Developing the University of Tartu in Estonia into a well-networked Patient Safety Research Centre (PATSAFE): A study protocol

Background Patient safety (PS) is a serious global public health problem affecting all countries. Estimates show that around 10 percent of the patients are harmed during hospital care, resulting in 23 million disability-adjusted life years lost per year. Experts emphasize research advancements as a key precondition for safer care. Aim The Patient Safety Research Centre (PATSAFE) project enhances the Institute of Clinical Medicine of the University of Tartu’s (ICM-UT) research potential and capacities in PS in order to improve and strengthen knowledge and skills in methods, techniques and experience for PS research. Methods A strategic partnership with Avedis Donabedian Research Institute in Spain, and IQ Healthcare in the Netherlands, both international leaders in PS research, enables the development of a long-lasting knowledge exchange, allowing the ICM-UT to capitalise on its current achievements and to overcome gaps in scientific excellence in the field of PS research. These twining activities will strengthen and raise the research profile of the ICM-UT academic staff and early-stage researchers (ESRs), by implementing the hands-on training on methods, techniques, and experience in PS research. The project also encourages the active participation of ESRs in PS research by increasing their soft skills, to ensure the continuity and sustainability of PS research in ICM-UT. Finally, development of the research strategy on PS contributes to the long-term sustainability of PS research in Estonia. To implement these activities, PATSAFE foresees a comprehensive strategy consisting of knowledge exchange, soft research skills capacity building, strategic planning, and strong dissemination and exploitation efforts. Expected results As a result of the project, ICM-UT will have the capacity to carry out PS research using the appropriate methodology and the competences to apply state-of-the-art evidence-based strategies for PS research.


Aim
The Patient Safety Research Centre (PATSAFE) project enhances the Institute of Clinical Medicine of the University of Tartu's (ICM-UT)

