PROTECT-Study: Prospective Research on Optimizing Atropine Concentration Escalation for Children's Myopia Prevention
Phase: PHASE1
Conditions: Pre-myopia
Sponsor: Tianjin Medical University Eye Hospital

PROTECT Study: A Prospective Study to Optimize the Atropine Concentration Staircase Protocol for Myopia Prevention in Children Version:
V1.0 Version Date: January 19,2026
PROTECT Study: A Prospective Study to Optimize the Atropine Concentration Staircase
Protocol for Myopia Prevention in Children Version: V1.0 Version Date: January 19,2026
PROTECT Study: A Prospective Study on Optimizing the Atropine
Concentration Staircase Protocol for Myopia Prevention in
Children
PROTECT-Study: Prospective Research on Optimizing Atropine Concentration Escalation for Children’s Myopia
Prevention
Study drug: Atropine Sulfate Eye Drops (0.01%,0.02%,0.04%)
Version date: 2026-01-19
Version: V1.0
Principal Investigator: Ruihua Wei
Lead unit: Tianjin Medical University Eye Hospital
Address: No.251 Fukang Road, Nankai District, Tianjin
Contact: 022-86428750

PROTECT Study: A Prospective Study to Optimize the Atropine Concentration Staircase Protocol for Myopia Prevention in Children Version:
V1.0 Version Date: January 19,2026
PROTECT Study: A Prospective Study to Optimize the Atropine Concentration Staircase
Protocol for Myopia Prevention in Children Version: V1.0 Version Date: January 19,2026
catalogue
1. List of Participating Institutions and Principal Investigators 3....................................................................................... 3
2. Abstract 4................................................................................................................................................................................. 4
2.1 Overview 4.....................................................................................................................................................................4
2.2 Flowchart 6.................................................................................................................................................................... 6
2.3 Research Schedule 8......................................................................................................................................................8
3. Background 10.......................................................................................................................................................................10
4. Objective 10...........................................................................................................................................................................10
5. Research Methods 10.............................................................................................................................................................10
5.1 Experimental Design 11...............................................................................................................................................10
5.2 Inclusion and Exclusion Criteria 11.............................................................................................................................11
5.2.1 Eligibility Criteria 11................................................................................................................................................ 11
5.2.2 Exclusion Criteria 11................................................................................................................................................ 11
5.3 Sample Size 12.............................................................................................................................................................11
5.4 Process 12.................................................................................................................................................................... 12
5.5 Evaluation of Research Findings 16............................................................................................................................16
6. Combined Therapeutic Measures 16..................................................................................................................................... 16
7. Medication Compliance 16....................................................................................................................................................16
8. Extension Research Program 16............................................................................................................................................16
9. Observation, Recording, and Management of Adverse Events 17........................................................................................17
9.1 Definition of Adverse Event (AE) 17..........................................................................................................................17
9.2 Observation and Evaluation of Adverse Events 17.....................................................................................................17
9.3 Assessment of Adverse Event Severity 17.................................................................................................................. 17
9.4 Determination of Correlation Between Adverse Reactions/Adverse Events and the Investigational Drug 17..........17
10. Compliance with Ethical Principles and Relevant Regulations 19.....................................................................................19
10.1 Medical Ethics Requirements 19...............................................................................................................................19
10.2 Subject Protection 19.................................................................................................................................................19
10.3 Benefits and Risks 19................................................................................................................................................ 19
11. Statistical Analysis 19..........................................................................................................................................................19
11.1 Statistical Analysis Data Set 19................................................................................................................................. 19
11.2 Statistical Analysis Plan 20........................................................................................................................................20
12. Economic Evaluation 20......................................................................................................................................................20
12.1 Data Definition and Data Sources 20........................................................................................................................ 20
12.2 Cost Estimation Formula 20......................................................................................................................................20
12.3 Cost-Effectiveness Analysis 20................................................................................................................................. 20
12.4 Long-term Economic Value Prediction Model (Markov Model) 21.........................................................................21
13. Analysis of the Effect of Drug Proportion 22......................................................................................................................22
13.1 Definitions and Scope of Measurement 22............................................................................................................... 22
13.2 Data Collection and Methods 22............................................................................................................................... 22
13.3 Comparison Benchmark 23....................................................................................................................................... 23
13.4 Analytical Methods 23...............................................................................................................................................23
14. Test Schedule 23.................................................................................................................................................................. 23

PROTECT Study: A Prospective Study to Optimize the Atropine Concentration Staircase Protocol for Myopia Prevention in Children Version:
V1.0 Version Date: January 19,2026
PROTECT Study: A Prospective Study to Optimize the Atropine Concentration Staircase
Protocol for Myopia Prevention in Children Version: V1.0 Version Date: January 19,2026
1. List of Participating Institutions and Principal Investigators
province
Hospital Name
investigato
r
Tianjin
Ophthalmology Hospital of Tianjin Medical University
Wei
Ruihua
Guizhou
Affiliated Hospital of Guizhou Medical University
Gu Hao
Guangdong
Foshan First People's Hospital
Shen
Peiyang
Anhui
The First Affiliated Hospital of South Anhui Medical College
Wu
Changfan
Yunnan
The First Affiliated Hospital of Dali University
Liu Fang
Hubei
Xiangyang Central Hospital
Mao
Xiaochun
Hubei
Yellowstone City Central Hospital
Luo Steel
Jiangsu
Nanjing Maternal and Child Health Hospital
Wu
Guangqiang
Shaanxi
Province
Baoji People's Hospital
megacarp
Shaanxi
Province
Xijing Hospital, Air Force Medical University
Dou Guorui
Tianjin
Tianjin Children's Hospital
Guo Zhen
Jiangsu
Affiliated Hospital of Jiangnan University
Wang
Jihong
Fujian
Quanzhou Children's Hospital
Chen
Yinhua
Sichuan
Chengdu Third People's Hospital
Huang
Keke

PROTECT Study: A Prospective Study to Optimize the Atropine Concentration Staircase Protocol for Myopia Prevention in Children Version:
V1.0 Version Date: January 19,2026
PROTECT Study: A Prospective Study to Optimize the Atropine Concentration Staircase
Protocol for Myopia Prevention in Children Version: V1.0 Version Date: January 19,2026
province
Hospital Name
investigato
r
Hubei
Union Hospital Affiliated to Tongji Medical College, Huazhong University of
Science and Technology
Cheng
Yang
Hunan
Chenzhou First People's Hospital
Li Zheng

