Characterization of Patients With Geographic Atrophy (GA) in the US
Conditions: Geographic Atrophy
Sponsor: Boehringer Ingelheim

001-MCS-90-118_RD-23 (3.0)
TITLE PAGE
Non-Interventional Study (NIS) Protocol 
TITLE PAGE
Document Number:
N/A
BI Study Number:
1484.0014
BI Investigational
Product(s):
N/A
Title:
Characterization of patients with Geographic Atrophy (GA) in 
the US
Brief lay title:
Patients with Geographic Atrophy and their patient journey in 
the US
Protocol version 
identifier:
V1.0
Date of last version of 
protocol:
04-05-2023
PASS:
No
EU PAS register 
number:
N/A
Active substance:
N/A
Medicinal product:
N/A
Product reference:
N/A
Procedure number:
N/A
Marketing authorisation 
holder(s):
N/A
Joint PASS:
NO
Research question and 
objectives:
To describe and quantify patients with a GA diagnosis in at least 
one eye, and the progression to wAMD (including how many 
receive Anti-Vascular Endothelial Growth Factor (Anti-VEGF) 
treatment) in both eyes and the progression to GA (in the fellow 
eye).
Country(-ies) of study:
United States of America
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001-MCS-90-118_RD-23 (3.0) 
1. 
TABLE OF CONTENTS 
TITLE PAGE .................................................................................................................. 1 
1. 
TABLE OF CONTENTS ....................................................................................... 3 
2. 
LIST OF ABBREVIATIONS ................................................................................ 5 
3. 
RESPONSIBLE PARTIES .................................................................................... 6 
4. 
ABSTRACT ........................................................................................................... 7 
5. 
AMENDMENTS AND UPDATES ....................................................................... 9 
6. 
MILESTONES ..................................................................................................... 10 
7. 
RATIONALE AND BACKGROUND ................................................................ 10 
8. 
RESEARCH QUESTION AND OBJECTIVES ................................................. 11 
9. 
RESEARCH METHODS .................................................................................... 11 
9.1 
STUDY DESIGN ............................................................................................ 11 
9.1.1 
Study population ..................................................................................... 12 
9.2 
SETTING ........................................................................................................ 14 
9.2.1 
Study sites ............................................................................................... 14 
9.2.2 
Study visits .............................................................................................. 15 
9.2.3 
Study discontinuation .............................................................................. 15 
9.3 
VARIABLES .................................................................................................. 15 
9.3.1 
Exposures ................................................................................................ 15 
9.3.2 
Outcomes ................................................................................................. 16 
9.3.2.1 
Primary outcomes ............................................................................. 16 
9.3.2.2 
Secondary outcomes ......................................................................... 18 
9.3.3 
Covariates ................................................................................................ 18 
9.4 
DATA SOURCES ........................................................................................... 20 
9.5 
STUDY SIZE .................................................................................................. 21 
9.6 
DATA MANAGEMENT ................................................................................ 21 
9.7 
DATA ANALYSIS ......................................................................................... 22 
9.7.1 
Main analysis ........................................................................................... 22 
9.7.3 
Safety Analysis ........................................................................................ 26 
9.8 
QUALITY CONTROL ................................................................................... 26 
9.9 
LIMITATIONS OF THE RESEARCH METHODS ...................................... 26 
9.10 
OTHER ASPECTS ......................................................................................... 27 
9.10.1 
Data quality assurance ............................................................................. 27 
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9.10.2 
Study records ........................................................................................... 28 
9.10.3 
Completion of study ................................................................................ 28 
10. 
PROTECTION OF HUMAN SUBJECTS .......................................................... 28 
10.1 
STUDY APPROVAL, PATIENT INFORMATION, AND INFORMED 
CONSENT ...................................................................................................... 28 
10.2 
STATEMENT OF CONFIDENTIALITY ...................................................... 28 
11. 
ADVERSE EVENT AND SERIOUS ADVERSE EVENT COLLECTION AND 
REPORTING ....................................................................................................... 28 
12. 
REPORTING TO HEALTH AUTHORITIES .................................................... 29 
13. 
PLANS FOR DISSEMINATING AND COMMUNICATING STUDY RESULTS
 ............................................................................................................................. 29 
14. 
REFERENCES .................................................................................................... 29 
14.1 
PUBLISHED REFERENCES ......................................................................... 29 
14.2 
UNPUBLISHED REFERENCES ................................................................... 29 
15. 
ANNEX 1. ADDITIONAL INFORMATION ..................................................... 29 
Codes Appendix.xlsx .................................................................................................... 29 
ANNEX 2. REVIEWERS AND APPROVAL SIGNATURES ................................... 30 
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2. 
LIST OF ABBREVIATIONS 
ADR 
Adverse Drug Reaction 
AE 
Adverse Event 
AESI 
Adverse Event of Special interest 
CA 
Competent Authority 
CCDS 
Company Core Data Sheet 
CI 
Confidence Interval 
CML 
Local Clinical Monitor  
CRA 
Clinical Research Associate 
CRF 
Case Report Form 
CTCAE 
Common Terminology Criteria for Adverse Events 
CTP 
Clinical Trial Protocol 
eCRF 
Electronic Case Report Form 
ENCePP  
European Network of Centre’s for Pharmacoepidemiology and Pharmacovigilance  
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GEP 
Good Epidemiological Practice 
GPP 
Good Pharmacoepidemiology Practice 
GVP 
Good Pharmacovigilance Practices 
IB 
Investigator’s Brochure 
IEC 
Independent Ethics Committee 
IRB 
Institutional Review Board 
MAH 
Marketing Authorization Holder 
MedDRA 
Medical Dictionary for Regulatory Activities 
NIS 
Non-Interventional Study 
PASS 
Post-Authorization Safety Study 
SAE 
Serious Adverse Event 
Anti-VEGF 
Anti-Vascular Endothelial Growth Factor 
CPT 
Current Procedural Terminology 
CRT 
Central Retinal Thickness 
DCC 
Distance with correction 
DSc 
Distance without correction 
EHR 
Electronic Health Records 
EMR 
Electronic Medical Records 
ETDRS 
Early Treatment Diabetic Retinopathy Study 
HCPCS 
Healthcare Common Procedure Coding System 
ICD 
International Classification of Diseases 
IOI 
Intraocular inflammation 
I/E 
Inclusion/Exclusion 
wAMD 
Neovascular Age-Related Macular Degeneration 
NCC 
Near with correction 
NSc 
Near without correction 
OCT 
Optical coherence tomography 
PH 
Pinhole 
PHI 
Protected Health Information 
SD 
Standard deviation 
SQL 
Structured query language 
VA 
Visual Acuity 
GA 
Geographic Atrophy 
eCNV 
Exudative choroidal neovascularization 
 
