Non-ST segment elevation acute coronary syndrome (non-ST-elevation ACS, NSTE-ACS) is a clinical syndrome in which patients have acute chest pain but no sustained ST-segment elevation in electrocardiogram [
Traditional Chinese medicine (TCM) has a history of thousands of years and obtains a unique understanding and methods of therapy for various diseases. According to the clinical manifestations, NSTE-ACS belongs to the category of “Xiong Bi (chest pain)”, “Xin Ji (palpitation),” and “Zhen Xin Tong (pain of the heart)” for TCM’s theory [
Goal Attainment Scale (GAS) is a method of evaluation in order to quantify progress toward defined rehabilitation goals [
This study protocol was based on the empirical observational research, adopting the method of evidenced-based GAS and collecting the information of diagnosis and treatment about the TCMs individualized therapy of NSTE-ACS, to evaluate the clinical effectiveness and variation of therapy for TCM objectively.
The objective of this research is to evaluate the individualized clinical efficacy of TCM in the quantitative way (evidence-based GAS) by long-term observing the variation of symptoms and the corresponding adjustment of prescriptions after the individualized treatment of TCM on NSTE-ACS.
This is observational research which will conduct at the Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine (BUCM), the Third Affiliated Hospital of BUCM, and the Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University. This research has a prospective feature, which means that the admission period of patients will be between March 1, 2020, and August 31, 2020. We will include 200 hospitalized patients who were diagnosed as NSTE-ACS. Each included patient will be followed up by telephone or door visit every 2 weeks, collecting the individualized intervention of TCM and evaluating through the table of evidence-based GAS. The whole procedure of the research will consist of 6 times of follow-up. This protocol conforms to the statement of Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) [
Patients will exit based on the situation as follows: (a) physicians will make a decision if patients have allergic reactions, serious adverse events, complications, or special physiological changes and were not suitable for this research or have poor compliance affecting clinical judgment. (b) Patients are unable to continue follow-up and file an application. The discontinuance of research is followed by orders from the sponsor or administrative department. The rejection criteria are based on the inclusion and exclusion criteria, insufficient information, or lost to follow-up.
This protocol is the observational setting with no controlled group. The method of self-control is used to compare therapeutic efficiency. All included participants will not apply any particular interventions for the aim of scientific research. The tool of evidence-based GAS is the way of analysis and evaluation, which represents patients who can receive the individualized treatment of TCM or western medicine based on their situations. The only requirement is they should choose the TCM or combined therapy if they have a need to be treated by physicians.
This observational research cannot estimate the sample size accurately because of the lack of reference and data support. Two hundred qualified participants will be observed and followed-up according to the support of the foundation, hospitalized reality of the cardiology department previously, and the potential location of NSTE-ACS patients in three hospitals. The materials and methods section should contain sufficient detail, so that all procedures can be repeated. It may be divided into headed subsections if several methods are described. The flow diagram of this research is listed as follows (Figure
Flow diagram of observational research by the evidence-based Goal Attainment Scale.
This part will be accomplished by patients based on the guidance of researchers. The score of weight that constitutes the evidence-based GAS will be obtained by multiplying the
The classification of score of weight for
Importance | Difficulty |
---|---|
0 = not important | 0 = not difficult |
1 = slightly important | 1 = slightly difficult |
2 = important | 2 = difficult |
3 = very important | 3 = very difficult |
The goal of treatment from physicians and evidence-based medicine (3 to 5 goals among the 8 goals can be selected form the table).
