Indigenous Tobacco Control Initiative and Tackling Indigenous Smoking Measure were both announced by the Australian Government at a time when its rhetoric around the importance of evidence-based policy making was strong. This article will (1) examine how the Rudd Government used evidence in Indigenous tobacco control policy making and (2) explore the facilitators of and barriers to the use of evidence.The Freedom of Information Act 1982  and (2) interviews with senior politicians, senior bureaucrats, government advisors, Indigenous health advocates, and academics. Through the Freedom of Information Act process, 24 previously undisclosed government documents relevant to the making of Indigenous tobacco control policies were identified. Interviewees  were identified through both purposive and snowball recruitment strategies. The Framework Analysis method was used to analyze documentary and interview data.Data were collected through (1) a review of primary documents largely obtained under the Government policy design was heavily influenced by the recommendations presented in government authored/commissioned literature reviews. Resulting policies were led by equivocal evidence for improved tobacco control outcomes among Indigenous Australians. Many of the cited studies had methodological limitations. In the absence of high-quality evidence, some policy makers supported policy recommendations that were perceived to be popular among the Indigenous community. Other policy makers recognized that there were barriers to accumulating rigorous, generalizable evidence; in the absence of such evidence, the policy makers considered that the “need for action” could be combined with the “need for research” by introducing innovative strategies and evaluating them.Despite the absence of high-quality evidence, the formulation and adoption of Indigenous tobacco policy was neither irrational nor reckless. The decision to adopt an innovate and evaluate strategy was justifiable given (a) the potential for the gap between Indigenous and non-Indigenous health outcomes to worsen in the absence of an imminent policy response; (b) the existence of circumstances, which made it difficult to obtain high-quality evidence to guide policy; and (c) the need for policy solutions to reflect community preferences, given sociohistorical sensitivities. This arWhen the Labor Party assumed government in 2007 under the leadership of Prime Minister Kevin Rudd, Indigenous Australians were expected to have lives that were 17 years shorter than their non-Indigenous counterparts . The LabIndigenous Tobacco Control Initiative and Tackling Indigenous Smoking Measure committed over AUD 120 million in government funds and marked the beginning of a period “that has seen more action on Indigenous smoking than any other time in our history”  examine how the Rudd Government used evidence in Indigenous tobacco control policy making and (2) explore the facilitators of and barriers to the use of evidence relative to other factors.In so doing, this article reveals difficulties in the application of evidence-based policy making. These difficulties include debates as to what constitutes “evidence” and a tension between the need for good evidence and the need for urgent policy action. The article also demonstrates how, in some circumstances, the need for evidence of effectiveness can be exceeded by the need to empower the target population in the decision-making process.Data were collected through a combination of document reviews and interviews. The overarching purpose of data collection with respect to each method is set out in Table It is considered prudent to combine these two methods when conducting policy process analyses to mitigate their respective limitations , 10. TheDepartment of Health and Ageing (DoHA) (“Publications” and “Media Release and speech archive” sections only);Australian Indigenous HealthInfoNet (“Policies” and “Tobacco” sections only);Tobacco Control Supersite ;National Aboriginal and Torres Strait Islander Health Equality Council;National Preventative Health Taskforce;Australian National Council on Drugs;Ministerial Council on Drug Strategy;Intergovernmental Committee on Drugs;Quit;Factiva .A two-stage process was adopted to identify relevant documents. In the first instance, publicly available documents were obtained by searching the following websites/databases:Where search functions were available, the search was limited to items containing the search terms “ AND (tobacco OR smok*).” Where search functions were not available, items were individually screened by title for relevance. Relevant documents were limited to those produced between 2007 (election of Rudd Government) and 2008 (announcement of policies).Freedom of Information Act 1982 (FOI).The second-stage of the document review was focused on obtaining relevant documents produced for the private use of members of the policy-making community. These documents were either provided by the interview respondents or accessed under the federal Indigenous Tobacco Control Initiative was discussed;minutes of meetings held between December 2007 and 20 March, 2008 in which the Indigenous Tobacco Control Initiative in 2008–09;minutes of any meetings relevant to the selection of the first six multicomponent projects funded as part of the National Partnership Agreement on Closing the Gap in Indigenous Health Outcomes were discussed;minutes of meetings held between December 2007 and December 2008 in which the tobacco elements of the Tackling Smoking Measure specifically;any research commissioned before December 2008 to inform the Indigenous Tobacco Control Initiative is mentioned;memoranda or advice prepared between December 2007 and 20 March, 2008 in which the Tacking Indigenous Smoking Measure is mentioned.memoranda, advice, or briefing papers drafted before December 2008 in which the The initial request (FOI Request 309-112) for “written reports/letters of advice and internal reports or memoranda used by the Government to inform the design of the Indigenous Tobacco Control Initiative” resulted in an estimated charge of AUD 10,845 for the time that FOI officers and document custodians would likely spend searching for, retrieving, and assessing the documents. Further particularized requests were then submitted (FOI Requests 006-1314 and 067-1213) seeking access to the following:The revised requests yielded 24 previously undisclosed documents relevant to the making of the policies. One document was not disclosed on the basis that it was produced for Cabinet deliberations and therefore exempt under the legislation.Interview participants were recruited through a combined purposive and snowballing sampling strategy, as recommended for studies of this nature , 11. A pFifty potential respondents were invited to participate in interviews. A source population of 50 policy actors was considered reasonable, given that the study was limited to two specific policies. Thirty-one individuals agreed to participate in the study, representing a response rate of 62%. The response rate is consistent with those obtained in other studies of the public services sector .n = 2), senior Federal politicians (n = 2), senior Federal health bureaucrats (n = 4), members of and assistants to the National Preventive Health Taskforce and its Tobacco Working Group (n = 9), members of the National Indigenous Drug and Alcohol Committee (n = 2), researchers/academics (n = 4), and Indigenous health advocates (n = 8). Anonymity was guaranteed to protect reputations and interests. Of those individuals who did not respond to or declined interview invitations, four were politicians, seven were government advisory group members, one was a senior bureaucrat, four were researchers, and three were Indigenous advocates.The sample comprised advisors to the Federal Minister for Health  and Deakin University (Ref: 2012-218).Data were analyzed using the Framework Analysis method. The process involved (1) becoming familiar with the data by listening to/transcribing the recordings and reading the transcripts and documents; 2) noting down recurring themes and subthemes  were current daily smokers, compared to 23% of the general population  the appointment of a Health Minister committed to tobacco control, perhaps best evidenced in the Rudd Government’s decision to make Australia the first country in the world to introduce a law to mandate plain cigarette packaging.The interview findings suggest that the increased political attention given to Indigenous smoking in 2008 was the product of a confluence of three factors – namely – (1) the publication of evidence showing that tobacco was the single largest contributor to the “gap” between Indigenous and non-Indigenous health outcomes; (2) the success of the Six respondents cited a burden of disease study by Vos et al. published in 2007  as an explanation for why Indigenous smoking became more politically prominent in 2008 . The stu“the study was so important.” The significance of the Vos study was that it “show[ed] people what were the contributing factors to excess mortality” (senior bureaucrat). An Indigenous leader and health advocate, recalled that Vos’ work prompted an Indigenous research organization to focus on smoking:[The Cooperative Research Centre for Aboriginal and Torres Strait Islander Health] put briefings together and all that and started to tell their story to the Minister … And then they did this presentation in Parliament House. Within a fortnight [the Government] found $14 million.One senior bureaucrat said of the Vos study, “that was probably an absolutely crucial event” (Indigenous tobacco control academic). A Ministerial advisor considered that the event “helped crystallise the view that tobacco was a critical factor.”The presentation to which the respondent referred formed part of the Parliamentary Showcase of Aboriginal Health Research, which was held in March 2008 and opened by the Health Minister. As part of the program, Viki Briggs of the Centre for Excellence in Indigenous Tobacco Control (CEITC) delivered a presentation entitled “Reduce Smoking, Reduce the Gap” in which the findings of the Vos study were highlighted . AnotherFour respondents were of the view that the impact of the Vos study must be considered in its sociopolitical context. The study was published in 2007 at a time when the Closing the Gap campaign for Indigenous and non-Indigenous equality was gaining momentum . In the [W]hile the strong research helped galvanise people around [Indigenous tobacco control] I don’t think it was the cause or catalyst for action … [T]he very successful campaign around Close the Gap … helped create political momentum and interest – the research is vital in this context but could’ve gone unnoticed without the broader campaign.Evidence demonstrating the impact of smoking on the gap between Indigenous and non-Indigenous health outcomes found fertile ground in this sociopolitical landscape. According to a senior politician:“catalyst” for political action “was that we had a figure, a statistic that said smoking causes 20% of all mortality. It came at the same time as Closing the Gap. So, okay, to close the gap … you’ve got to prevent premature mortality.” A Ministerial advisor agreed that “we were never going to achieve this [aim to close