 
 
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3. 
RESPONSIBLE PARTIES 
Associate 
 of Ophthalmology 
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4. 
ABSTRACT 
 
Name of company: 
Boehringer Ingelheim 
Name of finished medicinal product:  
NA 
Name of active ingredient:  
NA 
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Protocol date:  
05-04-2023 
Study number: 
1484.0014 
Version/Revision: V1.0 
Version/Revision date: 
 
Title of study: 
Characterization of patients with Geographic Atrophy (GA) 
Rationale and 
background: 
There are many unknowns regarding the natural history of patients with GA, and 
limited data on the natural history of the disease. Recent results, presented in 
2021 [1] 
 developed for the treatment of GA found a 
substantial number of patients with exudative choroidal neovascularization 
(classified as wAMD throughout the protocol) in the fellow eye or converting to 
eCNV in the study eye during the studies. These data might have affected the 
, and this population of patients may potentially 
impact the planned activities of BI. In 
clinical trial, a 
high rate of conversion in the study eye occurred. This high rate of conversion 
may be influenced by the proportion of patients with wAMD present in the 
fellow eye.  This project aims to provide clarity on the proportion of patients in 
the real world with GA, eCNV and focuses on both the study eye and fellow eye 
conversion rates, while also describing functional and imaging results, as well as 
treatment patterns. 
Research 
question and 
objectives: 
This study aims to quantify and describe patients with a GA diagnosis in one eye,  
and progression in the study eye and the fellow eye to wAMD, or to GA (in the 
fellow eye), and the associated treatment journey. 
Study design: 
This is an observational study, using existing data; The
 Database. 
Population: 
Patients attending a retina specialist, contributing to the 
Database. Patients will be identified in the database from January 1, 2015, to 
April 30, 2023. 
From those, our study population will be patients ≥50 years with a GA diagnosis 
in at least one eye will be eligible for this study.  
 
The study period was selected to be able to identify patients with GA using the 
ICD-10 codes introduced in that year. The period from January 2015 until 
October 1st, 2015 will be used to identify patients diagnosed with ICD-9 codes 
and further classify them as new cases or patients with an previous diagnoses. 
Variables: 
A primary outcome variable is visual acuity (VA), reported using converted 
Early Treatment Diabetic Retinopathy Study (ETDRS) letters. 
 
 
Demographic characteristics – including age, gender, patient history, visit 
history 
Clinical Characteristics – including ocular comorbidities, lens status, systemic 
conditions   
Data sources: 
The
 database consists of de-identified Electronic Health 
Records from a geographically diverse panel of 360+ United States based 
private retinal specialists contributing data from 70+ practices. Over the datasets 
entire history, there have been about 2 million patients and about 13 million 
patient visits.   
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Study size: 
All patients available in the database and meeting the study criteria will be 
included. 
 The 
 includes approximately 400,000 patient eyes diagnosed 
with dry AMD, and around 70,000 patients diagnosed with GA during the study 
period. After the initial feasibility analysis, it is expected, given the study criteria, 
that there will be around 100,000 eyes included. However, this number might 
change in the final analysis. 
Data analysis: 
In this study, both patients and eyes will be considered as the analysis unit.  
Baseline characteristics will be summarized using descriptive statistics. For 
continuous variables, the mean, standard deviation, median and range will be 
presented. For categorical variables frequency and proportion will be used. 
Variables are identified and calculated at the index diagnosis and throughout the 
follow-up period for primary outcomes like VA. 
In the progression analysis, the population will be restricted to patients with a 
minimum follow–up time (i.e. multiple visits at least one year apart, at least two 
year), or patients with valid VA reading at the index diagnosis and a second 
follow-up timepoint.
 
  
The analysis of incident and prevalent calculations will use as the denominator, 
all patients referred to the retinal specialist. The proportion of patients with a 
GA diagnosis referred to the retinal specialist will be put into perspective by 
comparing to other conditions, such as proportion of patients referred to the 
retinal specialist with a diabetic macular edema (DME) diagnosis, or with a 
diabetic retinopathy (DR) diagnosis etc. Additionally, extrapolations will be 
done to approximate to a population-based estimate.  
Milestones: 
 
  Start of data collection 
05/2023 
End of data collection 
06/2023 
Final report of study results 
06/2023 
5. 
AMENDMENTS AND UPDATES 
None 
 
 
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6. 
MILESTONES 
 
Milestone 
Planned Date 
IRB/IEC approval 
NA 
Start of data collection 
05/2023 
End of data collection 
06/2023 
Registration in the EU PAS register 
NA 
Final report of study results 
06/2023 
 
7. 
RATIONALE AND BACKGROUND 
GA is the late-stage form of dry age-related macular degeneration (AMD) and responsible for 
10-20% of the legally blind cases. Currently, there is only one treatment for GA available for 
patients, 
 is not approved by EMA yet and 
therefore not available for patients in Europe Patients with wet AMD (wAMD), another 
advanced form of AMD, can be treated with Anti-VEGF treatment.  
 
Presently, Boehringer Ingelheim (BI) is developing potential treatments for the target 
population of patients with GA secondary to AMD 
 
 
  
There are many unknowns regarding the natural history of patients with GA, and limited data 
on the prevalence, incidence, and progression of the disease. Recent results from clinical 
trials developing treatments for GA
 found a 
substantial number of patients with wAMD in the fellow eye or converting to wAMD (20 to 
40%) 
 
 
 the 
 a high rate of conversion to wAMD 
in the study eye occurred. This high rate of conversion may be influenced by the proportion 
of patients with wAMD present in the fellow eye.  This project aims to provide clarity on the 
proportion of patients in the real world, with GA, wAMD in both study and fellow eyes, and 
the conversion rates, describing also functional and imaging results and treatment patterns. 
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8. 
RESEARCH QUESTION AND OBJECTIVES 
Research Question 
 
To quantify and describe patients with a GA diagnosis in at least one eye,
 
 
 
 
 
Primary objectives 
To describe the characteristics* of patients with GA in at least one eye.  
 
To describe characteristics* of the study eye and the fellow eye, at index diagnosis  
 
 
 
To evaluate and characterize the progression of newly diagnosed patients with GA during 
each year for 5-year follow-up period. In particular, to describe patients’ characteristics, 
study eye and the fellow eye characteristics over the 5-years follow up.
 
 
 
  
 
Secondary objectives 
To determine the first time occurrence  of GA in the study eye, during the study period.  
 
To determine the proportion of patients with GA in the study eye, over the study period.  
 
To compare the GA first time occurrence and the proportion of GA, relative to other retinal 
conditions, and relative to proportion of retinal specialist contributing to 
 and the 
overall US retinal specialist.  
 