PROTECT Study: A Prospective Study to Optimize the Atropine Concentration Staircase Protocol for Myopia Prevention in Children Version:
V1.0 Version Date: January 19,2026
PROTECT Study: A Prospective Study to Optimize the Atropine Concentration Staircase
Protocol for Myopia Prevention in Children Version: V1.0 Version Date: January 19,2026
2、Abstract
2.1 Overview
research
design
Prospective, multicenter clinical trial.
purpose of
research
1. The efficacy of switching to higher-concentration (0.02% and 0.04%) atropine eye drops
for delaying myopia progression in children with insufficient hyperopia reserve who show
poor response to 0.01% atropine eye drops was clearly demonstrated.
2. To explore the threshold of myopia progression in children using 0.01% atropine eye drops
when transitioning to higher concentrations (0.02% and 0.04%) of atropine eye drops.
Selection
criteria
Subjects must meet all the following criteria to be enrolled
1. A written informed consent form signed by the child and their legal guardian has been
obtained.
2. Children aged 6 to 9 years (inclusive).
3. Equivalent spherical diopter of computerized refraction after bilateral ciliary muscle
paralysis: 0D<SE. The upper limit standards for SE are set as follows for different age
groups: 6 years old: P25 = +1.13D,7 years old: P25 = +1.00D,8 years old: P25 = +0.88D,9
years old: P25 = +0.63D.
4. After bilateral ciliary muscle paralysis, the astigmatism detected by computerized refraction
is ≤1.00D.
5. Anisometropia ≤1.5D.
6. No other organic lesions affecting visual acuity in both eyes.
7. Unaided visual acuity ≥0.8.
8. Ocular intraocular pressure (IOP) ≤21 mmHg.
exclusion
criteria
Participants who meet any of the following criteria will not be eligible for enrollment:
1. Subjects who may have ocular diseases affecting vision or refractive errors (such as lens
damage diseases like cataract, glaucoma, macular degeneration, corneal lesions, uveitis,
retinal detachment, severe vitreous opacity, etc.).
2. Systemic diseases: Immune system disorders, central nervous system diseases, Down
syndrome, asthma, severe cardiopulmonary dysfunction, and a history of severe hepatic or

PROTECT Study: A Prospective Study to Optimize the Atropine Concentration Staircase Protocol for Myopia Prevention in Children Version:
V1.0 Version Date: January 19,2026
PROTECT Study: A Prospective Study to Optimize the Atropine Concentration Staircase
Protocol for Myopia Prevention in Children Version: V1.0 Version Date: January 19,2026
renal dysfunction.
3. Bilateral or unilateral ocular involvement with dominant strabismus or any other
pathological ocular changes or acute inflammatory eye diseases.
4. Patients who have undergone myopia control treatments, including pharmacological therapy
(e.g., atropine or piperazine), orthokeratology, multifocal soft lenses, multifocal hard
lenses, functional eyeglass frames, or red light therapy.
5. Exclude patients who have used drugs affecting efficacy evaluation (e.g., anticholinergic
agents: atropine, piperazine; cholinergic agents: pilocarpine) for systemic or local use
within the preceding 3 months.
6. Patients with hypersensitivity to atropine, cipretosil, or other drugs used in this study.
7. Exclude participants who have participated in other drug clinical trials within the past 3
months.
8. Other circumstances deemed unsuitable by the investigator.
9. Individuals with chronic mental disorders or psychiatric abnormalities.
10. Those with an adjustment range below 8D.
trial group
1. Phase 1: 0-24 weeks (0-6 months)
0.01% Atropine Eye Drops, once daily, instill into both eyes.
2. Phase 2: 24-48 weeks (6-12 months)
Adjust the atropine concentration in a stepwise manner based on the myopia progression
rate from 0 to 24 weeks (6 months), administered once daily with instillation into both eyes.
Group A: Good response (∆SE≤0.25D), continue to maintain 0.01% atropine.
Group B: Moderate response (0.25D <∆SE ≤0.375D), switched to 0.02% atropine.
Group C: Poor response (∆SE>0.375D), switched to 0.04% atropine.
trial
PERIOD
AND
FOLLOW
@-@ UP
1.
The trial lasted a total of 12 months, with Phase I involving 6 months of self-administered
medication follow-up for patients, and Phase II including follow-up with research support
medications.
2.
Drug retrieval, distribution, and follow-up examinations were conducted at the 3rd, 6th,
9th, and 12th months post-administration (time windows: 3rd month ± 2 weeks, 6th

PROTECT Study: A Prospective Study to Optimize the Atropine Concentration Staircase Protocol for Myopia Prevention in Children Version:
V1.0 Version Date: January 19,2026
PROTECT Study: A Prospective Study to Optimize the Atropine Concentration Staircase
Protocol for Myopia Prevention in Children Version: V1.0 Version Date: January 19,2026
month-2 weeks, 9th month ±2 weeks, 12th month-2 weeks).
3.
Children with pre-existing myopia (ciliary muscle paralysis refraction SE ≤-0.5D) who
exhibited a decline in uncorrected visual acuity below 0.8, requiring monocular glasses,
were enrolled in the follow-up and continued medication monitoring.
evaluating
indicator
1. Primary endpoint: Change in equivalent spherical refraction from baseline at 12 months.
2. Secondary endpoints:
(1) Change in axial length from baseline at 12 months.
(2) 12-month rapid myopia progression rate.
(3) Safety: Incidence of adverse reactions.
* Rapid myopia drift rate, defined as the percentage of children with a 6-month SER change <
−0.25D
3. Exploratory indicators: Pharmacoeconomic evaluation indicators
(1) Cost-effectiveness Ratio (CER)
(2) Incremental Cost-Effectiveness Ratio (ICER)
sample
capacity
1.
According to previous studies, during the first stage (0–6 months), there were significant
differences in the change of SER between the three groups compared to baseline: Group A
showed a decrease of −0.03 D (SD = 0.18), Group B a decrease of −0.31 D (SD = 0.07),
and Group C a decrease of −0.53 D (SD = 0.12). To achieve Research Objective 1
(significant differences among the three groups in the first stage), a one-way ANOVA
(assuming homogeneity of variance) was used for sample size estimation. The population
variance was set at 0.5, the significance level at α = 0.05, and the statistical power at 1−
β = 0.80. The calculation results indicated that at least 21 cases per group were required.
Considering that the proportion of children with myopia progression>0.375 D (Group C)
was the smallest among the three groups, the sample size for this group determined the
total sample size. Assuming that the proportion of Group C was at least 10%, the study
required at least 210 children to be enrolled.
2.
To achieve Research Objective 2 (Phase 2: No significant differences among the three

PROTECT Study: A Prospective Study to Optimize the Atropine Concentration Staircase Protocol for Myopia Prevention in Children Version:
V1.0 Version Date: January 19,2026
PROTECT Study: A Prospective Study to Optimize the Atropine Concentration Staircase
Protocol for Myopia Prevention in Children Version: V1.0 Version Date: January 19,2026
groups at 6 – 12 months), based on previous studies, the change in SER from June to
December was −0.19 D (SD=0.22) in Group A, −0.09 D (SD=0.22) in Group B, and −
0.02 D (SD=0.18) in Group C. Under the sample size conditions (21 cases per group), the
statistical power of one-way ANOVA was 0.58, and the ANOVA test failed to reject the
null hypothesis, indicating that the differences among the three groups were not
statistically significant. Therefore, 21 cases per group can simultaneously meet the
research objective of "no significant differences" in Phase 2. Considering an attrition rate
of approximately 10%, a total of 233 children are required.
2.2 Flowchart

