Point-of-care in vitro diagnostics (POC-IVD) are increasingly becoming widespread as an acceptable means of providing rapid diagnostic results to facilitate decision-making in many clinical pathways. Evidence in utility, usability and cost-effectiveness is currently provided in a fragmented and detached manner that is fraught with methodological challenges given the disruptive nature these tests have on the clinical pathway. The Point-of-care Key Evidence Tool (POCKET) checklist aims to provide an integrated evidence-based framework that incorporates all required evidence to guide the evaluation of POC-IVD to meet the needs of policy and decisionmakers in the National Health Service (NHS).A multimethod approach will be applied in order to develop the POCKET. A thorough literature review has formed the basis of a robust Delphi process and validation study. Semistructured interviews are being undertaken with POC-IVD stakeholders, including industry, regulators, commissioners, clinicians and patients to understand what evidence is required to facilitate decision-making. Emergent themes will be translated into a series of statements to form a survey questionnaire that aims to reach a consensus in each stakeholder group to what needs to be included in the tool. Results will be presented to a workshop to discuss the statements brought forward and the optimal format for the tool. Once assembled, the tool will be field-tested through case studies to ensure validity and usability and inform refinement, if required. The final version will be published online with a call for comments. Limitations include unpredictable sample representation, development of compromise position rather than consensus, and absence of blinding in validation exercise.The Imperial College Joint Research Compliance Office and the Imperial College Hospitals NHS Trust R&D department have approved the protocol. The checklist tool will be disseminated through a PhD thesis, a website, peer-reviewed publication, academic conferences and formal presentations. Multimethod approach incorporating all stakeholders.Agreement of independent National Institute of Health Research Diagnostic Evidence Co-operatives to prospectively field-test and provide feedback on the developed tool.Collaborative approach of academia and industry.Delphi methodology may lead to a compromise position rather than true consensus.Small sample size with unpredictable representation.Point-of-care in vitro diagnostics (POC-IVD) provide rapid results near patient or at the bedside to facilitate real-time clinical decision-making. POC-IVD devices are well established in medical, industrial and military environments. Clinical examples include blood glucose, anticoagulation and pregnancy testing. These offer potential advantages such as decreasing the time to definitive treatment, improved cost-effectiveness,Point-of-care tests are a disruptive innovation that is used by both healthcare professionals and patients at clinical facilities or at home to prompt an immediate clinical decision. Evidence generation on such technology should include not only the assessment of the device itself, but also the test processes  and system dynamics . Clinical pathway examination is fundamental to incorporate healthcare benefits, consequences of misdiagnosis and the impact on alternative diagnostic workforce. Accumulating appropriate evidence results in a long lead-time from innovation to clinical adoption, with some technologies never making the transition to the bedside.Quality evidence on POC-IVD is required for regulation, policy making and implementation. Currently, the pathway for evidence generation in diagnostics is fragmented and does not follow the linear sequence of evaluations that has become mainstream for drug evaluation.There are several reports in the medical literature to improve the quality of evidence in diagnostic devices. Examples include the standards for reporting of diagnostic accuracy studies (STARD)Point-Of-Care Key Evidence Tool (POCKET); as a ‘one-stop’ multidimensional evaluation checklist and reporting standard incorporating validity, utility usability, cost-effectiveness and patient experience in POC-IVD at a device, process and system level. The motivation for POCKET is to aid industry and academic researchers when undergoing the development and evaluation of POC-IVD to ensure the combined evidence requirements of users and policy decisionmakers are met efficiently, reducing the lead time for the adoption of new technologies and allowing demonstrable benefits to patients and the National Health Service to be effectively realised.The aim of this study is to develop a The POCKET checklist will be developed and refined by a multimethod approach utilising stakeholders in the POC-IVD field and experts in methodology. The study design is outlined in Recruitment and semistructured interviews (stage 1) started in August 2014. The questionnaire round of the Delphi survey will be sent out in August 2015 and the expert workshop is planned for the final quarter of 2015.A comprehensive literature review preceded the interview protocol development to identify the potential evidence requirements for tool inclusion and at what stage of the device development pathway these reports can be generated. Electronic searches of medical and design databases were searched using a search strategy consisting of keywords and MeSH headings designed to identify articles related to POC-IVD.Patients are recruited from the public through the patient information forum, patient associations and diagnostic research public engagement events. They will have experience of home POC-IVD use for the monitoring of chronic disease. They will not be directly recruited from the NHS. Patient records will not be accessed for recruitment.Industry representatives include personnel currently employed by a point-of-care industry and are recruited by an invitation included in their trade association BIVDA (British In Vitro Diagnostics Association) newsletter.Clinicians are recruited directly by electronic mail based on expertise in point-of-care diagnostics as demonstrated by academic output or their role on point-of-care committees.Commissioners include current members of clinical commissioning groups in northwest London and are recruited directly by electronic mail following an introduction from the Department of Primary Care and Public Health at Imperial College.Regulators will include current members of the NICE Diagnostic Advisory Committee and the Medicines and Healthcare Products Regulatory Agency (MHRA), and are recruited through their partnerships with the Diagnostic Evidence Co-operative.A semistructured interview study is being undertaken with stakeholders relating to POC-IVD in order to collect primary data. Five stakeholder groups are being invited: patients and patient group representatives, clinicians, industry, regulators and commissioners. A minimum of eight participants from each group will be interviewed as a pragmatic sample size, given time and resources. However, the final number of participants will be guided by the interview results, as more interviews will be carried out until no new themes emerge. The majority of participants will be from the UK, but where relevant experience or expertise exists abroad such participants will be included in the study. Every effort will be made to recruit a representative and diverse sample across each participant group. Inclusion criteria and method of recruitment will vary by stakeholder group:Exclusion criteria include those unable to give informed consent to participate in the study, inability to understand and communicate in English, and members of the public from vulnerable groups .The interview structure has been designed by a clinician (JRH) in conjunction with an expert in qualitative research (SM) to permit the collection of quantitative and qualitative data while allowing for flexibility and original suggestions. The interviews aim to understand the role different stakeholders have and the evidence that is required at each step in the adoption pathway of POC-IVD. This pathway includes device design, evaluation and implementation. Interviews are tailored to the role and level of experience of the interviewee, with significant tailoring required for interviews with patients. This ensures the interviews remain relevant to the different stakeholders. In the situation that the interviewee has a role in more than one stakeholder group, the interview focuses on their primary interest with subsequent roles recorded for analysis.The interview questions were piloted to fine-tune the protocol prior to the study interviews. Interviews will be carried out face-to-face by one interviewer (JRH), with telephone or ‘Skype’ interviews reserved for when this is not feasible. Interviews will last for approximately 30–40 min, be digitally recorded and then transcribed verbatim for analysis. The main researcher and an additional team member with expertise in qualitative research will coanalyse the data independently in order to minimise bias. Initially, interview data will be coded based on the predetermined interview themes; it is expected that additional themes will emerge and be coded during the interview analyses. If required, participants will be contacted to clarify interpretation of data. Data will be analysed with NVivo V.10.1.1 software .Round 2 will allow experts to respond to questions that aim to reach a consensus on the required evaluation process for point-of-care diagnostic tests and add to the evidence base for the development of the POCKET checklist for multidimensional evidence generation.All emergent themes relating to evidence requirements from the interview study will be translated into a series of statements and the survey questionnaire will be sent to an expert panel comprised of those interviewed in round 1 (with the exception of patients) as well as experts in research methodology identified by academic output. The Delphi study cohort will include a minimum of eight participants from each stakeholder group. As for round 1, this is a pragmatic sample size given the time and resources available for the study. The questionnaire statements will be responded to on a five-point Likert scale (1 (strongly disagree) to 5 (strongly agree)) in respect to checklist inclusion. Responders will also be able to add free text comments with each statement if needed to justify responses or suggest items that should be added and have been dismissed. The survey will be administered online using Qualtrics software  with personalised invitations sent out by electronic mail. Reminders will be sent at 4 and 6 weeks after initial contact for non-responders. Survey responses will be entered into SPSS and descriptive analyses carried out .priori definition of consensus for this study.The survey will be repeated following feedback to the experts on the collated responses from the previous round. Any new items suggested in free text responses to round 2 will be added at this stage. This method will allow participants to reconsider their responses in light of the group results and they will be encouraged to justify their responses when there is a significant degree of divergence. This process will be repeated until consensus is reached. The aim of the POCKET tool is to meet the evidence requirements of all stakeholders. Therefore, stakeholder groups will be analysed individually and any statement deemed necessary by at least one group will be included in the tool. Consensus will be set at ≥80% across items that receive ≥4 (agree or strongly agree). Cronbach's α will be used to assess reliability. Previous studieset al in the development of the STARD guidelines.A 2-day consensus workshop will be arranged for invited experts from researchers, editors, methodologists, industry and professional organisations. The workshop will follow the approach taken by Bossuyt The draft of the POCKET checklist will be discussed on the second day of the workshop and additional changes made. The checklist will be field-tested through a series of case studies of POC-IVD devices to ensure consistency, validity and usability. POC-IVD devices that have had demonstrable market success or failure in respect to clinical adoption will be identified through industry and expert feedback obtained during the Delphi process. Small groups will be provided with published research articles, conference abstracts and input from industry relating to devices and asked to retrospectively assess their adherence to the POCKET checklist. The groups will be not be informed to market results; however, it is possible that through their own experience they will already have an insight into the level of success many devices have had.The output data from the groups will be analysed and a comparative evaluation undertaken to determine if devices that met the checklist requirements performed better in the IVD market and had successful implementation into the NHS. This exercise will inform further amendments to the tool if required. The final POCKET checklist will be published on the NIHR Diagnostic Evidence Co-operative London website with a call for comments. Following dissemination of the POCKET checklist users, including the NIHR Diagnostic Evidence Co-operatives in Leeds, Newcastle and Oxford, will be asked to provide feedback and further validation will be undertaken by real-world use of the tool in prospective POC device evaluations.Participation in this study is voluntary. During the recruitment phase, all potential participants will be provided with a detailed information sheet in order to allow them to make an informed decision regarding their participation. The right of the participant to refuse to participate or withdraw at any time without giving reasons will be respected. Initially, informed consent was obtained for the interview study in isolation and these participants will require a further consent process for inclusion in subsequent Delphi rounds. However, an amendment was approved on 27 October 2014 requiring consent for the interview study and Delphi process together. No financial or other remuneration will be directly offered to participants. However, in some circumstances an honorarium will be offered to the practice of participants to compensate for their missed clinical time. This was agreed following advice from the Imperial College School of Primary Care. The protocol has been approved by the Joint Research Compliance Office Imperial College, London, and the Imperial College Hospitals NHS Trust R&D department . The checklist tool will be disseminated through a PhD thesis (JRH), the NIHR-DEC website, peer-reviewed publications, academic conferences and formal presentations to industry, policymakers and practitioners.this study design has several limitations. Many of these are common to qualitative research techniques and particularly, the Delphi process. The Delphi process may lead to a compromise position rather than a true consensus. The sample size of at least eight participants in each stakeholder group is small and the extent to which included participants will be representative is unknown. The recruitment protocol aims to recruit a broad selection of participants but the authors acknowledge that a degree of convenience sampling may be required. This could only be overcome by a random sampling approach that would not be feasible in the present study. The validation exercise that will be undertaken as part of the workshop is not blinded; therefore, the previous experiences of participants in respect to a particular technology may introduce a bias. A period of refinement has been included at the end of the study so that any evidence requirements not identified during the study can be added if required.