To evaluate patients’ management (i.e. patients visits and procedures) over the study period. 
 
To describe 
 
the overall GA population. 
 
9. 
RESEARCH METHODS 
9.1 
STUDY DESIGN 
This is an observational cohort study based on existing data.  
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9.1.1 
Study population 
Study inclusion criteria: All patients ≥50 years, with a GA diagnosis in at least one eye, 
including in the 
 database identified during the study period (January 2015 to April 
2023). 
 
Exclusion criteria: Patients without the information of laterality will be excluded.  
No other exclusion criteria are applied for the identification of the study population and 
description of the patients and eye at baseline.  
 
Additional note: 
For certain analysis the patient population will be restricted to those with at least 12, 24, 36, 
48, or 60 months of history following diagnosis of GA. For the analysis requiring a VA 
reading, a restriction to those patients with valid VA readings at the index diagnosis and the 
respective follow-up times will be applied.   
 
For analysis estimating the size of the GA population relative to other retinal diseases, the 
same timeframe requirements that the study population will be applied. In this population, 
any patient in the database will be eligible, and the diagnosis of DME, DR or other conditions 
may be used for subgroup comparisons.  
 
Primary Disease Definitions  
In the 
Database, retinal and other diseases are identified using the 
International Classification of Diseases (ICD), Tenth Revision, Clinical Modification. ICD 10 
codes were launched in the USA in October 2015, and are the only version of ICD codes with 
adequate descriptions of GA and dry AMD severity. As such, only ICD 10 codes will be 
analyzed in this study and the study period defined above is directly related to the launch of 
ICD 10 plus a small buffer allowing for physician familiarity.  
These codes are entered by the physician at patient visit, with an associated laterality. This, 
along with the ICD 10 laterality is used in combination to confirm in which eye the disease is 
occurring.  For this study, a patient eye will be considered to have the study disease so long 
as there is an accompanying ICD code. The primary study diseases to be analyzed are dry 
AMD, GA and wAMD, and will be identified using the ICD codes in Table 1 below.  
 
Table 1. Study disease definitions-codes. 
*a comprehensive list of all AMD ICD codes is included in the Appendix 
 
Study Disease Definitions 
 
Dry AMD* 
Dry AMD with GA* 
wAMD* 
ICD 10 
H35.311X, 
H35.312X, 
H35.313X, 
H35.319X 
H35.3113, H35.3114, 
H35.3123, H35.3124, 
H35.3133, H35.3134, 
H35.3193, H35.3194 
H35.321X, H35.322X, 
H35.323X,  H35.329X 
ICD 9 (2015 only) 
362.51 
N/A 
362.52 
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Patients could have simultaneously a diagnosis of wAMD and GA in the same eye. If both 
conditions are present, wAMD will be described as part of the comorbidities of the study or 
fellow eye. Patients could also have other ocular comorbidities affecting VA (section 9.3.3), 
those will be described and for the progression analysis will be analyzed separately.  
 
For the follow-up analysis in the study eye or fellow eye, results will be described for all GA 
patients, patients with GA and wAMD, and patients with patients with GA only (without 
wAMD or other ocular comorbidities).  
 
As the progression analysis tracking multiple different metrics across 2 eyes, it will be 
conducted at the patient level. Bilateral AMD disease is quite common (and will be 
identified), therefore the following methodology will be used to identify the ‘Study’ 
(primary) eye and the ‘Fellow’ (secondary) eye: 
 
Study Eye – The first study eye in patient history identified with GA in the 
 database.  
GA is the only identifying disease in this case, and wAMD or dry AMD (without GA) in the 
study eye is not taken into account for study eye definition. If patients are bilaterally 
diagnosed, the study eye will be selected at random. 
Fellow Eye – is defined as the other eye in a patient having their study eye diagnosed with 
GA. The fellow eye can have dry AMD, wAMD, GA or other retinal conditions. The fellow 
eye will be followed for progression purposes throughout the study. 
 
Disease Status 
Patient eyes will be identified at every visit throughout the study period to estimate the first 
time occurrence of GA and to estimate the proportion of patient with the disease over the 
years of the study period. Each visit will be classified as either an incident or a prevalent 
visit, defined below: 
Incident visit – The first visit in patient eye history identified with GA in the
 
database. This timepoint also acts as each patients’ index diagnosis. The incident visit may 
only occur once and contribute to one calendar year.  
Prevalent visit – all visits following the incident visit in patient eye history while identified 
with GA in the 
 database. Prevalent visits may occur year after year throughout the 
patients’ journey. 
 
Study period  
Patients will be identified from January, 2015 to April, 2023.  
 
Selection period: Eligible patients must have at least one GA diagnosis between October 
2015 and April 2023. The date of the first GA diagnosis will be considered as index date. For 
all follow up analysis, eligible patient eyes should be divided in those with at least 12, 24, 36, 
48 and 60+ months of follow up. follow up requires multiple visits spanning over the outlined 
durations and total follow up is defined as the time between incident diagnosis and the final 
visit in the dataset.  
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Follow-up period: up to 60-month period following the index diagnosis date of GA 
(exploratory follow-up of 1, 2, 3, 4, 5 years may be run as cutoff points) 
 
Pre-selection period: January 2015-September 2015. This period will be used to identify 
patients who have dry AMD using ICD9 coding, and will help to assign patients into the 
incidence or prevalence status.  
 
9.2 
SETTING 
9.2.1 
Study sites 
All data in this study is de-identified, from existing electronical health records from the 
retinal specialist practices included in the 
 Database (US).  
 
The
database consists of data from a geographically diverse panel of United 
States based private retina specialists (RS). 
 has physician coverage from 
2015 onwards, totaling up to 360+ physicians coming from 70+ practices. These practices 
span across the USA geographically, with the regional distribution as follows: Midwest 
(20%), Northeast (17%), Southeast (27%), Southwest (11%), West (26%). This collection of 
practices has contributed 2+ million patients and 13+ million patient visits over the lifetime 
of 
and is estimated to account for 15-20% of all retina specialists practicing 
in the USA. This dataset represents a collection of private practicing retina specialists in the 
USA, no data is collected from hospital or public institutions. 
 
The 
 Database therefore includes longitudinal measures of physician findings 
and patient outcomes. This includes health related outcomes such as deterioration of visual 
acuity, poor adherence, subretinal fluid, intraocular pressure, and geographic atrophy. Patient 
phenotypes and individual outcomes can be described by individual comorbidities, 
demographics, visits, prescriptions, and other relevant clinical characteristics gathered from 
clinical codes, patient provided information and text mining of patient notes.  
 
