How should we set consumption thresholds for low risk drinking guidelines? Achieving objectivity and transparency using evidence,expert judgement and pragmatism

Most high‐income nations issue guidelines on low‐risk drinking to inform individuals’ decisions about alcohol consumption. However, leading scientists have criticized the processes for setting the consumption thresholds within these guidelines for a lack of objectivity and transparency. This paper examines how guideline developers should respond to such criticisms and focuses particularly on the balance between epidemiological evidence, expert judgement and pragmatic considerations. Although concerned primarily with alcohol, our discussion is also relevant to those developing guidelines for other health‐related behaviours. We make eight recommendations across three areas. First, recommendations on the use of epidemiological evidence: (1) guideline developers should assess whether the available epidemiological evidence is communicated most appropriately as population‐level messages (e.g. suggesting reduced drinking benefits populations rather than individuals); (2) research funders should prioritize commissioning studies on the acceptability of different alcohol‐related risks (e.g. mortality, morbidity, harms to others) to the public and other stakeholders; and (3) guideline developers should request and consider statistical analyses of epidemiological uncertainty. Secondly, recommendations to improve objectivity and transparency when translating epidemiological evidence into guidelines: (4) guideline developers should specify and publish their analytical framework to promote clear, consistent and coherent judgements; and (5) guideline developers’ decision‐making should be supported by numerical and visual techniques which also increase the transparency of judgements to stakeholders. Thirdly, recommendations relating to the diverse use of guidelines: (6) guideline developers and their commissioners should give meaningful attention to how guidelines are used in settings such as advocacy, health promotion, clinical practice and wider health debates, as well as in risk communication; (7) guideline developers should make evidence‐based judgements that balance epidemiological and pragmatic concerns to maximize the communicability, credibility and general effectiveness of guidelines; and (8) as with scientific judgements, pragmatic judgements should be reported transparently.     

2019 Chinese Clinical Practice Guidelines for the Prevention of Mother-to-child Transmission of Hepatitis B Virus

To develop the evidence-based guidelines for managing mother-to-child transmission of hepatitis B virus in China, a multidisciplinary guideline development group was established. Clinical questions were identified from two rounds of surveys on the concerns of first-line clinicians. We conducted a comprehensive search and review of the literature. A grading of recommendations’ assessment, development, and evaluation system was adopted to rate the quality of evidence and the strength of recommendations. Recommendations were formulated based on the evidence, overall balance of benefits and harms (at individual and population levels), patient/health worker values and preferences, resources available, cost-effectiveness, and feasibility. Eventually, recommendations related to 13 main clinical concerns were developed, covering diagnostic criteria, treatment indications, antiviral therapy choice, timing to initiate and discontinue treatment, immunoprophylaxis strategy at birth, and how to deal with special situations, such as unintended pregnancy, assisted reproduction, and breastfeeding. The guidelines are intended to serve as guidance for clinicians and patients, to optimize the management of majority of pregnant women who are positive for hepatitis B surface antigen. Guideline registration: International Practice Guide Registration Platform (IPGRP-2018CN040).     

A Framework for Crafting Clinical Practice Guidelines that are Relevant to the Care and Management of People with Multimorbidity

Many patients of all ages have multiple conditions, yet clinicians often lack explicit guidance on how to approach clinical decision-making for such people. Most recommendations from clinical practice guidelines (CPGs) focus on the management of single diseases, and may be harmful or impractical for patients with multimorbidity. A major barrier to the development of guidance for people with multimorbidity stems from the fact that the evidence underlying CPGs derives from studies predominantly focused on the management of a single disease. In this paper, the investigators from the Improving Guidelines for Multimorbid Patients Study Group present consensus-based recommendations for guideline developers to make guidelines more useful for the care of people with multimorbidity. In an iterative process informed by review of key literature and experience, we drafted a list of issues and possible approaches for addressing important coexisting conditions in each step of the guideline development process, with a focus on considering relevant interactions between the conditions, their treatments and their outcomes. The recommended approaches address consideration of coexisting conditions at all major steps in CPG development, from nominating and scoping the topic, commissioning the work group, refining key questions, ranking importance of outcomes, conducting systematic reviews, assessing quality of evidence and applicability, summarizing benefits and harms, to formulating recommendations and grading their strength. The list of issues and recommendations was reviewed and refined iteratively by stakeholders. This framework acknowledges the challenges faced by CPG developers who must make complex judgments in the absence of high-quality or direct evidence. These recommendations require validation through implementation, evaluation and refinement.     

