0.312\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-9.750/75.300\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.010*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e2.2 Comparison of output results\u003c/p\u003e\n\u003cp\u003eBased on the cost-effectiveness analysis using matched outcome indicators, the changes in visual analog scale (VAS) and swelling grading scores over 14 days were used as effect measures. The results of these effect measures at 4, 7, and 14 days, as well as the average health utility values of the two groups during different rehabilitation periods after propensity score matching at 1, 4, 7, and 14 days, are presented in Table 2-2. The differences were as follows: for the improvement in the visual analog scale (VAS) after 14 days of treatment, the Pan Long Qi Tablet group showed a 0.144-point greater improvement compared to the Bone-setting Qi Li Tablet group; for the swelling grading score, the Pan Long Qi Tablet group improved by 0.287 points more than the Bone-setting Qi Li Tablet group; and for the utility QALYs after 14 days of treatment, the Pan Long Qi Tablet group had a 0.00063-point higher value than the Bone-setting Qi Li Tablet group (see Table 2-3). In conclusion, the Pan Long Qi Tablet group demonstrated superior effectiveness.\u003c/p\u003e\n\u003cp\u003eTable 2-2 Output results after matching\u003c/p\u003e\n\u003cdiv align=\"center\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"99%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003enorm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003etreatment plan\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1d\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e4d\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e7d\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e14d\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e4d Improvement\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e7d Improvements\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e14d improvement\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003eVAS\u003c/p\u003e\n \u003cp\u003ePain scores\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003etest group\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e7.733\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e6.308\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e4.677\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.972\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.425\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3.056\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e4.761**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003econtrol subjects\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e7.662\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e6.263\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e4.651\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3.045\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.399\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3.011\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e4.617\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003einternal bruising\u003c/p\u003e\n \u003cp\u003emarking\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003etest group\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3.602\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.847\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.598\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.618\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.775\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.004*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.984**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003econtrol subjects\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3.388\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.584\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.484\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.691\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.804\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.904\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.697\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003eutility value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003etest group\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.313\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.431\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.609\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.743\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.118\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.296**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.430**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003econtrol subjects\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.335\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.452\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.618\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.741\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.117\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.283\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.406\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003eefficient\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003etest group\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\"\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e9.14%**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e56.75%**\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e87.20%**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003econtrol subjects\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\"\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e6.16%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e52.77%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e80.57%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e2.3 Pharmacoeconomic analysis\u003c/p\u003e\n\u003cp\u003eCost-effectiveness analysis and cost-utility analysis were conducted based on the matched outcome indicators. The changes in visual analog scale (VAS) and swelling grading scores over 14 days were used as outcome measures, and the incremental cost-effectiveness ratios (ICERs) were $282.43 per point and $141.71 per point, respectively. This indicates that, compared to the control group, the test group required an additional $282.43 for each point reduction in fracture pain and $141.71 for each point reduction in fracture swelling grading scores. As shown in Table 2-3, the latest bid-winning prices of the two drugs were selected as the drug costs for this specification because both drugs were exclusive products. No adverse reactions requiring intervention were observed in the study; therefore, the adverse reaction management costs for both groups were zero. From the perspective of the health system, the incremental cost-effectiveness ratio (ICER) of the 14-day recovery period Pan Long Qi tablets program compared to the Bone-splitting Qilian tablets program was $10,179.445 per QALY, and the ICER of the 60-day recovery period Pan Long Qi tablets program compared to the Bone-splitting Qilian tablets program was $9,213.291 per QALY. According to data published by the National Bureau of Statistics, China’s per capita GDP in 2023 was 89,358 yuan, and the ICER for the 14-day versus 60-day treatment periods in the two groups was below the established threshold (0.5 times per capita GDP). Based on the analysis results, the Pan Long Qi Tablet regimen was relatively more advantageous compared to the Elderberry Qili Tablet regimen.