How evidence-based medicine has shaped international guidelines over the past 25 years




Stephen COLAGIURI, MBBS, FRACP
Boden Institute of Obesity, Nutrition & Exercise, University of Sydney, New South Wales
AUSTRALIA
Ruth COLAGIURI,BEd
Health and Sustainability Unit Menzies Centre for Health Policy, University of Sydney
New South Wales AUSTRALIA

Diabetes has reached epidemic proportions throughout the world. There is overwhelming evidence that the diabetes burden can be reduced through prevention and improving overall diabetes management. Despite the available evidence, strategies have not been widely incorporated into clinical practice, and the care received by many people with diabetes is less than optimal worldwide. Evidence-based diabetes guidelines are an essential tool for redressing this situation. The evidence-based guideline movement has evolved over many years in response to the explosion of medical knowledge, a perceived need to protect against the potential for biases in the consensus approach, and the ever-increasing need to optimize the cost-effectiveness of treatment interventions. Evidence-based medicine is designed to complement and integrate clinical experience. The International Diabetes Federation is leading a worldwide movement to make diabetes care more consistent, more systematic, and more accountable through engagement of the international diabetes community in the development and implementation of guidelines. There has been much progress over the past 25 years. Evidencebasedmedicine is now firmly entrenched as an essential component of healthcare services and delivery. Evolution and refinement of the guideline development process continues with moves towards simplifying and reducing the human and financial cost of preparing guidelines without compromising integrity. In addition, the focus has shifted from guideline development to addressing the, as yet, unresolved challenge of guideline implementation.

Medicographia. 2011;33:42-46 (see French abstract on page 46)

The May 13, 2010 resolution of the United Nations (UN) General Assembly to hold a UN summit on chronic diseases is testimony to the impact of the global tsunami of diseases such as diabetes. Diabetes has reached epidemic proportions throughout the world and is a major contributor to the growing burden of chronic disease, especially in developing countries.1 It is associated with significant morbidity and decreased life expectancy due to its complications, which include heart disease, stroke, amputation, blindness, and kidney failure. Diabetes reduces quality of life and is associated with increased psychosocial problems, including depression and anxiety. Diabetes results in a heavy socioeconomic burden for people with the disease, the health-care system, and society.2 Over and above the burgeoning health-system costs attributable to diabetes, in both developed and developing countries, diabetes incurs huge costs due to lost productivity as a result of its debilitating complications and early mortality in the productive years of life.3,4

The World Health Organization (WHO) proposes that 80% of all diabetes is preventable,4 and there is overwhelming evidence that diabetes complications can be prevented or delayed by processes and practices of care aimed at: improving overall diabetesmanagement; correcting blood glucose, blood pressure, and lipid abnormalities; avoiding smoking and excessive food intake; increasing physical activity; and controlling body weight. The cost-effectiveness of interventions to improve diabetes care has been well established by many international studies. Despite the available evidence, prevention strategies have not been widely incorporated into clinical practice, and the care received by many people with diabetes is less than optimal worldwide.5

The reasons for this disappointing situation are unclear, but are likely to be multifactorial and may include lack of practitioner awareness of the evidence, deficiencies in undergraduate and continuing medical education, and/or a mismatch between provider education and workplace culture and constraints, eg, insufficient material and human resources to implement the evidence.Whatever the reason, given the extent of the evidence that the morbidity and premature mortality associated with diabetes are reduced when care is closely aligned with guidelines,6 the globally endemic wide variations in the clinical care of diabetes are unacceptable.

Evidence-based diabetes guidelines are an essential tool for redressing this situation. Their recommendations synthesize the evidence to identify which clinical practices and processes of diabetes care lead to better outcomes. They provide practitioners and consumers with objective information about which interventions are likely to work best for most people with diabetes in most situations, and provide a solid foundation for clinical policy and protocols. Similarly, guideline recommendations establish standards and benchmarks that can assist funders and policy makers to allocate resources judiciously and assess the need for services and workforce development to achieve desired standards of care and, ultimately, improved health outcomes.