In 2013 Australia introduced Wiki-based Clinical Practice Guidelines for the Management of Adult Onset Sarcoma. These guidelines utilized a customized MediaWiki software application for guideline development and are the first evidence-based guidelines for clinical management of sarcoma. This paper presents our experience with developing and implementing web-based interactive guidelines and reviews some of the challenges and lessons from adopting an evidence-based (rather than consensus-based) approach to clinical sarcoma guidelines. Digital guidelines can be easily updated with new evidence, continuously reviewed and widely disseminated. They provide an accessible method of enabling clinicians and consumers to access evidence-based clinical practice recommendations and, as evidenced by over 2000 views in the first four months after release, with 49% of those visits being from countries outside of Australia. The lessons learned have relevance to other rare cancers in addition to the international sarcoma community. Sarcomas are rare malignant tumours of bone and soft tissue . They inThe rarity of sarcoma and its subtypes makes it challenging to determine optimal treatment strategies. Multidisciplinary input, including specialist pathology and radiology expertise, is essential to providing best clinical practice outcomes . HoweverExisting clinical practice guidelines for the management of sarcoma, such as those released by European Society of Medical Oncology (ESMO), National Institute for Health and Clinical Excellence (NICE), and National Comprehensive Cancer Network (NCCN), are consensus-based guidelines –7. As suSuch differences include marked geographic disparity in sarcoma management. For example, the probability of radiotherapy as a primary  modality in Australia is largely determined by centre-based preferences and access to sarcoma specialist centres. Similarly, availability as well as involvement of paediatric oncology expertise in treating patients in the Adult and Young Adolescent (AYA) age range varies by referral centre and co-location of paediatric and adult treatment centres and/or local networks. In addition, the mixture of private and public health funding models in Australia and national approval processes and funding for drugs have implications for Australian practice guidelines. For example, trabectedin is approved and reimbursed for the treatment of sarcomas in Europe, but not Australia.Low levels of evidence often underpin clinical sarcoma practice. Balanced with this is a pragmatic requirement for clinicians to make decisions on the optimal management of their individual patients. Treatment algorithms rely heavily on individual clinician experience and consensus of the multidisciplinary team. As a consequence, variance in care between clinicians and centres is common. Similarly, access to clinical trials varies by geography and centre and translational research integration is often opportunistic, rather than nationally coordinated.Increasingly, new prognostic factors and therapeutic approaches for sarcoma are being identified. The rapidly expanding knowledge base, particularly in areas of targeted therapy and molecular genetics, along with changes to pathological coding, new imaging modalities, and advances in surgery and radiotherapy, makes keeping up to date with the latest development in sarcoma management a challenge for all involved .The primary aim of the Sarcoma guidelines process was to bring together lead clinicians managing sarcoma, across a range of disciplines, to develop common shared understanding of the current evidence and to identify key research gaps in an Australasian setting. By promoting consistency in decision making through provision of best evidence, the development of pathways of care, both state and national, was identified as natural sequelae to this process.Traditional printed clinical practice guidelines are resource intensive and become out of date almost as soon as released, by virtue of new evidence constantly being published .Wide stakeholder engagement and consultation is important in any guidelines process but adds to the delay. Nonautomatic electronic searching of bibliographic databases makes literature searches time consuming and expensive. In addition, there is a paucity of evidence demonstrating the impact on practice of printed guidelines .Confronted with these challenges, the small size of the Australian sarcoma community and the pragmatic reality of “time poor” clinical practitioners, an innovative solution was required.The Australian sarcoma community was fortunate to be able to utilize a relatively new and modern methodology for guidelines developed by Cancer Council Australia.The sarcoma guidelines project was a collaborative project between the Australasian Sarcoma Study Group (ASSG) and Cancer Council Australia (CCA) which commenced in 2011 and utilized Cancer Council Australia's Wiki platform.The term Wiki is derived from “swift” in Hawaiian and is a web application that allows the creation and editing of interlinked web pages via a web browser using simplified markup language to facilitate online collaboration .CCA has modified and customized the MediaWiki, an open source Wiki software application, to facilitate the guideline development process.The methodology and guideline development process has been translated into an online environment and adheres closely to that of traditional printed guidelines. The process is illustrated in A multidisciplinary working party including consumer representation was established in 2011. Expressions of interest were sought across the Australian sarcoma community, with the intent of providing both cross-discipline and geographic representation.The working party comprised 42 members. The working party met at an initial “face to face” meeting to decide the clinical questions that were most relevant to their disciplines and determine the scope of the guidelines. The selected questions reflected the gaps in knowledge that impacted most on daily management decisions. ab initio set of guidelines, the original scope of these guidelines was broad. The key areas covered have been refined to includediagnosis,multidisciplinary treatment,chemotherapy (systemic therapies),radiotherapy,surgery,follow-up.Sarcomas affect children and adolescents, as well as adult members of the community. However, for reasons of pragmatism and resource, the scope of this first iteration is restricted to adult onset bone and soft tissue sarcoma. Gastrointestinal stromal tumours (GIST), Kaposi's sarcoma, and aggressive (desmoid) fibromatosis were excluded.As anChildhood, adolescent (AYA), and gynaecological sarcomas are priorities for the next iteration of the guidelines.Historically, clinical guidelines have been accompanied by a separate set of consumer guidelines. A decision was made not to do this with the clinical practice guidelines for adult onset sarcoma and reflects the availability of “online” consumer resources within Australia and the international community. The Wiki platform allows direct linkage to other relevant organisations' websites containing already available useful information for consumers. This has been integrated and linked to relevant sites from the guidelines table of contents page.In addition, a number of external linkages have been embedded. These include links to the Australasian Sarcoma Study Group, geographic sarcoma specialist expertise, and multidisciplinary centres across Australia and linkage to available clinical trials sites such as the National Health and Medical Research Council (NHMRC) trials registry and sites presenting detailed treatment protocols such as EviQ.As with traditional printed guidelines, following definition of the clinical questions and standardised PICO  formats were developed online. The next step involved literature search retrieval and assessment. The use of online literature search tools facilitated this process. Systematic search strategies were developed for a range of databases, such as PubMed, Embase, Trip database, and others using predetermined search term fields and predefined inclusion/exclusion criteria. Retrieved literature was made available via the Wiki platform as designated to individual working party authors and reviewers to assess using the online critical appraisal form, providing a body of evidence from which guideline content development was undertaken . ManuscrThe online nature of the Wiki provides a uniquely interactive format, where chapter authors and others can easily view all recommendations via the summary of recommendations page  were received. The site received 488 visits . These led to further edits, which were reviewed in detail by the working party.http://wiki.cancer.org.au/australia/Guidelines:Sarcoma. From release in November 2013 to May 15, 2014, the guidelines received 3,475 page views with 1,344 visits and an average of 2.6 pages per visit. Of these 52% of visits were from Australia, 8.9% from USA, 6% from United Kingdom, 6% from India, 2% from Singapore, 1.9% from Germany, and the remaining 25.3% from 39 additional countries.The guidelines were released nationally on 15 November 2013 and can be accessed at The guidelines highlight the importance of early referral to multidisciplinary centers that specialize in treating sarcoma. Caseload and experience is associated with improved rates of functional limb preservation, lower rates of local recurrence, good rates of overall survival, and improved quality of life. These centers are usually involved in ongoing clinical trials, in which sarcoma patients' enrollment is highly encouraged.The importance of the multidisciplinary team in initial assessment, diagnosis, and making decisions about treatment is strongly endorsed by the recommendations in the guidelines. A multidisciplinary approach , or within reference networks sharing expertise and treating a high number of patients annually, is preferred.It should be noted that participants in this guideline development process found