Using patient-reported outcomes in clinical studies for cardiovascular diseases of Traditional Chinese medicine worldwide: a cross-sectional study

Using patient-reported outcomes in clinical studies for cardiovascular diseases of Traditional Chinese medicine worldwide: a cross-sectional study | 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 Using patient-reported outcomes in clinical studies for cardiovascular diseases of Traditional Chinese medicine worldwide: a cross-sectional study Hao Liu, Xinmiao Guan, Yuanyuan Lin, Minjing Luo, Changhao Liang, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4678899/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 11 You are reading this latest preprint version Abstract Background and purpose: Patient-reported outcomes (PROs) are health condition assessments directly expressed by patients, providing a precise reflection of the patient's perspective. We aim to understand how PROs were being used to provide suggestions for conducting high-quality clinical studies of Traditional Chinese medicine (TCM) for cardiovascular diseases (CVD). Methods: We searched clinical studies of TCM for CVD from the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) registered between January 1, 2010, and December 31, 2023. Trial phases, study types, age, gender, TCM interventions, regions and countries, time trends, PROs as primary/secondary/co-primary outcomes, and PRO instruments explicitly specified or implicitly specified were analyzed. We classified the studies that explicitly specified PROs into 14 categories based on the International Classification of Diseases-11 (ICD-11) ,and compared their PRO instruments with the Core Outcome Measures in Effectiveness Trials (COMET). Results: 487 TCM CVD studies were identified. 194 studies did not mention the use of PRO instruments. 250 studies explicitly specified the PRO tool, while 43 studies implicitly (studies registration mentioned the use of PROs, but PRO instruments were not specified). Out of the 293 studies that included PROs, 84 (17.2%) listed PROs as their primary outcomes, 144 (29.6%) as secondary outcomes and 65 (13.3%) as co-primary outcomes. Chronic coronary heart disease (26.96%), hypertension (15.70%), and heart failure (14.68%) were the most common diseases in that 250 studies. Furthermore, their PRO instruments partially complied with COMET's recommendations ,while other diseases did not. Frequently used PRO instruments included the SAQ (Seattle Angina Questionnaire), the TCMSS (TCM syndrome score), the SF-8/12/36 (Short-Form 8/12/36-item Health Survey), and the VAS (Vsual Analog Scale). Conclusion: Over the past decade, there has been a continued increase in the use of PROs as a measure in clinical investigations focused on TCM for CVD. Research and development of PROs core endpoints for different CVD could be improved. Given the current challenges surrounding the use of PROs in clinical studies of TCM, such as the inconsistent availability and absence of standardized PRO instruments for TCM, it is crucial to prioritize research on establishing standardized and normalized scales specifically designed for TCM. Traditional Chinese medicine patient-reported outcomes cardiovascular disease clinical trial registry Figures Figure 1 Figure 2 Figure 3 Figure 4 1. Introduction Cardiovascular disease (CVD) is a term used to refer to the range of diseases that impact the heart and blood vessels, including hypertension, coronary heart disease, cerebrovascular disease, heart failure, and various other cardiac ailments[1]. CVD persists as the foremost cause of mortality globally, significantly impacting both health outcomes and healthcare expenditure[2, 3]. In 2019, CVD caused 9.6 million deaths in males and 8.9 million deaths in females, accounting for approximately one-third of the global mortality rate, with 6.1 million of these deaths occurring in people aged 30 to 70 years, in addition to China reporting the highest number of CVD-related deaths[2]. CVD stems from a myriad of pathological factors, including atherosclerosis, hypertension, hyperlipidemia, and diabetes mellitus, among others. These factors are associated with disorders in energy metabolism, abnormalities in mitochondrial structure, oxidative stress injuries, cardiomyocyte apoptosis, and inflammatory reactions. However, the precise pathogenesis remains incompletely understood[4–7]. The treatment modalities for CVD mentioned above typically encompass drug therapy, interventional procedures, and surgical techniques, these approaches aim to enhance patient health through various perspectives and mechanisms[8]. Among these, drug therapy serves as a primary approach in addressing CVD in clinical practice[9]. Given the intricate pathophysiological mechanisms of cardiovascular disease, recommended treatments include angiotensin-converting enzyme inhibitors, angiotensin receptor antagonists, β-receptor antagonists, vasodilators, diuretics, α-receptor antagonists, positive inotropes, lipid-lowering agents, antiarrhythmic agents, and calcium channel blockers. In recent years, natural medicines and complementary alternative medicine, particularly Traditional Chinese medicine (TCM), have demonstrated significant potential in the field of cardiovascular diseases[10, 11], such as Tongxinluo for acute myocardial infarction[12], acupuncture for Chronic Stable Angina[13]. TCM embodies a distinct paradigm of medical practice, characterized by a holistic approach to patient care. Within this framework, therapeutic interventions frequently incorporate natural herbal and other remedies tailored to specific conditions, aiming to enhance overall health and well-being[14]. In contrast to modern medicine's emphasis on individual symptoms, TCM practitioners prioritize the holistic well-being of the patient, viewing them as a unified entity[15]. Therefore, it is difficult for clinical research in TCM to focus only on the improvement of a single symptom or sign, as is the case in modern medicine. Consequently, there is a lack of universally accepted standards for evaluating treatment outcomes in TCM[16]. In 2006, the U.S. Food and Drug Administration (FDA) issued guidance[17] to support patient-reported outcomes (PROs) measures used as validity endpoints in clinical studies and to support the development and use of study results measured by PRO instruments in support of medical device marketing authorization[18]. PROs are health condition assessments directly expressed by patients, without the need for a clinician or third-party interpretation of patient responses[19]. This methodology holds paramount importance in evaluating health status, behaviors, and the patient's care experience within clinical and research domains, effectively capturing the patient's viewpoint with precision[20–22]. PRO instruments are standardized questionnaires designed to gather information on health outcomes directly from patients[23].PROs and PRO instruments have found extensive application in assessing health-related quality of life, physical capacity, mental and cognitive changes, functional status, symptoms, and overall well-being[24]. They offer greater reproducibility compared to clinician-elicited measures, which may be constrained by both intraclinician and interclinician reporting variability[25–28]. Consequently, PROs have gained widespread utilization in comprehending patients' perspectives in randomized clinical trials[29] and clinical practice[30], offering several advantages such as noninvasiveness, patient-centeredness, and easy accessibility[31]. The concept of PROs has garnered attention within the TCM community due to its alignment with the traditional emphasis on subjective patient reporting inherent in TCM. Throughout history, TCM practitioners have relied on the patient's chief complaint as a primary indicator of treatment outcomes. Consequently, PROs have been embraced by researchers in TCM as a promising method for establishing an evidence base for traditional practices. Moreover, researchers in China have explored alternative methodologies tailored to better suit the unique characteristics of TCM[16]. The number of clinical studies of PROs in the field of TCM for cardiovascular disease has continued to increase over the past few years, and despite the recognized importance of PROs in clinical and research settings, they are still underutilized in CVD studies[32–34]. Exploring the application of PROs in clinical studies of TCM is crucial to discern its utilization and offer recommendations for conducting high-quality studies in this field. Therefore, this study reviews and evaluates the use of PROs in the field of TCM for CVD based on the World Health Organization International Clinical Trials Registry Platform, in order to provide suggestions for conducting high-quality clinical studies of TCM. 2. Materials and methods 2.1. Study design This cross-sectional study set out to count and evaluate the features of clinical studies for CVD using PROs as primary or secondary endpoint that were carried out worldwide in the field of TCM between January 1, 2010, and December 31, 2023. Data was collected from the World Health Organization International Clinical Trials Registry Platform (ICTRP), ( http://apps.who.int/trialsearch ) (Search strategy in Supplementary Method S1 ). We included clinical studies for CVD of TCM worldwide. And looked for the PRO instruments that were most frequently employed in studies for certain target diseases. This study adhered to The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline. 2.2 Data Collection Strategy TCM clinical studies for CVD were included (Fig. 1 . Flowchart of study identification). CVD are defined as diseases of the circulatory system included in Chap. 11 of ICD-11(International Classification of Diseases-11), similar disorders were grouped together in the same categories due to the significant heterogeneity in the target diseases according to ICD-11 (Classification of specific diseases in Supplementary Method S2 ). Repeated studies we keep only one. The information gathered to evaluate the conditions and characteristics of studies encompassed two categories: 1) fundamental information, such as registration number, date of registration, scientific title; regions and countries, participant age and gender, clinical study phases; 2) crucial information, such as outcomes (including PRO instruments), Chinese medicine interventions, target disease. We also searched the the Core Outcome Measures in Effectiveness Trials (COMET) for the recommended use of PRO instruments for these diseases ( https://www.comet-initiative.org/ ). 2.3 Data classification The eligible studies were categorized into four groups based on the reported outcomes: (1) studies that registered PROs as primary endpoints; (2) studies that registered PROs as secondary outcomes; (3) studies that registered PROs as both primary and secondary endpoints; (4) studies that did not mention the use of PROs in their registration. 2.4 Statistical Analysis Data on the features of the included studies were extracted independently by two of us (Hao Liu and Yuanyuan Lin), using predesigned data extraction tables. The PRO instruments used in each study were summarized using our condition classification to determine the most and least commonly utilized instruments. For quantitative analysis, we only considered entries that mentioned the names of the PRO instruments. Descriptive statistics were used to characterize the clinical trial phases, study type, participant’s age, gender, TCM interventions, regions and countries, diseases, and the PRO instruments for included studies by SPSS software, version 22.0 (IBM Corp). 3 Results 3.1 Search results A total of 545 studies were retrieved, 44 duplicates and 14 non-cardiovascular-related research were eliminated, leaving 487 suitable studies for analysis. Figure 1 depicts a flow chart for the study identification process. Out of the 487 studies that were analyzed, 194 (39.8%) studies did not utilize any PRO instruments, whereas 293 studies employed PROs for their outcomes. Out of the 293 PRO studies, 250 (85.3%) studies clearly mentioned the specific PRO instruments they used, whereas the remaining 43 (14.7%) studies mentioned PROs but did not provide details on the specific PRO instruments utilized. On the other hand, of these 293 PRO studies, 84 (17.2%) studies used PROs as their primary outcome, 144 (29.6%) studies used PROs as their secondary outcomes and 65 (13.3%) studies used PROs as co-primary outcomes (Fig. 1 ). ICTRP: International Clinical Trials Registry Platform; CVD: cardiovascular diseases; PROs: patient-reported outcomes. 3.2 Studies characteristics The number of TCM clinical registration studies increased between 2010 and 2023, as shown in Fig. 2 , which also demonstrates the proportion of studies that list PROs as the outcomes among the TCM studies. (Fig. 2 ) Table 1 displays the overall characteristics of the included studies. Of the 293 PRO studies, the most prevalent result was PROs as secondary outcomes 144 (29.6%), followed by primary outcomes 84 (29.6%) and co-primary outcomes 65 (22.2%). Among both the all clinical studies and PRO studies analyzed, the most prevalent stage was the early stage, accounting for 122 (25.1%) and 79 (27.0%), respectively. This was followed by phase 4, which accounted for 101 (20.7%) and 66 (22.5%) of the studies, respectively. It is important to mention that a considerable proportion of studies did not include information on the phase of the trial. This was observed in both the all clinical studies and the PRO studies, with a total of 177 (36.3%)and 100 (34.1%) studies, respectively. Out of the total 293 PRO studies, the majority, 288 (98.3%), were interventional, while just a small number, 4 (1.4%), were observational. Additionally, there was only one study focused on etiology. As can be observed, the majority of clinical studies on TCM for CVD are interventional investigations. Of all the studies, the great majority 419 (80.6%) had a minimum age of inclusion of 18 years or more, 12 (2.5%) studies had a minimum age of 60 years or more, and two studies contained participants under the age of 18. Similar outcomes were observed when only considering studies using PROs. Of all studies, 462 (94.9%) included both men and women, with just 9 (1.8%) studies including only men and 12 (2.5%) studies including only women. Similar results were found when considering only PRO studies. The use of herbal medicine as an intervention was the most common among all studies with 258 (53.0%) items. This was followed by acupuncture 174 (35.7%). TCM exercises, tuina and cupping were 25 (5.1%), 15 (3.1%) and 2 (0.4%) respectively. 