Application of Personalized Minimal Residual Disease in Predicting Therapeutic Efficacy in Metastatic Hormone-sensitive Prostate Cancer
Conditions: MRD, Prostate Cancer, mHSPC
Sponsor: Anhui Medical University

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Application of personalized minimal residual disease in predicting therapeutic 
efficacy in metastatic hormone-sensitive prostate cancer
NCT number: NCT07112612
Document date: January 8th, 2026

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Project name ：Application of personalized minimal residual disease in predicting 
therapeutic efficacy in metastatic hormone-sensitive                 
Sponsor:              The First Affiliated Hospital of Anhui Medical University                                    
Responsible departments: Urology                                 
Main researchers: Sheng Tai                        
Contact number: 18355159268                       
Participating units: Anhui University                              
Years of research: From January 2026  to August 2027
Version number: V2.0           Version date:  January 8th, 2026

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Program summary
Project name
Application of personalized minimal residual disease in predicting 
therapeutic efficacy in metastatic hormone-sensitive prostate cancer
Research 
purpose
A prospective, single-center, observational study is conducted on 
patients initially diagnosed with metastatic hormone-sensitive 
prostate cancer (mHSPC). minimal residual disease (MRD) testing 
is used to explore the real-world efficacy responses of mHSPC 
patients with different gene mutation characteristics to treatment 
regimens, and further analyze the relevant factors affecting the 
efficacy, providing a basis for the clinical precision diagnosis and 
treatment of mHSPC patients.
research 
design
Prospective, single-center, observational study
study 
population
Patients with Metastatic hormone-sensitive prostate cancer
Total number 
of cases
50 cases

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Case 
selection
1. Inclusion criteria:
●
Aged over 18 and under 85;
●
Histopathological diagnosis is prostate acinar adenocarcinoma, 
ductal adenocarcinoma, and intraductal carcinoma;
●
Clear distant metastases found by imaging (meeting RECIST 
criteria);
●
Patients diagnosed with locally advanced (N1) and metastatic 
(M1) prostate cancer.
●
Have not received endocrine therapy or other systemic anti-
tumor treatment before;
●
ECOG score 0-2 points, expected survival time> 6 months;
●
The patient has normal organ function;
●
Blood test (no blood transfusion or blood products within 14 
days):
●
Hemoglobin (HGB) ≥90 g/L;
●
Absolute neutrophil count (ANC) ≥ 1.5 × 109/L （1500 
/mm3）；
●
Platelets (PLT) ≥75×109/L；
●
White blood cell count (WBC) ≥3 × 109/L；
●
Biochemical examination:
●
Total bilirubin (TBIL) ≤ upper limit of normal (ULN);
●
Alanine aminotransferase (ALT) and aspartate aminotransferase 
(AST) ≤ 2.5 ULN;
●
Creatinine clearance (CCr) ≥ 30 ml/min (Cockcroft-Gault 
formula);
●
Coagulation function: prothrombin international normalized 
ratio (INR) ≤1.5 or prothrombin time (PT) < 4 seconds;
●
Patients agree to sign informed consent and are able to attend 
planned study visits, provide clinical information, and cooperate 
with other study procedures.

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Exclusion criteria
●
Histopathological diagnosis is neuroendocrine/small cell 
prostate cancer;
●
No clear distant metastases are found by imaging (in accordance 
with RECIST criteria);
●
Previous treatment history: including neoadjuvant and adjuvant 
therapy;
●
The samples submitted for inspection fail to meet quality control 
requirements.
●
Patients with endocrine, metabolic system diseases or other 
serious digestive system diseases;
●
Patients with chronic hepatitis, cirrhosis, chronic nephritis, renal 
insufficiency and other diseases;
●
Patients with a history of immunodeficiency, including HIV 
positive or suffering from other acquired or congenital 
immunodeficiency 
diseases, 
or 
a 
history 
of 
organ 
transplantation;
●
History of other malignant tumors;
●
Enrollment in other clinical trials;
●
Unable to obtain clinical information required for the study (e.g., 
patients lost to follow-up);
●
Other cases that the researchers consider unsuitable for 
inclusion.
intervention 
plan
This is a prospective, single-center, observational study designed to 
observe the therapeutic response of metastatic hormone-sensitive 
prostate cancer (mHSPC) patients with different gene mutation 
characteristics to treatment regimens. The study will recruit 50 
mHSPC patients from the First Affiliated Hospital of Anhui Medical 
University and design a personalized minimal residual disease 
(MRD) kit based on the data of the biopsy before treatment. The 
blood routine, biochemical indicators, sex hormone levels, prostate 
multi-parameter 
magnetic 
resonance 
imaging 
(Mp-MRI), 

