Dissecting the Role of miR-3916 and miR3613-5p in Breast Cancer and Developing a Metastases Predictor PORTENT Algorithm
Conditions: Breast Cancer Early Stage Breast Cancer (Stage 1-3)
Sponsor: Casa Sollievo della Sofferenza IRCCS

 
Ospedale Casa Sollievo della Sofferenza 
ISTITUTO DI RICOVERO E CURA A CARATTERE SCIENTIFICO 
OPERA DI SAN PIO DA PIETRELCINA 
Viale Cappuccini, 1 - 71013 San Giovanni Rotondo (FG)  
Laboratori di Ricerca - Laboratorio di Oncologia 
 
Pag. 1 of 9 
 
Official Title: 
Dissecting the Role of miR-3916 and miR-3613-5p in Breast Cancer and 
Developing a Metastases Predictor PORTENT Algorithm 
 
This document is a translation from the original Italian Clinical Study 
Protocol and Statistical Analysis Plan. 
 
Ethical Committee Approvals 
Latest Approval from Ethical Commettee: December 19th, 2024 
    (Original documents available in Italian only) 
 
 
 
 

 
Ospedale Casa Sollievo della Sofferenza 
ISTITUTO DI RICOVERO E CURA A CARATTERE SCIENTIFICO 
OPERA DI SAN PIO DA PIETRELCINA 
Viale Cappuccini, 1 - 71013 San Giovanni Rotondo (FG)  
Laboratori di Ricerca - Laboratorio di Oncologia 
 
Pag. 2 of 9 
 
1. Background and Rationale 
2. Study Objectives 
3. Study Design 
4. Patient Selection 
 4.1 Inclusion Criteria 
 4.2 Exclusion Criteria 
5. Description of Patient Cohorts 
 5.1 CSS_Cohort_2 
 5.2 External_Cohort 
 5.3 INT_Milan_Cohort 
6. Interventions and Study Procedures 
 6.1 Clinical Data Collection 
 6.2 Laboratory Analyses 
7. Ethical Considerations and Informed Consent 
8. Data Management and Confidentiality 
9. IPD Sharing Plan 
10. Documents to Be Shared 
11. Recruitment Timeline 
Statistical Analysis Plan (SAP) 
12. Statistical Objectives 
13. Endpoints 
14. Analysis Populations 
15. Statistical Methods 
 15.1 Descriptive Statistics 
 15.2 Inferential Analyses 
 15.3 Handling of Missing Data 
 15.4 Software Used 
16. Timeline for Data Analysis 
17. References 

 
Ospedale Casa Sollievo della Sofferenza 
ISTITUTO DI RICOVERO E CURA A CARATTERE SCIENTIFICO 
OPERA DI SAN PIO DA PIETRELCINA 
Viale Cappuccini, 1 - 71013 San Giovanni Rotondo (FG)  
Laboratori di Ricerca - Laboratorio di Oncologia 
 
Pag. 3 of 9 
 
Study Protocol and Statistical Plan 
 
1. INTRODUCTION 
1.1 State of the Art 
Metastasis development is the leading cause of mortality in female breast cancer 
patients. In clinical practice, prognostic markers based on immunohistochemical 
evaluation and certain expression profiles are used. These biomarkers are highly 
relevant for breast cancer subtyping and guiding therapy but are less effective in 
identifying the risk of disease progression. Indeed, about 30% of patients will 
develop metastases regardless of tumor subtype (1-3). 
1.2 Rationale 
MicroRNAs (miRNAs) are small non-coding RNAs now recognized for their active 
involvement in tumor development and progression (4-9). In previous studies 
using an internal cohort (CSS_1 cohort), we identified two miRNAs, miR-3916 
and miR-3613-5p, differentially expressed in tumors that developed distant 
metastases within 5 years of follow-up compared to disease-free cases over the 
same period. Furthermore, including expression levels of these two miRNAs 
significantly improved the performance of a multivariate logistic regression model 
that incorporates currently used clinical prognostic markers. Specifically, the 
clinical model’s AUC (95% CI) improved from 0.76 (0.68-0.84) to 0.85 (0.79-0.91) 
(delta AUC (p-value) = 0.001, DeLong test) when adding the combined 
logarithmic expression values of miR-3916 and miR-3613-5p. Based on these 
data, we developed an algorithm that integrates clinicopathological data and 
miRNA expression to assess the risk of metastasis development in women with 
breast cancer (PORTENT → Prediction Of bReasT cancEr distaNt meTastases). 
The predictive multivariate logistic model is as follows: 
Linear Predictor (LP) = -2.498 + (b1×V1) + (b2×V2) + (0.018×V3) + (-0.915×V4) 
+ (0.731×V5) 