PROTECT Study: A Prospective Study to Optimize the Atropine Concentration Staircase Protocol for Myopia Prevention in Children Version:
V1.0 Version Date: January 19,2026
PROTECT Study: A Prospective Study to Optimize the Atropine Concentration Staircase
Protocol for Myopia Prevention in Children Version: V1.0 Version Date: January 19,2026

PROTECT Study: A Prospective Study to Optimize the Atropine Concentration Staircase Protocol for Myopia Prevention
in Children Version: V1.0 Version Date: January 19,2026
PROTECT Study: A Prospective Study to
Optimize the Atropine Concentration Staircase Protocol for Myopia Prevention in Children Version: V1.0 Version Date:
January 19,2026
2.3 Research Schedule
project visit
V1
V3
V4
V5
V6
D-14 to D0
M3±2W
M6-2W
M9±2W
M12±2W
informed consent
X
demography
X
Medical history/Ocular
history
X
Risk Factor Survey Questionnaire 1
X
Computerized refraction
for anisocoria
X
X
X
X
X
intra-ocular tension
X
X
X
X
X
Vision 2
X
X
X
X
X
Ocular Biometric Measurements 3
X
X
X
X
X
Adjustment range measurement 4
X
X
X
X
X
slit lamp
X
X
X
X
X
Eye Position and Ocular Movement 5
X
X
X
Ciliary muscle paralysis computerized
refraction 6
X
X
X
Ciliary muscle paralysis
subjective refraction
X
X
X
eye-ground photography
X
X
X
OCTA7
X
X
X
X
X
orthopedic glasses
X
compliance
X
X
X
X
Treatment Satisfaction Questionnaire 8
X
X
Visual Quality Questionnaire 9
X
X
X
X
Post-administration ocular
tolerance
X
X
X
X
Inquiry about
X
X
X
X
X

PROTECT Study: A Prospective Study to Optimize the Atropine Concentration Staircase Protocol for Myopia Prevention
in Children Version: V1.0 Version Date: January 19,2026
PROTECT Study: A Prospective Study to
Optimize the Atropine Concentration Staircase Protocol for Myopia Prevention in Children Version: V1.0 Version Date:
January 19,2026
transportation costs
adverse event
X
X
X
X
Concomitant medication and concurrent
therapy 10
X
X
X
X
X
remarks
1. Risk factor questionnaire: Time spent on outdoor activities (exercise, leisure, etc.), time spent on close-up
visual tasks (watching TV, using tablets), and parents' myopia levels
2. Visual acuity: including best corrected distance and near vision, recorded in decimal form
3. Biological measurements: IOL master measures anterior chamber depth, axial length, pupillary diameter,
and corneal curvature
4. Adjustment range: measure the adjustment range using the approach method
5. Eye position and ocular motility: Assess eye position and ocular motility. If abnormalities are detected,
document the specific type of abnormality.
6. Ciliary muscle paralysis computerized refraction: 0.5% compound tropicamylamine eye drops,
administered every 5 minutes for a total of 3 times. The final instillation should be followed by a pupillary
light reflex examination 30 minutes later. If the pupillary light reflex is absent, refraction should be
performed; otherwise, the frequency of instillation should be increased.
7. OCTA: Choroidal Thickness and Blood Flow: Personalized Examination Based on Device Configuration
8. Therapeutic Satisfaction Questionnaire: Drug Therapy Satisfaction Scale-Second Edition (TSQM II)
9. Visual Quality Questionnaire: National Eye Institute Visual Function Questionnaire (NEI-VFQ-25)
Chinese Version
10. Inquire whether other myopia prevention interventions are being administered concurrently

PROTECT Study: A Prospective Study to Optimize the Atropine Concentration Staircase Protocol for Myopia Prevention
in Children Version: V1.0 Version Date: January 19,2026
PROTECT Study: A Prospective Study to
Optimize the Atropine Concentration Staircase Protocol for Myopia Prevention in Children Version: V1.0 Version Date:
January 19,2026
3、background
Myopia is the most common type of refractive error worldwide and has become a
major public health issue threatening the eye health of children and adolescents. The World
Health Organization predicts that by 2050, the global prevalence of myopia will reach 50%,
with high myopia accounting for nearly 10%, and the situation is particularly severe in East
Asia. The prevalence of myopia among children in China has already ranked first in the
world [1-3]. Myopia not only leads to decreased vision, but high myopia is also more likely
to cause irreversible complications such as retinal detachment, choroidal atrophy, and
macular degeneration, significantly increasing the risk of blindness [4]. Previous studies
have shown that delaying the onset of myopia by one year can reduce the final myopia level
by at least 0.75 D. Therefore, it is necessary to adopt effective myopia prevention measures
to reduce the prevalence of myopia and the proportion of moderate and high myopia [5].
Thus, exploring safe and effective myopia prevention strategies is imperative.
Among various preventive measures, low-concentration atropine eye drops have
garnered significant attention due to their remarkable therapeutic efficacy. As a
non-selective muscarinic receptor antagonist, atropine can delay axial length growth by
modulating scleral and choroidal signaling pathways. However, the optimal concentration
for preventing myopia onset and progression remains inconclusive, with numerous studies
focusing on different concentrations, most of which concentrate on 0.01%–0.05% [6-8].
Atropine eye drops at concentrations of 0.01%,0.025%, and 0.05% have been shown to
improve refractive error and axial length growth in children with presbyopia, reduce the
incidence of myopia in children, and not impair normal daily life or academic performance.
Currently, 0.01% atropine eye drops are widely used in clinical practice. However,
individual variations in efficacy are observed due to factors such as ethnicity, visual habits,
age, and environmental conditions.
It is noteworthy that there are significant individual variations in the progression rate
of myopia, and fixed-concentration regimens may fail to meet clinical needs. The stepwise
concentration adjustment strategy has emerged, with the core principle being the
modulation of drug concentration. Some scholars have proposed that initial use of 0.01%
atropine eye drops yields suboptimal responses, and increasing the concentration can

