Background: SASHA, which stands for "evidence-informed health policy-making (EIHP)" in Persian, is a national project to draw a roadmap for strengthening EIHP in Iran. As a part of SASHA, this research aimed to develop evidence-based and context-aware policy options for increasing the capacity of decision-makers to apply EIHP in Iran.Methods: This was a qualitative study, which was informed by a literature review of pull efforts’ capacity building programs. Based on the review, we developed policy options and validated them through an expert panel that involved twelve experts. Data were analyzed using a content analysis method. Results: We extracted data from 11 articles. The objectives of capacity building programs were: single-skill development, personal/professional development, and organizational development. According to these objectives, the contents and training methods of the programs vary. Capacity building programs have shown positive impacts on individual knowledge/attitudes to use EIHP. However, the impacts of programs at the organizational or the health system level remain under-researched. We followed several threads from the literature review through to the expert panel that included training the management team, instead of training managers, training for problem-solving skills, and designing tailored programs. Barriers of capacity building for EIHP regard the context of the health system (weak accountability and the widespread conflict of interest) and healthcare organizational structures . Experts suggested interventions on the barriers, particularly on resolving the conflict of interests before launching new programs. A proposed framework to increase the capacity of health policy-makers incorporates strategies at three levels: capacity building program, organizational structure, and health system context. Conclusion: To prepare the context of Iranian healthcare organizations for capacity building programs, the conflict of interests needs to be resolved, decision-makers should be made more accountable, and healthcare organizations need to provide more knowledge management infrastructures and decision support systems. Implications for policy makersThe results of this work could be used to inform progresses for developing locally adapted policy options to increase the capacity of healthcare decision-makers for applying evidence to real-life health policies and management decisions. This work defined the characteristics of locally adapted capacity building programs. It also identified prominent dimensions of organizational structure and the wider context of the health systems that need to be considered for developing local policy options for evidence-informed decision-making. This work sheds light on the aspects of accountability mechanisms and the conflict of interest as preconditions for effective capacity building programs. Policy options need to consider three threads for designing capacity building programs: training management teams instead of only training managers, focusing the training on problem-solving skills, and designing dedicated programs based on the needs of target groups.  Implications for the public Evidence-informed health policy-making (EIHP) is the systematic and transparent process to access and appraise evidence as an input into the decision-making process. Capacity building through training and continuing education is a key strategy to foster EIHP. Capacity building programs that are informed by local needs and contextual factors, may increase skills and confidence of health policy-makers to make decisions that generate better outcomes and serve underprivileged populations. As such, identifying the barriers and facilitators of capacity building programs allows developing effective, context-aware, and problem-based capacity building programs. So far, capacity building programs have shown positive impacts on individual knowledge and attitudes of decision-makers towards the use of EIHP. Yet, fundamental improvements are needed in the way that programs are designed and delivered so that they can improve the functions of healthcare organizations as well as health systems.1 This phenomenon is coupled with a growing belief that evidence-informed health policy-making (EIHP) should result in quality decisions in contemporary healthcare.3 During the past decades, there has been a meaningful shift in the view of professionals to the use of research evidence for policy-making. The notion ‘evidence-informed policy-making’ has been considered not only in the healthcare arena but also in social science and business management.4 Evidence, typically, refers to the scientific outputs of research activities that provide information on the effectiveness of an intervention. Evidence has been viewed in a hierarchy, grading evidence from the results of randomized controlled trials as the gold standard to expert opinion.5 EIHP is defined as “an approach to policy decisions that aims to ensure that decision-making is well-informed by the best available research evidence. It is characterized by the systematic and transparent access to, and appraisal of, evidence as an input into the policy-making process.”6 This criticism can be grasped in the light of the way that ‘policy’ is defined. Policy can be safely defined as a decision that is taken through an authoritative process.7 In practice, there are plenty of policy instances for which no evidence of randomized controlled trials exists. In such cases, other forms of knowledge such as stakeholder views and knowledge of front-line workers contribute to making decisions. Still, EIHP provides decision-makers with tools to support them in following systematic and transparent processes to identify and appraise research evidence and to apply appropriate evidence.4 For issues surrounded with imperfect evidence, EIHP helps reduce the risk of decision-making when the consequence of the decisions does not meet expectations.8 Emerging literature criticizes the appropriateness of the hierarchy of evidence and particularly its gold standard for policy issues.9 EIHP builds the backbone of the WHO program to strengthening health systems. At the heart of this program lies capacity building efforts to enable decision-makers to appreciate the value of the evidence and to identify, appraise and apply research findings into health policies and practices.9 The scarcity of resources in developing countries leaves no room for health policies that deliver no ideal results. To enhance the effectiveness, efficiency, and equity of the health systems in the low- and middle-income countries, the World Health Organization (WHO) recommended focusing on strategies to get the best available research evidence into policy and practice.10 Based on this, “capacity building” is a systematic process of education and training, human resource development, knowledge management and knowledge networks to develop and continuously improve competencies and capabilities of health personnel, health organization, and health system to identify, appraise, select, and apply best available evidence to improve equity, efficiency, and effectiveness of health services.11 Two main types (among others) of capacity building efforts can be distinguished12; ‘pull effort’ refers to training or continuing education for decision-makers that are initiated and funded by healthcare organizations to increase the capacity of decision-makers to acquire, access, assess, and apply research evidence. In comparison, push effort refers to training or educations by educational institutions that are provided by these organizations within their educational missions.12 Capacity is defined as “the ability to carry out stated objectives.”13 At this level, decision-makers are trained to use the tools and techniques of EIHP  and gain confidence to apply them in practice. Training is also used to reduce resistance to change as it is one of the main barriers of EIHP.18 Training in the form of provision of skills to staff is a bottom-up organizational approach to enhance the capacity of organizations to be effective in their operations.19 Individual capacity building is widely used to increase the understanding and use (hereafter ‘uptake’) of EIHP among healthcare managers and policy-makers.13 Ellen et al report general recommendations in terms of enablers and barriers of pull-type capacity building.18 Yet, questions as ‘what program,’ for ‘which target group,’ ‘what objective,’ ‘what contents,’ and ‘what method of training’ remain. Therefore, a full-fledge review of capacity building programs to guide designing new programs is urgently needed. Designing capacity building programs is a hefty task requiring a strong evidence base. Previous systematic reviews shed light on certain options for training programs. Haynes et al recommend that tailored workshops conducted with goal-focused mentoring in a collaborative manner are promising interventions for capacity building.20 which in turn affect the success of capacity building programs. Institutional factors such as democratization and decentralization affect the use of evidence.21 Decentralized organizations grant a greater degree of authority for decision-making, but at the same time, take a greater risk of misuse or underuse of evidence.20 Schleiff et al reported common enablers and barriers in several countries for strengthening institutional capacity for uptake of evidence that revolve around leadership and political will, infrastructure and access to health data, and the structures and processes of EIHP.22 Yet, further research is needed to shed light on enablers and barriers of strengthening EIHP through capacity building programs. In this research, we review the literature to synthesize a taxonomy of pull-type capacity building programs and we propose contextualized strategies to increase the capacity of policy-makers for applying EIHP in Iran. The use of evidence is not only a technical exercise but also a political issue. Various institutional and broader contextual factors in the outer setting of organizations impede the use of evidence for decision-making,Siasatgozari e Agah az SHAvahed ” (SASHA))” was funded by the Iranian National Institute for Medical Research Development (NIMAD) to draw a roadmap for strengthening EIHP in Iran.23 At the first phase of the SASHA project, the barriers of EIHP were identified, which raised fundamental questions on how to empower decision-makers for applying EIHP in the Iranian health system. In this manuscript, we present a literature review of pull efforts’ capacity building programs that synthesizes evidence on the objectives of capacity building programs, learning contents, training methods, and the impacts of programs on participants and organizations. Subsequently, we report a qualitative study that we conducted to validate policy options for capacity building programs among policy-makers to apply EIHP in Iran. Based on the review and the qualitative study, we developed strategies for pull efforts’ capacity building programs in Iran. A multi-phase national project “Evidence-Informed Health Policy-making”  of capacity building programs in terms of, for instance, increase in knowledge of evidence-informed policy-making. Learning materials, modules, or packages that are presented in a program. Target groups, including policy-makers or healthcare managers at a strategic, tactical, or operational level, who have participated in programs. Learning methods, describing how programs have been implemented; learning methods  to enhance knowledge or applied skills. Evaluating whether and how improvements in knowledge, attitude, and/or practice of participants were assessed. Participant selection, describing whether programs’ participants were selected through a competitive application or by invitation. Program duration, indicating the length of time that takes from onset to complete the program.  