In a decentralised health system, district health managers are tasked with planning for health service delivery, which should be evidence based. However, planning in low-income countries such as Uganda has been described as ad hoc. A systematic approach to the planning process using district-specific evidence was introduced to district health managers in Uganda. However, little is known about how the use of district-specific evidence informs the planning process. In this study, we investigate how the use of this evidence affects decision-making in the planning process and how stakeholders in the planning process perceived the use of evidence.A convergent parallel mixed-methods study design was used, where quantitative data was collected from district health annual work plans for the financial years 2012/2013, 2013/2014, 2014/2015 and 2015/2016 as well as from bottleneck analysis reports for 2012, 2013, 2014 and 2015. Qualitative data was collected through semi-structured interviews with key informants from the two study districts.District managers reported that they were able to produce more robust district annual work plans when they used the systematic approach of using district-specific evidence. Approximately half of the prioritised activities in the annual work plans were evidence based. Procurement and logistics, training, and support supervision activities were the most prioritised activities. Between 4% and 5.5% of the total planned expenditure was for child survival, of which 47% to 94% was from donor and other partner contributions.District-specific evidence and a structured process for its use to prioritise activities and make decisions in the planning process at the district level helped systematise the planning process. However, the reported limited decision and fiscal space, inadequate funding and high dependency on donor funding did not always allow for the use of district-specific evidence in the planning process. The health sector in Uganda has undergone several changes and reforms since the Harare Declaration, which introduced the district health system (DHS)  and the In 1997, Uganda took on political, administrative and fiscal decentralisation, thereby transferring administrative, political and fiscal authority from the central government to the local government authorities, mainly in the form of devolution , 8. UnliThe provision of healthcare is the responsibility of two levels of government – the central (macro) and the local (meso and micro) levels Fig. . The DHSAlthough planning should be evidence based to prioritise activities , 12, in Similarly, in Uganda, the lack of tools to assess performance in the DHS prevents the identification of gaps in service delivery and the definition of priorities for actions to bridge the gaps during the annual planning process . A systeDistrict-specific evidence in this study refers to the data that was collected through routine Health Management Information Systems and other surveys, for example, Lots Quality Assurance Surveys. Evidence also includes information from community dialogues with care givers of children under 5 years of age, health workers and village health teams. The structured process refers to how this evidence was analysed by the DHMT to identify gaps in service delivery and prioritise solutions to overcome those gaps .the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients”  that are expensive we cannot plan for them, we keep on postponing them.” Manager, disrict B“Activities that either had no direct financial implications or were considered to have very high financial implications were not always included in the annual health work plans, for example, procurement of expensive equipment.A wide range of child survival activities were prioritised in the district health annual work plans. For purposes of this analysis, activities were categorised into (1) support supervision, (2) planning/meetings, 3) mobilisation and advocacy, (4) data-related activities, (5) training, (6) logistics and procurement, and (7) immunisation outreach. These categories were used because they represented all child survival activities in the district health annual work plans (see Table  mobilisaFigure Further analysis of the procurement and logistics category, which accounted for the majority of the planned activities, showed variation in the kind of activities that were prioritised in each of the districts Fig. . This vaThere was an increase in the planned budget for child survival activities between 2012/2013 and 2015/2016 in both districts. In district A, the planned expenditure increased from US$ 4550 to US$ 45,185, while in district B it rose from US$ 6626 to US$ 28,327. Child survival activities accounted for between 4% and 5.5% of the total planned expenditure on health services with per capita funding of US$ 0.3 and US$ 0.1 in districts A and B, respectively (Fig. The funding is very, very little when you look at what we have planned and what has come as a contribution from the PHC [primary healthcare], and funds are minimal.” Manager, district A“Although funding for child survival activities increased over the 4-year period, the levels were still low, and one of the district managers emphasised this:There was a variation in the sources of funding over the four financial years Fig. b, c. GovSo, we still feel that the money is little and if we had no partners, I think we would not be doing anything.” Manager, district B“Results from both districts showed that the districts were dependent on partner/donor funding for child survival activities, although donors sometimes had their own priorities that were not necessarily those informed by the district-specific evidence. For example, the geographical area of implementation of programmes may not necessarily be in the areas that have the most need. The managers also expressed dependence on partner funding:If they [funds] are conditional, they have guidelines that come with those funding; they are not supposed to be reallocated, they are supposed to be used for whatever activities that they are supposed to do. If it is immunisation, it must be immunisation, not any other thing.” Manager, district A“District managers reported that they were further constrained by the difficulty in reallocating resources as the funding came with guidelines for its use and could not be easily reallocated.I must say the work plans we have now are more real and genuine and factual. Using data has enabled us to have realistic work plans.” Manager, district A“District managers reported that the use of district-specific evidence in planning was minimal before the introduction of evidence-based planning by the CODES project. They also stated that they were able to prioritise activities backed by evidence and produce more robust work plans. For instance, one of them said:I think the most important [outcome] is that the process has inculcated in us the habit of discussion, of dialogue regarding deciding what is important for the district.” Manager, district A“Some few innovations have resulted from this; we might not measure their effect now but maybe in future. For example, we set up an intensive care unit [for children], it is not big, but an area with everything available, and kids are better.” Manager, district B“The managers also reported having fewer disagreements with elected officials when evidence was used in the planning process, which made their work easier than before. DHMT members also said that using district-specific evidence encouraged dialogue and better teamwork and allowed them to think outside the box for innovative solutions to identified problems.I think evidence means using data and facts derived from data, so using evidence is somehow connected to data.” Manager, district A“Despite having a different understanding of the meaning of evidence, district managers said that evidence was the data they collect for the health department. Some of the respondents understood evidence as having proof about something, or that something works, while others thought that it refers to the use of quantitative data that was collected through Health Management Information Systems or surveys like Lots Quality Assurance Surveys. Others reported that evidence was information that was relevant to establishing the actual situation of the health department irrespective of its source and this could include community members and information collected from other sources, for example, from the political or religious leaders in the district.Findings showed that district managers included in the district health annual work plans approximately half of the activities that were identified to bridge gaps for child survival. There was a slight increase in the number of prioritised activities over the 2012/2013 to 2015/2016 period. However, the proportion of activities included in the annual work plans remained practically the same over the 4-year period. Although procurement and logistics-related activities, such as reproducing guidelines, accounted for the most substantial proportion of planned funding in both districts, there was a wide variation in what those activities included. The variation might be an indication that the districts prioritised activities according to their local needs. Child survival activities accounted for between 4% and 5.5% of the total planned expenditure on health services, with per capita funding of US$ 0.3 in one district and US$ 0.1 in the other. Over the 4 years, donors’ contributions accounted for between 47% and 94% of the funding for child survival activities.DHMT members acknowledged that the use of district-specific evidence resulted in practical and robust annual work plans and was beneficial to the district health system. This is similar to findings in a study conducted in India, Nigeria and Ethiopia, where district managers viewed the use of locally generated evidence positively . HoweverThe DHMT considered the lack of autonomy or decision space a constraint to the use of district-specific evidence. Similar concerns have been documented in other LIC settings like Ghana, Zambia and the Philippines –52. AlthAnother consideration while using district-specific evidence was the political nature of decision-making and priority-setting. This is not unique to Uganda, Bryant et al.  and GoddThe absence of a standard format for the district annual work plan meant that the work plans varied between the districts and even between the different planning cycles. The variation was not as a result districts identifying context-specific priorities. The difference in formats makes the analysis more difficult to standardise and generalise. As this study was carried out in only two districts that were part of an intervention to improve the use of district-specific evidence in setting priorities in the planning process, results cannot be generalised to all other districts; however, they can be used to inform the planning process in Uganda and countries with similar settings. During the annual health work plan review, analysis of planned activities and not their implementation was done. The analysis also included the proposed expenditure for child survival activities and not the actual spending.This study revealed that use of district-specific evidence and a structured process for its utilisation to prioritise activities and make decisions in the planning process at the district level helped systematise an otherwise ad hoc process. By using district-specific evidence, health management teams were able to articulate and advocate for priorities related to child survival. However, the reported limited decision and fiscal space, human resource gaps and inadequate funding did not always allow for the use of district-specific evidence in the planning process. As reflected in the district health annual work plans, districts were heavily dependent on donor funding for child survival activities, which may constrain their ability to use district-specific evidence in the planning process.The heavy dependence on donor funding raises the question about the usefulness of using district-specific evidence in the reported absence of adequate resources to finance and operationalise the district health annual work plans and the limited decision and fiscal space that the DHMT has to address the gaps identified using the local evidence. Related to this is whether district managers can prioritise activities that reflect the needs of the district as opposed to the interests of the funding partners who provided the bulk of funding for child survival activities.


