Improving the use of research evidence in guideline development: 13. Applicability, transferability and adaptation

BACKGROUND: The World Health Organization (WHO), like many other organisations around the world, has recognised the need to use more rigorous processes to ensure that health care recommendations are informed by the best available research evidence. This is the thirteenth of a series of 16 reviews that have been prepared as background for advice from the WHO Advisory Committee on Health Research to WHO on how to achieve this. OBJECTIVES: We reviewed the literature on applicability, transferability, and adaptation of guidelines. METHODS: We searched five databases for existing systematic reviews and relevant primary methodological research. We reviewed the titles of all citations and retrieved abstracts and full text articles if the citations appeared relevant to the topic. We checked the reference lists of articles relevant to the questions and used snowballing as a technique to obtain additional information. We used the definition "coming from, concerning or belonging to at least two or all nations" for the term international. Our conclusions are based on the available evidence, consideration of what WHO and other organisations are doing and logical arguments. KEY QUESTIONS AND ANSWERS: We did not identify systematic reviews addressing the key questions. We found individual studies and projects published in the peer reviewed literature and on the Internet. Should WHO develop international recommendations? • Resources for developing high quality recommendations are limited. Internationally developed recommendations can facilitate access to and pooling of resources, reduce unnecessary duplication, and involve international scientists. • Priority should be given to international health problems and problems that are important in low and middle-income countries, where these advantages are likely to be greatest. • Factors that influence the transferability of recommendations across different settings should be considered systematically and flagged, including modifying factors, important variation in needs, values, costs and the availability of resources. What should be done centrally and locally? • The preparation of systematic reviews and evidence profiles should be coordinated centrally, in collaboration with organizations that produce systematic reviews. Centrally developed evidence profiles should be adaptable to specific local circumstances. • Consideration should be given to models that involve central coordination with work being undertaken by centres located throughout the world. • While needs, availability of resources, costs, the presence of modifying factors and values need to be assessed locally, support for undertaking these assessments may be needed to make guidelines applicable. • WHO should provide local support for adapting and implementing recommendations by developing tools, building capacity, learning from international experience, and through international networks that support evidence-informed health policies, such as the Evidence-informed Policy Network (EVIPNet). How should recommendations be adapted? • WHO should provide detailed guidance for adaptation of international recommendations. • Local adaptation processes should be systematic and transparent, they should involve stakeholders, and they should report the key factors that influence decisions, including those flagged in international guidelines, and the reasons for any modifications that are made

A systematic review of frameworks for the interrelationships of mental health evidence and policy in low- and middle-income countries

Background: The interrelationships between research evidence and policy-making are complex. Different theoretical frameworks exist to explain general evidence–policy interactions. One largely unexplored element of these interrelationships is how evidence interrelates with, and influences, policy/political agenda-setting. This review aims to identify the elements and processes of theories, frameworks and models on interrelationships of research evidence and health policy-making, with a focus on actionability and agenda-setting in the context of mental health in low- and middle-income countries (LMICs). Methods: A systematic review of theories was conducted based on the BeHeMOTh search method, using a tested and refined search strategy. Nine electronic databases and other relevant sources were searched for peer-reviewed and grey literature. Two reviewers screened the abstracts, reviewed full-text articles, extracted data and performed quality assessments. Analysis was based on a thematic analysis. The included papers had to present an actionable theoretical framework/model on evidence and policy interrelationships, such as knowledge translation or evidence-based policy, specifically target the agenda-setting process, focus on mental health, be from LMICs and published in English. Results: From 236 publications included in the full text analysis, no studies fully complied with our inclusion criteria. Widening the focus by leaving out ‘agenda-setting’, we included ten studies, four of which had unique conceptual frameworks focusing on mental health and LMICs but not agenda-setting. The four analysed frameworks confirmed research gaps from LMICs and mental health, and a lack of focus on agenda-setting. Frameworks and models from other health and policy areas provide interesting conceptual approaches and lessons with regards to agenda-setting. Conclusion: Our systematic review identified frameworks on evidence and policy interrelations that differ in their elements and processes. No framework fulfilled all inclusion criteria. Four actionable frameworks are applicable to mental health and LMICs, but none specifically target agenda-setting. We have identified agenda-setting as a research theory gap in the context of mental health knowledge translation in LMICs. Frameworks from other health/policy areas could offer lessons on agenda-setting and new approaches for creating policy impact for mental health and to tackle the translational gap in LMICs

Genome-Wide Study of Gene Variants Associated with Differential Cardiovascular Event Reduction by Pravastatin Therapy