We relied on a narrative summary of literature for synthesizing data extracted from the included studies. We aimed to present an explicit picture of the capacity building programs on the programs’ dimensions for which information is collected from multiple studies. For this purpose, we outlined the programs’ objectives, learning contents, learning methods, evaluation of capacity building outcomes, duration of programs, and participant selection methods of the included studies. Within the dimensions of programs (see Data Extraction section), we also applied classification that revolves around program objectives. Therefore, the classification of program objectives provided other dimensions with a basis for classification. We also reported overall numbers of studies selected for inclusion in the review. The qualitative study was conducted once the review results were synthesized. In the qualitative study, we assembled an expert panel to discuss the validity of policy options for local contexts. We sent a policy brief, developed based on the review results, to the members of the expert panel, two weeks before the due date of the panel. We began the panel by presenting the results of the literature review in terms of objectives, contents, and methods, and duration of capacity building programs. Experts discussed the implementation challenges of policy options proposed in the policy brief.27 This sampling method was used since participants should have an in-depth understanding of and be experienced in the topic of interest. We invited 15 experts who had several years of experience in developing and implementing capacity building programs and/or the experience of management of healthcare organizations. The expert panel was conducted at the Knowledge Utilization Center of Tehran University of Medical Sciences in August 2019. A policy brief containing a list of policy options was sent to experts beforehand. The policy dialogue started with 20 minutes presentation of literature review results and continued with questions on the feasibility, barriers, and facilitators of policy options developed through the review. All discussions were recorded and verbatim transcribed. The participants of the expert panel were selected based on a theoretical sampling.28 Decontextualization refers to obtaining the sense of the whole transcribed text and identifying meaning units ie, codes. We analyzed the text around the main categories that we aimed to elaborate on the knowledge elicited from the expert panel. These categories comprised of the barriers, facilitators, and feasible interventions for implementing the capacity building program for the Iranian health system. For recontextualization, we went through the transcribed text to assure that all the dimensions of the text have been converted into codes. Categorization refers to condensing the text, identifying sub-categories, categories, and themes. The fourth step refers to the process of writing up. To maintain credibility, we conducted a member check and two researchers analyzed data. We conducted content analysis in four steps: de-contextualization, recontextualization, categorization, and compilation. Study results are presented in two separate subsections: the literature review and the qualitative study. We included 11 articles, which contained three programs in Canada, three programs in Nigeria, two programs in the United States, one program per country in the United Kingdom, Fiji, and Malawi, one program was shared between Mexico and Nicaragua and one was shared between South Africa and Cameroon. Some articles included more than one program. Details of data extracted from included studies are given in Table S1 see .31 The core of single-skill programs rests on creating the capacity to acquire, understand, assess, and apply research evidence. Personal/professional development programs aim to develop the whole person as a professional decision-maker rather than only developing a single skill. In these programs, leadership development is the main objective.33 We distinguished objectives into three types : single- Organizational development programs aim to enhance decision-making in healthcare organizations by enhancing the capacity of decision-makers and providing them with opportunities to exercise increased knowledge and skills of EIHP. Three programs ‘Executive Training for Research Application (EXTRA), ‘Swift, Efficient Application of Research in Community Health’ (SEARCH), and ‘Service Delivery and Organization’ (SDO) programs mentioned objectives to enhance personal/professional development. These programs address skills for EIHP and skills for leadership, change management, and understanding the context of the healthcare organization. These programs also provide participants with opportunities to execute skills for solving real-life problems of their host organizations. In the EXTRA and SEARCH programs, participants used their acquired skills and knowledge to solve organizational or policy issues pertinent to the state or provincial health systems.34 mid-level managers, policy-makers, and policy advisers in the health sector or non-profit organizations. Moreover, healthcare delivery managers were targeted by some programs. In Canada, EXTRA and SEARCH programs focused on strategic healthcare management positions at the provincial and/or national levels. In the United Kingdom, the SDO program aimed at increasing research application among mid-level managers with potential for growth to top-level management positions.35 In the United States, public health professionals were trained for EIHP.36 In developing countries, capacity building programs were provided to a wide variety of decision-makers, policy advisers, and operational managers of healthcare delivery organizations.33 Programs considered various target groups including strategic managers,37 Some programs used standard tools, eg, Supporting the Use of Research Evidence (SURE), Grading of Recommendations, Assessment, Development, and Evaluations (GRADE), A Measurement Tool to Assess systematic Reviews (AMSTAR), for training seven technical skills of EIHP.33 Contents on how to synthesize evidence, eg, research summary, were included in certain single-skill programs. Personal/professional development programs additionally included materials for increasing soft skills such as networking, thinking styles, partnership building, and getting an endorsement from provider organizations for policy briefs and review findings.33 In addition to the materials mentioned for single-skill and professional development programs, organizational development programs comprised contents on the context of the healthcare organization, culture change, change management, and leadership skills so that participants learn to understand organizations, mobilize resources, and initiate and sustain changes based on research evidence that was collected during research projects.34 Programs’ contents were essentially consistent with the programs’ objectives. The single-skill programs mostly consisted of seven technical skills for EIHP such as skills to access, identify, evaluate, and use research findings.35 Contents for research skills eg, rapid review, systematic review, empirical research, and problem-solving skills were intensive in EXTRA and SEARCH programs. The UK fellowship program however included no pre-specified contents as it meant to be a tailored training. The contents of this program were defined based on the specific needs of participants.34 Module 1 promotes the use of research evidence in healthcare organizations through learning to deal with policy factors and policy context. Module 2 increases research literacy. Module 3 teaches skills to use research evidence in healthcare organizations. Module 4 focuses on learning individual leadership skills as well as the way that organizational culture and politics influence the conception and use of evidence. Module 5 considers skills, strategies, and resources to monitor and sustain long-term change in organizations. And module 6 provides participants with opportunities to present the value of their research. The most comprehensive program was EXTRA with six modules.38 research summaries,33 literature reviews,37 and research projects.34 Programs used various supporting methods to assist participants in applying skills to solve real-life problems. Mentorship methods were used to support participants in applying skills in practice.37 The majority of programs provided some types of mentoring supports for participants.32 However, the duration of mentoring varied between programs. Programs also reported using information technologies such as emails, web tools as well as telephone calls to support participants. Most programs used tailored training, which defines educational contents according to the requirements of participants.38 Three common training methods were: lectures and workshops, conducting or participating in research activities, and goal-oriented mentoring. Almost all programs included online or face-to-face lectures or workshops to increase the theoretical knowledge on the key skills of EIHP. Programs then continued with research activities to apply acquired knowledge to solve or to exercise solving real-life problems through writing policy briefs, In SDO and EXTRA programs, participants take part in a research process from writing a research proposal to data collection, data analysis, and the presentation of findings. The difference between these two programs was that in EXTRA, participants write and conduct research projects with the support of mentors, but in the UK’s fellowship, participants take part in a university research project and learn by being involved in the project. It is worth noting that participants in SDO, EXTRA, and SEARCH programs work on real-life problems of their organizations.34 Depending on the type of program, other methods of evaluation included document analysis, interviews, and focus group discussion.37 The evaluation of programs has been conducted at the individual, program, and organizational levels. The evaluation of the program’s results relied on both quantitative and qualitative research methods. In most of the quantitative analysis, the assessment was based on the pre-and post-self-assessment tests.39 For instance, in the EXTRA program, a cohort of participants consisting of health service executives, physicians, and nurses reported the positive impact of the program at the individual level. This program improved research literacy by 55% and the ability to promote the use of research evidence in an organization by 70%.34 The evaluation at an individual level assesses increases in knowledge and enhanced perceived skills to apply EIHP tools in practice. At least three programs reported positive impacts on knowledge and perceived skills at the individual level.34 which showed a modest positive impact of the program. A study assessing the impact of training to apply EIHP in public health reported that 45% of participants think that training increased evidence-based public health in their organizations.38 Moreover, programs were evaluated regarding practical improvement in skills related to EIHP such as writing policy briefs,38 conducting a systematic review, and doing applied research.34 The frequency of referring to course materials later on in planning or evaluating public health operations was also used as an indicator of program impact at the organizational level.36 Few studies reported the results of the evaluation at the organizational level. The impacts of the SEARCH program at the organizational level were evaluated using qualitative