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quantitative whole-body bone examination, and PSMA-PET-CT 
examination of the study cohort patients will be recorded. During the 
treatment, MRD will be tested every three months, and the MRD 
level, blood routine, biochemical markers, sex hormone levels, and 
PSA levels; patients in the study cohort will undergo prostate 
multiparametric magnetic resonance imaging (Mp-MRI) and 
quantitative whole-body skeletal examination every three months. If 
PSA progression occurs during follow-up, the PSA recheck 
frequency will be customized. This prospective, observational study 
will explore the response efficiency of mHSPC patients with 
different gene mutation types to treatment regimens through MRD 
detection, analyze the relevant factors affecting the efficacy, and 
provide a basis for the precise clinical diagnosis and treatment of 
mHSPC patients.
Effectiveness evaluation index
●
Diagnostic accuracy: MRD positive rate, the fluctuation of MRD 
value, etc.
●
Clinical efficacy: progression-free survival (PFS), overall 
survival (OS), biochemical recurrence rate, and clinical 
remission rate.
Evaluation 
index
Safety evaluation index
●
Incidence of related drug allergy adverse events (AE) and 
serious adverse events (SAE)
Statistical 
methods
Descriptive statistical analysis, survival analysis, missing data 
processing
Study period
January 2026 - August 2027

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Chapter1
Research Background
Prostate cancer is a global health problem. It is the second most common 
malignant tumor in the world, with the sixth highest incidence among all male tumors 
and the fifth leading cause of cancer death in men [1]. In the United States, prostate 
cancer ranks first in the male incidence spectrum, accounting for 29.06% of all male 
cases, and second in the male malignant tumor death spectrum, accounting for 10.92% 
of all male cancer deaths [2]. The incidence and mortality of prostate cancer in Asia are 
much lower than those in Europe and the United States, but have shown a clear upward 
trend in recent years, and its growth rate is faster than that of developed countries in 
Europe and the United States [3,4]. The number of prostate cancer patients in China has 
also increased significantly in recent years: according to the latest data released by the 
National Cancer Center Cancer Registry Office in 2022, the 2016 cancer incidence 
results in China based on statistics from 487 tumor registries across the country show 
that the age-standardized total incidence of prostate cancer has surpassed kidney tumors 
and bladder tumors, ranking first among male genitourinary tumors [5].
The age of onset of prostate cancer gradually increases after the age of 50, with 
the peak age being around 75 years old, and the highest incidence rate is between 81 
and 90 years old. In addition to the influence of age, environmental factors, obesity and 
genetic factors are also related to the occurrence of prostate cancer [6]. Related studies 
have shown that only 1/3 of patients with newly diagnosed prostate cancer have 
clinically localized prostate cancer. Most patients are diagnosed with prostate cancer in 
the middle and late stages, and most patients have already progressed to distant 
metastasis or local metastasis [7].
The metastasis of prostate cancer is an important stage of the disease that seriously 
affects the prognosis of prostate cancer patients. According to data from China, patients 
with metastatic prostate cancer account for 51.4% to 54% of new prostate cancer 
patients [8]. According to the sensitivity of prostate cancer cells to androgens, 
metastatic prostate cancer can be divided into metastatic hormone-sensitive prostate 
cancer (mHSPC) and metastatic castration-resistant prostate cancer (mCRPC). The 
results of the UFO (A Sub-group Analysis of United in Fighting for Prostate Cancer 
Registry) analysis of 705 cases of metastatic prostate cancer patients from 7 centers in 
China showed that 76.9% of patients in the middle and late stages of the disease in my 