Developing sexually transmitted disease guidelines in the USA and the UK

Management guidelines for sexually transmitted diseases are reviewed and updated every four years at a workshop of experts convened by the US Centers for Disease Control and Prevention. They are disseminated in paper and electronic formats, and are widely accessed. Their recommendations are graded according to quality of evidence, benefits versus harms, and applicability. In the UK, guidelines are commissioned by the Clinical Effectiveness Group, following a specific methodology, then modified after consultation within the specialty of genitourinary medicine. Some issues are problematic for both guidelines, notably areas where the evidence is weak, where diagnostics and treatments are changing rapidly, and in knowing the extent to which guidelines actually influence practice.     

Misconceptions, challenges, uncertainty, and progress in guideline recommendations

Although the quality of clinical practice guidelines has improved over the last decade, current guideline systems have limitations that reduce their validity and limit their acceptance. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) working group, a worldwide collaboration of guideline developers, methodologists, and clinicians, has constructed a system for developing guidelines that addresses these shortcomings. The system includes a transparent and rigorous methodology for rating the quality of evidence, an explicit balancing of benefits and harms of healthcare interventions, an explicit acknowledgement of the values and preferences that underlie the recommendations, and whether the intervention represents a wise use of resources. These four elements determine whether a recommendation is strong or weak. A guideline panel offers strong recommendations when virtually all informed patients would choose the same management strategy. Weak recommendations imply that choices will differ across the range of patient values and preferences. The GRADE system has been tested in multiple practice settings and for a large spectrum of questions, refined and re-evaluated to ensure that it captures the complex issues involved in evidence assessment and grading recommendations while maintaining simplicity and practicality. Many guideline organizations and medical societies have endorsed the system and adopted it for their guideline processes.     

A randomized trial of three videos that differ in the framing of information about mammography in women 40 to 49 years old

OBJECTIVE: To assess the effect of providing structured information about the benefits and harms of mammography in differing frames on women's perceptions of screening. DESIGN: Randomized control trial. SETTING: General internal medicine academic practice. PARTICIPANTS: One hundred seventy-nine women aged 35 through 49. INTERVENTION: Women received 1 of 3 5-minute videos about the benefits and harms of screening mammography in women aged 40 to 49. These videos differed only in the way the probabilities of potential outcomes were framed (positive, neutral, or negative). MEASUREMENTS AND MAIN RESULTS: We measured the change in accurate responses to questions about potential benefits and harms of mammography, and the change in the proportion of participants who perceived that the benefits of mammography were more important than the harms. Before seeing the videos, women's knowledge about the benefits and harms of mammography was inaccurate (82% responded incorrectly to all 3 knowledge questions). After seeing the videos, the proportion that answered correctly increased by 52%, 43%, and 30% for the 3 knowledge questions, respectively, but there were no differences between video frames. At baseline, most women thought the benefits of mammography outweighed the harms (79% positive frame, 80% neutral frame, and 85% negative frame). After the videos, these proportions were similar among the 3 groups (84%, 81%, 83%, P =.93). CONCLUSIONS: Women improved the accuracy of their responses to questions about the benefits and harms of mammography after seeing the videos, but this change was not affected by the framing of information. Women strongly perceived that the benefits of mammography outweighed the harms, and providing accurate information had no effect on these perceptions, regardless of how it was framed.     