13 (2.7%) studies used TCM co-interventions or did not have any TCM interventions. Similarly, out of 293 PRO studies, herbal medicine was the most used as an intervention with 160 (54.6%), followed by acupuncture 91 (31.1%). Geographically, the 487 studies that were analyzed were carried out in 21 countries spanning the WHO Western Pacific Region, the WHO Eastern Mediterranean Region, the WHO Region of the Americas, the WHO European Region, and the WHO South-East Asia Region. The majority 385 (79.1%) of these studies were conducted in China. (Table 1 ) Table 1 Characteristics of all studies and studies Including PROs Total, No. (%) Characteristics All studies PRO studies No. 487 293 Type of outcomes Primary outcomes 84 (17.2) 84 (17.2) Secondary outcomes 144 (29.6) 144 (29.6) Co-primary outcomes 65 (13.3) 65 (13.3) PROs not mentioned 194 (39.8) 0 (0) Whether the PRO instruments are explicitly mentioned PRO instruments explicitly specified 250 (51.3) 250 (51.3) PRO instruments implicitly specified 43 (8.8) 43 (8.8) PROs not mentioned 194 (39.8) 0 (0) Study Type Interventional study 473 (97.1) 288 (98.3) Observational study 13 (2.7) 4 (1.4) Cause/Relative factors study 1 (0.2) 1 (0.3) Clinical study phases Early stage 122 (25.1) 79 (27.0) 1 18 (3.7) 11 (3.8) 2 30 (6.2) 16 (5.5) 3 16 (3.3) 9 (3.1) 4 101 (20.7) 66 (22.5) Other clinical study phases* 1 23 (4.7) 12 (4.1) Unclear 177 (36.3) 100 (34.1) Minimum age Under 18 2 (0.4) 2 (0.7) 18–60 419 (86.0) 258 (88.1) Over 60 12 (2.5) 5 (1.7) Unclear 54 (11.1) 28 (9.6) Gender Male 9 (1.8) 4 (1.4) Female 12 (2.5) 8 (2.7) Both 462 (94.9) 279 (95.2) Unclear 4 (0.8) 2 (0.7) Chinese medicine interventions Chinese herbal medicines 258 (53.0) 160 (51.9) Acupuncture 174 (35.7) 91 (31.1) Traditional Chinese Medicine Exercise Therapy 25 (5.1) 21 (7.2) Massage 15 (3.1) 10 (3.4) Copping 2 (0.4) 1 (0.3) Other interventions* 2 13 (2.7) 10 (3.4) Regions WHO Western Pacific Region China 385 (79.1) 235 (80.2) South Korea 13 (2.7) 7 (2.4) Australia 6 (1.2) 5 (1.7) Japan 2 (0.4) 1 (0.3) Singapore 2 (0.2) 1 (0.3) WHO Eastern Mediterranean Region Iran 39 (8.0) 21 (7.2) Pakistan 1 (0.2) 1 (0.3) WHO Region of the Americas United States 9 (1.9) 5 (1.7) Brazi1 8 (1.6) 3 (1.0) Canada 1 (0.2) 1 (0.3) WHO European Region Spain 2 (0.4) 2 (0.7) Germany 2 (0.4) 2 (0.7) United Kingdom 2 (0.4) 2 (0.7) Turkey 2 (0.4) 1 (0.3) Denmark 1 (0.2) 1 (0.3) France 1 (0.2) 0 Nederland 1 (0.2) 0 Sweden 1 (0.2) 0 WHO South-East Asia Region India 5 (1.0) 4 (1.4) Thailand 2 (0.4) 1 (0.3) Nepal 1 (0.2) 0 Notes: ① Other clinical study phases* 1 : Including combined phases 1–2 or 2–3 or 3–4, and including observational studies; ② Other interventions* 2 : Including merged utilizing a variety of TCM therapies or no interventions. 3.3 Health conditions and PROs To assess the disease distribution of the 293 PRO studies and the application of PRO instruments, we categorized similar target diseases into 15 conditions according to ICD-11. The number of conditions and participants in PRO studies is shown in Fig. 3 . Of 293 PRO studies, chronic coronary heart disease (26.96%), hypertension(15.70%), and heart failure (14.68%) were the top 3 conditions for which PROs were considered as outcomes, followed by post-operative circulatory system disorders(7.51%), arrhythmias(8.53%), peripheral arterial or small artery disease(5.12%), acute coronary heart disease(8.53%), venous diseases(4.44%). Myocardial or intracardiac diseases(1.02%), pulmonary heart disease or pulmonary circulatory disease(0.68%), and heart valve disease(0.34%) were the least common conditions considered. (Fig. 3 ) Mix: means the study's target disorders included the combination of two or more cardiovascular conditions, such as hypertension and coronary heart disease complicated with heart failure, coronary heart disease with slow arrhythmias, atrial fibrillation with chronic heart failure. Others: means that the included studies were recruiting patients with cardiovascular disease combined with other systemic conditions, such as coronary artery disease combined with diabetes. Of the 62,986 individuals in PRO studies data, 25.9% (n = 16,291) were diagnosed with chronic coronary heart disease, 20.2% (n = 12,742) were experiencing hypertension and 19.1% (n = 12,046) had heart failure. Less than500 participants in this group had arterial or small artery disease 0.33% (n = 209), myocardial or intracardiac diseases 0.50%(n = 318), pulmonary heart disease or pulmonary circulatory disease 0.25% (n = 128), and heart valve disease 0.10% (n = 60 ). (Fig. 4 ) Mix: means the study's target disorders included the combination of two or more cardiovascular conditions, such as hypertension and coronary heart disease complicated with heart failure, coronary heart disease with slow arrhythmias, atrial fibrillation with chronic heart failure. Others: means that the included studies were recruiting patients with cardiovascular disease combined with other systemic conditions, such as coronary artery disease combined with diabetes. 3.4 PRO instruments used in clinical studies There were 250 studies that explicitly specified PRO instruments, among these studies, chronic coronary heart disease, hypertension, and heart failure had the highest number of studies, with 74, 36, and 42 respectively. TCM symptom score (TCMSS) is the predominant PRO instruments utilized in heart failure, hypertension, arrhythmias, myocardial or intracardiac diseases, and heart valve disease. Additionally, it is the second most commonly employed PRO instruments in chronic coronary heart disease, acute coronary heart disease, venous diseases, peripheral arterial or small artery disease, and Mix. Visual analog scale (VAS) is primarily utilized in the treatment of post-operative circulatory system disorders, peripheral arterial or small artery diseases, venous diseases, and is secondarily employed in the management of diseases of lymphatic vessels or lymph nodes. Seattle Angina Questionnaire (SAQ) is primarily utilized in cases of chronic coronary heart disease, acute coronary heart disease, and is the second most commonly employed in post-surgical circulatory system diseases. The Short Form-8/12/36 (SF-8/12/36) is also extensively utilized. They were commonly employed in the diseases of lymphatic vessels or lymph nodes, ranking second in their usage for hypertension and arrhythmias. It is also the third most frequently used PRO instruments for chronic coronary heart disease, heart failure, and post-operative circulatory system disorders. We discovered that the usage of PRO instruments with the three most common diseases—chronic coronary heart disease, hypertension, and heart failure, partialy aligns with the recommendations provided by COMET ,while other diseases did not. ( Table 2 ) Table 2. Frequency of the use of PRO instruments by conditions Conditions PRO instruments Core outcome set of PROs in the COMET #1 No.(%) S/L* Name No. (S/L) Name No. (S/L) Name No. (S/L) Name No. (S/L) Name No. (S/L) Name No. (S/L) Total No. 250 (100) Chronic coronary heart disease 74 (29.6) 28/46 SAQ 44 (14/30) TCMSS 29 (7/22) SF-8/12/36 14 (8/6) VAS 11 (5/6) SAS 6 (2/4) SDS 6 (1/5) SAQ-7 / Rose Dyspnea Score/ PHQ-2/QLI/ QLMI-2/MacNew/ SF-8/36 [35, 36] Heart failure 42 (16.8) 18/24 TCMSS 18 (6/12) MLHFQ 18 (8/10) SF-8/12/36 5 (2/3) EQ-5D 4 (4/0) QOL 4、(1/3) PSQI 3 (2/1) MLHFQ /KCCQ/CHFQ/ EQ-5D / SF-36 [37] Hypertension 36 (14.4) 15/21 TCMSS 17 (3/14) SF-8/12/36 7 (4/3) PSQI 7(4/3) QOL 3(0/3) MLHFQ 2(0/2) VAS 2(2/0) EQ-5D-3L/VR-12/PROMIS-10/ SF-12 Arrhythmias 21 (8.4) 13/8 TCMSS 9 (6/3) SF-8/12/36 7 (4/3) EQ-5D 4 (4/0) SAQ 3 (1/2) QOL 3 (2/1) VAS 2 (2/1) No core outcome set studies Acute coronary heart disease 21 (8.46) 10/11 SAQ 14 (5/9) TCMSS 11 (5/6) PSQI 3 (1/2) NRS 2 (1/1) VAS 2 (2/0) EQ-5D 1 (0/1) No core outcome set studies Post operative circulatory system disorders 17 (6.8) 10/7 VAS 6 (5/1) SAQ 3 (5/9) SF-8/12/36 3 (0/3) PHQ-9 2 (0/2) QOL 1 (0/1) NRS 1 (1/0) No core outcome set studies Peripheral arterial or small artery disease 15 (6.0) 13/2 VAS 6 (6/0) TCMSS 2 (1/1) QOL 1 (1/0) EQ-5D 1 (1/0) NRS 1 (1/0) PSQI 1 (1/0) Ongoing in core outcome set studies Venous diseases 7 (2.8) 3/4 VAS 2 (1/1) TCMSS 2 (0/2) QOL 2 (1/1) SF-8/12/36 1 (0/1) NRS 1 (1/0) CIVIQ/Charing Cross/EQ-5D/RAND-36/AVVQ[38] Mix #1 6 (2.4) 2/4 SAQ 3 (2/1) TCMSS 2 (0/2) MLHFQ 2 (0/2) KCCQ 1 (0/1) MPQ 1 (1/0) QOL 1 (0/1) Not applicable Diseases of lymphatic vessels or lymph nodes 5 (2.0) 4/1 SF-8/12/36 2 (0/2) VAS 1 (1/0) TCMSS 1 (0/1) QOL 1 (1/90) MYMOP 1 (1/0) No core outcome set studies Myocardial or intracardiac diseases 2(0.8) 2/0 TCMSS 2 (2/0) MLHFQ 1 (1/0) No core outcome set studies Pulmonary heart disease or pulmonary circulatory disease 2(0.8) 2/0 CAT 2 (2/0) STAI 1 (1/0) HADS 1 (1/0) Ongoing in core outcome set studies Heart valve disease 1(0.4) 1/0 TCMSS 1 (1/0) MLHFQ/ KCCQ[39] Other #3 1(0.4) 1/0 BES 1 (1/0) Not applicable Note: Only the precise number of PRO instruments is reported, not the proportion of conditions, because a study may use many PRO instruments. * S : Small sample size (N <median); L : Large sample size (N ≥ median). #1 The COMET: The COMET Initiative brings together people interested in the development and application of agreed standardised sets of outcomes, known as ‘core outcome sets’ (COS). These sets represent the minimum that should be measured and reported in all clinical trials of a specific condition, but COS are also suitable for use in routine care, clinical audit and research other than randomised trials. The existence or use of a core outcome set does not imply that outcomes in a particular study should be restricted to those in the relevant core outcome set. Rather, there is an expectation that the core outcomes will be collected and reported, making it easier for the results of studies to be compared, contrasted and combined as appropriate; while researchers continue to explore other outcomes as well. COMET aims to collate and stimulate relevant resources, both applied and methodological, to facilitate exchange of ideas and information, and to foster methodological research in this area. ( https://www.comet-initiative.org/ ) #2 Mix means the study's target disorders included the combination of two or more cardiovascular conditions, such as hypertension and coronary heart disease complicated with heart failure、coronary heart disease with slow arrhythmias、atrial fibrillation with chronic heart failure. #3 Other indicates that the included studies were recruiting patients with cardiovascular disease combined with other systemic conditions, such as coronary artery disease combined with diabetes. 4 Discussion This cross-sectional study analyzed the use and characteristics of PROs in clinical studies of TCM in the field of cardiovascular disease conducted worldwide from 2010 to 2023. We found that 250 (51.33%) of 487 studies explicitly used PRO instruments to assess patients' subjective experiences. Our study's reported PROs would have been lower if we had been successful in carefully examining the procedures of these 51.33% of studies. When procedures were examined in a rigorous scientific way, researchers discovered that PROs were typically insufficient[40–43]. We posit that the remaining 48.67% of the studies failed to seize the chance to gather patients' subjective assessments. In addition, 43 (14.7%) of the 487 studies implicitly specified PROs but did not specify which PRO tool was used. This implies that going forward, when registering clinical research, the use of a particular PROM tool should be explicitly disclosed when thinking about using PROs as an outcome indicator. The early stage accounted for the largest proportion in all included studies, indicating that patient participation was crucial for assessing the efficacy and safety of medications[44]. Phase 4 came after the early stages. By assessing TCM intervention among diverse, large, and heterogeneous patient groups, phase 4 clinical trials provide a better representation of efficacy, tolerability, and safety in the real world, influencing regulatory and reimbursement choices and aiding in the creation of health policies[45]. The high proportion of Phase 4 showed that when the research did not focus primarily on marketing, patients' subjective feelings should be given greater weight. Furthermore, a sizable fraction of studies (36.3%) did not state explicitly which phases of clinical trials they were, which is indicative of a lackluster reporting of clinical trial protocol registrations. The bulk of the studies (97.1%) conducted in the field of cardiovascular disease therapy utilizing TCM were interventional trials, whereas a tiny fraction (2.7%) were observational studies. This suggests that much of the present research in the field of CVD therapy using TCM mostly focuses on interventional studies. This is more in keeping with the growing popularity of clinical research in TCM over the last ten years. The majority of these studies are interventional, with small sample sizes and often poor methodological quality. As a result, they provide a limited amount of evidence-based data and are also expensive. It is not surprising that coronary heart disease has the largest number of PROs utilized in clinical research of TCM for CVD. One reason for this is that coronary heart disease is responsible for the majority of cases of CVD[46]. Chinese herbal formulas have been shown to enhance the outcomes of patients with coronary heart disease in various aspects, including reducing angina pectoris symptoms, improving electrocardiogram (ECG) results, and positively impacting biomarkers[47]. Additionally, certain non-pharmacological therapies of Chinese medicine, such as acupuncture, have been found to improve angina symptoms and ECG readings; Baduanjin has been found to enhance the health-related quality of life for patients with coronary heart disease, specifically by improving somatic