Introduction
Patient safety (PS) represents a serious global public health problem which affects all countries worldwide.Estimates show that there are 421 million hospitalisations in the world annually, and approximately 42.7 million adverse events, i.e., one in 10 patients is harmed while receiving hospital care.These adverse events result in 23 million disability-adjusted life years lost per year, thus, adverse events due to clinical care could be considered a relevant source of morbidity and mortality globally 1 .
The publication of 'To Err is Human' 2 by the American Institute of Medicine in 2000 helped launch the field of PS: an issue of growing professional awareness was converted to one of public concern.Shortly after this report, PS research became an international priority 3 .
Research is an essential cornerstone for tackling the alarming situation in PS, and a key precondition for safer care.As well as helping to understand the magnitude and nature of patient harm and focus on critical improvement areas, it also contributes to devising evidence-based strategies and evaluating the effectiveness of potential solutions.Thus, using different research methods and approaches, research initiatives in PS focus on three different stages: identification of risks and hazards; design, implementation, and evaluation of PS practices; and maintaining a safe environment and PS culture 4 .
In 2008, WHO Patient Safety published the global priorities for PS research 5 , followed by a set of core competencies for PS research 6 , and a guide for developing training programmes in PS research 7 .To complement the WHO's PS initiatives, in June 2009 the Council of the European Union (EU) published recommendations on PS 8 , calling on Member States to support the establishment and development of national policies and programmes on PS, and develop and promote research on PS.Moreover, the most recent definition of patient safety refers to the importance of an evidence-based approach: "Patient safety is a framework of organized activities that creates cultures, processes, procedures, behaviours, technologies, and environments in health care that consistently and sustainably: lower risks, reduce the occurrence of avoidable harm, make error less likely and reduce its impact when it does occur." 9ovision of safe and high-quality health services was one of the priorities in the National Health Plan of Estonia 2009-2020 10 , and the importance of PS in the Estonian health system is also significantly emphasized in the National Health Plan 2021-2030 11 .Quality efforts started in Estonia in the second half of the 1990s with a focus on patients and professionals' satisfaction.A motive for the further development was the Quality Policy for Estonian Health Care, which was published in 1998 12 .In 2002, a set of legislative acts came into force supporting the further development of healthcare quality -basic requirements for the quality and accessibility of health services, minimum standards for health care staff, equipment and rooms to establish the quality of the structure, and some procedural requirements.To adjust to these requirements, most health organizations have introduced and continually developed quality management systems.In general, a lot of attention has been paid to organizational management, occupational safety, and risk management in working environments, and to the patient-centred approach: assessment and documentation of patient health risks, and the implementation of patient satisfaction surveys and complaint management 13,14 .However, as suggested by World Bank experts in 2015 15 "a much more fundamental change may be needed in Estonia to create a culture that is open to acknowledging errors and failures, and willing to make the necessary modifications in practice to achieve quality improvement."Technological improvements alone, without this fundamental behavioural change, will do very little to assure and improve quality.This kind of change could be achieved if healthcare professionals are well trained in the principles of performance measurement, quality improvement, and especially in PS and risk management that are specific to their practice specialties.Research on PS and implementation of evidence-based approaches will be key to enhance clinicians' interest and involvement and can also make a difference in practical health care.
Even though the Estonian PS strategy is still not formulated at the national level, a number of initiatives dealing with PS have already been launched, e.g., incident reporting systems in hospitals and pilot record reviews 16 .Still, there are no common standards for incident reporting in Estonia, and the collected information is hardly methodically analysed and used for safety improvement.Successful implementation of planned initiatives will require evidence-based information about PS events to assess the existing situation, identify risks to patients, and find the most effective solutions to improve PS and safety culture in general.Therefore, development of research capacity is envisaged as the key driver for enhancing Estonia's capacity to develop PS.To achieve the project's main goal, the following specific objectives were defined: 1.To strengthen the scientific and technological capacity of ICM-UT and raise ESRs and staff research profiles for identifying and measuring risks and hazards in PS.
2. To increase research capacity and to ensure the continuity and sustainability of PS research at ICM-UT by focusing on patient safety culture and patient empowerment regarding their safety.
3. To increase the soft skills of ESRs.Soft skills are the elementary management, personal, and interpersonal abilities that are vital for an individual to be efficient at workplace or in their personal life 17 .In this project, soft skills are defined as skills that provide additional competencies and improve existing skills in research methods, as well as in research management, including proposal writing, research ethics, intellectual property rights and commercialization, and clinical human resources management.

To increase the visibility of ICM-UT's excellence
in PS research and its potential as a partner with internationally leading European and global research and policy counterparts, as well to strengthen ICM-UT´s networking capacity and credibility at the national and international levels.

Ethics policies
The PATSAFE project activities do not raise any ethical issues.
As the H2020 WIDESPREAD Twinning call does not cover research and associated costs (which may require various ethics permits) as eligible, such costs and activities have not been applied to the PATSAFE project.On the contrary, through training activities supported by the PATSAFE project, we are raising awareness among project target groups (students on all levels and research, clinical and teaching staff) on how to conduct ethical research and provide for PS.In case partners identify the need for an ethics permit at any time during the PATSAFE implementation, the permit will be applied for and implementing related actions will be postponed until the permit is granted.

Project concept
The concept of this project is based on the core competencies for PS research as well as on the guide for developing training programmes in PS research defined by the WHO's PS branch.Overall methodology PATSAFE is based on a dynamic and interactive process with iterative improvement cycles and feedback, ongoing communication, incorporation of new ideas and insight and peer-to-peer exchange and focuses on increasing capacities and achieving impact goals (Figure 2).
Advanced cooperation between two international leading research centres -the Avedis Donabedian Foundation at the UAB in Barcelona (FAD), and IQ healthcare at the Radboud Institute for Health Sciences, Radboud university medical center (IQ-HC) -and the research organization of the wider region -helps ICM-UT address the gaps in PS research via knowledge and experience transfer, (Figure 3), from 2019 to 2022.Identifying common research interests and exploring synergies and knowhow to address specific research questions paves the way for achieving the ICM-UT's sustainable development.
Project activities PATSAFE project includes four activities, which are planned according to the SWOT analysis findings, to deliver maximum impact on ICM-UT's scientific excellence and contribute to ICM-UT's long-term research sustainability.