methods,36 Depending on the program objectives, the duration of the program varies. The EXTRA program had a short-term or midterm duration for professional/personal development objectives and a long-term duration for the health system development. The SEARCH program took 2 years. The SDO fellowship was a 12-month full-time program or if part-time, then equal to 12 months. Most other programs, given being focused on enhancing single skills, took some days.34 and SDO programs.39 Single skill-focused programs were running for a short period of time, at most a couple of weeks. Participants of these programs eg, decisionmakers or field managers were generally invited to participate in the training, regardless of their interest, time, or motivation. In contrast, EXTRA, SEARCH and SDO required long term (at minimum 1 year) efforts, thus participants were selected thoughtfully considering their interest, time, and potential. In the SEARCH program, a committee at the provincial level, including a top policy-maker, selected program participants. SDO fellowship had clear eligibility criteria for candidates. In SDO, individuals with managerial positions and those at mid-level but highly motivated, with great potential to promote to a senior management level, or infigdividuals with a willingness to participate in the research were selected for the program. Participant selection was not performed in most programs with explicit criteria or a long-term perspective, except in EXTRA, SEARCH, Based on the review, we developed the following policy options.40In the short term, the Iranian Ministry of Health and Medical Education (MoHME), as the main actor of EIHP, develops and implements personal/professional development programs to create a critical mass .In the long-term, MoHME develops and implements capacity building programs to enhance the performance of healthcare organizations through a change in organizational culture towards EIHP. For capacity building programs, MoHME uses current national healthcare management training programs . MoHME takes steps to break the causal chain or to change contextual factors that blur the needs for EIHP skills, training programs, and to apply EIHP in real-life practice.  The expert panel affirmed the value and use of research for both policy and practice. They reflected on the design of the capacity building programs and barriers and facilitators. Informants also suggested interventions to tackle barriers or address constraints to promote EIHP. Experts made a distinction between the characteristics of capacity building programs before- and after-assignment of individuals to management or policy-making positions. They believe that training programs through residency sessions, workshops, and mentoring could be effective before assigning individuals to management positions and after assignment, those methods cannot change the behaviors of decision-makers to apply EIHP. They suggested practical training such as project-based learning or learning by doing for after assignment to a decision-making position. Regarding this, a quote from one experienced trainer and healthcare provider follows:Training such as residency sessions, workshops, and mentoring are effective methods before an assignment and could prepare a person for finding, analyzing, and using research evidence for a future managerial or policy-making position.… Training after assignment [include training] such as project-based training systems ‘learning by doing’ and giving adequate training during occupying a position.  in Iran since person receives organizational authority and power from elsewhere [than the legitimate sources of power], this way of training would be feasible on paper and in practice would not find a possibility for implementation.”  “ Codes on making a distinction between capacity building programs for policy-makers versus those who identify policy options, and between healthcare managers versus policy-makers emerged in several places in the transcribed text. The qualifications, roles, and authorities of these groups are different; consequently, there should be different methods and the contents for their capacity building programs. Particularly, managers are focused on organizational issues; whereas, policy-makers are dealing with systems that are more complex than organizations. Tailoring capacity building programs to the educational needs, requirements and contingencies of these target groups were emphasized by experts. Informants also emphasized training to create capacity for problem-solving in healthcare organizations. Given this, one participant was concerned that the proposed programs are unlikely to increase capacity of policy-makers. For instance, she remarked that the proposed policy options for capacity building programs and the contents proposed are unlikely to address the needs of the policy-making bodies at the MoHME and the Health Commission of the Iranian Parliament. Some of the suggestions pointed out to the experiences of previous programs. The selection of trainees was a key issue in earlier capacity building programs, as some trainees were at the end of their career in the public sector, and they were about to leave the system without any return on the training. Experts also pointed other types of conditions before the implementation of new capacity building programs. One expert mentioned that we have already an adequate number of management training programs but evaluating previous programs before implementing new ones is more important than just launching a new one. It was emphasized that prior capacity building programs should be evaluated, and the evaluation should be based on clear, transparent, and specific criteria. Having learned about the capacity building programs, experts suggested several interventions to help facilitate the implementation of EIHP and reinforce the capacity building programs. These interventions considered prerequisites and supportive contexts for EIHP, addressing capacity building at the team level rather than individual level, and learning from the past capacity building programs. Barriers include accountability and responsiveness, conflict of interests in the context of the healthcare system, and organizational structures and processes. Based on the experts’ views, the style of decision-making, which is largely a factor in the context of the Iranian health system, does not make any commitment to the use of evidence. This style, like an established culture, forms decisions and determines the quality of decisions. The style is shaped by the lack of accountability and responsiveness in the whole context of the health system. Informants state that managers should be kept responsible for their decisions. For example, one informant who has significant experience in training and strategic management stated that responsiveness should be embedded in the structure of organizations and the health system and also be demanded by employees at the bottom of the organizational hierarchy. The sense of responsibility encourages decision-makers to follow training and to make evidence-based decisions.“The decision-making style in Iran does not commit to the use of evidence. Decision-makers are not questioned about the base or motivation of their decisions. If managers were kept responsible for their performance, [they] will pursue training and making decisions based on evidence… Demanding [responsiveness] should begin from the bottom [of organizations] and keep governing systems responsible. If responsiveness increases, the manager commits to behaving based on evidence. The structure should be designed in a manner that keeps the manager responsive at every moment. For being responsive, the manager needs to involve others and as a result, evidence would be collected, [in turn] leading to collective logical and rational decisions”(Policy-maker and trainer). Several experts emphasized understanding what real problems that prohibit EIHP. According to the experts, managers know existing evidence and know how to use it, but one real problem, among others, is the conflict of interest. As a result, managers look for pieces of evidence that support their decisions. Below, a quote from a trainer follows:“Research has shown that in most cases, policy-makers know the evidence and know that they should use [evidence] but do not use it. Managers are not looking to find the right evidence, but [they are] up to make up evidence to justify what they have in their mind. Thus, the problem is not knowing [evidence] or capacity building [programs] only. Other issues are also involved such as the conflict of interests.”  The expert panel also provided recommendations to tackle the contextual challenges. One key decision-maker with several years of experience remarked that prerequisites in the context of health systems or in the structure of organizations need to be present to ensure that the context is receptive to individuals who have developed capacity for EIHP. Preparing the context requires resolving critical issues, notably the conflict of interests, in the context and structure; “The capacity building programs could be effective contingent on satisfying prerequisites and meeting requirements that rest in the context or structure of healthcare organization; otherwise, in undeveloped organizations, developed individuals make no difference. Unless certain problems such as the conflict of interest, are resolved in the health system, the path discussed in the meeting would not be possible to be implemented.”  Organizational structure in terms of management authority, decision support systems, and knowledge management infrastructures were referred to as the barriers in the organizational structures. While participants discussed the chain of causes that hinder EIHP, the structure of healthcare organizations was emphasized as the root cause of the lack of EIHP. As one healthcare provider and trainer stated, the structure acts as a bottleneck that limits the overall use of evidence. “In practice, a chain of causes leads to the current situation [of the lack of EIHP in Iran]; therefore, our conversation today about training and empowerment may have other main root cause as the main barrier or driver [of EIHP]. One of these main causes is the structure of organizations. Therefore, opinions that are offered [in this meeting] may independently and individually be right, but when run in the context of an organization, somewhere stop and are trapped, and out of this discussion that intended solution may not be immediately obtained and needs integration [into the context of organization].” “having a greater authority for decision-making does not have a very clear relationship with acting based on evidence, it may even lead to making inappropriate decisions via this inappropriate authority.” One informant remarked that the management authority to make key decisions is limited; policies are determined at a higher level. On the other hand, there was a counterargument that  Management tenure is so short, which prohibits focusing on main solutions such as EIHP. Furthermore, there is a high expectation from managers to deliver results, at the same time, no decision support system exists to assist them in handling a pile of tasks. Knowledge management and the free circulation of information are not yet institutionalized in our organizations. In this situation, healthcare managers tend to embark on short-run projects. Participants stated that managers have no time to think, thus it is necessary to support managers through think tanks, advisors, and management teams. In addition to decision-makers, individuals whose job is to develop or to identify policy options, need capacity building programs. Furthermore, management teams and not only