limitations, angina stability, and angina stability as measured by the SAQ[48]. Because the majority of these disorders need surgical treatments, VAS is the most commonly used PRO instruments in diseases post operative circulatory system disorders, peripheral arterial or small artery diseases, venous diseases, and the second most commonly used PROM in diseases of lymphatic vessels or lymph nodes. This is because the majority of these patients experience pain during surgeries. SF-8/12/36 has been extensively utilized in virtually all domains of TCM for the treatment of cardiovascular disease in the 250 studies that explicitly specified PRO instruments. SF-36 is a generic short-form instrument that was widely applied to assess important quality of life domains in medical outcomes studies[49]. SF-36 questionnaire includes eight domains that measure quality of life: physical functioning (PF), role physical (RP), bodily pain (BP), general health (GH), vitality (VT), social functioning (SF), role emotional (RE), and mental health (MH)[50]. The first four aspects are related to physical health, whereas the final four are related to mental health. The SF-12, an abbreviated version of the SF-36, was developed by Ware and colleagues, which reduced the number of items from 36 to 12[51, 52]. The SF-8, which also is a condensed form of the SF-36 and the most concise SF Health Survey, is favored by numerous studies[53]. Research has indicated that SF-8 and SF-12 can serve as suitable alternatives to SF-36, especially in large-scale observational studies where survey administration time and respondent burden are important considerations[54, 55]. According to our findings, TCMSS was extensively utilized. Some researchers had begun to independently design new PRO instruments, which were correctly targeted for TCM syndrome and more widespread in clinical trials[56–58]. TCMSS is a scoring scale for TCM symptoms, which contains some daily symptoms of the patient, such as appetite, sleep conditions, pain area, urine color, stool shape, dry mouth, sweating, etc. These are all conditions that the patient can fill in by himself. However, the TCM doctor's observation of the patient's tongue and pulse must be included in order to accurately assess the patient's TCM diagnosis or TCM effectiveness. Additionally, this provides some insight into how PRO instruments for TCM may grow in the future. The precise definition of PRO instruments in contemporary medicine cannot be fully replicated if we want to create a PRO instruments that is appropriate for TCM. The patient's PROs cannot suffice to evaluate the effectiveness of TCM since it is a complicated intervention that stresses communication between the doctor and patient during both diagnosis and therapy. Assessing TCM's effectiveness using traditional randomized controlled trials for its treatment based on syndrome differentiation is challenging. References for the effectiveness and safety of treatments may be found in PROs, which are also a crucial foundation for labeling claims made in non-innovative drug trials, including bioequivalency studies[59–61]. TCM has a long history of utilizing many traditional prescriptions and treatments that date back thousands of years. It will be possible to more precisely evaluate the effectiveness of these therapies by integrating PROs with post-marketing real-world large-sample observational studies, as real-world research has increased in recent years. In the future, this will be an indispensable method for evaluating the effectiveness of TCM. In 2021, the Guidelines for the Application of Patient-Reported Outcomes in Drug Clinical Research were issued by the Chinese government, which highly focused on the clinical strengths of PROs. But it's possible that the existing PROs aren't sensitive enough to gather crucial data pertinent to TCM[62]. Investigators should join their efforts to perform high-quality trials to enhance the well-established protocols of PROs in TCM studies based on the current status of trials of TCM including PROs based on the current status of trials of TCM including PROs. Considering the unique and esoteric terminology utilized in TCM treatments, such as "Shen Xu" and "Na Dai," it is crucial to contemplate the dissemination of PRO instruments that are easily understandable and available to those lacking a TCM educational background in clinical settings. 5 Limitation Our study has several limitations. Firstly, while doing the data extraction procedure, we discovered that the registration information for several trials had not been updated. Secondly, several trials were discovered to have been completed in an irregular or wrong manner, making it impossible for us to assess the methodological and normative quality of their reports. While the World Health Organization mandates the registration of all clinical studies, we have concerns regarding potential exclusions in some instances. 6 Conclusion Over the past decade, there has been a continued increase in the use of PROs as a measure in clinical investigations focused on TCM for CVD globally. The predominant PROs utilized in the domain of TCM for cardiovascular disease include chronic coronary heart disease, hypertension, and heart failure. The most often utilized professional instruments include TCMSS, VAS, SAQ, and SF-8/12/36. Given the current challenges surrounding the use of PRO in clinical studies of TCM, such as the inconsistent availability and absence of standardized PROs for TCM, it is crucial to prioritize research on establishing standardized and normalized scales specifically designed for TCM. Abbreviations AVVQ Aberdeen Varicose Vein Questionnaire BES The Basic Empathy Scale CAT COPD Assessment Test CHFQ The Chronic Heart Failure Questionnaire CIVIQ Chronic Venous Insufficiency Quality of Life Questionnaire EQ-5D European Quality of Life Five Dimension Five Level Scale Questionnaire HADS Hospital Anxiety and Depression Scale KCCQ Kansas City Cardiomyopathy Questionnaire MPQ McGill Pain Questionnaire NRS Numeric Rating Sale MLHFQ Minnesota Living with Heart Failure Questionnaire PHQ-2/9 Patient Health Questionnaire-2/9 PROMIS-10 PROs Measurement Information System-10 PSQI Pittsburgh Sleep Quality Index QOL Quality of Life Questionnaire Scores QLI Quality of Life Index QLMI-2/MacNew MacNew Quality of Life after Myocardial Infarction SAQ Seattle Angina Questionnaire SAS Self-Rating Anxiety Scale SDS Self-rating Depression Scale SF-8/12/36 Short-Form 8/12/36-item Health Survey STAI State-Trait Anxiety Inventory MYMOP Measure Your Medical Outcome Profile TCMSS Traditional Chinese Medicine symptom score VAS Vsual Analog Scale VR-12 Veterans RAND 12-Item Health Survey. Declarations CRediT authorship contribution statement Yutong Fei, and Hongguo Rong conceived the protocol; Hao Liu wrote the article, Hongguo Rong, and Yuanyuan Lin,and Xinyue Zhang contributed to analysis and interpretation of data; Xinmiao Guan , Minjing Luo ,Changhao Liang and Yutong Fei, critically revised the manuscript. Every author unanimously accepts complete responsibility for guaranteeing the honesty and precision of the content and has thoroughly reviewed and endorsed the final draft. The author in charge had complete access to all the data in the research and took the ultimate responsibility for deciding to submit the manuscript for publication. Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Funding This work was supported by the program of Beijing Traditional Chinese Medicine Science and Technology Development Funding Program (No.BJZYZD-2023-04). and Special Fund of Basic Scientific Research Business Expenses for Central Public Welfare Scientific Research Institutes (No. 2022-JYB-PY-013). Ethical statement Not applicables Data availability The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author. Acknowledgments Not applicable References Gaidai O, Cao Y, Loginov S. Global Cardiovascular Diseases Death Rate Prediction. Curr Probl Cardiol. 2023;48:101622. Roth GA, Mensah GA, Fuster V. The Global Burden of Cardiovascular Diseases and Risks: A Compass for Global Action. J Am Coll Cardiol. 2020;76:2980–1. Mensah GA, Roth GA, Fuster V. The Global Burden of Cardiovascular Diseases and Risk Factors: 2020 and Beyond. J Am Coll Cardiol. 2019;74:2529–32. 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Eur J Health Econ. 2019;20:1195–206. Ware JEJ. SF-36 Health Survey Update. Spine. 2000;25:3130. Tucker G, Adams R, Wilson D. New Australian population scoring coefficients for the old version of the SF-36 and SF-12 health status questionnaires. Qual Life Res. 2010;19:1069–76. Windsor TD, Rodgers B, Butterworth P, Anstey KJ, Jorm AF. Measuring physical and mental health using the SF-12: implications for community surveys of mental health. Aust N Z J Psychiatry. 2006;40:797–803. Ware JE, Kosinski M, Dewey JE, Gandek B. How to score and interpret single-item health status measures: a manual for users of the SF-8 health survey. Lincoln, RI: QualityMetric Incorporated. 2001;15:5. Ware J, Kosinski M, Keller SD. A 12-Item Short-Form Health Survey: construction of scales and preliminary tests of reliability and validity. Med Care. 1996;34:220–33. Lang L, Zhang L, Zhang P, Li Q, Bian J, Guo Y. Evaluating the reliability and validity of SF-8 with a large representative sample of urban Chinese. 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Relative importance of doctor-reported outcomes vs patient-reported outcomes in DMARD intensification for rheumatoid arthritis: the DUO study. Rheumatology (Oxford, England). 2013;52:391–9. Kyte D, Ives J, Draper H, Calvert M. Management of Patient-Reported Outcome (PRO) Alerts in Clinical Trials: A Cross Sectional Survey. PloS One. 2016;11:e0144658. Jiang M, Yang J, Zhang C, Liu B, Chan K, Cao H, et al. Clinical studies with traditional Chinese medicine in the past decade and future research and development. Planta Med. 2010;76:2048–64. Additional Declarations No competing interests reported. Supplementary Files Supplementary.docx Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 09 Jan, 2025 Reviews received at journal 18 Nov, 2024 Reviewers agreed at journal 04 Nov, 2024 Reviewers agreed at journal 29 Oct, 2024 Reviews received at journal 08 Oct, 2024 Reviewers agreed at journal 26 Sep, 2024 Reviewers invited by journal 18 Aug, 2024 Editor invited by journal 16 Aug, 2024 Editor assigned by journal 17 Jul, 2024 Submission checks completed at journal 17 Jul, 2024 First submitted to journal 03 Jul, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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01:05:22","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":94641,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart of study identification.\u003c/p\u003e","description":"","filename":"Fig.1.Flowchartofstudyidentification.png","url":"https://assets-eu.researchsquare.com/files/rs-4678899/v1/796943e437ad2a71c6f7a4e3.png"},{"id":62651962,"identity":"fe6dc9b8-cf2b-4c41-9132-34cad02bc6ae","added_by":"auto","created_at":"2024-08-17 00:57:21","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":80699,"visible":true,"origin":"","legend":"\u003cp\u003eNumber of clinical studies analyzed\u003c/p\u003e","description":"","filename":"Fig.2Numberofclinicalstudiesanalyzed.png","url":"https://assets-eu.researchsquare.com/files/rs-4678899/v1/1200eb4bda7796259a67b896.png"},{"id":62651963,"identity":"ddf5baf2-bcba-46e4-8e54-d978922cfe19","added_by":"auto","created_at":"2024-08-17 00:57:21","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":304080,"visible":true,"origin":"","legend":"\u003cp\u003eNumber of studies including PROs\u003c/p\u003e","description":"","filename":"Fig.3NumberofstudiesincludingPROs.png","url":"https://assets-eu.researchsquare.com/files/rs-4678899/v1/324f1adaedcc13d1491be5ff.png"},{"id":62651964,"identity":"800668c9-d2cd-4186-89aa-5d6d61a37eb1","added_by":"auto","created_at":"2024-08-17 00:57:21","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":310189,"visible":true,"origin":"","legend":"\u003cp\u003eNumber of participants in studies including 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Introduction","content":"\u003cp\u003eCardiovascular disease (CVD) is a term used to refer to the range of diseases that impact the heart and blood vessels, including hypertension, coronary heart disease, cerebrovascular disease, heart failure, and various other cardiac ailments[1]. CVD persists as the foremost cause of mortality globally, significantly impacting both health outcomes and healthcare expenditure[2, 3]. In 2019, CVD caused 9.6\u0026nbsp;million deaths in males and 8.9\u0026nbsp;million deaths in females, accounting for approximately one-third of the global mortality rate, with 6.1\u0026nbsp;million of these deaths occurring in people aged 30 to 70 years, in addition to China reporting the highest number of CVD-related deaths[2].\u003c/p\u003e \u003cp\u003eCVD stems from a myriad of pathological factors, including atherosclerosis, hypertension, hyperlipidemia, and diabetes mellitus, among others. These factors are associated with disorders in energy metabolism, abnormalities in mitochondrial structure, oxidative stress injuries, cardiomyocyte apoptosis, and inflammatory reactions. However, the precise pathogenesis remains incompletely understood[4\u0026ndash;7]. The treatment modalities for CVD mentioned above typically encompass drug therapy, interventional procedures, and surgical techniques, these approaches aim to enhance patient health through various perspectives and mechanisms[8]. Among these, drug therapy serves as a primary approach in addressing CVD in clinical practice[9]. Given the intricate pathophysiological mechanisms of cardiovascular disease, recommended treatments include angiotensin-converting enzyme inhibitors, angiotensin receptor antagonists, β-receptor antagonists, vasodilators, diuretics, α-receptor antagonists, positive inotropes, lipid-lowering agents, antiarrhythmic agents, and calcium channel blockers.