challenges in assigning conventional levels of evidence for many recommendations. The heterogeneity and rarity of sarcomas, along with the increased molecular stratification of clinical trials, means that few studies reached what would be considered the “gold standard” in other diseases , including more common cancers. The absence of evidence, however, does not exonerate clinicians from the necessity to make clinical judgments in caring for patients with sarcomas. This raises questions about the need to develop standards of evidence that recognize the challenges of research in rare diseases, including sarcoma. Consequently these guidelines emphasise the need for increased participation in collaborative research and trials programs as a standard of care.The Wiki platform provides the sarcoma guidelines with an iterative and constantly updating framework. Infrastructure is in place to automatically feed literature updates from PubMed and Embase to relevant question authors . In addiExpert working party authors will continue at regular intervals to assess new evidence and comments and update the content where necessary, ensuring that this remains an iterative and current guideline. We will work towards empowering small writing groups, to whom we will provide new literature as it is published, with the ability to update their section of the guidelines without requiring specific public consultation. While reliant on small working groups, any bias is mitigated by the design of the platform where the public and experts can post comments at any time. In addition to this, the larger working group will meet annually to review all updates.The working party will meet in November 2014 as part of an annual process to review the content and updates and formulate the next generation of clinical questions (Paediatric/AYA). Gynaecological sarcoma questions will be incorporated in 2016.Defining the “research gaps” in sarcoma care has been an important outcome of this process. In each section these are included in the form of future research questions that need to be addressed by good quality collaborative trials.As a strategy for boosting implementation, Cancer Council Australia is developing educational modules to accompany each of the online guidelines established. This process will be managed by adopting spaced education  techniques for online education. Qstream utilises clinical scenarios presented in a short answer test question format . FurtherEducation modules can be linked to key stakeholder groups such a radiology, pathology, primary care provider, and surgical colleges. Such web-based education resources provide a cost-effective way of engaging with health providers and consumers who may not otherwise have been able to access these opportunities and can be stratified by level of expertise  and by resource availability.These guidelines are intended to be a resource to help create awareness, for use in medical education and as a resource in multidisciplinary team meetings. Engagement from the breadth of the sarcoma community, both in Australia and internationally, via comments and submissions of new evidence, is actively encouraged .Australia is situated within a region containing the largest growing population in the world: currently over 4.3 billion . There iWe hope these guidelines will provide an accessible up-to-date platform for dissemination of current evidence in a rapidly changing landscape and assist in clinical management of adult onset sarcoma. In addition, the guidelines provide a national and regional resource for multidisciplinary sarcoma teams, individual clinicians, students, and consumers. Cancer Council Australia are developing a suite of Wiki based guidelines for other cancers including melanoma and lung cancer. Sharing our methodology with international guideline developers has allowed the sharing of literature searches. Such international collaboration and sharing is key to expanding the reach of the guidelines.Advances in multidisciplinary care have improved the evaluation and care of patients with sarcoma. One of the key principles underlying the development of these guidelines was to address issues where the evidence was unclear, where divergent interpretations of evidence existed, or where particular issues unique to the Australian setting needed to be considered.The Australian Clinical Practice Guidelines for the Management of Adult Onset Sarcoma are the first step towards more standardised care for patients with sarcoma across the nation and provides a framework to educate the community about referral pathways and develop more formal communications between sarcoma centres and clinicians, particularly in relation to current trials and access.The Cancer Council Australia Cancer Guidelines Wiki platform used to develop these guidelines is unique. It enables iterative, ongoing, and interactive guideline development and revision processes and provides a cost-effective, efficient methodology and transparent assessment of the available evidence in sarcoma management. There are significant opportunities to leverage this platform for further international engagement and collaboration.


The World Health Organization in its recent statement has highlighted the potential of the evolving field of E-Health . It defiThe adoption of technology by healthcare professionals is not something new, as a previous systematic review  has highGiven the current advances in E-health and technologies, it is thus key in determining whether psychiatry has embraced these technologies developments and to what extent psychiatry has utilized these technological advances. A review of the existing published literature revealed that in psychiatry, these technologies advances have been utilized in several areas, such as the application of text-messaging services in reinforcing the medication compliance for schizophrenic patients , and alsGiven that one of the core limitations identified pertaining to the implementation of E-health, especially so for smartphone applications for patient care, is the concern with regards to the safety of the application and the evidence base of the application, it is the aim of the authors to address this issue. One of the solutions might be getting psychiatrists to be involved in the identification of a collection of safe healthcare applications using systematic self-certification model. There have been previous studies conducted  that havAnother model, known as the Silberg scale , has alsThrough the introduction of these scales, the authors hope that healthcare professionals could appreciate that there are methods that could be used to determine whether an application is evidence based or not.By providing psychiatrists with the above criteria, it is thus hoped that more psychiatrists could make use of the above-mentioned criteria to identify more evidenced-based applications. However, psychiatrists could tap upon the full potential of E-health if they could embrace methodologies of developing applications catered to the areas to which they could use smartphone applications in, for example, in education, research, and even in clinical care. Previous published research has encouraged clinicians to take upon more ownership of publishing application by means of educating them how best to make use of an Internet browser as well as a text editor to create applications . Zhang eIn conclusion, given the advances in technology in today’s day and age, it is essential for clinicians to tap upon technology and harness the full potential of today’s technologies. In order to empower psychiatrists, it is the perspective of the authors that psychiatrists could either make use of evidence-based methodologies to identify applications that are suitable for their usage, or empower themselves to be web-based and smartphone developers using simple methodologies shared previously. Given the simplicity and the low-cost involved using the methods introduced , 18, it The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer Jérôme Favrod and handling Editor Stéphane Bouchard declared a current collaboration (working on the current Research Topic). The handling Editor states that the process nevertheless met the standards of a fair and objective review.


To facilitate implementation of evidence-based practice in the field of child and adolescent mental health in Norway.Although more knowledge about effective interventions is frequently developed, most services in Norway are not evidence based. Part of the reason might be that practitioners and decision-makers do not know which interventions have scientific evidence for effectiveness and that they don’t search for information in traditional research literature. Although the evidence base of available interventions is growing, little research has been conducted on implementation strategies to bridge the gap between research and practice.http://www.ungsinn.no [http://ungsinn/] (Youngmind) has been developed to facilitate access to information about interventions and their evidence base. The website contains available interventions for the practice field in Norway. Each intervention is presented by a description followed by a classification of evidence level. A review of existing research with emphasis on effect studies is an important part of the presentation.The Norwegian web-site Establishing evidence-based practices within human services may be challenging, even though the practice in itself has been proven effective in efficacy and effectiveness research. To facilitate an evidence-based practice within psycho-social services for children, strategies should encompass more than just rigorous research on interventions. Knowledge transfer is a key concept, in terms of implementation quality and sustainability. A strategy that has a well-defined plan for knowledge transfer is more likely to be successful. It is important to simultaneously establish a substantial base of well documented interventions and additionally create strategies for successful knowledge transfer.