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country belong to metastatic hormone-sensitive prostate cancer (mHSPC). Newly 
diagnosed mHSPC will eventually develop into mCRPC, and patients with mCRPC 
generally have a poor prognosis. Both domestic and foreign prostate cancer diagnosis 
and treatment guidelines point out that delaying the entry of patients in the mHSPC 
stage into the mCRPC stage and prolonging the survival of patients are the main 
treatment goals of the mHSPC stage.
In recent years, breakthroughs have been made in the diagnosis and treatment of 
mHSPC patients. Compared with traditional combined treatment models, the overall 
survival rate of patients with metastatic prostate cancer has been significantly improved 
through new combined treatment regimens based on castration therapy (new endocrine 
therapy drugs or chemotherapy drugs) [9]. However, there is currently no effective 
program for early efficacy testing and follow-up of patients undergoing drug treatment. 
Commonly used clinical methods include serum PSA monitoring and serum 
testosterone monitoring; PSA may rise briefly after inflammation, hyperplasia, 
bleeding, or some medical procedures, resulting in false positive results, and some 
patients may experience clinical progression without PSA elevation, resulting in false 
negative results [10]; approximately 13% to 38% of patients undergoing medical 
castration have serum testosterone levels that cannot be reduced to castration levels, 
and 24% of patients will experience a temporary increase in testosterone levels to more 
than 50 ng/dl during long-term treatment, also known as the "breakthrough effect" [11]. 
Therefore, there is currently no standardized and effective testing program during 
treatment.
Metastatic hormone-sensitive prostate cancer is a disease with high genetic and 
clinical heterogeneity. Although clinical studies have confirmed that new endocrine 
combined castration therapy can effectively improve the prognosis of such patients, 
patients vary in their economic situation, physical condition, tumor stage, tumor 
metastasis site, molecular differences, etc., and their individualized prognosis is also 
different. How to accurately monitor the efficacy of medication regimens is of great 
significance for determining the most suitable population, assessing prognosis, 
adjusting treatment plans, disease stratification, and reducing the burden on patients 
and society.
Minimal residual disease (MRD) refers to a small amount of tumor cells or tiny 

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lesions that remain in the patient's body during or after treatment and cannot be detected 
by imaging. It is the primary cause of tumor recurrence [12]. Studies have shown that 
continuous MRD liquid biopsy monitoring based on circulating tumor DNA (ctDNA) 
can predict the time of postoperative recurrence of tumor patients earlier, which is an 
average of 8.7 months earlier than the median time of recurrence that can be detected 
by imaging [13]. A hidden gram tumor may contain up to 1×108cells, all of which are 
associated with blood circulation due to their need for oxygen and nutrients [14]. 
Therefore, it is possible to detect these radiologically occult tumors through ctDNA 
analysis. A new generation of highly sensitive and specific ctDNA tests has been 
developed for solid tumors, called molecular residual disease (MRD) tests, which can 
detect micro metastases. MRD tests have a deep detection limit of more than 98% 
analytical sensitivity and a high specificity of more than 95% under certain conditions 
to ensure the detection of occult diseases [15]. Related studies have shown that 
quantifying ctDNA changes is not only associated with tumor activity, but also can 
predict patient prognosis. In particular, the assessment of ctDNA growth rate or 
doubling time can further stratify ctDNA-MRD-positive patients (dividing them into 
better and worse prognosis groups), providing an effective solution to guide clinical 
decision-making. Studies have shown that personalized tumor ctDNA analysis is more 
valuable than ctDNA-MRD positive or negative results, and has certain advantages in 
determining the risk of recurrence, predicting tumor outcomes, identifying patients who 
may need additional treatment after radical resection, detecting recurrence during 
monitoring, and predicting the growth rate of tumor burden [16]. MRD testing is of 
great significance for determining the efficacy of drugs, judging the patient's current 
stage of prostate cancer, adjusting treatment plans, and evaluating prognosis [17]. It is 
conducive to formulating effective individualized and precise treatment plans for 
metastatic hormone-sensitive prostate cancer.
Based on the above background, this study aims to construct a cohort of patients 
with mHSPC and conduct a prospective, observational study. We will obtain prostate 
tissue and peripheral blood specimens from newly diagnosed mHSPC patients for 
whole-exome sequencing (WES) and develop a personalized MRD detection kit for 
single mHSPC patients. We will test the efficacy of castration combined with novel 
endocrine therapy in these patients. We will also investigate the genetic mutation 