\u003c/p\u003e \u003cp\u003eIn recent years, natural medicines and complementary alternative medicine, particularly Traditional Chinese medicine (TCM), have demonstrated significant potential in the field of cardiovascular diseases[10, 11], such as Tongxinluo for acute myocardial infarction[12], acupuncture for Chronic Stable Angina[13]. TCM embodies a distinct paradigm of medical practice, characterized by a holistic approach to patient care. Within this framework, therapeutic interventions frequently incorporate natural herbal and other remedies tailored to specific conditions, aiming to enhance overall health and well-being[14]. In contrast to modern medicine's emphasis on individual symptoms, TCM practitioners prioritize the holistic well-being of the patient, viewing them as a unified entity[15]. Therefore, it is difficult for clinical research in TCM to focus only on the improvement of a single symptom or sign, as is the case in modern medicine. Consequently, there is a lack of universally accepted standards for evaluating treatment outcomes in TCM[16].\u003c/p\u003e \u003cp\u003eIn 2006, the U.S. Food and Drug Administration (FDA) issued guidance[17] to support patient-reported outcomes (PROs) measures used as validity endpoints in clinical studies and to support the development and use of study results measured by PRO instruments in support of medical device marketing authorization[18]. PROs are health condition assessments directly expressed by patients, without the need for a clinician or third-party interpretation of patient responses[19]. This methodology holds paramount importance in evaluating health status, behaviors, and the patient's care experience within clinical and research domains, effectively capturing the patient's viewpoint with precision[20\u0026ndash;22]. PRO instruments are standardized questionnaires designed to gather information on health outcomes directly from patients[23].PROs and PRO instruments have found extensive application in assessing health-related quality of life, physical capacity, mental and cognitive changes, functional status, symptoms, and overall well-being[24]. They offer greater reproducibility compared to clinician-elicited measures, which may be constrained by both intraclinician and interclinician reporting variability[25\u0026ndash;28]. Consequently, PROs have gained widespread utilization in comprehending patients' perspectives in randomized clinical trials[29] and clinical practice[30], offering several advantages such as noninvasiveness, patient-centeredness, and easy accessibility[31].\u003c/p\u003e \u003cp\u003eThe concept of PROs has garnered attention within the TCM community due to its alignment with the traditional emphasis on subjective patient reporting inherent in TCM. Throughout history, TCM practitioners have relied on the patient's chief complaint as a primary indicator of treatment outcomes. Consequently, PROs have been embraced by researchers in TCM as a promising method for establishing an evidence base for traditional practices. Moreover, researchers in China have explored alternative methodologies tailored to better suit the unique characteristics of TCM[16]. The number of clinical studies of PROs in the field of TCM for cardiovascular disease has continued to increase over the past few years, and despite the recognized importance of PROs in clinical and research settings, they are still underutilized in CVD studies[32\u0026ndash;34]. Exploring the application of PROs in clinical studies of TCM is crucial to discern its utilization and offer recommendations for conducting high-quality studies in this field.\u003c/p\u003e \u003cp\u003eTherefore, this study reviews and evaluates the use of PROs in the field of TCM for CVD based on the World Health Organization International Clinical Trials Registry Platform, in order to provide suggestions for conducting high-quality clinical studies of TCM.\u003c/p\u003e"},{"header":"2. Materials and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1. Study design\u003c/h2\u003e \u003cp\u003eThis cross-sectional study set out to count and evaluate the features of clinical studies for CVD using PROs as primary or secondary endpoint that were carried out worldwide in the field of TCM between January 1, 2010, and December 31, 2023. Data was collected from the World Health Organization International Clinical Trials Registry Platform (ICTRP), (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://apps.who.int/trialsearch\u003c/span\u003e\u003cspan address=\"http://apps.who.int/trialsearch\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e) (Search strategy in \u003cb\u003eSupplementary Method S1\u003c/b\u003e). We included clinical studies for CVD of TCM worldwide. And looked for the PRO instruments that were most frequently employed in studies for certain target diseases. This study adhered to The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Data Collection Strategy\u003c/h2\u003e \u003cp\u003eTCM clinical studies for CVD were included (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Flowchart of study identification). CVD are defined as diseases of the circulatory system included in Chap.\u0026nbsp;11 of ICD-11(International Classification of Diseases-11), similar disorders were grouped together in the same categories due to the significant heterogeneity in the target diseases according to ICD-11 (Classification of specific diseases in \u003cb\u003eSupplementary Method S2\u003c/b\u003e). Repeated studies we keep only one. The information gathered to evaluate the conditions and characteristics of studies encompassed two categories: 1) fundamental information, such as registration number, date of registration, scientific title; regions and countries, participant age and gender, clinical study phases; 2) crucial information, such as outcomes (including PRO instruments), Chinese medicine interventions, target disease. We also searched the the Core Outcome Measures in Effectiveness Trials (COMET) for the recommended use of PRO instruments for these diseases (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.comet-initiative.org/\u003c/span\u003e\u003cspan address=\"https://www.comet-initiative.org/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Data classification\u003c/h2\u003e \u003cp\u003eThe eligible studies were categorized into four groups based on the reported outcomes: (1) studies that registered PROs as primary endpoints; (2) studies that registered PROs as secondary outcomes; (3) studies that registered PROs as both primary and secondary endpoints; (4) studies that did not mention the use of PROs in their registration.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4 Statistical Analysis\u003c/h2\u003e \u003cp\u003eData on the features of the included studies were extracted independently by two of us (Hao Liu and Yuanyuan Lin), using predesigned data extraction tables. The PRO instruments used in each study were summarized using our condition classification to determine the most and least commonly utilized instruments. For quantitative analysis, we only considered entries that mentioned the names of the PRO instruments. Descriptive statistics were used to characterize the clinical trial phases, study type, participant\u0026rsquo;s age, gender, TCM interventions, regions and countries, diseases, and the PRO instruments for included studies by SPSS software, version 22.0 (IBM Corp).\u003c/p\u003e \u003c/div\u003e"},{"header":"3 Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e3.1 Search results\u003c/h2\u003e \u003cp\u003eA total of 545 studies were retrieved, 44 duplicates and 14 non-cardiovascular-related research were eliminated, leaving 487 suitable studies for analysis. Figure\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e depicts a flow chart for the study identification process. Out of the 487 studies that were analyzed, 194 (39.8%) studies did not utilize any PRO instruments, whereas 293 studies employed PROs for their outcomes. Out of the 293 PRO studies, 250 (85.3%) studies clearly mentioned the specific PRO instruments they used, whereas the remaining 43 (14.7%) studies mentioned PROs but did not provide details on the specific PRO instruments utilized. On the other hand, of these 293 PRO studies, 84 (17.2%) studies used PROs as their primary outcome, 144 (29.6%) studies used PROs as their secondary outcomes and 65 (13.3%) studies used PROs as co-primary outcomes (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eICTRP: International Clinical Trials Registry Platform; CVD: cardiovascular diseases; PROs: patient-reported outcomes.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e3.2 Studies characteristics\u003c/h2\u003e \u003cp\u003eThe number of TCM clinical registration studies increased between 2010 and 2023, as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, which also demonstrates the proportion of studies that list PROs as the outcomes among the TCM studies. (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e displays the overall characteristics of the included studies. Of the 293 PRO studies, the most prevalent result was PROs as secondary outcomes 144 (29.6%), followed by primary outcomes 84 (29.6%) and co-primary outcomes 65 (22.2%). Among both the all clinical studies and PRO studies analyzed, the most prevalent stage was the early stage, accounting for 122 (25.1%) and 79 (27.0%), respectively. This was followed by phase 4, which accounted for 101 (20.7%) and 66 (22.5%) of the studies, respectively. It is important to mention that a considerable proportion of studies did not include information on the phase of the trial. This was observed in both the all clinical studies and the PRO studies, with a total of 177 (36.3%)and 100 (34.1%) studies, respectively.\u003c/p\u003e \u003cp\u003eOut of the total 293 PRO studies, the majority, 288 (98.3%), were interventional, while just a small number, 4 (1.4%), were observational. Additionally, there was only one study focused on etiology. As can be observed, the majority of clinical studies on TCM for CVD are interventional investigations. Of all the studies, the great majority 419 (80.6%) had a minimum age of inclusion of 18 years or more, 12 (2.5%) studies had a minimum age of 60 years or more, and two studies contained participants under the age of 18. Similar outcomes were observed when only considering studies using PROs. Of all studies, 462 (94.9%) included both men and women, with just 9 (1.8%) studies including only men and 12 (2.5%) studies including only women. Similar results were found when considering only PRO studies.\u003c/p\u003e \u003cp\u003eThe use of herbal medicine as an intervention was the most common among all studies with 258 (53.0%) items. This was followed by acupuncture 174 (35.7%). TCM exercises, tuina and cupping were 25 (5.1%), 15 (3.1%) and 2 (0.4%) respectively. 13 (2.7%) studies used TCM co-interventions or did not have any TCM interventions. Similarly, out of 293 PRO studies, herbal medicine was the most used as an intervention with 160 (54.6%), followed by acupuncture 91 (31.1%).\u003c/p\u003e \u003cp\u003eGeographically, the 487 studies that were analyzed were carried out in 21 countries spanning the WHO Western Pacific Region, the WHO Eastern Mediterranean Region, the WHO Region of the Americas, the WHO European Region, and the WHO South-East Asia Region. The majority 385 (79.1%) of these studies were conducted in China. (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics of all studies and studies Including PROs\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal, No. (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAll studies\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePRO studies\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e487\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e293\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType of outcomes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrimary outcomes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e84 (17.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e84 (17.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSecondary outcomes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e144 (29.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e144 (29.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCo-primary outcomes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e65 (13.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e65 (13.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePROs not mentioned\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e194 (39.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWhether the PRO instruments are explicitly mentioned\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePRO instruments explicitly specified\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e250 (51.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e250 (51.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePRO instruments implicitly specified\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e43 (8.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e43 (8.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePROs not mentioned\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e194 (39.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStudy Type\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInterventional study\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e473 (97.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e288 (98.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eObservational study\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (2.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (1.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCause/Relative factors study\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (0.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical study phases\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEarly stage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e122 (25.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e79 (27.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18 (3.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (3.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30 (6.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (5.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (3.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (3.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e101 (20.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e66 (22.