Judgments underlying guideline recommendations are seldom recorded and presented in a systematic fashion. The GRADE Evidence-to-Decision Framework (EtD) offers a transparent way to record and report guideline developers’ judgments. In this paper, we report the experiences with the EtD frameworks in 15 real guideline panels.Following the guideline panel meetings, we asked methodologists participating in the panel to provide feedback regarding the EtD framework. They were instructed to consider their own experience and the feedback collected from the rest of the panel. Two investigators independently summarized the responses and jointly interpreted the data using pre-specified domains as coding system. We asked methodologists to review the results and provide further input to improve the structure of the EtDs iteratively.The EtD framework was well received, and the comments were generally positive. Methodologists felt that in a real guideline panel, the EtD framework helps structuring a complex process through relatively simple steps in an explicit and transparent way. However, some sections  required further development and clarification that were considered in the current version of the EtD framework.The use of an EtD framework in guideline development offers a structured and explicit way to record and report the judgments and discussion of guideline panels during the formulation of recommendations. In addition, it facilitates the formulation of recommendations, assessment of their strength, and identifying gaps in research.The online version of this article (doi:10.1186/s13012-016-0462-y) contains supplementary material, which is available to authorized users. Clinical practice guidelines are an efficient way to bridge the gap between research evidence, expert experience, and decision-making –4. In orwww.gradeworkinggroup.org), a collaborative of over 500 scientists, clinicians, and people with other backgrounds, has developed an approach to assessing the certainty in the body of evidence summarized in systematic reviews that support a decision or guideline recommendation, called the GRADE approach  and see the outcome.”The sections “values and preferences” and “balance of benefits and harms” posed difficulties in several panels. Regarding the “values and preferences” section, the GRADE approach requires guideline panelists to judge whether there is important variability in how patients’ value the main outcomes and to what extent there is important uncertainty about this. In case of any of the two, panels should consider issuing a weak recommendation. The main concern with this question was that the answer options did not differentiate between the variability and uncertainty in patients’ values and preferences, creating some confusion among panelists. Four methodologists suggested dividing this question in two.Regarding the balance between benefits and harms, this section features three questions requiring panelists to judge the magnitude of desirable and undesirable effects, as well the relation between the two. Panelists struggled judging the size of the benefits and harms consistently. Two methodologists considered the three questions redundant and suggested to drop the questions about the size of the benefit and harms and maintain only the one addressing their balance.www.gradepro.org) [This is the first study evaluating the use of the GRADE EtD framework in the context of real guideline development. Given the widespread application of GRADE, this study provides important information and rationale for utilizing EtDs in guidelines. In general, the response to the use of the EtD framework was positive, although some sections  required improvements, in particular the choice of answer options. These improvements have been implemented in the current final option of GRADE EtD frameworks (pro.org) –13.There are some limitations to this study. The use of iteratively developed formats of the EtD framework in different guideline panels could have introduced some variability in the provided answers. However, it was necessary as part of the development and improvement of the EtDs. For example, early testing with the World Health Organization and World Allergy Organization panels revealed difficulties with providing responses to the available answer options. In order to make best use of the EtDs, they were modified for use in the work of later guideline panels. While methodologists were prospectively instructed before the panel meetings to record challenges with the EtDs during the panel meetings, there was no independent evaluation of challenges with the EtD frameworks. However, the data were recorded without delay and we believe that recall of the encountered issues does not lead to bias as all methodologists had an interest in improving the frameworks.The strengths of this study include the strategies taken to ensure the trustworthiness of our findings: prospective data collection, independent and duplicate analysis, and member checking of the conclusions. The most important strength of this work is the application of the EtD frameworks in the context of real guideline development by international panels in a broad range of topics, including diagnostic and therapeutic questions.Our findings strongly suggest that the EtD framework can enhance the transparency of guideline developers’ judgments, allowing decision makers to truly assess the recommendation. This is not only corroborated by this work but by the adoption of the EtD approach by major organizations such as WHO . What haThe EtD framework also offers the opportunity to identify and potentially avoid inappropriate recommendations. One potential problem of recommendations is the mismatch between the strength of the recommendation and the underlying information about the certainty in effect estimates , the balance between the benefits and harms, values and preferences, and resource considerations . The EtDwww.gradepro.org) and described elsewhere [In conclusion, the use of an EtD framework in guideline development offers an explicit and transparent way to record and report the judgments and discussion of guideline panelists. The EtD framework may facilitate the assessment of recommendations and also their potential adaptation and implementation. As result of this work, a new section was added to the EtD framework. This section allows summarizing the judgments of guideline panelists just prior to the deliberations regarding the direction and strength of recommendations. The currently latest version of the EtD resulting from this and other work including an interactive version of the EtD based on this and other work is available in GRADE’s online GRADEpro Guideline Development Tool  Framework example. (DOC 188 kb)Additional file 2:Example of a EtD framework. (XLSX 21 kb)


Healthcare consumers, researchers, patients and policy makers increasingly use systematic reviews (SRs) to aid their decision-making process. However, the conduct of SRs can be a time-consuming and resource-intensive task. Often, clinical practice guideline developers or other decision-makers need to make informed decisions in a timely fashion . Possible approaches to address the issue of timeliness in the production of SRs are to (a) implement process parallelisation, (b) adapt and apply innovative technologies, and/or (c) modify SR processes . Highly parallelised systematic reviewing requires substantial resources to support a team of experienced information specialists, reviewers and methodologists working alongside with clinical content experts to minimise the time for completing individual review steps while maximising the parallel progression of multiple steps. Effective coordination and management within the team and across external stakeholders are essential elements of this process. Emerging innovative technologies have a great potential for reducing workload and improving efficiency of SR production. The most promising areas of application would be to allow automation of specific SR tasks, in particular if these tasks are time consuming and resource intensive . Modification of SR processes involves restricting, truncating and/or bypassing one or more SR steps, which may risk introducing bias to the review findings. Although the growing experiences in producing various types of rapid reviews (RR) and the accumulation of empirical studies exploring potential bias associated with specific SR tasks have contributed to the methodological development for expediting SR production, there is still a dearth of research examining the actual impact of methodological modifications and comparing the findings between RRs and SRs. This evidence would help to inform as to which SR tasks can be accelerated or truncated and to what degree, while maintaining the validity of review findings. Timely delivered SRs can be of value in informing healthcare decisions and recommendations, especially when there is practical urgency and there is no other relevant synthesised evidence. Systematic reviews (SRs) are transparent and succinct evidence synthesis summaries of empirical results of primary research studies addressing one or more questions regarding any given health problem, intervention(s) or policy decision , 2. The The conduct of SRs can be a time-consuming, cost- and resource-intensive task, which may take on average from 6 months to several years –6. This Three approaches taken alone or in conjunction may be considered as possible solution(s) to address the issues of timeliness in the production of SRs: 1) implement process parallelisation, (2) adapt and apply innovative technologies allowing automation and (3) modify some SR processes. Although the latter two approaches are expected to also reduce the review production costs, both may introduce some form of bias into the review. Implementing the process of parallelisation will not reduce the costs but it will not increase the risk of bias either , thereby reducing the time needed to complete a SR. Parallelisation of SR tasks can be analogous to the process of parallel computing , the metHighly parallelised systematic reviewing requires a team experienced in literature search, clinical epidemiology and research methodology, often working alongside advisors with clinical, statistical and economic expertise. Effective coordination and management within the review team and across the network of external experts and stakeholders are essential parts of a successful process parallelisation. The effective management of parallelisation should not affect the quality of a review produced. However, resources required to maintain such a model of reviewing can be considerable. The assessment groups undertaking health technology assessments for the National Institute for Health and Care Excellence in the UK and the Evidence-Based Centres carrying out comparative effectiveness reviews for the Agency for Healthcare Research and Quality in the US are good examples of such type of management.Current developments in innovative technologies (automated or semi-automated) applicable to the production of SRs are a promising armamentarium for reducing costs and workload in expediting the SR process . Of courThe most efficient use and application of the machine-learning technologies would be in the areas allowing automation of specific SR processes, in particular those involving time-consuming and resource-intensive tasks such as language translation , study sAlthough fully automated SRs may remain an aspiration for the near future, the current achievements in machine-learning technologies are promising steps into automation of several SR tasks which in turn will help to expedite the production and dissemination of SRs. Collaboration between SR practitioners and experts in informatics, computer sciences and linguistics will become increasingly important in harnessing the potential of automation and artificial intelligence to increase the efficiency of systematic reviewing.An alternative approach to synthesise evidence more expeditiously lies in modifying the SR methodology by restricting, curtailing or bypassing one or more SR steps , while maintaining the same degree of transparency as in traditional SRs. Although cost saving, these modifications may pose a threat to validity of the review findings. Therefore, empirical evidence informing which traditional SR steps can be accelerated or curtailed and to what degree without gravely compromising the validity of findings would be very useful.In response to the challenge of timeliness, there has been a growing number of ‘rapid reviews’ (RRs), described as ‘literature reviews that use methods to accelerate or streamline traditional systematic review processes’ , 21–23. The term ‘rapid review’ incorporates an array of products that vary greatly in their purpose, methodological rigour, comprehensiveness, resources used, transparency and the time spent for their production, ranging from 1 to 32 weeks , 26. PlaThus, is there sufficient evidence to reliably guide us how best to expedite SRs without compromising their validity? The majority of RR methodology overviews represent surveys that either describe or compare the methods and processes used for conducting RRs and SRs , 24–26. Over the last two decades, empirical evidence has accumulated from studies investigating different sources of bias related to specific SR tasks. For example, several authors evaluated study location strategies , 28, stuAnother area worthy of consideration is the restriction of inclusion criteria by language of publication. The inclusion of studies regardless of the language of publication would provide a more complete coverage and a greater precision of an effect estimate. However, the evidence whether or not the exclusion of non-English language study publications of conventional healthcare interventions introduces bias has been inconsistent, some authors showing meta-analyses of only English language studies yielding more conservative estimates , and othThe evidence regarding the need for quality assessment of studies included in SRs is more consistent in indicating that bypassing this important step may lead to substantial bias in the review estimates , 49, 50.Much of the above evidence has been focused on SRs of randomised trials of health interventions. While these studies have been crucial in guiding current approaches to undertaking full or reduced methodology SRs, more empirical evidence is needed as the uptake of SR methodology expands into the evaluation of other types of questions beyond clinical effectiveness .In situations of clinical urgency (e.g. outbreaks and epidemics of life threatening infections), when there is no relevant systematically reviewed evidence, timely delivered SRs can be of great value in informing healthcare decisions and recommendations. SRs conducted expeditiously may also be relevant if an existing SR is in need of updating or when the available resources are limited , 52. ForFuture empirical evidence comparing RRs to SRs and comprehensive synthesis of methodological studies exploring the magnitude of bias arising from a modification of any given SR step are needed to provide essential foundations for the development of evidence-based methodology for conducting SRs more timely. This evidence could also highlight specific SR steps or subtasks that are either of critical importance or redundant. Assessing the validity of RRs through comparison of their findings with SRs rests on the crucial assumption that current SR methodology is the gold standard which reflects the best available approach. This may be true regarding transparency and theoretical justification for instigating various standard procedures to minimise different forms of potential bias in the review process. But to what extent is current SR methodology supported by empirical evidence to guide practice, taking into account the efficiency of SR production?Some of the new initiatives and developments in the field are likely to inform the above-mentioned gaps in knowledge. For example, Cochrane Innovations initiated the programme of Rapid Response Review, which is designed to produce expedited reviews by using ‘abbreviated’ and ‘accelerated’ SR methods, while maintaining the methodological rigour and transparency of traditional SRs. This process implies iterative interactions between the commissioners and reviewers in formulating and refining the research question and scope of the review, thereby streamlining the review process through expeditious delivery of the response to any given research question .Systematic Reviews has published a thematic collection of articles highlighting important developments in the RR methodology which will likely help addressing the issues related to timely production of SRs [The January 2015 issue of n of SRs , 26, 54.n of SRs .In addition to making use of automation to expedite the conduct of individual SRs, collective efforts need to be made to improve the platform for the retrieval and synthesis of research information. This can be achieved through standardisation of data collection, reporting and archiving. The best examples are clinical trial registries, the EMBASE Screening Project  and the We hope that ongoing and future research initiatives will generate further relevant empirical data to better inform how best to conduct and deliver SRs timely. This evidence may also indicate contexts and/or content areas where this reduced methodology could become a standard SR approach.