 
Ospedale Casa Sollievo della Sofferenza 
ISTITUTO DI RICOVERO E CURA A CARATTERE SCIENTIFICO 
OPERA DI SAN PIO DA PIETRELCINA 
Viale Cappuccini, 1 - 71013 San Giovanni Rotondo (FG)  
Laboratori di Ricerca - Laboratorio di Oncologia 
 
Pag. 4 of 9 
 
 
 
Using the inverse formula (“expit” function), the individual probability (%) of 
developing distant metastases can be calculated. 
2. STUDY OBJECTIVES 
The primary objective of the study is the clinical validation of the PORTENT 
metastasis risk assessment algorithm in women with breast cancer. Secondary 
objectives are: 
- To evaluate the association of miR-3916 and miR-3613-5p with overall survival 
(OS). 
- To assess the association between the expression of the target genes of miR-
3916 and miR-3613-5p and clinicopathological parameters (hormone receptors, 
lymph node status, Ki67-Mib1, etc.), as well as disease-free survival (PFS), 
metastasis-free survival (MFS), and overall survival (OS). 
- To evaluate the performance of the PORTENT algorithm in molecular 
subgroups identified by PAM50 classification. 
3. STUDY DESIGN 
This is a retrospective observational study conducted on three cohorts of patients 
with confirmed breast cancer diagnosis. 
3.1 Patient Selection 
3.1.1 CSS-cohort_2: This cohort will include 350 cases with at least 5 years of 
follow-up, selected from a prospectively recruited cohort between 2014 and 2019 
within the TRANSCAN-BREMIR Study (Protocol References: Prot 116/CE dated 
30/09/2014; Prot 140/CE dated 28/10/2014; Prot 150/CE dated 24/10/2018), 
carried out at the Oncology Laboratory of Fondazione “Casa Sollievo della 
Sofferenza”, IRCCS. Residual tumor tissue must be available at the Pathology 
Unit, Fondazione “Casa Sollievo della Sofferenza” – IRCCS. 

 
Ospedale Casa Sollievo della Sofferenza 
ISTITUTO DI RICOVERO E CURA A CARATTERE SCIENTIFICO 
OPERA DI SAN PIO DA PIETRELCINA 
Viale Cappuccini, 1 - 71013 San Giovanni Rotondo (FG)  
Laboratori di Ricerca - Laboratorio di Oncologia 
 