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther clinical study phases*\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23 (4.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (4.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnclear\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e177 (36.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100 (34.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMinimum age\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnder 18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (0.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (0.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e18\u0026ndash;60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e419 (86.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e258 (88.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOver 60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (2.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (1.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnclear\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e54 (11.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28 (9.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (1.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (1.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (2.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (2.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBoth\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e462 (94.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e279 (95.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnclear\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (0.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (0.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChinese medicine interventions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChinese herbal medicines\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e258 (53.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e160 (51.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAcupuncture\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e174 (35.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e91 (31.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTraditional Chinese Medicine Exercise Therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25 (5.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21 (7.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMassage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (3.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (3.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCopping\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (0.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (0.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther interventions*\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (2.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (3.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRegions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWHO Western Pacific Region\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChina\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e385 (79.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e235 (80.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSouth Korea\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (2.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (2.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAustralia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (1.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (1.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eJapan\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (0.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (0.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSingapore\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (0.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (0.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWHO Eastern Mediterranean Region\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIran\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39 (8.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21 (7.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePakistan\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (0.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWHO Region of the Americas\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnited States\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (1.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (1.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBrazi1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (1.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (1.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCanada\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (0.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWHO European Region\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSpain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (0.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (0.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGermany\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (0.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (0.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnited Kingdom\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (0.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (0.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTurkey\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (0.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (0.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDenmark\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (0.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFrance\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNederland\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSweden\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWHO South-East Asia Region\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIndia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (1.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (1.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThailand\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (0.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (0.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNepal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003eNotes: ① Other clinical study phases*\u003csup\u003e1\u003c/sup\u003e: Including combined phases 1\u0026ndash;2 or 2\u0026ndash;3 or 3\u0026ndash;4, and including observational studies; ② Other interventions*\u003csup\u003e2\u003c/sup\u003e: Including merged utilizing a variety of TCM therapies or no interventions.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e3.3 Health conditions and PROs\u003c/h2\u003e \u003cp\u003eTo assess the disease distribution of the 293 PRO studies and the application of PRO instruments, we categorized similar target diseases into 15 conditions according to ICD-11. The number of conditions and participants in PRO studies is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. Of 293 PRO studies, chronic coronary heart disease (26.96%), hypertension(15.70%), and heart failure (14.68%) were the top 3 conditions for which PROs were considered as outcomes, followed by post-operative circulatory system disorders(7.51%), arrhythmias(8.53%), peripheral arterial or small artery disease(5.12%), acute coronary heart disease(8.53%), venous diseases(4.44%). Myocardial or intracardiac diseases(1.02%), pulmonary heart disease or pulmonary circulatory disease(0.68%), and heart valve disease(0.34%) were the least common conditions considered. (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eMix: means the study's target disorders included the combination of two or more cardiovascular conditions, such as hypertension and coronary heart disease complicated with heart failure, coronary heart disease with slow arrhythmias, atrial fibrillation with chronic heart failure.\u003c/p\u003e \u003cp\u003eOthers: means that the included studies were recruiting patients with cardiovascular disease combined with other systemic conditions, such as coronary artery disease combined with diabetes.\u003c/p\u003e \u003cp\u003eOf the 62,986 individuals in PRO studies data, 25.9% (n\u0026thinsp;=\u0026thinsp;16,291) were diagnosed with chronic coronary heart disease, 20.2% (n\u0026thinsp;=\u0026thinsp;12,742) were experiencing hypertension and 19.1% (n\u0026thinsp;=\u0026thinsp;12,046) had heart failure. Less than500 participants in this group had arterial or small artery disease 0.33% (n\u0026thinsp;=\u0026thinsp;209), myocardial or intracardiac diseases 0.50%(n\u0026thinsp;=\u0026thinsp;318), pulmonary heart disease or pulmonary circulatory disease 0.25% (n\u0026thinsp;=\u0026thinsp;128), and heart valve disease 0.10% (n\u0026thinsp;=\u0026thinsp;60 ). (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eMix: means the study's target disorders included the combination of two or more cardiovascular conditions, such as hypertension and coronary heart disease complicated with heart failure, coronary heart disease with slow arrhythmias, atrial fibrillation with chronic heart failure.\u003c/p\u003e \u003cp\u003eOthers: means that the included studies were recruiting patients with cardiovascular disease combined with other systemic conditions, such as coronary artery disease combined with diabetes.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e3.4 PRO instruments used in clinical studies\u003c/h2\u003e \u003cp\u003eThere were 250 studies that explicitly specified PRO instruments, among these studies, chronic coronary heart disease, hypertension, and heart failure had the highest number of studies, with 74, 36, and 42 respectively. TCM symptom score (TCMSS) is the predominant PRO instruments utilized in heart failure, hypertension, arrhythmias, myocardial or intracardiac diseases, and heart valve disease. Additionally, it is the second most commonly employed PRO instruments in chronic coronary heart disease, acute coronary heart disease, venous diseases, peripheral arterial or small artery disease, and Mix. Visual analog scale (VAS) is primarily utilized in the treatment of post-operative circulatory system disorders, peripheral arterial or small artery diseases, venous diseases, and is secondarily employed in the management of diseases of lymphatic vessels or lymph nodes. Seattle Angina Questionnaire (SAQ) is primarily utilized in cases of chronic coronary heart disease, acute coronary heart disease, and is the second most commonly employed in post-surgical circulatory system diseases. The Short Form-8/12/36 (SF-8/12/36) is also extensively utilized. They were commonly employed in the diseases of lymphatic vessels or lymph nodes, ranking second in their usage for hypertension and arrhythmias. It is also the third most frequently used PRO instruments for chronic coronary heart disease, heart failure, and post-operative circulatory system disorders. We discovered that the usage of PRO instruments with the three most common diseases\u0026mdash;chronic coronary heart disease, hypertension, and heart failure, partialy aligns with the recommendations provided by COMET ,while other diseases did not. (\u003cb\u003eTable\u0026nbsp;2\u003c/b\u003e)\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Taba\" border=\"1\"\u003e \u003ccolgroup cols=\"16\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c13\" colnum=\"13\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c14\" colnum=\"14\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c15\" colnum=\"15\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c16\" colnum=\"16\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"15\" nameend=\"c15\" namest=\"c1\"\u003e \u003cp\u003eTable\u0026nbsp;2. Frequency of the use of PRO instruments by conditions\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c16\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eConditions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"13\" nameend=\"c15\" namest=\"c3\"\u003e \u003cp\u003ePRO instruments\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c16\"\u003e \u003cp\u003eCore outcome set of PROs in the COMET\u003csup\u003e#1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo.(%)\u003c/p\u003e \u003cp\u003eS/L*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eName\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNo. (S/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eName\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo. (S/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eName\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNo. (S/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eName\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNo. (S/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eName\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eNo. (S/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eName\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003eNo.\u003c/p\u003e \u003cp\u003e(S/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c16\" namest=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal No.