the gap in health outcomes] if we didn’t do something about Indigenous smoking.”Similarly, a senior bureaucrat explained that a “[w]henever we put a case around a smoking intervention, every minister would say, ‘yeah, well who the hell’s going to run it because they [Aboriginal health staff] all smoke anyway?’”While the confluence of evidence and political agendas created a positive environment for Indigenous tobacco control to become more politically salient, four respondents emphasized the crucial role of the Health Minister in actually securing policy action. It was noted that DoHA’s interest in Indigenous tobacco control predated the policy developments in 2008 but that, despite this, the issue never gained political attention. According to a senior bureaucrat, “bottom line is Nicola Roxon … got it and put money into it” (Tobacco Working Group member). Similarly, an Indigenous leader and health advocate was of the view that “you can put it [policy action] down to a couple of people in the Minister’s office and the Minister herself. She was committed to saying, ‘if that’s what the evidence is telling us, we need to put a bigger effort into here.”By contrast, the new Health Minister, Nicola Roxon, was described as someone who understood and championed the importance of Indigenous tobacco control. A Government advisor explained that the Indigenous Tobacco Control Initiative, which occurred over a short period of time due to political and organizational pressures. A Ministerial advisor noted “there was a sense that after the Apology [to the Stolen Generations in February 2008] that … [the] goodwill created by that needed to be translated into some sort of firm commitments” .Both interview data and documents obtained under FOI confirmed that DoHA played a lead role in the design of the I do remember this being an example where we were kind of going, ‘Ergh! I think the PM might want to announce something’ … [A]s I say, it was all a little bit chaotic in those early days. So it meant that a lot of the sort of detailed policy development was done at the Departmental level more so than at the Ministerial level.The Indigenous Health Equality Summit was scheduled to take place in Parliament House in March 2008 and was expected to culminate in the signing of a partnership agreement between government and non-government organizations to achieve health equality between Indigenous and non-Indigenous Australians. The interview data suggested that the Prime Minister had expressed an intention to attend the event, and that this served as a catalyst for the development of the policy. A Ministerial advisor said:“the Department [of Health and Ageing] sort of came up with this bunch of proposals and said, ‘look … we’ll give you something to announce at this event.’”Media reports, to which the respondent referred, revealed that the Health Minister had been dissatisfied with unrealistic time pressures imposed by Prime Minister Rudd . AccordiIndigenous Tobacco Control Initiative was announced by Prime Minister Rudd at the Indigenous Health Equality Summit. Through the Initiative, the Government committed AU$14.5 million over 4 years to:train Indigenous health staff in smoking-cessation strategies;trial innovative community interventions, including culturally appropriate communication activities, in five or six pilot sites; andsupport Indigenous tobacco control research to “help build the evidence base around what works” .The offer support and training for local health staff to deliver brief tobacco cessation interventions and programs that include nicotine replacement therapy;provide more intensive interventions in targeted communities/regions;develop media campaigns featuring local identities or artwork;fund the CEITC to audit evaluations of tobacco control initiatives.One of the documents obtained under FOI was a literature review (dated June 2007) authored by an employee of DoHA Program Management and Evaluation Unit. The review proposed five policy options, four of which seem to have been incorporated into the Initiative developed by DoHA – namely:Table Tackling Indigenous Smoking Measure – formed part of the Council of Australian Governments’ National Partnership Agreement on Closing the Gap in Indigenous Health Outcomes, which was signed in December 2008  coupled with a strong research focus to ensure that resources are not wasted on misdirected initiatives.An innovate and evaluate approach was accepted as being an appropriate solution in the circumstances. Internal documents obtained under FoI demonstrate the extent to which policy makers considered that it was both necessary and justifiable to act without a strong evidence base, so long as there was a commitment to accumulating knowledge in the process:[W]e need to look at ways of finding types of intervention that would resonate better with Aboriginal communities and I think a part of what came with that [was] also an acceptance that certainly when it comes to mainstream programs, it is driven by research … but … when it comes to Aboriginal smoking there’s a need to be willing to take a few more risks, and trial different ways of addressing the problem.The alternative approach – that is, waiting for evidence to emerge before taking policy action – was not considered practical. Two policy makers noted that the Indigenous context presented distinct challenges to the conventional understanding of evidence-based policy making, arguing that evidence needed to play more of a back-end role. According to a Tobacco Working Group member:[T]he logistics of doing high level randomised controlled trials in [remote] populations … it’s ridiculous … There were a whole lot of issues with cross-contamination between communities … We did the numbers for a randomised control trial in giving quit advice … the numbers to do a proper randomised control trial in the Northern Territory were going to be 30,000 participants. You couldn’t get it … (Indigenous tobacco control academic).Researchers with links to policy makers expressed the view that the Indigenous research context presented distinct challenges. One respondent offered the following example of the limitations:[T]here’s always challenges from the remoteness of going out to do the pre- and post-questionnaires … a lot of these people move around in their communities … They will travel around and visit family and the neighbouring community. Could be anything … even the weather … From all those kind of logistic things, to even language being a barrier.An Indigenous advocate with research experience added:“overdoing the differences” and noted that “Aboriginal people are people. They smoke like other people. They quit like other people. And I think we need to be almost wary of assuming that you need to have something incredibly and dramatically different.” Another Working Group member concurred, arguing that “there is absolutely zero evidence that those [mainstream] approaches do not impact Indigenous people in the same sort of was as they affect the rest of us.” Longitudinal studies lend some support for this view showing that, in the absence of major Indigenous-specific policies, daily smoking prevalence for Indigenous males over the age of 18 years decreased from 58.5% in 1994 to 52.6% in 2008 with a statistically significant annual decrease of 0.4% per year .The apparent mismatch between the advice provided to Government and the view of some respondents that some Indigenous-specific interventions were not necessary was explained in the following way:[P]eoples outside of mainstream Australia have a right and should be involved in leading the progression of policy development around those marginalised populations … [I]t’s time for the policy developers in Australia to now say to Aboriginal Australians, ‘you must develop the policies and you must assist us on the pathways out’ .… An expert government advisor agreed that, in light of the history of exclusion, Indigenous perspectives need to be incorporated into the policy process:[B]ecause of the awful history for Aboriginal people in this country there’s a real strong desire amongst representatives of the Aboriginal community that you’ll be working with … wanting it to be Aboriginal-determined, controlled etc.[A] lot of Aboriginal people were really keen on the idea of local workers. Would it be in my core program? Not necessarily. But if it’s the price we pay for getting Aboriginal people [to] support the rest of the program – willingly pay it.Other members of the Tobacco Working Group confirmed the importance of ensuring that the policies were developed with and supported by Indigenous people:competition with other policy factors, this case study presents evidence as being dependent on them.This case study has demonstrated empirically what the theoretical models of policy making suggest – namely – that evidence does not exist and cannot be used in a vacuum. Rather than viewing evidence as being in The intuitive appeal of evidence-based policy making lies in the perception of objectivity – evidence “speaks for itself” . CertainIn this instance, there were two factors that enabled the evidence to “speak” in the policy process. First, the evidence emerged against the backdrop of a popular sociopolitical campaign to reduce health disparities between Indigenous and non-Indigenous Australians; this aligns with both Walt and Gilson’s notion of “context” and Lin’s definition of “cultural rationality” as “what (perceived) societal opinions feel is right” , 5. SecoIndigenous Tobacco Control Initiative, “political rationality” and “context” seem to be major explanations for the fact that most of the recommendations emerging from the literature review were adopted in the policy. The political pressure to make a major policy announcement at the Indigenous Health Equity Summit meant that policy proposals needed to be developed by DoHA within a short period of time. In this situation, the importance of the evidence seems, at least in part, to have been associated with its accessibility . The accessibility of research has been identified as a facilitator to evidence-based policy making in other studies (The symbiotic relationship between evidence and other policy factors was further demonstrated in the policy design stage. The recommendations presented in the government authored/commissioned literature reviews (obtained under FoI) seem to have heavily influenced the content of the policies. In relation to the  studies –58.Tackling Indigenous Smoking Measure closely reflected the recommendations in another literature review commissioned by DoHA and authored by the CEITC. Viewed through the prism of Walt and Gilson’s model of health policy making, the value that was placed on the CEITC’s research can be partly ascribed to the organization being regarded as a key “actor” in the policy community. If the policy community is conceptualized as a network of interconnected individuals and organizations, CEITC’s influence derived from its centrality in that network  found that the policy “diminished its own effectiveness through its failure to engage constructively with the Aboriginal people it was intended to help” . For somEvidence cannot trump all other factors; rather it must coexist with other inputs in the policy process, including the “thoughtful identification