managers need training. Experts also made statements about the process to fill in management positions. The process for selecting, assigning, and changing managers should be updated. One participant cast doubt on the efficacy of capacity building programs to empower policy-makers, as they are not selected based on their capabilities. Facilitators that were identified are related to the current infrastructures, rules, and regulations that promote capacity building programs. One informant underscored the capacity of current healthcare management graduates, which are almost abandoned in the health system. The capacity of the educational systems of the country can also be used to deliver capacity building programs. There was a remark that decision-makers and managers have a ‘Life Course View’ indicating that they prefer to leave a legacy behind. This view may reinforce the capacity building programs if the managers are convinced that they could even have a more significant legacy by using evidence-informed decision-making tools and techniques. We mixed findings from the literature review and the expert panel in  We configured policy options at three levels: program, organizational, and the context of the health system. Starting with the program level, we envisaged two distinctive lines; designing capacity building programs for before-assignment and programs for after-assignment to management or policy positions. These two lines have distinctive target groups, objectives, training methods, contents, and impacts. The surrounding issues of both lines regard the way that programs are designed and considerations that are taken into account for designing programs. These considerations include scrutinizing previous programs, lessons learned from past programs, and developing transparent and specific criteria for the evaluation of programs. Furthermore, the right participants should be selected for programs, given training is like an investment that needs to have a return. At the second level, the policy options address factors in the structure of organizations. This level, on one hand, suggests increasing management authority, and on the other, it suggests increasing the management responsiveness to make a balance between authority and responsibility. To support management authority for making a decision based on evidence, it suggests establishing advisory systems and information infrastructures and building decision-making teams. Interventions at this level also consider selecting the right people for management positions and free circulation of information. At the third level, there are contextual factors that also impede the impact of capacity building programs. Resolving the conflict of interest for decision-making positions is a key factor. Change in the context may regard strengthening two lines of accountability, through top-down mechanisms and bottom-up mechanisms. The majority of reviewed programs were focused on developing a single skill rather than on professional development or organizational development. Programs that were focused on professional or organizational development were delivered in resource-rich countries such as Canada. By moving from single-skill programs towards the personal/professional and then organizational development programs, learning contents also include materials on soft skills, decision-making mindset, networking and partnerships, change management, and leadership skills to execute and sustain changes.3 When participants held the central role and/or leadership positions in their organizations, the change of attitude towards EIHP was facilitated.2 It is worth noting that, there is no report for the evaluation of capacity building programs at the health system level, which indicates the lack of research or the presence of publication biases.34 The evaluation of programs at the individual level showed positive impacts of the programs on the knowledge and confidence of participants. Few studies assessed the impacts of programs at an organizational level. The evaluation of programs’ impacts at this level assessed the spread of knowledge and attitude of EIHP to other members in organizations for which very little evidence is generated.3 Reinforcing this theme, the participants of the expert panel also emphasized dedicated programs and made a distinction between the characteristics of programs before versus after assigning to management positions. We incorporated this as the core of our framework in  The literature review showed that dedicated programs attract management attention to the program and make them more committed to participating.41 Problem-solving was a common thread between the review and the expert panel. Programs such as EXTRA and SEARCH, which also intended to impact organizations, were organized around helping program participants to be able to solve real-life problems. After assignment to management positions, problem-solving skills are more important as they accommodate the real needs of organizations. When individuals hold management positions, learning by doing via support from mentors with local knowledge could be an effective method for capacity building. As given in the framework to increase the capacity of policy-makers on EIHP, efforts to increase the capacity of policy-makers need to prioritize interventions for breaking the chain of causes that leads to inadequate uptake of EIHP. Within the chain of causes, the contextual factors and organizational structure were overrepresented by the expert panel.42 Therefore, in the first place, conflict of interest should be resolved, otherwise, interventions on other factors would not bring about desired outcomes.43 It is however worth noting that interventions to resolve conflict of interest may take a long path or may never succeed. Among contextual factors, informants insisted on the intervention to resolve the widespread conflict of interest in the health system as a prerequisite or even a bottleneck that limits the overall progress of EIHP in Iran. The conflict of interest has been growing in the health sector in the past decades. Several factors give rise to this issue, such as the regulatory capture and mixed responsibility of both policy-making and service provision in a single body ie, MoHME. As a result, many evidence-based reforms find no chance to be implemented, such as family physician programs. As mentioned in the expert panel, the context of the Iranian healthcare system is not aligned with EIHP. As a result, little sense of responsibility exists to support learning or to motivate pursuing training programs to improve the quality of decisions. An accountability mechanism, either top-down, as a management control mechanism, or bottom-up, as a public demand mechanism was recommended to make decision-makers more accountable.3 Therefore, investments in advanced decision support systems and knowledge management infrastructures are essential to ensure facilitated access to evidence. Weak accountability mechanisms are accompanied by poor advisory or decision support systems and knowledge management infrastructures for management positions with a pile of unimportant tasks to do and staffing shortage.36 Another study reported that training a team or group of individuals from the same organization had positive organizational impacts by spreading the attitude of EIHP in the organization.3 This however requires a certain degree of decentralization for which there were two different views among the panellists; one refers to limited managerial authority, another indicates that practicing EIHP has nothing to do with authority and that with less-developed decision-makers, a larger authority leads to even more inappropriate decisions. Another closely related intervention is that to support decision-makers by building a management team or decision-making team and training the teams. However, these arrangements could be developed through organizational processes instead of waiting for reforming organizational structures. Jacobs and colleagues reported that the team as a whole should be able to practice the EIHP process.34 Even though most of the suggested interventions on their own make sense, implementing them might be time-consuming. Aligning the context of the health system and structure of healthcare organizations with EIHP may take a long time. Therefore, instead of waiting for fully ready context and organizations for EIHP, decision-makers should learn to work in the existing context and make and sustain changes. In EXTRA and SEARCH programs, participants learned skills to understand the complex context of health organizations and to create and sustain improvements through change management and leadership skills in the current contexts. This study faced several limitations. First, while experts shed great light on the structural and contextual factors that are pivotal for effective capacity building programs, we provided experts with no review of structural or contextual factors in the literature. Other subprojects of the Iran EIHP study synthesize policy options to address dimensions of structures of healthcare organizations. Second, our search strategies may have overlooked certain relevant articles that present training for research skills or problem-solving skills among decision-makers. In other words, we likely did not identify a representative sample of the literature in our review. To deal with this limitation, we searched the Department of Health in Australia, Canada, and the United kingdom for the pull efforts that were presented in annual reports and so forth. These departments were selected based on consultation with experts in evidence-informed decision-making. The search in these departments was not as systematic as the search strategy applied to the databases. The positive impacts of capacity building programs on the knowledge and attitude of policy-makers are reported. However, a long path remains to accomplish the impacts of programs at policy-maker behaviours, healthcare organizations, and health systems. Paving this path requires the rearrangement of capacity building programs. We followed various threads from the literature review through to the expert panel so to develop our framework and strategies for capacity building programs in Iran. These threads included, but not limited to, building and training a management team instead of only training managers, focusing the training on problem-solving skills, and designing dedicated programs based on the needs of target groups. Based on the proposed framework in  We are grateful to all who contributed to conducting this research. This research was approved by the ethics committees of Tehran University of Medical Sciences (IR.TUMS.VCR.REC.96.02.159.35954) and the National Institute for Medical Research Development (IR.NIMAD.REC.1397.476). Authors declare that they have no competing interests. Conception and design: MM, HSS, BY, and RM. Acquisition of data: MM, SN, RM, JSK, SHGH, RT, HD, LD, HSS, and BY. Analysis and interpretation of data: MM and RM. Drafting of the manuscript: MM. Critical revision of the manuscript for important intellectual content: RM, HSS, EE, and LD. Obtaining funding: RM. Administrative, technical, or material support: SN. Supervision: RM. This work was supported by the Deputy for Research and Technology at the Iranian Ministry of Health and Medical Education (Grant Number 700.1953) and Iranian National Institute for Medical Research Development (NIMAD) (Grant Number 958431). Funders had no role in any part of the work including design and conduct of the study, data collection, data management, data analysis and interpretation, preparation, review and approval of the manuscript.Supplementary file 1 contains Table S1.Click here for additional data file.


