**Introduction:** The EU Tinnitus Database will be used for the storage of
clinical data whithin the UNITI project. Historically, the EU Tinnitus
Database is based on the ESIT Database which is used in the H2020 project ESIT
and hosted by the tinnitus group from the University of Regensburg.

**Types of data:** The following types of data are stored in the EU Tinnitus
Database: Medical and tinnitus-related history; audiological examinations;
questionnaire data. It also allows uploading and storing data files for
individual patient.

**Sources of data:** The EU Tinnitus database is fed with data collected by
the individual clinical partners.

**Ownership of data:** The owner of the data is always the Centre where the
data was collected. This centre is represented by the principal investigator
who is responsible for it.

**Pseudonymisation of data:** The EU Tinnitus database does not store personal
information like names, addresses, phone numbers, e-mail addresses, or IP
addresses that can be used to identify a certain participant directly. A
system of two-level pseudo identifiers will be used to anonymise the data. The
first pseudo identifier (PSID1) will be generated in the system(s) by the
system that is the source of the data (i.e., it generates them or it is used
to record them in the first place). Data communicated to the unified UNITI
database will have PSID1 but before stored in it, PSID1 will be replaced by a
second pseudo identifier (PSID2) which will be generated by the UNITI
database. Subsequently, data will be recorded with PSID2. PSID1 will PSID1 and
PSID2 will be used to link and combine data from different sources. In cases
where the data are inserted directly into the UNITI database only PSID2 will
be generated from the real identifier.

To enable responses to requests made under GDPR, the association between the
real identifier of a patient and PSID1 (PSID2) will be maintained in encrypted
form at the source system that provided the data for the particular patient.
The association between PSID2 and PSID1 (when necessary) will also be
maintained separately and in encrypted form. These associations will be
accessible only to authorised and authenticated software components of the
UNITI platform and users with appropriate authorisation rights, who may need
to access the real identity of a patient.

Furthermore, when the data are exported for further analysis, PSID2 is removed
and replaced by a random unique identifier. All types of data analysis can
only be executed upon the anonymised data set.

Personal information of individual patients is maintained only within the
system of the local centre, which has responsibility for the patient and,
therefore, needs to identify the patient. If a patient can be identified
individually, e.g. by the value of the external identifier attribute, and
requests for their data to be anonymised or deleted according to the rules set
by the General Data Protection Regulation (GDPR), the database administrative
staff of the local systems of the centres anonymise or delete the participants
data permanently, as requested.

**Data quality:** The first step taken to ensure high-quality data within this
framework was to implement the user interface using standardised input fields
that can be used to assist and restrict user input where reasonable. One
example is the use of standardised inputs for integral values that will report
ill-formed input to the user automatically. Whenever a participant decides to
save their current progress, the data are validated on the server side and the
results will be reported to the user in different ways. For every validation
error, the corresponding question is highlighted and the part that includes
the error is indicated. Furthermore, the overall state of data entry is
indicated with localised status messages and textual instructions.

**Languages:** The database offers support for different languages. These
include Dutch, German, Greek, Italian, Polish, Spanish, and Swedish. The
available languages cover all languages of the UNITI clinical centres, plus
additional languages. The language settings of the database can be changed by
the different users.

**Web access:** The database can be reached via www.tinnitus-database.eu. Only
contributors and members of the EU Tinnitus Database have access to it.

**Database manager:** The database will be managed by Jorge Simoes from UHREG
who is overseeing the database, ensuring the maintenance, the data handling
plan, data quality and further developments, if needed.

**Role based access control.** Different levels of access to the database are
provided subject to the roles of individual users. Users are members of staff
of the different clinical centres. In general, users are researchers and they
can only see the data of their own centre. At the moment, the roles supported
(Clinical) Centre Editors, Experts and Administrators. Role based access
control is enforced by a role management system, allowing Centre Editors to
view and edit individual patient datasets of their respective centre. In
addition to the rights of Centre Editors, Centre Experts can export data of
all the patients of their centre for data analysis. Centre Administrators have
all rights of the Centre Editors and Centre Experts but they can also add new
users to the database or remove users from it. There is also a database
administrator user (Superadmin) based at the University of Regensburg, who has
access to the data from all centres. Our expectation is that the above role
types will remain in UNITI and may be expanded by other additional roles
(e.g., Centre admin users with enhanced rights.