\u003c/p\u003e\n\u003cp\u003eTable 2-3 Cost-Effectiveness Analysis and Cost-Utility Analysis\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"560\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003esports event\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003enorm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003etest group\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003econtrol subjects\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003edifference (the result of subtraction)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eIncremental Cost-Effectiveness Ratio ($/cents)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eIncremental cost-utility ratio ($/QALYs)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\"\u003e\n \u003cp\u003ecosts\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eCost of medication (dollars)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e63.430\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e22.760\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e40.670\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eAdverse reaction disposal costs ($)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eTotal cost (dollars)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e63.430\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e22.760\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e40.670\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003eeffect\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e14-day VAS improvement value (points)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e4.761\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e4.617\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.144\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e282.430\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e14-day swelling score improvement value (points)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.984\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.697\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.287\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e141.710\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eQALYs earned in 14 days\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.00894\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.00831\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.00063\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e10179.445\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eQALYs earned in 60 days\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.08616\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.08174\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.00442\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e9213.291\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e2.4 Sensitivity analysis\u003c/p\u003e\n\u003cp\u003eThe results of the one-way sensitivity analysis are presented in Figure 1. The parameters with the greatest impact on the ICER, ranked by magnitude, are the QALY increment of Bone-setting Qi Li Tablets, the QALY increment of Pan Long, and the unit price of the winning bid for Pan Long Qi Tablets. The results of the base-case analysis demonstrate robustness.\u003c/p\u003e\n\u003cp\u003eThe cost-utility plane scatter plot of the probabilistic sensitivity analysis (PSA) is shown in Figure 2. Using 0.5 times the 2023 GDP per capita of our country as the willingness-to-pay threshold, the Pan Long Qi Tablets treatment regimen has a 70.1% probability of being cost-effective.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study is a pharmacoeconomic evaluation based on real-world observational studies, where the utilization of real-world data (RWD) plays a critical role. Fracture patients are characterized by complexity and individual differences, and the drugs and methods used in actual treatment vary depending on patient conditions, disease progression, and physician choices. Compared with randomized controlled trials, RWD originates from real clinical environments, providing a more comprehensive reflection of the actual efficacy of Pan Long Qi Tablets in diverse populations and offering physicians valuable evidence-based insights. Using fracture patients from real-world clinical settings as the research subjects, we grouped them based on the actual medications prescribed and evaluated the effects of different treatments on pain relief, quality of life, and total cost of ownership. To minimize the impact of confounding factors, this study employed propensity score matching (PSM) to match patients, compared outcome indicators in the matched samples, and conducted cost-effectiveness and cost-utility analyses. After matching, a total of 6102 patients who met the criteria for the common support domain were included in the final sample. The analysis revealed that, for 14 days, the experimental group showed a greater decrease in the visual analog score (VAS) by 0.144 points, a better reduction in the swelling grading score by 0.287 points, and a higher QALY by 0.00063 points compared to the control group. At 60 days, the QALY in the experimental group was also superior by 0.00442 points.\u003c/p\u003e\n\u003cp\u003eAccording to the WHO recommendations, the incremental cost-utility ratio (ICUR) is considered\u0026nbsp;fully worthwhile\u0026nbsp;when it is lower than the gross domestic product (GDP) per capita;\u0026nbsp;acceptable\u0026nbsp;when it is lower than three times the GDP per capita; and\u0026nbsp;not worthwhile\u0026nbsp;when it exceeds three times the GDP per capita. In 2023, China’s GDP per capita was 89,358 yuan. Based on this threshold, the incremental cost of applying\u0026nbsp;Pan Long Qi Tablets\u0026nbsp;for the treatment of bone fractures is considered acceptable when it is\u0026nbsp;0.5 times the GDP per capita. Compared to\u0026nbsp;Bone-setting Qi Li Tablet, the increased cost of using\u0026nbsp;Pan Long Qi Tablet\u0026nbsp;for treating bone fractures falls within the acceptable range.\u003c/p\u003e\n\u003cp\u003eIn conclusion,\u0026nbsp;Pan Long Qi Tablet\u0026nbsp;demonstrates superior efficacy in reducing pain and swelling, as well as improving the quality of life in patients with bone fractures, compared to\u0026nbsp;Bone-setting Qi Li Tablet. Based on the WHO’s incremental cost-utility criteria,\u0026nbsp;Pan Long Qi Tablet\u0026nbsp;also exhibits a more favorable cost-effectiveness profile.