Despite sophisticated study designs and measurement tools, we have yet to create an innovative space for diet and dietary supplements in the health care system. The path is challenging due to current hierarchies of scientific evidence and regulatory affairs. The role of the randomized, double-blind, placebo-controlled clinical trial (RCT) as a research approach functions well to characterize the benefits and risks of drugs but lacks the sensitivity to capture the efficacy and safety of nutraceuticals. While some facets of RCTs can be relevant and useful when applied to nutraceuticals, other aspects are limiting and potentially misleading when taken in their entirety. A differentiation between guidelines for evidence-based medicine and the evidence required for nutrition spotlight the need to reconceptualize constituents of the RCT and their applicability with relevance to health promotion. This perspective identifies the limitations of the traditional RCT to capture the complexities of nutraceuticals and proposes the N-of-1 as Level 1 evidence better suited for the proof of efficacy of nutraceuticals. Nutraceuticals, such as dietary supplements, are defined as products isolated or purified from foods that are generally sold in medicinal forms not usually associated with food and demonstrated to have a physiological benefit or provide protection against chronic disease . HoweverFrom a regulatory perspective, nutraceuticals are categorized under a variety of terms, depending on the country's regulatory framework. For example, in Canada there are natural health products (NHPs) and supplemented foods, under which nutraceuticals can be included. The European Food Safety Authority (EFSA), US Food and Drug Administration (FDA), and Health Canada use evidence-based reviews to evaluate the strength of scientific evidence that support marketing claims for foods and dietary supplements, specific to the terms used by each country. This review process assesses causation and is largely based on evidence-based medicine (EBM), a concept where the underlying hypothesis is that the intervention mitigates a condition in a causal manner . EBM aimThis perspective will discuss limitations of the RCT and will show that the traditional RCT drug model is neither sensitive nor relevant to nutraceuticals because (i) true placebos are not possible, (ii) effect sizes in ‘healthy' volunteers are most often modest, (iii) statistical analyses need to be refocused, (iv) endpoints must be global or multifunctional, (v) proof of efficacy should advance to that of probable harm due to lack of the intervention, and (vi) of the requirement for ‘healthy' participant enrollment. Therefore, we propose N-of-1 studies as Level 1 evidence better suited for nutraceuticals.Currently over 400,000 RCTs, are being conducted throughout the US and in 220 other countries –8. For eAreas of research such as in psychotherapy where individualized interventions cannot be generalized or applied via the RCT have been accepted in treatment modalities , 13. PreEasily obtained victories for pharmaceuticals have been based on crowd-based medicine efforts such as vaccinations and other population-based interventions. Indeed, though RCTs were originally designed to decrease bias in research, they have become a point of “conflicting interest” , 26.Sackett et al. stated: “individual patient care is not restricted to randomized trials and meta-analyses. It involves tracking down the best external evidence with which to answer our clinical questions” . HoweverThe application of RCTs to disciplines not related to testing drugs, such as foods, beverages, and dietary supplements, is fraught with challenges, the most prominent of which are the inherent differences between drugs and nutrients. Drugs are directed toward treatment of disease. They have isolated functions and are designed to target single organs or tissues and are not homeostatically controlled by the body. Unlike most drugs, nutrients work in complex networks, target all cells and tissues, and have multifaceted effects and outcomes. Therefore, RCTs for nutrients must be designed to capture this multifunctionality. Since many nutrients are homeostatically regulated, the body's baseline status affects the response to a nutraceutical intervention. For those not homeostatically regulated, excessive amounts are either not bioavailable, or are metabolized relatively quickly and/or eliminated, thus leading to their generally high level of safety.Large effect sizes can be expected in drug studies, intended to show superiority or comparability, as there is a no-intake control group or a true placebo. There is a distinction in the reduction of the symptoms of disease, which is present in the enrolled population and the absence of the intervention does not cause disease , 28.In contrast, true placebos are not possible with nutraceutical studies and the interventions involve the intake of nutrients, the absence of which may cause disease. In the absence of a true placebo group, and the requirement of ‘healthy' participants, nutrients have a smaller effect size and a longer response time to detect health outcomes. Essential nutrients are necessary for health and thus the underlying hypothesis that low or inadequate intake of nutrients causes or contributes to disease . Heaney The regulatory requirements of enrollment of populations “defensible as healthy” in studies intended for substantiation of structure/function claims limit the purpose of nutraceutical investigations. This accentuates the small effect size, decreasing the gap between the placebo/control and intervention . In the Persistent advocacy and requirements result in findings of clinical trials being limited to narrow and unrepresentative populations. This is a disservice to consumers seeking alternative solutions to improve their health. More recently, the concept of ‘healthy' has been upended by investigations showing that those previously considered ‘healthy' may in fact be metabolically unhealthy . A paradp values as the “gold standard of statistical validity,” above and beyond other frameworks for data analysis, which include statistical power, false positives and negatives have been challenged , EFSA, and New England Journal of Medicine (New Engl J Med) point away from such requirements that are founded on misinformation and urge movement toward providing clinical significance. “The .05 era” .p values stating that nutrient studies should be directed to solve a health indication, not for statistical convenience , has been discussed in detail by a Nutrition Research Task Force of the American Society for Nutrition . They stWhen compared to the traditional RCT, N-of-1 provides greater strength and more reliable data in clinical decision-making . FurtherThe N-of-1 trial allows for rapidly identifying responders vs. non-responders, requires enquiry into clinical significance, and provides a venue for the use of a global index outcome that is more generalizable to the nutraceutical industry . FurtherThe conventional RCT model does not withstand the scrutiny required to make it useable as a source of evidence for the proof of efficacy of nutraceuticals. The N-of-1 RCT design obviates the limitations and lack of sensitivity of the traditional RCT used to test drugs in the therapeutic milieu. The N-of-1 design provides a more relevant control group, addresses concerns about effect size, can capture global or multifunctional outcomes, allows for advancing from proof of efficacy to that of probable harm in the absence of an intervention, and measures clinical significance. N-of-1 studies provide faster information for identifying optimal individualized interventions, and facilitating translational research by capturing principles that can be generalized to population subgroups . AccumulThe original contributions presented in the study are included in the article, further inquiries can be directed to the corresponding author.ME and JB contributed to conception and design of the perspective. ME, EL, JA, and JB wrote the first draft of the manuscript. All authors contributed to manuscript revision, read, and approved the submitted version.Authors ME, EL, DC, JA, and NG are/were employed by KGK Science Inc. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Robust evidence-based guidelines are important in everyday clinical practice, especially when delivering and managing oral care needs to a vulnerable group such as children with special healthcare needs (SHCNs). Methods: To assess the quality of guidelines on the management of oral care for children with special healthcare needs (SHCNs) and to find appropriate guidelines, an electronic search of MEDLINE Ovid was carried out alongside an additional search of common guideline websites. The AGREE II tool was used to assess the quality of the guidelines. Assessment was undertaken independently by three assessors. Furthermore, the underlying evidence used to formulate recommendations in the identified guidelines was qualitatively assessed. Results: There were nine guidelines, with 41 recommendations, that met the eligibility criteria. The quality of the guidelines was generally found to be poor. Only one guideline was assessed as “recommended” by the assessors, based on the quality of the methods, the reporting, or both. Only 2 of the 41 sets of recommendations, made across the nine guidelines, were judged to be valid and based on a rigorous systematic review of the evidence. Conclusions: The current state of guidelines on oral care management for children with special healthcare needs (SHCNs) is, on the whole, of very low quality. The scientific community should work together to enhance the quality and strength of the current clinical guidelines and to ensure that they are trustworthy prior to implementation. Children are categorized as having a special healthcare need if they are living with a health condition that limits their ability to function in one or multiple aspects. These can include physical mobility, cognitive or sensory functions, memory, or self-control, among a variety of other aspects . ChildreDeterioration of oral health among children with SHCNs can, in part, be attributed to various underlying factors such as enamel irregularities, craniofacial birth defects, impaired salivary function, malocclusion, periodontal disease, and more frequent oral infections ,13. AddiOral health conditions for children with special healthcare needs (SHCNs) are often poorer when compared with healthy children ,14,15. OThe receipt of optimal oral healthcare is fundamental for children with SHCNs as it can provide them with confidence, thereby allowing them to reach their full potential as well as take part in society. Providing children with SHCNs with appropriate oral healthcare necessitates additional treatment and care from all health workers, where they take into consideration the physical and medical limitations of the child . One impGuidelines are mainly aimed at providing oral health practitioners and clinicians with a set of explicit recommendations and suggestions regarding how to deal with certain situations, as well as to minimize the use of harmful, ineffective, or unnecessary actions or measures. Those developed recommendations should be the result of a long process of consideration of valid and up-to-date evidence for the correct management and treatment of the dental patient. By reducing inconsistencies and variations between clinical practice and scientific evidence, clinical guidelines can enhance the quality of dental care that is delivered to the patients. Guidelines should be rigorously developed and precise, ensuring that any resulting recommendations are clear and reproducible .Several factors can limit the usefulness and/or the applicability of clinical guidelines. These include the guideline development methodology, the availability of sound research evidence, the uniqueness of individuals, and how the research findings can be generalized. On that basis, guidelines for the management of oral health in children with SHCNs should be appraised as it is very important to identify and analyze any potential flaws in their development ,24. IndeThe AGREE II tool is an instrument that is used widely for the assessment of transparency, accuracy, and the methodological rigor of guideline development and has been tested for its reliability as well as validity. The AGREE II tool is to be applied or used by guideline developers to properly guide their work and to evaluate or assess the quality of their methodology (the AGREE Collaboration). In addition, it also offers a preferred methodological framework for the development of content for the guideline. This instrument has been designed and developed to assist in the standardized and objective