Pag. 5 of 9 
 
3.1.2 External_cohort: Patients will be retrospectively enrolled at the centers 
listed in Table 1. At least 450 patients will be selected with available residual 
tumor tissue at the respective Pathology Units. Each center will enroll at least 75 
patients: 60 disease-free after at least 5 years of follow-up and 15 with metastatic 
progression after at least 3 years. 
Table 1. List of recruiting centers for the External_cohort: 
IRCCS Oncological Referral Center of Basilicata, Rionero in Vulture (PZ) 
(CROB): Onco-Hematology Department (Dr. Michele Aieta) 
National Cancer Institute IRCCS- Fondazione Pascale, Naples (INT-Nap): 
Experimental Clinical Oncology of Senology (Dr. Michelino De Laurentis) 
HUMANITAS Cancer Center, Milan (HUM): Oncology and Hematology 
Department (Dr. Rita De Sanctis) 
IRCCS Policlinico San Matteo Foundation, Pavia (SM-PAV): Medical Oncology 
Unit (Dr. Elisa Ferraris) 
Cancer Institute “Giovanni Paolo II” – IRCCS, Bari (IT-Bari): Molecular 
Diagnostics and Pharmacogenetics (Dr. Stefania Tommasi, Dr. Francesco 
Giotta) 
National Cancer Institute “Regina Elena” – IRCCS, Rome (INT-Roma): Phase IV 
Clinical Trials Unit (Dr. Patrizia Vici) 
3.1.3 INT_Milan cohort: This cohort will include 300 cases of Luminal A breast 
cancer treated with neoadjuvant therapy, with residual tumor material available 
from pre-treatment biopsy and, if available, surgical specimens. This cohort is 
available at the National Cancer Institute of Milan (INT_Milan), Department of 
Applied Research and Technological Development (Contact: Dr. Serena Di 
Cosimo). 
3.2 Inclusion Criteria 
1. Willingness to participate in the study through acceptance and signature of 
Informed Consent and Privacy Notice. 
2. Age ≥ 18 years. 
3. Tumor stage I, with or without lymph node involvement; or stage II, with or 
without lymph node involvement; or stage III without lymph node involvement. 

 
Ospedale Casa Sollievo della Sofferenza 
ISTITUTO DI RICOVERO E CURA A CARATTERE SCIENTIFICO 
OPERA DI SAN PIO DA PIETRELCINA 
Viale Cappuccini, 1 - 71013 San Giovanni Rotondo (FG)  
Laboratori di Ricerca - Laboratorio di Oncologia 
 
Pag. 6 of 9 
 
3.3 Exclusion Criteria 
1. Age < 18 years. 
2. Tumor stage IV at diagnosis. 
3. Failure to accept and sign Informed Consent and Privacy Notice. 
3.4 Study Duration 
According to the original GANTT chart (see page 16 of the file 
ApplicationSubmission_Parrella_Paola_IG_2021), patient enrollment was initially 
planned within the first 24 months following Clinical Protocol approval by the 
recruiting centers, with a deadline of 31 December 2024. However, due to delays 
in recruitment at participating centers, the Ethics Committee of Foggia, now the 
competent authority for the coordinating institution following recent changes in 
Italian law (art. 2, D.Lgs. 52/2023), granted an extension of the patient 
recruitment period until 31 June 2026. Consequently, patient recruitment can 
continue under the same protocol, ensuring compliance with ethical and 
regulatory requirements. 
4. PROCEDURES 
4.1 Collection of Clinical History 
The Principal Investigator or a designated delegate will collect patient medical 
history and enter relevant clinicopathological data (age, histology, receptor 
status, lymph node status, etc.) and follow-up information (presence or absence 
of metastasis) into a dedicated platform. Follow-up updates (metastasis status, 
patient alive/deceased) are planned by month 48 of the project (31/12/2025). 
4.2 Laboratory Analysis 
Pathology Units of each center will prepare sections from residual tumor tissue to 
be sent to the Oncology Laboratory of Fondazione “Casa Sollievo della 
Sofferenza”, IRCCS for RNA extraction according to standard experimental 
procedures. Expression of miR-3916, miR-3613-5p, and miRNA target genes will 
be analyzed by quantitative real-time PCR (RT-qPCR) at the Oncology 
Laboratory. Protein expression of miRNA target genes will be assessed by 
immunohistochemistry. The extracted RNA will also be analyzed at the 
Gerobiomics and Exposomics Laboratory of the Romagna Institute for Tumor 
Studies “Dino Amadori” – IRST - IRCCS (Contact: Dr. Bravaccini) to evaluate 
gene expression involved in molecular classification of female breast cancer. 