Carnivore predation on livestock often leads people to retaliate. Persecution by humans has contributed strongly to global endangerment of carnivores. Preventing livestock losses would help to achieve three goals common to many human societies: preserve nature, protect animal welfare, and safeguard human livelihoods. Between 2016 and 2018, four independent reviews evaluated >40 years of research on lethal and nonlethal interventions for reducing predation on livestock. From 114 studies, we find a striking conclusion: scarce quantitative comparisons of interventions and scarce comparisons against experimental controls preclude strong inference about the effectiveness of methods. For wise investment of public resources in protecting livestock and carnivores, evidence of effectiveness should be a prerequisite to policy making or large-scale funding of any method or, at a minimum, should be measured during implementation. An appropriate evidence base is needed, and we recommend a coalition of scientists and managers be formed to establish and encourage use of consistent standards in future experimental evaluations. Carnivores, such as lions and wolves, are killed in many regions over real or perceived threats to human interests. Combined with habitat loss and fragmentation, human-induced mortality has contributed to widespread carnivore population declines, along with declines of their important ecosystem functions . BalanciBetween 2016 and 2018, we independently published four reviews examining evidence for the effectiveness of interventions to reduce livestock predation by carnivores . Here, wWe suspect that the striking paucity of rigorous evaluation is due to the tendency for decisions about predator control to depend on factors other than evidence-based evaluation of whether a given intervention effectively protects livestock. These other factors—including ethics (should one implement the intervention?), feasibility (can one implement the intervention?), and perception (does one believe the intervention will work?)—might be important subsequent considerations in the implementation and decision-making processes. However, objective scientific evidence of an intervention’s functional effectiveness must remain a foundational prerequisite on which subjective inquiries later build. The lack of scientific synthesis and consensus about functional effectiveness has allowed more subjective factors to dominate decision-making about predator control and likely wasted time and money on interventions that do not optimally protect livestock. Furthermore, shifting ethics and public values in some communities are enabling the return of carnivores to landscapes worldwide or leading to the increased use of nonlethal predator control interventions. We support these initiatives from the perspective of conserving carnivores but insist that scientific evidence for functional effectiveness be considered first to ensure that interventions intended to protect livestock accomplish that goal. This will prevent the inefficient—or worse yet, counterproductive—use of limited resources to protect animals long term.Additionally, although our reviews collectively reveal a need for more evidence, scientists alone cannot fill this gap. Livestock owners, natural resource managers, and decision-makers each have an important role to play in research partnerships to collaboratively guide the testing of predator control interventions. Here, we appeal to these groups by summarizing the advantages of evidence-based effective interventions, the best practices of scientific inference, and the role of policy in promoting effective predator control strategies. We start by synthesizing the results of our four independent reviews to provide scientific consensus on the evaluations of predator control interventions. We urge managers and policy decision-makers to use this discussion as a basis for creating policy that promotes evidence-based, effective strategies for protecting domestic animals from carnivore predation.Our four reviews –9 jointlAmong the 114 studies that passed screening in one or more reviews , represeWe summarize our four sets of results by category of intervention in Societal values and, accordingly, policies for human–carnivore coexistence have changed over the millennia. The almost exclusive use of lethal interventions has given way to nonlethal interventions as important supplements to or replacements for prior lethal methods. Immense logistical and financial resources are invested in protecting livestock and carnivores, so the scarcity of rigorous scientific evidence for effectiveness should be a concern. We encourage governments to adopt proven methods from similar systems of carnivores and human interests, with systems in place to review and adapt management actions as new evidence becomes available. When governments contemplate large-scale implementation or funding for interventions, scientific evidence of functional effectiveness deserves priority to avoid wasting resources on ineffective methods, no matter if the latter are ethical or easy to implement. When no proven method is available, scientific evaluation of functional effectiveness should coincide with implementation.Strong inference in any scientific field demands control over potentially confounding variables and testable claims about functional effectiveness of interventions . In our Vicugna pacos) and llamas (Lama glama) joined a randomized reverse treatment (crossover) experiment to evaluate light devices in deterring carnivores [The strongest inference results from experiments that achieve the “gold standard” through “random assignment to control and treatment groups without bias (systematic error) in sampling, treatment, measurement, or reporting” . This rernivores . Moreovernivores .“Silver standard” designs provide weaker inference because of nonrandom assignment to treatment and then repeated measures of the replicate at two or more time points . Both time passing and the treatment might explain changes in replicates, in addition to the extraneous “nuisance” variables present in agro-ecosystems at the outset .The weakest standard of evidence is the correlative study, which compares livestock predation among herds that varied haphazardly in past protection or varied systematically if people intervened only where livestock had died. In correlational studies, confounding variables inevitably create selection or sampling bias. Although correlative studies may be useful as an initial exploratory step and help direct further research, confidence in their findings should be low, especially if there is large variation in the results. Correlative studies cannot substitute for the silver or gold standards described above.Implementation of interventions must be consistent to avoid treatment bias. For example, the functional effectiveness of livestock-guarding dogs might vary with breed, individual, training, and maintenance of the dog. Likewise, tests of lethal methods have never controlled the simultaneous use of several methods of intervention , which is inadvisable for strong inference. Consistent maintenance of interventions throughout a study should also minimize treatment bias .Well-designed experiments should incorporate evaluation along multiple dimensions. Was the intervention implemented as planned? Did attacks on livestock diminish? Measurement bias arises from systematic error in documenting implementation or losses in treatment or response variables. As in biomedical research, which sometimes uses patient self-reports as a subjective measure of effectiveness alongside objective measures of health outcomes, there are valid reasons to measure owners’ perceptions of effectiveness of interventions. In human–wildlife interactions, people’s attitudes can influence the adoption or rejection of interventions independently of scientific evidence ,19. SeveWe recognize that gold or silver standards may be difficult to achieve. Systematic errors can be difficult to eliminate entirely, so we urge careful consideration of methods during the design process, including peer review prior to initiation. Ethical considerations about exposing animals to lethal risks may limit experimental designs. This inherent difficulty for controlled experiments may explain why some published experiments were completed in artificial settings . Although most of our reviews omitted experiments for protecting property other than livestock, strong inference from such studies merit tests for livestock protection. Nonetheless, given that several examples of gold standard experiments overcame the complexities of people and wild ecosystems , 11, 12,Canis lupus), and 345 cougars (Puma concolor) [C. dingo) on their property.Many governments have institutionalized support for livestock protection from predators and implemented various interventions at landscape scales. The European Council Directive 98/58/EC, concerning protection of animals kept for farming purposes, states that “animals not kept in buildings shall where necessary and possible be given protection from adverse weather conditions, predators and risks to their health.” The Swedish Animal Welfare Act of 1988 mandates care should be given to injured animals as soon as possible. This obligation is in practice relevant subsequent to carnivore attacks. When trained field observers confirm livestock attacks by large carnivores, they also implement rapid response interventions, such as fladry and portable electric fences, to prevent recurrent attacks . In the oncolor) . SimilarGiven the weak state of current evidence about effectiveness, decisions to use interventions are most likely based on subjective factors  or nonscientific (and thus possibly biased) evidence. For example, many people have deeply rooted perceptions that an intervention is effective or not . TherefoHowever, scientists alone cannot transform policies for implementation. The pursuit of science-based management must be truly interdisciplinary and involve carnivore ecologists, animal husbandry scientists, social scientists, natural resource managers, ethicists, and other scholars and practitioners. Political leaders can also play a role to prioritize, coordinate, and fund partnerships across government agencies and nongovernment organizations. Because we anticipate continued debate over the standards of effectiveness, we recommend a coalition be formed to clearly distinguish standards for evaluation and experimental protocols, which would be distinct from coalitions convened to consider local factors that affect decisions. Through collaboration, scientists, managers, and policy leaders can help to protect livestock within healthy ecosystems that include carnivores. Constituents worldwide increasingly support the restoration of carnivore populations and accordingly are calling for human–carnivore coexistence and minimizing conflicts . EnablinS1 TableMethods have been simplified for comparison. Refer to the original articles for a full account of methods used and justification for the use of these methods.(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.S1 Fig(TIF)Click here for additional data file.