and compassionate use of individual patients’ [or populations’] predicaments, rights and preferences” . This caIdeally, solutions that are “acceptable” to the target population will also be supported by evidence of their likely effectiveness. However, the Indigenous tobacco control case study demonstrates that there are situations in which it may be justifiable to introduce policies in the absence of high-quality evidence.the fact that the Indigenous Australian source population is small , meaning that sample populations in Indigenous-specific studies are also likely to be small, and only very large program impacts are likely to be statistically significant ;Indigenous distrust of research on the basis that it was historically associated with “the politics of colonial control” and, in the present day, can be perceived to be exploitative, stigmatizing, or unresponsive to Indigenous needs and concerns –67; andthe fact that, in order to be culturally sensitive, there is often a call for research in Indigenous communities to be participatory, which can result in a conflict between “the values of the academic setting and those of the community” , 68.It has been noted that barriers to research in Indigenous contexts includeThe consequence is that “‘best’ evidence is often gathered on simple interventions and from groups that are easy to reach in a population,” and evidence from those that are harder to reach tends to be regarded as inferior .This research bias is not unique to the Indigenous Australian context. It has been noted that low-income countries often have limited resources to invest in research, and cultural minorities within high-income countries are often excluded from research protocols because of the logistical and financial costs, such as those related to translation . With reIf there is no evidence of effectiveness among the most deprived group… [e]fficient use of scarce resources… would imply the intervention not be given to these individuals with the anticipated increase in social inequalities in health. The resources of a health care system would become increasingly concentrated on less deprived populations. This results not necessarily because the problems of the more deprived groups are insoluble, but because the mechanisms we choose to evaluate for dealing with the observed problems are particularly suited to less deprived groups, i.e. it is a feature of the ‘service focus’ .Birch presents the potential resulting paradox of a “no action without supporting evidence” mentality thus:Applied to the Indigenous tobacco control context, a rigid adherence to the belief that there should be “no policy without evidence” could feasibly have resulted in a widening of the health gap between Indigenous and non-Indigenous Australians simply because there was more research to demonstrate the effectiveness of interventions in the latter population.Indigenous Tobacco Control Initiative and Tackling Indigenous Smoking Measure in the absence of strong evidence is justifiable. The policies were not made with reckless disregard for what would work; instead, evidence from other settings and expert opinions were used to generate conceptually plausible responses to the policy problem in a manner that accommodated the apparent preferences of members of the Indigenous community. Moreover, the policy proposals were accompanied by a commitment to evaluate their effectiveness. This approach is consistent with that advocated by Sanderson, who suggests that policies should be viewed as hypotheses to be tested through pilots or trials and/or rigorous monitoring and evaluation  is a separate entity to the Commonwealth Department of Health and Ageing.


The WHO Model List of Essential Medicines for Children (EMLc) covers medicines for globally high-burden diseases. Regulatory approval in high-income countries ensures evidence and dosage form but usually focuses on diseases common in those countries and not in low- and middle-income countries.This cross-sectional study assessed supporting evidence for the 346 medicines in the 5th WHO EMLc and their approval data from the United States, United Kingdom, and Japan.Of the 346 EMLc medicines, 307 were approved in one or more of the three countries, 278 of which had supporting evidence of efficacy. The percentage of medicines approved in one or more of the three countries was lowest for antiparasitics (60%) whereas 100% for medicines for cancers and musculoskeletal and respiratory conditions were approved. Five of the 30 EMLc antineoplastics had no supporting paediatric evidence. Of the 39 EMLc medicines unapproved in all three countries, 26 were indicated for neglected infectious diseases (NIDs). Ten of the 26 had supporting paediatric evidence. Seventeen of the 39 unapproved medicines had no paediatric dosage form available, and all 17 were indicated for NIDs.Most EMLc medicines for diseases common in the three countries had supporting evidence, which was closely associated with approval, whereas a substantial number of medicines for NIDs were unapproved in the three countries, regardless of whether they had supporting evidence. Because of the limited contribution to the EMLc from high income countries, appropriate incentive mechanisms for pharmaceutical companies are required to make paediatric development for NIDs feasible and effective.The online version of this article (doi:10.1186/s40545-016-0094-2) contains supplementary material, which is available to authorized users. The lack of authorised medicines for children has been an issue of global concern –4. PharmAge-appropriate dosage forms represent another obstacle in paediatric medication. The absence of an appropriate dosage form for children often results in suboptimal compliance with recommended drug regimens and undermines efficacy or safety . World HThe World Health Organization (WHO) Model List of Essential Medicines for Children (EMLc)  providesCompared with reviews in EMLc, clinical trials to provide evidence are essential for regulatory approval of medicines for children in HICs. Development and regulation of medicines are coordinated among International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) countries, all of which are HICs. The ICH Tripartite Guideline  stipulatHICs have not directly improved access to the EMLc medicines  and may The aim of the present study was to investigate the implications of approval in HICs and supporting evidence of efficacy for the EMLc medicines. For this purpose, we analysed the evidence and approval status of EMLc medicines in the US, United Kingdom (UK), and Japan, which are all members of the ICH.This study included medicines appearing on the 5th EMLc . We idenWhen the product label covered the indication, dosage, and route of administration for children at any age, the label was considered to be approved for paediatric use . If a meTo evaluate the supporting evidence for each medicine, we used the DRUGDEX® System  , which iThere were a total of 346 medicines on the 5th EMLc  of the 346 EMLc medicines were unapproved for children whereas 78 (22%) and 66 (19%) were unapproved in the US and UK, respectively  have aimed to improve the availability of medicines for children . In contThe approval status of EMLc medicines in the three countries varied depending upon therapeutic area. Medicines for diseases common in HICs, e.g., HIV infection, respiratory diseases and cancers, were all approved in one or more of the three countries. Although all 30 antineoplastics were approved, their evidence was not always robust; five cytotoxic agents were categorised as having no evidence. This means that when reviewing antineoplastics, regulatory authorities in these three countries might give priority to effectiveness rather than to efficacy. The recent proposal of the WHO Expert Committee’s 2015 meeting with respect to antineoplastics  opened uAmong the 39 medicines unapproved in all three countries studied, there were differences in the gradient of supporting evidence and in the availability of a paediatric dosage form. Although evidence is essential for regulatory approval in HICs, medicines with good evidence do not always receive approval. Of the 39 medicines, 13 with supporting evidence were for diseases rare among children in HICs; 10 of the 13 were for NIDs. Because of the small market and low financial interest, there are few financial incentives for pharmaceutical companies to seek approval for the 13 medicines with supporting evidence in children. Although paediatric dosage forms are unavailable in the US, UK, and Japan for five of these 13 medicines, appropriate dosage forms may be available in another country or could be developed via options other than full development , 31.Of the other 26 medicines unapproved in all three countries without supporting paediatric evidence, 17 had evidence in adults. The lack of paediatric evidence likely results from limited numbers of study participants, probably because the prevalence of most indications for the 17 medicines is very low in HICs. The need for separate paediatric development may be reduced by extrapolating prior knowledge acquired during the development of these medicines for adults, on the basis of assuming a similar disease for the proposed paediatric indication , 32. TheThe distribution of EMLc medicines according to therapeutic area shows that the EMLc addresses the most pressing public health concerns of children around the world, namely, NIDs . Our stuPharmaceutical companies, in association with researchers, are the key stakeholders in paediatric development. Incentives are imperative for them to develop medicines for NIDs , 34 becaSeveral limitations of this analysis should be noted. First, we used DRUGDEX as the only source, to classify supporting evidence of efficacy. Whereas this database is well recognised and is easily available, it is compiled by an expert working group in an HIC, namely, the US. By defining the presence or absence of supporting evidence according to DRUGDEX, the evidence we identified as “no evidence” may include varying degrees of scientific evidence that fell short of our definition. This limitation would be particularly applicable to medicines for NIDs. Second, because we had to rely on data collected for different purposes by other groups, we were limited in our ability to capture the gradient of evidence for EMLc medicines. Third, we could not address social obstacles to accessing EMLc medicines such as cost, intellectual property, or logistics, because we focused on the scientific aspects of the EMLc. Finally, we were limited to collecting approval data from the US, UK, and Japan and omitted approvals and development outside these regions.HICs have made a substantial contribution to improve the scientific evidence and availability of paediatric dosage forms for EMLc in some therapeutic areas, such as antiretrovirals and antineoplastics. To date, however, there has been little commitment of HICs to NIDs given their large economies. Deficiencies in the ability to meet the critical needs of children worldwide remain, particularly with respect to NIDs. To make paediatric development for NIDs feasible and effective, appropriate incentive mechanisms for pharmaceutical companies should be applied towards the eradication and elimination of NIDs.