Statin therapy reduces the risk of coronary heart disease (CHD), however, the person-to-person variability in response to statin therapy is not well understood. We have investigated the effect of genetic variation on the reduction of CHD events by pravastatin. First, we conducted a genome-wide association study of 682 CHD cases from the Cholesterol and Recurrent Events (CARE) trial and 383 CHD cases from the West of Scotland Coronary Prevention Study (WOSCOPS), two randomized, placebo-controlled studies of pravastatin. In a combined case-only analysis, 79 single nucleotide polymorphisms (SNPs) were associated with differential CHD event reduction by pravastatin according to genotype (P<0.0001), and these SNPs were analyzed in a second stage that included cases as well as non-cases from CARE and WOSCOPS and patients from the PROspective Study of Pravastatin in the Elderly at Risk/PHArmacogenomic study of Statins in the Elderly at risk for cardiovascular disease (PROSPER/PHASE), a randomized placebo controlled study of pravastatin in the elderly. We found that one of these SNPs (rs13279522) was associated with differential CHD event reduction by pravastatin therapy in all 3 studies: P = 0.002 in CARE, P = 0.01 in WOSCOPS, P = 0.002 in PROSPER/PHASE. In a combined analysis of CARE, WOSCOPS, and PROSPER/PHASE, the hazard ratio for CHD when comparing pravastatin with placebo decreased by a factor of 0.63 (95% CI: 0.52 to 0.75) for each extra copy of the minor allele (P = 4.8×10−7). This SNP is located in DnaJ homolog subfamily C member 5B (DNAJC5B) and merits investigation in additional randomized studies of pravastatin and other statins

Strategies and tensions in communicating research on sexual and reproductive health, HIV and AIDS: a qualitative study of the experiences of researchers and communications staff

<p>Abstract</p> <p>Background</p> <p>Sexual and Reproductive Health (SRH) and HIV issues are often controversial and neglected, leading to challenges with engaging policy actors. Research evidence is complex, posing further challenges for ensuring that policy and practice are evidence-based. Many health researchers are adopting innovative approaches to engaging stakeholders in their research, yet these experiences are not often shared. This qualitative study focuses on the research communication and policy influencing objectives, strategies and experiences of four research consortia working on SRH, HIV and AIDS.</p> <p>Methods</p> <p>We carried out 22 in-depth interviews with researchers and communications specialists (research actors) from the four consortia and their partners, working in nine countries in sub-Saharan Africa and Asia. Using the ‘framework’ approach to qualitative data analysis, we identified factors that affect the interaction of research evidence with policy and practice. We used the ODI RAPID analytical framework to present these results, adapting this tool by incorporating the actions, strategies and positionality of research actors.</p> <p>Results</p> <p>The characteristics of researchers and their institutions, policy context, the multiplicity of actors, and the nature of the research evidence all play a role in policy influencing processes. Research actors perceived a trend towards increasingly intensive and varied communication approaches. Effective influencing strategies include making strategic alliances and coalitions and framing research evidence in ways that are most attractive to particular policy audiences. Tensions include the need to identify and avoid unnecessary communication or unintended impacts, challenges in assessing and attributing impact and the need for adequate resources and skills for communications work.</p> <p>Conclusions</p> <p>We contend that the adapted RAPID framework can serve as a tool for research actors to use in resolving these tensions, through facilitating a reflexive approach to considering their own combination of attributes, skills, networks and objectives and the ways these relate to policy contexts, actors and processes.</p

Improving the use of research evidence in guideline development: 14. Reporting guidelines

BACKGROUND: The World Health Organization (WHO), like many other organisations around the world, has recognised the need to use more rigorous processes to ensure that health care recommendations are informed by the best available research evidence. This is the 14(th )of a series of 16 reviews that have been prepared as background for advice from the WHO Advisory Committee on Health Research to WHO on how to achieve this. OBJECTIVES: We reviewed the literature on reporting guidelines and recommendations. METHODS: We searched PubMed and three databases of methodological studies for existing systematic reviews and relevant methodological research. We did not conduct systematic reviews ourselves. Our conclusions are based on the available evidence, consideration of what WHO and other organisations are doing and logical arguments. KEY QUESTIONS AND ANSWERS: There is little empirical evidence that addresses these questions. Our answers are based on logical arguments and standards put forward by other groups. What standard types of recommendations or reports should WHO use? • WHO should develop standard formats for reporting recommendations to facilitate recognition and use by decision makers for whom the recommendations are intended, and to ensure that all the information needed to judge the quality of a guideline, determine its applicability and, if needed, adapt it, is reported. • WHO should develop standard formats for full systematically developed guidelines that are sponsored by WHO, rapid assessments, and guidelines that are endorsed by WHO. • All three formats should include the same information as full guidelines, indicating explicitly what the group preparing the guideline did not do, as well as the methods that were used. • These formats should be used across clinical, public health and health systems recommendations. How should recommendations be formulated and reported? • Reports should be structured, using headings that correspond to those suggested by the Conference on Guideline Standardization or similar headings. • The quality of evidence and strength of recommendations should be reported explicitly using a standard approach. • The way in which recommendations are formulated should be adapted to the specific characteristics of a specific guideline. • Urgent attention should be given to developing a template that provides decision makers with the relevant global evidence that is needed to inform a decision and offers practical methods for incorporating the context specific evidence and judgements that are needed