Systematic reviews (SRs) of randomized controlled trials (RCTs) have demonstrated acupuncture’s effectiveness in stroke rehabilitation. The current study reviews the quality of evidence in SRs of acupuncture in stroke rehabilitation, and rates the strength of recommendation for its use based on this evidence using the GRADE  approach. A comprehensive literature search was performed using multiple databases  with advanced search strategies. Two authors independently selected articles, collected data, and assessed the methodological quality of each identified SR according to AMSTAR (a measurement tool to assess systematic reviews) and OQAQ . Outcomes related to stroke rehabilitation were evaluated. SRs of high methodological quality (AMSTAR score ≥9 and OQAQ score ≥7) were graded using GRADE. Ultimately, acupuncture yields benefits in stroke rehabilitation . Poor evidentiary quality and insufficient information about harm led to weak recommendations. In conclusion, acupuncture may improve stroke rehabilitation, as the GRADE approach indicated a weak recommendation for acupuncture’s usage in this context. Stroke has increased the economic burden imposed on health care systems, accounting for 2% to 4% of total health care costs3571012Systematic reviews (SRs) of high-quality randomized controlled trials (RCTs) are considered the best evidence regarding specific healthcare interventions1515179101419202122242526Despite the availability of numerous publications regarding the use of acupuncture in stroke rehabilitation10141920212228The Population, Intervention, Comparator, Outcome and Study design (PICOS) approach was used to frame our research objectives.SRs containing at least one RCT were included in this study.Patients with either hemorrhagic or ischemic stroke, at any stage or severity , who were either (1) diagnosed via brain computed tomography (CT) scan or brain magnetic resonance imaging (MRI) or (2) diagnosed clinically according to the World Health Organization definition . SRs in which the acupuncture treatment did not involve needling, such as those using point injection, acupressure, laser acupuncture, tap-pricking or cupping on pricked superficial blood vessels, were excluded.The control interventions included sham acupuncture, placebo acupuncture or other conventional treatments . Sham treatment included the following: (1) needle pricking on the skin surface (needles placed close to but not at the acupuncture points)We convened a panel of twelve experts in neurology, neurosurgery, cerebrovascular disease, acupuncture and traditional Chinese medicine at our hospital. These experts collected as many outcomes associated with stroke rehabilitation as possible and subsequently rated each outcome numerically from 1 to 9 points based on clinical importance  and privately recorded their judgments. Generally, outcomes of long-term patient interest, as well as acupuncture-associated outcomes , were defined as important outcomes. The individual judgments were then aggregated statistically to derive the median score for each outcome. We subsequently classified the importance of each outcome. Three outcome categories were specified based on their importance regarding clinical decision making: critical (median score of 7 to 9), important but not critical (median score of 4 to 6) and limited importance (median score of 1 to 3)We searched “pre-appraised” evidence resources , Embase , the Cochrane Database of Systematic Reviews , Psych-info (-2014.9), ScienceDirect (-2014.9), the China National Knowledge Infrastructure/China Academic Journals Full-text Database , the Chinese Biomedical Literature Database , the Chinese Scientific Journals Database , the Traditional Chinese Medicine (TCM) Database (1949-2014.9) and the Wanfang Database (1998-2014.9). No language restriction was imposed during the study search. The search strategies used in Medline (Ovid) are listed in Appendix 1 and were appropriately adapted for the other databases and the Chinese electronic databases using Chinese terms. We manually searched through four Chinese journals relevant to acupuncture  for articles published between 1980 and November 2014. We checked the reference lists of all relevant SRs identified, and their authors were contacted as a means of identifying additional relevant SRs.Two authors (Zhang X and Liu XT) independently checked the titles and abstracts of the articles and retrieved the full texts of potentially eligible articles for further review based on the selection criteria outlined above. In cases of disagreement between the two authors, a third member of our research group (Kang DY) reviewed the information to determine whether it should be included or excluded.The methodological quality of each SR was independently assessed by two reviewers using “A measurement tool to assess the methodological quality of systematic reviews” AMSTAR and the 3435Using a standardized form, two authors (Zhang X and Liu XT) independently extracted data from the SRs, including participant characteristics , intervention details, measured outcomes, number of included trials, sample sizes of each group, diagnostic criteria, TCM syndrome classification, study methodology, original RCT quality, and disease duration and state. The intervention details included meridian points, stimulation sources, drugs, medication doses, therapeutic regimens and treatment durations. Additional data and methodological information were obtained from the original RCT reports. We sought clarification from SR and RCT authors if an SR did not include clear descriptions of either the information or the methodologies used. Disagreements were resolved via discussion and consensus with a third researcher (Kang DY).The GRADE approachnd Cochrane Colloquium . For each SR, the authors independently utilized the GRADE tool to evaluate the evidence pertaining to key outcomes. The methodological criteria by which evidence was upgraded or downgraded were dependent on five primary domains , as well as the overall quality of the evidence Two authors  were trained to use the GRADE tool, which was obtained from the 22The second component of the GRADE approach entails determining the strength of a recommendation, i.e., the level of confidence that the desirable effects (benefits) of acupuncture outweighed the undesirable effects (harms) or vice versaEvidence quality was considered along with three additional key factors—the best estimates of the magnitudes of the effects on both desirable and undesirable outcomes, the importance of the outcomes, and the confidence in the magnitudes of the estimates of the effects of acupuncture on the important outcomes The data were entered into EpiData 3.1A total of 4750 SRs were initially screened. Eleven SRs were finally selected for quality assessment using PRISMA, AMSTAR and OQAQ. Three SRs with high-quality evidence (an AMSTAR score ≥9 or an OQAQ score ≥7) that met the inclusion criteria were identified . The det(1) Acupuncture (2) Rehabilitation therapy(3) Physical therapy(4) Occupational therapy(5) Speech therapy(6) Traditional Chinese medicine(7) Use of aspirinThe three included SRs assessed 19 RCTs. The following interventions were investigated within the original RCTs and varied in duration, frequency and intensity:The outcome measures, intervention effects, risk of bias assessments and other characteristics of the included RCTs and SRs are presented in Only quantitative analyses from the three included SRs  were useAlthough the included SRs were of good quality, indicated by a median AMSTAR score of 9 and a median OQAQ score of 8, the original RCTs were of poor quality. Four of the original RCTs4243442 = 63% (P = 0.04). As a result, we considered the level of inconsistency to be serious. Inconsistencies regarding the other outcomes were primarily attributed to differences in interventions, acupuncture details, stroke stages and methodological quality among the studies (downgraded by one level)  .The SRBecause the total number of participants was small (<400)Publication bias could not be ruled out because of the limited number of trials pertaining to the included outcomes .The quality of SR evidence was assessed using five components to grade the recommendations while taking into account the patients’ characteristicsThree high-quality SRs were identified, in which seventeen RCTs reporting nine critical outcomes with quantitative analyses were used to determine the overall quality of the evidence supporting the GRADE recommendation that acupuncture yields benefits in stroke rehabilitation . Virtually none of the authors of the included SRs were aware of negative effects caused by acupuncture, which can occur even when it is performed by a well-trained, licensed acupuncturist. The weak strength of the recommendation to use acupuncture in stroke rehabilitation implies that the decision to prescribe acupuncture for a patient suffering from stroke symptoms and sequelae should be approached with caution. In this study, we did not rate the recommendations of the domains of values and preferences or resource use, as reliable data were unavailable.Rating an overall body of evidence using the GRADE approach is becoming an important and recommended step in evidence synthesis initiativesSeveral organizations have summarized the evidence regarding the use of acupuncture in stroke rehabilitation; however, conflicting conclusions have been drawn. The Ottawa Panel2 statistic with which to determine heterogeneity. Although a qualitative approach may be utilized to assess consistency across multiple studies , such an approach is both subjective and unreliable. Similarly, imprecision assessments across studies are particularly problematic in the absence of a meta-analysis. We included only outcomes with quantitative analyses. In addition to confidence intervals (CIs) and the lines of no effect, another criterion, the optimum information size (OIS), should be used to ensure adequate precision. OIS is defined by the number of patients generated by a conventional sample size calculation for a single trial. If the total number of patients included in an SR is less than the OIS, the quality of the SR should be downgraded due to imprecisionWe encountered several challenges using GRADE. During the first round of risk bias assessment, we struggled in determining how to integrate the quality assessments of the original RCTs into a whole body of evidence. Additionally, poor reporting on “sequence generation”, “incomplete outcome data”, “allocation concealment” and “selective reporting” downgraded the risk of biasThere are several limitations to this study. A highly sensitive search strategy was utilized to identify current SRs; however, only three SRs were included for grading. This low number may have been due to methodological quality. The purpose of utilizing GRADE was to obtain both valid and reliable information to guide evidence-based decisions. The production of both comprehensive and