Obesity and non-communicable diseases are significant public health issues globally and particularly in the Pacific. Poor diet is a major contributor to this issue and policy change is a powerful lever to improve food security and diet quality. This study aims to apply systems thinking to identify the causes and consequences of poor evidence use in food-related policymaking in selected government ministries in Fiji and to illicit strategies to strengthen the use of evidence in policymaking.The Ministry of Health and Medical Services and the Ministry of Agriculture in Fiji were invited through their respective Permanent Secretaries to participate in the study. Three 180-minute group model building (GMB) workshops were conducted separately in each ministry over three consecutive days with selected policymakers who were instrumental in developing food-related policies designed to prevent non-communicable diseases. The GMB workshops mapped the process of food-related policymaking and the contribution of scientific and local evidence to the process, and identified actions to enhance the use of evidence in policymaking.An average of 10 policymakers participated from each ministry. The causal loop diagrams produced by each ministry illustrated the causes and consequences of insufficient evidence use in developing food policies or precursors of the specific actions. These included (1) consultation, (2) engagement with stakeholders, (3) access and use of evidence, and (4) delays in policy processes. Participants agreed to potential leverage points on the themes above, addressing pertinent policymaker challenges in precursor control, including political influence, understanding of trade policies, competing government priorities and level of awareness on the problem. Specific actions for strengthening evidence use included training in policy development and research skills, and strengthening of coordination between ministries.The GMB workshops improved participants’ understanding of how different parts of the policy system interact. The causal loop diagrams and subsequent action plans enabled the identification of systems-level interventions in both ministries to improve evidence-informed policy development. A guide for integrating multi-sectoral consultation and stakeholder engagement in developing cross-cutting policies is currently being developed. Pacific Islands have a high burden of non-communicable diseases (NCDs), with some of the highest rates of obesity and diabetes in the world –3. AmongPoor diet is a key determinant of NCDs, and a serious global public health problem , 9. DietPolicy is a particularly powerful tool for reshaping food systems since it can influence price, availability and promotion of both healthy and unhealthy foods along the supply chain. With healthier foods available, consumers have more opportunity to make healthier choices . The fooFood-related policymaking processes vary widely between sectors. We define effective food policies as those that successfully influence any of the key determinants of obesity and poor diet . In ordeThe WHO’s Alliance for Health Policy and Systems has promoted systems thinking as a strategic approach to strengthening health systems in order to achieve global and national health goals . SystemsDrawing on systems thinking, this study aims to identify the causes and consequences of poor evidence use in food-related policymaking in the health and agriculture ministries in Fiji and to illicit strategies to strengthen the use of evidence informed by the following research question: Where could evidence levers be applied within the food-related policymaking processes in Fiji?A purposive and convenience sampling approach was used to select and recruit policymakers from the Ministry of Health and Medical Services (MoHMS) and the Ministry of Agriculture (MOA). We aimed to recruit senior policymakers who were involved with food-related policymaking, and had the power to influence change in the government system. Both the ministries were chosen because they are key stakeholders in food systems and NCD prevention and policy, and had been previously involved in the Pacific Obesity Prevention In Communities project 2004–2009 , and theThis study used group model building (GMB) and a system dynamics approach , 35 to gWe conducted GMB in line with a system dynamics approach , 35, 36 First, the participants were given an overview of NCDs and the policymaking process to draw on their understanding of the dynamic nature of the underlying drivers. Because of participants’ previous experience in developing policies and consulting and/or engaging with other stakeholders who may be affected by the policy, they were considered to be skilled and interested in addressing dynamic problems in the policy systems. Participants identified causes and consequences of poor evidence use in food-related policymaking within their ministry from the inception of the policy problem through to policy implementation , 36. ForAll variables that participants considered important, feasible and measureable were arranged around a circle on a white board. Participants then identified connections between two or more variables, and specified the direction of causation and the nature of relationships (positive or negative) between them , 36. A pThe process of listing and reviewing variables in the connecting circles was also performed simultaneously using Vensim software  to creatAfter they had time to think about and review the diagrams, participants were invited to a final session where they identified as many action ideas as they could that would improve the use of evidence in food-related policymaking. Note-takers captured discussions and participants placed feedback directly on the CLDs using sticky labels. The action ideas shared by participants in the third and final workshop were collated into four themes; from these, strategies were developed using the World Café approach . ParticiData were analysed after each session. Data collected included change-over-time graphs, connection circles, CLDs, prioritised action ideas, an action plan and the notes on the discussions. The team leader audited all notes for accuracy and to ensure confidentiality.Eighteen participants from the MoHMS (n = 9) and the MOA (n = 9) participated in separate GMB workshops in August 2015. The majority of participants (72%) were senior managers  who were directly involved in policymaking, whilst 28% were middle managers (persons directly responsible to the senior managers) with potential to share evidence that influences the policymaking process. The majority (72%) were male. The selection of senior staff ensured a strong understanding of and expertise in policymaking processes, plus awareness of the workings of their organisation. The participants also used relevant and familiar case studies to help understanding of the GMB process.The four themes of related variables, connections and feedback loops observed on the CLDs were labelled as 1) consultation; (2) engagement with stakeholders; (3) access and use of evidence; and (4) delays. These dynamics are captured on both maps in Fig.  consultaConsultation on new policy involves informing and receiving counsel from those with an interest in the policy. It represents the first step in policy development and the aim of consultation is to build trust and start a conversation so that policies reflect individuals’ needs and are relevant to their circumstances.We identified one balancing feedback loop (B1 or ‘frustration’ loop) and two reinforcing loops (R1 ‘appreciative’ and R2 ‘trust’) . B1 for This refers to the willingness of those who have a particular interest in the policy to work together following consultation. Figure This sector of the maps captures factors such as gaps in research that influence access to and use of evidence Fig. . When MoThis theme captures delays in the policy process due to bureaucracy , politics  and vested interests (e.g. private sector involvement). This was captured in the concern balancing loop 2 (B2) in Fig. The maps were used to help ministry participants identify actions they could be taken to improve evidence use in policymaking. The MOA sought to influence the consultation sector of the map by publishing guidelines on consultation with partners. The MoHMS sought to minimise delays by producing strategic health communication messages to the general population to balance industry’s influence on consumers’ food choices. Both ministries agreed to strengthen engagement by endorsing a government policy for data sharing to improve access and use of evidence. The MoHMS endorsed the development of a guide around multi-sectoral consultation and stakeholder engagement in developing cross-cutting policies, while the MOA opted to build staff capacity in developing policy briefs using reliable evidence.A GMB process with two government ministries in Fiji revealed that aspects of consultation, engagement with stakeholders, physical access to evidence, and delays due to bureaucracy and vested interests limited the use of evidence in food-related policy development. This study was designed to provide a deeper understanding of the use of evidence by government sectors. However, future GMB processes could include representation from the private sector, which would provide new insights into the CLD. To our knowledge, this is the first time GMB has been used to strengthen food-related policymaking, and outcomes from the process were the development of a consultation guide and training on policy development and research skills. Although the lead researcher had existing relationships with some of the participants, through joint involvement in the Pacific Obesity Prevention In Communities and Translational Research on Obesity Prevention In Communities projects and other research, there were just as many participants without a prior relationship; therefore, we are comfortable that there was no participation bias.Identifying and consulting with relevant parties is complex, requiring the coordinated efforts of government, private sectors and civil societies . An examThe motivation loop showed in R3 Fig.  is an inPolitical and technical support for ensuring data availability and integrity is needed to strengthen the use of evidence in policymaking in Fiji. Policymakers in the health and agriculture ministries were aware of the importance of using evidence in policymaking. However, it is important to note that their initiative of accessing and applying evidence increased understanding of how their organisation’s systems are positioned to support evidence use when developing policies across sectors. The ability to effectively communicate and integrate evidence into the policymaking process requires that policymakers have the knowledge and technical skills to use reliable evidence which adds value and can influence decisions , 48. OthA major strength was the endorsement and high-level support received from selected government Ministries with the sense of ownership that allowed the release of policymakers as participants to the GMB workshops. Scriptapedia helped the team rehearse and choreograph GMB workshops so they ran smoothly.A limitation was that the total time allocated for workshops was short, especially for action planning, and that there was not enough time to review the CLDs to ensure they reflected the organisation’s views. There was no involvement of other ministries/private sector who contribute to and influence food-related policymaking in Fiji and therefore the views expressed here are limited to those of the health and agriculture ministries. Lastly, the process was new to participants and this may have affected their level of engagement.A GMB process, drawing on systems dynamics, helped government ministries in Fiji to identify consultation, stakeholder engagement, access and use of evidence, and delays due to bureaucracy or vested interests as causes and consequences of poor evidence use in the policymaking process, and to develop appropriate remedial actions. In response, a guide for integrating multi-sectoral consultation and stakeholder engagement in developing cross-cutting policies is currently being developed in one ministry.