Identification and definition of the main priorities in short-, medium-, and long-term PS research.
These activities are planned to increase the research capacity and visibility of the ICM-UT in PS research, and directly address the need for international visibility in PS and low involvement of patients in healthcare safety research.In the short term, staff exchanges of two to three researchers from the ICM-UT will visit FAD and IQ-healthcare to identify and envisage research topics that are currently addressed at these institutions and the international level and how they are implemented.We identify the researchers who are interested in doing PS research or are already involved in PS research.Identification of research topics is based on the national and international priorities in PS research, by involving national and international level experts, i.e. representatives of researchers, practitioners, patients and policymakers.To prioritize the research topics, we use the Delphi technique.Additionally, a multidisciplinary workshop is organized to reach a consensus on prioritization of research topics, including qualitative techniques and a prioritization matrix to find the primary short-, medium-, and long-term research needs and challenges.The results include a list of specific topics, care levels, and most important methodologies, appropriated and adapted to the ICM-UT and Estonia.In this process, patients are involved, to integrate their perspective into the priority's definition of research topics that primarily focus on the procedures and outcomes most important for them.We involve the patients through their representative organizations by inviting the patient representatives to take part in the priority setting for patient safety research.We contact the potential  participants using the publicly available contact information; the participation is voluntary for all participants, including the patients' representatives.The prioritization process leads to the development of the national PS research strategy.Participants can choose which version to follow based on their learning goals or prior experience, supporting their self-directed learning.

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The program includes activities and assignments closely linked to participants' workplace and interests.
• Activities and assignments are performed in collaboration with colleagues or peers.

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The feedback on the assignments is provided by PATSAFE teachers and peer participants (peer feedback).The training program is developed in several steps.First, a needs assessment is undertaken to get insight into potential participants' learning needs and preferences regarding the content and learning activities.Based on this assessment, the transnational curriculum development team formulates general learning goals regarding the main themes.This team comprises experts on various topics concerning PS and healthcare quality, researchers, a research ethicist, an educational advisor and technical administrators from the universities involved in the PATSAFE project.
Based on the general learning goals, the program is structured into three modules, each consisting over several courses: In order to spread the information about the training program and to recruit the participants, we organize an introductory workshop at the beginning of the project.Additionally, for every course a flyer is developed and spread amongst potential participants: academic staff ESRs, and healthcare practitioners, using mailing lists in the Faculty of Medicine of the University of Tartu and Faculty's information letter, the project webpage and university's continuous education program.
Theoretical topics from paths one and two are addressed by face-to-face interactive seminars, including case studies and discussions.For the virtual training, all the materials prepared are organized via modules and pathways using a Moodle e-learning platform of the University of Tartu.This e-learning platform is also used to promote exchange and facilitate work between face-to-face activities.

Stakeholder engagement, dissemination, and exploitation.
This activity coordinates the engagement of relevant stakeholders and implements an ambitious plan of innovative activities to increase the impact of the project research.These activities directly address weaknesses like the lack of international visibility and scepticism towards PS research and data collection.
During this activity the integration of PS research into the development plans of the ICM-UT, the Faculty of Medicine of the University of Tartu, and the Estonian National Health Plan is covered.By elaborating the long-term strategic development plan, and involving relevant stakeholders, the effects of structural funds are maximised, and research and innovation resources attainment to critical mass is ensured.Moreover, the strategy will increase the visibility of ICM-UT's scientific excellence and its potential as an equal partner within European academia and health politics.At the end of the project, we organize a national conference on PS and PS research.As an exploitation strategy, the consortium takes advantage of the material, methodology, and experience developed during phases one, two, and three and organizes a virtual training course on PS research open to other potential interested professionals in Europe.To carry out the course implementation, we perform a business case study, combining marketing, diffusion, and launching.