**Local data analysis:** Local data analysis means a data analysis that is
based on the data set that has been collected at the Centre that is performing
the data analysis. The person who is responsible for the local data analysis
is identical to the owner of the data. Individual centres (i.e., clinical
partners in UNITI) can perform data analysis on their own data. This right
arises from their role.

**Multi-centre analysis:** The standardised data assessment and storage in the
EU Tinnitus database allows efficient multi-centre data analysis of the
participating partners. Multi-centre analysis means a data analysis that is
based on data that have been collected by two or more partner centres. If one
or more partner centres plan to perform a multi-centre data analysis, they
need to contact the owners of the datasets that will be included in the
envisaged analysis. An agreement on the aim of multi-centre data analysis and
the authorships for the paper that might result of the analysis need to be
settled and signed by all data owners. After sending this data analysis
agreement to the database administrator, the administrator provides access to
the respective data set as determined by the agreement. Multi-centre analysis
can only be applied to anonymised datasets.

**Data Handling Plan.** A data handling plan has been developed as a manual
for understanding and analysing the data stored in the EU Tinnitus Database
that will be included in the UNITI database. This plan gives and overview of
how to interpret data, how questionnaire items are coded, how missing values
are coded, the rules for calculating sum scores of the clinical questionnaires
and all other information that are needed for unified interpretation of the
data. The data handling plan is written in English and is accessible to all
contributors via the EU

Tinnitus Database in a dedicated download section. The data handling plan is
kept up to date by UHREG using a revision numbering system. The database
adminsitrator is overseeing the updates of the data handling plan.

**Data protection:** Data protection is considered and relevant ethical, legal
and privacy concerns will be addressed respectively. The Data Protection
Officer (DPO) of the University of Regensburg (Germany) is also the Data
Protection Officer of the EU Tinnitus Database. He is responsible for
overseeing the data protection strategy and implementation to ensure
compliance with the EU General Data Protection Regulation (GDPR, 2016/679).
Furthermore to ensure that the project will be able to respond to data subject
access requests (DSA) under GDPR associations between the pseudo identifiers
and real identifiers of subjects will be maintained separately from the
clinical data, in encrypted form and in

**Data transfer:** The rules for the secure data transfer within the UNITI
consortium is regulated by UNITI Consortium Agreement under chapter 12.

**Data export and data analysis:** Within the internal section of the
database, the staff can monitor and review data entry and export the data when
needed. Authorised staff can configure custom selection criteria depending on
analysis or study requirements. For example, the data export can be configured
to exclude datasets that are not fully validated, are missing certain items,
or meet other criteria for exclusion. Each data export will be automatically
recorded in a log file, that contains all configuration settings by the user
and a time stamp. This allows reconstruction of the data export, if needed.
The data will be exported without any personal information of the participants
and the pseudonymization code will be removed automatically. Therefore, all
data analysis will be performed on so-called anonymized data sets. The data
export will be saved in a CSV file, with horizontal or vertical data format.
The CSV file is readable by all major statistical software packages. The
majority of data analyses will be executed using the open source statistical
software package R (www.r-project.org). However, each researcher is free to
use the statistical software of choice.

**Physical database:** The data is stored in a relational database format
using Maria DB 11 (www.mariadb.org), which runs in a Linux environment (Debian
Buster, www.debian.org/releases/buster/) and a LAMP technology stack

(www.whatis.techtarget.com/definition/LAMP-Linux-Apache-MySQL-PHP).

**Backup:** A backup of the database is performed every night for data
security reasons whereby the database is backed up to a server hosted by the
Strato AG (Berlin, Germany) and to a second server located at the DBIS
institute. All servers are located in Germany. A Secure Sockets Layer (SSL)
protocol is used for all data transfers.

##  Unified database for smartphone data

**Introduction:** The unified database for smartphone data has the purpose to
store the data that is collected with the smartphone apps within UNITI.

**Types of data:** The following types of data are stored in the app database
and the local smartphone devices:

  * questionnaire data collected using Ecological Momentary Assessment (EMA) methodology; 

  

  * time stamps of app usage; 

  

  * in case of auditory stimulation: subjective ratings of the tinnitus suppression; 

  

  * in case of psychoeducation app: results of the quiz; 

  

  * in case users allow it: GPS location and sound pressure of the surrounding environment while filling out the EMA questionnaires. 

  

**Sources of data:** The smartphone device, its sensors and the UNITI app
running on it. **Ownership of data:** The patient who uses the smartphone
device and UNITI app.