PROTECT Study: A Prospective Study to Optimize the Atropine Concentration Staircase Protocol for Myopia Prevention
in Children Version: V1.0 Version Date: January 19,2026
PROTECT Study: A Prospective Study to
Optimize the Atropine Concentration Staircase Protocol for Myopia Prevention in Children Version: V1.0 Version Date:
January 19,2026
achieve better outcomes, thereby more effectively controlling the progression of myopia.
However,
existing
"stepwise
concentration"
protocols
lack
multicenter
evidence,
particularly for prophylactic applications in children with early-stage myopia. Therefore,
rigorous clinical trials are urgently needed to clarify the efficacy and safety of concentration
escalation protocols in preventing myopia onset.
In conclusion, low-concentration atropine eye drops represent a critical option for
myopia prevention and control. Further research is required to evaluate the efficacy of
switching to higher-concentration (0.02% and 0.04%) atropine eye drops in children with
insufficient hyperopia reserve who exhibit poor response to 0.01% atropine eye drops, as a
means to delay myopia progression. Additionally, it remains necessary to investigate the
threshold for myopia progression in children using 0.01% atropine eye drops when
transitioning to higher-concentration (0.02% and 0.04%) formulations.
4、purpose
Clarify the efficacy of switching to higher-concentration (0.02% and 0.04%) atropine
eye drops for delaying myopia progression in children with insufficient hyperopia reserve
who exhibit poor response to 0.01% atropine eye drops. Explore the threshold for myopia
progression
in
children
using
0.01%
atropine
eye
drops
when
transitioning
to
higher-concentration (0.02% and 0.04%) atropine eye drops.
5、research technique
5.1 Experimental Design
Prospective, multicenter clinical trial.
5.2 Eligibility Criteria
5.2.1 Eligibility Criteria
(1) Written informed consent was obtained from the child and legal guardian.
(2) Children aged 6 to 9 years (inclusive).
(3) After bilateral ciliary muscle paralysis, the equivalent spherical diopter of
computerized refraction is: 0D<SE. The upper limit standards for SE are set as
follows for different age groups: 6 years old: P25 is +1.13D,7 years old: P25 is
+1.00D,8 years old: P25 is +0.88D,9 years old: P25 is +0.63D.
(4) The astigmatism degree detected by computerized refraction after bilateral ciliary

PROTECT Study: A Prospective Study to Optimize the Atropine Concentration Staircase Protocol for Myopia Prevention
in Children Version: V1.0 Version Date: January 19,2026
PROTECT Study: A Prospective Study to
Optimize the Atropine Concentration Staircase Protocol for Myopia Prevention in Children Version: V1.0 Version Date:
January 19,2026
muscle paralysis was ≤1.00D.
(5) The anisometropia of both eyes was ≤1.5D.
(6) No other organic lesions affecting visual acuity were found in both eyes.
(7) The eyes had the visual acuity of ≥0.8.
(8) The intraocular pressure in both eyes was ≤21 mmHg.
5.2.2 Exclusion Criteria
Participants who meet any of the following criteria will not be eligible for enrollment:
(1) Subjects who may have ocular diseases affecting vision or refractive errors (such
as lens damage diseases like cataracts, glaucoma, macular degeneration, corneal
lesions, uveitis, retinal detachment, severe vitreous opacity, etc.).
(2) Systemic diseases: immune system disorders, central nervous system diseases,
Down syndrome, asthma, severe cardiopulmonary dysfunction, and a history of
severe hepatic or renal dysfunction.
(3) Bilateral or unilateral ocular involvement with dominant strabismus or any other
pathological ocular changes or acute inflammatory eye diseases.
(4) Treatment methods for myopia control include: pharmacological therapy (e.g.,
atropine or pilocarpine); orthokeratology lenses, multifocal soft lenses, multifocal
hard lenses, or functional eyeglass frames; and red light therapy.
(5) Use of drugs affecting efficacy evaluation (e.g., anticholinergic agents: atropine,
piperazine; cholinergic agents: pilocarpine) systemically or topically within the
preceding 3 months.
(6) Patients with hypersensitivity to atropine, cyclopentolide, or other drugs used in
this study.
(7) Participants who had participated in other drug clinical trials within the first 3
months prior to screening.
(8) Other circumstances deemed unsuitable by the investigator.
(9) Individuals with chronic mental disorders or psychiatric abnormalities.
(10)The adjustment range was lower than 8D.
5.3 Trial Grouping

PROTECT Study: A Prospective Study to Optimize the Atropine Concentration Staircase Protocol for Myopia Prevention
in Children Version: V1.0 Version Date: January 19,2026
PROTECT Study: A Prospective Study to
Optimize the Atropine Concentration Staircase Protocol for Myopia Prevention in Children Version: V1.0 Version Date:
January 19,2026
(1) Phase 1: 0-24 weeks (0-6 months). 0.01% atropine eye drops, once daily, instilled
into both eyes.
(2) Phase 2: 24-48 weeks (6-12 months). Based on the progression rate of myopia
from 0-24 weeks (6 months), the atropine concentration is incrementally increased;
administered once daily, instilled into both eyes.
Group A: Good response (∆SE≤0.25D), continue to maintain 0.02% atropine.
Group B: General response (0.25D <∆SE ≤0.375D), switched to 0.02% atropine.
Group C: Poor response (∆SE>0.375D), switched to 0.04% atropine.
5.4 Sample Size
(1) According to previous studies, during the first stage (0 – 6 months), there were
significant differences in the change of SER between the three groups compared to
baseline: Group A showed a decrease of −0.03 D (SD = 0.18), Group B a decrease
of −0.31 D (SD = 0.07), and Group C a decrease of −0.53 D (SD = 0.12). To
achieve Research Objective 1 (significant differences among the three groups in
the first stage), a one-way ANOVA (assuming homogeneity of variance) was used
for sample size estimation. The population variance was set at 0.5, the significance
level at α = 0.05, and the statistical power at 1−β = 0.80. The calculation results
indicated that at least 21 cases per group were required. Considering that the
proportion of children with myopia progression>0.375 D (Group C) was the
smallest among the three groups, the sample size for this group determined the
total sample size. Assuming that the proportion of Group C was at least 10%, the
study required at least 210 children to be enrolled.
(2) To achieve Research Objective 2 (Phase 2: No significant differences among the
three groups at 6–12 months), based on previous studies, the change in SER from
June to December was −0.19 D (SD=0.22) in Group A, −0.09 D (SD=0.22) in
Group B, and −0.02 D (SD=0.18) in Group C. Under the sample size conditions
(21 cases per group), the statistical power of one-way ANOVA was 0.58, and the

PROTECT Study: A Prospective Study to Optimize the Atropine Concentration Staircase Protocol for Myopia Prevention
in Children Version: V1.0 Version Date: January 19,2026
PROTECT Study: A Prospective Study to
Optimize the Atropine Concentration Staircase Protocol for Myopia Prevention in Children Version: V1.0 Version Date:
January 19,2026
ANOVA test failed to reject the null hypothesis, indicating that the differences
among the three groups were not statistically significant. Therefore, 21 cases per
group can simultaneously meet the research objective of "no significant
differences" in Phase 2. Considering an attrition rate of approximately 10%, a total
of 233 children are required.
5.5 Process
v.1 Baseline Assessment
For subjects intended for inclusion, the investigator shall explain the purpose,
methodology, effects of the investigational drug, and potential adverse effects of the trial,
obtain consent from the subject and their parent/guardian, and obtain a signed informed
consent form. Subsequently, screening tests shall be conducted to determine whether the
subject meets the case selection criteria.
The relevant processes include:
(1) Sign the informed consent form
(2) Collect demographic data (including age, gender, date of birth, and ethnicity)
(3) Medical history/Ocular history
(4) Risk Factor Questionnaire
(5) Computerized refraction for anisocoria
(6) intra-ocular tension
(7) Visual acuity: best corrected distance and near vision
(8) Ocular biometric measurements: axial length, anterior chamber depth, pupillary
diameter, corneal curvature
(9) amplitude of accommodation
(10) Slit-lamp and anterior segment photography: external eye and conjunctiva, tear film,
cornea, lens
(11) Eye Position and Ocular Movement
(12) Ciliary muscle paralysis (specific medication standards refer to SOP)
(13) Ciliary muscle paralysis computerized refraction
(14) Ciliary muscle paralysis subjective refraction
(15) eye-ground photography