Impact
The PATSAFE project substantially and measurably improves scientific and innovation capabilities and the performance of ICM-UT in PS research methodology.Thus, it also improves Estonia's PS research and innovation, and overall health care quality (Figure 3).The current data suggest that about one in 10 patients is harmed while receiving hospital care, and about 15% of hospital expenditure and activity in Organisation for Economic Co-operation and Development (OECD) countries can be attributed to treating safety failures 18 .Currently, there are no reliable data about the prevalence of healthcare-related patient harm in Estonia, but adjustment of the international data to Estonian health system demonstrates that in 2016 about 21,675 patients or 1,647 per 100,000 inhabitants could potentially have been harmed during their hospital stays, and that about 98,850,000 Euros were spent treating these failures.These calculations are based on the data provided by Estonian Health Statistic and HEalth REsearch Database : https://statistika.tai.ee/pxweb/en/Andmebaas/Andmebaas__04THressursid/ Increasing Estonian PS research capabilities and performance enables researchers to investigate the magnitude and nature of patient harm in Estonia and, ultimately, promote the development of evidence-based strategies and evaluate the effectiveness of potential solutions.This approach can eventually decrease the high burden on healthcare-caused harm to the loss of capacity and productivity of patients being harmed, and to the loss of trust in the health system, and lead to additional available resources within the health system 19 .
The impact of the project can be seen in different areas: research, education, clinical field, society, and policy.
The research impact is expressed in increased research excellence, improved scientific and innovation capabilities, and better performance by the ICM-UT and is revealed through the following indicators: • increased number of peer reviewed publications in the field of PS and citations, • increased visibility such as number of submitted, accepted and invited presentations in international events, • new research topics and proposals which emerge from the project, • successful participation in new national or EU level competitive research and innovation programs The educational impact of the project is expressed new and improved courses with new educational methods available in person or online and integrated in the curricula of partner universities.
The expected long-term impacts of the project are seen as clinical, societal and policy impacts.The clinical impact is seen when PS practices are applied in clinical environment: patients will be treated by healthcare professionals who are trained in PS.Improvement of PS reporting and learning systems and implementation of evidence-based safety practices is expected to result in fewer adverse events and patient harm.The expected societal impact is expressed first of all in increased PS as a result of improvements following PATSAFE training.More information will be available on PS research, and this leads to deeper understanding of the role of patients in PS as well.
The project's policy impact is expressed in successful collaboration with stakeholders -providers of health services, the Estonian Health Insurance Fund, and the Ministry of Social Affairs, but also promoted by the national PS research strategy in Estonia.Moreover, this project provides an opportunity for researchers to partner with consumers to co-design patient safety research and healthcare services.

Conclusion
As a result of the project, the ICM-UT will apply state-of-theart evidence-based strategies to PS research.The ICM-UT has better capacity to conduct PS research using appropriate methodology, promote PS research among ESRs and healthcare staff, and involve patients in PS research, thus contributing to Estonia's overall healthcare quality and PS performance.For partner institutions, participation in this project provides new opportunities for networking and expanding their research methods to a new culture and setting.Therefore, this innovative project will have the impact on the overall healthcare quality and safety.Bringing together national and international experts to exchange knowledge and experience will maximise the impact of the research for the benefit of the patients and clients of health system not only in Estonia but provides new knowledge and skill that could be implemented in other European countries as well.
6. Please explain how you set up the collaboration with IQ Healthcare and UAB in Barcelona.Briefly introduce both institutions.
7."In the short term, staff exchanges of two to three researchers from the ICM-UT will visit FAD and IQ-healthcare to identify and envisage research topics that are currently addressed at these institutions and the international level and how they are implemented.We identify the researchers who are interested in doing PS research or are already involved in PS research.Identification of research topics is based on the national and international priorities in PS research, by involving national and international level experts, i.e. representatives of researchers, practitioners, patients and policymakers." Please add more information on the methodology you will use to identify international research priorities.How are you going to involve international experts etc.?" The objectives are rather broad and cover a range of activities, and it will be difficult to assess whether they have been accomplished or not.They are more on a visionary level (enhancing, strengthening etc.) that will be hard to quantify or qualify.Bullet points in the SWOT analysis could perhaps be used as/to identify baselines -that will help in assessing fulfillment of the objectives.
The design or rather the activities are rather overall described in relation to the activities.However, the protocol includes many activities and it is hard to describe them all in detail.The description is sufficient to see what they intend to do, but the description does not really support replication of the project.Maybe this format of a study protocol is not the best for such a large initiative as developing a center.

