Efficacy and Safety of Chinese Medicine in the Treatment of Chikungunya Fever: A Real-World Observational Study
Conditions: Chikungunya Fever
Sponsor: Guangzhou University of Traditional Chinese Medicine

Efficacy and Safety of Chinese Medicine in the Treatment of Chikungunya Fever: A Real-World Obser
vational Study Version date/version number: July, 2025/2.0
Efficacy and Safety of Chinese Medicine in the Treatment of Chikungu
nya Fever: A Real-World Observational Study
Study Protocol and Statistical Analysis Plan
Official Title:
Efficacy and Safety of Chinese Medicine in the Treatment of Chikun
gunya Fever: A Real-World Observational Study
Sponsor:
The Second Affiliated Hospital of Guangzhou University of Chinese
Medicine (Guangdong Provincial Hospital of
Chinese Medicine)
Principal Investigator:
Zhang Zhongde
NCT Number：
ZE2025-299-01
Date:
24 July, 2025
Table of contents
Project Summary .......................................................................................................................1
1 Research Background .............................................................................................................4
2 Research Objectives ................................................................................................................4

Efficacy and Safety of Chinese Medicine in the Treatment of Chikungunya Fever: A Real-World Obser
vational Study Version date/version number: July, 2025/2.0
3 Overall design of the study .....................................................................................................4
3.1 Sample size ..........................................................................................................................4
3.2 Visit .....................................................................................................................................4
4Case Selection ..........................................................................................................................5
4.1 Diagnostic criteria and Chinese medicine syndrome differentiation criteria ......................5
4.2 Selection criteria ..................................................................................................................5
4.3 Exclusion criteria .................................................................................................................5
4.4 Case Source .........................................................................................................................6
4.5 Exit Criteria .........................................................................................................................6
4.6 Treatment of dropout cases.....................................................................................................
4.7 Case exclusion criteria: ........................................................................................................6
4.8 Termination test criteria .......................................................................................................6
5 Observation of confrontation and medication ........................................................................7
5.1 Observation cohort medication ............................................................................................7
5.2 Observation period and follow-up .......................................................................................7
6 Observation content and evaluation during observation ........................................................7
6.1 Clinical characteristics .........................................................................................................7
6.2 Effectiveness Observation Content ......................................................................................8
6.3 Safety Information .............................................................................................................10
7 Safety Observation ...............................................................................................................10
7.1 Definition ...........................................................................................................................10
(1) Adverse events ...................................................................................................................11
(2) Serious adverse events Adverse Event, SAE 11......................................................................​
(3) Important adverse events ...................................................................................................11
(4) Adverse drug reactions drug reaction, (ADR)
.................................................................11
(5) Suspected and unexpected serious adverse ........................................................................11
7.2 Recording of adverse events ..............................................................................................11
7.3 Grading of severity of adverse events ...............................................................................12
7.4 Determination of the causal relationship between adverse events and drugs ....................12
7.5 Management of adverse events ..........................................................................................14
7.6 Handling and reporting of serious adverse events .............................................................14

Efficacy and Safety of Chinese Medicine in the Treatment of Chikungunya Fever: A Real-World Obser
vational Study Version date/version number: July, 2025/2.0
7.6.1 Handling of serious adverse events ................................................................................14
7.6.2 Reporting of Serious Adverse Events .............................................................................15
7.7 Adverse events that were not resolved during follow-up ..................................................15
8 Data Management .................................................................................................................16
8.1 Data Management Plan ......................................................................................................16
8.2 Database Management .......................................................................................................16
8.3 Data collection and recording ............................................................................................16
8.4 Data Monitoring ................................................................................................................16
8.5 Data Cleaning ....................................................................................................................17
8.6 Data Review ......................................................................................................................17
8.7 Locking and unlocking the database ..................................................................................17
8.7.1 Database Locking ...........................................................................................................17
8.7.2 Database Unlock .............................................................................................................18
9 Quality Control of Research .................................................................................................18
9.1.1 Selectivity bias control ...................................................................................................18
9.1.2 Information Bias Control ................................................................................................18
9.1.3 Control of attrition bias ...................................................................................................19
9.1.4 Control of confounding bias ...........................................................................................19
9.2 Design of the scheme and guarantee of sample representativeness ..................................19
9.3 Monitoring and Auditing ...................................................................................................19
9.3.1 Audit ...............................................................................................................................19
9.3.2 Inspection ........................................................................................................................19
9.4 Project Implementation SOP and Training ........................................................................19
10 Statistical Analysis .............................................................................................................20
11 Ethical requirements ...........................................................................................................20
12 Data preservation ................................................................................................................20

Efficacy and Safety of Chinese Medicine in the Treatment of Chikungunya Fever: A Real-World Obser
vational Study Version date/version number: July, 2025/2.0
1
Program Summary
Study Name
Efficacy and Safety of Chinese Medicine in the Treatment of Chikungunya Fever: A Real-
World Observational Study
Purpose
1. To explore the epidemiological characteristics and Chinese medicine syndrome
distribution of Chikungunya fever;
2. To evaluate the effectiveness and safety of Chinese medicine in the treatment of
Chikungunya fever.
Overall Design A prospective observational study design based on real-world data
Sample size
Routine observation: all patients that can be collected during the observation period.
Diagnostic
criteria
Suspected or confirmed cases of Chikungunya fever were included based on the diagno
sis criteria of Chinese Guidance of the Diagnosis and Treatment for Chikungunya Fever
(2017 Edition) published by the Chinese Center for Disease Control and Prevention.
Inclusion and
exclusion
criteria
Inclusion Criteria
(1)
Meets the suspected or confirmed diagnostic criteria for chikungunya fever;
(2)
Symptom onset ≤3 days before enrollment;
(3)
Actual prescribed treatment aligns with the study's group assignment (Chines
e medicine, Western medicine, or combined therapy);
(4)
Sign the informed consent form.
Exclusion criteria
(1)
Severe chikungunya fever;
(2)
Participation in another drug clinical trial within the past 3 months;
(3)
Any other condition deemed by the investigator as unsuitable for enrollment.
Observation G
rouping
Chinese medicine group: Patients receive only Chinese medicine treatments, which may
include herbal formulas or acupuncture, tailored to their syndrome differentiation (e.g., heat-
clearing, detoxifying, or dampness-resolving therapies);
Western medicine group: Patients receive only standard Western medical care, which may
include antipyretics (e.g., acetaminophen), NSAIDs for pain, and supportive treatments
(e.g., hydration);
Integrated Therapy Group: Patients receive both Chinese and Western treatments.
Observation
period
Visit
Maximum observation period: 28 days
Visit time:
Screening period/baseline: First visit D0, with lab assessments: complete blood count,
CRP, and chikungunya nucleic acid tests;
Treatment observation period: D1-D5, daily follow-up with clinical and lab assessments,

Efficacy and Safety of Chinese Medicine in the Treatment of Chikungunya Fever: A Real-World Obser
vational Study Version date/version number: July, 2025/2.0
2
D5 or before discharge: complete blood count, CRP, and chikungunya nucleic acid tests;
Follow-up after treatment; telephone follow-up on D7, D14, and D28.
General
information
and medical
history
1. Demographic information: gender, age, height, weight, ethnicity, etc.;
2. Medical history: past medical history, current medical history, epidemiological history
and allergy history.
Effectiveness
evaluation
1.
Joint Pain and Swelling Relief Rate (DAS44 Score)
2.
Change in Rash Severity (Modified EASI Score)
3.
Time to Complete Fever Resolution
4.
Time to Viral RNA Clearance (RT-PCR Negative)
5.
Recovery of Laboratory Markers
6.
Time to Symptom Recovery
7.
Incidence of Complications
Safety
evaluation
Incidence of adverse events/adverse reactions.