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profiles of mHSPC patients and observe, record, and follow up patients according to 
specific treatments. The results will be described, compared, and analyzed. We will 
explore how MRD testing can be used to assess efficacy and prognosis under different 
genetic mutation profiles, thereby enabling precise medication and efficacy testing for 
mHSPC patients.
Chapter2
Research purpose
A prospective, single-center, observational study is conducted on patients newly 
diagnosed with mHSPC. MRD testing is used to explore the real-world efficacy 
responses of mHSPC patients with different gene mutation characteristics to treatment 
regimens, and further analyze the relevant factors affecting the efficacy, providing a 
basis for the clinical precision diagnosis and treatment of mHSPC patients.
Chapter3
Research method
3.1
Research design
This is a prospective, single-center, observational study designed to observe the 
therapeutic response of metastatic hormone-sensitive prostate cancer(mHSPC) patients 
with different gene mutation characteristics to treatment regimens. The study will 
recruit 50 mHSPC patients from the First Affiliated Hospital of Anhui Medical 
University and design a personalized minimal residual disease (MRD) kit based on the 
data of the biopsy before treatment. The blood routine, biochemical indicators, sex 
hormone levels, prostate multi-parameter magnetic resonance imaging (Mp-MRI), 
quantitative whole-body bone examination, and PSMA-PET-CT examination of the 
study cohort patients will be recorded. During the treatment, MRD will be tested every 
three months, and the MRD level, blood routine, biochemical markers, sex hormone 
levels, and PSA levels; patients in the study cohort will undergo prostate 
multiparametric magnetic resonance imaging (Mp-MRI) and quantitative whole-body 
skeletal examination every three months. If PSA progression occurs during follow-up, 
the PSA recheck frequency will be customized. This prospective, observational study 
will explore the response efficiency of mHSPC patients with different gene mutation 
types to treatment regimens through MRD detection, analyze the relevant factors 

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affecting the efficacy, and provide a basis for the precise clinical diagnosis and 
treatment of mHSPC patients.
3.2
Study population
This study plans to recruit 50 mHSPC patients from the First Affiliated Hospital 
of Anhui Medical University between September 2025 and April 2027. Patients with 
metastatic hormone-sensitive prostate cancer from the First Affiliated Hospital of 
Anhui Medical University and cooperative units who met the enrollment conditions and 
signed informed consent forms will be included. 
3.2.1 Inclusion criteria:

Aged over 18 and under 85;

Histopathological 
diagnosis 
is 
prostate 
acinar 
adenocarcinoma, 
ductal 
adenocarcinoma, and intraductal carcinoma;

Clear distant metastases found by imaging (meeting RECIST criteria);

Patients diagnosed with locally advanced (N1) and metastatic (M1) prostate cancer.

Have not received endocrine therapy or other systemic anti-tumor treatment before;

ECOG score 0-2 points, expected survival time> 6 months;

The patient has normal organ function;

Blood test (no blood transfusion or blood products within 14 days):

Hemoglobin (HGB) ≥90 g/L;

Absolute neutrophil count (ANC) ≥ 1.5 × 109/L（1500 /mm3）；

Platelets (PLT) ≥75×109/L；

White blood cell count (WBC) ≥3 × 109/L；

Biochemical examination:

Total bilirubin (TBIL) ≤ upper limit of normal (ULN);

Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 ULN;

Creatinine clearance (CCr) ≥ 30 ml/min (Cockcroft-Gault formula);

Coagulation function: prothrombin international normalized ratio (INR) ≤1.5 or 
prothrombin time (PT) < 4 seconds;

Patients agree to sign informed consent and are able to attend planned study visits, 
provide clinical information, and cooperate with other study procedures.

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3.2.2 Exclusion criteria:

Histopathological diagnosis is neuroendocrine/small cell prostate cancer;

No clear distant metastases are found by imaging (in accordance with RECIST 
criteria);

Previous treatment history: including neoadjuvant and adjuvant therapy;

The samples submitted for inspection failed to meet quality control requirements.

Patients with endocrine, metabolic system diseases or other serious digestive 
system diseases;

Patients with chronic hepatitis, cirrhosis, chronic nephritis, renal insufficiency and 
other diseases;

Patients with a history of immunodeficiency, including HIV positive or suffering 
from other acquired or congenital immunodeficiency diseases, or a history of organ 
transplantation;

History of other malignant tumors;

Enrollment in other clinical trials;

Unable to obtain clinical information required for the study (e.g., patients lost to 
follow-up);

Other cases that the researchers consider unsuitable for inclusion.