Prisoners' attitudes towards cigarette smoking and smoking cessation: a questionnaire study in Poland

BACKGROUND: In the last decade Poland has successfully carried out effective anti-tobacco campaigns and introduced tobacco control legislation. This comprehensive strategy has focused on the general population and has led to a considerable decrease in tobacco consumption. Prisoners constitute a relatively small part of the entire Polish population and smoking habits in this group have been given little attention. The aim of the study was to assess the prevalence of cigarette smoking in Polish male prisoners, factors determining smoking in this group, prisoners' attitudes towards smoking cessation, and to evaluate prisoners' perception of different anti-tobacco measures. METHODS: An anonymous questionnaire including personal, demographic and smoking data was distributed among 944 male inmates. Of these, 907 men aged between 17 and 62 years (mean 32.3 years) met the inclusion criteria of the study. For the comparison of proportions, a chi-square test was used with continuity correction whenever appropriate. RESULTS: In the entire group, 81% of the subjects were smokers, 12% – ex-smokers, and 7% – never smokers. Current smokers had significantly lower education level than non-smokers (p < 0.0001) and ever-smokers more frequently abused other psychoactive substances than never smokers (p < 0.0001). Stress was reported as an important factor in prompting smoking (77%). Forty-nine percent of daily smokers were aware of the adverse health consequences of smoking. The majority of smokers (75%) had attempted to quit smoking in the past. Forty percent of smoking prisoners considered an award for abstaining from cigarettes as the best means to limit the prevalence of smoking in prisons. CONCLUSION: The prevalence of cigarette smoking among Polish prisoners is high. However, a majority of smokers attempt to quit, and they should be encouraged and supported. Efforts to reduce cigarette smoking in prisons need to take into consideration the specific factors influencing smoking habits in prisons

Building the Field of Health Policy and Systems Research: Social Science Matters

In the second in a series of articles addressing the current challenges and opportunities for the development of Health Policy and Systems Research (HPSR), Lucy Gilson and colleagues argue the importance of insights from the social sciences

Stress-Induced Reinstatement of Drug Seeking: 20 Years of Progress

In human addicts, drug relapse and craving are often provoked by stress. Since 1995, this clinical scenario has been studied using a rat model of stress-induced reinstatement of drug seeking. Here, we first discuss the generality of stress-induced reinstatement to different drugs of abuse, different stressors, and different behavioral procedures. We also discuss neuropharmacological mechanisms, and brain areas and circuits controlling stress-induced reinstatement of drug seeking. We conclude by discussing results from translational human laboratory studies and clinical trials that were inspired by results from rat studies on stress-induced reinstatement. Our main conclusions are (1) The phenomenon of stress-induced reinstatement, first shown with an intermittent footshock stressor in rats trained to self-administer heroin, generalizes to other abused drugs, including cocaine, methamphetamine, nicotine, and alcohol, and is also observed in the conditioned place preference model in rats and mice. This phenomenon, however, is stressor specific and not all stressors induce reinstatement of drug seeking. (2) Neuropharmacological studies indicate the involvement of corticotropin-releasing factor (CRF), noradrenaline, dopamine, glutamate, kappa/dynorphin, and several other peptide and neurotransmitter systems in stress-induced reinstatement. Neuropharmacology and circuitry studies indicate the involvement of CRF and noradrenaline transmission in bed nucleus of stria terminalis and central amygdala, and dopamine, CRF, kappa/dynorphin, and glutamate transmission in other components of the mesocorticolimbic dopamine system (ventral tegmental area, medial prefrontal cortex, orbitofrontal cortex, and nucleus accumbens). (3) Translational human laboratory studies and a recent clinical trial study show the efficacy of alpha-2 adrenoceptor agonists in decreasing stress-induced drug craving and stress-induced initial heroin lapse

Improving the use of research evidence in guideline development: 8. Synthesis and presentation of evidence