Goal of treatment | Importance | Difficulty | Weight | Baseline | Results |
---|---|---|---|---|---|
1. Whether can improve the symptom of chest pain | |||||
2. Whether can improve the quality of life (based on the SF-36 form) | |||||
3. Whether can reduce the drug use | |||||
4. Whether can reduce finical burden of patients | |||||
5. Whether can improve prognosis of patients based on the report of MACE | |||||
6. Whether can improve the physical-chemical indexes (blood lipids, vascular endothelial function, blood rheologic indexes, oxidative stress, blood routine, liver and kidney functions, and blood coagulation factor) | |||||
7. Whether can improve imaging indexes (LVEF, chest radiography, CT, and MRI) | |||||
8. Whether can improve syndrome efficiency of TCM | |||||
9. Handwritten: the first goal of treatment that patients they want | |||||
10. Handwritten: the second goal of treatment that patients they want | |||||
The goal of treatment for evidence-based GAS should be consistent with clinical practice. Goals should be set through mutual consultation among physicians, patients, and their families. These goals are people who want to achieve in the course of the treatment. Evidence from the published systematic review and guideline will be used as the support for the establishment of a goal and are listed in Table
It should define the classification of outcomes with the 5-level Likert scale after the setting of the goal of treatment to confirm the reliability and validity of results. The related discussion of the classification of outcomes is shown in Section
The expected result of every goal is generally defined as the level 0 for the most likely to occur after treatment based on the 5-level Likert scale (Table
Scale for evidence-based GAS.
Scale for evidence-based GAS | −2 | −1 | 0 | 1 | 2 |
---|---|---|---|---|---|
1. Symptom of chest pain | Increase of the frequency of attack and the degree of pain, prolong for duration | No change of the frequency of attack, the degree of pain, and duration | A little bit relieves of the frequency of attack, the degree of pain, and duration | Obvious relieves of the frequency of attack, the degree of pain, and the duration | No any symptoms of chest pain |
2. Quality of life based on SF-36 (1physiological function, 2physical function, 3body pain, 4general health, 5vitality, 6social function, 7emotional function, and 8mental health) | Aggravate obviously for 2 or more among the 8 dimensions of SF-36 | No clearly improvement among the 8 dimensions of SF-36 | Obvious amelioration for 1 to 2 among the 8 dimensions of SF-36 | Obvious amelioration for 3 to 4 among the 8 dimensions of SF-36 | Obvious amelioration for more than 4 among the 8 dimensions of SF-36 |
3. Situations of drug use | Obvious increase of dosage and categories | No obvious variations for dosage and categories | Decrease of dosage and categories (1 to 2) | Obvious decrease of dosage and categories (more than 2) | Discontinue drug followed by the doctor’s advice |
4. Financial burden | Obvious increase of financial input | No obvious change of financial input compared with before | Decrease of financial input and relieve of the burden | Obvious decrease of financial input and relieve of the burden | No financial burden |
5. Prognosis of patients (MACE: 1death, 2MI, 3stroke, 4TIA, 5PCI, 6peripheral vascular intervention, and 7readmission) | 1 or more new events (MACE) report compared with before | Events were observed similar to before and no new events report | No event (MACE) reports | No event (MACE) reports for a long time (six months to one year) | No event (MACE) reports for a long time (more than one year) |
6. Physical and chemical indicators (1blood lipid, 2vascular endothelial function, 3blood rheologic indexes, 4oxidative stress, 5myocardial injure marker, 6liver and kidney functions, and 7blood coagulation factor) | Obvious aggravated more than 2 indicators | No obvious change compared with before | Amelioration of 1 to 2 indicators compared with before | Amelioration of 3 to 4 indicators compared with before | Amelioration of more than 4 indicators compared with before |
7. Imaging indexes (1LVEF, 2chest radiography, 3CT, and 4MRI) | Obvious aggravated more than 2 indexes | No obvious change compared with before | Amelioration of 1 to 2 indexes compared with before | Amelioration of 2 to 3indicators compared with before | Amelioration of more than 3 indicators compared with before |
8. Efficiency of TCM syndrome [ | Obvious aggravated of the TCM syndrome compared with before | No obvious variation of the TCM syndrome compared with before | A little bit amelioration of the TCM syndrome compared with before | Obvious amelioration of TCM syndrome compared with before | Enormous amelioration of TCM syndrome compared with before |
9. Handwriting: the goal 1 that patients want to achieve) | |||||
10. Handwriting: the goal 2 that patients want to achieve |
Professional evaluators will assign corresponding scores according to the completion of each goal at the arranged time point after the therapy.