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3.3
 Research Technology Route (Figure 1)
Figure 1 Technology Roadmap

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3.3.1 Calculate the number of cases required to achieve the intended 
purpose of the study based on statistical principles
This study is an observational study. According to previous studies, the actual 
number of patients required is approximately 50 [17-19]. The clinical and auxiliary 
examination items to be conducted, the number of measurements, the amount of blood 
or tissue samples collected each time, the number of collections, and the total number 
of samples collected.
3.3.2 Initial diagnosis process
A personalized MRD kit is constructed based on the prostate needle biopsy tissue, 
bone metastasis needle biopsy tissue, whole genome sequencing (WGS), single-cell 
sequencing, spatial transcriptomics sequencing (STS) of the first puncture tissue for 
subsequent testing, and the blood routine, biochemistry, sex hormones, prostate multi-
parameter magnetic resonance imaging (Mp-MRI), quantitative whole-body bone 
imaging, PSMA-PET-CT examination, etc. of the patients in the study cohort are 
recorded.

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3.3.3 Genetic testing sample collection plan (Figure 2)
           
Figure 2. Sample collection plan
3.3.4 Follow-up process
Follow-up visits are conducted every three months during treatment. These visits 
included MRD levels, complete blood counts, biochemical profiles, sex hormones, and 
serum PSA levels. Multiparametric magnetic resonance imaging (MRI) of the prostate 
and quantitative whole-body bone scintigraphy are also performed every three months. 
If PSA progression occurred during follow-up, the frequency and frequency of PSA 
rechecks could be adjusted as appropriate.

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3.3.5 Criteria for evaluating therapeutic efficacy, including methods for 
evaluating parameters, observation time, recording, and analysis;

Main indicators: MRD positivity rate and changes in MRD levels

Secondary indicators: clinical remission rate, progression-free survival 
(PFS)and overall survival (OS)
3.3.6  Prognostic Assessment

Association analysis: The association between MRD level and recurrence risk 
and overall survival is evaluated.

Risk stratification: Patients are divided into high-risk, intermediate-risk, and 
low-risk groups according to their MRD levels, and the prognostic differences 
among the groups are analyzed.

Time to progression to CRPC: the time from patient enrollment to progression 
to CRPC (CRPC criteria: The patient's testosterone level reaches a castrate 
level of <50 ng/dL or <1.7 nmol/L, and one of the following conditions occurs: 
Biochemical progression, Radiographic progression)

Time to biochemical progression: from the time of enrollment to the time 
when the patient has two consecutive PSA elevations;

6ne-year biochemical progression-free rate: the percentage of patients without 
biochemical recurrence within 1 year among all enrolled patients
3.3.7 The storage procedures for subject codes, random number tables, 
and case report forms;

The enrolled patients are coded sequentially before and after enrollment and 
recorded in the case report form.
Chapter4
Recording requirements for adverse events and the reporting 
methods, handling measures, follow-up methods, timing, and outcomes of 
serious adverse events;
This study is an observational study. All treatment regimens are clinical standard 
treatment regimens. Adverse events are handled according to standard treatment. Any 
clinical adverse events and abnormal laboratory test results that occur during clinical 

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treatment must be recorded in detail, their relevance to treatment must be evaluated, 
and the severity of all adverse events must be judged.
4.1
Adverse events
Regardless of whether they are related to the study drug, any adverse medical 
event or clinically significant abnormality in laboratory test parameters that occurs 
during clinical treatment is considered an adverse event (AE). All adverse events must 
be described with respect to their onset, duration, treatment, and outcome, their 
severity, and their relevance to clinical treatment.
4.2
Severity of adverse events: The severity of adverse events is divided into 
mild, moderate and severe, and can be evaluated according to the 
following standards.

Mild: Mild subjective symptoms that are tolerable and do not affect daily life 
activities. Symptoms are transient and resolve on their own during continued 
medication. No treatment is required.

Moderate: Symptoms are severe, affecting the subject's daily activities, 
persisting for a long time, and resolving on their own or with symptomatic 
treatment. There is a possibility of interference with study medication use, 
requiring dose reduction or discontinuation.