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e250 (100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c16\" namest=\"c15\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChronic coronary heart disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e74 (29.6)\u003c/p\u003e \u003cp\u003e28/46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eSAQ\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e44\u003c/p\u003e \u003cp\u003e(14/30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTCMSS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e29\u003c/p\u003e \u003cp\u003e(7/22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003eSF-8/12/36\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e14\u003c/p\u003e \u003cp\u003e(8/6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eVAS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e11\u003c/p\u003e \u003cp\u003e(5/6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eSAS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e6\u003c/p\u003e \u003cp\u003e(2/4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eSDS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e6\u003c/p\u003e \u003cp\u003e(1/5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c16\" namest=\"c15\"\u003e \u003cp\u003e\u003cb\u003eSAQ-7\u003c/b\u003e/ Rose Dyspnea Score/ PHQ-2/QLI/ QLMI-2/MacNew/ \u003cb\u003eSF-8/36\u003c/b\u003e[35, 36]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHeart failure\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e42 (16.8)\u003c/p\u003e \u003cp\u003e18/24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTCMSS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18\u003c/p\u003e \u003cp\u003e(6/12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003eMLHFQ\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e18\u003c/p\u003e \u003cp\u003e(8/10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003eSF-8/12/36\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e5\u003c/p\u003e \u003cp\u003e(2/3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003eEQ-5D\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e4\u003c/p\u003e \u003cp\u003e(4/0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eQOL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e4、(1/3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003ePSQI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e3\u003c/p\u003e \u003cp\u003e(2/1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c16\" namest=\"c15\"\u003e \u003cp\u003e\u003cb\u003eMLHFQ\u003c/b\u003e/KCCQ/CHFQ/\u003cb\u003eEQ-5D\u003c/b\u003e/ \u003cb\u003eSF-36\u003c/b\u003e[37]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36 (14.4)\u003c/p\u003e \u003cp\u003e15/21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTCMSS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e17\u003c/p\u003e \u003cp\u003e(3/14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003eSF-8/12/36\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7\u003c/p\u003e \u003cp\u003e(4/3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003ePSQI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e7(4/3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eQOL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e3(0/3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eMLHFQ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e2(0/2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eVAS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e2(2/0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c16\" namest=\"c15\"\u003e \u003cp\u003eEQ-5D-3L/VR-12/PROMIS-10/\u003cb\u003eSF-12\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eArrhythmias\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21 (8.4)\u003c/p\u003e \u003cp\u003e13/8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTCMSS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9\u003c/p\u003e \u003cp\u003e(6/3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSF-8/12/36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7\u003c/p\u003e \u003cp\u003e(4/3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eEQ-5D\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e4\u003c/p\u003e \u003cp\u003e(4/0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eSAQ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e3\u003c/p\u003e \u003cp\u003e(1/2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eQOL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e3\u003c/p\u003e \u003cp\u003e(2/1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eVAS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e(2/1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c16\" namest=\"c15\"\u003e \u003cp\u003eNo core outcome set studies\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAcute coronary heart disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21 (8.46)\u003c/p\u003e \u003cp\u003e10/11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSAQ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14\u003c/p\u003e \u003cp\u003e(5/9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTCMSS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e11\u003c/p\u003e \u003cp\u003e(5/6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003ePSQI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3\u003c/p\u003e \u003cp\u003e(1/2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNRS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e(1/1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eVAS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e(2/0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eEQ-5D\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e(0/1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c16\" namest=\"c15\"\u003e \u003cp\u003eNo core outcome set studies\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePost operative circulatory\u003c/p\u003e \u003cp\u003esystem disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17 (6.8)\u003c/p\u003e \u003cp\u003e10/7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eVAS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6\u003c/p\u003e \u003cp\u003e(5/1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSAQ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3\u003c/p\u003e \u003cp\u003e(5/9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eSF-8/12/36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3\u003c/p\u003e \u003cp\u003e(0/3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003ePHQ-9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e(0/2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eQOL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e(0/1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eNRS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e(1/0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c16\" namest=\"c15\"\u003e \u003cp\u003eNo core outcome set studies\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeripheral arterial\u003c/p\u003e \u003cp\u003eor small artery disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (6.0)\u003c/p\u003e \u003cp\u003e13/2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eVAS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6\u003c/p\u003e \u003cp\u003e(6/0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTCMSS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e(1/1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eQOL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e(1/0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eEQ-5D\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e(1/0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNRS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e(1/0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003ePSQI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e(1/0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c16\" namest=\"c15\"\u003e \u003cp\u003eOngoing in core outcome set studies\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVenous diseases\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (2.8)\u003c/p\u003e \u003cp\u003e3/4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eVAS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e(1/1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTCMSS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e(0/2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eQOL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e(1/1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eSF-8/12/36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e(0/1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNRS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e(1/0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c16\" namest=\"c15\"\u003e \u003cp\u003eCIVIQ/Charing Cross/EQ-5D/RAND-36/AVVQ[38]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMix\u003csup\u003e#1\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (2.4)\u003c/p\u003e \u003cp\u003e2/4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSAQ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3\u003c/p\u003e \u003cp\u003e(2/1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTCMSS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e(0/2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eMLHFQ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e(0/2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eKCCQ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e(0/1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eMPQ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e(1/0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eQOL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e(0/1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c16\" namest=\"c15\"\u003e \u003cp\u003eNot applicable\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiseases of lymphatic vessels or lymph nodes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (2.0)\u003c/p\u003e \u003cp\u003e4/1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSF-8/12/36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e(0/2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eVAS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e(1/0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eTCMSS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e(0/1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eQOL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e(1/90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eMYMOP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e(1/0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c16\" namest=\"c15\"\u003e \u003cp\u003eNo core outcome set studies\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMyocardial or intracardiac diseases\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2(0.8)\u003c/p\u003e \u003cp\u003e2/0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTCMSS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e(2/0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMLHFQ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e(1/0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c16\" namest=\"c15\"\u003e \u003cp\u003eNo core outcome set studies\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePulmonary heart disease\u003c/p\u003e \u003cp\u003eor pulmonary circulatory disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2(0.8)\u003c/p\u003e \u003cp\u003e2/0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCAT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e(2/0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSTAI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e(1/0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eHADS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e(1/0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c16\" namest=\"c15\"\u003e \u003cp\u003eOngoing in core outcome set studies\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHeart valve disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(0.4)\u003c/p\u003e \u003cp\u003e1/0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTCMSS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e(1/0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c16\" namest=\"c15\"\u003e \u003cp\u003eMLHFQ/ KCCQ[39]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther\u003csup\u003e#3\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1(0.4)\u003c/p\u003e \u003cp\u003e1/0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBES\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e(1/0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c16\" namest=\"c15\"\u003e \u003cp\u003eNot applicable\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"16\"\u003eNote:\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eOnly the precise number of PRO instruments is reported, not the proportion of conditions, because a study may use many PRO instruments.\u003c/p\u003e \u003cp\u003e \u003cb\u003e* S\u003c/b\u003e: Small sample size (N \u0026lt;median); \u003cb\u003eL\u003c/b\u003e: Large sample size (N\u0026thinsp;\u0026ge;\u0026thinsp;median).\u003c/p\u003e \u003cp\u003e \u003cb\u003e#1\u003c/b\u003e The COMET: The COMET Initiative brings together people interested in the development and application of agreed standardised sets of outcomes, known as \u0026lsquo;core outcome sets\u0026rsquo; (COS). These sets represent the minimum that should be measured and reported in all clinical trials of a specific condition, but COS are also suitable for use in routine care, clinical audit and research other than randomised trials. The existence or use of a core outcome set does not imply that outcomes in a particular study should be restricted to those in the relevant core outcome set. Rather, there is an expectation that the core outcomes will be collected and reported, making it easier for the results of studies to be compared, contrasted and combined as appropriate; while researchers continue to explore other outcomes as well. COMET aims to collate and stimulate relevant resources, both applied and methodological, to facilitate exchange of ideas and information, and to foster methodological research in this area. (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.comet-initiative.org/\u003c/span\u003e\u003cspan address=\"https://www.comet-initiative.org/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003cb\u003e#2\u003c/b\u003e Mix means the study's target disorders included the combination of two or more cardiovascular conditions, such as hypertension and coronary heart disease complicated with heart failure、coronary heart disease with slow arrhythmias、atrial fibrillation with chronic heart failure.\u003c/p\u003e \u003cp\u003e \u003cb\u003e#3\u003c/b\u003e Other indicates that the included studies were recruiting patients with cardiovascular disease combined with other systemic conditions, such as coronary artery disease combined with diabetes.