Eye care professionals should have access to high quality clinical practice guidelines that ideally are underpinned by evidence from robust systematic reviews of relevant research. The aim of this study was to identify clinical guidelines with recommendations pertaining to dietary modification and/or nutritional supplementation for age-related macular degeneration (AMD), and to evaluate the overall quality of the guidelines using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument. We also mapped recommendations to existing systematic review evidence. A comprehensive search was undertaken using bibliographic databases and other electronic resources for eligible guidelines. Quality appraisal was undertaken to generate scores for each of the six AGREE II domains, and mapping of extracted nutritional recommendations was performed for systematic reviews published up to March 2017. We identified 13 national and international guidelines, developed or updated between 2004 and 2019. These varied substantially in quality. The lowest scoring AGREE II domains were for ‘Rigour of Development’, ‘Applicability’ (which measures implementation strategies to improve uptake of recommendations), and ‘Editorial Independence’. Only four guidelines used evidence from systematic reviews to support their nutritional recommendations. In conclusion, there is significant scope for improving current Clinical Practice Guidelines for AMD, and guideline developers should use evidence from existing high quality systematic reviews to inform clinical recommendations. Age-related macular degeneration (AMD) is an ocular disease affecting the central area of the retina (the macula), which is responsible for high-resolution daytime vision . In the AMD is a complex disorder with several non-modifiable and modifiable risk factors . The retBased on accumulating research evidence, dietary modification and/or nutritional supplementation has been proposed as a simple and potentially cost-effective strategy for modifying the risk of AMD. Although there is a large body of research in this area, the quality of studies is highly variable and conflicting results have been reported. These factors pose challenges for clinicians, when attempting to provide evidence-based recommendations to patients about the relative risks and benefits of nutrition-based interventions. Clinical practice guidelines can be used to aid clinical decision-making in such circumstances. These documents should contain recommendations that are informed by a systematic review of the available research evidence, and a consideration of the benefits and harms of alternative interventions . In the (1) Identify clinical practice guidelines for AMD that contain nutritional recommendations, based upon a systematic literature search; (2) Evaluate the quality of these guidelines using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool; and (3) Map clinical practice guideline recommendations, as related to nutrition and AMD, to relevant systematic reviews.We included national and international clinical practice guidelines for AMD that contained nutritional recommendations, including dietary modification or nutritional supplementation, as strategies to prevent or slow the progression of the disease. https://www.cadth.ca)  and the Turning Research into Practice (TRIP) database (https://www.tripdatabase.com/), and undertook a search of the webpages of national and international professional organisations for ophthalmology and optometry. The search was not limited by language and we used Google Translate to extract recommendations and appraise guidelines that were not written in English.We searched the Ovid MEDLINE and Embase bibliographic databases from January 1999 to January 2019 using search filters for identifying clinical guidelines that were developed by the Canadian Agency for Drugs and Technologies in Health (.ca) see . In addiFollowing removal of duplicates, two reviewers (JL/LD) independently screened the titles and abstracts identified from the bibliographic searches and resolved any discrepancies by discussion and consensus. We obtained full-text copies of potentially eligible guidelines and these were independently assessed by all three authors, working in pairs, to determine whether they met the inclusion criteria. Reasons for exclusion were documented at this stage. Two reviewers  independently extracted general characteristics of each guideline  and details of the specific nutritional recommendations.https://www.agreetrust.org/). The AGREE II instrument evaluates the process of practice guideline development, and the quality of reporting, using 21 items organised into six key domains, as follows: (1) Scope and Purpose; (2) Stakeholder Involvement; (3) Rigour of Development; (4) Clarity of Presentation; (5) Applicability; and (6) Editorial Independence. The quality of each clinical guideline was independently evaluated by two reviewers  using the Appraisal of Guidelines for Research and Evaluation (AGREE) II tool  . Five guThe overall inter-rater agreement on scoring of the individual items was excellent  0.76 to 0.84)).The quality of each guideline, across each of the AGREE II domains, is shown in We extracted individual recommendations relating to nutritional strategies for both preventing and slowing the progression of AMD   recommenOnly one guideline  guideline NG82) achieved high scores in all of the AGREE II assessment domains. This is perhaps unsurprising, since the NICE guideline development manual states that NICE guidelines “are based on internationally accepted criteria of quality as detailed in the Appraisal of Guidelines of Research and Evaluation II (AGREE II) instrument”. The development and implementation of high quality clinical practice guidelines requires substantial time, expertise and resources. Less formal guideline development groups, such as those produced by ‘expert panels’ or professional organisations, may lack the resources and/or methodological expertise to produce guidelines of the highest quality. In such circumstances, adapting existing high quality guidelines to local contexts may be an alternative to de novo development. The AMD Preferred Practice Patterns (PPP) Philippines (2016)  is an exMany robust systematic reviews have considered the merit of a variety of dietary and nutritional recommendations for AMD. In the present study, we used the systematic evidence searches performed by Lindsley et al.  and DownOf the nine guidelines that considered nutritional approaches for the primary prevention of AMD, most considered the potential merit of dietary modification, although some also made recommendations in relation to nutritional supplementation. Several epidemiological studies have investigated whether specific dietary patterns and/or foods are associated with a reduced risk of developing AMD. A meta-analysis of prospective cohort, case-control and cross-sectional studies concluded that consumption of two or more servings of oily fish per week was beneficial in the primary prevention of AMD . AnotherNutritional strategies for secondary prevention of AMD  were included in all of the clinical guidelines. Five guidelines ,28,33,34With respect to high-dose anti-oxidant vitamin and mineral supplements for managing AMD, there were divergent recommendations. Notably, only the U.K. NICE guideline  did not eporting of methodological details for clinical guideline development was poor and therefore it was not possible to make a judgement as to whether the guidelines had used an appropriate evidence-based approach in their development.A key strength of the current study was the comprehensive search to identify eligible clinical practice guidelines. Data extraction and quality appraisal were conducted independently by two reviewers, using a recognised assessment tool (AGREE II), which has established metrics of reliability and validity . OverallDespite the availability of robust systematic reviews evaluating the efficacy and safety of nutritional interventions for AMD, this study found evidence that these resources are infrequently used to support recommendations in AMD clinical practice guidelines. Consequently, guidelines often present conflicting recommendations that could lead to variations in clinical care. The AGREE II quality evaluations of the included guidelines identified several key areas that require improvement, particularly the rigour of development, managing potential conflicts of interests, and presenting strategies for implementing guideline recommendations into daily practice.


Venous thromboembolism (VTE) is a major global cause of morbidity and mortality. Low molecular weight heparin (LMWH) and fondaparinux (FDP) are frequently used to treat and prevent VTE and have a variety of safety and practical advantages over other anticoagulants, including use in outpatient settings. These medications are commonly listed on drug formularies, which act as a gateway for health plan prescription coverage by outlining the circumstances under which patients will be covered for specific drugs and drug products. Because patient access to medications is impacted by the nature of their listing on formularies, they must be rigorously reviewed and modernized as new evidence emerges.As part of a broader drug class review team, we completed a systematic review of clinical practice guidelines to determine whether the recommendations they reported aligned with the indications listed for the coverage of LMWH and FDP in an outpatient drug formulary. Guideline quality was assessed using the Appraisal of Guidelines for Research & Evaluation (AGREE) II tool. Recommendation matrices were used to systematically compare, categorize, and summarize included recommendations.applicability) was poorly addressed. Most recommendations were based on moderate- to low-quality/limited evidence and reported on the use of LMWHs generally; few reported on specific agents.Twenty-seven guidelines were included from which 168 eligible recommendations were identified. Generally, AGREE II domains were adequately addressed; however, domain five (Our findings contributed to the recommendation that the formulary listing for LMWH and FDP be streamlined to include coverage for specific outpatient indications. The paucity of available evidence on the comparative efficacy of specific LMWH agents against each other and FDP limited agent-specific listing recommendations, highlighting the need for high-quality comparative studies on this topic. Venous thromboembolism (VTE) is a major global cause of morbidity and mortality –3. No siTheir applicability across a broad spectrum of clinical scenarios makes LMWH and FDP appealing for prescribers; however, research has shown that prescribing decisions are not based solely on clinical indication and medical knowledge –16. IndeWhile the exact nature of formularies can vary across jurisdictions, they often employ a tiered reimbursement scheme that includes: coverage for listed medications for all patients with no restrictions , coverage for listed medications for patients meeting specific clinical criteria (limited use), or no coverage offered (non-benefit) , 18. CerTo ensure that formularies are kept up to date, they must be rigorously reviewed as new evidence emerges , 19–21. We completed a SR of CPGs that reported recommendations on the use of LMWH and FDP for ten specific outpatient indications see  that evoA literature search strategy was developed and tested through an iterative process by an experienced medical information specialist in consultation with the review team. Using the Ovid platform, CPGs were identified from Ovid MEDLINE, Ovid MEDLINE In-Process & Other Non-Indexed Citations and Embase. All searches were performed on October 26, 2015 and updated in May 2017. The 2017 update also included searches for systematic reviews and health technology assessments using the databases mentioned previously in addition to the Cochrane Library (Wiley version). The search strategies used a combination of controlled vocabulary  and keywords, . Vocabulary and syntax were adjusted across the databases. Search results were limited to those published in English and with the publication dates 2005 to present. When possible, animal-only and opinion-pieces were removed from the results. Grey literature was searched using CADTH’s Grey Matters Light . SpecifiTable 1). The same two reviewers then independently screened the full text of potentially eligible records for inclusion in ‘blocks’ by publication year , beginning with the most recently published records. If supplemental documents  were available and potentially important in making a decision about a record’s eligibility, they were also retrieved and screened along with the primary guideline document. When the two reviewers agreed that at least one CPG published in each publication year block was fully eligible for inclusion, the recommendations reported within each eligible guideline were screened for inclusion and simultaneously extracted. DistillerSR online systematic review software  was used to manage the CPG eligibility screening and selection process. Discrepancies about inclusion were resolved through consensus.Two reviewers (AJ & SH) independently screened the titles and abstracts of all records returned from the literature search against the eligibility criteria outlined in our ‘Population & Clinical Areas, Interventions, Comparators, Attributes of CPGs, and Recommendation characteristics’ (PICAR) statement  and independently verified for accuracy and completeness by a second reviewer. Discrepancies were resolved through consensus. General guideline information, including year of publication, developing organization and/or authors and country or countries of publication, was extracted from all included CPGs. Two reviewers (AJ & SH) independently screened each recommendation reported by included CPGs for eligibility against the PICAR statement . As soon as a recommendation was deemed eligible, it was extracted by the reviewer. To facilitate data synthesis (see further details below), reviewers assigned a thematic code  to each recommendation during data extraction. The general