Maximizing early treatment with biologics in patients with rheumatoid arthritis: the ultimate breakthrough in joints preservation

Rheumatoid arthritis (RA) is a chronic, systemic, progressive inflammatory disease that, if left untreated, can lead to irreversible joint damage and serious disability. In Central and Eastern Europe, RA treatment varies widely, partly due to economic factors, restrictive treatment guidelines, and access to practicing rheumatologists. The recent treatment paradigm shift of treating to target in RA with early, aggressive therapy has proven to be a successful strategy for achieving optimal clinical outcomes. Several clinical studies demonstrate that utilizing this strategy with anti-tumor necrosis factor biologics leads to improved clinical, radiographic, and functional outcomes. Patient education is also a critical component of the treating to target strategy, and the patient’s version of the treat-to-target recommendations is an important tool for successful implementation. This review discusses the evidence for the treat-to-target approach and describes areas to improve the disparity of treatment between patients in Western European compared with Central and Eastern European countries.     

Cardiovascular disease prevention in women: A rapidly evolving scenario

The past decade has witnessed a long overdue recognition of the importance of CVD in women, accompanied by an increasing awareness of gender differences in risk factors, natural history, preventive strategies, treatment, and prognosis of CVD. Reflecting the disease burden and the specific aspects of CVD in women, the American Heart Association has developed women-specific evidence-based guidelines and consensus documents for CVD prevention. The most recent update of these guidelines, published in 2011, is a milestone in the field and shows the rapidly evolving scenario of CVD prevention in women. We discuss some novel aspects of the 2011 update. The new guidelines change the focus from evidence-based to effectiveness-based, with consideration of both benefits and harms/costs of preventive interventions. The guidelines also introduce “ideal cardiovascular health” as the lowest category of risk, which implies the need of communitywide preventive, educational and policy initiatives to promote healthy lifestyles in the general population. Furthermore, the guidelines emphasize long-term overall CVD risk rather than short-term coronary risk. We also address several barriers and open questions in the evaluation and implementation of these guidelines, including how to increase the small proportion of women with ideal cardiovascular health; how to increase implementation and compliance with the recommendations; how to provide effectiveness-based recommendations for lifetime prevention goals based on short-term trials; how to obtain the best possible evidence in women; how to identify subgroups of women with different cardiovascular risk profiles or who may require tailored preventive strategies; and how to adapt current guidelines to international settings, particularly to low- and middle-income countries.     

Analysis of the ADA’s Standard of Diabetes Care Recommendation for Continuous Glucose Monitoring System

Transparency is a key factor to understand how recommendations were reached and to decide whether to adopt them or not. Currently, the American Diabetes Association (ADA) recommends the usage of real-time continuous glucose monitors in certain subgroups of people living with type 1 diabetes mellitus. In this commentary we sought to critically appraise this recommendation, mainly regarding the outcomes assessed, the evidence used for each outcome, and how the balance of benefits and harms was made. We found that the decision-making process followed to reach the ADA recommendation was not clear, and that the final recommendation does not seem to be supported in the assessed evidence.     

Guidelines on diagnosis,prognosis, and management of peripheral artery disease in patients with foot ulcers and diabetes (IWGDF 2019 update)

The International Working Group on the Diabetic Foot (IWGDF) has published evidence‐based guidelines on the prevention and management of diabetic foot disease since 1999. This guideline is on the diagnosis, prognosis, and management of peripheral artery disease (PAD) in patients with foot ulcers and diabetes and updates the previous IWGDF Guideline. Up to 50% of patients with diabetes and foot ulceration have concurrent PAD, which confers a significantly elevated risk of adverse limb events and cardiovascular disease. We know that the diagnosis, prognosis, and treatment of these patients are markedly different to patients with diabetes who do not have PAD and yet there are few good quality studies addressing this important subset of patients. We followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology to devise clinical questions and critically important outcomes in the patient‐intervention‐comparison‐outcome (PICO) format, to conduct a systematic review of the medical‐scientific literature, and to write recommendations and their rationale. The recommendations are based on the quality of evidence found in the systematic review, expert opinion where evidence was not available, and a weighing of the benefits and harms, patient preferences, feasibility and applicability, and costs related to the intervention. We here present the updated 2019 guidelines on diagnosis, prognosis, and management of PAD in patients with a foot ulcer and diabetes, and we suggest some key future topics of particular research interest.     