Note:
Symptoms of chest pain should be asked by physicians and replenished by family members. Symptoms should be around the frequency of attack, the degree, the duration, the location, the timing, the quality, and the accompanying discomforts which are related to the judgment of TCM syndrome. The discomforts should be on the basis of cold and heat, sweat, head and body, excrement, diet, and so on [
The information of the quality of life comes from the short-form health survey with 36 items (SF-36) [
The drug contains the application of TCM and western medicine. The situation of drugs for TCM and western medicine will be measured by types, dosage, frequency, duration, and side effects. It should be highlighted that the reasons for the change of drug should be recorded clearly. The application of drugs should follow the medical advice of doctors strictly.
The financial burden is an essential part of patients [
The prognosis of patients will be asked by the report of major adverse cardiovascular events (MACEs) [
The indicators including 7 categories will be measured as follows: (1) blood lipid: cholesterol (CHO), triglycerides (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL). (2) Vascular endothelial function: C-reactive protein (CRP), nitric oxide (NO), and endothelin (ET). (3) Blood rheologic indexes: erythrocyte sedimentation rate (ESR). (4) Oxidative stress: malondialdehyde (MDA) and superoxide dismutase (SOD). (5) Myocardial injure marker: creatine kinase-MB (CK-MB), creatine kinase (CK), cardiac troponin T (cTnT), cardiac troponin I (cTnI), and lactate dehydrogenase (LDH). (6) Liver and kidney functions: aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin (ALB), blood urea nitrogen (BUN), and serum creatinine (SCR). (7) Blood coagulation factor: prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), and fibrinogen (FIB).
The indexes will be collected and inquired including echocardiography (left ventricular ejection fraction, LVEF), chest radiography, chest tomography (CT), and magnetic resonance imaging (MRI).
The efficiency will be evaluated on the basis of the degree of TCM syndrome improvement before and after therapy [
This definition contains the appearance or deterioration of any syndrome, symptom, or disease that may affect the health of patients during the observation period. The adverse events can be new diseases, deterioration of symptoms, treatment, or disease, and a combination of one or more factors, which does not represent the direct causal relationship with the individualized treatment of TCM.
These events include death, life-threatening events, prolonged hospitalization, disability, congenital malformation, crucial medical events (events that may not immediately endanger life or result in death or hospitalization but may endanger the patient or require action to prevent consequences mentioned above), and medical treatment to prevent permanent damage.
(1) Whether there is a reasonable relationship between the time of TCM individualized treatment and suspicious adverse reactions. (2) Whether the suspected adverse reactions are consistent with types of adverse events that are already known for TCM individualized treatment. (3) Whether suspected adverse reactions can be reduced and disappear on the basis of drug withdrawal and dosage reductions. (4) Whether the same reaction occurs again after using the same drug. (5) Whether the suspected adverse reactions can be explained by the pathological status, combination of drugs, and previous therapy of patients.
The variation of the condition of patients should be recorded for individualized TCM treatment faithfully. Adverse reactions or unexpected toxic side effects (including symptoms, signs, and laboratory indicators) should be paid attention during the evaluation of the efficacy with the evidence-based GAS. The symptoms, degree, occurrence time, duration, and measures of adverse reactions during hospitalization and follow-up should be recorded in the questionnaire and marked with the date.
The software SPSS version 19.0 will be used for statistical analysis. All statistical analysis will be in the significance level 0.05 and expressed by the 95% confidence interval (CI) or two-sided test. The description of quantitative indicators for baseline and the demographic feature will calculate the mean, standard deviation, median (distributed data), and maximum (distribution data). The description of qualitative indicators will calculate the frequency and percentage. Results of evidence-based GAS on different times will be analysed by the repeated measures ANOVA to observe the dynamic characteristics of individualized curative effect. Among the repeated measures ANOVA, the multivariable test (Pillai’s trace, Wilks’ lambda, Hotelling’s trace, and Roy’s largest root) will be used to judge the difference of efficiency at different time points; Mauchly’s test of sphericity will be applied to determine whether the corrected test (Greenhouse–Geisser, Huynh–Feldt, and lower-bound) is needed; tests of within-subjects effects will be judged whether the result is consistent with the multivariable test; tests of within-subjects contrasts will evaluate whether the change of curative effect was in accordance with the form of the curve; tests of between-subjects effects will be used to determine whether the efficacy of pairwise comparison at each time point was statistically significant.