accessible pre-appraised resources supports the use of an evidence-based approach to decision making. If SRs are to be useful, serious consideration must be given to how they are conducted. When the SR evidence gathered is strong and its implications are clear, the generated body of evidence should subsequently influence decision-making and shape health policy. The ultimate test of an SR is whether conducting it produced confidence that it is evidence-based and that it accurately reflects a process during its various stages. Evaluating the validity of SRs should influence the analysis, interpretation and conclusions of the GRADE approach. In particular, an SR of invalid studies may produce a misleading GRADE result, yielding a narrow confidence interval (good precision) around the wrong intervention effect estimate. Therefore, only high-quality SRs were selected for our study. Furthermore, our results may have been biased, as our selection process missed primary articles included in lower-quality SRs (which were excluded during the selection process). The objective of this research was to synthesize evidence from SRs; therefore, we did not consider these potentially missing primary articles. Future research may synthesize the evidence from primary articles, such as RCTs and cohort studies, using the GRADE approach; the results of these two research studies could then be compared. Moreover, almost none of the authors of the included SRs were aware of the negative effects caused by acupuncture—even when it is performed by a well-trained, licensed acupuncturist—other than occasional bruising. Finally, we did not perform sensitivity analyses to explore the differences among the results.Additionally, although two reviewers independently utilized the GRADE tool to rate the SRs, an agreement assessment was not performed because of the small number of SRs included in this analysis. It is important to emphasize that some subjectivity exists when assessing both the quality of evidence and the strength of a recommendation. However, our decision process was transparent, and frequent discussions took place among all authors regarding any queries. Finally, we did not assess publication bias, as we did not have a sufficient number of studies with which to formally evaluate it. Thus, publication bias may have existed in our findings, although a sensitive search strategy was utilized.In summary, we systematically assessed current evidence from SRs regarding the use of acupuncture in patients suffering from stroke. Moreover, an innovative approach was utilized to assess the quality of the SR evidence and the strength of recommendations pertaining to specific clinical procedures. Recent SRs that have evaluated RCTs describe the potential benefits of using acupuncture in stroke patients to improve rehabilitation; however, the overall body of evidence was found to be of low quality. Our critical appraisal of the evidence using the GRADE approach resulted in the formulation of a weak recommendation regarding the use of acupuncture in the setting of stroke rehabilitation. High-quality, well-designed SRs and RCTs are warranted to support the utilization of acupuncture in the setting of stroke rehabilitation.How to cite this article: Xin, Z. et al. GRADE in Systematic Reviews of Acupuncture for Stroke Rehabilitation: Recommendations based on High-Quality Evidence. Sci. Rep.5, 16582; doi: 10.1038/srep16582 (2015).


A cross-cultural analysis of trust and cooperation networks in Northern Ghana (NGHA) and Oaxaca (OAX) was carried out by means of ego networks and interviews. These regions were chosen because both are inhabited by several ethnic groups, thus providing a good opportunity to test the cultural group selection hypothesis. Against the predictions of this approach, we found that in both regions cooperation is grounded in personal trust groups, and that social cohesion depends on these emotional bonds. Moreover, in agreement with Fiske's notion of “evolved proclivities,” we also found two distinct kinds of trust networks, one for each region, which vary in terms of the degree of ethnic interrelation. This pattern suggests that social cohesion increases when environmental resources are scarce. Multiple agent-based models of the evolution of human sociality have tried to pin down the reasons why cooperation is biologically advantageous –kin selection   contributes to strengthening internal bonds; its persistence calls into question the second prediction of CGS, that cultural homogenization is to be expected.The psychology of trust is adapted to the needs of the environment: in the most difficult environments, where individuals need more help, more cohesive networks will emerge, that can cross the group boundaries.To address all the above questions, a cross-cultural approach turns out to be mandatory. We decided to compare two different regions, Northern Ghana (NGHA) and the Oaxaca region (OAX), both inhabited by several ethnic groups. Previous research on Ghana :  Spores,  from YolMestizos , Toto-zoquean languages , and the Hokan languages from southern area .Kussasis  and the city of Garu . In the former, we had access to is Syme, , 2001, Fas Hart, , Bissas s Zahan, , and memRattray, , 1932, as Wilks, ; all of Mamprusis , Gur , Mande (Bissas), and Fulbe (Fulanis). However, each of these branches has resulted in different languages and dialects for each of these groups.Both areas have a wide diversity of ethnic groups. However, the circumstances in which such multiple groups have emerged and the levels of interaction among groups are different. In both zones, the different cultural groups have coexisted for a long time, but a sense of their own identity has been maintained, despite interacting or sharing a common history. In order to better understand this issue, below, there is a brief review of the historical context in which both social and cultural network structures were created.The settlements in the current region of Oaxaca followed different stages: agricultural settlements (9000–1500 B.C), “villages” (1500–500 B.C.), urban settlements (500 B.C.–800 A.D.), and “city-states” (750–1521 A.D.). These concentrations were constituted by the union of family lineages , and Tikal (Mayan city) during the Early Classic period (200–600 A.D.), and with the Toltec people in the Late Classic period (600–900 A.D.) and the Early Post-classic period (800/900–1100 A.D.). In the Late Post-classic period (1100–1521/1694 A.D.) a period of wars began, in which some groups invaded others' territory, such as the Mixtec people who forced the Zapotec people toward the Isthmus regions, and the Aztecs –the Mexica people– who were moving toward Oaxaca and Yucatán from the North. However, the Aztecs allowed self-management in the conquered territories in exchange for receiving tributes.This same autonomy in the management of their own affairs was maintained during the Spanish colonization. Despite the exploitation of indigenous people and the inclusion of new taxes that squeezed their resources, the Spanish Crown in many cases allowed the Indians to keep their self-management, through the communal possession of territory  system –their self-management–, that guaranteed participation of the community members in community decisions, including the communal possession of land. In this way, territory, community, and cultural identity merged into the same goal of individuals' subsistence against their exploitation and marginalization by the powerful elite –first, the Spanish nobles, and later, the Creoles and wealthy Mestizos. Not in vain, the inherited Mesoamerican beliefs already largely linked group identity to a specific territory  settled between the 13th and 15th centuries, coming from north-east African areas, which dominated the acephalous people installed there. The Kussasi, Frafra, and Sissala people, who also inhabit some areas of northern Ghana, came from west of Sudan and migrated to the area in the 17th century, although other Sissala people seem to be descendants of the Mole-Dagbane groups. The Fulani people came from Niger and Senegal in the 16th century but they migrated to northern Ghana practically at the beginning of the 20th century. The Bissa or Busanga people settled in the White Volta in the 14th century. The Bimoba people are a mixture of the Moba people, who migrated from Burkina Faso in the 17th century, and the Mamprusi and Konkomba people, after being driven to the north by the Mamprusi and Dagomba people. Regarding the Konkomba people, it seems that they are some of the few original groups of these lands. The Waala people, from the city of Wa, capital of the upper-west region, arose from the conjunction in the 17th century of the warrior traditions of the Dagomba and Mamprusi people and Islamic traditions transmitted through small groups of Mande immigrants from Niger. Both the Mamprusi and the Mossi people in the north and the Asante people in the center of Ghana were centralized and hierarchical groups that gained more power, compared to the other mentioned groups, which were acephalous. In these cases, however, the more powerful groups were assimilating the social forms of the groups that were mixed with Rattray, . There aIn short, all of these groups are the result of the creation of different lineages that were forming their own cultural traits over time. The dynamics of separation and union to form new lineages with their own cultural traits have been continuous. Cultural diversity is observed in their different languages and dialects, beliefs, customs, festivals, etc.; differences either actually based on history or on a common imaginary.In the 15th century, the Portuguese people exploited the mineral resources of this country and subsequently, the British, French and Dutch people arrived (in the 16th century). In the 17th century, the Asante Confederation unified the groups. Solidarity among groups was appropriate because of the competition to acquire farmlands, control trade routes, and protect each other. In 1901, the areas of northern Ghana became an English Protectorate. The existing rivalries among certain ethnic groups because of fights for territory or slave trade increased with the English colonization, which promoted inequality of power among them and granted certain social and economic courtesies to some ethnic groups in detriment to others. In 1957, the country became independent but the differences before and during the colonial period are the origin of the current inter-ethnic tensions and the cultural reaffirmation of groups.There are, in this case, groups that also have influenced each other at a cultural level, but the survival pressures and their different allocation of power regarding others have led them to strengthen their ethnic identity.The resources and economic development of the two countries are also different. Whereas in OAX, the gross domestic product (GDP) per capita by purchasing power parity (PPP) –GDP per capita converted