 
Ospedale Casa Sollievo della Sofferenza 
ISTITUTO DI RICOVERO E CURA A CARATTERE SCIENTIFICO 
OPERA DI SAN PIO DA PIETRELCINA 
Viale Cappuccini, 1 - 71013 San Giovanni Rotondo (FG)  
Laboratori di Ricerca - Laboratorio di Oncologia 
 
Pag. 7 of 9 
 
4.3 Biological Material Storage 
Biological material will be stored for 15 years at the Oncology Laboratory of 
Fondazione IRCCS “Casa Sollievo della Sofferenza” and at the Gerobiomics and 
Exposomics Laboratory of IRST IRCCS (Contact: Dr. Bravaccini). Unused 
material after this period will be destroyed. 
5. STATISTICAL METHODS 
Study data will be analyzed at the Biostatistics Unit of Fondazione “Casa Sollievo 
della Sofferenza” IRCCS. Disease progression is defined by local recurrence or 
distant metastases assessed by mammography, CT, PET-CT, MRI, or bone 
scintigraphy. 
5.1 PORTENT Algorithm Validation 
The prognostic ability of the PORTENT algorithm will be tested on 
CSS_cohort_2, External_cohort, and INT_Milan cohort for internal and external 
validation, verifying robustness and generalizability (11). The algorithm will 
calculate individual risk probabilities for distant metastasis separately for each 
cohort. Discriminatory power will be assessed by comparing the Area Under the 
ROC Curve (AUC) of predicted probabilities, including 95% confidence intervals 
(DeLong et al., 12). Calibration will be evaluated by calibration curves and 
Integrated Calibration Index (ICI) (13). Differences in AUCs between the original 
and independent cohorts will be tested by Gönen et al.’s modification of 
DeLong’s test (14). A p-value < 0.05 will be considered statistically significant. 
5.2 Descriptive Analysis and Survival Correlations 
Clinicopathological characteristics will be summarized as mean ± SD for 
continuous variables and frequencies/percentages for categorical variables. Data 
distribution will be tested by Kolmogorov-Smirnov and Shapiro-Wilk tests. Non-
normally distributed variables will be log-transformed. miRNA and target gene 
expression will be correlated with clinicopathological features and follow-up data. 
Group comparisons will use chi-square for categorical and t-tests for continuous 
variables. Pearson correlation coefficients will assess correlations among 
continuous variables. p<0.05 is significant. Survival analyses will use Cox 
proportional hazards models reporting Hazard Ratios (HR) and 95% confidence 
intervals. 

 
Ospedale Casa Sollievo della Sofferenza 
ISTITUTO DI RICOVERO E CURA A CARATTERE SCIENTIFICO 
OPERA DI SAN PIO DA PIETRELCINA 
Viale Cappuccini, 1 - 71013 San Giovanni Rotondo (FG)  
Laboratori di Ricerca - Laboratorio di Oncologia 
 
Pag. 8 of 9 
 
5.3 Software 
Analyses will be performed using SAS Release 9.4 (SAS Institute, Cary, NC, 
USA). Graphs will be generated with R Foundation for Statistical Computing 
(version 4.04, packages: pROC, rms, gweissman/gmish). 
6. ADMINISTRATIVE REQUIREMENTS 
The study will be conducted according to ethical principles derived from the 
Declaration of Helsinki and in compliance with Good Clinical Practice and 
applicable regulations on observational studies. 
6.1 Informed Consent 
Prior to participation, the written informed consent form must be personally 
signed and dated by the participant or legally authorized representative and by 
the person conducting the informed consent discussion. 
6.2 Consent Copy 
Before participation, the participant or representative will receive a dated and 
signed copy of the informed consent form. 
 