characteristics of each code  were agreed upon before data extraction began. Details on the level of evidence  associated with each recommendation were also extracted.a priori limits on the number of CPGs that were eligible for inclusion , a process was required to judge whether or not the recommendations extracted from guidelines published in (reverse) consecutive years continued to provide unique information, or they were becoming repetitive and, thus, were no longer informative. As such, we implemented a process to assess whether data saturation [As we did not set any turation  had beenBriefly, after a full set of recommendations were extracted (and independently verified for accuracy) from all included CPGs in each publication year, two reviewers (AJ & SH) reviewed all data collected to that point and made independent judgements about whether or not data saturation had been met for each indication. That is, each reviewer made a judgement as to whether the recommendations reported across CPGs were similar over time, or they were mostly different and, therefore, it was possible that further recommendations from additional CPGs could report unique information. When it became apparent to both reviewers that the data had become saturated for most indications, members of the internal review team provided a full set of recommendations to the broader stakeholder group for review. After consulting with the broader stakeholder group, a decision was made to stop screening CPGs for inclusion if they were published prior to 2011. Although we did not identify eligible recommendations for all indications of interest up to that point, all team members recognized that CPGs published prior to 2011 would be based on dated information and would, therefore, be of limited value.The Appraisal of Guidelines for Research and Evaluation II (AGREE II)  tool wasAll guidelines were assessed a score for each AGREE II item on a seven-point scale by two independent reviewers  using a standardized form designed for use in DistillerSR. For each item assessed, reviewers provided comments justifying their decision. Scores were exported to Microsoft Excel where the percentage for each domain was calculated using the formula provided in the AGREE II user’s manual :. If three or more domains were adequately addressed, except for domain three, CPGs were considered to be of ‘moderate quality’. CPGs were also assessed as being ‘moderate’ in overall quality if they adequately addressed at least two AGREE II domains, except domain three, but were assessed a score of at least 50% in that domain. All other guidelines not meeting the criteria for ‘high’ or ‘moderate’ quality were considered to be of ‘low’ overall quality.Judgements on each guideline’s overall quality were made by employing a standardized scoring rubric. Guidelines were considered to be of ‘high quality’ if they adequately addressed at least three of the six AGREE II domains, including domain three  was composed of eight columns and each row contained one recommendation. The first column contained identifying information about the CPG from which the recommendation was extracted (first author/publishing organization and review identification number) and the second column contained the CPG’s publication year. In the third column, we listed the CPG’s quality (e.g. ‘high’ or ‘moderate’) as assessed using the AGREE II tool and, in the forth column, we listed the recommendation. The subsequent four columns contained 1) the recommendation’s standardized level of evidence , 2) its thematic code, 3) whether or not the intervention or comparator was recommended over another (‘comparative preference’), and 4) what medications were mentioned in the recommendation.We employed thematic analysis  to help Across included CPGs, a variety of systems were used to assess the quality of evidence underpinning recommendations . To faciThe results of the screening and guideline selection process have been summarized in a Preferred Reporting Items for Systematic Reviews (PRISMA) flow diagram . A totalGeneral characteristics of the 27 included CPGs are available in Most guidelines (63%) used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group approach k = 6 , 57, 59), 5957, 5clarity of presentation, was the best-scoring domain with all CPGs having been assessed scores greater than 60 percent (range 69 to 100 percent). Domain five (applicability) was the worst scoring domain, with a median score of 10 percent (range 0 to 96 percent). Nine CPGs each scored 100 percent in a single domain and eight [editorial independence. The median score for AGREE II domain five (applicability) was 10 percent; however, one CPG [As shown in nd eight –43, 57 s one CPG  was assemethodological rigour) and were judged to be of high overall quality. An additional five CPGs [Specific AGREE II scores for each domain (by CPG) are provided in ive CPGs , 54, 55 ive CPGs , 55 wereive CPGs , 48, 54 ive CPGs , 57, 59 We included a total of 168 recommendations on the use of LMWH (as a drug class or any specific agent) or FDP addressing nine of our ten indications of interest. We did not identify any recommendations on the use of LMWH or FDP for the post-operative prophylaxis of VTE in patients undergoing hip or knee surgery who cannot use warfarin. Across all indications, LMWH was mentioned 154 times, while specific LMWH agents  were mentioned only 19 times and only in recommendations for patients with cancer and the prevention of VTE in patients undergoing non-orthopedic surgery. Fondaparinux was only mentioned on 35 occasions and not at all in any recommendation on the treatment of VTE in patients who cannot tolerate warfarin or in whom it is contraindicated and only once in a single recommendation on the prevention of VTE in patients with cancer. A detailed breakdown of the frequency with which each drug class and individual LMWH agents were discussed by indication is provided in We identified 81 recommendations for the use of LMWH and FDP in the treatment of VTE and 87 for the prevention of VTE (including peri-operative bridging). The greatest proportion of included recommendations were related to the use of LMWH or FDP for the prevention of VTE in patients undergoing non-orthopedic surgery (r = 48), while only one recommendation addressed the treatment of VTE in patients who cannot tolerate warfarin or in whom the drug is contraindicated. A summary of recommendations for treatment-related indications is provided in As summarized in Tables While FDP was recommended as a potential treatment option for six indications, it was never recommended as a first line of treatment, and its use was discouraged or cautioned in a variety of specific clinical scenarios Tables  and 4. FAs summarized in As shown in There was no apparent correlation between the quality of evidence underpinning recommendations on the use of LMWH or FDP in treating or preventing VTE and the quality of CPGs reporting them see . For exawww.wordle.com/create) showing the relative frequencies of key recommendation themes is provided in During data collection and synthesis, we noted a variety of recurring themes in the content of included recommendations. A word cloud  to assescope and purpose) and four (clarity of presentation) were particularly well-addressed, domain five (applicability), which addresses factors that may impact a guideline’s implementation, potential impact on resources, and strategies to improve uptake, was very poorly addressed. This finding is not unique to this review, rather, it appears to be a general criticism of many reviews of CPGs published on a variety of topics . Given t cancer ), futuret cancer , to systA key element of evidence-based CPGs is the systematic identification, and formal appraisal, of research evidence . Indeed,We created a standardized evidence quality rubric to compare and contrast the quality of evidence underpinning recommendations reported across CPGs; however, this system still presented us with certain challenges. First, while many included CPGs used the GRADE system (or various adaptations thereof) to assess evidence quality, others used systems that were quite different in terms of process and reporting. Thus, standardization required some subjectivity on our part and our rubric was heavily influenced by the GRADE approach. Second, while many CPGs presented the same general recommendation for a specific clinical scenario , they often provided a variety of additional details  and the strength of evidence provided was particularly influenced by presence of the additional details. Encouragingly, guideline development organizations and academic journals have started to adopt and promote the use of a single transparent framework (GRADE) , 71, whiWhen reported, we collected information on the strength of recommendations ; howeveAcross recommendations, LMWH was most frequently discussed in terms of a drug class, although comparatively few mentioned specific uses for individual LMWH agents. When specific LMWHs were discussed in recommendations, they were based on very low-quality/limited evidence. These findings highlight substantial limitations on the availability of evidence for the use of LMWHs as a whole. As noted by Merli et al. , althougThese findings contributed to the recommendation that an outpatient formulary listing for LMWH and FDP become streamlined to include coverage for the following indications: acute treatment of VTE in patients without cancer; acute treatment, and secondary prophylaxis, of VTE in patients with cancer; treatment and prophylaxis of VTE in pregnant or lactating women; post-operative prophylaxis of VTE in patients a) undergoing surgery of the lower limbs and b) patients undergoing non-orthopedic surgery who are at high risk for thromboembolic complications; and peri-operative bridging in patients who require long-term therapy with warfarin . The pauA streamlined formulary listing for LMWH and FDP is expected to reduce clinician burden in prescribing, and improve patient access to, these medications. As noted; however, a variety of factors influence prescriber decision-making, many of which fall beyond the scope of a single outpatient formulary listing –16. For Although this review focused on outpatient indications for LMWH and FDP, it should be noted that most patients begin treatment with these medications in-hospital and continue after discharge . As suchUltimately, decisions about patient care must be made by competent health care providers in consultation with patients whose values and treatment preferences may differ . For manWe conducted a rigorous SR of CPGs that enabled the development of a robust evidence base on the recommended uses of LMWHs and FPD across several outpatient indications of specific interest to clinicians and decision-makers. Because this study was specifically designed to produce evidence for policy decision-making, it was carried out in a hastened timeframe, and certain constraints were placed on inclusion criteria and methodological processes. These limits were, however, balanced against the broad inclusion of explicitly evidence-based CPGs developed by organizations located in a broad range of geographical locations. We evaluated the quality of CPGs using AGREE II, a validated international CPG quality assessment tool, and our use of the Seven-point AGREE II Score Calculator  facilitated efficient inter-rater comparisons and helped us quickly identify important discrepancies. Although AGREE II assessments were completed by two raters instead of the preferred four, even when inter-rater discrepancies were ‘low’ , both raters independently re-evaluated all domain item scores that differed by three points or greater. In doing so, we feel that additional reviewers would not likely impact overall scores. Importantly, while we made our best efforts to identify supplemental documents that could possibly have been useful during AGREE II assessments, we cannot rule out the possibility that some may have been missed. Furthermore, while our standardized evidence quality rubric allowed us to compare and contrast the quality of evidence underpinning recommendations reported across CPGs, we were unable to formally evaluate the clinical credibility and implementability of included recommendations.Drug formularies play an important role in allowing patients access to required medications; however, they need to be updated as new evidence emerges. We conducted a SR of CPGs to determine whether the recommendations they reported aligned with the indications for the use of LMWH and FDP in an outpatient drug formulary. As a drug class, LMWH was widely recommended as safe and efficacious for the treatment and prevention of VTE in outpatients. These findings contributed to the recommendation that the outpatient formulary listing for LMWH and FDP be modernized and streamlined to include coverage for specific outpatient indications. A notable paucity of evidence; however, precluded our ability to make recommendations on the use of individual agents. Given the distinct pharmacologic and biochemical profiles of each LMWH and FDP, further studies should be conducted to establish the comparative efficacy and safety of individual agents against each other and FDP across clinical scenarios. Once available, this information should be incorporated into CPGs to ensure that the most up to date evidence is considered by clinicians during the prescription decision-making process. This information will also be informative for researchers who wish to contribute to drug class reviews on these medications as new evidence emerges, and for decision-makers who will need to consider new evidence during future formulary reviews and updates on this drug class.S1 Appendix(PDF)Click here for additional data file.S2 Appendix(PDF)Click here for additional data file.S3 Appendix(PDF)Click here for additional data file.S4 Appendix(PDF)Click here for additional data file.S1 Table(PDF)Click here for additional data file.S2 Table(PDF)Click here for additional data file.S3 Table(PDF)Click here for additional data file.S4 Table(PDF)Click here for additional data file.S1 Fig(EMF)Click here for additional data file.


