Performance Study of Human KRAS Gene Mutation Detection Kit (Fluorescence PCR Method)
Study Name: Performance Study of Human KRAS Gene Mutation Detection Kit (Fluorescence PCR Method)
Site: Henan Provincial Cancer Hospital
Sponsor: Kaijie Enterprise Management (Shanghai) Co., Ltd.
Third-party Lab: Shanghai Sangon Health Medical Laboratory Co., Ltd.
HGRAC Approval Time: April 2024
Efficacy and Safety Study of Intense Pulsed Light and Hyaluronic Acid Injection
Study Name: Efficacy and Safety Study of Intense Pulsed Light and Hyaluronic Acid Injection
Site: Peking University First Hospital (Peking University First Clinical Medical College)
Sponsor: L'Oréal (China) Co., Ltd.
HGRAC Approval Time: April 2024
Note: HGRAC Approval or Filing (Human Genetic Resource Administration of China) is an important step before the first enrollment of subjects for clinical trials in China sponsored by foreign companies.
Clinical Study of U200 Extracorporeal Shock Wave Lithotripter for the Treatment of Urinary System Stones
Study Name: Clinical Study of U200 Extracorporeal Shock Wave Lithotripter for the Treatment of Urinary System Stones
Site: Zhongshan City Traditional Chinese Medicine Hospital
Sponsor: Shenzhen Huikang Precision Instruments Co., Ltd.
HGRAC Approval Time: April 2024
Development and Application of Methylation-based In Vitro Diagnostic Reagents for Cervical Cancer and Precancerous Lesions
Study Name: Development and Application of Methylation-based In Vitro Diagnostic Reagents for Cervical Cancer and Precancerous Lesions
Site: Guangzhou First People's Hospital
Sponsor: Boercheng (Beijing) Technology Co., Ltd.
Third-party Lab: Beijing Novogene Technology Co., Ltd.
HGRAC Approval Time: April 2024
Clinical Performance Verification and Application Research of Mindray In Vitro Diagnostic Products
Study Name: Clinical Performance Verification and Application Research of Mindray In Vitro Diagnostic Products
Site: Chinese Academy of Medical Sciences Fuwai Hospital Shenzhen Hospital (Shenzhen Sun Yat-sen Cardiovascular Hospital)
Sponsor: Shenzhen Mindray Bio-Medical Electronics Co., Ltd.
HGRAC Approval Time: April 2024
Exploratory Research on the Use of Focal Pulse Ablation Systems for Typical Atrial Flutter Ablation
Study Name: Exploratory Research on the Use of Focal Pulse Ablation Systems for Typical Atrial Flutter Ablation
Site: Fuwai Hospital, Chinese Academy of Medical Sciences
Sponsor: CardiPulse, Hangzhou
HGRAC Approval Time: March 2024
Clinical Application Study of the Domestic Endoscopic Robotic System
Study Name: Clinical application study of the domestic endoscopic robotic system
Site: 4 sites, Peking University First Hospital；Peking Union Medical College Hospital；Beijing Miyun District Hospital；Xuzhou Central Hospital
Target Disease: benign and malignant lesions of urinary system
Study Type: Interventional study
Study Design: Sequential
Study Objective: Based on the Suzhou Kangduo Endoscopic Surgical Robot System, Shandong Weigao Endoscopic Surgical Robot System, Beijing Shurui Endoscopic Surgical Robot System, and their preliminary researches, a multicenter clinical cohort study of domestic endoscopic surgical robot systems in urological surgery is conducted. This study completes evidence-based evaluations including clinical outcomes, applicability, usability, and reliability, to formulate product configuration schemes, technical operation specifications, surgical norms, expert consensus, and clinical diagnosis and treatment guidelines for medical institutions at different levels.
Inclusion Criteria: (1)Patients who need partial nephrectomy (TNM stage: T1, R.E.N.A.L score ≤ 10), radical prostatectomy (TNM stage : T1-3), upper urinary tract repair surgery, adrenal tumor resection, and radical resection of bladder cancer (TNM stage : T1-2). (2)Age 18-75 years old, regardless of gender. (3)Patients who agreed to sign the informed consent and could follow the doctor 's advice and regular follow-up.