**Physical database:** The data collected from the smartphone is stored in a
relational database using Maria DB 11, which runs in a Linux environment
(Debian Buster) and a LAMP technology stack. This database will be separate
from the UNITI database and may be referred to as the “smartphone database”.
The smartphone database will only be accessible to the patients through the
UNITI mobile app running on the smartphones of the patients. Access to it will
also require the authentication of the particular UNITI mobile app instance as
well as the authentication of the user of this app (the patient). Smart phone
data will also be stored separately in the UNITI database for analysis
purposes.

**Pseudonymization of data:** The smartphone database does not store personal
information like names, addresses, phone numbers, e-mail addresses, or IP
addresses that can be used to identify a certain participant directly. Data
from the smartphone will be stored in the smartphone database and the UNITI
database separately after pseudo-anonymisation as described in Section 2.1.
Furthermore, on the smartphone database, data will be stored in encrypted
form.

**Data quality:** Checks similar to those described for the UNITI database
will also be implemented for the mobile app in order to ensure the quality of
the data collected by it. **Languages:** The mobile app offers support for
different languages, as described for the UNITI database.

**Access of data:** The patients can see their own data on their smartphone
device. Such data will be maintained in encrypted form on the mobile
accessible only after proper authentication of the patient/user of the mobile.
This authentication will be based on password or fingerprint authentication.
Mobile app data will also be transferred and backed up periodically on a
backend server of the UNITI platform (separate from the UNITI unified
database), to ensure availability in the event of loss of the mobile device
and to ensure that the storage space on the device will always be sufficient
for storing the latest data of the patient. Backed up data will be stored in
encrypted form and will be accessible only to the client app running on the
mobile device. Users of the UNITI unified database will not have access to
such data (although they will have access to their pseudo-anonymised
counterparts).

##  Matching data from the EU Tinnitus Database with the app data

A unique patient identifier will be used in the EU Tinnitus Database as well
as for the smartphone apps. This identifier will be used to match the data
from the two SQL databases.

#  Data handling after the project and openly accessible data

##  Publication data

We envisage that a repository for depositing publications and data related to
them will be needed. Zenodo (zenodo.org) is a good candidate for such
repository and it will be considered further as a candidate repository for
publication data. Furthermore, the DataCite Metadata Schema
(schema.datacite.org), will be adopted in this case.

Furthermore, UNITI advocates the “FAIR” principles  1  with regards to
supporting open access to publication data and anonymised patient data. The
FAIR principles require data to be findable (F), accessible (A), interoperable
(I) and re-usable (R). These principles precede implementation choices and do
not necessarily suggest any specific technology, standard, or implementation-
solution. The measures that we will take to support these principles are
summarised below.

##  Findable data

**F1** : (meta)data are assigned a globally unique and persistent identifier

  * A persistent and unique Digital Object Identifier (DOI) is issued to every published record. Moreover, DOI versioning is supported and enables users to update the record’s files after they have been made public and researchers to easily cite either specific versions of a record or to cite, via a top-level DOI, all the versions of a record. 

  

**F2** : data are described with rich metadata (defined by R1 below)

  * The repository’s metadata schema will be compliant with DataCite's Metadata Schema minimum and recommended terms, with a few additional enrichments. As there are no specific metadata schemas that can be used with the UNITI data this more generic schema will be adopted. 

  

**F3** : metadata clearly and explicitly include the identifier of the data it
describes • The DOI is a top-level and a mandatory field in the metadata of
each record.

**F4** : (meta)data are registered or indexed in a searchable resource

  * Metadata of each record will be indexed and searchable directly in the repository’s search engine immediately after publishing. 

  

  * Metadata of each record is sent to DataCite servers during DOI registration and indexed there. 

  

##  Accessible data

**A1** : (meta)data are retrievable by their identifier using a standardized
communications protocol

  * Metadata for individual records as well as record collections are harvestable using the OAI-PMH protocol by the record identifier and the collection name. 

  

  * Metadata is also retrievable through the public REST API. 

  

**A1.1** : the protocol is open, free, and universally implementable

  * See point A1. OAI-PMH and REST are open, free and universal protocols for information retrieval on the web. 

  

**A1.2** : the protocol allows for an authentication and authorisation
procedure, where necessary

  * Metadata are publicly accessible and licensed under public domain. No authorization is ever necessary to retrieve it. 

  

**A2** : metadata are accessible, even when the data are no longer available •
Data and metadata will be retained for the lifetime of the repository.