Qualitative approaches are one of several methodologies utilised within the social sciences. New developments within qualitative methods are widening the opportunities for using qualitative evidence to inform health policy and systems decisions. In this commentary, we discuss how, in our work with the World Health Organization (WHO), we have explored ways of broadening the types of evidence used to develop evidence-informed guidance for health systems.Health systems decisions are commonly informed by evidence on the effectiveness of health system interventions. However, decision makers and other stakeholders also typically have additional questions, including how different stakeholders value different outcomes, the acceptability and feasibility of different interventions and the impacts of these interventions on equity and human rights. Evidence from qualitative research can help address these questions, and a number of WHO guidelines are now using qualitative evidence in this way. This growing use of qualitative evidence to inform decision making has been facilitated by recent methodological developments, including robust methods for qualitative evidence syntheses and approaches for assessing how much confidence to place in findings from such syntheses. For research evidence to contribute optimally to improving and sustaining the performance of health systems, it needs to be transferred easily between different elements of what has been termed the ‘evidence ecosystem’. This ecosystem includes primary and secondary evidence producers, guidance developers and those implementing and evaluating interventions to strengthen health systems. We argue that most of the elements of an ecosystem for qualitative evidence are now in place – an important milestone that suggests that we are entering a new era for qualitative research. However, a number of challenges and constraints remain. These include how to build stronger links between the communities involved in the different parts of the qualitative evidence ecosystem and the need to strengthen capacity, particularly in low and middle income countries, to produce and utilise qualitative evidence and decision products informed by such evidence. We invite others who want to support the wider use of qualitative evidence in decision processes to look for opportunities in their settings to put this into practice. The growing use of qualitative evidence to support decisions, and the availability of methods that can help us use this type of evidence in knowledge-to-action cycles , 2, suggHealth systems are complex, creating challenges for decision makers aiming to strengthen these systems and achieve the Sustainable Development Goals . Most stIn our work with the World Health Organization (WHO) we have explored ways of broadening the types of evidence that are used to develop health systems guidance , 8. WhilOne example of the use of qualitative evidence to inform WHO guidance is the recent set of WHO recommendations on ‘Antenatal care for a positive pregnancy experience’ . These iThe growing use of qualitative evidence to inform decision making has been facilitated by a number of key developments in the field, including better standards for reporting primary qualitative studies , 23; robFor research evidence to contribute optimally to improving and sustaining the performance of health systems, it needs to be transferred easily between different elements of what has been termed the ‘evidence ecosystem’ –33. ThisHaving the elements of a qualitative evidence ecosystem in place is an important milestone and suggests that we are entering a new and exciting era within the field of qualitative research. Of course, a number of challenges and constraints remain, as we have noted earlier. Other challenges include how to build stronger links between the communities involved in the different parts of the qualitative evidence ecosystem, including across all sectors relevant to the Sustainable Development Goals , and theAs we take this work forward, we should also not forget what is perhaps the most important role that qualitative evidence can play in decision-making: representing the views and experiences of stakeholders, including vulnerable and marginalised groups who are often not represented directly. By drawing on the global body of qualitative evidence, qualitative evidence syntheses have the potential, when used together with direct stakeholder engagement, to help ensure that decisions are guided by stakeholders’ views and that these decisions do not widen inequities. As we have noted elsewhere, using qualitative evidence in this way may also contribute to increased transparency and accountability in public decision-making .Our experiences of working with the WHO have taught us that the best way of learning is doing. We support Health Systems Global’s efforts to promote both primary and secondary social science research on health policies and systems, and to strengthen capacity and collaborations in this area . However


To provide resource-stratified, evidence-based recommendations on the treatment and follow-up of patients with early-stage colorectal cancer.ASCO convened a multidisciplinary, multinational Expert Panel that reviewed existing guidelines and conducted a modified ADAPTE process and a formal consensus process with additional experts for one round of formal ratings.Existing sets of guidelines from 12 guideline developers were identified and reviewed; adapted recommendations from six guidelines form the evidence base and provide evidence to inform the formal consensus process, which resulted in agreement of 75% or more on all recommendations.www.asco.org/resource-stratified-guidelines.For nonmaximal settings, the recommended treatments for colon cancer stages nonobstructing, I-IIA: in basic and limited, open resection; in enhanced, adequately trained surgeons and laparoscopic or minimally invasive surgery, unless contraindicated. Treatments for IIB-IIC: in basic and limited, open en bloc resection following standard oncologic principles, if not possible, transfer to higher-level facility; in emergency, limit to life-saving procedures; in enhanced, laparoscopic en bloc resection, if not possible, then open. Treatments for obstructing, IIB-IIC: in basic, resection and/or diversion; in limited or enhanced, emergency surgical resection. Treatment for IIB-IIC with left-sided: in enhanced, may place colonic stent. Treatment for T4N0/T3N0 high-risk features or stage II high-risk obstructing: in enhanced, may offer adjuvant chemotherapy. Treatment for rectal cancer cT1N0 and cT2n0: in basic, limited, or enhanced, total mesorectal excision principles. Treatment for cT3n0: in basic and limited, total mesorectal excision, if not, diversion. Treatment for high-risk patients who did not receive neoadjuvant chemotherapy: in basic, limited, or enhanced, may offer adjuvant therapy. Treatment for resectable cT3N0 rectal cancer: in enhanced, base neoadjuvant chemotherapy on preoperative factors. For post-treatment surveillance, a combination of medical history, physical examination, carcinoembryonic antigen testing, imaging, and endoscopy is performed. Frequency depends on setting. Maximal setting recommendations are in the guideline. Additional information can be found at It is the view of the American Society of Clinical Oncology that health care providers and health care system decision makers should be guided by the recommendations for the highest stratum of resources available. The guidelines are intended to complement but not replace local guidelines. The purpose of this guideline is to provide expert guidance on the treatment and post-treatment follow-up of patients with early-stage colorectal cancer to clinicians, public health leaders, and policymakers in all resource settings. The target population is people with early-stage colorectal cancer .1 Fifty-two percent of deaths resulting from colorectal cancer occur in these less developed regions.Historically, some of the highest incidence rates have been in so-called more-developed regions, including North America, Australia, New Zealand, Western Europe, Japan, and South Korea. However, approximately 45% of incident colorectal cancers in men and women occur in less developed regions (the definition of which often overlaps with the definition of low- and middle-income countries around the world and represent 9% to 10% of cancers among people in those regions).2 Different regions of the world, both among and within countries, differ with respect to access to early detection.  As a result of these disparities, the ASCO Resource-Stratified Guidelines Advisory Group chose colorectal cancer as a priority topic for guideline development.These numbers are increasing around the world .ASCO has established a process for resource-stratified guidelines, which includes mixed methods of guideline development, adaptation of the clinical practice guidelines of other organizations, and formal expert consensus. This article summarizes the results of that process and presents the practice resource-stratified recommendations, which are based in part on formal expert consensus and adaptation from existing guidelines  What is the optimal treatment of patients with colon cancer clinical stages I-IIIC in high-incidence and resource-constrained settings? (2) What is the optimal treatment of patients with rectal cancer stages I-III? (3) What are the optimal strategies for post-treatment surveillance for patients treated for early colorectal cancer?These recommendations were developed by an Expert Panel with multinational and multidisciplinary representation and with a patient representative and an ASCO guidelines staff member with health research methodology expertise Appendix . The Exp5 and consensus processes used together as an alternative to de novo guideline development for this guideline. Adaptation of guidelines is considered by ASCO in selected circumstances when one or more quality guidelines from other organizations already exist on the same topic. The objective of the ADAPTE process is to take advantage of existing guidelines to enhance efficient production, reduce duplication, and promote the local uptake of quality guideline recommendations.This guideline adaptation was also informed by the ADAPTE methodology6 The methodological review was completed by ASCO senior guideline staff (Methodology Supplement). The content review was completed by the ASCO Expert Panel.ASCO’s adaptation and formal consensus processes begin with a literature search to identify candidate guidelines for adaptation. Adapted guideline manuscripts are reviewed and approved by the Clinical Practice Guidelines Committee. The review includes two parts: methodological review and content review.7 Detailed information about the methods used to develop this guideline is available in the Methodology Supplement and Data Supplement at www.asco.org/resource-stratified-guidelines.The