Do the benefits of participation in sport and exercise outweigh the negatives? An academic review

Public health campaigns promote regular exercise and physical activity. These campaigns are founded on global recommendations that a combination of aerobic and resistance exercise is required, on a weekly basis, to maximise physical and mental health. However, participation in all forms of sports and physical activity has inherent risks that need to be considered by both health practitioners making activity recommendations and the people participating. This review examines biological, psychological and social benefits and harms of the three highest participation physical activities: walking/running, multidirectional sports and resistance exercise. While the remaining evidence indicates that the positives do outweigh the negatives, it demonstrates that moderate amounts of exercise provide the most optimal balance and that potential harms are typically associated with low or high participation.     

Practice guidelines, a new reality in medicine. II. Methods of developing guidelines.

Current methods for developing practice guidelines include informal consensus development, formal consensus development, evidence-based guideline development, and explicit guideline development. Informal consensus development is the oldest and most common approach, but guidelines produced in this manner are often of poor quality and lack adequate documentation of methods. Formal consensus development uses a systematic approach to assess expert opinion and to reach agreement on recommendations. Evidence-based guideline development links recommendations directly to scientific evidence of effectiveness; rules of evidence are emphasized over expert opinion in making recommendations. Explicit guideline development clarifies the rationale by specifying the potential benefits, harms, and costs of available interventions; estimating the possibility of the outcomes; and comparing the desirability of the outcomes based on patient preferences. Steps in the development of practice guidelines include introductory decisions (selection of topic and panel members, clarification of purpose); assessments of clinical appropriateness (review of scientific evidence and expert opinion); assessment of public policy issues (resource limitations, feasibility issues); and guideline document development and evaluation (drafting of document, peer review, and pretesting).     

Prioritization of clinical questions for the Australian Living Guideline for the Pharmacological Management of Inflammatory Arthritis

Aim

Living guidelines aim to reduce delays in translating new knowledge into practice by updating individual recommendations as soon as relevant new evidence emerges. We surveyed members of the Australian Rheumatology Association (ARA) to develop a list of priority questions for the Australian Living Guideline for the Pharmacological Management of Inflammatory Arthritis (ALG) and to explore clinicians' use of clinical practice guidelines.

Methods

An electronic survey of ARA members was performed in two phases. The first survey contained questions about current guideline use and beliefs and invited participants to submit at least three questions relevant to the management of rheumatoid arthritis (RA). In the second round, participants selected 10 questions they considered to be the highest priority from the collated list and ranked them in priority order. The sum of ranks was used to generate a final priority list.

Results

There were 115 (21%) and 78 (14%) responses to the first and second survey rounds respectively. 87% of respondents use existing rheumatology guidelines in their usual practice, primarily EULAR guidelines. Most respondents favored the development of Australian rheumatology guidelines. In total, 34 potential recommendation topics were identified and ranked in order of priority.

Conclusion

A list of 34 clinical questions about RA management, ranked in order of importance by clinicians, has informed the development of the ALG. Similar prioritization exercises in other contexts may permit guidelines to be tailored to the needs of guideline users in their specific context, which may facilitate international collaboration and promote efficient translation of evidence to practice.     