  * Metadata are stored in high-availability database servers at ULM, which are separate to the data itself. 

  

##  Interoperable data

**I1:** (meta)data use a formal, accessible, shared, and broadly applicable
language for knowledge representation.

  * Zenodo uses JSON Schema as internal representation of metadata and offers export to other popular formats such as Dublin Core or MARCXML. 

  

**I2:** (meta)data use vocabularies that follow FAIR principles

  * For certain terms it refers to open, external vocabularies, e.g.: license (Open Definition), funders (FundRef) and grants (OpenAIRE). 

  

**I3:** (meta)data include qualified references to other (meta)data

  * Each referenced external piece of metadata is qualified by a resolvable URL. 

  

##  Re-usable data

**R1:** (meta)data are richly described with a plurality of accurate and
relevant attributes

  * Each record contains a minimum of DataCite's mandatory terms, with optionally additional DataCite recommended terms and Zenodo's enrichments. 

  

**R1.1:** (meta)data are released with a clear and accessible data usage
license

  * License is one of the mandatory terms in Zenodo's metadata, and is referring to an Open Definition license, but within HOLOBALANCE restricted access will be chosen for the patient data. 

  

  * Data downloaded by the users is subject to the license specified in the metadata by the uploader. 

  

**R1.2:** (meta)data are associated with detailed provenance

  * All data and metadata uploaded is tracable to a registered Zenodo user. 

  

  * Metadata can optionally describe the original authors of the published work. 

  

##  Patient data

The UNITI project aims towards open data. However, depending on the
regulations of the local ethical committees, it might be that not all data can
be made open. Our overall aim is to turn as much data as possible into open
data, which will be provided only in anonymized form. To ensure the correct
usage of the data that will be made open, we aim for an open access
publication that will describe the data set, the interpretation of the values,
the recruitment procedure and all other details that will be needed for
further research on the particular open dataset.

It is foreseen, that at the end of the project, the associations between
pseudo identifiers enabling the pseudonymization of patient data, described in
Section 2, will be completely deleted. This will lead to full anonymisation of
the acquired data set. Nevertheless, it is possible that, different
regulations of the ethical committees of the different clinical partners or
legal interpretations of GDPR taken at national level, might enforce an
earlier or later time point of deletion.

After full anonymisation is carried out, our aim is to maintain the fully
anonymised EU Tinnitus Database for at least 10 years after the lifetime of
the UNITI project in order to ensure that the data are findable, accessible,
interoperable and re-usable (FAIR).

Towards this direction, the UNITI consortium will also consider the
possibility of offering the data set that may become open source in formats
that would enable the viewing of the data through commonly used software such
as video viewers and/or text editing software. For processing, it will also
consider making the dataset available in formats that would enable their
processing in open source data analysis software like, for instance:

  * GNU Octave (www.gnu.org/software/octave/) 

  

  * Scilab (www.scilab.org) 

  

The possibility of providing open source data through the Open Research Data
(ORD) pilot initiative  2  of the European Commission will also be
investigated. ORD has been created primarily with the intention to enable the
provision of data needed to validate the results presented in scientific
publications. It does cover however other types of data that are voluntarily
offered by beneficiaries of Horizon 2020 projects. A portal making available
such datasets has also been set up and maintained by the EU, i.e., the EU Open
Data Portal (ODP)  3  . The use of ORD and ODP will be considered as a means
of offering as open source data sets required for the validation of UNITI
publications and/or wider anonymised datasets, as discussed above.

All the above actions as well as any other action that may be necessary for
the purpose of providing anonymised datasets of UNITI as open source data will
be taken only after approval from the UNITI management board.

#  Conclusions

This deliverable is the first version of the data management plan of UNITI and
has described how data collected for the purposes of the project will be
handled during and after the end of the project.

In summary, UNITI commits the specific security and privacy control measures
to ensure the preservation of the integrity, availability and confidentiality
of the data that will be collected in the project as well as the preservation
of the regulatory requirements of the General Data Protection Directive
(GDPR). The project also commits to making the data about its publications and
the collected clinical data available as open source, if that will be allowed
by ethics and other requirements of the clinical partners who own the
datasets.

As a final concluding remark, it should be noted that although, we have
conducted an initial analysis aimed at envisaging what would be necessary for
the above purposes. a possibility to encounter a need to revise it. If such a
need arises during of the project, the data management plan will be amended
and communicated to all stakeholders, who should be notified about the
amendments.