guideline recommendations were crafted, in part, using the Guidelines Into Decision Support (GLIDES) methodology and accompanying BRIDGE-Wiz software.The ASCO Expert Panel and guidelines staff will work with co-chairs to keep abreast of any substantive updates to the guideline. On the basis of formal review of the emerging literature, ASCO will determine the need to update.www.asco.org/esource-stratified-guidelines. All funding for the administration of the project was provided by ASCO.This is the most recent information as of the publication date. For updates, the most recent information, and to submit new evidence, please visit The clinical practice guidelines and other guidance published herein are provided by the American Society of Clinical Oncology, Inc. (“ASCO”) to assist providers in clinical decision making. The information therein should not be relied upon as being complete or accurate, nor should it be considered as inclusive of all proper treatments or methods of care or as a statement of the standard of care. With the rapid development of scientific knowledge, new evidence may emerge between the time information is developed and when it is published or read. The information is not continually updated and may not reflect the most recent evidence. The information addresses only the topics specifically identified therein and is not applicable to other interventions, diseases, or stages of diseases. This information does not mandate any particular course of medical care. Further, the information is not intended to substitute for the independent professional judgment of the treating provider, as the information does not account for individual variation among patients. Recommendations reflect high, moderate or low confidence that the recommendation reflects the net effect of a given course of action. The use of words like “must,” “must not,” “should,” and “should not” indicate that a course of action is recommended or not recommended for either most or many patients, but there is latitude for the treating physician to select other courses of action in individual cases. In all cases, the selected course of action should be considered by the treating provider in the context of treating the individual patient. Use of the information is voluntary. ASCO provides this information on an “as is” basis, and makes no warranty, express or implied, regarding the information. ASCO specifically disclaims any warranties of merchantability or fitness for a particular use or purpose. ASCO assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of this information or for any errors or omissions.http://www.asco.org/rwc). All members of the Expert Panel completed ASCO’s disclosure form, which requires disclosure of financial and other interests, including relationships with commercial entities that are reasonably likely to experience direct regulatory or commercial impact as a result of promulgation of the guideline. Categories for disclosure include employment; leadership; stock or other ownership; honoraria, consulting or advisory role; speaker's bureau; research funding; patents, royalties, other intellectual property; expert testimony; travel, accommodations, expenses; and other relationships. In accordance with the Policy, the majority of the members of the Expert Panel did not disclose any relationships constituting a conflict under the Policy.The Expert Panel was assembled in accordance with ASCO’s Conflict of Interest Policy Implementation for Clinical Practice Guidelines , Cochrane Systematic Review, and National Guideline Clearinghouse (NGC) databases were searched for guidelines, systematic reviews, and meta-analyses published between 1966 and 2017 (2012 and 2017 for guidelines). Inclusion criteria identified publications that (1) were on the treatment of early-stage colon and early-stage rectal cancer, (2) developed by multidisciplinary content experts as part of a recognized organizational effort, and (3) published between 1966 and 2017. Searches for cost-effectiveness analyses were also conducted. Articles were excluded from the systematic review if they were (1) meeting abstracts or (2) books, editorials, commentaries, letters, news articles, case reports, or narrative reviews. After initial searches of primary literature, the panel leadership decided to primarily use guidelines to inform expert consensus. Searches for cost-effectiveness analyses were also conducted separately.As part of the systematic literature review, PubMed, Standards and Guidelines Evidence directory ,10 UK National Institute for Clinical Excellence (NICE),11 European Society for Medical Oncology (ESMO),12 and the ASCO endorsement of the CCO guideline.13 Appendix A total of 40 guidelines were found in the literature search, and 12 were reviewed in-depth for their currency, content, and methodology . On the basis of content and methodology reviews (the latter by either ASCO or NGC), the Expert Panel chose six evidence-based guidelines from five public health authorities/guideline developers: Society of American Gastrointestinal and Endoscopic Surgeons (SAGES),This ASCO guideline reinforces selected recommendations offered in the SAGES evidence-based guidelines for the laparoscopic resection of curable colon and rectal cancer and the National Guideline Alliance/NICE, ESMO, ASCO, and ASCR guidelines. This guideline also acknowledges the effort put forth by the authors and the aforementioned societies to produce evidence-based and/or consensus-based guidelines informing practitioners and institutions who provide guidance on colorectal cancer care and post-treatment follow-up of patients and caregivers.The identified guidelines were published between 2012 and 2017. If the NGC had not formally reviewed the methodology of a given guideline, ASCO used the AGREE II instrument. The Data Supplement includes an overview of these guidelines, including information on the clinical questions, target populations, development methodology, and key evidence.8 The NICE guideline population included adults (defined as 18 years of age and older) with surgically resectable colorectal cancer with newly diagnosed adenocarcinoma of the colon or the rectum or with relapsed adenocarcinoma of the colon or rectum.11 The NICE guideline focused on the effectiveness, including cost-effectiveness of laparoscopic surgery .14 Selected clinical questions relevant to this ASCO guideline included those on the sequence of treatments, indications for surgery, neoadjuvant chemotherapy (NACT), and adjuvant treatment for patients with stages I-III colon cancer and stages I-III rectal cancer.The maximal resource-level settings guidelines adapted in part by ASCO are listed in Appendix 12 ASCR used an organized search to address treatment issues for patients with rectal cancer.10 Clinical questions were not explicitly stated, and limited information on the guideline methodology was included within either guideline (ESMO has separate publications on its development methods).For the treatment of patients with early rectal cancer, this guideline used ASCR and ESMO guidelines as well as consensus to inform the recommendations. Clinical questions were not explicitly stated in the ESMO guideline; the studies it included reported on efficacy and toxicity outcomes. The ESMO guideline concerns various potential treatment modalities, including surgery, chemotherapy, and radiation.13 The primary clinical questions concerned benefits, test properties, and adverse events.For follow-up, this guideline refers to the ASCO endorsement of the CCO guideline and to the ESMO 2017 rectal cancer guideline.The SAGES guideline used a systematic literature review and rated recommendations with Grading of Recommendations Assessment, Development and Evaluation (GRADE). Evidence tables were not included. This guideline received a rating of 50% on the AGREE II from ASCO (Methodology Supplement).The NICE guideline met the 2013 NGC criteria, which ASCO used as a proxy for quality guidelines. The key evidence includes systematic reviews, meta-analyses, randomized clinical trials (RCTs), and case series, and the assessment methods included GRADE. The developers noted that there were limited high-quality studies comparing multiple interventions.The ESMO rectal cancer guideline methods included an ISDA-based method for grading evidence and received a 38% AGREE II score from ASCO. The ASCR rectal cancer guideline used GRADE and had a 43% AGREE II score from ASCO. The NGC reviewed the ASCR guideline but found that it did not meet 2013 NGC criteria. However, given the paucity of guidance on the treatment of patients with rectal cancer, the Expert Panel opted to use the ASCR guideline as part of the evidence base. The ASCO guideline endorsement of the CCO guideline on post-treatment follow-up was based on a systematic review of 11 other guidelines that CCO found concurred.The outcomes/end points in most studies reviewed by the adapted guidelines include efficacy ; quality of life; safety/adverse events; and, in some, cost-effectiveness.The methodological review of the guidelines was completed by two ASCO guideline staff members using the Rigor of Development subscale of the AGREE II instrument . The score for the Rigor of Development domain is calculated by summing the scores across individual items in the domain and standardizing the total score as a proportion of the maximum possible score. Detailed results of the scoring and the AGREE II assessment process for this guideline are available in the Methodology Supplement.The recommendations were developed by a multinational, multidisciplinary group of experts using evidence from existing guidelines and clinical experience as a guide. The ASCO Expert Panel underscores that health care practitioners who implement the recommendations presented in this guideline should first identify the available resources in their local and referral facilities and endeavor to provide the highest level of care possible with those resources.What is the optimal treatment of patients with colon cancer clinical stages I-IIIC in high-incidence and resource-constrained settings?15; any one of the following characteristics would be considered high risk and generally applies to stage II colon tumors: extramural vascular invasion, grade 3/poorly differentiated tumors, T4 stage/perforation, obstructive tumors, mucinous tumors, examination of fewer than 12 lymph nodes, and tumor budding. Overall, there is limited evidence on the relationship of these characteristics with risk, and evaluation of risk of recurrence in basic and limited settings may be challenging.The definition of high risk for recurrence in this guideline was defined by the NICE evidence-based review (NICE 2011)Most local and locally advanced colon cancer is treated with surgery. The primary types of surgery are laparoscopic and open resection. The choice of which surgery is performed depends on the