Exclusion Criteria:
(1) Patients with severe heart, lung, brain, liver, kidney disease, can not tolerate surgery or anesthesia ; (2) Patients can not tolerate pneumoperitoneum ; (3) Patients with severe coagulation dysfunction (activated partial thromboplastin time or prothrombin time more than 1.5 times the normal range or platelet count less than 100 × 10 ^ 9 / L ) ; (4) Patients with active pulmonary tuberculosis ; (5) Extensive metastasis of the tumor in the abdominal and pelvic cavity ; (6) Patients with severe uncontrolled disease or acute infection ; (7) Patients with cardiovascular and cerebrovascular diseases, blood system diseases and diabetes that can not be controlled, can not meet the surgical standards ; (8) Patients with immune system diseases that cannot be controlled, cannot meet the surgical standards ; (9) Patients with multiple pelvic and abdominal surgery history, or severe pelvic adhesions ; (10) Pregnant or lactating women.
Trial Group: Urological surgery using domestic endoscopic surgery robot system including partial nephrectomy, radical prostatectomy, upper urinary tract reconstruction surgery, adrenalectomy and radical cystectomy et al. Sample Size: 600
Primary Indicator: success rate of operation
Secondary indicator: rate of complications; operation time；hospital stay after operation
EC Approval Time: 13 March 2024
Multicenter, Randomized, Open, Parallel Controlled Clinical Trial of Diffracted Multifocal IOL for Vision Correction after Cataract Extraction
Study Name: Multicenter, randomized, open, parallel controlled clinical trial of diffracted multifocal IOL for vision correction after cataract extraction
Site: 8 sites, Eye Hospital, WMU Zhejiang Eye Hospital; Tianjin Medical University Eye Hospital; Eye Hospital of China Academy of Chinese Medical Sciences; Eye, Otolaryngology Hospital Affiliated to Fudan University; Xiangya Hospital, Central South University; Shenyang Aier Optometry Hospital; Wuhan Aier Eye Hospital; Tianjin Medical University General Hospital
Sponsor: Tianjin Shi Ji Kang Tai Biomedical Engineering Co.,Ltd
EC Approval Time: 23 December 2021
Target Disease: Cataract
Study Type: Interventional study
Study Design: Parallel
Study Objective: The purpose of this study is to evaluate the effectiveness and safety of the diffractive multifocal IOL developed by Tianjin Shijikangtai Biomedical Engineering Co., Ltd. for the correction of acuity without lens after cataract extraction, and to provide support for product registration.
Inclusion Criteria: 1. Age ≤ 18 years old; age ≤81 years old, gender unlimited; 2. For patients with cataract in one or both eyes, who plan to undergo phacoemulsification + intraocular lens implantation and have delens requirements, the affected eye with poor corrected vision or better fundus is selected to be enrolled in this study if both eyes of the patient meet the admission criteria. 3. Kappa Angle < 0.5mm or Kappa Angle less than half of the diameter of the refraction optical region in the center of the diffractive multi-focal intraocular lens (Kappa Angle: the distance from the center of the pupil to the optic axis); 4. The Total high-order aberration (Total HOA) in the central corneal diameter of 4 mm was less than 0.3um; 5.3.0mm≤ natural pupil diameter under dark room ≤5.5mm; 6. Preoperative depth of anterior room ≥ 2.00mm; 7. The axial length of the preoperative eye was 21 mm~28 mm; 8. Predicted corneal astigmatism ≤1.0D after surgery; 9. Intraocular lens correction diopter is expected to be between +5.0D and +30.0D; 10. Patients who can complete 12 months of follow-up; 11. Be able to understand the purpose of the trial, voluntarily participate in the clinical trial and sign the informed consent.