Study Subgroups 
Following analysis on the overall population, subjects will be placed into subgroups for 
further analysis. Below are the proposed subgroups which may be subject to modification 
following data readouts. An initial feasibility will be run to assess each threshold for each 
subgroup, following which a final subgroup will be chosen. Any analysis (i.e. description of 
patients characteristics and progression) on subgroups will be defined below. 
- 
Duration of follow up:  1+, 2+ 3+, 4+,5+ years of history 
- 
Newly diagnosed patients with GA vs. patients with an existing GA diagnosis  
- 
Conversion rates over time – Stratify the population into those that either progress/don’t 
progress in the 1+, 2+ 3+, 4+,5+ years of follow up;  
- 
 in the 1, 2, 3, 4 and 5 
years of follow up period. 
- 
 Patients 
 that do not in the 1, 2, 3, 4 and 
5 years of follow up period.  
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- 
GA lesion location (sub foveal vs extrafoveal) 
- 
GA lesion size. 
9.2.2 
Study visits 
As this is an observational study based on existing data, no study visit plan is applicable in 
this study.  
9.2.3 
Study discontinuation 
This is an observational study based on existing data. No enrollment of patients is planned.  
Boehringer Ingelheim reserves the right to discontinue the study overall at any time for the 
following reasons: 
1. Emergence of any effectiveness/safety information that could significantly affect 
continuation of the study, or any other administrative reasons 
2. Violation of Good Pharmacoepidemiology Practice (GPP), the study protocol, or the 
contract by a study site, investigator or research collaborator, disturbing the appropriate 
conduct of the study 
The investigator/ the study site/research collaborator will be reimbursed for reasonable 
expenses incurred in case of study/site termination (except in case of the third reason). 
9.3 
VARIABLES 
9.3.1 
Exposures 
Study Treatments 
The treatment variables below are identified at the patient eye level and will be used to 
describe the treatment patterns throughout the analysis. These treatment variables will be 
analyzed throughout the entire study period. Each treatment type can only occur once per 
patient eye visit and will be identified at every distinct visit where the following codes are 
present. Treatment must contain both the Current Procedural Terminology (CPT) codes for 
intravitreal injection and the J-codes specifying the study treatment (Table 2). 
Though not common, it is possible for multiple different treatment types to occur on the same 
day, in which case both treatments would be captured for analysis i.e., a patient could get a 
laser and an injection at the same visit. 
Table 2. Study Treatment Definitions 
 
Study Treatment Definitions 
Treatment 
CPT Code 
 
 
 
, C9214, C9257, 
Q9977 
Eylea- J0178, C9291, Q2046 
Lucentis-J2778, C9233 
Beovu- J0179 
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Susvimo – C9093, J2779 
Byooviz- Q5124 
Vabysmo- J2777, C9097 
Cimerli- C9097, Q5128 
 
Corticosteroids 
Intravitreal Injection – 67028 
Ozurdex-J7312 
Triamcinolone-J3300, J3301 
Iluvien-J7313 
Yutiq-J7314 
Laser 
Focal Grid Laser- 67210 
Panretinal Photocoagulation-
67228 
Not Applicable 
C3 Inhibitor 
 
J3490, C9399 
 
 will also accept an incoming procedure medication that is associated to an 
 
 
 
9.3.2 
Outcomes 
9.3.2.1 
Primary outcomes 
x 
 
This study will evaluate the disease progression over time.  The main progression 
endpoints will be for the study eye,
, changes in the GA 
lesion location, changes in the VA or changes in the size of the GA lesion.  For the 
fellow eye the progression endpoints will also include the developing of GA.   
*Please see Table 1, that includes the disease definitions (dry AMD, GA, and wAMD) based on ICD 
codes. 
x Position of GA lesion will be assessed over time. The position of GA lesion will be 
defined using ICD 10 coding defined below. Any change in location status will be 
identified as progression of GA 
Study Disease Definitions-lesion location 
 
GA without Subfoveal Involvement  
GA with Subfoveal Involvement  
ICD 10 
H35.3113, H35.3123, H35.3133, H35.3193,  
H35.3114, H35.3124, H35.3134, H35.3194 
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x Increase in the size of GA lesion will be assessed over time. The size of GA lesion 
will be further defined following feasibility of data availability, with the basis of the 
lesion size defined using text field extracts. An example of text entries available for 
classification are defined below. Note that any analysis involving lesion size will need 
to be run on a subset population where these data are available/documented;  
Small: “Non-Central Geographic Atrophy, Small.”;  
Medium: “Moderate Geographic Atrophy (Juxtafoveal)”; 
Large: “1.5 DD Central Geographic Atrophy, Large.”, “Central Geographic Atrophy, 
Large.”, “4+ Geographic Atrophy.” 
 
x Progression of GA by Visual Acuity 
Change in visual acuity over time will be tracked from the incident date of GA, and 
assessed on a yearly basis in order to track the progression of GA over time. In this 
study, visual acuity will be defined as follows: 
receives VA data from Snellen charts in over 98% of cases, with 
some other types (ex. Jaeger, charts) in the remainder.  There are no instances of 
ETDRS being received since all data are coming from private retina clinics. All VA 
entries are standardized and converted to LogMAR for reporting purposes. 
 
standard output for VA is in the form of
 
  
 will only compare VA results of a patient if vision is taken by the same 
measurement method; i.e., if a patient has their vision recorded using a DCC 
measurement at index diagnosis, for the remainder of the study, only DCC 
measurements will be accepted for comparison. This is done to ensure that any change 
in VA is due to actual change in the patients’ vision, and not due to them taking a 
different vision test. Further, where DCC is not available for VA, any other 
measurements will be used, ensuring the same type of measurement will be used for 
the same eye to estimate the changes over time. The ranking order for measurement 
types is DCC ->NCC ->PH ->DSc ->NSc. 
When capturing VA at different time points of interest, a buffer is allowed on either 
side of the date to increase the chances of each eye coming in for a visit. Should an 
eye have 2 readings inside the buffer window, the reading closest to the date of 
interest is taken. The buffers are proposed as follows: 
x Index Diagnosis: +/- 30 days 
x Follow up reading at Month 6, 12, or 18: +/- 30 days 
x Follow up reading at Month 24, 36, 60: +/- 60 days 
 