In this study, we reinvestigated the pathways using a water-soluble cyclic selenoxide reagent, trans-3,4-dihydroxyselenolane oxide (DHSox), as a strong and quantitative oxidant to oxidize the fully reduced form (R). In the presence of ethylenediaminetetraacetic acid (EDTA) , SS formation randomly proceeded, and N did not regenerate. On the other hand, two specific SS intermediates transiently generated in the presence of Ca2+. These intermediates could be assigned to  and des[6–120] having two common SS bonds, i.e., Cys61-Cys77 and Cys73-Cys91, near the calcium binding pocket of the β-sheet domain. Much faster folding to N was observed in the presence of Mn2+, whereas Na+, K+, Mg2+, and Zn2+ did not affect the pathways. The two key intermediates were susceptible to temperature and a denaturant. The oxidative folding pathways revealed were significantly different from those of hen egg white lysozyme, which has the same SS-bonding pattern as αLA, suggesting that the folding pathways of SS-containing proteins can alter depending on the amino acid sequence and other factors, even when the SS-bond topologies are similar to each other.Bovine α-lactalbumin (αLA) has four disulfide (SS) bonds in the native form (N). On the oxidative folding pathways of this protein, two specific SS folding intermediates, i.e.,  and des[6–120], which have two and three native SS bonds, respectively, accumulate predominantly in the presence of Ca Many SS-containing proteins have already been investigated for their oxidative folding pathways under neutral to slightly basic conditions , it, it43], ox for 1 min at pH 8.0 and 5 °C in the presence of 2 mM ethylenediaminetetraacetic acid (EDTA) , an ensemble of 1SS intermediates formed as a main product accompanied by small amounts of R and an ensemble of 2SS intermediates as revealed for 2-aminoethyl methanethiosulfonate (AEMTS)-quenched sample solution by electrospray ionization-mass spectrometry (ESI-MS) analysis  analysis of the acid-quenched samples indicated that the SS formation took place randomly to produce non-specific 1SS to 4SS intermediates  was clearly observed with a slight amount of N after 5 h  enhances the formation of I-1, I-2, and N, although it cannot accelerate air oxidation.To investigate whether the folding intermediates of αLA initially formed by the reaction of R with DHSatograms  remainedfter 5 h A. It is r 5 h  hydroxide at the concentration of 5 mM. In the case of ZnCl2, since the precipitation of zinc hydroxide occurred at pH 8.0, the oxidative folding was carried out at pH 6.8 and 5 °C (see 2). The HPLC chromatograms obtained in the presence of NaCl, KCl, and MgCl2  were much smaller than that with Ca2+ (3 × 108 M−1) at 20 °C  and , respectively, by comparing the observed HPLC retention times with those reported in the literature  < N. On the folding pathways  and des[6–120] intermediates by the presence of Capathways , only depathways . For HELred were obtained from Wako Pure Chemical Industries, Ltd. . GdmCl was obtained from Tokyo Chemical Industry, Ltd. . DHSox and AEMTS, both of which were not commercially available, were synthesized according to the literature methods


Recommendations on antenatal care for a positive pregnancy experience,As governments are developing schemes for universal health coverage (UHC) and progressing towards the sustainable development goals (SDGs), they need relevant and context-sensitive evidence to support different policies and interventions. Decision-makers are increasingly using qualitative evidence to understand various socioeconomic contexts, health systems and communities. This type of evidence is useful to assess the needs, values, perceptions and experiences of stakeholders, including policymakers, providers, communities and patients, and is thus crucial for complex health decision-making. For instance, during the development of the World Health Organization (WHO) Qualitative evidence syntheses, which combine and analyse evidence from individual qualitative studies, have emerged as a key approach to inform guideline development and address implementation considerations in diverse country settings and complex health systems.Beyond global guidance, qualitative evidence is invaluable for national and local decision-makers and practitioners to understand factors influencing the implementation and scale-up of health policies and programmes. For instance, policy-makers require evidence on factors that influence vaccination coverage, satisfaction and retention of health-care workers or quality of care in health facilities. Qualitative data have proven essential in planning, developing and implementing health policies and interventions, including in low- and middle-income countries, for example to prevent and treat malaria during pregnancy,Yet, despite the relevance of findings from qualitative evidence syntheses, there is limited guidance on how to assess and use this evidence in policy and practice. To address this need, the Alliance for Health Policy and Systems Research and the WHO Department of Reproductive Health and Research have supported the development of a new approach called GRADE-CERQual . The GRADE-CERQual approach is used to describe how much confidence decision-makers and other users can place in findings from qualitative evidence syntheses by transparently assessing methodological limitations, coherence, adequacy and relevance.New guidance on how to apply the GRADE-CERQual approach is now available as a special series of articles to support stakeholders conducting reviews of qualitative research and using their findings to inform decision-making.,The GRADE-CERQual approach was developed as a global public good to advance research methods and promote the uptake of qualitative findings in decision-making within and beyond the health sector. This guidance is also aligned with a global movement towards the generation and use of a wide array of evidence in policy-making.