to international dollars using PPP rates–was $16,463 in 2013, in NGHA, it was $3974 (World Bank data).Whereas OAX is one of the poorest regions of Mexico, it is in a better position than NGHA, because of the productive resources of its environment and its level of economic development.In OAX, people live mainly from agriculture, as well as tourism, the services sector, crafts, fishing, salt in some coastal areas of the Isthmus region, and recently, wind energy. The climatic diversity in OAX allows cultivation of a wide range of products such as cane sugar, lemon, orange, alfalfa, barley, corn, avocado, pineapple, rice, melon, watermelon, agave, coffee and tobacco. In general, the landscape of OAX offers abundant vegetation and the rains per year are 1550 mm.http://data.worldbank.org/country/ghana). Its economy has grown, mainly due to improvements in agriculture, the development of the extractive industries, the natural resources of the country , the services sector, and manufacturing. However, the north of the country, where we conducted the study, is the poorest region, dominated by the Savannah with large areas of grasses, baobabs, and acacia trees. These arid areas −1.015 mm of rain per year– are used mostly for slash-and-burn farming and livestock. Also, the effects of the Harmattan, a dry wind from the wilderness, which reduces moisture and increases the number of hot days, last about 4 months of the year. Due to the previously mentioned, conflicts because of farmland distribution and the rudimentary and small-scale farming techniques, the inhabitants only have a subsistence economy.Ghana, however, is in the lower middle income countries of the world, with a 24.2% of the population under the threshold of poverty, according to World Bank data for 2012 , and the trust level they maintain toward cooperators. In Supplementary Materials are presented the forms for the OAX and NGHA groups  and 32 females (48.5%). The participants' ethnic groups are: 15 Chontales (22.7%), 10 Mestizos (15.2%), 1 Mixe (1.5%), 1 Mixtec (1.5%), 17 Zapotecs from Juchitán (25.8%), 12 Zapotecs from Teotitlán del Valle (18.2%) and 10 Zoques (15.2%). The distribution of these ethnic groups by gender is shown in Figure In NGHA, 46 persons participated: 33 males (71.7%) and 13 females (28.3%). The participants' ethnic groups are: 9 Bimobas (19.6%), 1 Frafra (2.2%), 9 Konkombas (19.5%), 11 Kussasis (23.9%), and 16 Mamprusis (34.8%). The distribution of these ethnic groups by gender is shown in Figure In OAX, 35 persons were interviewed: 19 males (65.5%) and 10 females (34.5%). The ethnic groups of participants are: 6 Chontales (17.1%), 8 Mestizos (22.9%), 2 Mixes (5.7%), 3 Mixtecs (8.6%), 5 Zapotecs (14.3%), 8 Zapotecs from Juchitán (22.9%), 3 Zoques (8.6%). The distribution of the interviewees by gender is presented in Figure In NGHA, 29 persons were interviewed: 19 males 65.5%) and 10 females (34.5%). The ethnic groups of participants are: 1, Akan (3.4%), 1 Asante (3.4%), 4 Bimobas (13.8%), 1 Bissa (3.4%), 1 Frafra (3.4%), 3 Fulanis (10.3%), 1 Gruni (3.4%), 4 Konkombas (13.8%), 5 Kussasis (17.2%), and 4 Mamprusis (13.8%), 1 Mossi (3.4%), 1 Sissala (3.4%) and 2 Waalas (6.9%). The distribution of the interviewees by gender is shown in Figure 5.5% and We report first the global measures of trust and cooperation for each region: size of personal networks of cooperation, trust levels of usual cooperators, and size of trust circles, and report statistically significant differences between OAX and NGHA for these measures. Given there were some differences in the types of settlements where participants of OAX and NGHA lived , the Supplementary Material In both territories, the number of usual cooperators reported by the participants in the interviews is not very high. The mean does not exceed 15 people. The mean of usual cooperators is smaller in OAX (9.36) than in NGHA (14.39) . There are more usual cooperators with middle trust level in OAX than NGHA (2.38 and 1.65 respectively)  than in NGHA 23.67)  and trustees  between OAX and NGHA: a higher number of people in both cases in NGHA.There are significant differences –one-tailed Mann-Whitney test– with respect to the number of usual cooperators  between both regions. But significant differences were found between the number of cooperators with very high , high  and middle  trust levels: a higher level of very high and high trusted cooperators in NGHA and middle trusted cooperators in OAX , and then friends and neighbors (16.99 and 15.86% respectively). However, in the case of NGHA, most of the usual cooperators are friends (49.24%), followed by relatives (28.33%) and neighbors (11.67%). In both cases, higher trust levels toward usual cooperators also seem to go together with higher levels of reciprocity in their cooperative exchanges.A bias toward “ethnic endogamy” in cooperation can be found in OAX with respect to NGHA because participants' networks of usual cooperators show fewer individuals of different ethnicity. In OAX just 1 (Mixtec) out of the 7 ethnic groups analyzed had more than the 20% of their usual cooperators of different ethnic group. In NGHA 3  out of 5 ethnic groups had more than the 20% of their usual cooperators with different ethnicity.With respect to the types of cooperation most often mentioned with the networks of usual cooperators, there also are differences between OAX and NGHA. The most mentioned in NGHA respect to OAX are advices (30.37 and 17.65%), information (17.76 and 5.37%) and secrets (15.23 and 11.74%). However, OAX refers more to services (18.58 and 7.22%) and lending objects (15.86 and 3.53%) and lending money (12.21 and 7.57%).There also are differences in the level of reciprocity of the cooperation between the two regions: even when the highest percentage of cooperation among usual cooperators is reciprocal in both territories, this percentage in OAX is higher than in NGHA (84.20 and 74.28%). However, in NGHA there is a higher percentage than in OAX of cases of usual cooperators with no reciprocal cooperation, both when the participant is who receives (13.20 and 7.59%) as the giver (12.53 and 8.20%).Finally, family plays a greater role in OAX than in NGHA, since for any type of cooperation the percentage of relatives as usual cooperators is higher, except for information exchanges. In NGHA these percentages are divided between family and friends: more relatives than friends for lending money, secrets and services; and more friends than relatives for information, advices, learning and jobs.Circles of trust are mostly composed of relatives in both cases , with more friends in NGHA (7.95 and 13.52%). Relatives' social relevance is also indicated by the proportion of good relationships with relatives (74 and 68.97% respectively) and the proportion of interviewees that declare to trust always the family (51.42 and 44.83% respectively). Relatives are also the preferred recipients of secrets (71.93 and 70.82% respectively), but in NGHA we don't find participants who declared not to tell their secrets to anybody, while in OAX we find the 15.28% of participants.compadres” (63.64%) and community members (65.75%), in OAX. Besides, in OAX more people declare having little relationship with these networks than in NGHA (28.89 and 12.33% respectively). Together with the higher proportion of interethnic cooperation, these data suggests that in NGHA trust and cooperation extends beyond family. As a matter of fact, family is a more encompassing structure in NGHA. People in NGHA mention more frequently than in OAX the meanings of lineage –“identity and origins” (14.05 for 2.44% in OAX)–, unity of persons –“be together” (26.57 and 3.66% respectively)–, and to a lesser extent, mutual help (29.70 and 24.38%), as relevant dimensions of family. In OAX, on the contrary, family involves an emotional dimension: “something valuable” (12.19 and 9.38% respectively), “give love” (7.32 and 1.56%), and components just mentioned in OAX: “respect” (2.44%), “happiness” (3.66%), “pride” (1.22%). Thus, in NGHA family extends to a greater number of individuals –a lineage– for mutual help.On the other hand, there is a higher proportion in NGHA than in OAX of participants who declare having good relationships with their nearest network of people: same clan (78.13%) in NGHA; and extended family (62.22%), “In NGHA there is more interaction among ethnic groups than in OAX: the 57.78% of participants in OAX declare not having contact with other ethnic groups but nobody says so in NGHA. Accordingly, more interaction in NGHA translates into a higher proportion of answers of having good (12.35%) and bad (19.35%) relationships with other ethnic groups than in the OAX sample (8.89 and 11.10% respectively). However, the 17.25% of NGHA answers doesn't show clearly how the relationships are with other ethnic groups.The greater interaction among ethnic groups in NGHA than in OAX has to do with a higher proportion of people who declare trusting other ethnic groups in absolute terms (44.4 and 35.29% respectively). However, the percentage of answers not trusting other ethnic groups is also higher in NGHA respect to OAX (22.22 and 14.71%). The mistrust is also implicit in the expression “it depends” that has a higher proportion in OAX than in NGHA (38.24 and 30.56%).But a way to clearly measure general trust is the attitude toward unknown people. Although the decision of trusting for the first time in both countries is mostly based on the other's behavior (47.95% in OAX and 48% in NGHA), greater signs of general trust are found again in NGHA. There are a higher percentage of answers in NGHA than OAX of “trust in advance” (18 and 2.74%) and relying on “appearance” (14 and 1.37%). However, in OAX “references” are more needed than in NGHA (15.07 and 12%), where many declare “not be able to trust in advance” (21.92%) nobody says so in NGHA.As regards newcomers, the NGHA interviewees show an attitude more open than those from OAX. In NGHA, there is a larger number of responses than in OAX that refer to offering a special treatment to the newcomer (20.44% for 9.67%), having meetings and sharing activities (17.18% for 12.89%), communicating (12.90% for 9.68%), giving donations (16.14% for 12.90%), sharing (2.14% for 0), and transmitting the group values and norms (6.46% for 1.07%) with them. In the case of OAX, however, these differences in the percentages with respect to the above-mentioned answers are replaced by attitudes such as “do nothing” (7.53%), the simple coexistence (4.30%) or just know the new person (7.53%).With respect to the activities to foster trust, in both areas, meetings (45.26% in OAX and 43.65% in NGHA) and shared activities (34.75% in OAX and 29.58% in NGHA) were mentioned. Again, helping has a higher proportion of answers in NGHA than OAX (7.04 and 2.10%), but “doing nothing” has a higher proportion of answers in OAX than NGHA (9.47 and 4.22%). However, a difference can be found with respect to the kinds of meetings