Alport Syndrome Foundation Alport Patient Registry
Conditions: Alport Syndrome, Thin Basement Membrane Disease, Hereditary Nephritis
Sponsor: Alport Syndrome Foundation

 
Cover Page 
Alport Syndrome Foundation Alport Patient Registry 
NCT06526741 
04/07/2026 
 
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Alport Syndrome Foundation – Alport Patient Registry 
Protocol Title:​
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         ​ Alport Syndrome Foundation Registry​
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Protocol ID:​
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Pulse-ALP-101-000 
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Principal Investigator:​
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Makabe Aberle 
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Research Coordinator 
Alport Syndrome Foundation 
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Address: ​
P.O. Box 4130 
Scottsdale, AZ    85261-4130 
 
Co-Investigator:​
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Dr. Bradley A. Warady, MD 
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Director, Division of Pediatric Nephrology 
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Director, Division of Dialysis and Transplantation 
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Children’s Mercy Kansas City 
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Address: ​
2401 Gillham Rd., 2MOB.17 
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Kansas City, MO   64108 
 
Sponsor: ​
Alport Syndrome Foundation in collaboration with Pulse 
Infoframe 
Protocol Date:​
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April 7, 2026  
Protocol Version(s):​
1.4 
 
 
 
 
© 2023 All Rights Reserved www.pulseinfoframe.com 
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TABLE OF CONTENTS 
List of Abbreviations and Definition of Terms​
3 
Synopsis/Summary​
4 
1​
Background / Introduction​
7 
2​
Rationale​
8 
3​
Registry Objectives​
8 
4​
Registry Methods​
9 
4.1​
Registry Design​
9 
4.2​
Registry Population, Enrollment and Withdrawal Process​
9 
4.2.1​
Eligibility Criteria​
9 
4.2.2​
Enrollment Process​
10 
4.3​
Informed Consent Process​
10 
4.4​
Participant Withdrawal​
11 
4.5​
Registry Duration and Number of Participants​
11 
5​
Data Source and Data Management​
11 
5.1​
Data Source and Data Collection​
11 
5.2​
Data Management​
12 
5.3​
Data Access​
12 
5.4​
Data Quality and Monitoring​
12 
5.5​
Missing Data​
12 
5.6​
Registry Sample Size and Statistical Power​
13 
6​
Strengths and Limitations of Registry Methods​
13 
6.1​
Strengths​
13 
6.2​
Limitations​
13 
7​
Protection of Participant Confidentiality​
13 
8​
Adverse Events​
14 
9​
Providing Result to Participants​
14 
10​ Use of Information and Publications​
14 
11​ References​
15 
 
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LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
ABBREVIATION 
DEFINITION 
ACE 
Angiotensin Converting Enzyme  
ADAS 
Autosomal Dominant Alport Syndrome 
ADL 
Activities of Daily Living 
API  
Application Programming Interface  
ARAS 
Autosomal Recessive Alport Syndrome 
AS 
Alport Syndrome 
ASF 
Alport Syndrome Foundation 
CDM 
Common Data Model 
EC 
Ethics Committee 
ECRF 
Electronic Case Report Form 
ESRD 
End Stage Renal Disease 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GDPR 
General Data Protection Regulation 
GFR 
Glomerular Filtration Rate 
GUID  
Globally Unique Identifier 
HIPAA  
Health Insurance Portability and Accountability Act 
HITRUST 
The Health Information Trust Alliance 
IRB 
Institutional Review Board 
MDS 
Minimal Data Set 
OMOP 
Observational Medical Outcomes Partnership 
PARTICIPANT 
Subject enrolled in the registry 
PHI 
Protected health information 
PHIPA 
Personal Health Information Protection Act 
PII 
Person Identifying Information 
PRO 
Patient Reported Outcome 
PULSE 
Pulse Infoframe 
QOL 
Quality of Life 
RWD 
Real-World Data 
SAB 
Scientific Advisory Board 
SUBJECT 
An unenrolled potential participant for the registry 
XLAS 
X-linked Alport Syndrome 
 
 
 
 
 
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SYNOPSIS/SUMMARY 
Protocol 
Alport Syndrome Foundation Registry 
Protocol ID 
Pulse-ALP-101-000 
Objectives of the Registry 
This open-ended, ambispective registry will collect longitudinal 
RWD from participants of all ages diagnosed with Alport 
syndrome (AS) in the US or Canada to enable, characterize, and 
address current and future needs of the participants and the 
drug development initiatives, including: 
▪​
Medical history, treatment history, etiology, and natural 
history. 
▪​
Participant surveys, lifestyle factors and other patient 
reported outcomes. 
▪​
Prospective collection of clinical and laboratory data from 
participants. 
 