REFERENCES 
1. Sung H, et al. Global cancer statistics 2020: GLOBOCAN estimates of 
incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J 
Clin. 2021. PMID: 33538338 
2. Duffy MJ, et al. Clinical use of biomarkers in breast cancer: Updated 
guidelines from the European Group on Tumor Markers (EGTM). Eur J Cancer. 
2017; 75:284-298. PMID: 28259011. 
3. Pasculli B, et al. Epigenetics of breast cancer: Biology and clinical implication 
in the era of precision medicine. Semin Cancer Biol. 2018; 51:22-35. PMID: 
29339244 
4. Cao R, et al. miR-3613-5p enhances the metastasis of pancreatic cancer by 
targeting CDK6. Cell Cycle 2020; 19(22):3086-3095. PMID: 33073681. 
5. He T, et al. MicroRNA-3613-5p Promotes Lung Adenocarcinoma Cell 
Proliferation through a RELA and AKT/MAPK Positive Feedback Loop. Mol Ther 
Nucleic Acids 2020; 22:572-583. PMID: 33230458. 
6. Ma J, et al. Screening potential microRNAs associated with pancreatic cancer: 
Data mining based on RNA sequencing and microarrays. Exp Ther Med 2020; 
20(3):2705-2715. PMID: 32765765. 

 
Ospedale Casa Sollievo della Sofferenza 
ISTITUTO DI RICOVERO E CURA A CARATTERE SCIENTIFICO 
OPERA DI SAN PIO DA PIETRELCINA 
Viale Cappuccini, 1 - 71013 San Giovanni Rotondo (FG)  
Laboratori di Ricerca - Laboratorio di Oncologia 
 
Pag. 9 of 9 
 
7. Bai X, et al. A seven-miRNA expression-based prognostic signature and its 
corresponding potential competing endogenous RNA network in early pancreatic 
cancer. Exp Ther Med. 2019; 18(3):1601-1608. PMID: 31410115. 
8. Qin L, et al. Integrated analysis of clinical significance and functional 
involvement of microRNAs in hepatocellular carcinoma. J Cell Physiol 2019; 
234(12):23581-23595. PMID: 31210353. 
9. Larsen AC, et al. MicroRNA Expression Profile in Conjunctival Melanoma. 
Invest Ophthalmol Vis Sci. 2016;57(10):4205-12. 
10. Barbano R, et al. Stepwise analysis of MIR9 loci identifies miR-9-5p to be 
involved in Oestrogen regulated pathways in breast cancer patients. Sci Rep. 
2017; 7: 45283. PMID: 28345661. 
11. Vergouwe Y, et al. Substantial effective sample sizes were required for 
external validation studies of predictive logistic regression models. J Clin 
Epidemiol 2005; 58:475-483. PMID: 27548891. 
12. Elisabeth R. DeLong, et al. Comparing the areas under two or more 
correlated receiver operating characteristic curves: a nonparametric approach. 
Biometrics 1988; 44:837–845. 
13. Austin PC, Steyerberg EW. The Integrated Calibration Index (ICI) and related 
metrics for quantifying the calibration of logistic regression models. Stat Med. 
2019; 38(21):4051-4065. 
14. Gönen M. Analyzing Receiver Operating Characteristic Curves with SAS. 
Cary, NC: SAS Institute Inc, 2007. 

Page 1 
 
INFORMED CONSENT FORM FOR PARTICIPATION IN A RESEARCH STUDY 
 
Study Title: Dissecting the Role of miR-3916 and miR-3613-5p in Breast Cancer and Developing a 
Metastases Predictor PORTENT Algorithm. (for brevity, referred to as the “Study” or “Project”) 
 
Italian Title: Studio del ruolo dei miR-3916 e miR-3613-5p nel Tumore al Seno e sviluppo dell'algoritmo di 
predizione delle metastasi PORTENT* 
 
Coordinating Centre: Fondazione “Casa Sollievo della Sofferenza” – Opera di San Pio da Pietrelcina 
Scientific Institute for Research, Hospitalization and Healthcare (IRCCS) 
Viale Cappuccini s.n.c., 71013 – San Giovanni Rotondo (FG), Italy 
 