appraisals of guidelines, as not all clinical guidelines are developed or conducted transparently and rigorously . The aimA systematic review was undertaken to identify clinical guidelines and recommendations focusing on oral healthcare and treatment of children with SHCNs in dentistry. The AGREE II instrument was used in this study to critically evaluate clinical guidelines for the treatment and care of children with SHCNs.Guidelines published in the English language and within the past ten years;Only guidelines listed for specific or clinical circumstances or conditions for children and with SHCNs related to oral healthcare were included;Only guidelines intended for or directed towards practitioners to assist in handling, as well as treating, oral health for children with SHCN in pediatric dentistry were included.We included guidelines that met all of the following inclusion criteria:Guidelines that have been superseded or modified by a more recent version carried out by the same group of guideline developers;Guidelines that were reproduced versions of previous or current guidelines and have not been reproduced with amendment.The exclusion criteria for the guidelines were:A search of the MEDLINE Ovid database was conducted using the search terms that are shown in One assessor examined and evaluated the titles as well as the abstracts of each of the retrieved records to determine which ones were appropriate and should be selected as per the eligibility criteria. If the retrieved records were not clear from the titles and abstracts, a full-text copy was checked for any potential eligibility.The AGREE II instrument aims to provide a framework to assess or analyze the quality of clinical guidelines; to provide a procedural and systematic strategy for guideline development; to inform or explain the preferred content and the reporting of the content in clinical guidelines. The AGREE II instrument is comprises 23 key items within six domains, with two additional global rating items. The six domains are presented in strongly disagree) vs. score of 7 (strongly agree)).All 23 items, across the six domains, are rated on a 7-point scale, where a score was assigned based on reporting quality and completeness. A score between two and six was given when the reports of the item failed to address all the item considerations or full criteria . All the included guidelines scored greater than 60%. However, clinical guidelines are likely to score high in this domain, as this is a fundamental part of the guideline development process. Meanwhile, the second domain, “Stakeholder Involvement”, generally fared less well, with a median score of 28% (range 17 to 83%) and only two guidelines scored greater than 60% ,33. FurtThe third domain, “Rigor of Development”, was judged as poor, with a median score of 28% (range 3 to 88%) and with only one guideline that scored > 60% . All the included guidelines had noticeably low scores across all items in the “Rigor of Development” domain, especially items 13  and 14 (guideline updating procedure provided). In addition, we judged the fourth domain, “Clarity of Presentation”, to be poor for four guidelines, scoring <60%, with a median score of 63% (range 35% to 85%). Furthermore, a high score in this domain by presenting the recommendations in a clear format should not be too difficult to achieve; however, four guidelines fell short in this area ,26,28,31When inadequate focus is applied to the underpinning evidence in guidelines, there is a chance that incorrect recommendations may be given, subsequently leading to clinicians’ performance being potentially less than optimal for their patients. Recognizing the relevance and quality of the underpinning evidence can of course mitigate such negative outcomes. The majority of guidelines do not take into account the extent to which evidence can be generalized for people, interventions, and outcomes ,36. WhilThe main researcher, with a background in the topic covered in the included guidelines, documented the recommendations and underlying evidence cited by each guideline. Striving for an objective review, all guidelines were thoroughly investigated to determine whether high-quality evidence (systematic reviews) had been used as the foundation for any recommendations by appraising the references presented. References to systematic reviews were examined independently and in duplicate to determine the quality and the relevance of the underlining evidence.Overall, 41 sets of recommendations were reviewed in the included guidelines. Naturally, some guidelines dealt with multiple conditions rather than just one. The most frequently mentioned issue was the use of general anesthesia, sedation, and behavior management of children with SHCNs (in seven of the nine guidelines). This was followed by the use of clinical holding and the use of fluoride. Among the recommendations reviewed, only two were deemed to be sufficiently supported by a high-quality systematic review. Furthermore, the recommendations in just two of the reviewed guidelines had been allocated a grade/level that the remaining guidelines failing to do .It is important to acknowledge that certain limitations in the review process may have had an impact on this guideline appraisal work. Firstly, it is important to emphasize that, despite our best efforts, this was not a comprehensive or exhaustive assessment of clinical guidelines in relation to oral healthcare for children with SHCNs. Some clinical guidelines may have been missed as a result of human error or due to the electronic search strategy. Some clinical guidelines do not include children with SHCNs in their headings or abstracts as a potential beneficiary, which makes it challenging to identify potentially eligible guidelines. Further, guidelines are rarely indexed and are not always published, making their identification and retrieval difficult. For guidelines to have any chance of improving clinical practice, as is their primary intention, they need to be easily accessible.The AGREE II tool has certain limitations in the search for quality evidence that underlines the final set of recommendations in a guideline. The AGREE II instrument cannot highlight such a deficiency, as the focus on methodological issues that are linked to guideline development is insufficient to ensure that the final set of recommendations is valid. Hence, this tool is used to evaluate the process of guideline development and the way it is reported . FurtherUsing the AGREE II tool, most guidelines had the highest scores in the “Scope and Purpose” domain. Indeed, this had been anticipated as this domain comprises fundamental components of a guideline that cannot be easily neglected, such as the target population, the health questions that are being addressed, and the objectives of the guidelines. Therefore, guideline developers usually focus more on these parts of the guideline when developing their papers.Participation in or co-development of guidelines was especially limited, as indicated in the “Stakeholder Involvement” domain. Only two clinical guidelines included members belonging to other professional groups as developers of guidelines ,33. FurtThe “Rigor of Development” domain is a strong indicator of the quality of clinical guidelines as it represents the methodology part as compared with other domains. A high score in this domain indicates that the guideline has been developed with minimum bias and is based on evidence, whereas a low score, on the other hand, indicates potentially serious problems in the methodological approach that is used for the development of guidelines . HoweverGuideline developers in pediatric dentistry make use of rigorous methods that include the participation and opinions of all the relevant stakeholders. It is also important that clinical guidelines should have a detailed and structured approach in order to assess the quality and to evaluate the strength of evidence that they use to support their final recommendations. Such clinical guidelines must also have a clear link between the final recommendations and the evidence. Clinical guidelines should ideally be transparent with regard to the methodological strategy used, with the support of evidence that helps to produce the final recommendations of their work .In general, it is very much evident that all the included clinical guidelines, except for one, failed to perform well with regard to the “Stakeholder Involvement” and the “Rigor of Development” domains . The priIn the fourth domain, “Clarity of Presentation”, four of the included guidelines score poorly, as they failed to present the recommendations in a clear format. Even if the underlining evidence is unclear, the uncertainty should be highlighted as it is. Furthermore, in the “Applicability” domain, almost all the guidelines attained a low score except for one . The priThe clinical guidelines must include a clear and detailed statement showing that the final recommendations have not been influenced by the interests or views of the funding body, and they must also include a clearly stated description of any sector’s contribution to the development of guidelines. Even though the bodies that fund these guidelines are mainly academic institutions and governmental agencies, it was noted by the appraisers that additional details on the purpose and role of these funding bodies or agencies were missing in the content of the guidelines. In order to accomplish the criteria of the AGREE II tool, there needs to be a detailed statement that shows how the interests of the funding body have not influenced or affected the final recommendations. Simultaneously, the authors of all the guidelines should offer a disclosure or report of all competing interests. Nonetheless, as per the reviewers or assessors, this information has not been reported adequately in all the clinical guidelines. This aspect is important, as it is clear that conflicts of interest among guideline authors are very common and the quality of final recommendations may be affected as a result of this. It is therefore important to pay attention to this domain’s quality .The second part of the research  examinedIn addition, most guidelines did not include evidence that included children with SHCNs. It should not be implied that recommendations ought not be made when there is no high-quality evidence relevant to the population of interest; however, the applicability of evidence extrapolated from other populations/settings should be discussed. This transparency for any extrapolation of evidence is vital, particularly for end-users of clinical practice guidelines implementing recommendations labeled as “evidence-based” .To conclude, we discovered that very few guidelines had a clear link between evidence and final recommendation and very few applied clear grades to demonstrate the quality of evidence referred to. When rendering evidence-based recommendations more open, it would be advisable for evidence-rating frameworks to be more broadly applied (such as the GRADE system) . This woIn general, the most recent guidelines  receivedThe quality of clinical guidelines has been defined as “the confidence that the potential biases of guideline development have been addressed adequately and that the recommendations are both internally and externally valid, and are feasible for practice” . The ratThis study aimed to present a closer analysis of the existing state of the clinical guidelines in this specific area, which considers children with SHCNs and determines how much attention is provided to this particular group in the area of oral healthcare and dental treatment. The quality and reporting of the included guidelines for children with SHCNs in pediatric dentistry are very poor. Despite the existing number of guidelines and recommendations for children with SHCNs in dentistry, the current situation is not acceptable. The scientific community must come together to ensure that all children with SHCNs are treated optimally and equally.The development and content of clinical guidelines in the area are concerning in terms of the low score attributed to the majority of the domains. Therefore, the scientific community must recognize the urgent need to enhance the quality and strength of the existing clinical guidelines on oral healthcare for children with SHCNs in the field of pediatric dentistry by the use, as well as the implementation, of current Clinical Practice Guideline reporting standards. Evidence-based practice has become very popular and is widely adopted across many disciplines. It will be advantageous for all stakeholders to work collaboratively to develop a comprehensive and meticulous evidence base that can be used to build clinical guidelines that are directly applicable to children with SHCNs.