Exclusion Criteria:
1. Pregnant or lactating women, and those who plan to become pregnant within 12 months after the operation;
2. Preoperative best corrected far vision, middle vision under best corrected far vision, or near vision under best corrected far vision >20/40 (LogMAR chart);
3. Preoperative corneal endothelial cell count < 2000 /mm2;
4. Participants in clinical trials of other drugs or medical devices;
5. Contraindications for intraocular lens implantation, such as small eyeballs, glaucoma, severe corneal dystrophy, obvious macular/pigmentation epithelial cell disease, diabetic retinopathy, severe optic atrophy, severe anterior chamber hypertrophy, choroidal hemorrhage, massive vitreous loss, uncontrolled ocular pressure increase, chronic uveitis, etc. Posterior capsular rupture or separation of ciliary bands (unable to hold the intraocular lens), vitreous hemoperitoneum or severe turbidity, dislocation or subluxation of the lens, and other serious ocular diseases associated with it;
6. Concomitant ocular infectious diseases, such as chronic dacryocystitis;
7. Complicated with severe corneal disease;
8. Corneal injury or corneal scar;
9. Had retinal detachment or retinopathy;
10. Had eye trauma within 3 months before screening;
11. Had undergone intraocular or corneal surgery;
12. Severe dry eye or meibomian gland dysfunction (MGD);
13. Traumatic cataract or congenital cataract;
14. Contralateral amblyopia or disregard function determined by researchers;
15. Combined eye surgery is required;
16. Eye or systemic medications being used or required during the study may affect vision or postoperative outcome judgment;
17. Patients with serious or unstable heart, liver, kidney, lung, endocrine (including thyroid insufficiency), blood, mental diseases and other diseases that seriously affect surgery, or any of the liver and kidney function indicators (TBIL, ALT, AST, ALP, BUN, Cr) greater than 2.5 times the upper limit of the normal reference value of this research center;
18. Diabetes mellitus (fasting blood glucose > 8 mmol/L), or a history of diabetes associated with eye diseases or conditions affecting postoperative vision;
19. Results of electrocardiogram or laboratory examination indicate contraindications to surgery;
20. Unsupervised or unable to follow medical advice;
21. Other conditions that the investigator judged unsuitable for participation in the experiment.
Group 1: Control group, The control group diffractive multifocal intraocular lens was implanted, sample size of 93
Group 2: Trial group, Diffractive multifocal intraocular lens of the experimental group was implanted, sample size of 93
Primary Indicator: The percentage of best corrected far vision, medium vision under best corrected far vision, and near vision under best corrected far vision all reach 20/40
Secondary Indicator: Best corrected far vision, medium vision under best corrected far vision, and near vision under best corrected far vision
Randomization Procedure: The central stratified block is random.
miR-92a Detection Kit (fluorescent RT-PCR method)_NMPA Approval in March 2018
Product Name: miR-92a detection kit (fluorescent RT-PCR method)
Category: Domestic Class III
Registration Pathway: Innovation
NMPA Approval Time: March 2018
Product Structure and Composition: miR-92a reverse transcription reaction solution; miR-92a PCR reaction solution; miR-92a reverse transcription primer; miR-92a PCR primer, probe; quality control sample 1; quality control sample 2; reverse transcriptase; RNAse inhibitor; Taq enzyme; 0.1% DEPC water.
Scope of Application: This product is used for qualitative detection of miR-92a nucleic acid in human fecal samples. It is intended for patients with positive fecal occult blood, combined with other symptoms such as changes in bowel habits, changes in stool shape, chronic constipation, urgency in defecation, etc., recommended by clinical doctors for colonoscopy but refused for various reasons. It is used as an auxiliary diagnostic tool for colorectal cancer in clinical practice. A positive test result is not evidence for early diagnosis or confirmation of colorectal cancer, and a negative result does not rule out the possibility of colorectal cancer. The final diagnosis should be based on colonoscopy results. This product is not intended for general population tumor screening.
Colorectal cancer is classified according to the TNM classification of malignant tumors, into stages 0, I, II, III, IV. Early stages typically present symptoms such as changes in bowel habits, changes in stool shape, blood in stool, chronic constipation, urgency in defecation, but these symptoms are often mild and atypical, leading to neglect. miR-92a, derived from the miR-17-92 gene cluster on human chromosome 13, is a type of small non-coding RNA. miR-92a promotes the proliferation and migration of colorectal cancer cells by targeting and inhibiting PTEN, KLF4, and downstream p21 genes. Studies have shown a characteristic increase in miR-92a content in fecal samples of colorectal cancer patients.
Packing Specification: 48 servings per box
Test Principle: The miR-92a detection kit (fluorescent RT-PCR method) uses an RNA extraction kit to extract RNA from feces, performs RT-PCR reactions, and utilizes primers and probes that specifically bind to miR-92a reverse transcription products for PCR amplification. During amplification, after the probe hybridizes with the miR-92a template in the reverse-transcribed cDNA chain, the fluorescent dye group at the 5' end of the probe is cleaved by Taq enzyme, releasing a fluorescent signal. The strength of the detected fluorescent signal reflects the content of miR-92a in the sample.