Background

Early consensus guidelines and position statements based on expert knowledge and clinical wisdom were a vital step in setting standards and benchmarks for promulgating and evaluating “best practice” and raising the profile and quality of diabetes care worldwide. As the next logical step, the evidence- based guideline movement evolved over many years in response to: (i) the explosion of medical knowledge enabled by technological advances; (ii) the associated proliferation of medical evidence in the form of journal reports; (iii) a perceived need to protect against the potential for biases in the consensus approach; and (iv) the ever-increasing need to optimize the cost-effectiveness of treatment interventions.

The role of clinical management guidelines is to synthesize and summarize research evidence into easily accessible information on the effects and possible consequences of available treatment options for use by clinicians and consumers. Field and Lohr7 defined evidence-based guidelines as: “…systematically generated statements which are designed to assist health care clinicians and consumers to make informed decisions about appropriate treatment in specific circumstances.”

Since then, guideline development has evolved into a highly sophisticated, technical, and resource-intensive model of research.8 Today, guideline methodology has its own body of evidence with each of several national research authorities around the world publishing their own requirements and grading criteria. In tandem with the evolution of guideline development methodology, a variety of clinical management guidelines across almost all common disease areas has proliferated in a global attempt to promote evidence-based clinical practice, reduce unacceptable variations in treatments, and minimize potential treatment harm.8

Evidence-based medicine aims to apply the best available evidence to medical decision-making. Evidence-based guidelines, which formulate recommendations based on evidence, influence policy and regulations, and are an essential starting point for improving clinical care. However, their application in evidence-based individual decision-making by the healthcare provider for the benefit of an individual patient needs to take into account the many other factors that influence treatment choices, including relevance to the individual and the patient’s expectations and values, cost, and cost-effectiveness. Evidence-based medicine should complement and integrate clinical experience.

The methodology for preparing evidence-based guidelines is well established and includes identifying specific research questions around important clinical issues. These questions are the focus of the subsequent systematic reviews and synthesis of the medical literature that generate the evidence for formulating clinically relevant recommendations to guide patient care. Several national research authorities set out strict criteria for developing guidelines, and the development process is rigorous, objective, replicable, and transparent. Nonetheless, it should be recognized that guideline methodology has some inherent limitations. The heavy reliance on randomized placebo-controlled trials unfairly undervalues qualitative studies, which are often particularly relevant to decisionmaking in diabetes. Treatment effectiveness reported in clinical studies may be higher than that achieved in subsequent routine clinical practice. Other problems include the validity of extrapolating evidence to different populations or over longer timeframes than those covered by the study, and bias related to nonpublication of negative studies.

Despite their acknowledged limitations, guidelines can be a powerful tool in reducing unacceptable variations in clinical practice. They are increasingly shaping best practice, and the promulgation of evidence in diabetes care and, subsequently, evidence-based medicine is increasingly shaping the content and focus of diabetes guidelines.

The International Diabetes Federation (IDF)

The International Diabetes Federation (IDF) is an umbrella international non-governmental organization (NGO) of over 200 national diabetes associations in over 160 countries and has been leading the global diabetes community since 1950. IDF’s mission is to promote diabetes care, prevention, and a cure worldwide. The IDF led the “Unite for Diabetes” campaign, which secured a UN resolution on diabetes in December 2006. The resolution encourages UN member states to develop national policies for the prevention, treatment, and care of diabetes in line with the sustainable development of their health-care systems, taking into account internationally agreed development goals, including the Millennium Development Goals.

There is now extensive evidence on the optimal management of diabetes, offering the opportunity of improving the immediate and long-term quality of life of people with diabetes. Unfortunately, such optimal management is not reaching many, perhaps the majority, of the people who could benefit. Reasons include the size and complexity of the evidence base, and the complexity of diabetes care itself.