Severe: The subject's body functions are impaired and he loses the ability to 
work and live normally. The symptoms last for a long time and can only be 
relieved after stopping the drug and receiving appropriate treatment.

Serious adverse events (SAEs): Serious adverse events are any unfavorable 
medical events that occur at any dose, such as those that lead to death or are 
life-threatening.
Note: In the definition of "serious," the term "life-threatening" refers to 
events/reactions in which the patient is already at risk of death at the time of the 
event/reaction; it does not refer to events/reactions in which death is 
hypothesized to occur if the severity of the event escalates. Important medical 

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events or reactions that may not be immediately life-threatening or result in death 
or hospitalization, but may endanger the patient or may require intervention to 
prevent one of the other outcomes listed in the above definition, should generally 
also be considered serious. Examples include: allergic bronchospasm requiring 
urgent treatment in the emergency room or at home; blood dyscrasias or 
convulsions that do not result in hospitalization; the development of drug 
dependence or drug abuse, etc. In the event of an SAE, the investigator should 
immediately implement treatment measures to ensure the safety of the subject 
and report the SAE to the ethics committee and relevant competent authorities 
within 24 hours of the occurrence of the SAE.

Important adverse events: Any event other than an SAE that results in the use 
of targeted medical measures (e.g., discontinuation of medication, dose reduction, 
and/or symptomatic treatment) or significant abnormalities in laboratory tests.
4.3
Evaluation of the association between adverse events and drugs
The association between the adverse event and the study drug is assessed as 
definitely related, probably related, possibly related, possibly unrelated, or definitely 
unrelated, based on whether the adverse event occurs in a reasonable time sequence 
with drug use, the type of drug reaction, and whether the reaction is alleviated, 
disappears, or reappears after drug discontinuation. The first three are considered 
possibly related to the study drug and are assessed as adverse drug reactions.
The relationship between adverse events and drugs is as follows:

Definitely related: There is evidence of study drug use, the adverse event 
occurs in a reasonable temporal sequence with study drug use, and the adverse 
event is more plausible with study drug than with other explanations. There 
is a positive reaction to discontinuation of the drug and a positive reaction to 
repeated administration (if feasible).

Probably related: There is evidence of drug use, and the adverse event occurs 
in a reasonable temporal sequence with the use of the study drug. The adverse 
event is more likely to be explained by the study drug than by other causes. 
There is a positive discontinuation reaction.

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
Possibly Related: There is evidence of drug use, and the adverse event is 
reasonably temporally related to the use of the study drug. The adverse event 
can also be explained by other causes. Positive withdrawal reaction.

Possibly unrelated: There is evidence of drug use, and the adverse event is 
more reasonably explained by other causes. The withdrawal reaction is 
negative or unclear.

Definitely unrelated: The drug is not used, or there is no correlation between 
the time of drug use and the adverse event, or there is another clear cause for 
the adverse event.
4.4
The establishment and maintenance of research drug codes, unblinding 
methods, and regulations for breaking the blind in emergency situations;

This study is an observational study and does not involve drug coding or 
unblinding.
4.5
Statistical analysis plan, definition and selection of statistical analysis 
data sets;

Descriptive statistics: basic characteristics of patients, distribution of MRD 
levels.

Full Analysis Set: According to the intention-to-treat (ITT) principle, efficacy 
analysis is performed on all cases of all enrolled patients who used the drug 
at least once.

Safety Analysis Set: All enrolled cases, all patients who have used the trial 
drug at least once and have safety records after using the drug.

Efficacy Analysis: The median time to CRPC progression and OS are 
estimated using the Kaplan-Meier method, and the median event and its one-
sided 95% confidence interval are presented. SPSS software is used to 
perform statistical analysis on the efficacy indicator of 1-year biochemical 
progression-free rate.