BACKGROUND: The World Health Organization (WHO), like many other organisations around the world, has recognised the need to use more rigorous processes to ensure that health care recommendations are informed by the best available research evidence. This is the eighth of a series of 16 reviews that have been prepared as background for advice from the WHO Advisory Committee on Health Research to WHO on how to achieve this. OBJECTIVES: We reviewed the literature on the synthesis and presentation of research evidence, focusing on four key questions. METHODS: We searched PubMed and three databases of methodological studies for existing systematic reviews and relevant methodological research. We did not conduct systematic reviews ourselves. Our conclusions are based on the available evidence, consideration of what WHO and other organisations are doing and logical arguments. KEY QUESTIONS AND ANSWERS: We found two reviews of instruments for critically appraising systematic reviews, several studies of the importance of using extensive searches for reviews and determining when it is important to update reviews, and consensus statements about the reporting of reviews that informed our answers to the following questions. How should existing systematic reviews be critically appraised? • Because preparing systematic reviews can take over a year and require capacity and resources, existing reviews should be used when possible and updated, if needed. • Standard criteria, such as A MeaSurement Tool to Assess Reviews (AMSTAR), should be used to critically appraise existing systematic reviews, together with an assessment of the relevance of the review to the questions being asked. When and how should WHO undertake or commission new reviews? • Consideration should be given to undertaking or commissioning a new review whenever a relevant, up-to-date review of good quality is not available. • When time or resources are limited it may be necessary to undertake rapid assessments. The methods that are used to do these assessments should be reported, including important limitations and uncertainties and explicit consideration of the need and urgency of undertaking a full systematic review. • Because WHO has limited capacity for undertaking systematic reviews, reviews will often need to be commissioned when a new review is needed. Consideration should be given to establishing collaborating centres to undertake or support this work, similar to what some national organisations have done. How should the findings of systematic reviews be summarised and presented to committees responsible for making recommendations? • Concise summaries (evidence tables) of the best available evidence for each important outcome, including benefits, harms and costs, should be presented to the groups responsible for making recommendations. These should include an assessment of the quality of the evidence and a summary of the findings for each outcome. • The full systematic reviews, on which the summaries are based, should also be available to both those making recommendations and users of the recommendations. What additional information is needed to inform recommendations and how should this information be synthesised with information about effects and presented to committees? • Additional information that is needed to inform recommendations includes factors that might modify the expected effects, need (prevalence, baseline risk or status), values (the relative importance of key outcomes), costs and the availability of resources. • Any assumptions that are made about values or other factors that may vary from setting to setting should be made explicit. • For global guidelines that are intended to inform decisions in different settings, consideration should be given to using a template to assist the synthesis of information specific to a setting with the global evidence of the effects of the relevant interventions

Forty-Three Loci Associated with Plasma Lipoprotein Size, Concentration, and Cholesterol Content in Genome-Wide Analysis

While conventional LDL-C, HDL-C, and triglyceride measurements reflect aggregate properties of plasma lipoprotein fractions, NMR-based measurements more accurately reflect lipoprotein particle concentrations according to class (LDL, HDL, and VLDL) and particle size (small, medium, and large). The concentrations of these lipoprotein sub-fractions may be related to risk of cardiovascular disease and related metabolic disorders. We performed a genome-wide association study of 17 lipoprotein measures determined by NMR together with LDL-C, HDL-C, triglycerides, ApoA1, and ApoB in 17,296 women from the Women's Genome Health Study (WGHS). Among 36 loci with genome-wide significance (P<5×10−8) in primary and secondary analysis, ten (PCCB/STAG1 (3q22.3), GMPR/MYLIP (6p22.3), BTNL2 (6p21.32), KLF14 (7q32.2), 8p23.1, JMJD1C (10q21.3), SBF2 (11p15.4), 12q23.2, CCDC92/DNAH10/ZNF664 (12q24.31.B), and WIPI1 (17q24.2)) have not been reported in prior genome-wide association studies for plasma lipid concentration. Associations with mean lipoprotein particle size but not cholesterol content were found for LDL at four loci (7q11.23, LPL (8p21.3), 12q24.31.B, and LIPG (18q21.1)) and for HDL at one locus (GCKR (2p23.3)). In addition, genetic determinants of total IDL and total VLDL concentration were found at many loci, most strongly at LIPC (15q22.1) and APOC-APOE complex (19q13.32), respectively. Associations at seven more loci previously known for effects on conventional plasma lipid measures reveal additional genetic influences on lipoprotein profiles and bring the total number of loci to 43. Thus, genome-wide associations identified novel loci involved with lipoprotein metabolism—including loci that affect the NMR-based measures of concentration or size of LDL, HDL, and VLDL particles—all characteristics of lipoprotein profiles that may impact disease risk but are not available by conventional assay