Efficacy and Safety of Chinese Medicine in the Treatment of Chikungunya Fever: A Real-World Observational Study Version date/version number: July, 2025/2.0
3
Flow chart
Stage
Screening
Period /
Baseline
Treatment observation period
Follow-up after treatment
(telephone follow-up)
Visit point (D, day)
Visit 1
Visit 2
Visit 3
Visit 4
Visit 5
Visit 6
Visit X
Visit 7
Visit 8
Visit 9
D0
D1
D2
D3
D4
D5
Before discharge
D7
D14
D28
Informed consent form
×
Chikungunya RNA test
×
×
×
Epidemiological data
×
General information and medical
history
×
Physical examination, vital signs
×
×
×
×
Body temperature
×
Patient diary card for body temperature record
Chikungunya Symptom Scale
×
×
×
×
×
×
×
×
×
×
Complication
×
×
×
×
×
×
×
×
×
Severe / critical illness
×
×
×
×
×
×
×
×
×
Laboratory tests
×
×
×
Patient diary card collection
×
×
×
Medication records
×
×
×
×
×
×
×
Adverse Events
×
×
×
×
×
×
×
×
×

Efficacy and Safety of Chinese Medicine in the Treatment of Chikungunya Fever: A Real-World Obser
vational Study Version date/version number: July, 2025/2.0
4
Program text
1
Background
Chikungunya fever is an acute infectious disease caused by chikungunya virus (CHIKV), transmitted by
Aedes mosquitoes, and characterized by fever, rash, and joint pain. The first outbreak of chikungunya
fever was confirmed in Tanzania in 1952, and the virus was isolated in 1956. The disease is mainly
prevalent in Africa and Southeast Asia. Since 2004, outbreaks of chikungunya virus have become more
frequent and widespread, partly because the virus has adapted to make it easier to spread through Aedes
albopictus, and people of all ages are susceptible. In areas where Aedes mosquitoes exist, when Aedes
mosquitoes reach a certain density and natural conditions are suitable, if CHIKV is introduced, it may
cause an epidemic or outbreak.
On July 8, 2025, an imported case of Chikungunya fever occurred in Foshan, Guangdong. Till July
19th, there have been a total of 1,873 confirmed cases had been reported in Foshan. The rapid spread of
the epidemic has brought certain treatment pressures to medical institutions. At present, there are no
available vaccines or specific drugs in China, and the clinical treatment plan is mainly symptomatic
treatment. In order to effectively respond to the recent surge in Chikungunya fever patients in medical
institutions, the Chinese medicine expert team of Guangdong has discussed and formed a Chinese
medicine agreement formula plan and applied it in clinical practice. In order to evaluate the
effectiveness of this plan, this observational study is planned to be carried out.
2
Purpose
(1) To explore the epidemiological characteristics and Chinese medicine syndrome distribution of
Chikungunya fever;
(2) To evaluate the effectiveness and safety of Chinese medicine in the treatment of chikungunya fever.
3
Overall study design
Prospective observational study design based on real-world data.
3.1 Sample size
Routine observation: all patients that can be collected during the observation period.
Maximum observation period: 28 days.
3.2 Visit
Screening period/baseline: First visit D0, complete blood count, CRP, chikungunya nucleic acid and liv
er and kidney function tests
Treatment observation period: D1-D5, daily follow-up, filling in the CRF, collecting the complete blood
count, CRP, and Chikungunya fever nucleic acid results on D5/Discharge day.
Follow-up after treatment; telephone follow-up was conducted on D7, D14, and D28.

Efficacy and Safety of Chinese Medicine in the Treatment of Chikungunya Fever: A Real-World Obser
vational Study Version date/version number: July, 2025/2.0
5
4
Case selection
4.1 Chikungunya fever diagnostic criteria
Suspected or confirmed cases of Chikungunya fever were included based on the diagnosis criteria of Ch
inese Guidance of the Diagnosis and Treatment for Chikungunya Fever (2017 Edition) published by the
Chinese Center for Disease Control and Prevention.
4.1.1 Basis of diagnosis
1) Epidemiological data: living in Chikungunya fever endemic areas or having a travel history to
epidemic areas within 12 days, and having a history of mosquito bites within 12 days before onset of the
disease.
2) Clinical manifestations: Acute onset, with fever as the first symptom, rash appears 2 to 5 days after
the disease, and severe pain in multiple joints.
3) Lab assessment: Chikungunya RNA detection from patient blood samples.
4.1.2 Diagnostic criteria
1) Suspected diagnosis: patients with the above-mentioned epidemiological history and clinical
manifestations; or patients without epidemiological history but with the above-mentioned typical
clinical manifestations.
2) Confirm the diagnosis: Patients with positive result of Chikungunya virus nucleic acid.
4.2 Inclusion Criteria
(1) Meets the suspected or confirmed diagnostic criteria for chikungunya fever;
(2) Symptom onset ≤3 days before enrollment;
(3) Actual prescribed treatment aligns with the study's group assignment (Chinese medicine, Wes
tern medicine, or combined therapy);
(4) Sign the informed consent form.
4.3 Exclusion criteria
(1) Severe chikungunya fever;
(2) Participation in another drug clinical trial within the past 3 months;
(3) Other conditions that the researchers consider unsuitable for inclusion .

Efficacy and Safety of Chinese Medicine in the Treatment of Chikungunya Fever: A Real-World Obser
vational Study Version date/version number: July, 2025/2.0
6
4.4 Source of Cases
At each research center, all eligible patients will serve as observation subjects for this cohort study.
Patients will be assigned to respective observation cohorts based on their actual prescription status, with
enrollment for each group continuing until the target number is reached.
4.5 Withdrawal Criteria
Eligible patients will undergo a 28-day follow-up, or until the occurrence of any of the following
events:
(1) Allergic reactions or serious adverse events (SAEs) that, in the investigator’s judgment, warrant
discontinuation of observation;
(2) Severe comorbidities or special pathological changes during the study that, in the investigator’s
opinion, make continuation inadvisable;
(3) Post-enrollment discovery of significant protocol violations by the patient;;
(4) Patient death, loss to follow-up, or voluntary withdrawal.
4.6 Handling of dropout cases
If a patient drops out, the investigator must document the reason in the eCRF, attempt to contact the
patient, complete all feasible assessments, and fill out the end-of-treatment follow-up record. The last
medication time should be recorded whenever possible, and follow-up should continue until the study
endpoint. If the dropout is due to an adverse event (AE) later judged to be related to the study treatment,
this must be recorded in the eCRF.
4.7 Criteria for case exclusion:
(1) Violation of inclusion criteria by the patient;
(2) Absence of any post-enrollment data;
(3) Joint determination by statisticians and investigators prior to database locking;
(4) Other criteria to be determined during data review based on actual circumstances.
4.8 Termination criteria​
(1) Patient requests to withdraw from the study.
5
Observation Cohorts and Treatments
5.1
Treatment Allocation by Cohort