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
Safety analysis: Descriptive statistical analysis is primarily used, with a table 
describing all AEs that occurred during the trial. Laboratory test results are 
described as normal before the trial but abnormal after treatment, as well as 
the relationship between abnormal changes and the trial drug.
Chapter5
Data Management and Information Confidentiality
5.1
Construction of electronic case report forms (eCRFs) or study record 
forms

The data manager constructs the eCRF based on the research plan, original 
case form and other information.
5.2
Data entry and modification
Data entry and modification are the responsibility of the researcher. Data should 
be sourced from and consistent with original documentation, such as original record 
sheets and laboratory test reports. All observations and test results from the trial should 
be entered into the form or database promptly, correctly, accurately, completely, clearly, 
in a standardized manner, and truthfully. The data manager is responsible for reviewing 
and managing the entered data. If any questions arise regarding the data, the data 
manager will send the corresponding queries to the researcher. The researcher will 
respond promptly to the queries sent by the data manager, and the data manager may 
raise further questions as necessary.
5.3
Confidentiality Plan for Research Participants (Subjects) Information
All information about research participants (subjects) must be kept strictly 
confidential. Participation in the study and personal data within the study are 
confidential. Information about research participants (subjects) and research data will 
be identified by study number, not by name. Identifiable information will not be 
disclosed to members outside the research team unless the participant (subject) has 
given their permission. All research team members are required to maintain the 
confidentiality of the identity of the research participants (subjects). Research 

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participant files will be kept in locked filing cabinets and accessible only to 
researchers. To ensure the research is conducted in accordance with regulations, 
members of government regulatory agencies or the ethics review committee may, if 
necessary, access the personal data of research participants (subjects) at the research 
site. No personal information about research participants (subjects) will be disclosed 
when the results of this study are published.
5.4
Research Data Confidentiality Plan
Research data are also confidential. All research members are required to keep 
the research data confidential. They are not allowed to disclose the research data to 
members outside the project team without the permission of the principal researcher, 
transfer the research data to external units without the permission of the hospital, or 
transfer research data involving human genetic resources to foreign units or domestic 
units with foreign capital without the approval of the National Human Genetics 
Office, except for the publication of research results that comply with regulatory 
requirements under normal circumstances.
Chapter6
 Quality control and quality assurance of clinical research;
6.1
relevant training
The principal investigator will organize relevant training to ensure that the study 
is conducted in accordance with standard procedures. The completion of case report 
forms, study record forms, and other reports adhere to GCP principles and the study 
protocol. All data and information must be verifiable; to ensure the reliability of the 
study data, all observations and findings must be verifiable. Quality control will be 
applied at every stage of the study to ensure the reliability of all data and the accuracy 
of the study procedures. The principal investigator should ensure that researchers 
adhere to the trial protocol, confirm the accuracy of data and the completeness of 
records and reports, and ensure that informed consent is obtained from all subjects 
before the study begins. Any violations or deviations from the protocol should be 
reported to the ethics committee promptly.

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6.2
research-related ethics;
This clinical trial must be conducted in accordance with the Declaration of 
Helsinki (2008 edition) and relevant Chinese clinical trial research standards and 
regulations. A trial protocol must be developed before the start of the clinical trial, 
jointly agreed upon and signed by the investigator and co-sponsor, and submitted to the 
hospital's ethics committee for approval before implementation. If this protocol needs 
to be revised during the actual implementation of the clinical trial, the revised protocol 
must be submitted to the ethics committee for approval before implementation. If 
significant new data regarding the investigational drug are discovered, the informed 
consent form must be revised in writing, submitted to the ethics committee for approval, 
and patient consent must be obtained again.
6.3
Methods of subject recruitment and process of obtaining informed 
consent;
This study is an observational study, and the enrolled patients are those receiving 
standard clinical treatment. Before the study begins, researchers must provide patients 
with detailed information about the clinical study, including the nature and purpose of 
the trial, possible benefits and risks, and the patient's rights and obligations. The clinical 
trial can only begin after the patient fully understands the information and agrees to it 
and signs the "Informed Consent Form."
6.4
The expected progress and completion date of the clinical study;
Expected start date: October 1, 2024
Estimated completion date for patient enrollment: March 20, 2025
Expected completion date: September 30, 2025
6.5
Follow-up and medical measures after the completion of the study;
This is an observational study that only collects patients' treatment and follow-up 
information. The end of the follow-up is the end point of the study, and there is no 
additional medical intervention.

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6.6
the responsibilities of each party and other relevant provisions;
The First Affiliated Hospital of Anhui Medical University is the study sponsor, 
protocol developer, and principal investigator and is responsible for patient follow-up.
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