that foster trust: festive meetings are mentioned more frequently in OAX than NGHA (26.31 and 15.48%), and religious meetings and rituals more mentioned in NGHA .Additionally, in NGHA there is a higher percentage of affirmative answers on the influence of religion (89.65%) in the level of cooperation than OAX (47.06%) -a factor thought to foster general trust-. Similarly, the Government is attributed a greater role in promoting cooperation in NGHA than in OAX (91.67 and 51.61% respectively).OAX has a lower percentage of people who forget the betrayal of trust (20% for 51.72% in NGHA), and a greater number of people who punish the betrayal of trust (86.35% for 52.73%).Consistent with the centrality of mutual help, NGHA shows a higher percentage of answers that mentioned the lack of help as a betrayal of trust (19.14% for 3.28% in OAX) or as a reason to break agreements (8.51%). In OAX, on the contrary, gossip is mentioned more frequently as a betrayal of trust (16.40% for 4.25%). Trust betrayal has more consequences in OAX than in NGHA, involving direct punishment (18.17% for 9.10%), and punishment by avoidance (68.18% for 43.63%). Conversely, in NGHA is more frequently answered not punishing the betrayal of trust (25.46% for 4.55%), and proposing measures of approximation (21.81% for 9.10%).In the same sense, it is also observed more communication (48.10% for 42.97%), less mediation (15.19% for 29.83%), more “forgive and forget” (10.12%) and more attitudes of self-assessment  as conflict solving strategies in NGHA than in OAX. By contrast in OAX, people mention more passive measures (8.77%) and just “some way” of approach (11.40%).The different economic situation in both regions, seem to play an indirect role on trust and cooperation, through the different sort of needs of the members of each group. Thus, in OAX only the 10.26% of participants say they feel insecure, while in NGHA, this percentage rises to 43.33%. Similarly, economic fears appear in 12.73% of responses in NGHA, but none in OAX; security fears are mentioned by 17.84% in NGHA, but just 5.12% in OAX; fear about health appears in 12.75% of NGHA respondents, but only in 2.57% from OAX. Security fears in NGHA are related to inter-ethnic conflicts , and thefts. In general, fears in NGHA have to do with economic scarcity. This pressing nature of necessity in NGHA also appears in the higher number of responses which explicitly mention the value of mutual help  as a way to keep trust. This connection between trust and greater necessity is also manifested in that the economic exchanges are thought to require high levels of trust in NGHA .Similarly, the different level of available resources of each region is also reflected in the role of reputation. While the importance of reputation is very high in both regions (97.14% in OAX and 93.10% in NGHA), the reasons to gain reputation are different: related to help, in NGHA; related to norm compliance, in OAX. Here reputation comes from “being considered a community member” ; while in NGHA, good reputation is more frequently associated than in OAX with “a greater level of help received” (27.10% for 9.09%), and with “being respected and trusted” (33.34% for 13.64%), as a way to warrant future support.This study supports the hypothesis that small groups are the basic structure around which networks of trust and cooperation organize. Across different regions and even diverse social groups, a common pattern can be discerned –a small-sized trust circle– as a sort of “evolved proclivity” Fiske,  to make Our results also support our third hypothesis that the efficacy of the trust network is related to the environmental demands the group faces, among other possible constraints, so that differences are to be expected in the particular arrangement this basic social structure will take in each case. In fact, our results suggest two different types of trust networks corresponding to each region, relative to environmental scarcity and the corresponding degree of group cohesion found:In OAX, trust circles seem to involve less people, and cooperation is also circumscribed to less people. In particular, high-trust cooperators are almost exclusively relatives, which share affection. General trust is also lower: cooperation takes place among same group members, reluctance to actively incorporate new group members is higher, trust betrayal is not forgotten, and requires punishment. Efforts are not made toward remedying conflicts.By contrast, in NGHA, both personal trust networks (trustees) and usual cooperators are bigger, with higher proportions of highly trusted usual cooperators. Cooperation also extends to a greater number of people, both from the same lineage and clan, but also from other ethnic groups. General trust is higher: more trustees among other ethnic groups, newcomers are integrated and conflicts solved through communication and active measures of approximation.These differences can be explained by reference to the different levels of economic and ecological scarcity: subsistence economy and few resources in NGHA, and environmental richness in OAX. Thus, it is observed how in NGHA, where the environmental conditions are harder, there are social networks of trust extended to a higher number of individuals, as a strategy that fosters greater cooperation and hence, guarantees greater chances of survival. Trust networks of type 2 are particularly effective in this sense. In addition to larger trust circles, the NGHA cooperation networks have higher levels of trust. Besides, the circles of cooperation are extended to more different people, thereby ensuring higher chances of survival. At the same time, such persons in NGHA are also more willing to increase trust circles –more active behavior to integrate new people– and to decrease the chances of breaking bonds –greater willingness to forget the betrayal of trust and less willingness to punish it.In addition, it has also been shown that groups in NGHA have more internalized the assistance to other group members in their system of values –they mentioned more frequently “help” as a necessary requirement to keep trust relationships and as a beneficial effect of having a good reputation. This is consistent with previous research in Ghana, which also found the importance of mutual help in friendship, and the awareness of the risks incurred when trust extends beyond relatives (Adams and Plaut, The type of trust network found in OAX, on the other hand, may have to do with the historical past events. In OAX, ethnic diversity is the outcome of a history in which different groups created their cultural identities over centuries, in spite of being in contact along periods of conquest and/or migratory movements. With the Spanish Colonization and Republic, the groups strengthened their identity and social enclosure as a way to protect their territorial rights and face the marginalization from the established powers. This may have pushed the communities to stay put, in spite of the syncretic transformations of their respective cultures by the Spanish hegemony. Together with this broad common culture, ethnic and linguistic diversity have persisted, against the predictions of cultural group selection theory.Another factor contributing to keeping with group diversity was may have to do with the orography of the area. Mountainous separation between villages added further difficulty to intergroup exchanges. In addition, cultural differentiation was also kept because of the expression of the “commonality” of municipalities as a group hallmark (Gerrero Osorio, NGHA, on the other side, has a long history of different cultural settlements regardless of national borders, with continuous migration and trading with other groups. However, in this case, groups have interacted more both during British Colonization and after Independence. Conflicts among different cultural groups settled in the same country already existed and with the British Colonization became more intense. This also led to the intensification of ethnic diversity to defend territories and administrative powers, similarly as in OAX.Taken together, the regions studied are examples of how the unity and association into social groups, is more cohesive when necessary to face contexts of scarcity and lack of power. While the cultural identity of the groups studied was affected by the colonization processes they respectively experienced, their respective patterns of cooperation, grounded in trust networks, provide the cement to keep them diverse –even if more open to intergroup exchange in one case than in the other.Even when cultural identity of the smaller ethnic groups allowed them to create some way of “emotional” ties that drives them to act together more frequently, trust groups are more basic pillars of cooperation. The psychology of personal trust might be more fostered, however, by emotional figures such as those of lineage and clan of NGHA, more attached to values of belonging, identity and group support than by the regulatory figures of OAX.A further level of analysis, which we haven't been able to carry out given the insufficient number of participants for this goal, would consist in comparing in more detail the different ethnic groups within each of the studied regions. Still, some relevant features can be discerned. Despite there are more conflicts among ethnic groups in NGHA than in OAX, higher levels of trust among members of different groups are found among them than in OAX, maybe due to the fact that inter-ethnic contact fosters personal trust –in OAX interaction among ethnic groups is rare. Only the Mixtecs from OAX happen to cooperate with non-Mixtecs in a significant proportion, while in NGHA it's more common to cooperate with members of other ethnic groups.In general, humans seem to become more individualistic in more developed societies, where the economic levels allow acquiring certain security –absence of survival concerns– because they don't have the same need of others for vital support. Culturally, the expression of this is reinforcing family bonds around the nuclear family. Not being so necessary reinforcing the values of unity and trust, new ties arise with lower levels of trust, which are good enough to provide the required benefits in the short term.In conclusion, this work supports our hypothesis that small groups of trust and cooperation are the basic, universal, form of sociality. This social form is modulated by the particular environment the group is placed and the cultural strategies developed to foster trust and cooperation beyond such a basic social unit. Comparing the NGHA and OAX groups reveals different strategies in this respect, which have to do with the differences in environmental and historical conditions. The more scarce the resources, the higher the degree of social cohesion needed to sustain the society and the greater the push toward keeping ethnic diversity.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.