Chinese Medicine Group: Chinese treatments, which may include herbal formulas (e.g.,
decoctions, granules) or acupuncture, tailored to their syndrome differentiation (e.g., heat-clearing,
detoxifying, or dampness-resolving therapies).;

Efficacy and Safety of Chinese Medicine in the Treatment of Chikungunya Fever: A Real-World Obser
vational Study Version date/version number: July, 2025/2.0
7

Western medicine group: Patients receive only standard Western medical care, which may include
antipyretics (e.g., acetaminophen), NSAIDs for pain, and supportive treatments (e.g., hydration);

Integrated therapy group : receive both Chinese and Western treatments.
5.2 Observation period and follow-up
Maximum observation period: 28 days
Visit time:
Screening period/baseline: First visit D0, with lab assessments: complete blood count, CRP, and chikun
gunya nucleic acid tests;
Treatment observation period: D1-D5, daily follow-up with clinical and lab assessments, D5 or before d
ischarge: complete blood count, CRP, and chikungunya nucleic acid tests;
Follow-up after treatment; telephone follow-up on D7, D14, and D28.
On D0, D5 or before discharge, collect 8 ml of whole blood (anticoagulant tube) for storage.
6
Observation items and evaluation during the study period
6.1 Clinical characteristics
(1) Patient demographic characteristics: gender, age, height, weight, ethnicity, etc.;
(2) Epidemiological data: living in chikungunya fever endemic areas or having a travel history to
epidemic areas within 12 days, and having a history of mosquito bites 12 days before onset of
illness;
(3) Past medical history and treatment history: past medical history, past medication history,
surgical history, allergy history, history of adverse drug reactions, etc.;
(4) Concomitant diseases and medications: disease name, treatment drugs, purpose of medication,
method of medication, time of medication, etc.
(5) The current illness situation: onset time, highest axillary temperature within 72 hours before c
onsultation, and diagnosis and treatment.
6.2 Effectiveness Observation Items
(1) Joint swelling and pain relief rate: After the first dose, DAS 44 score was < 1.6, and
decreased by more than 0.6 before and after treatment.
Disease Activity Score of 44 Joints Based on CRP (DAS 44 -CRP): It assesses the degree of joint
swelling and pain. The calculation formula is as follows:

Efficacy and Safety of Chinese Medicine in the Treatment of Chikungunya Fever: A Real-World Obser
vational Study Version date/version number: July, 2025/2.0
8
DAS44 - CRP = 0.54 ×
RAI + 0.065 ×
SJC44 + 0.17 × ln(CRP + 1) + 0.072 × GH + 0.45
44 assessed joints: including both hand metacarpophalangeal joints (MCP1-5), proximal
interphalangeal joints (PIP2-5), thumb interphalangeal joints, both wrists, both elbows, both shoulders
and both knees, as shown in the figure below:
Swollen joint count (SJC): The number of swollen joints among 44 joints was recorded .
CRP level: Record laboratory test results in mg/dL (CRP).
VAS score: Patients mark the disease activity on a 0-100 mm visual analog scale based on their
own feelings, with 0 representing no activity and 100 representing extreme activity.
2) Disease activity grading of joint swelling and pain (based on DAS 44 score):
Low activity ( DAS 44 < 1.6 )
Moderate activity ( 1.6≤DAS44 < 2.4 )​
High activity ( 2.4 ≤DAS 44 ≤3.7 )
Severe activity (DAS 44 > 3.7 )
3) Evaluation of treatment response at the time of disease remission (based on reduction in DAS 4
4 score):
Good response (DAS 44 >1.2)
General response (0.6<DAS 44 ≤1.2)
No response (DAS 44 ≤0.6)
(2) Rash scores compared with baseline: Changes in rash scores compared with baseline on
days 3 and 5 after medication ;
Affected area : The maximum affected area of each body part is 100% , and the affected area is locally
scored according to the following table, 0-6.
% Affected
area
0
1-9%
10 - 29%
30 - 49%
50 - 69%
70 - 89%
90 - 100%
cal scoring
0
1
2
3
4
5
6
Clinical symptom score: The severity of each symptom is rated from 0 to 3:
Severity of
illness
none
light
middle
Heavy
score
0
1
2
3
The average severity of the affected area. Half-grade points can be
recorded between each symptom grade, e.g. 2.5.
Erythema: 0 = none; 1 = mild (barely visible, pink); 2 = moderate (clearly visible, dark red); 3 = severe
(deep red or fiery red)
Papules: 0 = none; 1 = mild (barely noticeable raised areas); 2 = moderate (clearly visible raised areas
but not prominent); 3 = severe (prominent raised areas)
Rash Scoring Scale:
Body Parts
erythema
(0-3)
Edema / pimples
(0-3)
Local scoring
(0-6)
Body Parts
Score

Efficacy and Safety of Chinese Medicine in the Treatment of Chikungunya Fever: A Real-World Obser
vational Study Version date/version number: July, 2025/2.0
9
neck
(
+
+
）
trunk
(
+
+
）
Upper limbs
(
+
+
）
Lower limbs
(
+
+
）

VAS (Visual Analog Scale) pruritus score
No itching at all 0--1--2--3--4--5--6--7--8--9 — 10 Worst itching point​
(3) Complete fever reduction time: Complete fever reduction is defined as the body
temperature dropping to 37.2℃or below after the first dose and maintained for 24 hours or
more;
(4) Nucleic acid negative conversion time;
(5) Time for single symptom to disappear;
(6) Overall symptom disappearance time;
(7) Time for white blood cell count to return to normal: the time from the first dose to the first
observation of white blood cell count returning to normal;
(8) Time for platelet count to return to normal: the time from the first dose to the first observation
of platelet count returning to normal;
(9) Incidence of Chikungunya-related complications: Proportion of patients with recorded AEs for
Chikungunya-related complications (shock, DIC, encephalitis, acute liver injury, acute kidney
injury,
myocarditis,
pericarditis,
pneumonia,
respiratory
failure,
rhabdomyolysis,
acute
pancreatitis) after the start of treatment.
6.3 Safety Information
(1) Laboratory tests such as complete blood count/liver and kidney function , chest CT/X-ray,
electrocardiogram: collected based on actual clinical situations ;
(2) Incidence of adverse events/adverse reactions.
7
Safety observation
7.1 definition
(1)
Adverse Event, AE)