tumor characteristics, the local infrastructure, and surgical expertise. Patients with stage III tumors and some patients with high-risk stage II tumors may be eligible for chemotherapy following surgery, where chemotherapy is available. The results of the surgical pathology evaluation may affect the initial clinical staging classification and is one of the main factors driving adjuvant therapy decisions; a second important factor is the availability of chemotherapy itself. Therefore, the resource setting is an important factor in determining the type of treatment.The primary treatment of patients with colon cancer stages I-IIA is surgery to remove the cancer and draining nodal stations according to standard oncologic principles . Advance16 As in many systematic reviews, there was heterogeneity in elements, such as time of follow-up.The recommendations on surgery are based on NICE and SAGES recommendations. The NICE guideline was based on a 2006 (subsequently affirmed) evidence review of 19 RCTs and an unpublished individual patient meta-analysis.16 It is important to prioritize the goals of surgery. Good quality resection of the tumor is the primary goal. If providers can achieve this with a minimally invasive approach without changing the quality or the nature of the operation, then the patient would benefit from a minimally invasive approach, which the NICE guideline supports  based on evidence reviewed in 2006 and re-reviewed in 2010 in a guidance the main NICE guideline cites.16For settings with a clinician who is a surgical oncologist and/or colorectal surgeon with adequate training in laparoscopic techniques, laparoscopy is preferred because of decreased length of stay in the hospital. Other benefits, with less strong evidence, may include decreased surgical mortality. Risks include anastomotic leakage and conversion to open resection. The provision of the laparoscopic approach is more likely in maximal and enhanced settings. In basic and limited settings, open resection may be more appropriate; both have very similar clinically relevant outcomes according to NICE. The NICE guideline presents both options and found that efficacy outcomes were not statistically significantly different, for example, in three RCTS assessing the risk of mortality during and 30 days after surgery.During the informal consensus process, the Expert Panel discussed that patients would benefit more from having an en bloc resection performed in a facility where this was possible rather than having an incomplete (margin-positive or adjacent organs not included) resection at the lower-level facility unless it was an emergency .These recommendations are based on the SAGES and NICE guidelines. SAGES, which focuses on laparoscopy, recommends en bloc surgery for locally advanced adherent colon and rectal tumors , with weak evidence. There are no RCTs according to SAGES.Similar surgical principles for locally advanced (nonobstructing T4N0) tumors apply as in early stages of disease, with the primary aim of treatment to remove the tumor with negative resection margins. With locally advanced colon tumors with local invasion of other structures, this guideline recommends an en bloc resection. Clinicians should tailor the surgical approach based on the available expertise and technology. In basic and limited settings, if an en bloc resection to completely remove the malignancy is not possible, patients should be transferred to a facility where this is possible. In more well-resourced settings, the minimally invasive resection is preferred if technically feasible, and there may be a role for additional local-regional therapy  to assist in clearing the margin to reduce the risk of local-regional recurrence. In more technologically advanced settings, this guideline prefers the minimally invasive resection if it is technically feasible.As with nonobstructing tumors, the main treatment of patients with obstructing colonic lesions is surgery . However8In the maximal and enhanced settings, more-advanced local infrastructure and training play a role in surgical decision making. Specialty-trained surgical oncologists and/or colorectal surgeons are more common and available. With this increase in surgical expertise, an en bloc tumor resection should be safely performed without compromising oncologic principles. In the maximal setting, surgeons can perform surgery using the most advanced techniques, such as the laparoscopic approach, provided that they have adequate surgical expertise and oncologic principles are maintained. If resection is not feasible (see oncologic principles in previous paragraph), in addition to the option of diversion, for left-sided lesions, the surgical oncologist or colorectal surgeon may place or request the placement of a colonic stent as a temporizing measure. Although the evidence is weak, stenting may increase the likelihood of completing a one-stage procedure and may decrease the likelihood of an end colostomy.As in the nonobstructing scenario, the goal of surgery is complete removal of the tumor. However, the approach to resection should be tailored to the urgency of the clinical situation, the patient’s condition, the surgeon’s technical ability, and the available infrastructure and/or resources. While there is no specific literature to guide treatment in low-resource settings, these recommendations are based on the NICE, SAGES, and ASCR guidelines, as an obstructing colorectal tumor is a universally encountered problem. The NICE guideline makes specific recommendations regarding obstructing tumors and discusses stents; the guideline also addresses emergency situations. Colonic stents are given as an option in enhanced and maximal settings with appropriately trained and experienced clinicians, with the caveat that high-quality evidence of benefits that outweighs surgery was not available . For example, searches to inform the NICE question on colonic stents 3.2.1 found no direct evidence, even when they looked for the use of stents in palliative or emergency studies. Of the few and low-quality data found, there were no overall survival differences.For both obstructing tumors and tumors with invasion of other organs, multidisciplinary management is key, and the potential of using chemotherapy to downsize the tumor to make surgical resection more feasible should be discussed by the team.In basic and limited settings, a temporizing procedure may be most appropriate, whereas in a maximal setting, minimally invasive techniques, such as laparoscopy and robotic surgery, may be attempted insofar as oncologic principles are maintained. Temporizing procedures occur when a patient presents as an emergency , but surgeons cannot perform the definitive procedure that needs to be done for various reasons . Instead, a surgery is performed to relieve the obstruction, which provides the provider and patient with time to pursue other avenues .These recommendations are applicable to enhanced and maximal resource settings .15 An earlier ASCO guideline recommended clinical trials for this population.17The recommendations are based on NICE guidelines for patients with high-risk stage II colon cancer in whom adjuvant therapy is “considered.” NICE conducted an evidence review and found limited low-quality data, including pooled data; observational data; and limited RCT data.17 Although there are several tumor characteristics that are associated with a worse prognosis with stage II disease, there is no standard definition of high-risk stage II colon cancer as defined by the NICE evidence-based review15; any one of the following characteristics would be considered high risk: extramural vascular invasion, grade 3/poorly differentiated tumors, T4 stage/perforation, obstructive tumors, mucinous tumors, fewer than 12 lymph nodes harvested, and tumor budding. Because of the lack of data directly addressing the value of adjuvant therapy in patients with high-risk stage II colon cancer and the modest effect of adjuvant therapy in patients with standard-risk stage II disease, we suggest that patients with microsatellite stable/mismatch repair–proficient high-risk stage II colon cancer may receive adjuvant chemotherapy in the advanced and maximal settings after discussion of the risks and benefits with the patient.15 In these situations, mismatch repair or microsatellite instability assessment is necessary (where available) because it may influence decisions on adjuvant therapy, particularly for patients with stage II colon cancer. For more information on biomarkers in GI cancer, see the American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology, ASCO guideline on molecular biomarkers for the evaluation of colorectal cancer.18There is intermediate-strength data of moderate quality that suggests that patients with high-risk stage II colon cancer have a survival benefit with adjuvant chemotherapy.22 More recent data have examined the duration of adjuvant therapy, suggesting that for some tumors , 3 months of combination therapy, specifically with the combination of capecitabine and oxaliplatin, may be equivalent to 6 months in the adjuvant setting; however, this question is not yet settled.19 It is outside the scope of this resource-stratified guideline to review the comparative chemotherapy agent data , and clinicians in resource-constrained settings should be guided by national availability of agents, cost/patient finances, and clinician expertise in managing the administration and adverse effects of these agents regarding available effective agents. It is however recognized that there are significant ramifications of this discussion in basic and limited settings. For example, although it may be much easier and cost effective to receive 3 months of therapy that includes an oral medication than an alternative regimen for 6 months, the cost of the drug may not be equivalent, and thus, the decision to receive adjuvant therapy, which regimen, and what duration needs to be weighed against region-specific feasibility. The resources for the treatment of patients with stage III colon cancer are primarily in the maximal and enhanced settings; however, because this guideline does recommend further treatment in these settings, clinicians may explore using them in basic and limited settings as well. The caveats are availability of the medication and expertise in administrating the medication . The costs involved may require modifying the treatment regimen.Patients with stage III colon cancer should receive adjuvant chemotherapy in the enhanced and maximal settings based on the NICE recommendation for adjuvant chemotherapy for patients with stage III colon cancer. While the NICE guideline recommended specific agents , there is more recent evidence, from studies suggested by Panel members rather than found by systematic review, that the adjuvant therapy for patients with stage III include a combination chemotherapy regimen of fluoropyrimidine