Main Raw Materials:
1. Types of main raw materials: The main raw materials of this kit include Taq enzyme, reverse transcriptase, miR-92a reverse transcription primer, miR-92a upstream primer, miR-92a downstream primer, miR-92a probe, miR-92a gene RNA fragment, dNTP, and RNAse inhibitor.
2. Selection of main raw materials:
2.1 Externally purchased main raw materials include Taq enzyme, reverse transcriptase, dNTP, and RNAse inhibitor. By using these components to prepare the reaction system and conducting functional tests with positive fecal samples from colorectal cancer, the best suppliers are selected.
2.2 Self-designed main raw materials include miR-92a reverse transcription primer, miR-92a upstream primer, miR-92a downstream primer, miR-92a probe, and miR-92a gene RNA fragment. Confirmation is done through functional tests.
The applicant has designed a complete set of enterprise reference materials, including positive reference materials, negative reference materials, detection limit reference materials, precision reference materials, linear range reference materials, and interference substance reference materials. Negative reference materials include negative fecal samples from colorectal cancer, esophageal cancer patients, and gastric cancer patients; positive reference materials, precision reference materials, and interference substance reference materials use fecal samples from colorectal cancer patients. The detection limit reference material and linear range reference material are prepared by diluting synthetic miR-92a gene RNA fragments. The concentration of the detection limit reference material is 1×10^4 copies/μL of miR-92a gene RNA fragment, and the concentration of the linear range reference material is 1×10^7 copies/μL of miR-92a gene RNA fragment.
The various enterprise reference materials are used comprehensively for evaluating the sensitivity, specificity, and repeatability of the product. The kit includes quality control samples 1 and 2, where quality control sample 1 contains miR-92a gene RNA fragments, and quality control sample 2 is 0.1% DEPC water used for quality control during the detection process.
Research on Production Processes and Reaction Systems:
1. Reverse Transcription: The applicant optimized the concentrations and amounts of various main materials (reverse transcriptase, reverse transcription primer, RNAse inhibitor, dNTP, MgCl2, PCR reaction buffer) in the PCR reaction system and conducted optimization experiments on the reverse transcription process to determine the optimal production process and reaction system for reverse transcription reagents.
2. Fluorescent PCR Amplification: The applicant optimized the concentrations and amounts of various main materials (Taq enzyme, MgCl2, dNTP, primers, probes, PCR reaction buffer, 50% glycerol) in the PCR reaction system and conducted optimization experiments on the PCR reaction program to determine the optimal production process and reaction system for fluorescent PCR amplification reagents.
3. The applicant also conducted research on RNA concentration, reverse transcription template amount, PCR template amount, fecal sample amount, and sample collection methods to further determine the various parameters and indicators of the reaction system in the kit.
Analytical Performance Research:
The analytical performance of the product includes the evaluation of detection limit, negative agreement rate, positive agreement rate, precision, interference substances, and linear range.
In the assessment of the detection limit, the applicant used a high concentration of miR-92a positive reference material diluted in fecal samples without the miR-92a gene, and after 25 repeated tests, determined a concentration level of 100 copies/μL with a detection rate of 95% as the lowest detection limit for the reagent.
For the evaluation of positive agreement rate, samples from clinically diagnosed early-stage, mid-stage, and late-stage colorectal cancer patients were tested, and the results showed a 100% positive agreement rate.
In the precision study, fecal samples from late-stage and mid-stage colorectal cancer patients were used to evaluate the intra-batch and inter-batch precision of the product. The results indicated that the intra-batch and inter-batch detection Ct value CV% for three batches of reagents were not higher than 5%.
Regarding the assessment of negative agreement rate, samples including fecal samples from patients with various conditions were tested for non-specific reactions with miR-92a gene. The results showed no cross-reactivity with the specified conditions.
Interference tests revealed specific conditions that could interfere with the testing results, such as the presence of blood or certain substances in the fecal samples.
The linear range assessment showed a linear correlation coefficient of r2≥0.980 for a linear range of 102 copies/μL - 106 copies/μL.
The efficiency of the nucleic acid extraction reagent was found to be greater than 90% in the study conducted by the applicant.