Efficacy and Safety of Chinese Medicine in the Treatment of Chikungunya Fever: A Real-World Obser
vational Study Version date/version number: July, 2025/2.0
1
In drug clinical trials, any adverse medical event that occurs after a subject receives a test drug is called
an adverse event. Adverse events can manifest as diseases , symptoms, signs or laboratory
abnormalities, and adverse events do not necessarily have a causal relationship with the investigational
drug.
Events that meet the definition of adverse events include:
Exacerbation of a pre-existing chronic or intermittent illness, including an increase in frequency and/or
severity of illness;
New diseases detected or diagnosed after administration of the investigational drug, even though they
may have existed before the start of the study;
signs, symptoms, or clinical sequelae of suspected drug interactions;
Signs, symptoms, or clinical sequelae of suspected overdose of the investigational drug or co-
administered drug (overdose itself is not reported as an adverse event/serious adverse event).
(2)
Serious adverse events Adverse Event, SAE)
It refers to adverse medical events such as death, life-threatening, permanent or severe disability or loss
of function, the need for hospitalization or prolonged hospitalization, congenital abnormalities or birth
defects, etc. that occur after the subject receives the investigational drug.
(3)
Important adverse events
Refers to any clinical adverse event or significant abnormality in laboratory tests other than SAE that
leads to targeted medical measures (such as discontinuation of drug, dose reduction and/or symptomatic
treatment).
(4)
Adverse drug reactions drug reaction, ADR ）
In drug clinical trials, harmful or unexpected reactions to the human body caused by the test drugs are
called adverse reactions.
(5)
Suspected and unexpected serious adverse reactions
Refers to suspected and unexpected serious adverse reactions whose nature and severity of clinical
manifestations are beyond the existing information in the investigator's brochure of the investigational
drug, the instructions for use of the marketed drug, or the summary of product characteristics.
7.2 Recording of adverse events
The name, severity, time of occurrence, duration, treatment measures, and process of treatment of
adverse events, important adverse events, and adverse reactions that occur from the beginning of the
treatment period to the last visit should be recorded in the research medical record, and their relevance
to the trial drug should be evaluated based on comprehensive consideration of comorbidities and
concomitant medications, and recorded in detail by the researcher.

Efficacy and Safety of Chinese Medicine in the Treatment of Chikungunya Fever: A Real-World Obser
vational Study Version date/version number: July, 2025/2.0
1
When adverse events or adverse reactions are found, researchers can determine whether to discontinue
observation based on the patient's condition. Cases in which medication is discontinued due to adverse
events or adverse reactions should be followed up and the results recorded in detail.
If any abnormality is found in the safety test indicators such as vital signs, physical examination,
complete blood count, urine routine, liver function, kidney function, electrolytes, etc. during or after
treatment, the test must be repeated at an appropriate time and comprehensively analyzed with the
subjects' onset and treatment to determine whether it is related to the test drug.
7.3 Adverse event severity grading
According to the Common Adverse Events Evaluation Criteria (Common Terminology Criteria for
Adverse Events 5.0, CTCAE) evaluates the severity of adverse events that occur during the trial, and the
severity of adverse events is divided into 5 levels:
Grade 1: Mild; asymptomatic or mild; clinical or diagnostic observations only; no treatment
required.
Grade 2: Moderate; minor, local or non-invasive treatment required; limitation of instrumental
activities of daily living commensurate with age (instrumental activities of daily living include cooking,
shopping for clothes, using the telephone, managing finances, etc.).
Grade 3: severe or medically significant but not immediately life-threatening; leading to
hospitalization or prolonged hospitalization; causing disability; limiting self-care activities of daily
living (self-care activities of daily living include bathing, dressing and undressing, eating, washing,
taking medicine, etc., and not being bedridden).
Grade 4: Life-threatening, requiring urgent medical attention.
Grade 5: Death related to AE.
Records: Adverse events must be recorded in the original documents and the eCRF adverse event
page, and the investigator shall determine the relevance of the adverse event to the trial drug and sign.
7.4 Determination of causal relationship between adverse events and drugs
Technical Guidelines for the Evaluation of the Correlation of Adverse Events in Clinical Trials of Drugs
(Trial Implementation) [14] issued by the CDE , a comprehensive evaluation of the correlation between
individual adverse events in clinical trials and the test drugs was conducted based on five evaluation points
(whether there is a reasonable time relationship, whether it is consistent with the known drug mechanism,
characteristics or known adverse reactions of the drug, destimulation results, restimulation results, and
whether other reasonable reasons can be used to explain it). According to different situations, the judgment
results are divided into five categories: related, very likely related, possibly related, possibly unrelated, and
unrelated. Among them, "related, very likely related, and possibly related" are judged as adverse
reactions and included in the calculation of adverse reaction incidence. See Table 1 and Table 2 for
details.

Efficacy and Safety of Chinese Medicine in the Treatment of Chikungunya Fever: A Real-World Obser
vational Study Version date/version number: July, 2025/2.0
1
Table 1 Classification and basis for the results of adverse event correlation determination in
drug clinical trials
Five-point
method
Judgment basis
dichotomy
related

Have a reasonable time relationship

Comply with known drug mechanisms of action, properties, or
known adverse reactions

To stimulate positive

Re-stimulation positive

No other reasonable explanation
Related
Probably
related

Have a reasonable time relationship

Comply with known drug mechanisms of action, properties, or
known adverse reactions

To stimulate positive

Lack of positive evidence for rechallenge

No other reasonable explanation
May be
related

There is a reasonable time relationship ;

lack of positive evidence of rechallenge ;

Symptoms include any of the following:
①It is consistent with the known drug mechanism,
characteristics or known adverse reactions , and the positive
result is not stimulated, but it can also be explained by other
reasonable reasons;
②The condition complies with known drug mechanisms,
characteristics or known adverse reactions, lacks positive
evidence of de-stimulation, and has no other reasonable
explanation ;
③It does not conform to the known drug mechanism of
action, characteristics or known adverse reactions , and there is
no other reasonable reason to explain the positive result.
④It does not conform to the known mechanism of action,
characteristics or known adverse reactions, lacks positive
evidence of de-stimulation, and has no other reasonable
explanation;

Efficacy and Safety of Chinese Medicine in the Treatment of Chikungunya Fever: A Real-World Obser
vational Study Version date/version number: July, 2025/2.0
1
Special Notes:
1. The correlation between adverse events and drugs shall be evaluated by relevant personnel with
medical expertise.
2. Table 5 may not cover all situations in actual work. If it cannot completely correspond to the judgment
basis in Table 6, you can refer to the professional judgment logic of the correlation between adverse
events and drugs in the table to make the most reasonable judgment result.
3. When more information and evidence on the correlation between adverse events and drugs is collected
during the progress of clinical trials, the previous correlation judgment results can be modified as needed,
but sufficient reasons should be provided.
4. Lack of positive evidence for de-challenge includes the following situations: the de-challenge result is
negative; de-challenge has not yet been performed; de-challenge is not applicable; Lack of positive
evidence for re-challenge includes the following situations: the re-challenge result is negative; re-
challenge has not yet been performed; re-challenge is not applicable.
5. In order to facilitate the work, the main contents of Table 1 can be simplified to Table 2. The special
instructions for using Table 2 are the same as those for Table 1.
Table 2 Adverse events and drug causal relationship judgment table
Judgment result
Judgment basis
Definitely
related
Probably
related
May be related
Probably
not relevant
Unrelated
Is there a
reasonable time
relationship?
+
+
+
±
-
Does it conform to
known
mechanisms of
action, properties
+
+
+
-
+
-
-
Probably not
relevant