Anne Hogden
University of New South Wales, Sydney, New South Wales, Australia The revised version appears to address the issues identified in version 1.I am happy for version 2 to be accepted for indexing.
Is the rationale for, and objectives of, the study clearly described?Overall, the interventions remain vague and quite repetitive.I think the idea for identification of topics is good: staff exchanges, identification of topics, workshop for consensus of research topics and then a list of topics and methodologies.That said, the implementation of a training program is unclear.Is it just going to be advertised in the hospital generally where for "every course a flyer is developed and spread among potential participants : academic staff, healthcare practitioners".It seems that ICM-UT does not have the in house capacity to develop a course, and some staff exchanges is not going to give them the knowledge for course development.Will this be done with the other universities that they will collaborate with?All we know about the teachers is that they are "experts related to a topic in PS" (p9).There is no mention of the topics, types of experts that will teach, how to guarantee that people will attend, whether there is some kind of accreditation of mandatory participation to the courses, how long they will last, their scope, etc.Although the authors don't have the topics yet, they could have gotten some of the broad topics for patient safety improvement form the literature.
The three modules of the course on p9 mention three modules which include the fundamentals of PS, although on p6 it is specifically stated that the fundamental concepts of PS will not be focused on as they are discussed during the training of health professionals.(Although their course is not only targeting health professionals).
The second half of the proposal has a number of grammatical errors (p.7 speaks about 2019-2022 being in the future ("will help ICM-UT address"), the last sentence on p8 is not a sentence, p9 "this team comprises of experts", and "each module consists over several courses".
When speaking about improvement in the research number of papers and citations, it is very unclear how the 3 research proposals will be written, why there are 3, and what kind of proposals they are.There is no mention of implementing any types of interventions or anything.Although from what I understand, the main goal at this point is "to investigate the magnitude and nature of patient harm in Estonia and, ultimately promote the development of evidence-based strategies and evaluating the effectiveness of potential solutions" (sic), there is no concrete information about how their project will do this.I think that the authors should do a lot more research in patient safety in order to have a more solid project proposal.At the very least, they could identify very general categories such as reducing HAIs or reducing medical errors, etc and then begin to propose a more concrete project.
Minor comments -although it is repeated that "knowledge of PS research methodology needs to be improved" in Estonia (p.4), there is often mention of "increasing visibility of ICM-UT's excellence in PS research" (p4, p8, p9).
Is the rationale for, and objectives of, the study clearly described?Yes

Is the study design appropriate for the research question? Partly
Are sufficient details of the methods provided to allow replication by others?
researchers to partner with consumers to co-design patient safety research and healthcare services.
Is the rationale for, and objectives of, the study clearly described?Yes Is the study design appropriate for the research question?Yes

Are sufficient details of the methods provided to allow replication by others? Yes
Are the datasets clearly presented in a useable and accessible format?

Not applicable
Competing Interests: No competing interests were disclosed.
Reviewer Expertise: Patient-centred care and co-design of research with patients and families; codesigned decision-making tools; lecturer in safety and quality in healthcare.
I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.

Figure 1 .
Figure 1.Conception of the Patient Safety Research Centre (PATSAFE) project.

Figure 2 .
Figure 2. The overall methodology of the Patient Safety Research Centre (PATSAFE) project.
PS research methodology.The PATSAFE training program structure features two pathways.Path one focuses on methods for analysis and improvement, such as measuring and analysing risks and hazards, PS improvement interventions, and implementation research.Path two involves methods for researching PS awareness: patient safety culture and patient safety empowerment.This research methodology training program integrates the 'learning by doing' approach, using traditional training lectures, with more interactive and participatory activities, combined with mentoring and peer-to-peer exchange, to work in parallel with the development of specific scientific outputs (proposal, projects, publications, etc.).The training program development is based on a constructivist learning theory and principles from adult learning.A flipped classroom approach is used to develop the learning materials and activities.These principles lead to the following structure of the training program: • All courses consist of a basic and an advanced version.