Incidence (new cases) and prevalence of GA will be captured, based on the ICD 10 
diagnosis codes. On a calendar basis, all newly diagnosed patients will be identified and 
count as incident patients. Patients with a previous diagnosis of GA in the past years (with 
respect to a given calendar year), will be counted as prevalent cases during that calendar year. 
The yearly counts of newly diagnosed or prevalent cases, will help to understand the 
progression of the overall disease. 
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9.3.2.2 
Secondary outcomes 
x Retinal Disease Related HCRU Outcomes   
Change in physician care over time will be evaluated from the incident date of GA, and 
assessed on a yearly basis in order to assess if physician habits have changed over time, 
particularly following September 2021 and additionally following 
.  
Patient visits: A patient visit (or encounter) is identified in the database any time a patient 
visits one of the panel physicians. Since the 
database consists only of private 
practicing retina specialists, these are the only types of visits analyzed in the study.  
If a patient visits the physician at a hospital, institution, or has an emergency room 
admission, the event will not be captured. For all patient visits, it is assumed that both eyes 
are being seen/assessed even in the primary visit reason is for one particular eye. In this 
sense, all visits will contribute to both eyes and any outcomes at these visits will be available 
for assessment.  
Treatments: The documentation includes all treatments including injections, laser 
treatments, and other procedures. The type of diagnostic procedure done, and the results of 
these diagnostics are also recorded for most encounters. For any visit, it is assumed that both 
eyes are being seen, even if only one eye receives any treatment.  
Other medical procedures: for example, cataracts removal, eye lid (ptosis correction), etc.  
Checkups: While these eyes may be on a different treatment regimen and are only observed 
at this visit, the physician will still track VA, CRT and perform other general check-ups. 
Common reasons for visits include treatment, check-up, post operative follow up, sudden 
vision issues, etc. Visit burden to the retina specialist will be analyzed for the duration of the 
study period and tracked year over year. 
Ocular comorbidities (see section 9.3.3.2) will be described over the study period, yearly. 
9.3.3 
Covariates 
9.3.3.1 Demographic Characteristics: The demographic variables below are identified at 
the patient eye level and will be used to describe the demographic characteristics throughout 
the analysis. These demographic characteristics will be analyzed at the index diagnosis, 
unless specified elsewhere. 
Age: will be calculated based on DOB from index diagnosis (incident visit). 
Sex: identified at index diagnosis, or other visits if not specified.  
Diagnosis year: Identified as the calendar year of the index diagnosis.  
Months of History: will be defined as the time from index diagnosis to their last record in the 
database. 
Incident Visit: The first visit in the database where one of the study diseases is identified, per 
eye. This may include Dry AMD, GA and/or wAMD. At incident visits all clinical 
characteristics, ocular comorbidities, etc. will be also captured. 
Prevalent Visit: The first visit during a time period of interest where one of the study diseases 
is identified, per eye. This may include Dry AMD, GA and/or wAMD. This visit must not be 
the first diagnosis in the entire patient history. At prevalent visits changes in the clinical 
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characteristics, ocular comorbidities will be captured and described based on the first 
prevalent visit per calendar year.  
 
9.3.3.2 Clinical Characteristics  
Presence and Type of diabetes (T1DM/T2DM/Unspecified): Any ICD code identifying a 
specific type of diabetes will be used to identify a patient’s diabetes status. The entire patient 
history prior to or on index diagnosis will be used in the identification process. Diabetes will 
also be identified based on the systemic drugs a patient is taking. Any type 2 drug will 
supersede a type 1 drugs. In the event that a patient has conflicting diabetes status using ICD 
codes and drugs, the ICD code will be used. A list of diabetic drugs can be found in the 
Appendix.  
9.3.3.2.1 Ocular comorbidities defined using ICD codes (where available), listed in 
Appendix:  
Ischemic optic neuropathy    
Glaucoma 
High myopia-pathologic myopia 
Uveitis 
Corneal transplant 
Incisional glaucoma surgery 
Retinal detachment 
Vitrectomy 
Multifocal choroiditis 
Cataracts: Cataracts presence are defined using the ICD-9 and -10 codes to be listed in 
Appendix.  Patient eyes will be identified as having cataracts at the index diagnosis. 
Phakic Lens is an indication that the subject still has their natural lens intact, in the 
 database there will be no way to explicitly identify using “phakic” ICD codes. 
However, there will be several implicit ways in which phakic will be identified in this study: 
-Free-text searches in exam section will be explored, for presence of terms such as ‘clear 
lens’, ‘cataractous lens’ or ‘nuclear sclerosis’.  
-Any ICD code identifying presence of cataracts or nuclear sclerosis (NS) information not 
identified on presence of an intra ocular lens will be used a definition for phakic.  
Pseudophakic Lens will be defined using a combination of ICD Codes [ICD9] V43.1 
or [ICD10] Z96.1[ICD9] 362.83, [ICD10] H35.31, CPT codes and free text searches. 
Table 3: Other clinical conditions definitions-codes (ICD 9 and ICD 10) 
 
 
 
 
       
9.3.3.3 Other variables  
 
 
 
 
 
 
 
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Smoking status will be identified at the patient level (where available). This will be 
observed at or prior to index diagnosis. Free-text searches will be explored, for presence of 
terms such as ‘Tobacco’ or ‘Smoker’ or ‘Smoking’. Smoking status will be identified as one 
of these categories: Smoker, Ex-Smoker, non-smoker or unknown at index. 
Alcohol consumption will be identified at the patient level (where available). This will be 
observed at or prior to index diagnosis. Free-text searches will be explored, for presence of 
terms such as ‘used to drink daily or ‘1-2 week’ or ‘Never. Alcohol consumption status will 
be identified as one of three categories: Drinker, Ex-Drinker, non-Drinker or unknown at 
index. 
9.4 
DATA SOURCES 
Founded in 2014, 
 is the first-to-market EHR data analytics provider in the 
retina space. 
 was founded by practicing retina specialists and data-analytics experts 
with the mission to provide real-world insights from analyzing retina practices’ electronic 
health data. 
 database consists of de-identified data from EHRs from a 
geographically diverse panel of United States based private retina specialists. All data comes 
exclusively from private retina clinics; 
 not collect data from hospitals or 
institutions.
 
by an anonymized patient code assigned by the software vendor. 
Data from multiple sources are organized into the structured database residing in US-based 
cloud servers. Data is maintained in a secure, password-protected environment using 
standards associated with personal health information (PHI). 
 
Data Completeness  
The Electronic Medical or Health Record represents the entire patient file as maintained by 
the treating physician and practice with the exception of diagnostic images. Records are 
continuous regardless of the physician in the practice treating the patient but only to the 
extent the patient is treated in the same practice. The file is therefore a complete record of the 
treatments rendered through the practice.  
Data completeness within an EHR is entirely dependent on the treating physician recording 
diagnostic, treatment and other information. Completion rates vary by data element and 
depend on the treating physician’s opinion of the future utility of the information related to 
that patient’s clinical presentation. Crucial visit information such as Procedures, drugs 
administered, diagnoses, payer, are requires at every visit. Outcomes such as IOP and Visual 
Acuity are entered at 95+% of visits. Foveal thickness is recorded in approximately 30% of 
encounters where an OCT scan was taken. 
 neither adds nor removes information 
received. 
receives the key treatment and outcomes information but does not receive 
every field contained in an EHR.
 does extensive work with physicians analyzing 
their own data through clinical trials or other projects and have not found inconsistencies 
between the data and the physician’s expectation of the data. This iterative process is an 
integral step in ensuring data accuracy and completeness of our data. 
 