Rationale 
In order to better address the limitations and deficiencies of 
other registry approaches, Pulse Infoframe (Pulse) has developed 
and maintains the healthie™ 2.0 platform (“Pulse platform”) to 
orchestrate the curation (collection, ingestion, organization, and 
maintenance) of retrospective and prospective data for the 
Alport syndrome registry. The agile Pulse platform, in addition to 
providing a conventional registry model, enables a decentralized 
(site independent) federated data model that is direct-to-patient 
for recruitment, information gathering, advocacy and support. 
The Pulse platform is well positioned to fulfill the design and 
approach for rigorous rare disease evaluation, along with a full 
suite of features for additional RWD dimensions and analytical 
components. 
 
Registry Design 
The healthie™ 2.0 platform (“Pulse platform”) will orchestrate 
the curation of retrospective and prospective data for the Alport 
syndrome registry. The Pulse platform has a centralized registry 
data infrastructure with standardized rules, and a decentralized 
(i.e., site independent) federated data model to automate 
adherence to regulations for regional governance and the privacy 
of participant data. This allows the platform to quickly scale to 
transregional or transnational deployment.  
 
Registry Procedure 
This ambispective non-interventional real-world registry includes 
subjects of all age. The definition of an Alport syndrome 
diagnosis for this registry will be a clinical diagnosis by a certified 
genetic counselor, treating physician or nephrologist, based on 
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familial history, clinical signs, genetic test results, electron 
microscopy examination of renal biopsy (showing abnormalities 
of the glomerular basal membrane), or immunohistochemical 
findings on renal and cutaneous biopsy (even if it cannot 
establish the diagnosis in all the subjects). Molecular genetic 
testing will confirm the diagnosis but is not required for registry 
eligibility. Intronic mutations may account for approximately 5% 
of Alport mutations and likely missed by current standard exomic 
panel screens. See below reference. 
 
Data Capture and Management 
All data will be sourced directly from participants and/or their 
caregivers into the Pulse platform, directly into the electronic 
case report forms (eCRFs) that are part of the platform. 
Mandatory fields will be identified to collect a Minimal Data Set 
(MDS) on each patient to adequately profile the Alport syndrome 
patient population.  
The data workflow and schedule of assessments are provided for 
demographics, medical history, lifestyle factors, participant 
clinical profile, therapies, and laboratory data will be collected 
during enrollment. Medical history and laboratory data will be 
retrospectively collected from the date of clinical diagnosis of AS 
to the date of enrollment in the registry. When available, 
additional profiling, routine clinical care, genetic results, 
audiograms, and labs will be collected. Data will be collected for 
as long as the participant is enrolled or until registry termination. 
 
The healthie™ platform is managed and deployed in AWS cloud 
hosting solutions and adheres to country-specific security and 
privacy regulatory requirements. Data ingestion and 
management pipelines in healthie™ guarantee only high-quality 
data reside in the platform. Automated processes detect and 
rectify data anomalies prior to analysis time, and any single 
source of clinical data is qualified by external data sources. 
Incoming values are normalized based on industry and medical 
community standards to provide proper characterization of data, 
reusability of data sources, and ease of data mobility between 
platforms.  
 
Eligibility Criteria 
Inclusion Criteria 
I 01.​
Confirmed diagnosis of AS by a certified genetic 
counselor, treating physician or nephrologist. 
I 02.​
Signed informed consent/assent must be provided by the 
subject and/or caregiver (parent/legal guardian) 
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including compliance with the restrictions listed in the 
informed consent/assent form and in this protocol. 
Exclusion Criteria 
E 01.​
[No exclusion criteria.] 
 
Number of Participants and 
Duration of Participation 
The registry is an open-ended design to collect data about 
natural history, participant health status and care they receive 
over time. There is no cap to the enrollment of patients with AS.  
 