Principal Investigator: 
Dr. Paola Parrella 
Oncology Laboratory – U.O.C. of Oncology 
E-mail: [pparrella@operapadrepio.it](mailto:pparrella@operapadrepio.it) 
 
Funder: Italian Association for Cancer Research (AIRC) – Investigator Grant 25758 
Participating Centre: [INSERT NAME AND ADDRESS] 
Local Principal Investigator: [INSERT NAME, TITLE, CONTACTS] 
 
 
This document is a translation from the original Italian Privacy and Informed Consent FORM
Latest Approval from Ethical Commettee: December 19th, 2024
(Original documents available in Italian only)

Page 2 
 
INFORMATION FOR THE PARTICIPANT 
Dear Madam, 
You are invited to participate in a research project entitled: “Dissecting the Role of miR-3916 and miR-3613-
5p in Breast Cancer and Developing a Metastases Predictor PORTENT Algorithm.” 
This study will be conducted at the Oncology Laboratory – U.O.C. of Oncology of the Fondazione Casa 
Sollievo della Sofferenza and is funded by the Italian Association for Cancer Research (AIRC). 
Our research aims to identify molecular mechanisms involved in breast cancer. Specifically, we are studying 
microRNAs, small RNA molecules that play important roles in tumor development and progression. 
Preliminary studies have identified two candidates of interest: miR-3916 and miR-3613-5p. 
The purpose of this study is to determine how these two microRNAs may influence tumor progression and 
whether they could serve as biomarkers for identifying breast cancer patients at higher risk of developing 
metastases. 
1. Purpose of the Study 
Your biological material will be used exclusively for the objectives described above. 
Molecular analyses will be performed to assess variations in miR-3916 and miR-3613-5p expression and 
that of their target genes, along with other genes involved in breast cancer. 
The ultimate goal is to develop diagnostic tools enabling personalized, patient-specific treatments. 
2. Type of Biological Material Collected 
If you agree to participate, a portion of your archived tumor tissue (previously collected during your 
diagnostic surgery) may be used for research analyses. 
Samples will be reviewed by a pathologist, ensuring sufficient material remains for diagnostic and clinical 
purposes. 
Selected samples will be sent to: 
Fondazione Casa Sollievo della Sofferenza (Coordinating Centre) 
IRCCS Istituto Romagnolo per lo Studio dei Tumori “Dino Amadori” (IRST) 
Both institutions will store and use your material solely for this study. 
3. Use of Samples for Other Purposes 
Samples will be used only within this project, unless you provide explicit written consent for future studies. 
4. Voluntary Participation 
Participation is entirely voluntary. 
You are free to refuse or withdraw at any time without providing a reason. 
Refusal or withdrawal will not affect your clinical care, treatment, or relationship with your doctors. 
5. Potential Benefits 
While you may not receive direct personal benefit, your contribution may help improve breast cancer 
diagnosis and treatment in the future, benefiting other patients. 

Page 3 
 
6. Potential Risks 
No physical risk is associated with this study. 
Only material already collected for your diagnosis will be used, and only if sufficient tissue remains. 
7. Storage of Biological Material 
Samples will be securely stored for 15 years at: 
the Oncology Laboratory, Fondazione Casa Sollievo della Sofferenza, and 
the IRST “Dino Amadori” IRCCS. 
After this period, any unused material will be destroyed. 
8. Withdrawal of Consent 
You may withdraw your consent at any time without any consequence to your medical care. 
Upon withdrawal, any remaining samples will be destroyed, but analyses already completed will remain 
valid. 
9. Data Protection and Privacy 
Your biological material and related data will be pseudonymized, meaning your identity will be replaced by 
a unique code known only to your Participating Centre. 
Only authorized study staff will access the link between your code and your identity. 
All data and samples will be handled under strict confidentiality and security measures. 
Researchers will only access coded data, ensuring your privacy. 
10. Access to Your Data 
You may access your personal data at any time and request correction or deletion. 
Access may be temporarily restricted while the study is ongoing to maintain its integrity, but will be granted 
once the study is completed. 
11. Transfer and Sharing of Data 
Your pseudonymized data may be shared with the Coordinating Centre, IRST, and other scientific 
collaborators. 
For publications or presentations, data will be fully anonymized, ensuring that no individual can be 
identified. 
12. Use of Research Results 
Results derived from your biological samples may be used for: 
scientific publications (in anonymous, aggregated form); 
development of new diagnostic or therapeutic approaches; 
further research consistent with the objectives of this project. 
 