Justice practitioners have to react to these changes. New training offers should be quickly organised and made available” (emphasis added).1The new European judicial training strategy for 2021–2024 states, page 4, under “Equipping practitioners to address new challenges” that: “The COVID-19 pandemic has altered criminals’ modi operandi, leading to a significant increase in offences involving cybercrime and online criminal activities. Along these lines, also the Eurojust Annual Report 2020 states at page 53: “While the need for the digitalisation of the judiciary was clear long before the outbreak of the COVID-19 pandemic, the crisis was a catalyst in making ‘digital’ the default option in cross-border judicial cooperation to fight cross-border crime”.2Finally, the Europol Internet Organised Crime Threat Assessment (IOCTA) 2020 dedicates an entire chapter at page 9 on how “Covid-19 demonstrates criminal opportunism” by stating that: “The difference with COVID-19 is that due to the physical restrictions enacted to halt the spread of the virus, with a subsequent increase in working from home and remote access to business resources, many individuals and businesses that may not have been as active online before the crisis became a lucrative target ”.3modi operandi of criminals. Offences related to cybercrime and online criminal activities increased significantly. Trade of illicit goods and services has moved even more to the Darknet, the number of phishing attempts, cases in online fraud, investment fraud, cyberattacks in the health area and trade in counterfeit medical products have increased. As children spend more time on-line, number of child sexual exploitation cases has also sharply risen in Europe. Internet related crimes have had more opportunities to hit and isolation has made people more vulnerable. To this extent, the protection of fundamental rights became even more important.There is little doubt that COVID-19 did result in altering At operational level, judges, prosecutors and lawyers  had to adjust their working methods to the new situation by organising online meetings, interrogations and hearings. To comply with safety measures during the COVID Pandemic, certain investigation methods, such as face-to-face interviews, interrogations, surveillance, arrests, house and on-site searches and audits could not be applied. Open source intelligence, use of social media, internet-related searches, cyber patrolling, videoconferencing involving vulnerable victims got even higher importance in investigations; the COVID Pandemic has proved that criminal legal practitioners need to improve knowledge in internet/online investigations in all crime areas.Moreover, as a result of online investigations, almost all criminal courts are confronted with the question of whether or not electronic evidence presented in criminal proceedings is admissible. Rules governing the admissibility of electronic evidence vary in the legal framework of different Member States and are continuously challenged by the evolution of technological devices such as computers, mobile phones and digital cameras.In recent years, important steps have been made at European level to develop an adequate legal framework to address the challenges posed by the gathering of e-evidence.In April 2015, the European Union (EU) underlined possible solutions to allow for timely access to electronic evidence in its Communication ‘EU Agenda on Security’.As final preparatory paper, the European Commission issued an Impact Assessment in April 2018On 17 April 2018, the European Commission proposed new rules to better equip law enforcers and judicial authorities. As a matter of fact, the EIO and the MLA procedures will continue to exist, but there will be new avenues, or ‘fast tracks’ for the specific case of electronic evidence. The new legal framework that builds upon the provisions of the EIO, which effectively provides assistance between law enforcement and judicial authorities in different EU Member States, will complement it by creating a set of clear and coherent principles to enable requests by law enforcement and judicial authorities in one Member State to be made directly to a service provider in another Member State for the disclosure of data. This new set of rules consists of two proposals: 1) the Proposal for a Regulation on European Production and Preservation Orders for electronic evidence in criminal matters8In response to two recent European Commission Calls,The first series, 2021–2022, provided in-depth training on e-evidence, an area of law where future well-coordinated training schemes are needed to provide to the largest possible number of EU legal practitioners the basic skills necessary to cope with the handling of digital evidence in courts. Six training events organised across the European Union face to face and online.10https://era-comm.eu/postcovid-challenges-criminal-justice/.The second series, 2022–2024, focuses on the (post)COVID challenges in criminal justice for EU legal practitioners. The seven face to face training seminars contemplated in this series (40 participants per seminar x 7 seminars = 280 participants), to be implemented in various EU cities  will be complemented by six video podcasts, 45 mins each, related to the core topics, which can also be used as stand-alone product (e-learning). Moreover, audio podcasts will be produced and made available for a wider audience. In MP3 format, audio podcasts can be enjoyed on-the-go on portable devices (mobile learning or m-learning). The creation of a dedicated project subsite on ERA’s website, including video and audio podcasts, documentation and speakers’ contributions will also be further project results: By participating to the seven training courses of this Project EU judges, prosecutors and lawyers in private practice will be provided with the “key skills” necessary to cope with all those criminal offenses which present a strong tech/internet component. The seven training courses will address the challenges when investigating, engaging in pre-trial preparation and presenting the case involving a variety of scientific evidence and/or internet sources. To this extent, the training activities will be in line with the work carried out by the European Union in the field of e-evidence. If eventually adopted, all seminars contemplated in the series will dedicate ample space to the presentation of the new 2018 EU legal instruments on the Preservation and Productions Orders and on direct cooperation with service providers.The courses, all conducted in a “learning-by-doing” style which, through demos and simulations will offer an insight into what devices hold the most information and how sources such as PCs, tablets, smart phones, laptops and the Internet are investigated. As well as learning about the process, the participants will understand the results of investigations, their presentation/admissibility in court, gaining an understanding on what can and cannot be found in digital devices.Moreover, the courses will introduce participants to the concepts and the world around the internet and its supporting tools for investigation/research. Dedicated modules will unravel internet search engine tools and make legal practitioners aware of the sources of evidence available to them in online investigations.Undoubtedly, this Project will also contribute to the “knowledge of other legal systems” by involving experienced legal practitioners who will be able to compare national experiences and practices as practical experience to establish the admissibility, the authenticity and the validity of the electronic evidence is still very limited.