\u003c/p\u003e \u003c/div\u003e"},{"header":"4 Discussion","content":"\u003cp\u003eThis cross-sectional study analyzed the use and characteristics of PROs in clinical studies of TCM in the field of cardiovascular disease conducted worldwide from 2010 to 2023. We found that 250 (51.33%) of 487 studies explicitly used PRO instruments to assess patients\u0026apos; subjective experiences. Our study\u0026apos;s reported PROs would have been lower if we had been successful in carefully examining the procedures of these 51.33% of studies. When procedures were examined in a rigorous scientific way, researchers discovered that PROs were typically insufficient[40\u0026ndash;43]. We posit that the remaining 48.67% of the studies failed to seize the chance to gather patients\u0026apos; subjective assessments. In addition, 43 (14.7%) of the 487 studies implicitly specified PROs but did not specify which PRO tool was used. This implies that going forward, when registering clinical research, the use of a particular PROM tool should be explicitly disclosed when thinking about using PROs as an outcome indicator.\u003c/p\u003e\n\u003cp\u003eThe early stage accounted for the largest proportion in all included studies, indicating that patient participation was crucial for assessing the efficacy and safety of medications[44]. Phase 4 came after the early stages. By assessing TCM intervention among diverse, large, and heterogeneous patient groups, phase 4 clinical trials provide a better representation of efficacy, tolerability, and safety in the real world, influencing regulatory and reimbursement choices and aiding in the creation of health policies[45]. The high proportion of Phase 4 showed that when the research did not focus primarily on marketing, patients\u0026apos; subjective feelings should be given greater weight. Furthermore, a sizable fraction of studies (36.3%) did not state explicitly which phases of clinical trials they were, which is indicative of a lackluster reporting of clinical trial protocol registrations.\u003c/p\u003e\n\u003cp\u003eThe bulk of the studies (97.1%) conducted in the field of cardiovascular disease therapy utilizing TCM were interventional trials, whereas a tiny fraction (2.7%) were observational studies. This suggests that much of the present research in the field of CVD therapy using TCM mostly focuses on interventional studies. This is more in keeping with the growing popularity of clinical research in TCM over the last ten years. The majority of these studies are interventional, with small sample sizes and often poor methodological quality. As a result, they provide a limited amount of evidence-based data and are also expensive.\u003c/p\u003e\n\u003cp\u003eIt is not surprising that coronary heart disease has the largest number of PROs utilized in clinical research of TCM for CVD. One reason for this is that coronary heart disease is responsible for the majority of cases of CVD[46]. Chinese herbal formulas have been shown to enhance the outcomes of patients with coronary heart disease in various aspects, including reducing angina pectoris symptoms, improving electrocardiogram (ECG) results, and positively impacting biomarkers[47]. Additionally, certain non-pharmacological therapies of Chinese medicine, such as acupuncture, have been found to improve angina symptoms and ECG readings; Baduanjin has been found to enhance the health-related quality of life for patients with coronary heart disease, specifically by improving somatic limitations, angina stability, and angina stability as measured by the SAQ[48].\u003c/p\u003e\n\u003cp\u003eBecause the majority of these disorders need surgical treatments, VAS is the most commonly used PRO instruments in diseases post operative circulatory system disorders, peripheral arterial or small artery diseases, venous diseases, and the second most commonly used PROM in diseases of lymphatic vessels or lymph nodes. This is because the majority of these patients experience pain during surgeries. SF-8/12/36 has been extensively utilized in virtually all domains of TCM for the treatment of cardiovascular disease in the 250 studies that explicitly specified PRO instruments. SF-36 is a generic short-form instrument that was widely applied to assess important quality of life domains in medical outcomes studies[49]. SF-36 questionnaire includes eight domains that measure quality of life: physical functioning (PF), role physical (RP), bodily pain (BP), general health (GH), vitality (VT), social functioning (SF), role emotional (RE), and mental health (MH)[50]. The first four aspects are related to physical health, whereas the final four are related to mental health. The SF-12, an abbreviated version of the SF-36, was developed by Ware and colleagues, which reduced the number of items from 36 to 12[51, 52]. The SF-8, which also is a condensed form of the SF-36 and the most concise SF Health Survey, is favored by numerous studies[53]. Research has indicated that SF-8\u0026nbsp;and SF-12 can serve as suitable alternatives to SF-36, especially in large-scale observational studies where survey administration time and respondent burden are important considerations[54, 55].\u003c/p\u003e\n\u003cp\u003eAccording to our findings, TCMSS was extensively utilized. Some researchers had begun to independently design new PRO instruments, which were correctly targeted for TCM syndrome and more widespread in clinical trials[56\u0026ndash;58]. TCMSS is a scoring scale for TCM symptoms, which contains some daily symptoms of the patient, such as appetite, sleep conditions, pain area, urine color, stool shape, dry mouth, sweating, etc. These are all conditions that the patient can fill in by himself. However, the TCM doctor\u0026apos;s observation of the patient\u0026apos;s tongue and pulse must be included in order to accurately assess the patient\u0026apos;s TCM diagnosis or TCM effectiveness. Additionally, this provides some insight into how PRO instruments for TCM may grow in the future. The precise definition of PRO instruments in contemporary medicine cannot be fully replicated if we want to create a PRO instruments that is appropriate for TCM. The patient\u0026apos;s PROs cannot suffice to evaluate the effectiveness of TCM since it is a complicated intervention that stresses communication between the doctor and patient during both diagnosis and therapy.\u003c/p\u003e\n\u003cp\u003eAssessing TCM\u0026apos;s effectiveness using traditional randomized controlled trials for its treatment based on syndrome differentiation is challenging. References for the effectiveness and safety of treatments may be found in PROs, which are also a crucial foundation for labeling claims made in non-innovative drug trials, including bioequivalency studies[59\u0026ndash;61]. TCM has a long history of utilizing many traditional prescriptions and treatments that date back thousands of years. It will be possible to more precisely evaluate the effectiveness of these therapies by integrating PROs with post-marketing real-world large-sample observational studies, as real-world research has increased in recent years. In the future, this will be an indispensable method for evaluating the effectiveness of TCM. In 2021, the Guidelines for the Application of Patient-Reported Outcomes in Drug Clinical Research were issued by the Chinese government, which highly focused on the clinical strengths of PROs. But it\u0026apos;s possible that the existing PROs aren\u0026apos;t sensitive enough to gather crucial data pertinent to TCM[62].\u003c/p\u003e\n\u003cp\u003eInvestigators should join their efforts to perform high-quality trials to enhance the well-established protocols of PROs in TCM studies based on the current status of trials of TCM including PROs based on the current status of trials of TCM including PROs. Considering the unique and esoteric terminology utilized in TCM treatments, such as \u0026quot;Shen Xu\u0026quot; and \u0026quot;Na Dai,\u0026quot; it is crucial to contemplate the dissemination of PRO instruments that are easily understandable and available to those lacking a TCM educational background in clinical settings.\u003c/p\u003e"},{"header":"5 Limitation ","content":"\u003cp\u003eOur study has several limitations. Firstly, while doing the data extraction procedure, we discovered that the registration information for several trials had not been updated. Secondly, several trials were discovered to have been completed in an irregular or wrong manner, making it impossible for us to assess the methodological and normative quality of their reports. While the World Health Organization mandates the registration of all clinical studies, we have concerns regarding potential exclusions in some instances.\u003c/p\u003e"},{"header":"6 Conclusion","content":"\u003cp\u003eOver the past decade, there has been a continued increase in the use of PROs as a measure in clinical investigations focused on TCM for CVD globally. The predominant PROs utilized in the domain of TCM for cardiovascular disease include chronic coronary heart disease, hypertension, and heart failure. The most often utilized professional instruments include TCMSS, VAS, SAQ, and SF-8/12/36. Given the current challenges surrounding the use of PRO in clinical studies of TCM, such as the inconsistent availability and absence of standardized PROs for TCM, it is crucial to prioritize research on establishing standardized and normalized scales specifically designed for TCM.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eAVVQ\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAberdeen Varicose Vein Questionnaire\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eBES\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eThe Basic Empathy Scale\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCAT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eCOPD Assessment Test\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCHFQ\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eThe Chronic Heart Failure Questionnaire\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCIVIQ\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eChronic Venous Insufficiency Quality of Life Questionnaire\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eEQ-5D\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eEuropean Quality of Life Five Dimension Five Level Scale Questionnaire\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHADS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eHospital Anxiety and Depression Scale\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eKCCQ\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eKansas City Cardiomyopathy Questionnaire\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMPQ\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMcGill Pain Questionnaire\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNRS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eNumeric Rating Sale\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMLHFQ\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMinnesota Living with Heart Failure Questionnaire\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePHQ-2/9\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePatient Health Questionnaire-2/9\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePROMIS-10\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePROs Measurement Information System-10\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePSQI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePittsburgh Sleep Quality Index\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eQOL\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eQuality of Life Questionnaire Scores\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eQLI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eQuality of Life Index\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eQLMI-2/MacNew\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMacNew Quality of Life after Myocardial Infarction\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSAQ\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSeattle Angina Questionnaire\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSAS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSelf-Rating Anxiety Scale\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSDS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSelf-rating Depression Scale\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSF-8/12/36\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eShort-Form 8/12/36-item Health Survey\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSTAI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eState-Trait Anxiety Inventory\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMYMOP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMeasure Your Medical Outcome Profile\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTCMSS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eTraditional Chinese Medicine symptom score\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eVAS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eVsual Analog Scale\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eVR-12\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eVeterans RAND 12-Item Health Survey.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eCRediT authorship contribution statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eYutong Fei, and Hongguo Rong conceived the protocol; Hao Liu wrote the article, Hongguo Rong, and Yuanyuan Lin,and Xinyue Zhang contributed to analysis and interpretation of data; Xinmiao Guan , Minjing Luo ,Changhao Liang and Yutong Fei, critically revised the manuscript. Every author unanimously accepts complete responsibility for guaranteeing the honesty and precision of the content and has thoroughly reviewed and endorsed the final draft. The author in charge had complete access to all the data in the research and took the ultimate responsibility for deciding to submit the manuscript for publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the program of Beijing Traditional Chinese Medicine Science and Technology Development Funding Program (No.BJZYZD-2023-04). and Special Fund of Basic Scientific Research Business Expenses for Central Public Welfare Scientific Research Institutes (No. 2022-JYB-PY-013).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicables\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eGaidai O, Cao Y, Loginov S. 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Patient-reported outcomes: A new era in clinical research. Perspectives in Clinical Research. 2011;2:137\u0026ndash;44.