Based on the comprehensive evaluation, the applicant chose the nucleic acid extraction reagent produced by Jinbaihui Company as the method for nucleic acid extraction and purification for the product. The product is packaged in boxes of 48 units each, and performance evaluation data for six batches (batch numbers: 20131201, 20131202, 20131203, 20161001, 20161002, 20161003) on all applicable models were provided.
Research on Positive Judgment Value:
By using fecal samples from 150 healthy individuals and 120 colorectal cancer patients provided by Shenzhen People's Hospital, as well as 49 samples from normal individuals, 76 samples from colorectal cancer patients, 36 samples from polyp patients, 30 samples from liver cancer patients, 30 samples from enteritis patients, 30 samples from esophageal cancer patients, 30 samples from gastric cancer patients, 30 samples from adenoma patients, 30 samples from gastritis patients, 30 samples from appendicitis patients, 30 samples from colitis patients, 30 samples from peptic ulcer patients, 30 samples from pancreatic cancer patients, 30 samples from bile duct cancer patients, and 30 samples from oral cancer patients obtained from the Chinese University of Hong Kong, miR-92a test kits (fluorescent RT-PCR method) were used for testing. The results were analyzed using SPSS 15.0 statistical analysis software with ROC curve analysis. Based on the Youden index analysis results, the Ct value corresponding to the maximum Youden index was determined as the positive judgment value (Cut-off) at 30.75.
The effectiveness assessment of the test kit is determined as follows:
1. Quality Control Sample 1: Ct value within the range of 30.70-32.3 with a clear exponential growth phase.
2. Quality Control Sample 2: Ct value >36.00 or no Ct value, linear as a straight line or slightly slanted line, without a clear exponential growth phase.
For the results to be considered meaningful, they must meet the above criteria. Otherwise, the test should be repeated.
Result interpretation:
1. When the Ct value of a sample is greater than 30.75, the test result is determined as negative.
2. When the Ct value of a sample is less than or equal to 30.75, the test result is determined as positive.
Stability Research:
The applicant conducted a systematic study on the real-time stability, bottle-opening stability, and freeze-thaw stability of the product to determine the effective storage time under various conditions.
For the real-time stability study, three batches of test kits (batch numbers: 20131201, 20131202, 20131203) were stored at -20°C. Accuracy, analytical specificity, precision, detection limit, and interference substance tests were conducted at 0, 3, 6, 9, 12, and 15 months. After 12 months, all indicators met the quality requirements, confirming that the product can be stably stored at -20°C for 12 months.
The bottle-opening stability study involved three batches of test kits (batch numbers: 20131201, 20131202, 20131203) being opened and stored at -20°C. Accuracy, analytical specificity, precision, detection limit, and interference substance tests were conducted at the sixth and twelfth months of the validity period. All parameters met the quality requirements, indicating a bottle-opening stability of 12 months.
For the freeze-thaw stability study, three batches of test kits (batch numbers: 20131201, 20131202, 20131203) were opened, thawed at room temperature, refrozen at -20°C after complete thawing and a 15-minute rest. After undergoing a total of 8 freeze-thaw cycles, tests for accuracy, analytical specificity, precision, detection limit, and interference substances were conducted. The product met the quality requirements after 6 freeze-thaw cycles, but some performance indicators did not meet the quality requirements after 8 cycles. Therefore, it was determined that the product should not undergo more than 6 freeze-thaw cycles based on these experimental results.
Clinical Evaluation:
The applicant conducted clinical trials at three clinical trial institutions, namely Tianjin People's Hospital, Shenzhen People's Hospital, and Sun Yat-sen University Cancer Center. The clinical performance of the product was validated by comparing it with the "gold standard" of full colonoscopy diagnosis used for diagnosing the disease.
The study population included:
1. 459 individuals with positive fecal occult blood tests from local screenings underwent colonoscopy examinations at the clinical trial institutions. Among them, 56 cases were confirmed as colorectal cancer through colonoscopy, while the rest were healthy individuals or patients with other benign diseases.
2. 263 initial patients diagnosed by clinicians in outpatient settings requiring colonoscopy examinations. Symptoms included changes in bowel habits, changes in stool shape, bloody stools, chronic constipation, urgency or straining during bowel movements. Fecal samples were collected from all these patients before colonoscopy for testing with the test kit. 36 cases of colorectal cancer were confirmed through colonoscopy, with the remaining cases being healthy individuals or patients with benign diseases.