Figure 3 .
Figure 3. Improvement of research excellence of ICM-UT in patient safety research methodology.
because of its unique position in Estonia, although taking advantage of these opportunities is currently hindered by gaps in scientific excellence in the fields of specific methods and techniques for PS research.
health outcomes.Moreover, the ICM-UT has experience in the research of quality of care from patient perspectives as well as on the system and provider levels.PS research is currently in an early stage, but due to its position in Estonian health care, the ICM-UT is expected to have a leading role in this research area.ICM-UT offers excellent opportunities for research and innovation in PS

Table 1 . SWOT analysis -identification of gaps in scientific excellence at Institute of Clinical Medicine of the University of Tartu (ICM-UT).
4. Alignment with EC recommendation (2009/C 151/01). 5. High quality health services and patient safety are priorities of the national health strategy.6.Needs of society (pressure from patients).7.Unique possibility to link the national eHealth system and data about the risks and hazards of patient safety.1.Insufficient funding to further develop existing research competence and strengthen the collaboration between scientists and the medical community.2. Insufficient/unfavourable legislative framework for the implementation of patient safety research in practice.3. Poor safety culture and resistance from practicing physicians and nurses concerning risk and hazard data collection.
strategy on PS, and establishment of the Estonian Patient Safety Research Network will ensure the long-term sustainability of PS research in ICM-UT and Estonia as a whole.
The core competencies for PS research, such as fundamental concepts of PS, designing and conducting PS research, and putting research evidence into practice, -are proposed as a foundation for strengthening research capacity by guiding the development of training programmes for researchers in PS.PS researchers should be able to describe the fundamental concepts of the science of PS in their specific social, cultural, and economic context, design and conduct PS research, and be part of the process of translating research evidence to improve the safe care of patients.This project mainly focuses on developing competencies in methods, techniques, and experience for PS research among the ICM-UT's ESRs and staff.To ensure that the participants in the research training have the same level of knowledge, some basic concepts of PS are introduced as well.To ensure the sustainability and continuity of PS research in the future, the competencies for the successful translation of evidence into practice and Considering the SWOT analysis results, the PATSAFE twinning partnership activities involve continuous peer-to-peer collaboration, training academic staff and ESRs, and networking and coordination activities.Looking ahead, the active involvement of ESRs in the project, the development of the national research patients in health care safety research.To assess improvement, we define the indicators that are described in detail in the Impact section of this protocol.
lack of international visibility in PS research, scepticism towards PS research and data collection about the risks and hazards of PS among practicing clinicians, and the low involvement of

Is the rationale for, and objectives of, the study clearly described? Partly Is the study design appropriate for the research question? Yes Are sufficient details of the methods provided to allow replication by others? Partly Are the datasets clearly presented in a useable and accessible format?
8. "3.Development of a joint research proposal and publications".Not only does the perception and readiness of clinicians seem important, but so does the care management team?9. "3.Development of a joint research proposal and publications."What about developing position statements with recommendations for policymakers etc? 10. "As an exploitation strategy, the consortium takes advantage of the material, methodology, and experience developed during phases one, two, and three and organizes a virtual training course on PS research open to other potential interested professionals in Europe".Very useful initiative.

have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.
This is an open access peer review report distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Not applicable Is the study design appropriate for the research question? Not applicable Are sufficient details of the methods provided to allow replication by others? Not applicable Are the datasets clearly presented in a useable and accessible format
? Not applicableCompeting Interests: No competing interests were disclosed.I confirm that I

have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Version 1
https://doi.org/10.21956/openreseurope.16245.r32955I would recommend that the paper is revised before being Approved.