Capture of Concomitant Medications/Exposure   
 
Medications administered by the treating retina specialist are identified using the structured 
field containing the relevant J-Code. Each drug is validated during the curation stage. Dates 
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of administration are the dates of the patient visit describing the treatment delivered. Disease 
coding is usually restricted to ocular diseases. Items like diabetes, hypertension or statin use 
must be identified through systemic medications that are received along with the associated 
procedure record. CPT codes are used in conjunction with J-Codes to enable 
 to 
identify both the procedure performed and all associated medications used. When entering all 
fields stated above physicians are also required to attach a laterality code. This allows 
to confidently identify diseases, procedures, medications etc. by each specific eye. 
Anatomical outcomes are captured in our database through data entry fields and through free 
text fields. Physicians prefer to look at the images rather than a value, and 
 does not 
actively receive the images attached to the charts. 
 also receives information on fluid 
status (subretinal, intraretinal, sub-RPE, edema) which will include primarily present/not 
present but can also contain the severity level of the fluid. These are obtained and 
standardized from exam findings in free text fields, where physicians record information 
found during Optical Coherence Tomography (OCTs), Fluorescein angiographies, etc. 
Common descriptions of these types of entries are: “Subretinal fluid OD”, “findings 
consistent with subretinal fluid”. 
9.5 
STUDY SIZE 
During the development of the protocol and while running the projects viability, a feasibility 
was run on the database identifying both patients and eyes with Dry AMD, and specifically 
with GA. This analysis was run using only ICD 10 codes and with the use of exam notes. 
Actual population counts are subject to change based on the dataset available at first data run, 
but all analysis will be based on the assumption that population sizes are relative to these 
numbers.  
GEOGRAPHIC ATROPHY (PERIOD >=2016) (ICD 10 + Exam Notes) 
# of Patients 
72,718  
# of Eyes 
113,408  
Avg months of follow-up 
22  
# of Patients with visits after 3 years 
20,503  
# of Eyes with visits after 3 years  
31,647  
 
9.6 
DATA MANAGEMENT 
extracts data weekly from various EHR vendors where it is then stored on 
secure servers accessible only to 
 has multiple data warehouses 
where an iterative standardization is applied to the data to combine different sources and 
ensure data accuracy. 
Once all data cleansing and standardizing has been performed by 
, a static dataset is 
created specifically for the study to ensure there will be no variation in data for its duration. 
At this point, data accessible for analysis through Microsoft SQL Server Management Studio 
18 and the building of the patient population begins. Only after the study population is 
completed, and all metrics relevant to the analysis have been identified and extracted in 
aggregated form to excel for further analysis and output generation. The statistical software 
used for this analysis will be R – version 3.6.3, which will be used for any statistical analysis 
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performed (t-tests, chi-square test or proportion, Confidence intervals etc.). Graphs and tables 
will be generated using both R and Excel, where applicable. 
No personal data will be provided to Boehringer Ingelheim 
9.7 
DATA ANALYSIS 
9.7.1 
Main analysis 
All analysis will be performed individually on the study population(s). All study results will 
be provided in tables, and key findings will be highlighted and summarized. The analyses 
will be conducted at both the patient and patient eye level, as appropriate. 
 
Analysis for objective:  
To describe the characteristics* of patients with GA in at least one eye. 
To describe characteristics* of the study eye and the fellow eye, at index diagnosis (i.e., 
proportion of patients with GA in the fellow eye, 
 
 
 
All demographics, and clinical characteristics will be summarized at the index diagnosis date 
(first diagnosis of GA in the study eye).   
Characteristics include demographics, comorbidities, comedications (patient level).  
And at eye level; AMD, GA, eCNV, other ocular comorbidities, functional parameters i.e. 
VA. As well as treatments administered prior to or at index. 
Summary will include descriptive statistics; continuous variables will consist of mean (SD) 
and median (IQR) while categorical variables will be described using frequency and 
proportion. Absolute numbers (n) of the variables (either yes or patients as appropriate) will 
be always included in the description of the results.  
 
Analysis for objective:  
To evaluate and characterize the progression of newly diagnosed patients with GA 
during a 5-year follow-up period. To describe patients’ characteristics, study eye and 
the fellow eye characteristics.
 
 or progression of the GA lesion in the study eye. To evaluate changes 
in VA, to evaluate changes in the lesion location, and lesion size (where available).  
 
Patients with GA will be analyzed as an overall group. Subgroups will be also analyzed 
separately: only GA, GA and wAMD, GA and other comorbidities, and bilateral GA at 
baseline. 
Ocular comorbidities will also be tracked longitudinally (yearly) from index date (GA 
diagnosis in the database) to better understand the disease journey. 
 
Disease progression will be analyzed at both patient and each individual eye level. 
Progression to dry AMD,  to GA and to wAMD will be assessed independently using time to 
event analysis, and also the rate of progression that is seen in the study (2nd, 3rd, 4th, and 
5th) years. Bilateral GA eyes at baseline will be evaluated for progression to wAMD 
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For all time to event metrics, mean (SD), median and range will be summarized, while 
proportions will be summarized using N (%). 
 Kaplan Meier or Cox Hazard ratios may be applied when analyzing disease progression. 
Additionally, it will be determined how patients progress during the 1,2,3,4,5 years follow up 
according to the lesion location, and lesion size. 
 
 
Analysis for objective:   
 To determine the occurrence of GA in the study eye during the study period (at the 12 
(24, 36, 48, 60) month follow up period).  
 
The calculation of the occurrence (new cases) of GA will be tracked against the overall 
number of patients included in the retinal specialist database (
 database) in a time 
period (year) as the denominator initially.  
The analysis to calculate the prevalent cases will include all patients with a GA diagnosis 
active in the database in the given time period in the numerator, and all patients included in 
the retinal specialist database (
 database) will be used as the denominator initially.  
Since, this analysis is referring to a population attending a retinal specialist during a given 
time period and therefore is not a general population-based estimates, in order to give a 
context to the data, the proportion of other common diagnosis in patients over 50 years or 
older attending the clinic in the same time period (e.g. diabetic macular edema, diabetic 
retinopathy, proliferative diabetic retinopathy, and wAMD) will be calculated. The 
denominator will be all patients attending to the retina specialist in the given time period 
using the age group category that is applicable in this study (50 years or older).  
For the initial calculations, the look back period in 2015 will be used to discard patients with 
prevalence GA diagnosis in the subsequent years. prior diagnosis will be excluded and only 
new cases diagnosis in the time period will be considered in the numerator when calculating 
incidence. 
The calculations will be conducted by calendar year, and absolute numbers (n) and 
correspondent percentage (%) will be provided. As a sub analysis, it will be evaluated if 
changes occurred after the third quarter of 2021, corresponding with the
 
 
An additional analysis will be made to extrapolate the prevalent results to a national – US-
level. For that analysis, the prevalence of GA will be considering all patients seen by a retina 
specialist in the given year. With this metric, estimation on a national level will be done using 
an estimation of all practicing US retina specialists.  
When analyzing the rate of progression from dry AMD to GA, a conversion analysis will be 
done. This will include the overall rate of dry AMD eyes developing GA, along with a 
Kaplan Meier analysis assessing the rate of conversion over time. This analysis will track 
progression by month from diagnosis, censor any patient at the final visit in the database, and 
identify the incident GA diagnosis as an event. 
 