Ecosystem services (ES) are an increasingly popular policy framework for connecting biodiversity with human well-being. These efforts typically assume that biodiversity and ES covary, but the relationship between them remains remarkably unclear. Here we analyse >500 recent papers and show that reported relationships differ among ES, methods of measuring biodiversity and ES, and three different approaches to linking them . For spatial correlations, biodiversity relates more strongly to measures of ES supply than to resulting human benefits. For management comparisons, biodiversity of ‘service providers' predicts ES more often than biodiversity of functionally unrelated taxa, but the opposite is true for spatial correlations. Functional experiments occur at smaller spatial scales than management and spatial studies, which show contrasting responses to scale. Our results illuminate the varying dynamics relating biodiversity to ES, and show the importance of matching management efforts to the most relevant scientific evidence. Biodiversity can enhance ecosystem services such as crop pollination. Here, Ricketts et al. synthesize 14 years of literature to show that biodiversity-ecosystem services relationships depend on the service, how services and biodiversity are each measured, and the approach used to link them. Improving human well-being without destroying our planet's natural resources is a central challenge of the twenty-first century123468910These efforts depend on the assumption that biodiversity and ES covary1213151617171517Previous syntheses on this topic have typically pooled studies across these and other factors, reporting general findings that may mask important structure in the evidence1617121820Here we aim to more deeply understand the evidence linking biodiversity and four services: carbon storage; pest control; crop pollination; and water purification. We assess more than 500 recent peer-reviewed papers and quantify the distribution of positive, negative and non-significant relationships . We then compare that balance of evidence among five factors that may influence relationships between biodiversity and ES.First, we identify three recurring approaches for linking biodiversity and ES (hereafter linkage types): ‘spatial linkages', which compare levels of biodiversity and ES across space; ‘management linkages', which compare responses of biodiversity and ES to the same management intervention; and ‘functional linkages', which test specifically whether ES are a mechanistic function of biodiversity.  and grain  on the balance of evidence for each linkage type. Spatial scale is widely thought to influence the links between biodiversity and ES15Overall, our synthesis shows that reported relationships differ markedly among ES, ways of measuring biodiversity and ES, and approaches to relating them. Disaggregating the evidence in this way illuminates the varying dynamics linking biodiversity and ES, and illustrates the importance of matching management efforts to the most relevant scientific evidence.We read at least the top-ranked 100 papers published between 2001 and 2014 for each ES, according to Web of Science ; MethodsFrom these papers, we identified three recurring approaches to evaluating links between biodiversity and ES. We refer to these as linkage types. Each linkage type involves differing biophysical and social phenomena, and each has different strengths and weaknesses regarding the scientific inferences they support. We describe linkage types here and compare balance of evidence among them and other factors in the following section.et al.For spatial linkages , researcet al.For management linkages , researcFor functional linkages , researcWe find the balance of evidence differs significantly among ES , top rowThe balance of evidence is remarkably similar among linkage types when all four ES are pooled 7.ES differ in the frequency of relationships reporting ES supply or benefit . BecauseWhile a majority of the overall evidence involves service providers, more than half of relationships for water purification, and a substantial minority for the other three ES, do not . BecauseMost studies measure biodiversity at the species level . HoweverAs expected, functional linkages tend to be reported at finer scales than spatial or management linkages . Scale aTaken together, our findings suggest that pooled evidence linking biodiversity and ES could mislead both scientific syntheses and management interventions. We repeatedly find important differences in the balance of evidence that are masked by pooled data. Accounting for these differences will help to deepen our theoretical understanding of the relationship between biodiversity and ES, and support management efforts with the most relevant scientific evidence.Linkage types appear to interact with spatial scale, service providers and supply versus benefit measures in determining the relationship between biodiversity and ES. For spatial scale, we find opposing effects between management and spatial linkage types . Within Our findings underscore the caution required when applying evidence from one linkage type to decisions that relate to another  type of linkage , and tested differences in scale among positive, negative and non-significant relationships using analysis of variance. We used R for all analysesP<0.10 as significant, but we mark levels of significance clearly throughout.We analysed the distribution of relationships among positive, negative and non-significant categories, and refer to this distribution as the ‘balance of evidence'. We compare the balance of evidence among ES, linkage types, measures of ES and biodiversity, and spatial scales. This simple ‘vote-counting' approach, while less powerful than formal meta-analysis, allowed us to code studies consistently across widely varying disciplines, using data typically reported in the studies themselvesn=23) related the same biodiversity measure to both ES supply and benefit. To avoid double counting, we include only the benefit relationships from these papers, except in per se, we analysed only relationships that report some measure of diversity. Some papers  with DOI: 10.6084/m9.figshare.3775821 .Supplementary Figures 1-2, Supplementary Tables 1-3, Supplementary Note 1, Supplementary Methods and Supplementary References


Accreditation documents reflect the practice standards of health professions. No previous study has assessed the extent to which EBP has been taken up by chiropractic regulatory/licencing authorities, known as Councils on Chiropractic Education (CCEs), around the world. The purposes of this study were to examine CCEs’ educational standards for signs of a positive and negative approach to EBP as indicated by the prevalence and use of the words We undertook a systematic audit of the educational standard documents of the various CCEs. CCEs were selected on the basis of the World Health Organisation. Two investigators identified the occurrences of terms explicitly related to EBP: evidence, evidence-based, research, subluxation and vitalism. This information was tabulated for comparative purposes. The date of the study was March 2016.evidence, as it related to EBP, was highest in the CCE-Europe (n = 6), followed by CCE-Australia (n = 2), and CCE-USA (n = 1). None were found in the CCE-International or CCE-Canada documents. The term research appeared most frequently in the CCE-Europe documents (n = 43), followed by CCE-USA (n-32), CCE-Australia (n = 29), CCE-Canada (n = 9) and CCE-International (n = 8). The term subluxation was found only once (CCE-USA) and vitalism did not appear in any educational standard documents.Occurrences of the term Accreditation bodies are powerfully positioned to act as a driver for education providers to give greater priority to embedding EBP into entry-level programs and shaping future directions within the profession. Terminology relating explicitly to EBP appears to be lacking in the educational standard documentation of CCEs. Therefore, future revisions of accreditation standards should address lack of terminology. Evidence-based practice (EBP) has been defined as “the integration of the best research evidence with clinical expertise and patient values and circumstances ” and hasEducation standards have been shown to impact on the levels of evidence-based practice (EBP) in medicine and medical students’ clinical reasoning . The useConsideration has been given to the international implications of medical educational standards. There is evidence of varying levels of skill in medical practitioners internationally as a result of variable education accreditation standards and the concern has been raised that substandard quality may impact negatively on patient safety and levels of care with an increasingly internationally mobile workforce , 14. Theevidence, in documents for informing educational programs of required accreditation standards of the need for EBP. They found that chiropractic documents used evidence in relation to evidence-based health care once whereas the most prolific health professions were physiotherapy (8 times), podiatry (5 times), and medicine (4 times). Pharmacy, dentistry and occupational therapy did not mention evidence at all. It is noted that McEvoy et al., acknowledged that the frequency of inclusion of EBP-related terms did not necessarily relate to the quality of document [Educational standards adopted and monitored by educational regulatory agencies across 11 health profession bodies in Australia were compared in a recent study . The autdocument . They alResearch has shown that chiropractors are well suited to adopt and enact evidence-based practice guidelines , 18. Howresearch may provide insight into ways in which EBP is dealt with presently.It would seem quite obvious that research is an important component of EBP and health care training standards. Nonetheless there is evidence to suggest that research is not being targeted sufficiently to inform practice and improve its quality within medicine . InterveThe word “subluxation” in the chiropractic context has been variously interpreted and defined. One interpretation is that subluxation of the spinal column and other articulations can affect the nervous system function and the expression of health, which may result in symptoms, infirmity and disease . Others This vitalist/subluxation construct is known to often underpin unsubstantiated claims in patient brochures , wellnesVariable international practitioner profiles have been seen in chiropractic populations , 33. A gIt is believed that a high quality medical education and accreditation system would improve the quality of medical care . FurtherThe aim of this systematic audit was to investigate similarities and differences between the standards provided by various CCEs in their use of words that relate to EBP, both positively and negatively. A broader examination of other key terms in educational standards will be the subject of future research.EvidenceResearchSubluxationVitalism, andto make recommendations if significant deficiencies were found.The objectives were to examine CCEs’ educational standards for signs of a positive and negative approach, respectively to EBP as indicated by the prevalence and use of the wordsA systematic audit of current educational standards was