Statistical Considerations 
The registry is not hypothesis-driven, and the objectives are to 
obtain data for specific participant and disease domains. 
Statistical considerations will be considered independently of 
this protocol using study-specific protocols for data from this 
registry. 
Participant / Caregiver Data  
▪​
Screening & Consent 
▪​
Participant Identification 
▪​
Demographics  
▪​
Lifestyle Characteristics 
▪​
Disease diagnostics / Participant Clinical Profile 
▪​
Genetic Results 
▪​
Participant Surveys 
▪​
Medical History 
▪​
Treatment History 
▪​
Laboratory Data 
 
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1​ BACKGROUND / INTRODUCTION 
Alport syndrome (AS) is a genetically and phenotypically heterogeneous disorder of the glomerular, 
cochlear, and ocular basement membranes due to mutations in the collagen IV genes COL4A3, COL4A4, 
and COL4A5. AS can be transmitted as an X-linked (XLAS), autosomal recessive (ARAS), and/or autosomal 
dominant (ADAS) disorder (Savige et al., 2022). A fundamental feature of AS is the phenotypic 
heterogeneity of the network of type IV collagen α3, α4, and α5 chains (the collagen IVα345 network), 
resulting in a broad range of kidney outcomes and extra-renal manifestations (Kashtan, 2021a). AS 
patients often present progressive hematuric nephritis, hearing loss, and ocular degradation (Jais et al., 
2003). Males with XLAS demonstrate a strong genotype-phenotype correlation, whereas in females prior 
XLAS studies have not identified a genotype-phenotype correlation for kidney failure, hearing loss or 
ocular abnormalities (Gibson et al., 2022). In XLAS, there is often a family history of hematuria (with or 
without proteinuria) or renal failure. In ARAS, families with monoallelic variant carriers are often 
asymptomatic or show only microscopic hematuria (and mild proteinuria) (Nozu et al., 2019). In one 
study of ADAS, the median age for developing proteinuria was 17 years old, and the median renal 
survival time was 70 years (Kamiyoshi et al., 2016). However, reported median renal survival times in 
men with XLAS; men and women with ARAS; and combined were only 25, 21, and 22 years, respectively 
(Gross et al., 2020; Jais et al., 2000; Oka et al., 2014).  
Alport syndrome is a rare genetic disorder, but it is also underdiagnosed since the mutation can be 
unknown to the patient. The reported prevalence of Alport syndrome varies from one in 5000 to one in 
53,000 individuals (Gibson et al., 2021). The United States Renal Data System (USRDS) showed that 
approximately 0.2% of adults and 3% of children in the United States with end-stage renal disease (ESRD) 
carry a diagnosis of Alport syndrome (Kashtan, 2019).  
Urinalysis is an extremely effective method of screening for AS. Alport nephropathy begins with isolated 
hematuria, followed by moderate albuminuria, severe proteinuria, and decline in the Glomerular 
Filtration Rate (GFR) (Kashtan, 2021a).  Some patients will first present with sensorineural hearing loss 
and ocular abnormalities (Zhang & Ding, 2018).  
Clinical diagnosis of AS is based on familial history, clinical signs, electron microscopy examination of a 
renal biopsy, and the immunohistochemical findings on renal and cutaneous biopsy although it may not 
establish the diagnosis in all subjects. Genetic analysis should be considered the primary method of 
definitive analysis (Kashtan, 2022). However, intronic genetic variants can be missed by most 
next-generation genetic screening panels  (Wang et al., 2021). As such cohesive diagnosis based on 
combined familial history, clinical signs, and renal biopsy can be used for a definitive diagnosis. The 
clinical sensitivity (true positives) and specificity (true negatives) are dependent on variable factors such 
as age or family history. For XLAS, clinical specificity is nearly 100% by age 20 in males and is approaching 
100% for ARAS by age 20 in both males and females (Hertz et al., 2014) . 
There is no cure for AS, and currently the therapy goal for Alport kidney disease is to safely maintain and 
lengthen the intervals between the milestones of progression to ESRD with angiotensin converting 
enzyme (ACE) inhibitor treatment (Kashtan, 2021a) or similar (e.g., angiotensin receptor blockers). Gene 
therapy is now universally recognised as a possible therapeutic application for this rare disease, and 
using pharmacological repurposed chaperones are also under investigation (Daga et al., 2022).  
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2​ RATIONALE 
Given that Alport syndrome is a rare disease, the diagnosis and treatment modalities for AS are 
inadequate, and the mutation is often unknown to the patient, prevalence estimates are difficult to 
estimate and comprehensive long-term data on patients is limited. Additionally, the most commonly 
diagnosed Alport X-linked Alport syndrome (XLAS) is associated with higher severity of outcomes in 
males compared to the less commonly diagnosed ARAS and ADAS types. As a result, estimates of 
prevalence and other investigations have traditionally relied on data from case-series clinical care of 
males with significant burdens of illness; whereas females with a milder type are less tested and likely 
under-diagnosed even though their risk of having Alport is genetically two-fold compared to males 
(Savige et al., 2016).  
To better characterize and study Alport Syndrome, especially the future needs for patients and drug 
development initiatives, rare disease databases and registries models have been established. However, 
these models tend to be limited in a variety of ways due to intrinsic difficulties in the design and 
approach to rare disease evaluation. Existing models are often inadequately designed to answer 
questions about the disease and its treatment especially in small populations, and the rigid designs 
prevent the scalability to answer the intended question, or any new interrogations. Deficiencies also 
include insufficient duration in longitudinal data with most models being cross-sectional; lack of 
consistent and repeated follow-ups; no integration with disparate real-world data (RWD) sources; and 
are geographically bound to a specific region or nation. Additionally, for these rare diseases with 
well-known hereditary links, investigators have encountered registry scenarios where at-risk 
immediate-family members have never been tested (Kashtan, 2021b). 
In order to better address the limitations and deficiencies of other approaches, Pulse Infoframe (Pulse) 
has developed and maintains the healthie™ 2.0 platform (“Pulse platform”) to orchestrate the curation 
(collection, ingestion, organization, and maintenance) of retrospective and prospective data for the 
Alport syndrome registry. The agile Pulse platform, in addition to providing a conventional registry 
model, enables a decentralized (site independent) federated data model that is direct-to-patient for 
recruitment, information gathering, advocacy and support. The Pulse platform is well positioned to fulfill 
the design and approach for rigorous rare disease evaluation, along with a full suite of features for 
additional RWD dimensions and analytical components (see Section 4). 
3​ REGISTRY OBJECTIVES 
This open-ended, ambispective registry will collect longitudinal RWD from participants of all ages 
diagnosed with Alport syndrome (AS) in the US or Canada to enable, characterize, and address current 
and future needs of the participants and the drug development initiatives, including: 
 