\u003c/li\u003e\n\u003cli\u003eRumsfeld JS, Alexander KP, Goff DC, Graham MM, Ho PM, Masoudi FA, et al. Cardiovascular health: the importance of measuring patient-reported health status: a scientific statement from the American Heart Association. Circulation. 2013;127:2233\u0026ndash;49.\u003c/li\u003e\n\u003cli\u003eWilson IB, Cleary PD. Linking clinical variables with health-related quality of life. A conceptual model of patient outcomes. Jama. 1995;273:59\u0026ndash;65.\u003c/li\u003e\n\u003cli\u003eAnker SD, Agewall S, Borggrefe M, Calvert M, Jaime Caro J, Cowie MR, et al. The importance of patient-reported outcomes: a call for their comprehensive integration in cardiovascular clinical trials. Eur Heart J. 2014;35:2001\u0026ndash;9.\u003c/li\u003e\n\u003cli\u003eThe Lancet Neurology null. Patient-reported outcomes in the spotlight. The Lancet Neurology. 2019;18:981.\u003c/li\u003e\n\u003cli\u003eSnyder CF, Aaronson NK. Use of patient-reported outcomes in clinical practice. Lancet (London, England). 2009;374:369\u0026ndash;70.\u003c/li\u003e\n\u003cli\u003eRotenstein LS, Huckman RS, Wagle NW. Making Patients and Doctors Happier - The Potential of Patient-Reported Outcomes. N Engl J Med. 2017;377:1309\u0026ndash;12.\u003c/li\u003e\n\u003cli\u003eGoldfarb M, Drudi L, Almohammadi M, Langlois Y, Noiseux N, Perrault L, et al. Outcome Reporting in Cardiac Surgery Trials: Systematic Review and Critical Appraisal. Journal of the American Heart Association. 2015;4:e002204.\u003c/li\u003e\n\u003cli\u003eEliya Y, Averbuch T, Le N, Xie F, Thabane L, Mamas MA, et al. Temporal Trends and Factors Associated With the Inclusion of Patient-Reported Outcomes in Heart Failure Randomized Controlled Trials: A Systematic Review. Journal of the American Heart Association. 2021;10:e022353.\u003c/li\u003e\n\u003cli\u003eChen Y, Nagendran M, Gomes M, Wharton PV, Raine R, Lambiase PD. Gaps in patient-reported outcome measures in randomized clinical trials of cardiac catheter ablation: a systematic review. European Heart Journal Quality of Care \u0026amp; Clinical Outcomes. 2020;6:234\u0026ndash;42.\u003c/li\u003e\n\u003cli\u003eDaeter EJ, Timmermans MJC, Hirsch A, Lipsic E, Houterman S, Meetbaar Beter advisory board, et al. Defining and Measuring a Standard Set of Patient-Relevant Outcomes in Coronary Artery Disease. Am J Cardiol. 2018;121:1477\u0026ndash;88.\u003c/li\u003e\n\u003cli\u003eMcNamara RL, Spatz ES, Kelley TA, Stowell CJ, Beltrame J, Heidenreich P, et al. Standardized Outcome Measurement for Patients With Coronary Artery Disease: Consensus From the International Consortium for Health Outcomes Measurement (ICHOM). J Am Heart Assoc. 2015;4:e001767.\u003c/li\u003e\n\u003cli\u003eZannad F, Garcia AA, Anker SD, Armstrong PW, Calvo G, Cleland JGF, et al. Clinical outcome endpoints in heart failure trials: a European Society of Cardiology Heart Failure Association consensus document. Eur J Heart Fail. 2013;15:1082\u0026ndash;94.\u003c/li\u003e\n\u003cli\u003eHoms-Romero E, Romero-Collado A. Development of a Minimum Data Set Registry for Chronic Venous Insufficiency of the Lower Limbs. J Clin Med. 2019;8:1779.\u003c/li\u003e\n\u003cli\u003eKappetein AP, Head SJ, G\u0026eacute;n\u0026eacute;reux P, Piazza N, van Mieghem NM, Blackstone EH, et al. Updated standardized endpoint definitions for transcatheter aortic valve implantation: the Valve Academic Research Consortium-2 consensus document. J Thorac Cardiovasc Surg. 2013;145:6\u0026ndash;23.\u003c/li\u003e\n\u003cli\u003eChew DS, Whitelaw S, Vaduganathan M, Mark DB, Van Spall HGC. Patient-Reported Outcome Measures in Cardiovascular Disease: An Evidence Map of the Psychometric Properties of Health Status Instruments. Annals of Internal Medicine. 2022;175:1431\u0026ndash;9.\u003c/li\u003e\n\u003cli\u003eBylicki O, Gan HK, Joly F, Maillet D, You B, P\u0026eacute;ron J. Poor patient-reported outcomes reporting according to CONSORT guidelines in randomized clinical trials evaluating systemic cancer therapy. Annals of Oncology: Official Journal of the European Society for Medical Oncology. 2015;26:231\u0026ndash;7.\u003c/li\u003e\n\u003cli\u003eDirven L, Taphoorn MJB, Reijneveld JC, Blazeby J, Jacobs M, Pusic A, et al. The level of patient-reported outcome reporting in randomised controlled trials of brain tumour patients: a systematic review. European Journal of Cancer (Oxford, England: 1990). 2014;50:2432\u0026ndash;48.\u003c/li\u003e\n\u003cli\u003eEfficace F, Fayers P, Pusic A, Cemal Y, Yanagawa J, Jacobs M, et al. Quality of patient-reported outcome reporting across cancer randomized controlled trials according to the CONSORT patient-reported outcome extension: A pooled analysis of 557 trials. Cancer. 2015;121:3335\u0026ndash;42.\u003c/li\u003e\n\u003cli\u003eHaslam A, Herrera-Perez D, Gill J, Prasad V. Patient Experience Captured by Quality-of-Life Measurement in Oncology Clinical Trials. JAMA network open. 2020;3:e200363.\u003c/li\u003e\n\u003cli\u003eMaruszczyk K, Aiyegbusi OL, Cardoso VR, Gkoutos GV, Slater K, Collis P, et al. Implementation of patient-reported outcome measures in real-world evidence studies: Analysis of ClinicalTrials.gov records (1999\u0026ndash;2021). Contemp Clin Trials. 2022;120:106882.\u003c/li\u003e\n\u003cli\u003eMendis S, Puska P, Norrving B editors, Organization WH. Global atlas on cardiovascular disease prevention and control. World Health Organization; 2011.\u003c/li\u003e\n\u003cli\u003eLu X, Li J. Classical Chinese Herbal Formulas in the Treatment of Coronary Heart Disease: A Narrative Review. Chin J Integr Med. 2021;27:70\u0026ndash;9.\u003c/li\u003e\n\u003cli\u003eW J, L W, G P, X Z. Effects and Safety of Non-Pharmacological Therapies of Traditional Chinese Medicine for Coronary Heart Disease: An Overview of Systematic Reviews. Evidence-based complementary and alternative medicine : eCAM. 2022;2022.\u003c/li\u003e\n\u003cli\u003eYang F, Wong CKH, Luo N, Piercy J, Moon R, Jackson J. Mapping the kidney disease quality of life 36-item short form survey (KDQOL-36) to the EQ-5D-3L and the EQ-5D-5L in patients undergoing dialysis. Eur J Health Econ. 2019;20:1195\u0026ndash;206.\u003c/li\u003e\n\u003cli\u003eWare JEJ. SF-36 Health Survey Update. Spine. 2000;25:3130.\u003c/li\u003e\n\u003cli\u003eTucker G, Adams R, Wilson D. New Australian population scoring coefficients for the old version of the SF-36 and SF-12 health status questionnaires. Qual Life Res. 2010;19:1069\u0026ndash;76.\u003c/li\u003e\n\u003cli\u003eWindsor TD, Rodgers B, Butterworth P, Anstey KJ, Jorm AF. Measuring physical and mental health using the SF-12: implications for community surveys of mental health. Aust N Z J Psychiatry. 2006;40:797\u0026ndash;803.\u003c/li\u003e\n\u003cli\u003eWare JE, Kosinski M, Dewey JE, Gandek B. How to score and interpret single-item health status measures: a manual for users of the SF-8 health survey. Lincoln, RI: QualityMetric Incorporated. 2001;15:5.\u003c/li\u003e\n\u003cli\u003eWare J, Kosinski M, Keller SD. A 12-Item Short-Form Health Survey: construction of scales and preliminary tests of reliability and validity. Med Care. 1996;34:220\u0026ndash;33.\u003c/li\u003e\n\u003cli\u003eLang L, Zhang L, Zhang P, Li Q, Bian J, Guo Y. Evaluating the reliability and validity of SF-8 with a large representative sample of urban Chinese. Health Qual Life Out. 2018;16:55.\u003c/li\u003e\n\u003cli\u003eM J, Xe L, X Z, Q N, X G, H L. Development and validation of the diagnostic scale of traditional Chinese medicine syndrome elements for diabetic kidney disease. Annals of palliative medicine. 2021;10.\u003c/li\u003e\n\u003cli\u003eH Z, H L, Px H, Y L, Xc H, P L. Comparative Study of TCM Syndrome Scale for Liver Disease and Chronic Liver Disease Questionnaire Based on Assessment of Posthepatitic Cirrhosis. Evidence-based complementary and alternative medicine : eCAM. 2012;2012.\u003c/li\u003e\n\u003cli\u003eL S, Jj M, Y Y, Y X, Y Y. Patient Reported Traditional Chinese Medicine Spleen Deficiency Syndrome (TCM-SDS) Scale for Colorectal Cancer: Development and Validation in China. Integrative cancer therapies. 2021;20.\u003c/li\u003e\n\u003cli\u003eRivera SC, Kyte DG, Aiyegbusi OL, Slade AL, McMullan C, Calvert MJ. The impact of patient-reported outcome (PRO) data from clinical trials: a systematic review and critical analysis. Health Qual Life Outcomes. 2019;17:156.\u003c/li\u003e\n\u003cli\u003eDougados M, Nataf H, Steinberg G, Rouanet S, Falissard B. Relative importance of doctor-reported outcomes vs patient-reported outcomes in DMARD intensification for rheumatoid arthritis: the DUO study. Rheumatology (Oxford, England). 2013;52:391\u0026ndash;9.\u003c/li\u003e\n\u003cli\u003eKyte D, Ives J, Draper H, Calvert M. Management of Patient-Reported Outcome (PRO) Alerts in Clinical Trials: A Cross Sectional Survey. PloS One. 2016;11:e0144658.\u003c/li\u003e\n\u003cli\u003eJiang M, Yang J, Zhang C, Liu B, Chan K, Cao H, et al. Clinical studies with traditional Chinese medicine in the past decade and future research and development. Planta Med. 2010;76:2048\u0026ndash;64.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-complementary-medicine-and-therapies","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcam","sideBox":"Learn more about [BMC Complementary Medicine and Therapies](https://bmccomplementmedtherapies.biomedcentral.com/)","snPcode":"","submissionUrl":"","title":"BMC Complementary Medicine and Therapies","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Traditional Chinese medicine, patient-reported outcomes, cardiovascular disease, clinical trial registry","lastPublishedDoi":"10.21203/rs.3.rs-4678899/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4678899/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground and purpose:\u003c/h2\u003e \u003cp\u003ePatient-reported outcomes (PROs) are health condition assessments directly expressed by patients, providing a precise reflection of the patient's perspective. We aim to understand how PROs were being used to provide suggestions for conducting high-quality clinical studies of Traditional Chinese medicine (TCM) for cardiovascular diseases (CVD).\u003c/p\u003e\u003ch2\u003eMethods:\u003c/h2\u003e \u003cp\u003eWe searched clinical studies of TCM for CVD from the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) registered between January 1, 2010, and December 31, 2023. Trial phases, study types, age, gender, TCM interventions, regions and countries, time trends, PROs as primary/secondary/co-primary outcomes, and PRO instruments explicitly specified or implicitly specified were analyzed. We classified the studies that explicitly specified PROs into 14 categories based on the International Classification of Diseases-11 (ICD-11) ,and compared their PRO instruments with the Core Outcome Measures in Effectiveness Trials (COMET).\u003c/p\u003e\u003ch2\u003eResults:\u003c/h2\u003e \u003cp\u003e487 TCM CVD studies were identified. 194 studies did not mention the use of PRO instruments. 250 studies explicitly specified the PRO tool, while 43 studies implicitly (studies registration mentioned the use of PROs, but PRO instruments were not specified). Out of the 293 studies that included PROs, 84 (17.2%) listed PROs as their primary outcomes, 144 (29.6%) as secondary outcomes and 65 (13.3%) as co-primary outcomes. Chronic coronary heart disease (26.96%), hypertension (15.70%), and heart failure (14.68%) were the most common diseases in that 250 studies. Furthermore, their PRO instruments partially complied with COMET's recommendations ,while other diseases did not. Frequently used PRO instruments included the SAQ (Seattle Angina Questionnaire), the TCMSS (TCM syndrome score), the SF-8/12/36 (Short-Form 8/12/36-item Health Survey), and the VAS (Vsual Analog Scale).\u003c/p\u003e\u003ch2\u003eConclusion:\u003c/h2\u003e \u003cp\u003eOver the past decade, there has been a continued increase in the use of PROs as a measure in clinical investigations focused on TCM for CVD. Research and development of PROs core endpoints for different CVD could be improved. Given the current challenges surrounding the use of PROs in clinical studies of TCM, such as the inconsistent availability and absence of standardized PRO instruments for TCM, it is crucial to prioritize research on establishing standardized and normalized scales specifically designed for TCM.\u003c/p\u003e","manuscriptTitle":"Using patient-reported outcomes in clinical studies for cardiovascular diseases of Traditional Chinese medicine worldwide: a cross-sectional study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-08-17 00:57:17","doi":"10.21203/rs.3.rs-4678899/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-01-09T09:40:04+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-11-18T08:21:00+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"150715779731104793607249423574660665646","date":"2024-11-04T06:27:44+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"286618881555081752779672736619452817421","date":"2024-10-29T08:22:48+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-10-08T12:14:25+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"52651032763967251951113516454093339532","date":"2024-09-26T11:56:34+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-08-19T01:28:34+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-08-16T09:56:14+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-07-17T07:21:14+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-07-17T07:19:56+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Complementary Medicine and Therapies","date":"2024-07-03T08:40:09+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-complementary-medicine-and-therapies","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcam","sideBox":"Learn more about [BMC Complementary Medicine and Therapies](https://bmccomplementmedtherapies.biomedcentral.com/)","snPcode":"","submissionUrl":"","title":"BMC Complementary Medicine and Therapies","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"92155ffe-b1b2-49d9-9a18-4c98508ebd89","owner":[],"postedDate":"August 17th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-03-19T09:08:56+00:00","versionOfRecord":[],"versionCreatedAt":"2024-08-17 00:57:17","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4678899","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4678899","identity":"rs-4678899","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}