Time relations cannot be ruled out

Lack of positive evidence for dechallenge

Lack of positive evidence for rechallenge

Symptoms include any of the following:
①Although it is consistent with the known mechanism of
action, characteristics or known adverse reactions, it can be
explained by other more reasonable reasons;
②It does not conform to the known mechanism of action,
characteristics or known adverse reactions, and can be
explained by other reasonable reasons;
Not relevant
Unrelated

No reasonable time relationship

Does not conform to known drug mechanisms of action,
properties, or known adverse reactions

Lack of positive evidence for dechallenge

Lack of positive evidence for rechallenge

Other reasonable reasons can be used to explain

Efficacy and Safety of Chinese Medicine in the Treatment of Chikungunya Fever: A Real-World Obser
vational Study Version date/version number: July, 2025/2.0
1
or known adverse
reactions?
To stimulate the
results
+
+
+
－/?
+
-/?
－/?
－/?
Re-stimulation
results
+
－/?
—/?
－/?
－/?
Are there other
reasonable reasons
to explain this?
-
-
+
-
-
-
＋
＋
+
+
Note:
+ indicates affirmative, or positive result;
- Indicates a negative result, or a situation where no result has been obtained yet;
± indicates that a temporal relationship cannot be ruled out;
++ means that there are other "more" reasonable reasons to explain it;
-/? indicates that the dechallenge/rechallenge result is negative, or dechallenge/rechallenge has not been
performed, or dechallenge/rechallenge is not applicable.
7.5 Management of adverse events
If adverse events occur to the subjects during the trial, they shall be handled according to the
following procedures:
After discovering that a subject has an adverse event, the researcher needs to inquire in detail
about the subject's symptoms and signs at the time. If necessary, symptomatic treatment can be given
first. The research physician will preliminarily assess the severity of the adverse event and its relevance
to the trial drug, and provide further treatment advice:
①General adverse events: The outcome of the event can be closely and continuously observed
or corresponding symptomatic treatment can be performed;
②Important adverse events: The research physician should inform the principal investigator
promptly and take measures such as suspending treatment, adjusting drug dosage and providing targeted
treatment according to the subject's condition. If necessary, the principal investigator may decide
whether to urgently unblind the subject (if applicable).
③Serious adverse events: Handle and report as the following “serious adverse events”.
④The research physician will treat the subject according to the condition of the patient. If the
subject's injury exceeds the treatment capabilities of the research department, the relevant departments
will be consulted and assist in handling the situation.
7.6 Management and reporting of serious adverse events
7.6.1 Handling of serious adverse events
(1) When an SAE is considered, the attending physician shall notify the principal investigator or
other responsible physician to be present. If the condition is serious, the project leader should be
notified while emergency treatment is being given. If necessary, the trial drug should be discontinued
immediately.

Efficacy and Safety of Chinese Medicine in the Treatment of Chikungunya Fever: A Real-World Obser
vational Study Version date/version number: July, 2025/2.0
1
(2) If it is judged to be an SAE, appropriate treatment or rescue measures will be taken
immediately according to the clinical manifestations and the standards of clinical rescue treatment of
each specialty. If it is severe toxicity caused by drug overdose, the researchers will decide to give rescue
measures such as accelerating drug excretion, maintain the stability of the patient's vital signs as much
as possible, and perform ECG monitoring when necessary. If necessary, the relevant departments can be
consulted and assist in handling the matter.
(3) When an out-of-hospital subject is diagnosed with an SAE and is unable to come for treatment,
it is recommended that the subject return to the hospital or go to a local hospital for treatment in a
timely manner, and immediately inform the project leader to obtain further treatment advice; if
receiving treatment at a local hospital, contact the attending doctor to understand the specific situation
and provide treatment advice. If necessary, bring the unblinding envelope and go to the local hospital
for treatment or return to this hospital for treatment.
7.6.2 Reporting of Serious Adverse Events
The reporting of SAEs should follow the SAE reporting procedures of the Chinese regulatory
authorities or independent ethics committees. After an SAE occurs, the researcher must immediately
report all SAEs in writing to the sponsor via email, and then provide a detailed, written follow-up report
in a timely manner. For reports involving death events, the researcher should provide the sponsor and
the ethics committee with the information they need, such as autopsy reports and final medical reports.
Sponsors should report SAEs to the relevant regulatory authorities in accordance with the
requirements of regulatory authorities and local regulations, and during the implementation of the study,
they will strictly abide by the "Standards and Procedures for Rapid Reporting of Safety Data during
Drug Clinical Trials" to rapidly report suspected unexpected serious adverse reactions (SUSAR) to
regulatory authorities. After receiving safety-related information from any source, the sponsor should
immediately analyze and evaluate it, including the severity, relevance to the trial drug, and whether it is
an expected event. Sponsors should rapidly report SUSAR to all researchers, clinical trial institutions,
and ethics committees participating in clinical trials; sponsors should report SUSAR to drug supervision
and administration departments and health and health authorities. After receiving the relevant safety
information of the clinical trial provided by the sponsor, the researcher should sign for and read it in a
timely manner, consider the treatment of the subjects, whether to make corresponding adjustments,
communicate with the subjects as soon as possible when necessary, and report the SUSAR provided by
the sponsor to the ethics committee.
The sponsor determines whether to report the event to the regulatory agency on an expedited basis
based on the expected nature of the SAE and the results of the assessment of the relevance of the SAE
to the investigational drug. The sponsor unblinds the case before the expedited report. SAEs for which
the investigator has not assessed the causal relationship will be considered to be related to the
investigational product. Therefore, the investigator should always record the most likely cause of the
SAE in his or her judgment to avoid unnecessary unblinding of the case. After a more precise cause is

Efficacy and Safety of Chinese Medicine in the Treatment of Chikungunya Fever: A Real-World Obser
vational Study Version date/version number: July, 2025/2.0
1
determined, the causal relationship of the investigational drug in subsequent follow-up reports of the
trial can be revised.
During the implementation of the study, the "Standards and Procedures for Rapid Reporting of
Safety Data during Drug Clinical Trials" will be strictly followed and the requirements of China's GCP
and relevant regulations will be obeyed.
7.7 Adverse events that were not relieved during follow-up
Adverse events that have not yet resolved at the study endpoint or have not been resolved must be
followed up until one of the following events occurs:
(1) Incident mitigation;
(2) The event is stable;
(3) if the baseline value is acceptable, the event returns to the baseline level;
(4) When it is impossible to obtain additional information (the subject or the person who takes
care of him/her refuses to provide additional information, and the subject is lost to follow-up despite
follow-up efforts (at least 3 telephone contacts)).
Follow-up methods can be hospitalization, outpatient clinic, home visit, telephone,
correspondence, etc.
8
Data Management
8.1 Data Management Plan
This study uses an electronic data collection system (EDC) for data management. The data management
plan is written by the project data manager based on the clinical trial protocol and registration
observation form, describing the data management process, personnel division of labor, timetable and
file archiving, etc., to ensure the consistency, effectiveness and standardization of data management
work, promote communication and exchanges between various clinical research departments, and
establish a high-quality database for statistical analysis. During the clinical trial, if the user needs to
modify the data management plan, the data manager should be notified to revise and update it in real
time, publish it to all relevant responsible personnel, and sign and confirm it.
8.2 Database Management
The design and testing of the database shall be completed by the data management personnel based on
the finalized clinical trial plan and the registration observation form. The data management personnel
shall also mark the registration observation form and formulate variable descriptions. Logical
verification settings shall be performed for fields with logical relationships according to the data
verification plan.