●​ Medical history, treatment history, etiology, and natural history. 
●​ Participant surveys, lifestyle factors and other patient reported outcomes. 
●​ Prospective collection of clinical and laboratory data from participants. 
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4​ REGISTRY METHODS 
4.1​ REGISTRY DESIGN 
The healthie™ 2.0 platform (“Pulse platform”) will orchestrate the curation of retrospective and 
prospective data for the Alport syndrome registry. The Pulse platform has a centralized registry data 
infrastructure with standardized rules, and a decentralized (i.e., site independent) federated data model 
to automate adherence to regulations for regional governance and the privacy of participant data. This  
allows the platform to quickly scale to transregional or transnational deployment.  
The Pulse platform is a secure cloud-based Health Insurance Portability and Accountability Act (HIPAA) 
and General Data Protection Regulation (GDPR) compliant using the US Food and Drug Administration 
(FDA) endorsed Observational Medical Outcomes Partnership (OMOP). The OMOP common data model 
(CDM) leverages and delivers centralized standards and consistency enabling rapid synthesis and analysis 
of data.  
At the individual subject level, the decentralized approach enables decentralized consenting/assenting 
and enrollment with password-protected participant portals. The platform enables direct and continuous 
participant/caregiver clinical data entry and document upload functionalities for the participant and 
caregiver (parent or legal guardian) in real-world settings for treatment and outcomes in AS.  
Overall, the platform provides consistent, reliable, high-quality data collection, controlled access for 
users, along with administrative dashboards for population-level insights, and participant and caregiver 
(i.e., parent or legal guardian) journey dashboards and support capabilities. The platform is extensible to 
health care providers and advocacy and is a valuable collective resource and referral for future studies. 
4.2​ REGISTRY POPULATION, ENROLLMENT AND WITHDRAWAL PROCESS 
This ambispective non-interventional real-world registry includes all subjects regardless of age. The 
definition of an Alport syndrome diagnosis for this registry will be a clinical diagnosis by a certified 
genetic counselor, treating physician or nephrologist, based on familial history, clinical signs, genetic test, 
electron microscopy examination of renal biopsy (showing abnormalities of the glomerular basal 
membrane), or immunohistochemical findings on renal and cutaneous biopsy (even if it cannot establish 
the diagnosis in all the subjects). Molecular genetic testing will confirm the diagnosis if possible, but is 
not required for registry eligibility. 
4.2.1​
Eligibility Criteria 
Inclusion Criteria 
I 01.​
Confirmed diagnosis of AS confirmed by a certified genetic counselor, treating 
physician or nephrologist. 
I 02.​
Signed informed consent/assent must be provided by the subject and/or caregiver 
(parent/legal guardian) including compliance with the restrictions listed in the 
informed consent/assent form and in this protocol. 
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Exclusion Criteria 
E 01.​
[No exclusion criteria.] 
 