3. 248 preoperative inpatients with colorectal cancer, who were either outpatient patients with the aforementioned symptoms or suspected of having colorectal cancer based on other examinations and confirmed through colonoscopy. Fecal samples were collected before surgery for testing with the test kit.
4. Other cases included patients with other digestive system tumors (pre-treatment), such as esophageal cancer, gastric cancer, liver cancer, pancreatic cancer, bile duct cancer, and oral cancer, diagnosed through pathology before treatment. Fecal samples were collected for testing before treatment. Patients with benign diseases included gastritis, enteritis, appendicitis, colitis, peptic ulcers, colorectal polyps, and adenomas, as well as 65 postoperative inpatients with colorectal cancer.
A total of 1306 samples were included in the study, out of which 340 patients were diagnosed with colorectal cancer through colonoscopy, 901 patients were diagnosed as negative for colorectal cancer through colonoscopy, and 65 were postoperative colorectal cancer patients. Additionally, sequencing tests were conducted on 179 samples to validate the accuracy of the testing, which showed consistency between the detected sequences and the designed sequences.
Among the three clinical trial institutions, a total of 59 adenoma patients were included, with 8 testing positive with the test kit, resulting in a specificity of 86.44%. For patients with pancreatic cancer, bile duct cancer, liver cancer, oral cancer, esophageal cancer, and gastric cancer, the specificity ranged from 92.00% to 100%. For patients with enteritis, colitis, peptic ulcers, colorectal polyps, appendicitis, and gastritis, the specificity ranged from 92.22% to 95.83%.
A total of 65 postoperative colorectal cancer patients were included, with 11 testing positive with the test kit, resulting in a positivity rate of 16.92%. Overall data analysis indicated a sensitivity of 71.76% and a specificity of 90.23% for the product when compared to the gold standard of full colonoscopy diagnosis.
Clinical Application of Multimodal Ultrasound in Gynecologic Cancer
Study Name: Clinical application of multimodal ultrasound in gynecologic cancer
Site: The Third Affiliated Hospital of Sun Yat-sen University
Target Disease: Endometrial cancer
Study Type: Diagnostic test
Study Design: Diagnostic New Technique Clincal Study; Diagnostic test for accuracy
Study Objective: 1. The diagnostic efficacy of combining and comparing ultrasound microvascular imaging, contrast-enhanced ultrasound, and conventional ultrasound in differentiating benign and malignant endometrial lesions. 2. Exploring the reproducibility of different methods in evaluating benign and malignant endometrial lesions.
Inclusion Criteria: 1. Chinese female citizens, ≥ 45 years old; 2. The patient has symptoms of abnormal vaginal bleeding; 3. Having postoperative pathology or endometrial biopsy as the gold standard; 4. Voluntarily sign an informed consent form.
Exclusion Criteria:
1. Pregnant or lactating women; 2. Postoperative surgical pathology time and ultrasound examination time>120 days; 3. Patients with a history of treating endometrial malignancies in the past; 4. The patient refuses to undergo transvaginal or transrectal ultrasound examination; 5. It is known that the subject is allergic to any component of the contrast agents.
Diagnostic Tests：
Gold Standard or Reference Standard: Postoperative histopathological examination
Index test: 1. multimodal ultrasound (including normal ultrasound examination, contrast-enhanced ultrasound examination and micro-vascular flow imaging examination
Target condition: Endometrial cancer (Chinese women aged ≥ 45 years old with clinical manifestations such as abnormal vaginal bleeding, fluid discharge, and lower abdominal pain), Sample size: 234
Population with condition difficult to distinguish from the target condition, the normal population in a case-control study design should be avoid: (1) Abnormal uterine bleeding in menopausal transition period; (2) Senile Vaginitis; (3) Submucosal fibroids or endometrial polyps of the uterus; (4) Cervical tube carcinoma, Uterine sarcoma and fallopian tube carcinoma. Sample size: 73
Primary Indicator: Contrast-enhanced ultrasonography TIC; MV-flow ROI ratio; sensitivity; specificity; accuracy; area under the curve (ROC)
EC Approval Time: 19 September 2022