PROTECT Study: A Prospective Study to Optimize the Atropine Concentration Staircase Protocol for Myopia Prevention
in Children Version: V1.0 Version Date: January 19,2026
PROTECT Study: A Prospective Study to
Optimize the Atropine Concentration Staircase Protocol for Myopia Prevention in Children Version: V1.0 Version Date:
January 19,2026
(16) OCTA
(17) orthopedic glasses
(18) Record concomitant medications and combined therapies
(19) Inquiry on transportation costs to the hospital
For eligible participants who meet the enrollment criteria, schedule an appointment for
the next planned visit.
v.2 1 month after medication (M1 ±2 weeks)
(1) Computerized refraction for anisocoria
(2) intra-ocular tension
(3) Visual acuity: best corrected distance and near vision
(4) Ocular biometric measurements: axial length, anterior chamber depth, pupillary
diameter, corneal curvature
(5) amplitude of accommodation
(6) Slit-lamp and anterior segment photography: external eye and conjunctiva, tear film,
cornea, lens
(7) OCTA
(8) orthopedic glasses
(9) compliance
(10) Visual Quality Questionnaire
(11) Post-administration ocular tolerance
(12) adverse event
(13) Record concomitant medications and combined therapies
(14) Inquiry on transportation costs to the hospital
v.3 3 months after medication (M3±2W)
(1) Computerized refraction for anisocoria
(2) intra-ocular tension
(3) Visual acuity: best corrected distance and near vision
(4) Ocular biometric measurements: axial length, anterior chamber depth, pupillary
diameter, corneal curvature

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(5) amplitude of accommodation
(6) Slit-lamp and anterior segment photography: external eye and conjunctiva, tear film,
cornea, lens
(7) OCTA
(8) orthopedic glasses
(9) compliance
(10) Visual Quality Questionnaire
(11) Post-administration ocular tolerance
(12) adverse event
(13) Record concomitant medications and combined therapies
(14) Inquiry on transportation costs to the hospital
v.4 6 months after medication (M6-2W)
(1) Treatment Satisfaction Questionnaire
(2) Computerized refraction for anisocoria
(3) intra-ocular tension
(4) Visual acuity: best corrected distance and near vision
(5) Ocular biometric measurements: axial length, anterior chamber depth, pupillary
diameter, corneal curvature
(6) amplitude of accommodation
(7) Slit-lamp and anterior segment photography: external eye and conjunctiva, tear film,
cornea, lens
(8) Eye Position and Ocular Movement
(9) Ciliary muscle paralysis (specific medication standards refer to SOP)
(10) Ciliary muscle paralysis computerized refraction
(11) Ciliary muscle paralysis subjective refraction
(12) eye-ground photography
(13) OCTA
(14) orthopedic glasses
(15) compliance
(16) Visual Quality Questionnaire

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(17) Post-administration ocular tolerance
(18) adverse event
(19) Record concomitant medications and combined therapies
(20) Inquiry on transportation costs to the hospital
v.5 9 months after medication (M9±2W)
(1) Computerized refraction for anisocoria
(2) intra-ocular tension
(3) Visual acuity: best corrected distance and near vision
(4) Ocular biometric measurements: axial length, anterior chamber depth, pupillary
diameter, corneal curvature
(5) amplitude of accommodation
(6) Slit-lamp and anterior segment photography: external eye and conjunctiva, tear film,
cornea, lens
(7) OCTA
(8) orthopedic glasses
(9) compliance
(10) Visual Quality Questionnaire
(11) Post-administration ocular tolerance
(12) adverse event
(13) Record concomitant medications and combined therapies
(14) Inquiry on transportation costs to the hospital
v.6 12 months after medication (M12±2W)
(1) Treatment Satisfaction Questionnaire
(2) Computerized refraction for anisocoria
(3) intra-ocular tension
(4) Visual acuity: best corrected distance and near vision
(5) Ocular biometric measurements: axial length, anterior chamber depth, pupillary
diameter, corneal curvature
(6) amplitude of accommodation

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(7) Slit-lamp and anterior segment photography: external eye and conjunctiva, tear film,
cornea, lens
(8) Eye Position and Ocular Movement
(9) Ciliary muscle paralysis (specific medication standards refer to SOP)
(10) Ciliary muscle paralysis computerized refraction
(11) Ciliary muscle paralysis subjective refraction
(12) eye-ground photography
(13) OCTA
(14) orthopedic glasses
(15) compliance
(16) Visual Quality Questionnaire
(17) Post-administration ocular tolerance
(18) adverse event
(19) Record concomitant medications and combined therapies
(20) Inquiry on transportation costs to the hospital
5.6 Evaluation of Research Findings
5.6.1 Key Evaluation Indicators
The change of equivalent spherical diopter at 12 months was compared with that at
baseline.
5.6.2 Secondary Indicators
(1) The change of axial length at 12 months compared with baseline.
(2) 12-month rapid myopia progression rate (percentage of 6-month SER change <−
0.25D).
(3) Safety: Incidence of adverse reactions.
5.6.3 Economic Evaluation Indicators
1
Cost-effectiveness Ratio (CER)
2
Incremental Cost-Effectiveness Ratio (ICER)
6、Combined therapeutic measures
Children who have developed myopia during follow-up (ciliary muscle paralysis