4.2.2​
Enrollment Process 
4.2.2.1​
Alport Syndrome Foundation (ASF)  
ASF will directly contact potential subjects. Communication will be through direct email to its 
membership of more than 8,000 individuals, e-newsletters, webinars, nephrologists via ASF newsletters, 
all ASF patient events including ASF’s annual Alport Connect meeting, frequent online virtual meetings 
for patients, and through exhibiting and speaking at nephrology and other related conferences. Social 
media campaigns may be used in the future to educate the ASF community about this registry. If a 
subject expresses interest in joining the Alport Syndrome Registry, and if the patient or caregiver has any 
challenges with signing up, the ASF staff will guide the subject or caregiver (parent or legal guardian) 
through the enrollment steps. Subjects or caregivers will complete the online eligibility screening and 
informed e-consent process, or they can contact Alport Syndrome Registry personnel.  
4.2.2.2​
Enrollment Directed to the General Public 
Enrollment directed to the general public are: 
●​ Active electronic enrollment (e-enrollment) through email blasts (e-blasts), and passive 
e-enrollment through web page strategy mentions (e.g., via Facebook, twitter, etc.). 
●​ Recommendations through peer mentors of ASF. 
●​ National awareness campaigns (directed to the at-risk population). 
●​ Direct media campaigns raising awareness about the registry. 
●​ Other events directed towards the general public. 
4.3​     INFORMED CONSENT PROCESS 
All subjects and caregivers will undergo an Institutional Review Board (IRB) approved online 
consent/assent process prior to any study activity. Subjects/caregivers will be directed during the 
enrollment process to the AS Registry website registration page. Once the screening registration is 
completed, access to the platform will be provided through a secure email link for the Pulse healthie™ 
2.0 platform. Once they are logged in to their Pulse platform portal, the registrant will receive 
information and be guided through the applicable consent/assent process and complete the appropriate 
consent/assent online forms via e-Consent using the DocuSign® verification of e-signatures industry 
standard. General consent and assent guidelines follow (with age customization available to be 
accordant with local and regional minor/adult regulations and laws as needed): 
Age of Participant 
Assent Form Required Informed Consent 
Infant-6 years old 
No 
Yes 
7-12 years old 
Yes 
Yes 
13-17 years old 
Yes 
Yes 
18+ years old 
Not Applicable 
Yes 
 