\u003c/p\u003e\n\u003cp\u003eThe present study has the following limitations:(1) Although the use of propensity score matching (PSM) can balance observable differences between groups, it cannot eliminate potential biases caused by unobservable differences.(2) In the cost-effectiveness analysis, the worthiness of the costs incurred to reduce the visual analog scale (VAS) for pain or the swelling score cannot be determined due to the lack of comparable studies for reference.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eFunding:\u003c/h2\u003e \u003cp\u003eSHAANXI PANLONG PHARMACEUTICAL GROUP LIMITED BYSHARE LTD\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eL.B. participated in Project administration、Methodology、Writing-original draft、Writing-review\u0026amp;editing;F.S.Y. participated in Resources、Methodology、Writing-review\u0026amp;editing;Q.J. participated in Data curation、Methodology;Z.L.Y. , W.Z.R . , G.T.M. , D.T. , X.W. and Y.J.Z. participated in Investigation、Data curation;M.N.Y. participated in Methodology、Writing-review\u0026amp;editing;All authors reviewed the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHuman Ethics and Informed Consent Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cimg width=\"215\" height=\"237\" 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\" alt=\"image\"\u003e\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eQiao HJ, Hao YK, Li XF. Orthopaedics. [M]. Beijing: Ancient Chinese Medicine; 2009. p. 01.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYu Xinglei C, Daozhang Z, Qun, et al. Analysis of the burden of disease and trend change of hip fracture in China, 1990\u0026ndash;2019 [J]. Mod Prev Med. 2022;49(13):2305\u0026ndash;11.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhou Y, Zhu LY, Dai Y, et al. Effects of introducing appreciation intervention on negative psychology and complications in elderly fracture patients [J]. Int J Psychiatry. 2015;42(03):74\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCui Shuangshang Z, Likun M, Xinlong. Epidemiology and economic burden of disease of hip fracture in the elderly in China [J]. Chin J Integr Surg. 2020;26(03):567\u0026ndash;70.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJin-Hao HUANG, Jian-Hua RONG, Xin-Yi CHEN. 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Chin Med J. 2018;98(45):3653\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNIU X Y Y, YU J, SONG H, YU J, HUANG Q, LIU Y, ZHANG D, HAN T. Pan Long Qi tablet suppresses adjuvant-induced rheumatoid arthritis by inhibiting the inflammatory reponse in vivo and in vitro.[J]. J Ethnopharmacol. 2023;308:116250.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHao PENG, Che WANG, Hongsong FANG. Clinical efficacy of Pan Long Qi Tablets in the treatment of bone fracture [J]. Chin J Orthop Traumatol, 2006, (S2): 154\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShi-Qin WEI, Gan-Dan GAN. Therapeutic efficacy of Pan Long Qi Tablets in the treatment of traumatic limb fracture [J]. Mod J Integr Med. 2012;21(34):3802\u0026ndash;3.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZheng Xiaoyu. Guidelines for Clinical Research of New Chinese Medicines for Trial Implementation [M]. Beijing: China Medical Science and Technology; 2002.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLIU G G, WU H, LI M, et al. Chinese time trade-off values for EQ-5D health states [J]. Value Health. 2014;17(5):597\u0026ndash;604.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFei XU, Guo-En LIU. Application of propensity value analysis in pharmacoeconomic evaluation [J]. China Pharmacoeconomics. 2015;10(11):14\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"pharmacoeconomics, Pan Long Qi Tablet, Bone-setting Qi Li Tablet, propensity score matching","lastPublishedDoi":"10.21203/rs.3.rs-6681331/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6681331/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eOBJECTIVE: \u003c/strong\u003eTo evaluate the economy of Pan Long Qi Tablets compared with Bone-setting Qi Li Tablets in the treatment of fractures.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMETHODS: \u003c/strong\u003eA retrospective study was conducted to collect medical records of 6,654 fracture patients from more than 20 hospitals in China from July 2021 to September 2023, which were divided into 3,706 cases in the experimental group (Pan Long Qi tablets combined with the conventional regimen) and 2,948 cases in the control group (Bone-setting Qi Li tablets combined with the conventional regimen) according to the different treatment regimens. Based on the perspective of China's health system, propensity score matching was used to eliminate confounding factors, and a decision tree model was constructed to analyze the cost-effectiveness and cost-utility of the two treatment regimens for treating fractures. Using 0.5 times the per capita GDP of China in 2023 as the willingness-to-pay threshold, one-way sensitivity analysis and probabilistic sensitivity analysis were used to verify the robustness of the results.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e A total of 6102 samples met the matching requirements for inclusion in the analysis. After matching, the improvement in Visual Analogue Scale(VAS) after treatment in both groups was 0.144 points more in the test group than in the control group, and the improvement in swelling grading score was 0.287 points more in the test group than in the control group. The results of cost-effectiveness analysis showed that the total cost of the trial group regimen was $40.67 higher than that of the control group regimen, and patients in the 60-day recovery period could obtain 0.00442 QALYs more, with an incremental cost-utility ratio(ICER) of $9,213.30/QALY.Univariate sensitivity analyses showed that the incremental QALYs of Pan Long Qi Tablets and the smallest unit median bid price were the main factors influencing the ICER. The probabilistic sensitivity analysis showed that the probability of panax Pan Long Qi tablets combined with conventional treatment being economical was 70.1% when 0.5 times the per capita GDP of China in 2023 was used as the willingness-to-pay threshold.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCONCLUSION: \u003c/strong\u003ePan Long Qi Tablets are economical compared to Elderberry Qi Li Tablets in the treatment of fractures.\u003c/p\u003e","manuscriptTitle":"Pharmacoeconomic evaluation of Pan Long Qi Tablets in the treatment of bone fracture","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-03 13:19:03","doi":"10.21203/rs.3.rs-6681331/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"2767f430-dd8b-4231-8ae4-a21b35ce8b9f","owner":[],"postedDate":"June 3rd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-10-05T16:09:04+00:00","versionOfRecord":[],"versionCreatedAt":"2025-06-03 13:19:03","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6681331","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6681331","identity":"rs-6681331","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}