Guidelines are one part of a process that seeks to address these problems. Many guidelines have appeared internationally, nationally, and more locally in recent years, but most of these have not used the rigorous new guideline methodologies for identification and analysis of the evidence. The IDF is leading a worldwide movement to make diabetes care more consistent, more systematic, and more accountable through engagement of the international diabetes community in the development and implementation of guidelines. The IDF Clinical Guidelines Taskforce focuses on developing evidencebased guidelines and clinical care recommendations which are globally and locally relevant.9

A global guideline presents a huge and unique challenge. Many national guidelines address one group of people with diabetes in the context of one health-care system, with one level of national and health-care resources. This is not true in the global context where, although every health-care system seems to be short of resources, the funding and expertise available for health care vary widely between countries and even between localities.
_ Levels of diabetes care
All people with diabetes should have access to cost-effective evidence-based care. It is recognized that in many parts of the world the implementation of particular standards of care is limited by lack of resources. The IDF has developed a practical approach to promote the implementation of costeffective evidence-based care in settings between which resources vary widely. The approach that has been adopted is based on acknowledging and making recommendations in relation to three levels of care:
_ Standard care
Standard care is evidence-based care which is cost-effective in most nations with a well-developed health-service base, and with health-care funding systems consuming a significant part of national wealth. Standard care should be available to all people with diabetes and the aim of any health-care system should be to achieve this level of care. However, in recognition of the considerable variations in resources throughout the world, other levels of care are described which acknowledge low and high resource situations.
_ Minimal care
Minimal care is the lowest level of care which anyone with diabetes should receive. It acknowledges that standard medical resources and fully trained health professionals are often unavailable in poorly funded health-care systems. Nevertheless, this level of care aims to achieve with limited resources (medications, personnel, technologies, and procedures) a high proportion of what can be achieved by standard care. Only low-cost or highly cost-effective interventions are included at this level.
_ Comprehensive care
Comprehensive care includes the most up-to-date and complete range of health technologies that can be offered to people with diabetes, with the aim of achieving the best possible outcomes. However, the evidence-base supporting the use of some of these expensive or new technologies is relatively weak.

Approaches to guideline development

Developing guidelines is a time-consuming and costly process that is beyond the resources of many health-care systems. As the science of evidence-based medicine continues to evolve, there is now increasing questioning of the need for and the relevance of the traditional full guideline development process. In 2003, the IDF addressed this in its Guide for Guidelines10 which proposed two basic approaches to developing an evidence-based guideline:
_ Full-process guideline
_ Derived guideline

The full-process guideline involves a full and systematic development of the clinical questions to be addressed, and develops recommendations supported by complete and formal evidence searching and review, using primary sources.

The derived guideline similarly develops clinical questions, but then seeks out and adapts previously developed full-process guidelines, updating the evidence base and seeking supporting evidence to develop recommendations for local circumstances. Preparing a derived guideline, a relatively simple process, can be done without a complex management structure or considerable resources and time, without compromising the end result.

While the move to review the need for full-process guidelines is welcome, this should not imply a return to consensus statements prepared by a small group with a limited and often uncritical review of the literature.

Complexity of decision-making in clinical management

Diabetes care is complex and involves a range of interventions – education, lifestyle modification (diet, physical activity), medications for diabetes complications prevention and treatment (eg, cardiovascular and renal disease), and ongoing monitoring and review (including self-monitoring blood glucose [SMBG], clinical [blood pressure and weight], and pathological [glycated hemoglobin, lipids, etc]). While multifactorial intervention has been shown to reduce morbidity and premature mortality,11 demonstrating the efficacy of individual components of care has been more difficult (eg, education,12 SMBG13). Clinical decision making requires more than just taking into account efficacy of a particular treatment, and this should be taken into account in formulating and interpreting guideline recommendations. Factors which influence the treatment used in a particular patient include not only the evidence of effect on glycemic control and diabetes outcomes, but also include contraindications, potential side effects, patient preference, local availability, prescribing restrictions, and the cost to the individual and health-care system. Ultimately, diabetes care decision-making is based on a balance between benefit and safety in the context of availability and cost. Fortunately, there is considerable high-quality evidence available to guide clinical diabetes care. However, there are limited data on clinical outcomes comparing different treatment schedules.