Gekko gecko) across three contexts: when encountering novel prey, foraging near novel objects and entering a novel space. We also investigated individual consistency across trials using different novel stimuli, and correlation of individual responses across the three contexts. We found that geckos hesitate to attack novel prey and prey close to objects (familiar and novel). Geckos hesitated the most when entering novel space. Repeatability of behaviour within and across contexts was low (R = 0.101–0.190) indicating that neophobia might not be expressed similarly across contexts. The strength of a neophobic response can indicate how anxious or curious an individual is. This test has great potential to help answer questions about how captivity, enrichment, rearing environment and cognition affect fear responses in different contexts in lizards. By studying reptiles, we can better understand the universality of what is known about the causes leading to difference in neophobia across individuals and species.Neophobia, the fear of novelty, is an ecologically important response which enables animals to avoid potentially harmful situations. Neophobia is a cognitive process by which individuals distinguish novelty from familiarity. In this study, we aimed to quantify this cognitive process in captive tokay geckos (The online version contains supplementary material available at 10.1007/s10071-022-01693-7. Neophobia is the fear of novelty and is expressed by hesitation to approach or complete avoidance of a novel stimulus that has never been encountered before  tested object neophobia by measuring the time it took lizards to consume food next to an unfamiliar object  and the Geniez’s wall lizard (P. virescens) to quantify boldness. Object neophilia was also measured towards a novel cylinder to investigate its’ effect on inhibitory control in five skink species  to investigate novelty recognition (Kundey and Phillips Pogona vitticeps) latency to start moving in a novel environment was measured to investigate if such tests can be used to evaluate welfare  revealed that juveniles show lower neophobia compared to adults (e.g. birds: Gekko gecko). Tokay geckos are a medium sized, nocturnal, arboreal, insectivorous lizard species from South-East Asia which form temporary family groups  and 12 females (SVL range = 11.29–13.72 cm)  to accommodate their nocturnal lifestyle. A red light (PHILIPS TL-D 36W/15 RED) not visible to geckos Loew  is kept Acheta domesticus) three times per week on Monday, Wednesday and Friday. Crickets are gut loaded with cricket mix (reptile planet LDT), Purina Beyond Nature’s Protein™ Adult dry cat food and fresh carrots to ensure that they are provided optimal nutrition . We feed lizards with 25 cm long forceps to monitor their food intake. Water is provided ad libitum in a water bowl. To keep track of our lizards’ health, we weigh them once a month and measure their snout vent length every 2 months.Lizards are fed 3–5 adult house crickets  on top of the tank. Lizards were trained to expect food or testing when this light was placed on top of their tank. Next, a lizard was located and if under a refuge the refuge was gently removed to expose the lizard. Then, the experimenter presented the stimuli in 25 cm long forceps within 4–5 cm of the lizard’s snout for a maximum of 1 min. This distance was chosen as it represented the optimal attack distance . Lizards were tested with familiar and novel foods, coloured and natural, to test food neophobia and dietary conservatism and with familiar and unfamiliar objects in a feeding context to test object neophobia (see detailed description below). One session was given per day, the inter-session interval was 4 days and each test was repeated twice with 14 days in between using new novel food and a novel object. The order in which lizards were tested in each test was randomised but counterbalanced. Lizards first tested on food neophobia and then object neophobia in the first repetition were tested on object neophobia and then food neophobia in the second repetition. The order in which lizards were tested within a given session was randomised to account for order effects. Trials were recoded using a Samsung S20 smartphone . Testing was done between the 6th and 25th of October 2021 between 8:00 and 10:15 am.Lizards were tested in their home enclosures to reduce stress of handling (Langkilde and Shine Acheta domesticus) as familiar food. In the first repetition, we presented Tenebrio molitor larvae approximately last instar  approximately 4th immature instar  in the first repetition and a cardboard toilet paper roll  in the second repetition. Both novel objects were of similar size, material and colour but different in shape and were unfamiliar to lizards. Familiar and unfamiliar objects were attached to 2 cm long forceps Fig. d–f in th® LEDVANCE 3000K, 0.3 W, 17 lm) was placed in the top right corner of the terrarium and a camera  mounted on a tripod recorded trials from above at 40 cm distance from the terrarium mesh lid  with three sides covered on the outside with black plastic to make them opaque Fig. a. One teFirst, a lizard was captured in an opaque, plastic box . After capture, the individual was slowly carried to the testing terrarium and the box placed inside . Lizards were left alone for 5 min to calm down. Next, the experimenter started the video recording and opened a third of the box lid carefully. Using a wire, the lid was secured to stay open (space neophobia test) and provide an exit for lizards  while attack latency was not consistent across observers .We measured the time from when the lizard first noticed a food item until the first strike regardless of if the food was captured or not (capture latency) and from when an individual focussed on a prey item the last time before striking (strike latency). We assumed that a food item was first noticed when a lizard moved its’ head to focus on it (on rare occasions only the eyes moved not the whole head). As this study was the first of its kind in tokay geckos, we wanted to collect multiple measures to be able to select the best measure for neophobic responses to be used in future studies. We used the free behavioural coding software BORIS  a lizard exited the opaque box by lifting its’ tail base over the rim of the box (= exiting with their whole body not counting the tail). If a lizard did not exit the box, we assigned it a latency of 1200 s (= 20 min). We also scored if the lizard touched the cylinder hung in the middle of the empty testing enclosure  and at what time in the trial .First, we wanted to know if lizards time to attack prey was influenced by its novelty (new prey species or novel colour) or an object (familiar or novel) presented close to the prey. Furthermore, we were interested if capture and strike latency were appropriate measures of neophobia. To this end, we analysed each test  separately running two models one with the log-transformed capture latency as the response variable and one with log-transformed strike latency (food and object neophobia only). Latencies were log-transformed to conform to assumptions of normality. We used Bayesian generalised linear mixed models . To make latency measures comparable across tests, we calculated relative latency. We divided latency measured in the food and object neophobia (capture latency) test by 60 s  and the latency to exit into a novel environment by 1200 s . We ran a MCMCglmm with the log-transformed relative latency as the response variable and stage  as the fixed effect.Finally, we wanted to know if our lizards’ responses were correlated indicating a consistent trait and if responses were repeatable within individuals and across contexts. To this end, we performed a Spearman rank correlation test on the responses to novelty only to investigate if average measures of latency (capture and exit latency) correlated across tests . We also calculated adjusted repeatability accounting for test and stimulus using the package rptR for capture and exit latency. Finally, we plotted each individual’s response to novelty across contexts to visually look for individual differences.p > 0.1 no evidence, 0.1 < p < 0.05 weak evidence, 0.05 < p < 0.01 moderate evidence, 0.01 < p < 0.001 strong evidence, p < 0.001 very strong evidence. We only report results with at least moderate evidence within the text but provide all results in the electronic supplementary material. All raw data sets and code for analysis are available on the Open Science Framework (https://doi.org/10.17605/OSF.IO/FHW64).All MCMCglmm included a random intercept of animal identity and a random slope of trial nested in session to account for non-independence and auto-correlation across successive choices due to repeated measures of trial and session across individuals. In the case of the space neophobia, the random effect only included animal identity because we only tested one trial. In all cases, we ensured that lags did not correlate  regardless of colour  when we analysed capture latency  regardless of colour . We found moderate evidence that capture latency was shorter in lizards from room 5 , and we found moderate evidence for longer strike latency later in the day . Finally, trial had no effect on response time indicating that both novel foods were of similar novelty . None of the other fixed effects was affecting latency .We found very strong evidence that lizards hesitated to attack novel prey . We also found strong evidence for longer strike latency from lizards in small tanks . Finally, trial had no effect on latency indicating that both novel objects were of similar novelty . None of the other fixed effects was influencing our measurements .Our analyses revealed very strong evidence that lizards attacked prey close to objects more slowly than control prey regardless of familiarity both when capture latency . Furthermore, none of the lizards touched the novel object during the 20 min of the object neophilia test.low = − 3.012, CIup = − 1.833, p value < 0.00007) and when attacking prey near novel objects  compared to when exiting into a novel environment  and the time taken to exit a box into a novel environment  and strong evidence that capture latency was repeatable in the object neophobia test  albeit at a low value of R = 0.101  and R = 0.190 , respectively. Across tests, we found very strong evidence that responses were repeatable but also at a low value of only R = 0.12 . Figure We found moderate evidence that lizards capture latency was repeatable across trials in the food neophobia test , familiar food and food close to familiar and novel objects as well as entering a novel space. In the food neophobia test, our geckos hesitated to attack novel food regardless of colour showing food neophobia but not dietary conservatism . We measured capture latency from when a lizard first noticed the food until their first attack while strike latency was measured from the last time an individual adjusted its’ gaze until the first attack. Capture latency possibly incorporates the whole decision-making process including novelty recognition and decisions of how to best strike the prey for maximum capture success. Strike latency might only encompass decisions regarding capture efficiency including where to strike a novel prey item that has never been captured before or how to avoid interference of an object close to the prey. Regardless, it is more conservative to use capture latency as it is more likely to encompass the decision-making process regarding novelty and should be used in future studies. Furthermore, inter-observer reliability was high when capture latency was scored but low when attack latency was scored. This suggests that capture latency is a more unbiased and easier to score measure which further supports the use of capture latency in future studies.Lastly, in the food neophobia test, lizards from room 5 responded faster than lizards kept in room 2. We believe that this is caused by randomly assigning lizards to these rooms rather than any environmental factors which were identical in both rooms. By chance, we might have placed a larger number of less neophobic individuals in one room than the other or more food motivated individuals in one room than the other. This is, however, of no consequence to our results because our study design ensured that each lizard acted as its’ own control.In summary, our study reveals neophobia in different contexts in captive bred tokay geckos. Our analyses show the strongest neophobia towards entering novel space and only low repeatability and correlation across tests which might indicate that neophobia is not a single trait. Our methodology is robust providing us with the basis for future investigations into changes in neophobia related to captive conditions and rearing environment and the relationship of neophobia to different cognitive abilities.Supplementary file1 (DOCX 412 KB)Supplementary file2 (M4V 43950 KB)Below is the link to the electronic supplementary material.