Efficacy and Safety of Chinese Medicine in the Treatment of Chikungunya Fever: A Real-World Obser
vational Study Version date/version number: July, 2025/2.0
1
After the database is established, it should be tested and verified, fully tested by relevant personnel, and
entered after review and confirmation by the head of the data management department.
8.3 Data collection and recording
The registration observation form was designed according to the research protocol, and data collection
was completed by clinicians.
The registration observation form is used as the original record and is imported into the EDC system,
the database of this project.
8.4 Data Monitoring
The data verification plan is formulated by the data management department, medical technology
department and project manager after fully understanding the design of the plan and discussing all the
verification points of the plan's data management content. If modifications are required during the
implementation process, the data manager will revise and update the version, and the above departments
will sign and confirm again.
8.5 Data cleaning
Questions during the data verification process were generated in two forms: questions automatically
generated by the online system and questions raised manually. The researchers or their authorized CRCs
answered the questions online until the data were cleaned.
8.6 Data review
Before the data review meeting, samples will be drawn for quality control according to the ratio
specified in the relevant SOP of the Data Management Department for the queries manually closed by
the data administrator. If the quality control error rate is within the specified range, then the quality
control is passed; if the quality control error rate is not within the specified range, samples will be
drawn again for quality control according to the specified ratio. If it still fails, 100% quality control will
be performed on all manually closed queries.
After the data cleaning is completed, the sponsor will be notified to hold a data review meeting. The
sponsor, principal investigator, data management personnel, and statistician will conduct a final review
of unresolved data issues and discuss the data set division according to the data review report.
After all the data are confirmed, the principal researcher will electronically sign the electronic data.

Efficacy and Safety of Chinese Medicine in the Treatment of Chikungunya Fever: A Real-World Obser
vational Study Version date/version number: July, 2025/2.0
1
8.7 Locking and unlocking the database
8.7.1 Database Lock
Data locking should meet the following prerequisites:
(1)
All data have been collected and data processing such as data entry has been completed.
(2)
All data queries have been answered and the database has been modified based on the data
queries.
(3)
If coding is required, ensure that the review of the medical data coding list has been
completed to ensure the integrity and consistency of medical coding.
(4)
The final data logic and consistency check has been completed.
(5)
The data quality review has been completed and meets the requirements for statistical
analysis.
(6)
All trial related documentation was updated and saved.
After the data manager confirms that the trial meets the above conditions, he/she will submit a written
lock application, which will be signed and dated by trial-related personnel (data manager,
biostatistician, project manager, sponsor, principal investigator). Once the written approval document
for database locking is obtained, the database will be locked.
8.7.2 Database Unlock
In principle, locked data will not be changed unless there is very clear evidence that there are errors in
the data and that they significantly affect the analysis results. Unlocking should provide written
modification instructions from researchers and sponsors, detailing the content and reasons for the
modifications. The version before unlocking is retained. Written signatures of senior management (such
as the head of clinical implementation, the head of biostatistics, and the head of data management) are
required. All revised data have audit traces. The database is locked again following the same process as
the first time the database was locked.
9
Quality Control of the Study
Clinical research quality control runs through the entire process from protocol design, project
implementation, data management, statistical analysis to report writing. Possible quality problems in the
research are controlled in advance. The possible quality problems in this study involve multiple links of
the project. The main quality control plan is as follows:

Efficacy and Safety of Chinese Medicine in the Treatment of Chikungunya Fever: A Real-World Obser
vational Study Version date/version number: July, 2025/2.0
1
9.1 Bias Control
9.1.1 Selectivity bias control
Mainly in the design and implementation stage. The target population of the program design is accurate,
and the hospital and doctor selection ensure the representativeness of the sample cases; once the doctor
starts to register, there is no selection of registered cases, etc.
9.1.2 Information Bias Control
Information bias refers to the systematic errors caused by human factors in the integrity, authenticity,
logic and measurement of patient data when collecting patient data. This study mainly controlled the
possible information bias through the following methods.
(1)
Establish detailed data collection methods and strict quality control methods.
(2)
Collect information in a timely manner and ensure its accuracy.
(3)
Collect data strictly in accordance with the unified SOP to ensure consistency in data
collection by all researchers.
(4)
By verifying the original data, the authenticity and integrity of the data can be guaranteed.
(5)
Regularly check missing values, abnormal values, logical relationships between indicators,
etc. through electronic data logic verification and network verification, and send verification
reports to the corresponding research centers for inspection, confirmation and modification.
9.1.3 Control of attrition bias
Loss-to-follow-up bias is inevitable in prospective studies. We should try to minimize the impact of
patient loss-to-follow-up on the research results. We should strengthen physician education and increase
physicians’ attention to research. We should strengthen the responsibilities of research assistants and
establish corresponding systems to minimize the number of lost-to-follow-up.
9.1.4 Control of confounding bias
The final data were controlled using statistical methods such as stratified analysis, standardization,
multivariate analysis, and propensity score.
9.2 Program design and sample representativeness assurance
To ensure that the cases can represent the patients using Jingfang Heji, a multi-stage sampling method
was used to select an estimated 10 hospitals from different regions and levels as case collection
hospitals according to the regional distribution of clinical sales of Jingfang Heji and the hospital grade