and oxaliplatin.What is the optimal treatment of patients with rectal cancer stages I-III?Surgery is the primary treatment modality of early rectal cancer. Following the principle of total mesorectal excision (TME) is critical to achieve a good outcome in patients with rectal cancer. In basic and limited resource settings, this may need to be done with the best expertise available in that setting. Local general surgeons may do this if they understand and have been trained in TME. Local excision may be appropriate in certain situations. However, basic and limited local settings may not have the necessary infrastructure and expertise to select patients for local excision. In enhanced and maximal settings, the guideline recommends a surgeon with training and expertise in rectal cancer surgery. If the technology and expertise are available, clinicians may pursue minimally invasive approaches in these settings , and 8.9 The ASCR laparoscopic TME recommendation was based on two RCTs, a meta-analysis, and some  prospective trials, and the authors noted the need for more RCT results; the ESMO guideline does not explicitly recommend laparoscopic surgery. The evidence is not fleshed out in the ASCR guideline for TME . The ESMO transanal endomucosal microsurgery (TEM) and TME recommendations were based on prospective cohort studies, and they rated them both IIIA  .)”]12[p6]).These recommendations are largely based on the ASCR and ESMO guidelines. The ASCR surgical recommendations reflect a range of quality of evidence, including lack of RCT evidence; however, they rated the TME recommendation as high quality. For laparoscopy, they note that there is less high-quality evidence than for patients with colon cancer.24 Surgery by the TME approach has been proven to minimize the risk of local-regional recurrence. These good-risk cT3 rectal tumors are defined by the ESMO 2013 evidence-based guideline as follows: cT3a (< 1-mm invasion into the subserosa) without involvement of the mesorectal fascia and higher in the rectum (above the levator muscles). When all of these features of the tumor are met, TME surgery without neoadjuvant chemoradiation is recommended.Recommendations on chemotherapy and radiation start at 2.9 . An impo25 In this case, NACT alone (without neoadjuvant chemoradiation) is not recommended due to a lack of evidence. This recommendation will be revisited depending on emerging evidence. Advanced radiographic imaging may also not be available either, thereby limiting the ability to distinguish between low- and high-risk rectal cancer. Consequently, patients and clinicians in these settings should proceed to TME resection if imaging is available to determine resectability. The Expert Panel notes that surgical pathology evaluation may upstage some patients , and this may inform treatment decisions regarding adjuvant therapy. Following resection, patients who have pathologic higher-risk disease should receive adjuvant chemotherapy preferably with radiation, if available.However, radiation therapy and/or advanced imaging, such as magnetic resonance imaging, is not available or has limited availability in basic and limited settings.9 Potential risks include sexual morbidity and GI adverse events. When TME is not feasible , the role of chemotherapy with radiation in reducing the risk of local-regional recurrence is greater. For all patients who have undergone NACT with radiation therapy, postoperative chemotherapy is recommended,12 extrapolating largely from the colon cancer adjuvant data. A full discussion of adjuvant therapy following neoadjuvant chemoradiation and surgery for rectal cancer is beyond the scope of this resource-stratified guideline.Potential benefits of neoadjuvant therapy include lowering the risk of local recurrence.12(page iv31) because there was lower evidence of benefits outweighing risks.These recommendations on neoadjuvant and/or adjuvant therapy are largely based on the ASCR and ESMO guidelines. The neoadjuvant therapy recommendations are based on ASCR , citing two trials on radiation and one on chemoradiation, one small comparison of the two approaches, and one trial comparing neoadjuvant and adjuvant chemoradiation ; some were phase II trials. Therefore, ASCO would not likely call this high-quality evidence in a non–resource-stratified guideline. ASCR cites two Cochrane reviews on neoadjuvant therapy, so perhaps one could say that there is insufficient evidence on optimal sequencing for neoadjuvant therapy. The ESMO guideline states that “NACT alone is not recommended for the treatment of localised, non-metastatic disease outside clinical trials”For adjuvant chemoradiation, ASCR rates this 1B  and cites several RCTs, albeit commenting that they have limitations. For chemotherapy alone for patients who received neoadjuvant therapy, ASCR rates its recommendation 1A but does not review the evidence. The ESMO guideline states that when patients have not received neoadjuvant radiation therapy and have a high risk of recurrence, adjuvant chemoradiation is an option in selected cases, depending on postsurgical tests (with 1A rating). ESMO refers to trials and meta-analyses as evidence.What are the optimal strategies for post-treatment surveillance for patients treated for early colorectal cancer?The recommendations for follow-up for colon cancer are listed in There are multiple existing guidelines from maximal resource settings on follow-up. The recommendations that were adapted here, primarily to provide guidance to limited and basic settings, are based on the 2013 ASCO guideline endorsement of the CCO follow-up surveillance and secondary prevention . This endorsement was for patients with stage II and III colorectal cancer. There is a paucity of data on follow-up for patients with stage I colorectal cancer. In this resource-stratified guideline, therefore, the recommendations for the follow-up of patients with stage I were based on expert consensus due to the lack of evidence on this topic. The original CCO guideline was based on 11 other guidelines. The population covered was focused on survivors of stage II and III colorectal cancer. The recommendations for basic and limited settings are based on the probable lack of colonoscopy. In cases where a complete colonoscopy was not done at the time of diagnostic work-up, a colonoscopy should be done as soon as reasonable after completion of adjuvant therapy and not necessarily at the 1- to 2-year time point. In the basic setting, if colonoscopy is unavailable, clinicians may perform a double-contrast barium enema and/or for left-sided tumors, a sigmoidoscopy.28In the context of these guidelines, the Expert Panel recognizes that because these guidelines are applicable in many different cultures, cultural sensitivities are particularly important when communicating with patients and families regarding decisions based on either chronologic or functional age. It is not within the scope of this guideline to give this discussion the space it deserves, and the reader is referred to ASCO’s Practical Assessment and Management of Vulnerabilities in Older Patients Receiving Chemotherapy guideline; ASCO’s resource-stratified practice guideline on palliative care, specifically regarding spiritual assessment; and ASCO’s Patient-Clinician Communication guideline.26(p2326) as well as to assess life expectancy.26Although this guideline recommends chemotherapy regardless of age, age can be a factor in clinician-patient decision making. Chronologic age is mentioned in the follow-up recommendations based on existing guidelines. However, chronologic age may not be sufficient for decision making, and the Expert Panel encourages clinicians to use functional age. The Expert Panel would like to emphasize that life expectancy and underlying health status are important to assess and take into consideration in discussions with family and caregivers regarding chemotherapy. ASCO’s Practical Assessment and Management of Vulnerabilities in Older Patients Receiving Chemotherapy guideline states, “In patients ≥ 65 years receiving chemotherapy, geriatric assessment (GA) should be used to identify vulnerabilities that are not routinely captured in oncology assessments,”An ASCO literature search focusing on high-quality systematic reviews of published cost-effectiveness analyses in low-resource settings was conducted, and none were found. The Guideline Panel identifies the need for cost-effective analyses of the treatment of patients with early-stage colorectal cancer from low-resource settings.There were limitations of the evidence to inform some of the recommendations. There were limited published data on:Most studies were conducted with populations in high-resource settings.Treatment of patients with nonobstructing colon cancer stages IIB-IIC (T4N0), including the role for additional local-regional therapyWeak evidence on stenting of patients with colon cancer stages IIB-IIC obstructingSpecific literature to guide treatment in low-resource settings of patients with colon cancer stages IIB-IIC: T4N0 obstructing or T3N0 obstructingValue of adjuvant therapy in patients with high-risk stage II colon cancerTreatment of patients with rectal cancer stages I-III, especially with laparoscopic approachesRefining duration of adjuvant therapyCost-effectiveness research and modeling19 suggests that in some patients, 3 months of adjuvant therapy may be adequate. There is a large US intergroup study examining the role of radiation for more proximal rectal tumors . Further studies on the role of total neoadjuvant therapy are being developed, bolstered by the high pathologic complete response rates in phase II studies.29 These studies will help to define further the adjuvant treatment of localized colorectal cancer. In addition, future studies that tailor therapy based on molecular profiles of tumors may further refine our treatments.Refining adjuvant therapy is an ongoing research effort. For example, the large IDEA studyTherefore, the Expert Panel suggests that research, especially RCTs, be conducted and/or completed on the topics for which there are currently insufficient data.ASCO believes that cancer and cancer prevention clinical trials are vital to inform medical decisions and improve cancer care and that all patients should have the opportunity to participate.www.asco.org/resource-stratified-guidelines. Patient information is available there and at www.cancer.net.Additional Information including data supplements, evidence tables, and clinical tools and resources can be found at http://ascopubs.org/doi/10.1200/JGO.18.00026)27Palliative Care in the Global Setting: ASCO Resource-Stratified Practice Guideline (http://ascopubs.org/doi/10.1200/JCO.2017.75.2311)28Patient-Clinician Communication: American Society of Clinical Oncology Consensus Guideline (http://ascopubs.org/doi/10.1200/JGO.18.00213)Early Detection for Colorectal Cancer: ASCO Resource-Stratified Practice Guideline (