Analysis for objectives:  
To evaluate patients’ management (i.e. patients visits and procedures) over the study 
period. 
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Patients’ management  
All visits, treatment, checkups, procedures, and other will be summarized across the duration 
of the study time frame as well as between the index diagnosis and at the 12 (24, 36, 48, 60) 
month follow up period.  
An additional sub analysis will be conducted to evaluate the changes in the frequency of 
patients visits or procedures, checkups, after the third quarter of 2021 and after 
 
. 
Summary will include descriptive statistics; continuous variables will be described by 
absolute numbers, the mean (SD), median and range, while categorical variables will be 
described using frequency and proportion. Absolute numbers (n), and correspondent 
percentage (%) of the variables (either eyes or patients as appropriate) will be always 
included in the description of the results. 
 
Analysis for objective:  
To describe and compare patients’ characteristics in different progression subgroups 
(i.e. those that develop eCNV/those that not), of the overall GA population. 
 
The following groups will be evaluated to better understand progression:  
1. Patients that 
 
vs.  those that do not in the 1, 2, 3, 4 and 5 years of follow up period. 
2. Patients that 
 
 vs.  those that do not in the 1, 2, 3, 4 and 5 years of follow up period.  
3. Patients with subfoveal lesion location vs. those with extrafoveal lesion location. 
For this subgroup of patient’s characteristics will be described and compared.  
 
Subgroups will be compared against one another to identify any differences in populations 
leading to progression. The characteristics will be extracted at the time of assignation to the 
group i.e. patient do not 
 in year one is contributing with his characteristics 
extracted at year 1 to the group (no progressors), that patient 
 at year 5 is 
contributing with his characteristics extracted at year 5 to the progressor group.  
Summary will include descriptive statistics; continuous variables will be described by 
absolute numbers, the mean (SD), median and range, while categorical variables will be 
described using frequency and proportion. For discrete demographics or clinical 
characteristics, chi-squared test of proportion will be done to assess meaningful difference 
(standardized mean difference SMD may be used as an alternative), while continuous 
variables will be analyzed using SMD. Following univariate analysis on each metric, a 
multivariate logistic regression model will be run including relevant metrics identified in the 
univariate analysis.  
 
Additional information on the analysis is described below: 
Patient Demographics (at index and follow up): 
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N (%); Age, gender, region; Bilateral status, other eye related diagnosis in study and fellow 
eye; Distribution by months of follow up; Concomitant illnesses (diabetes, cataract, etc.); 
Lesion location and size (along with % capture rate) 
Progression : Progression of GA over time; Fellow eye AMD status; 
 
(study and fellow eye) Mean (median/IQR) time to conversion; Conversion to GA (fellow 
eye) Mean (median/IQR) time to conversion; Proportion of patients with wAMD and GA (N, 
%) 
Treatment Characteristics (follow up): Number of visits over time; Number of treatments 
over time, Mean (median) time to study treatment; Type of treatment – Anti-VEGF, Laser, 
Combination, Mean (median) time on therapy 
New cases occurrence and prevalent cases of GA (stratified by index year): N (%) 
x Age, gender 
x Distribution by months of follow up 
x Calculation to the % of patients attending the retinal specialist over the same time 
period for other retinal conditions i.e.  wAMD, DR, dry AMD or DME. 
Visual Acuity Outcomes  
N (% capture rate); Mean (median) VA at index; Mean (median) VA at month 12; Change in 
VA from index to the different follow up times, VA distribution by buckets, Change in VA 
based on progression dates  
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9.7.3 
Safety Analysis 
There will be no safety analysis performed in this study  
9.8 
QUALITY CONTROL 
The EMR information
receives is loaded into the input database unchanged. 
The incoming data are subject to quality control steps to ensure all the expected data are 
received and files are complete and readable. Changes in historic data are labeled as such and 
both original and modified values retained.   
 
Input data are transformed into the operational database through a quality assurance process 
to ensure the validity of each data point. Metrics are tracked longitudinally to ensure logical 
consistency visits over visit, and are required to fall within specified limits (thresholds have 
been set using clinical insight from active retina specialists). Incidental Personal Health 
Information (PHI) contained in text fields are removed, information in text strings that 
contain multiple data elements are broken down into separate analyzable and standardized 
cells. 
 
 
  
 
All data shared with BI will be at an aggregated stage, and will be fully de-identified and 
HIPAA compliant 
 
9.9 
LIMITATIONS OF THE RESEARCH METHODS 
As with real world data entered during patient encounters, there are limitations due to the 
entry process and general operations of both physicians and clinics. The 
 database 
includes only data from visits that occurred at the practices contributing to the database. 
Anything occurring during visits to a retina specialist/ophthalmologist in a different practice, 
state, country etc. is not captured.  
 does receive information on previous history, referrals, etc. from overall patient 
history fields in attempt to gain insights on potential previous physicians, however 
 
completely relies upon the physician to enter these data. This is a limitation of the study 
regarding the incidence and prevalence of the study diseases.  
 