Efficacy and Safety of Chinese Medicine in the Treatment of Chikungunya Fever: A Real-World Obser
vational Study Version date/version number: July, 2025/2.0
2
distribution, as well as the sales share of hospitals of different grades. Based on the previous cases of
using Jingfang Heji, a quota was used to allocate the sample size.
9.3 Monitoring and Auditing
9.3.1 Audit
At a ratio of 20%, we randomly select research centers to conduct audits to check problems encountered
by researchers in data collection and by CRAs in the monitoring process. All centers are required to
conduct self-inspections and make corrective actions based on the content and focus of the problems to
ensure the quality of project research.
9.3.2 Monitoring
Formulate a strict monitoring plan, and CRA will regularly conduct routine monitoring of the research
center to check the project progress and the implementation of the researcher's plan; the authenticity of
the data and the traceability of the original data, etc. And promptly require the researcher to track and
correct the problems in the monitoring report.
9.4 Project implementation SOP and training
(1) Formulate the SOP for this study and require that the project be implemented strictly in
accordance with the corresponding SOP.
(2) Establish a strict training system and provide project training to all project participants (project
managers, CRAs, researchers, and researcher assistants, etc.).
10
Statistical analysis
SAS version 9.4 or above was used for data statistical analysis.
All statistical tests were two-sided, and P < 0.05 was considered to be statistically significant.
The description of quantitative indicators will calculate the number of cases (N), mean (Mean), standard
deviation (SD), median (Median), minimum (Min) and maximum (Max). When comparing between
groups, t-test or analysis of variance was used. The description of categorical indicators uses the number
of cases (N) and percentage (%) of each category. When comparing between groups, chi-square test or
Fisher's exact probability method was used. The Kaplan-Meier (KM) test was used to estimate the
survival function and calculate the median time for time-to-event variables. The survival curves
between different groups were compared based on the Log-Rank test, and the corresponding P value
was calculated.

Efficacy and Safety of Chinese Medicine in the Treatment of Chikungunya Fever: A Real-World Obser
vational Study Version date/version number: July, 2025/2.0
2
11
Ethical requirements
Since this study is an observational study, it does not interfere with normal clinical medical services, nor
does it interfere with patients' medical treatment and medication behavior. Therefore, in addition to
passing the ethics review at the clinical lead unit, other research centers can conduct ethics filing as
needed, or conduct ethics review of this project, but the focus of the review should be the feasibility of
this project in the center. After the review and approval, if major modifications to the trial protocol are
required, it should be submitted to the ethics committee of the clinical lead unit for review and approval
again.
Only researchers and monitors involved in clinical research may have access to the personal medical
records of the research subjects, and they will include confidentiality in the signed researcher statement
or confidentiality commitment. The ethics committee and the drug supervision and administration
department have the right to review the clinical research records. When processing data, the data will be
anonymous, omitting information that can identify the individual identity of the research subjects. The
medical records of the research subjects are kept in the data archives of the drug clinical research
institution with strict security and confidentiality measures.
12
Data Retention
All paper and electronic materials (investigator's manual, research plan, case observation form,
monitoring and audit record report, etc.) of this study will be kept by Guangdong Provincial Hospital of
Chinese Medicine. All materials will be kept for at least 5 years after the termination of the study.

V 2 .0
20250724
Efficacy and Safety of Chinese Medicine in the Treatment of
Chikungunya Fever: A Real-World Observational Study
Informed consent form and informed disclosure page (research
introduction)
Information Leaflet for Informed Consent
Dear Patient:
Your doctor has confirmed that you may have or have Chikungunya.
We will invite you to participate in an observational study on the treatment of Chikungunya
fever with Chinese medicine . This study will observe the TCM syndrome manifestations and
clinical characteristics of Chikungunya fever, and evaluate the effectiveness and safety of Chinese
medicine in the treatment of Chikungunya fever.
Before you decide whether to participate in this study, please read the following content as
carefully as possible. It can help you understand the study and why it is being conducted, the
procedures and duration of the study, and the possible benefits, risks, and discomforts that may arise
from participating in the study. If you wish, you can ask your doctor to explain it, or you can discuss
it with your family members and friends to help you make a decision.
Research
1. Research background and purpose
Chikungunya fever is an acute infectious disease caused by chikungunya virus (CHIKV),
transmitted by Aedes mosquitoes, and characterized by fever, rash, and joint pain. The first outbreak
of chikungunya fever was confirmed in Tanzania in 1952, and the virus was isolated in 1956. The
disease is mainly prevalent in Africa and Southeast Asia. Since 2004, outbreaks of chikungunya
virus have become more frequent and widespread, partly because the virus has adapted to make it
easier to spread through Aedes albopictus, and people of all ages are susceptible. In areas where
Aedes mosquitoes exist, when Aedes mosquitoes reach a certain density and natural conditions are
suitable, if CHIKV is introduced, it may cause an epidemic or outbreak.
On July 8, 2025, an imported case of Chikungunya fever occurred in Foshan, Guangdong .
Since then, the epidemic has spread rapidly, with more than a thousand confirmed cases in a short
period of time, which has brought certain treatment pressure to medical institutions. At present,
there are no available vaccines or specific drugs in China, and the clinical treatment plan is mainly
symptomatic treatment. In order to effectively respond to the recent surge in Chikungunya fever
patients in medical institutions, a team of traditional Chinese medicine experts in Guangdong
Province has formed a traditional Chinese medicine agreement formula plan after discussion and
applied it in clinical practice. In order to evaluate the effectiveness of this plan, this observational
study is planned to be carried out.
Under the guidance of the expert group of Guangdong Provincial Hospital of Traditional
Chinese Medicine, this study will collect all patients that can be collected during the observation
period in medical institutions in Foshan and other places where epidemics may occur in the
future .
The principal investigator of this study is Professor Zhang Zhongde from Guangzhou
University of Chinese Medicine and Guangdong Provincial Hospital of Chinese Medicine. As a
member of the expert advisory group for the National Joint Prevention and Control Mechanism,
Professor Zhang has participated in multiple TCM treatment guidance programs for emerging
infectious diseases. Through these practical experiences, he has accumulated substantial expertise
in applying traditional Chinese medicine to treat novel and sudden infectious disease outbreaks.
The Ethics Committee of Guangdong Provincial Hospital of Traditional Chinese Medicine has
reviewed that this study complies with the principles of the Declaration of Helsinki and meets the
requirements of medical ethics.
2. Who is suitable to participate in the study?
1. You can participate in this study if you meet all of the following conditions:
(1) Meets the suspected or confirmed diagnostic criteria for chikungunya fever;