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refraction SE ≤-0.5D) and whose uncorrected visual acuity has decreased below 0.8,
wearing monocular glasses, should continue to complete medication follow-up and be noted
in the case report form.
7、compliance
During each follow-up visit, inquire about the actual medication use of the subject and
calculate the subject's medication adherence.
Medication adherence = (actual number of doses administered/theoretical number of
doses administered) × 100%
Theoretical medication frequency = daily medication frequency
×
theoretical
medication days.
8、Trial Duration and Follow-up
The trial lasted a total of 12 months. Phase 1: Patients self-purchased medications and
underwent 6-month follow-up. Phase 2: Scientific research medication support and free
medication follow-up. Drug retrieval, distribution, and inspection follow-ups were
conducted at the 3rd, 6th, 9th, and 12th months post-administration (time windows: 3rd
month ±2 weeks, 6th month-2 weeks, 9th month ±2 weeks, 12th month-2 weeks).
9、Observation, Recording, and Management of Adverse Events
9.1 Definition of Adverse Event (AE)
Any adverse medical event occurring during the follow-up study period (from the time
of the subject's signing of the informed consent form to the last follow-up) is classified as
an adverse event, regardless of whether there is a causal relationship with the study product.
Therefore, an adverse event may be any adverse or unexpected signs, symptoms, or diseases
that are temporally related to the study treatment, irrespective of whether they are
treatment-related.
9.2 Observation and Evaluation of Adverse Events
The safety of post-marketing follow-up studies is evaluated through adverse event
reporting by subjects or direct observation by investigators. During visits, investigators will
inquire about adverse events in a non-inductive manner. Additionally, investigators are
responsible for verifying test results. For abnormal (outside the normal range) test results,

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they must confirm whether there is a deviation from baseline levels. If necessary, repeat
testing or additional tests may be performed.
To confirm the original test results. If the test results show a meaningful abnormality
compared to the baseline level, it should be classified as an adverse event.
9.3 Assessment of Adverse Event Severity
When completing the adverse event form, investigators will refer to the grading
criteria of the "Common Terminology Criteria for Adverse Events (CTCAE) 5.0 (Chinese
Version)" (November 27,2017) issued by HHS/NIH/NCI to comprehensively assess the
severity of adverse events. To standardize the criteria, the grading of AE event severity is as
follows:
Level 1:
Mild, asymptomatic or mild; only clinically or diagnostically apparent; no treatment required.
Level 2:
Moderate, requiring minor, localized, or non-invasive treatment; limited instrumental
Level 3:
Severe
or
medically
significant
but
not
immediately
life-threatening;
resulting
in
Level 4:
Life-threatening; requires urgent treatment.
Level 5:
AE-related deaths.
Note: Activities of Daily Living (ADL)
*: Instrumental activities of daily living refer to the use of telephones, etc.
9.4 Determination of Correlation Between Adverse Reactions/Adverse Events and the
Investigational Drug
Adverse reactions refer to adverse events associated with the investigational drug.
Low-concentration atropine eye drops are known to occasionally cause the following
adverse reactions: ocular irritation, blurred vision, photophobia, allergic conjunctivitis, etc.
If these occur, they will be closely monitored and quantitatively assessed, and recorded in
the adverse event form.
Investigators should endeavor to explain each adverse event and establish their
relationship with the investigational drug. Potential associations between adverse events,
the investigational drug, and concomitant medications should be evaluated using the
following five-level classification criteria:
(1) Negative correlation: The adverse event occurs at a time inconsistent with the

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rational sequence after medication administration, and the event does not match the
suspected type of drug reaction. However, the clinical status of the subject or other
treatments may have caused the reaction, or the disease improved or other treatments were
discontinued, leading to the resolution of the event.
(2) Possible unrelated: The occurrence of adverse events does not align with the
reasonable temporal sequence after medication administration, the event does not
correspond to the known reaction type of the suspected drug, and the clinical status of the
subject or other treatment modalities may also have contributed to the reaction.
(3) May be related: The occurrence of adverse events follows a reasonable temporal
sequence after medication administration, and the events correspond to known types of
reactions associated with the suspected drug. However, the clinical status of the subject or
other treatment modalities may also have contributed to the observed reactions.
(4) Highly probable: The adverse event occurred in a reasonable temporal sequence
after medication administration, the event corresponds to the known reaction type of the
suspected drug, the symptoms alleviated after discontinuation of the drug, and the event
cannot be reasonably explained by the known clinical status characteristics of the subject.
(5) Relevance confirmation: The adverse event occurs in a reasonable temporal
sequence after medication administration, matches the known reaction type of the suspected
drug, improves after discontinuation, and reappears upon repeated administration.
In this clinical study, adverse events classified as definitely related, very likely related,
and possibly related were counted as the drug adverse reaction rate. Investigators should
follow up on adverse reactions until symptoms resolve or stabilize.
9.5 Pharmacovigilance (PV) and Safety Data Reporting
(1) Scope of Reporting: The sponsor (healthcare institution) shall provide the
sponsor/farmaceutically active substance (FAS) provider with the following safety data
(including but not limited to): adverse reactions (ARs) occurring in subjects after
administration of the investigational product (defined as harmful reactions unrelated to the
intended use of the product under normal dosage and administration, including those
potentially caused by product quality issues or associated with off-label use, overdose, etc.).
(2) Reporting timeline and method: During the study, if any drug safety information

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related to the product is identified, it should be reported to the sponsor/pharmaceutical
provider's pharmacovigilance department within 3 calendar days via the Wenjuanxing
mini-program (scan the QR code below).
Note: All shared data must undergo subject privacy desensitization.
Wenjuanxing Mini Program
10、Compliance with ethical principles and relevant regulations
10.1 Medical Ethics Requirements
In compliance with the ethical review guidelines for biomedical research involving
humans (2016) issued by the Ministry of Health, the WMA Declaration of Helsinki (2013),
the CIOMS International Ethical Guidelines for Health-Related Research Involving Human
Subjects (2016), and the ethical principles of Good Clinical Practice (GCP), the study will
be conducted under the guidance of Good Clinical Practice (GCP) and in accordance with
the protocol approved by the ethics committee. This ensures the scientific rigor of the study
and protects the health rights of the participants.
10.2 Subject Protection
The informed consent process provides continuous explanations to participants and
their parents/guardians, enabling them to make informed decisions about whether to initiate
or continue participation in the study after thorough understanding and consideration.
Investigators will discuss the study content with participants and their parents/guardians.
Participants and their parents/guardians have the opportunity to raise questions before,
during, and after the study. Participants and their parents/guardians are entitled to the right to
be informed throughout the study and may withdraw from the study at any time without
justification. The informed consent form provides an overview of the study, including its
purpose, procedures and planned activities, potential risks and benefits, as well as alternative

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treatments available. The informed consent form also explains the rights of participants once
they have participated in the study. Participants and their parents/guardians should be given
sufficient time to consider whether to participate in the study. If they agree to participate,
they must sign the informed consent form for the participant and their parents/guardians.
10.3 Benefits and Risks
Participants who enroll in this study will receive a free medication box per follow-up
visit. During the follow-up period, investigators will provide one-on-one priority medical
consultations, and personalized treatment plans will be formulated based on the examination
results.
At the initial stage of low-concentration atropine eye drops administration, patients may
experience varying degrees of photophobia, glare, blurred near vision, and localized allergic
reactions. Relevant parameter changes should be monitored through pupil diameter
measurement, accommodation function assessment, and intraocular pressure examination.
For subjects intolerant to photophobia or glare, corrective measures such as wearing
photochromic lenses can be implemented. Those with blurred near vision due to inadequate
accommodation function may benefit from specialized accommodation training.
11、statistical analysis
11.1 Statistical Analysis Data Set
(1) Full Analysis Set (FAS): Conduct efficacy analysis on all subjects who received at
least one dose of the drug, in accordance with the intention-to-treat (ITT) principle.
(2) Per-protocol Set: All cases that comply with the trial protocol, demonstrate good
adherence, do not use prohibited medications during the trial period, and complete the
required content in the case report form. The efficacy of the drugs is statistically analyzed
simultaneously in both the FAS and PPS.
(3) Safety Analysis Set (SAS): All enrolled cases that have received at least one dose
of the investigational drug and have complete post-administration safety records are
included in the Safety Analysis Set. This dataset is used for safety analysis.
11.2 Statistical Analysis Plan
For each subject, the right eye was included in the analysis.
12、economics evaluation