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4.4​ PARTICIPANT WITHDRAWAL 
Participants may withdraw from the Alport Syndrome Registry by communicating through the participant 
portal expressing their intention to withdraw, or by communicating directly with the Alport Syndrome 
Registry personnel. Participants who withdrawal will receive a confirmation email sent by the registry 
team. In case of withdrawal, the reason for withdrawal, when available, will be documented. Any data 
collected prior to withdrawal will be kept and be made available for inclusion in all analyses. Participants 
who withdraw will be allowed to re-enroll/re-activate at a future date.  
4.5​ REGISTRY DURATION AND NUMBER OF PARTICIPANTS 
The registry is open-ended with no cap on the number of participants.  
5​ DATA SOURCE AND DATA MANAGEMENT 
5.1​ DATA SOURCE AND DATA COLLECTION 
All data will be sourced directly from participants and/or their caregivers into the Pulse platform, directly 
into the electronic case report forms (eCRFs) that are part of the platform. Mandatory fields will be 
identified to collect a Minimal Data Set (MDS) on each patient to adequately profile the Alport syndrome 
patient population. For example, race and sex at birth are mandatory, but a response to receiving genetic 
testing is optional. The full set of fields to be collected (mandatory and optional fields) will be found in 
the registry data dictionary. 
The data workflow and schedule of assessments are provided in Table 1. Participant data for 
demographics, medical history, lifestyle factors, participant clinical profile, therapies, and laboratory data 
will be collected during enrollment. Medical history and laboratory data will be retrospectively collected 
from the date of clinical diagnosis of AS to the date of enrollment in the registry. When available, 
additional profiling, routine clinical care, genetic results, and labs will be collected longitudinally and 
entered in the participant/caregiver portal and/or by direct document upload. Optional follow-up data, 
such as participant surveys and patient reported outcomes (PROs) may be collected longitudinally. Data 
will be collected for as long as the participant is enrolled or until registry termination. 
Table 1: Categories and schedule of assessments for participants and caregivers 
 Data 
Screening  
Enrollment 
Prospective 
Screening & Consent 
X 
 
 
Participant Identification 
X 
 
 
Demographics  
 
X 
 
Lifestyle Characteristics 
 
X 
 
Disease diagnostics / Participant Clinical Profile 
X 
X 
X 
Genetic Results 
 
X 
X 
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 Data 
Screening  
Enrollment 
Prospective 
Participant Surveys 
 