V 2 .0
20250724
(2) Symptom onset ≤3 days before enrollment；
(3) Actual prescribed treatment aligns with the study's group assignment (Chinese medicine,
Western medicine, or combined therapy);
(4) Sign the informed consent form.
2. However, if you have any of the following conditions, you should not participate in this
study:
(1) Severe Chikungunya fever;
(2) Participation in another drug clinical trial within the past 3 months;
(3) Any other condition deemed by the investigator as unsuitable for enrollment.
Your study doctor will evaluate you and tell you whether you are suitable for participating in
this study. After obtaining your informed consent and signature, we will officially start the study.
3. What to do if you participate in the study
(1) Before you are selected for the study, the doctor will ask questions, record your medical
history, and evaluate you to determine whether you can participate in the study.
(2) If you participate in the research, the research will be conducted as follows:
At the beginning of the study, the doctor will record your demographic information (gender,
date of birth, etc.), medical history, symptoms and signs during the visit, test results, and treatment
plan;
During your hospitalization, your treatment plan will be entirely determined by your attending
physician and will not be affected by this study. You may receive Chinese medicine treatment, or
only conventional symptomatic treatment of Western medicine, or both. At the same time, the
doctor will follow up on you as follows:
On the 1st to 5th day after enrollment, the doctor will follow up with you every day to inquire
about and record your medication status and symptoms and signs;
On the 7th day after enrollment, the doctor will make the first follow-up call to you to inquire
about and record your medication status and symptoms and signs;
On the 14th day after enrollment, the doctor will make a second telephone follow-up call to
inquire about and record your medication status and symptoms and signs;
On the 28th day after enrollment, the doctor will make a third follow-up call to you to inquire
about and record your medication use and symptoms and signs.
Before you are discharged from the hospital, your doctor will follow up with you to ask and
record your medication use and symptoms and signs.
If your actual hospitalization time does not meet the above time points, the doctor will conduct
a final follow-up visit with you before you are discharged according to the actual time.
(3) In addition to routine diagnosis and treatment, we will collect additional blood samples
from you for future medical and scientific research. The samples will be collected when you are
enrolled, 5 days after enrollment, or before discharge. The number of samplings will be determined
based on your actual hospitalization time, and 8 ml of venous blood will be collected each time.
Your samples will be permanently stored in the Guangdong Provincial Hospital of Traditional
Chinese Medicine's biological sample bank until they are used up. When samples are stored or sent
for testing, they will be numbered instead of personal information to ensure that your privacy will
not be leaked. Your samples will only be used by researchers at the Guangdong Provincial Hospital
of Traditional Chinese Medicine for scientific research related to Chikungunya fever and will not
be used for commercial purposes. Before researchers use your remaining samples for each study,
they must obtain approval from the Ethics Committee.
(4) The study may be terminated if:
Patient withdrawal and termination of the study include the following situations: patients
experience serious adverse events that are considered to be related to the study procedures.
The complete termination of research includes the following aspects: the researcher requests
to terminate the research due to funding or management reasons and the government department
requires to terminate the research .
4. Possible benefits of participating in the study
You will not benefit directly, but research using your identifiable information and identifiable
biospecimens may help us understand health and disease, lead to improved medical care, make
diagnoses and treatments safer or more effective, and advance new scientific knowledge.

V 2 .0
20250724
5. Possible adverse reactions, risks, discomfort and inconvenience of participating in the study
This study is a non-interventional observational clinical study. In principle, it will not cause
harm to your body. If you are harmed due to participating in the study, you will be given
corresponding financial compensation in accordance with the law.
During the study, you will need to cooperate in completing some symptom information
reporting. This information is collected during daily ward rounds and will help the doctor understand
changes in your condition without causing you any additional trouble or inconvenience.
6. Relevant Fees
You do not need to pay any research-related expenses, such as blood collection fees and sample
retention fees, to participate in the study. This study does not incur any additional costs for you.
This study is only conducted during your hospital stay, and there will be no additional transportation
costs.
This study is a non-interventional observational clinical study and will not cause any harm to
your body in principle. If you are harmed as a result of participating in the study, you will be given
appropriate financial compensation in accordance with legal provisions.
7. Is personal information kept confidential?
Your medical records (research medical records/CRFs, laboratory test reports, etc.) will be
kept intact in the hospital, and the doctor will record the test results in your outpatient medical
record. The researcher, the sponsor's representative (if applicable) and the ethics committee will be
allowed to access your medical records. Any public report on the results of this study will not
disclose your personal information. We will make every effort to protect the privacy of your
personal medical information within the scope permitted by law.
8. How to get more information?
You may ask any questions about this study at any time. Your doctor or researcher will give
you his or her phone number so he or she can answer your questions.
If you have any complaints about your participation in the study, please contact the Ethics
Committee Office of Guangdong Provincial Hospital of Traditional Chinese Medicine (Tel: 020-
81887233-35943).
Your doctor will promptly notify you if any important new information becomes available
during the study that may affect your willingness to continue participating in the study.
9. Participants can voluntarily choose to participate in the study or withdraw from the study
Whether to participate in the study is entirely voluntary. You can refuse to participate in this
study or withdraw from this study at any time during the study, which will not affect the relationship
between you and the doctor, nor will it affect the loss of other interests in your medical treatment.
Your doctor or the investigator may terminate your participation in this study at any time if it
is in your best interest.
If you do not take part in this study, or if you leave the study, it will not affect your treatment
options. You do not have to take part in this study to get your disease treated.
If you withdraw from the study for any reason, you may be asked about your treatment. You
may also be asked to undergo laboratory tests and a physical examination if your doctor thinks it is
necessary. This is very important to protect your health.
10. What to do now?
Before you decide to take part in the study, please ask your doctor as many questions as
possible until you fully understand the study.
It is up to you to decide whether to take part in this study. You can discuss this with your family
or friends before making a decision.
Thank you for reading the above information. If you decide to participate in this study, please
tell your doctor or research assistant, who will arrange all matters related to the study for you.
Please keep this information.

V 2 .0
20250724
Informed consent form and consent signature page
Signature Leaflet for Informed Consent
Project Title: Efficacy and Safety of Chinese Medicine in the Treatment of Chikungunya Fever:
A Real-World Observational Study
Sponsor/Project issuing unit: None
Ethics review approval committee: Ethics Committee of Guangdong Provincial Hospital of
Traditional Chinese Medicine
Statement of consent
I have read the above description of this study and have had the opportunity to discuss and ask
questions about this study with the physician. All of my questions have been answered to my
satisfaction.
I understand the possible risks and benefits of participating in this study. I know that
participating in the study is voluntary, I confirm that I have had enough time to think about it, and
I understand that:
●I can always ask the doctor for more information.
●I can withdraw from this study at any time without being discriminated against or retaliated
against, and my medical treatment and rights will not be affected.
I also understand that if I withdraw from this study midway, especially if I withdraw from the
study due to medication reasons, it will be very beneficial to me and the entire study if I tell the
doctor about the changes in my condition and complete the corresponding physical examination
and physical and chemical examinations.
If I need to take any other medication due to my illness, I will seek the doctor's advice in
advance or tell the doctor truthfully afterwards.
I agree that the drug regulatory authorities, ethics committee or sponsor's representative may
review my research data.
I will be provided with a signed and dated copy of the informed consent form.
Finally, I decided to agree to participate in this study.
Subject's Signature:
date:
Daily contact number:
Guardian/Authorized Person Signature:
Relationship with the subject:
(Note: If the subject cannot sign the informed consent due to lack of/limited behavioral capacity, his/her
guardian or authorized person shall sign it)
Contact Number:
date:
I consent□or deny□the use of my medical records and biological specimens for research other
than this study.
Study Participant Signature:
date:
Guardian/Authorized Person Signature:
Relationship with participants:
date:
(Note: If the participant is unable to sign the informed consent due to incapacity, etc., his/her guardian
or authorized person shall sign it)
I confirm that the details of the trial, including their rights and possible benefits and risks, have
been explained to the research participants and a copy of the signed informed consent form has been
given to them.
Researcher’s Signature:
date:
Researcher's work phone number:
Phone number:
Contact number of the Ethics Committee Office of Guangdong Provincial Hospital of Traditional
Chinese Medicine: 020-81887233-35943

V 2 .0
20250724