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12.1 Data Definition and Data Sources
(1) Direct costs: Focus on the consumption of medical resources directly related to the
use of low-concentration atropine eye drops
(2) Indirect costs: Non-medical expenses (transportation costs) incurred by families
due to children's participation in this study and the use of low-concentration atropine eye
drops.
To clearly delineate the components of this evaluation metric, all relevant parameters
were systematically collected and documented in a self-designed form (see Appendix 2).
12.2 Cost Estimation Formula
Total cost of investigational drug = unit price × total number of required boxes
Total required boxes = Total required units / Units per box. If the total is less than one
box, it is rounded up to one box.
Total required quantity = Daily usage frequency × Number of usage days
If the drug packaging specifications change during the research process, the 'number of
units per box' parameter must be updated immediately, and the total required number of
boxes and costs must be recalculated to avoid deviations from the actual procurement costs.
12.3 Cost-Effectiveness Analysis
Based on the clinical efficacy indicators established in this study protocol, the
cost-effectiveness relationship of low-concentration atropine eye drops was quantified
without setting up an additional control group, with economic evaluation solely based on its
own efficacy data:
1. Effectiveness indicators:
1) Reduction rate of equivalent spherical error progression within 12 months (ΔSE,
unit: D)

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2) Reduction in axial length growth within 12 months (△AL, unit: mm)
3) Adverse reaction incidence rate (refer to the adverse reaction type statistics in the
package insert), with "1-Adverse reaction incidence rate" serving as a supplementary safety
efficacy indicator
Key indicator calculation
Unit efficacy cost = Total input cost of low-concentration atropine / Corresponding
efficacy index value
2. Analytical Methods
The following analyses were conducted using "external real-world controls" as the
benchmark for comparison.
(1) Cost-Effectiveness Ratio (CER): Calculate the "cost per 0.25D delay in equivalent
spherical lens progression" and "cost per 0.1mm delay in axial length growth" for the trial
group, and compare these with the CER of the external control to evaluate the
cost-effectiveness of the product.
(2) Incremental cost-effectiveness ratio (ICER): ICER = (total cost of the trial
group-total cost of the control group) / (effect of the trial group-effect of the control group).
Using 3 times China's per capita GDP as the economic threshold, if the ICER is below this
threshold, the trial drug is considered to have economic advantages.
3. Sensitivity Analysis
The robustness of the results was verified through single-factor sensitivity analysis
(fluctuation simulation of ±10% for product procurement price, ±5% for diagnosis and
treatment costs, and ± 15% for efficacy indicators) and probabilistic sensitivity analysis
(Monte Carlo simulation 1000 times, assuming costs follow a Gamma distribution and
efficacy follows a Beta distribution).
12.4 Long-term Economic Value Prediction Model (Markov Model)
Based on the clinical characteristics of low-dose atropine treatment for pediatric
myopia (long-term progression and dynamic changes in complication risk with myopia
severity) and the "China Pharmacoeconomic Evaluation Guidelines (2011 Edition)", the
Markov model (for long-term cost-effectiveness analysis) and the Budget Impact Analysis

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(BIA) model (for short-term health insurance budget prediction) were selected as core
prediction tools.
1. Health Status Classification
health status
Definition (SER range/clinical characteristics)
S1: Mild myopia
SER (Equivalent Sphere Refractive Power): -0.5 to>-3.0D, no
complications
S2: Moderate myopia
SER: -3.0 to>-6.0D, no complications
S3: High myopia
SER ≤-6.0D, no complications
S4:
Myopia-Related
Complications
concomitant with one or more complications such as retinal
detachment, macular degeneration, or glaucoma
S5: Death
All-cause death (model termination state)
2. Key Model Assumptions
1) Basic case analysis
•
Core outputs: Incremental cost-effectiveness ratio (ICER) (formula: ICER = (total cost of
low-concentration
atropine
group-total
cost
of
SVL
group)
/
(total
QALY
of
low-concentration atropine group-total QALY of SVL group)), lifetime QALY gain, and
lifetime cost difference.
•
Predictive logic: Low-dose atropine reduces the incidence of high myopia and its
subsequent complications by decreasing the transition probability from S1 to S2 to S3,
thereby achieving "cost increment ≤health benefit increment".
2) Sensitivity Analysis
•
Single-factor sensitivity analysis: Testing the impact of key parameter fluctuations on ICER,
with key parameters including low-concentration atropine efficacy, drug price, and high
myopia complication risk
•
Probability sensitivity analysis: Monte Carlo simulation (1000 iterations) was employed to
randomly sample all parameters (cost parameters followed a gamma distribution,
utility/transit probabilities followed a beta distribution), generating cost-effectiveness
acceptable curves (CEACs) to evaluate the probability of low-concentration atropine being
cost-effective under different payment thresholds.

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3) Subgroup Analysis
Calculate the ICER separately for key subgroups in clinical practice that may affect
cost-effectiveness:
•
Age: 4–8 years (early-onset myopia) vs. 9–16 years (late-onset myopia)
•
Combined optical interventions: monocular glasses vs combined orthokeratology (OK)
lenses vs combined defocused spectacle frames
•
Medication adherence: High adherence (adherence rate ≥70%) vs. Moderate adherence
(70%> adherence rate ≥30%) vs. Low adherence (adherence rate <30%)
13、Analysis of drug proportion effect
13.1 Definitions and Scope of Measurement
Definition of drug cost proportion: The proportion of "drug expenses" incurred by
subjects during the trial period (from screening to 6-month follow-up, potentially extended
to 48 weeks as appropriate) relative to the "total medical expenses" during the same period.
•
Medication costs: including the cost of low-concentration atropine eye drops, medications
for adverse reaction management (e.g., anti-allergic eye drops), and ocular medications
permitted for concomitant therapy (to be noted in the case report form).
•
Total treatment cost: Medication cost + Examination cost (essential/optional examinations
for this study) + Basic orthodontic consumables cost (e.g., off-focus frame lenses, OK
lenses, only for combined treatment-related purposes) (see Appendix 1)
13.2 Data Collection and Methods
(1) Data Sources
•
Hospital system data: Extract "drug revenue" and "examination revenue" for
subjects at each visit point (screening period, 1M,3M,6M) through the hospital
HIS system, and cross-reference with the "Cost Detail Record Form" in the CRF to
ensure data traceability.
•
Manual verification: For consumables expenses related to combined therapies (e.g.,
OK lenses), the brand, procurement date, and amount must be recorded in the CRF
to exclude non-study period consumable replacement costs.
(2) Collection Time Nodes