 
X  
Medical History 
 
X 
X 
Treatment History 
 
X 
X 
PROs1 
 
 
X 
Laboratory Data 
 
X 
X 
1 PROs are optional future additions. 
5.2​ DATA MANAGEMENT 
The healthie™ platform is managed and deployed in AWS cloud hosting solutions and adheres to 
country-specific security and privacy regulatory requirements. Data ingestion and management pipelines 
in healthie™ guarantee only high-quality data reside in the platforms. Strong confidence can be placed 
in resultant analyses since automated processes detect and rectify data anomalies prior to analysis time, 
and any single source of clinical data is qualified by external data sources to enhance the value of any 
piece of data ingested. Incoming values are normalized based on industry and medical community 
standards to provide proper characterization of data, reusability of data sources, and ease of data 
mobility between platforms.  
5.3​ DATA ACCESS 
All data access requests are processed by Application Programming Interface (API) methods that require 
authentication and authorization.  Authorizations require that the requesting identity has a role that 
permits the operation to be performed and that the identify has permission to the data requested. Roles 
include participant, site administrator, clinician, investigator, and system administrator. The healthie™ 
2.0 platform uses role-based access control in authorizing data access following the principle of least 
privilege—granting minimum system resources and authorizations that are needed to perform the given 
function.  
5.4​ DATA QUALITY AND MONITORING 
Data quality measures include data profiling for analysis and the application of rules and algorithms for 
refinement. During data entry, healthie™ 2.0 performs normalizations, validations, and range checks and 
applies relational constraints for data consistency. A designated Pulse clinical data specialist will manage 
the database curation process over the life of the registry. 
5.5​ MISSING DATA  
Since the registry is non-interventional and ambispective, it is understood and expected that some data 
points will be missing. Missing data will be monitored by the Pulse team to ensure that there is not one 
data point that is routinely not being captured. Several processes will be put into place to ensure the 
accuracy and reliability of data.  Pulse analysts review data collection, the rate of missing data, and any 
concerns about compliance with data entry. Data entry forms (e.g., data element constraints, such as 
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independent range and/or format limitations or ‘relative’ referential integrity limitations) and automated 
error checking will be employed.  
Within healthie™ 2.0, data standards tools allow for quality assessment at the point of data entry. Task 
completion indicators will flag unanswered questions as a reminder, and the participant will not be able 
to advance to the next screen until answers are provided for required questions (e.g., items within 
validated instruments). 
In addition, periodic checks of completed data will ensure data quality and identify potential issues, 
including end-to-end monitoring and assessment via data provenance and lineage. Manual checks will be 
conducted to evaluate data completeness and the ratio of “unsure/unknown” and blank answers. When 
issues arise, they will be routed for evaluation and triage. Remediation of issues may include the 
following:  
●​ If participant questionnaires are incomplete, reminder emails will be sent to encourage 
completion of the information for the minimal dataset (MDS). 
●​ If data are identified as being low quality, they can be marked to be excluded from analytics (the 
submission is never deleted, but the data is not used in downstream analytics or visualizations). 
5.6​ REGISTRY SAMPLE SIZE AND STATISTICAL POWER 
The registry, by definition, is not hypothesis-driven. It is an open-ended design to collect data about 
natural history, participant health status and care they receive over time. There is no cap to the 
enrollment of patients with AS.  
6​ STRENGTHS AND LIMITATIONS OF REGISTRY METHODS 
6.1​ STRENGTHS 
The main strength of this registry is the ability to recruit participants with a confirmed AS diagnosis and 
treated data provided by participant or caregiver in real-world routine clinical practice that will enable 
more comprehensive data collection for the natural course of the disease and treatment modalities of 
interest both in clinical and in real life setting. 
6.2​ LIMITATIONS 
The general limitation in a non-interventional observational registry is that the causal relationship of 
treatments and clinical outcomes cannot be rigorously ascertained. 
7​ PROTECTION OF PARTICIPANT CONFIDENTIALITY  
All personal data collected and/or processed in relation to this study will be handled in compliance with 
all applicable Privacy & Data Protection laws and regulations, including the GDPR (General Data 
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Protection Regulation). When archiving or processing personal data pertaining to the participants or 
caregiver 
s, Pulse takes all appropriate measures to safeguard and prevent access to this data by any unauthorized 
third party. 
Several precautions will be taken to assure the confidentiality of participants. Immediately after 
enrollment, each participant will be assigned a Globally Unique Identifier (GUID) and the registry specific 
identifier, which will be used to identify the participant’s database records. This unique identifier will not 
contain any participant identifiers. The database will employ multiple security features to limit access to 
any Protected health information (PHI) to authorized registry team members only. Data will be collected 
and processed with adequate precautions to ensure confidentiality and compliance with applicable data 
privacy protection laws and regulations. The computerized database will tag all PHI data and not permit 
the viewing of such data except by authorized parties. Strict control over data viewing based on 
role-based permissions will be enforced. All registry Personnel, whose responsibilities require access to 
personal data will agree to keep the identity of registry participants confidential. Data containing direct 
identifiers or person identifying information (PII) will be restricted from access and not be available for 
export at any time. Qualified Researchers, who apply for access to the database, will have a limited 
dataset access after receiving proper approval with direct participant identifiers removed and 
transmitted securely using downloadable Excel compatible file formats.  
8​ ADVERSE EVENTS 
As it is a non-interventional observational registry and consists of primarily secondary data (originally 
collected by someone other than the patient for other purposes), no risk of adverse events resulting 
from physical harm is expected from participation in this registry.  
9​ PROVIDING RESULT TO PARTICIPANTS  
Through the Pulse platform portal, the participant/caregiver can track previously entered data. As more 
data becomes available, population-level summaries of the data will populate the portal so the 
participant/caregiver can visualize and compare their data characteristics with the broader population. 
When data from the registry are used in a research publication, the title and abstract from the 
publication may be shared through the portal.  
10​USE OF INFORMATION AND PUBLICATIONS 
The information that will be accrued during the conduct of this registry will be strictly confidential.  This 
information may be disclosed only as deemed necessary. All informational distributions outside of the 
reporting and dashboards in this registry protocol will be done under the auspice of a Study Protocol 
with Alport Syndrome Foundation and Pulse. 
 
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List of Supplements 
•​
Informed Consent form 
•​
Assent forms 
•​
Data Variables/Dictionary 
•​
Recruitment Materials 
11​REFERENCES 
Daga, S., Ding, J., Deltas, C., Savige, J., Lipska-Ziętkiewicz, B. S., Hoefele, J., Flinter, F., Gale, D. P., Aksenova, M., 
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