Retinal specialists are the primary specialty that will observe and treat all forms of AMD. 
However, there is a portion of mild dry AMD patients who are being observed by their 
general ophthalmologist. As this study will focus on GA specifically, there should not be a 
concern with underrepresentation in the database, as it is the most severe form of dry AMD. 
Out of the 1.6 million eyes with 1+ visit to in the 
 in 2022, dry AMD was 
the most prominent disease with ~180,000 eyes, twice as large as those with wAMD.  
While this study will identify newly diagnosed cases of GA and wAMD, there is a possibility 
that a patient was diagnosed prior by an ophthalmologist or other retina specialist. As these 
are severe versions of AMD that are handled only by retina specialists in the USA, it is a 
limitation that must be addressed.  
Prevalent cases are less affected as per the study definitions they are being seen over a 
multiple year span in the same dataset. While it is possible, they are seeing other healthcare 
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professionals during this time frame, they are continuing to visit their retina specialist for 
follow up. Patients who leave the panel for any number of reasons (death, moving, poor 
experience) are only able to be identified as lost to follow up. No other claim can be made on 
these cases, and for the study purposes they would no longer be included in any analysis from 
that point onwards.   
For portions of the analysis where visual acuity (or other key clinical outcomes) is the 
primary outcome, patients are only included in the analysis when a visual acuity reading was 
available. In this way, it is possible that a bias is occurring in patients who are willing to have 
their vision recorded at every visit, or who are visiting their doctor on a more regular basis. 
 can only analyze visits where VA is taken, any visual acuity gains or losses that 
occur between visits cannot be captured. The last VA taken, or other clinical measures, is not 
automatically carried forward between visits, or in other words, last observation carried 
forward or other automatically carried forward outcomes are not utilized as 
 
standards. These methods are available for exploration, but also carry their own limitations. 
 
Regarding the progression analysis over a 5-year period, one limitation using this database is 
the length of patient follow-up time. While running feasibility, the 
 database showed 
a mean of 1.9 years of follow up. This however also includes patient who were diagnosed in 
2022 for example and do not have the opportunity for 3 years of follow up. One way to 
address this limitation is to restrict those analysis to those patients with at least two entries 
with available data on progression during the follow up, however this may have the caveat to 
reduce the cohort of patients available for analysis. This will be explored during data 
readouts. Alternative methods of analysis such as Kaplan Meier may be a useful alternative to 
mitigate bias when analyzing rates over time. 
 
As an overall limitation of the dataset, Data in the EHR is recorded by the physician or scribe 
under the direction of the physician. Physicians do not tend to enter data that is not directly 
relevant to the patient’s current condition and tend not to enter null information. There is no 
real time validation of the information entered during the encounter either in terms of 
completeness or accuracy. However, 
 works extensively with the physicians 
providing analysis of their own data. As such, this is a crucial step in the data validation 
process, as physicians analyzing their own data over the years has provided insights on better 
coding, data entry and completeness. This limitation will affect the covariates related to 
comorbidities outside of retina. The current workaround is to use the systemic medications 
list provided to identify the treatment of these comorbidities (diabetes, hypertension etc.). 
However, this field also comes with its own limitation of relying on the physician/patient to 
provide an accurate summary of each patient’s medication list.  
 
9.10 
OTHER ASPECTS 
9.10.1 
Data quality assurance 
As this data is retrospective and de-identified in nature, there is no opportunity for patient 
influence and is therefore exempt from IRB review.  
A quality assurance audit/inspection of this study may be conducted by the sponsor. The 
quality assurance auditor will have access to the database. 
 
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Study number: 1484.0014 
Document number: <insert> 
 
001-MCS-90-118_RD-23 (3.0) 
9.10.2 
Study records 
This is a study based on existing data, 
 is an existing database that contained the 
electronical medical records of patients as described in the data source section. 
 
The investigator/institution will permit study-related monitoring, audits, IRB/IEC review and 
regulatory inspection, providing direct access to all related source data/documents. 
CRFs/eCRFs and all source documents, including progress notes and copies of laboratory and 
medical test results must be available at all times for review by the sponsor’s clinical study 
monitor, auditor and inspection by health authorities (e.g. US Food and Drug Administration 
(FDA)).  
 
9.10.3 
Completion of study 
This is a study based on existing data, and there is no EC competent for the use of the 
 database.  
10. 
PROTECTION OF HUMAN SUBJECTS 
This is a study based on existing data and the data analysis will be conducted using 
anonymized patient level information. The use of the 
 database do not require any 
submission or approval from an Institutional Review Board (IRB). 
 
10.1 
STUDY APPROVAL, PATIENT INFORMATION, AND INFORMED 
CONSENT 
The conduct of the study using the 
 database does not required of any Institutional 
Review Board/Independent Ethics Committee approval. No additional Competent Authority 
should be consulted to the initiation of this NIS. As this study is based on existing data, 
patients consent is not necessary to be obtained. 
 
 
10.2 
STATEMENT OF CONFIDENTIALITY 
Individual patient medical information obtained as a result of this study is considered 
confidential and disclosure to third parties is prohibited with the exceptions noted below. 
Patient confidentiality will be ensured by using patient identification code numbers. 
 
Treatment data may be given to the patient’s personal physician or to other appropriate 
medical personnel responsible for the patient’s welfare. Data generated as a result of the 
study need to be available for inspection on request by the participating physicians, the 
sponsor’s representatives, by the IRB/IEC and the regulatory authorities (when applicable).  
11. 
ADVERSE EVENT AND SERIOUS ADVERSE EVENT 
COLLECTION AND REPORTING                                                                        
Not applicable based on secondary use of data without any potential that any employee of BI 
or agent working on behalf of BI will access individually identifiable patient data.  
DocuSign Envelope ID: AEA7567F-2164-4FDD-87EB-978ADEEAF25F

BOEHRINGER INGELHEIM Group of Companies 
NIS Protocol Template 
Page 29 of 30 
Study number: 1484.0014 
Document number: <insert> 
 
001-MCS-90-118_RD-23 (3.0) 
12. 
REPORTING TO HEALTH AUTHORITIES 
Adverse event reporting to regulatory agencies are done by the Marketing Authorization 
Holder (MAH) according to local and international regulatory requirements.  
13. 
PLANS FOR DISSEMINATING AND COMMUNICATING 
STUDY RESULTS 
The rights of the investigators, and of the sponsor with regard to publication of the results of 
this study are described in the “terms of collaboration” document. As a general rule, no study 
results should be published prior to finalization of the Study Report. 
14. 
REFERENCES 
14.1 
PUBLISHED REFERENCES 
[2] Wykoff CC, Rosenfeld PJ, Waheed NK, Singh RP, Ronca N, Slakter JS, Staurenghi G, 
Monés J, Baumal CR, Saroj N, Metlapally R, Ribeiro R. Characterizing New-Onset 
Exudation in the Randomized Phase 2 FILLY Trial of Complement Inhibitor Pegcetacoplan 
for Geographic Atrophy. Ophthalmology. 2021 Sep;128(9):1325-1336. doi: 
10.1016/j.ophtha.2021.02.025. Epub 2021 Mar 10.PMID: 33711380 
 
 
 
 
 
15. 
ANNEX 1. ADDITIONAL INFORMATION 
All definitions of variables outlined during the protocol are summarized in an excel file to 
keep this document concise and for ease of reference. The file has been sent along with the 
protocol and a link can be found here: 
CODES APPENDIX.XLSX 
 
 
DocuSign Envelope ID: AEA7567F-2164-4FDD-87EB-978ADEEAF25F

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Certificate Of Completion
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