undertaken for the CCEs who are currently recognized by the World Health Organization . This inevidence, research, subluxation, and vitalism in the respective educational standardssearching for the words determining if the term was related to education/trainingtabulating the results for each CCE to establish any similarities and differences.The systematic audit consisted of three phases:The first phase of the audit aimed to locate the specified words of interest. The PDF texts were searched using the full reader search in Adobe Reader (XI). All occurrences of the word were copied verbatim and extracted into a spreadsheet by two of the authors (SI and CL-Y). Disagreements were resolved by discussion; a third author was available if a word categorization could not be agreed upon.evidence was searched for to ensure that variations of the full phrase, such as EBP or EB health care, were not missed. The level of the use was then determined by following the categorization of “heading”, “text” or “other”. A “heading” was determined to be a first heading in larger font or bold indicating a section of information. “Text” was allocated when the word was found within a sentence describing a standard. “Other” was used when the word was related to an irrelevant context eg, “a program should provide evidence of financial records for the past 3 years”. Thereafter the frequency of use was established for each word and category.The second phase of the audit aimed to determine the frequency of the use of the word in a manner that indicated if it was being directed toward training or educational standards. For example the term In the third phase of the audit, the extracted spreadsheet was limited to the “text” words. Common themes in the sentences which the word appeared were identified. Lists were created under identified common themes. These were then compared across all CCEs for similarities and differences.research, subluxation and vitalism.This process was repeated for the words There were no disagreements on word categorization between the two authors during the extraction process.evidence appeared 85 times with nine of these being specific to EBP or health care  followed by CCE-Australia (n = 2) and CCE-USA (n = 1). CCE-Canada and CCE-International made no mention of evidence-based practice or evidence-based health care.Across the five CCEs, the word re Table . This raEvidence-based health care”. The second occurrence in the CCE-Australia standards was for the principles of “Evidence-based health care” to be taught throughout the curriculum. The CCE-USA expected students to be introduced to the value of EB scientific thinking.The CCE-Europe expected programs to teach EBP and the best use information technology in this process. The standards for the CCE-Europe stated that evidence should inform knowledge and principles of practice and keep the curriculum up to date. Documents from the CCE-Australia standards were found to have the requirement that information technology should be part of the education for “research appeared 147 times (Table n = 43) followed by CCE-USA (n = 32) CCE-Australia (n = 29), CCE-Canada (n = 9) and finally CCE-International (n = 8). The term research was classified as “other” three times.Across the five CCEs, the word All CCEs stated that programs should train students to be good consumers of research by teaching them how to acquire, appraise and apply evidence within an environment that encourages research”. Further it was commonplace for CCE educational standards to state that students should be trained in research methods and be given the opportunity to become producers of research by conducting research projects. All CCEs expected adherence to high standards of research conduct and ethics.However, differences emerged over the scope of research Table . Two CCE“assess and document a patient’s health status....including subluxation/neuro-biomechanical dysfunction ”.The word “Subluxation” was found only once (CCE-USA standards). It stated that chiropractic education programs should train its graduates to “Vitalism” was not found in any of the CCE documents.This study was the first to systematically audit all CCE Education Standards for indicators of EBP and/or EB health care using keywords that were indicators of the adoption of EBP and others that indicated a non-adoption. Although we found only some references to the key words indicative of the presence of EBP it was encouraging that the keyword “subluxation”, which we considered an indicator of an inconsistent or incomplete adoption of EBP was found only once and that “vitalism”, in our opinion, also an indicator of non-adoption of EBP was absent in these standards.Of the five chiropractic regulatory bodies only the CCE-Europe and CCE-Australia contained statements requiring an EB approach to be taught throughout the curriculum. The CCE-USA’s only mention was the expectation that students should be introduced to scientific thinking. The support for EBP with the use of explicit terms was generally disappointing in the CCE educational standards. These documents have the potential to act as drivers for education providers to embed EBP into practice . EBP hasNevertheless, the word research was more widely included in CCE educational standards. There appears to be uniform agreement that research is a core component to CCE educational standards. This as reflected in the common statement that research should be established, resourced, and taught in programs. This reflects the view that programs should be, at a minimum, producing skilled clinicians who are competent consumers of research through teaching basic skills of EB medicine . This “cMedical educators believe that evidence-based education is not possible without adequate research support and funding . Likewissubluxation and vitalism as being unsupported by evidence. Subluxation was found once whereas vitalism was not found in this audit. The CCE-USA adopted the position that chiropractic programs should train their graduates to be able to detect subluxations. This raises several questions. Should a non-evidence based construct like subluxation be mandated to be taught in an educational program via educational standards? Some chiropractic educators have made a decision not to teach subluxation/vitalism, other than as a historical concept, because of a lack of evidence. Should educators be supported in this evidence-based approach by regulatory/licencing agencies actively promoting the non-teaching of subluxation/vitalism by making specific mention of its appropriate context in CCE educational standards? The absence of the words subluxation and vitalism may be interpreted as either a reluctance of regulatory bodies to actively prescribe against the use of this non-evidence based agenda from chiropractic programs or that these terms are out dated, historical and of no current importance. We contend that silence on these matters is inappropriate and could open the door to chiropractic practice programs teaching a doctrinal dogma unsupported by evidence.As previously mentioned the leaders of a large number of chiropractic educational programs have signed the “Clinical and Professional Chiropractic Education: a Position Statement” . They deThis was a comprehensive audit of the available educational standards for the CCEs recognized by the WHO. All public domain material was scrutinized. The screening method was automatic and the authors remain confident that they have found the terms and appropriately classified them according to “heading, text or other”. The search for other terms, however, could perhaps have resulted in other findings and conclusions.It should also be borne in mind that the frequency of terms does not necessarily relate to the quality of the document. We did not include competency standards as this was studied in a previous paper . Also weEducational standards have the potential to act as initiators and promoters of quality educational programs by improving the competency of entry-level graduates. Relevant terms used in these documents have the potential to clearly specify what standards educators should and can teach and use for training. CCE choice of specific vocabulary in relation to evidence-based practice in their accreditation documents has been slow and incomplete in the uptake of contemporary evidence-based trends. The absence of malevolent terms such as “subluxation” and “vitalism” and firm statements about their undesirability may provide opportunities for aberrant chiropractic programs to be accredited. Future revisions of accreditation standards should address this.CCE, council on chiropractic education; EBP, evidence-based practice; USA, United States of America


Despite the rapid proliferation of health interventions that employ digital tools, the evidence on the effectiveness of such approaches remains insufficient and of variable quality. To address gaps in the comprehensiveness and quality of reporting on the effectiveness of digital programs, the mHealth Technical Evidence Review Group (mTERG), convened by the World Health Organization, proposed the mHealth Evidence Reporting and Assessment (mERA) checklist to address existing gaps in the comprehensiveness and quality of reporting on the effectiveness of digital health programs.We present an overview of the mERA checklist and encourage researchers working in the digital health space to use the mERA checklist for reporting their research.The development of the mERA checklist consisted of convening an expert group to recommend an appropriate approach, convening a global expert review panel for checklist development, and pilot-testing the checklist.The mERA checklist consists of 16 core mHealth items that define what the mHealth intervention is (content), where it is being implemented (context), and how it was implemented . Additionally, a 29-item methodology checklist guides authors on reporting critical aspects of the research methodology employed in the study. We recommend that the core mERA checklist is used in conjunction with an appropriate study-design specific checklist.The mERA checklist aims to assist authors in reporting on digital health research, guide reviewers and policymakers in synthesizing evidence, and guide journal editors in assessing the completeness in reporting on digital health studies. An increase in transparent and rigorous reporting can help identify gaps in the conduct of research and understand the effects of digital health interventions as a field of inquiry. Over the last decade, there has been a dramatic increase in health programs employing digital tools, such as mobile phones and tablets, to stimulate demand for or the delivery of health care services. This is especially true in low- and middle-income countries, where public health practitioners are tapping into the unprecedented growth in the use of mobile phones to overcome information and communications challenges ,2. DonorTo address gaps in the comprehensiveness and quality of reporting on the effectiveness of digital programs, the mHealth Technical Evidence Review Group (mTERG)—an expert committee convened by the World Health Organization (WHO) to advise on approaches to strengthening digital health evidence—proposed guidelines for reporting evidence on the development and evaluation of digital health interventions. These guidelines—presented as the mHealth Evidence Reporting and Assessment (mERA) checklists—were published in March 2016  and haveThe design of the mERA checklist followed a systematic process for the development of reporting guidelines . In OctoThe mERA checklists comprises 2 components. The core mHealth checklist see  identifiIntroduction1. Rationale/scientific rationale2. Objectives/hypotheses3. Logic model/theoretical frameworkMethods4. Study design5. Outcomes6. Data collection methods7. Participant eligibility8. Participant recruitment9. Bias10. Sampling11. Setting and location12. Comparator13. Data sourcesResult14. Enrollment15. Description of study population16. Reporting on outcomesDiscussion17. Summary of evidence18. Limitations19. Generalizability20. ConclusionsConflicts21. Funding22. Ethical considerations23. Competing interestsAdditional criteria for quantitative study methods24. Confounding25. Statistical methods26. Missing dataAdditional criteria for qualitative study methods27. Analytic methods28. Data validation29. Reflexivity of accountThe methodology checklist see  outlinesWe present an overview of the mERA checklist. For details about each of the checklist items under the core checklist items and the methodology items, we refer the readers to the complete publication . The mEREven as the numbers of digital health interventions continue to increase, the evidence to support such interventions remains sparse. Without the support and shared commitment of the diverse digital health community in advancing the quality of evidence, the state of the much-critiqued “pilotitis” in mHealth will not change . Transpa