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Visit stage
Collect content
Screening period (D-14
to D0)
Basic examination fee, initial prescription fee (if required)
3M follow-up (M3±2W)
Drug costs (adjusted accounting), follow-up examination fees, and combined
treatment consumables costs (if newly added)
6-month
follow-up
(M6-2W)
Drug costs (adjusted accounting), follow-up examination fees, and combined
treatment consumables costs (if newly added)
9M follow-up (M9±2W)
Drug costs (adjusted accounting), follow-up examination fees, and combined
treatment consumables costs (if newly added)
12-month
follow-up
(M12-2W)
Summary of drug costs, end-of-life examination fees, and cumulative
drug/examination/consumable expenses over 6 months
13.3 Comparison Benchmark
(1) Internal benchmark: The average proportion of medication costs for myopic
patients aged 4-16 years in the pediatric ophthalmology outpatient department of the
hospital during 2024-2025 (provided by the hospital's medical insurance office, excluding
cases of non-standard medications such as systemic anti-infective drugs)
(2) External benchmark: The "Target for Controlling the Proportion of Pediatric
Outpatient Medications in Secondary and Above Hospitals by 2025" issued by the National
Health Commission (NHC) (subject to the latest policy documents)
13.4 Analytical Methods
(1) Descriptive analysis: Calculate the mean proportion of medication (±standard
deviation) for all subjects, and perform subgroup analysis based on "frequency of
medication (once daily/twice daily)" and "whether adverse reactions occurred (yes/no)", to
observe differences in the proportion of medication among subgroups and their underlying
causes.
(2) Compliance assessment: Compare the proportion of trial drugs with internal
benchmarks and external control targets
•
If the proportion of trial drugs is ≤the control target, it is determined to comply
with the hospital's drug proportion management requirements;

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•
If the proportion of trial drugs exceeds the control target, a detailed analysis of the
reasons for the overrun (e.g., increased dosage of trial drugs, increased use of
medications for adverse event management, etc.) should be conducted, and
optimization recommendations should be proposed.
14、test schedule
Upon receiving the ethics committee approval and the investigational drug, each
clinical unit shall conduct clinical studies in accordance with the clinical research protocol,
aiming to complete the assigned number of clinical trial cases within 14 months.
Principal Investigator: Date: Year Month Day
Principal Investigator: Date: Year Month Day

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Appendix 1 Basic Medical Related Cost Record Form
order
number
cost item
unit
Fill in by center
(RMB)
Data source/Notes
1
Unit
purchase
price
of
low-concentration
atropine
eye drops
Yuan
per
box
Hospital
Drug
Procurement
Ledger/HIS
System
Drug
Outbound Record
2
Total medication cost for a
6-month
basic
medication
cycle
Yuan
Hospital
Drug
Procurement
Ledger/HIS
System
Drug
Outbound Record
3
Cost of cycloplegic refraction
CNY
per
session
Hospital
Medical
Service
Price List/Patient Visit
Fee
Details
4
Number
of
cycloplegic
refraction tests
Next
Patient
Visit
Fee
Details/Medical Record
5
Cost
of
ocular
biological
parameter measurements
CNY
per
session
Hospital
Medical
Service
Price List/Patient Visit
Fee
Details
6
Number of ocular biometric
parameter measurements
Next
Patient
Visit
Fee
Details/Medical Record
7
Intraocular
pressure
measurement cost
CNY
per
session
Hospital
Medical
Service
Price List/Patient Visit
Fee
Details
8
Number
of
intraocular
pressure measurements
Next
Patient
Visit
Fee
Details/Medical Record
9
Fundus photography cost
CNY
per
session
Hospital
Medical
Service
Price List/Patient Visit
Fee
Details
10
Number
of
fundus
photographs
Next
Patient
Visit
Fee
Details/Medical Record
11
cost
of
anterior
segment
CNY
Hospital
Medical
Service

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photography
per
session
Price List/Patient Visit
Fee
Details
12
Number of anterior segment
photographs
Next
Patient
Visit
Fee
Details/Medical Record
13
Cost of slit lamp examination
CNY
per
session
Hospital
Medical
Service
Price List/Patient Visit
Fee
Details
14
Number
of
slit
lamp
examinations
Next
Patient
Visit
Fee
Details/Medical Record
15
Adjustment fee for functional
testing
CNY
per
session
Hospital
Medical
Service
Price List/Patient Visit
Fee
Details
16
Adjust
the
number
of
function tests
Next
Patient
Visit
Fee
Details/Medical Record
17
OCTA cost
CNY
per
session
Hospital
Medical
Service
Price List/Patient Visit
Fee
Details
18
OCTA number of times
Next
Patient
Visit
Fee
Details/Medical Record
19
Cost of glasses
CNY
per
session
Patient
Visit
Fee
Details/Medical Record
20
Number of glasses fitted
Next
Patient
Visit
Fee
Details/Medical Record
21
Other related examinations,
training costs, and frequency
CNY
per
session
Hospital
Medical
Service
Price List/Patient Visit
Fee
Details

PROTECT Study: A Prospective Study to Optimize the Atropine Concentration Staircase Protocol for Myopia Prevention
in Children Version: V1.0 Version Date: January 19,2026
PROTECT Study: A Prospective Study to
Optimize the Atropine Concentration Staircase Protocol for Myopia Prevention in Children Version: V1.0 Version Date:
January 19,2026
Appendix 2 Record Form of Economic Indicators
definition
unit
Fill in by
center
statistical description
direct
cost
Drug cost
Yuan
Total
medication
cost
for
a
6-month
basic
medication cycle
Cost
of
spectacles
Yuan
Total cost of glasses for 6 months
check cost
Yuan
Total number of required examinations during the
follow-up
period
(ciliary
muscle
paralysis
computerized
refraction,
axial
length
measurement, intraocular pressure testing, fundus
photography) and associated costs
adverse
reaction
management
cost
Yuan
Additional medical expenses incurred due to
adverse drug reactions (e.g., photophobia, allergic
conjunctivitis), including costs for symptomatic
medications (e.g., antihistamine eye drops) and
adjunctive interventions (e.g., tinted contact lens
fitting).
indirect
cost
family
transportation
expenses
Yuan
Transportation
costs
for
children
and
accompanying parents to visit the research center
for follow-up
Incremental
Cost-Effectiveness
Ratio (ICER)
Yuan
/QALY
ICER
=
Incremental
Cost/Preventive
Effect,
between groups