All researchers will be received the train of protocol and method of evidence-based GAS. All physicians should conduct the protocol according to the standard operating procedure (SOP) in the future.
(1) Admission bias (Berkson’s bias) [
(1) Recall bias: the systematic bias due to the variation of accuracy and integrity when patients recall their previous therapy. (2) Reporting bias: patients are deliberately exaggerating or narrowing some information. (3) Detection bias: the collection of inaccurate information due to incomplete records and the error analysis. As for the method of control, detailed data collection and strict quality control methods will be developed; the information will be collected by objective indicators or methods; questionnaires should be designed strictly, and researchers should remain scientific [
This bias will be controlled by (1) preventing confounding factors with restriction and match; (2) collecting detailed and accurate data that may include confounding factors; and (3) taking various measures in the stage of analysis with the methods of standardization and multivariate analysis.
Every participant should follow the instruction during the observational period, and their related information should be recorded and stored as a paper document (CRF). The electrical document should be stored in SPSS along with the procedure of filling in the paper document. All basic information of participants will be protected by the researching group, and a unique identified number will be applied during the procedure of follow-up. The informed consent will be stored in the office of Dongzhimen Hospital of Beijing University of Chinese Medicine along with the CRF.
A researcher from the researching group will be assigned as the clinical research coordinator (CRC) to assist experts in nonmedical judgment related affairs. CRC will compare the data between the paper and electrical document, and any modification of the data will be monitored and recorded in detail.
The evaluation of clinical efficiency for modern western medicine paid close attention to the variation of laboratory indexes or pathohistological structure [
There are some obvious advantages of evidence-based GAS on the clinical application of TCM. Firstly, mutual communication in-depth between patients and physicians will be done to assist the construction of much more rational plan of TCM. Secondly, personal clinical experience and objective clinical evidence will be well combined to better show the character of TCM and promote to the whole world. Thirdly, this method primarily focuses on the dynamic and quantitative evaluation for TCM personalized treatment, which is much more suitable for TCM than standardized grouping evaluation.
Limitations for evidence-based GAS on clinical practice for observational research are listed as follows: (1) evidence-based GAS comes from the optimization of GAS, in which the process of evaluation is conducted according to the personalized intention of patients. Although evidence-based GAS combined with the evidence-based medicine of TCM and western medicine, the practicability and acceptability of it for personalized evaluation for TCM is still in at the centre of controversy; (2) working efficiency of researchers will be influenced on the basis of long-term observation and follow-up, and some of the events such as recall bias and follow-up bias cannot deal with appropriately; (3) although the clinical evidence from this observational study design can reflect the characteristics of individualized therapy for TCM, the evidence is still in a low level (II-3 level of the US Preventive Services Task Force [
No data were used to support this study.
This study was approved by the Medical Ethics Committee of the Dongzhimen Hospital, Beijing University of Chinese Medicine (DZMEC-KY-2020-07) (see Supplementary File 3).
The authors declare that they have no conflicts of interest.
All authors contributed to the design and revision of the protocol. CZ and HCS contributed to the design of statistical analysis. ZFS and MKG contributed to the application of ethical approval documents. XXW, MKG, XYZ, and ZFS performed the collections of systematic reviews. ZFS, JYH, and ML contributed to the making of figures and tables. HCS contributed to the guidance of evidence-based GAS for the protocol.
This work was supported by Prof. Yan Liu, who provided the guidance and explanation of the checklist of STROBE. This research was supported by the National Science Fund for Distinguished Young Scholars (no. 81725024).
Supplementary File 1: informed consent form. Supplementary File 2: checklist of STROBE. Supplementary File 3: document of ethical approval.