N = 164), the current study thus sought to investigate gene-environment associations between triarchic psychopathy dimensions  and (1) early social rearing experiences and (2) polymorphisms in the promoter region of the V1A receptor gene (AVPR1A). Among chimpanzees raised by their biological conspecific mothers, AVPR1A was found to uniquely explain variability in disinhibition and in sex-specific ways for boldness and a total psychopathy score; however, in contrast, no significant associations were found between AVPR1A and any of the triarchic psychopathy dimensions in chimpanzees raised the first 3 years of life in a human nursery. Thus, when considered in its entirety, results suggest an important contributory influence of V1A receptor genotype variation in the explanation of the development of psychopathy under some but not all early rearing conditions. Results of the current study provide additional support for the assertion that psychopathic tendencies are rooted in basic, evolutionarily-meaningful dispositions, and provide support for a primate-translational operationalization of key neurobehavioral constructs relevant both to psychopathy and to broader forms of psychopathology.Vasopressin is a neuropeptide known to be associated with the development and evolution of complex socio-emotional behaviors including those relevant to psychopathic personality. In both humans and chimpanzees, recent research suggests a strong genetic contribution to individual variation in psychopathic traits. To date, however, little is known concerning specific genes that might explain the observed heritability of psychopathy. In a relatively large sample of captive chimpanzees ( Although historically studied predominantly in adult forensic samples, it has become clear that psychopathy is a multi-faceted condition that includes tendencies grounded in basic biobehavioral dispositions that vary continuously within the human population , a phylogenetically conserved neuropeptide, constitute a particularly promising candidate, given the role of AVP in a range of complex social behaviors in both humans and nonhuman animals 6−14(GT)8−24). In chimpanzees, approximately 65% of the AVPR1A alleles have a complete deletion of the DupB region, resulting in a 357 bp difference between the DupB+ and DupB− alleles  and 96 adult and sub-adult chimpanzees at NCCC, including 46 females and 50 males ranging in age from 8 to 41 years . After removing 14 chimpanzees for whom AVPR1A data were not available  participants from both colonies were combined for analyses resulting in a final sample of 164 chimpanzees.Chimpanzees were members of two genetically distinct colonies of apes housed at the Yerkes National Primate Research Center (YNPRC) in Atlanta, Georgia and at the National Center for Chimpanzee Care (NCCC) at The University of Texas MD Anderson Cancer Center in Bastrop, Texas. Participants for the current study included 82 adult and sub-adult chimpanzees at YNPRC, including 57 females and 25 males ranging in age from 9 to 53 years  to 7 (most descriptive of the chimpanzee). Internal consistencies  for the three scales have been shown to be acceptable, especially considering their brevity: 0.82 for Boldness, 0.77 for Disinhibition, and 0.67 for Meanness  scales previously developed through a consensus-based approach  and 26 males and 31 females had the long allele (DupB+/−), yielding overall genotype frequencies of 65.2 and 34.8%. These frequencies are consistent with those previously identified in wild-caught chimpanzees . Specifically, we used CHMP-Tri scores as the dependent variables and sex as a fixed factor, and, given the age range of the sample, we included age as a covariate. The potential moderating role of sex was examined for a number of reasons. In addition to vasopressin systems in the brain being (1) found to be sexually dimorphic and (2) thought to regulate social behaviors in sex-specific ways  = 8.78, p < 0.001, ηp2 = 0.10] in the prediction of CHMP-Tri scores. Subsequent univariate F-tests revealed a significant main effect association for DupB genotype with CHMP-Tri Disinhibition . Mean standardized CHMP-Tri Disinhibition scores in DupB−/− and DupB+/− are shown in Figure +/− apes scored significantly higher in disinhibitory tendencies than DupB−/− apes. By contrast, no direct effects between the DupB genotype and either CHMP-Tri Boldness  or Meanness emerged .Within the mother-reared sample, a significant main effect was found for AVPR1A was found in predicting CHMP-Tri scores as a whole. Subsequent univariate F-testsrevealed that this omnibus effect was attributable mainly to the predictive effect of the AVPR1A*sex interaction for Boldness . Mean standardized CHMP-Tri Boldness scores in DupB−/− and DupB+/− males and females are shown in Figure −/+ apes evidenced higher scores on this trait dimensions, male Dup−/+ apes showed lower scores on CHMP-Tri Boldness. No significant effects for the AVPR1A*sex interaction term were found in predicting CHMP-Tri Meanness  or Disinhibition .However, a significant two-way interaction between AVPR1A and sex  or interactions  were found. No predictive effects were found for any individual CHMP-Tri scale .Within the nursery-reared sample, no significant main effects , a significant two-way interaction between AVPR1A genotype and sex  was found in the prediction of total CHMP-Tri scores. Mean standardized CHMP-Tri total scores in DupB−/− and DupB+/− are shown in Figure −/+ apes evidenced lower scores, male Dup−/+ apes showed higher scores on CHMP-Tri total score; the opposite was true for DupB−/− apes. Within the nursery-reared sample, no significant main effects  or interactions  were found.Finally, the association between DupB genotype and total CHMP-Tri psychopathy was investigated. Within the mother-reared sample, whereas no significant main effect for AVPR1A emerged [*sex as potential covariates within full polygenic models were next run. Consistent with MANOVA findings, these post-hoc analyses suggested a significant specific effect for AVPR1A DupB genotype for CHMP-Tri Disinhibition explaining 8.56% of the proportion of variance (p = 0.01). Further, also consistent with MANOVA findings described above, AVPR1A*sex evidenced a significant effect for both CHMP-Tri Boldness explaining 8.32% of the variance (p = 0.0009) and CHMP-Tri Total score explaining 5.86% of the variance (p = 0.005).As described above, to confirm the robustness of our MANOVA findings within the mother-reared group, tests of AVPR1A and AVPR1AThe current study represents the first investigation to date of the association between variation in AVPR1A, a gene that underlies AVP, and psychopathy tendencies as a function of differences in early rearing experiences. Consistent with expectations, AVPR1A DupB genotype was found to explain variability in psychopathy dimensions uniquely and in sex-specific ways. Results underscore the translational value of a nonhuman primate model for investigating psychopathy dimensions and provide strong support for the notion of triarchic psychopathy dimensions as biologically-based and evolutionarily derived  construct within the Negative Valence System, a construct with direct links to boldness in the triarchic model.Although the current study focused specifically on psychopathy subdimensions described within the triarchic model and associations with the AVPR1A RS3 polymorphism, taken together with a growing body of research . Additionally, while widely-used in both the human and nonhuman primate literatures, our use of scores on the CHMP-Tri scales, derived from caretaker ratings of a set of adjective descriptors with accompanying narrative definitions, is only one of a number of potential approaches to assessing the dimensions described within the triarchic model. Indeed, multi-domain operationalizations of triarchic dimensions are possible through the use of composite psychoneurometric indices of the various dimensions (e.g., Patrick et al., The current study is not without limitations. First, the sample size, particularly in the case of the nursery-reared subgroup, was relatively modest. Additional research is thus needed to replicate the current findings and establish more stable estimates for contributions of AVP to psychopathy. Nonetheless, it is important to note that although potential concerns regarding sufficient power to detect effects within the nursery-reared sample are appropriate, effect sizes for these associations approached zero (e.g., ηAdditionally, there have been a number of replicability concerns raised with regard to candidate gene studies (e.g., Munafo, Finally, it is important to note that chimpanzees encounter a variety of potentially impactful early experiences, whether raised by their biological mothers or in human-managed nursery settings. Given this, as noted previously (i.e., Latzman et al., Using a powerful and unparalleled animal model, the current study points to contributions of AVP influences to psychopathic tendencies, with an important role for a specific environmental factor—early rearing experience—in affecting this contribution. Taken together, results suggest an important contributory influence of neuropeptide variation in the explanation of the development of psychopathy. Results of the current study further provide additional compelling evidence that psychopathic tendencies are rooted in basic, evolutionarily-meaningful dispositions (Fowles and Dindo, RL and WH conceived of the study. WH and SS oversaw data collection. RL performed all analyses and drafted the paper. WH and SS provided critical revisions.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.