Evidence, Values, Guidelines and Rational Decision-making

Medical decision-making involves choices, which can lead to benefits or to harms. Most benefits and harms may or may not occur, and can be minor or major when they do. Medical research, especially randomized controlled trials, provides estimates of chance of occurrence and magnitude of event. Because there is no universally accepted method for weighing harms against benefits, and because the ethical principle of autonomy mandates informed choice by patient, medical decision-making is inherently an individualized process. It follows that the practice of aiming for universal implementation of standardized guidelines is irrational and unethical. Irrational because the possibility of benefits is implicitly valued more than the possibility of comparable harms, and unethical because guidelines remove decision making from the patient and give it instead to a physician, committee or health care system. This essay considers the cases of cancer screening and diabetes management, where guidelines often advocate universal implementation, without regard to informed choice and individual decision-making.     

Guidelines on offloading foot ulcers in persons with diabetes (IWGDF 2019 update)

The International Working Group on the Diabetic Foot (IWGDF) has published evidence‐based guidelines on the prevention and management of diabetic foot disease since 1999. This guideline is on the use of offloading interventions to promote the healing of foot ulcers in people with diabetes and updates the previous IWGDF guideline. We followed the GRADE methodology to devise clinical questions and critically important outcomes in the PICO format, to conduct a systematic review of the medical‐scientific literature, and to write recommendations and their rationale. The recommendations are based on the quality of evidence found in the systematic review, expert opinion where evidence was not available, and a weighing of the benefits and harms, patient preferences, feasibility and applicability, and costs related to the intervention. For healing a neuropathic plantar forefoot or midfoot ulcer in a person with diabetes, we recommend that a nonremovable knee‐high offloading device is the first choice of offloading treatment. A removable knee‐high and removable ankle‐high offloading device are to be considered as the second‐ and third‐choice offloading treatment, respectively, if contraindications or patient intolerance to nonremovable offloading exist. Appropriately, fitting footwear combined with felted foam can be considered as the fourth‐choice offloading treatment. If non‐surgical offloading fails, we recommend to consider surgical offloading interventions for healing metatarsal head and digital ulcers. We have added new recommendations for the use of offloading treatment for healing ulcers that are complicated with infection or ischaemia and for healing plantar heel ulcers. Offloading is arguably the most important of multiple interventions needed to heal a neuropathic plantar foot ulcer in a person with diabetes. Following these recommendations will help health care professionals and teams provide better care for diabetic patients who have a foot ulcer and are at risk for infection, hospitalization, and amputation.     

Applying the Ecological Model to understand pregnant women's perspectives on the modifiable constraints to physical activity during pregnancy: A qualitative research study

The benefits of physical activity (PA) during pregnancy are widely reported; however, PA practice is seemingly not a valued habit among pregnant women attending public antenatal health centres in the Eastern Cape of South Africa. Guided by the ecological model, we sought to explore modifiable barriers to PA among pregnant women.Semi-structured interviews involved a purposive sample of 15 pregnant women. Interview questions were guided by the ecological model constructs at intrapersonal, interpersonal, and environmental level. Thematic analysis was applied to summarise the modifiable barriers to PA during pregnancy.Three main themes emerged, based on the modifiable barriers to PA during pregnancy that belong to the varying Ecological Model constructs. On the intrapersonal level, 5 themes emerged, namely, time-constraint beliefs, feeling of tiredness, low energy, lack of motivation, and a lack of knowledge on benefits and types of PA. Two themes emerged for the interpersonal level, lack of PA advice and lack of information on PA recommendations and guidelines. Another theme defined the environmental level lacking resources. Most themes related to individual factors, which prevent PA-promoting behaviour.Overall, intrapersonal factors relating to tiredness and exhaustion, lack of time beliefs, work and household commitments, and lack of motivation were key modifiable barriers to PA by the women. The findings provide insights into possible interventional strategies to optimise PA during pregnancy among women in this setting. Appropriate knowledge, education and advice on the benefits, types, and intensity of PA in pregnancy are needed.     