 

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PROCESSING OF PERSONAL DATA 
(in compliance with EU Regulation 2016/679 – GDPR) 
 
The Participating Centre [INSERT NAME], the Coordinating Centre, and other sites are joint data controllers 
responsible for processing your personal and health data only within the limits necessary for this study. 
Your written consent is the legal basis for this processing. 
Data will be collected, coded, and transmitted in pseudonymized form to the Coordinating Centre. 
Authorized staff, auditors, or regulatory bodies may access data only under confidentiality to verify 
compliance with ethical and scientific standards. 
The study physician may, with your consent, contact your general practitioner to collect relevant medical 
information. 
You may also choose to receive updates on study results or be contacted for potential future studies. 
At the end of the study, your data will be stored for the legally required period. 
Data may be included in aggregated statistical analyses or publications, but no identifying information will 
ever appear. 
You have the right to: 
access, rectify, restrict, or erase your data; 
withdraw consent at any time; 
contact the Data Protection Officer (DPO) of your Centre at [INSERT EMAIL]; 
lodge a complaint with the Italian Data Protection Authority 
([https://www.garanteprivacy.it](https://www.garanteprivacy.it)). 
Your data will be securely stored and handled according to GDPR and Good Clinical Practice (ICH-GCP) 
principles. 
 
 

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CONSENT FORM 
 
Participant Information 
Name and Surname: ............................................................................................................... 
Date of Birth: ............................................. Tax Code: ....................................................... 
Address: .............................................................................................................................. 
City/Province: ........................................................... Telephone: .................................... 
 
☐ I am signing on my own behalf 
☐ I am signing as Legal Guardian / Curator / Representative of the Participant 
 
Participant’s Name (if applicable): ...................................................................................... 
 
Declarations 
I hereby declare that: 
1. I have read and understood this information sheet and consent form. 
2. I have had the opportunity to ask questions and received satisfactory answers. 
3. I have received a copy of this document, signed and dated. 
4. I understand that participation is voluntary and that I may withdraw at any time without affecting my 
care. 
5. I consent to the collection and processing of my personal and sensitive data. 
6. I consent to participate in the study described above. 
7. I consent to the storage and use of my biological material for this study only. 
 
Optional Authorizations 
☐ I wish / ☐ I do not wish to be informed of study results by phone. 
☐ I wish / ☐ I do not wish my general practitioner Dr. ................................................ 
to be informed of my participation and results. 
☐ I wish / ☐ I do not wish to be contacted for potential participation in future research studies. 
City: .............................................  Date: ____ / ____ / ____ 
Participant’s Signature (or Legal Representative): ........................................................ 

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SECTION FOR INDEPENDENT WITNESS (if applicable) 
I, the undersigned ....................................................................................., 
certify that Dr. .................................................. explained the content of this document to the participant, 
who has agreed verbally to participate. 
 
City: .............................................  Date: ____ / ____ / ____ 
Signature of Independent Witness: ............................................................. 
 
### **SECTION FOR STUDY PHYSICIAN** 
 
I confirm that I have explained to the participant the study objectives, procedures, risks, and benefits, and 
that they have understood this information. 
 
**City:** .............................................  **Date:** ____ / ____ / ____ 
**Physician’s Name and Signature:** ..............................................................................