Overdiagnosis of gastric cancer by endoscopic screening

Gastric cancer screening using endoscopy has recently spread in Eastern Asian countries showing increasing evidence of its effectiveness. However, despite the benefits of endoscopic screening for gastric cancer, its major harms include infection, complications, falsenegative results, false-positive results, and overdiagnosis. The most serious harm of endoscopic screening is overdiagnosis and this can occur in any cancer screening programs. Overdiagnosis is defined as the detection of cancers that would never have been found if there is no cancer screening. Overdiagnosis has been estimated from randomized controlled trials, observational studies, and modeling. It can be calculated on the basis of a comparison of the incidence of cancer between screened and unscreened individuals after the follow-up. Although the estimation method for overdiagnosis has not yet been standardized, estimation of overdiagnosis is needed in endoscopic screening for gastric cancer. To minimize overdiagnosis, the target age group and screening interval should be appropriately defined. Moreover, the balance of benefits and harms must be carefully considered to effectively introduce endoscopic screening in communities. Further research regarding overdiagnosis is warranted when evaluating the effectiveness of endoscopic screening.     

A framework for tailoring clinical guidelines to comorbidity at the point of care

BACKGROUND: Evidence is accumulating to suggest that clinical guidelines should be modified for patients with comorbidities, yet there is no quantitative and objective approach that considers benefits together with risks. METHODS: We outline a framework using a payoff time, which we define as the minimum elapsed time until the cumulative incremental benefits of a guideline exceed its cumulative incremental harms. If the payoff time of a guideline exceeds a patient's comorbidity-adjusted life expectancy, then the guideline is unlikely to offer a benefit and should be modified. We illustrate the framework by applying this method to colorectal cancer screening guidelines for 50-year-old men with human immunodeficiency virus (HIV) and 60-year-old women with congestive heart failure (CHF). RESULTS: We estimated that colorectal cancer screening payoff times for 50-year-old men with HIV would range from 1.9 to 5.0 years and that colorectal cancer screening payoff times for 60-year-old women with CHF would range from 0.7 to 2.9 years. Because the payoff times for 50-year-old men with HIV were lower than their life expectancies (12.5-24.0 years), colorectal cancer screening may be beneficial for these patients. In contrast, because payoff times for 60-year-old women with CHF were sometimes greater than their life expectancies (0.6 to >5 years), colorectal cancer screening is likely to be harmful for some of these patients. CONCLUSION: Use of a payoff time calculation may be a feasible framework to tailor clinical guidelines to the comorbidity profiles of individual patients.     

Evidence supporting the best clinical management of patients with multimorbidity and polypharmacy: a systematic guideline review and expert consensus

The complexity and heterogeneity of patients with multimorbidity and polypharmacy renders traditional disease‐oriented guidelines often inadequate and complicates clinical decision making. To address this challenge, guidelines have been developed on multimorbidity or polypharmacy. To systematically analyse their recommendations, we conducted a systematic guideline review using the Ariadne principles for managing multimorbidity as analytical framework. The information synthesis included a multistep consensus process involving 18 multidisciplinary experts from seven countries. We included eight guidelines (four each on multimorbidity and polypharmacy) and extracted about 250 recommendations. The guideline addressed (i) the identification of the target population (risk factors); (ii) the assessment of interacting conditions and treatments: medical history, clinical and psychosocial assessment including physiological status and frailty, reviews of medication and encounters with healthcare providers highlighting informational continuity; (iii) the need to incorporate patient preferences and goal setting: eliciting preferences and expectations, the process of shared decision making in relation to treatment options and the level of involvement of patients and carers; (iv) individualized management: guiding principles on optimization of treatment benefits over possible harms, treatment communication and the information content of medication/care plans; (v) monitoring and follow‐up: strategies in care planning, self‐management and medication‐related aspects, communication with patients including safety instructions and adherence, coordination of care regarding referral and discharge management, medication appropriateness and safety concerns. The spectrum of clinical and self‐management issues varied from guiding principles to specific recommendations and tools providing actionable support. The limited availability of reliable risk prediction models, feasible interventions of proven effectiveness and decision aids, and limited consensus on appropriate outcomes of care highlight major research deficits. An integrated approach to both multimorbidity and polypharmacy should be considered in future guidelines.