The United Kingdom Prospective Diabetes Study (UKPDS) reported similar improvements with sulfonylurea- and insulinbased treatment policies on microvascular complications and on any diabetes-related end point.14 Although metformin therapy was associated with improved cardiovascular outcomes in a subgroup of overweight individuals, it should be noted that this was against a backdrop of no improvement in microvascular outcomes and no significant reduction in glycated hemoglobin.15

Most of the data relating to pharmaceutical interventions are based on efficacy in improving blood glucose, which is generally similar between agents depending on whether it is used as first-, second-, or third-line therapy. Therefore, individual treatment choices are ultimately more often based on other considerations. These include unwanted consequences, such as the risk of hypoglycemia and weight gain, which are inevitable with insulin, but which differ between other agents and between studies. The cost to the individual, the healthcare system, and society is an important consideration, and cheaper, well-established, and efficacious treatments (eg, metformin and sulfonylureas) continue to be widely used and recommended in guidelines globally.

Guideline implementation

The translation of guidelines into everyday practice remains a vexed problem with little clear direction about what works best across all circumstances. According to Grimshaw et al,16 failure to translate guidelines into everyday practice features among the commonest findings of health-service research.

Nonetheless, there is some evidence, although variable, on the effectiveness of certain strategies for improving the uptake of guidelines by health professionals in clinical practice.17 Many approaches have been used with varying success, but the most effective have been multidimensional and locally specific. The main targets of guideline implementation strategies are health-care professionals, health-care funders, and people with diabetes. However, other stakeholders, such as government and industry, have an important role in promoting and facilitating guideline implementation.

Successful guideline implementation requires more than its formulation and publication. Together, with its wide distribution among organizations worldwide, the IDF has been holding regional workshops to present its guidelines, explain their aims and evidence-based methodology, and analyze faceto- face with health-care organizations and providers the difficulties of successful implementation and possible strategies to solve such problems.

During these workshops the guidelines are presented, and attendees explain their approach to improving diabetes care and the problems identified for successful implementation and acceptance of care strategies. Small groups consider the pros and cons of the guideline, barriers to successful implementation, and possible strategies to overcome such barriers.18

Greater attention and support is needed for guideline implementation. Indeed, guideline development is rarely indicated unless there are plans, developed at the same time, for implementation of the recommendations. This should be considered an integral part of the planning stage of guideline development. Guideline implementation requires participation of people with diabetes, official support from government andhealth-financing entities, adequate distribution of a simplified version for daily use at primary health-care level, and training of providers/users. These strategies imply the appropriate allocation of human and economic resources.

There has been much progress over the past 25 years. Evidence- based medicine is now firmly entrenched as an essential component of health-care services and delivery. Evolution and refinement of the guideline development process continues with moves towards simplifying and reducing the human and financial cost of preparing guidelines without compromising integrity. Finally, the focus has shifted from guideline development to addressing the, as yet, unresolved challenge of guideline implementation. _

References
1. Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract. 2010;87:4-14.
2. Ringborg A, Cropet C, Jönsson B, Gagliardino JJ, Ramachandran A, Lindgren P. Resource use associated with type 2 diabetes in Asia, Latin America, the Middle East and Africa: results from the International Diabetes Management Practices Study (IDMPS). Int J Clin Pract. 2009;63:997-1007.
3. American Diabetes Association. Economic costs of diabetes in the U.S. In 2007. Diabetes Care. 2008;31:596-615.
4. WHO. Preventing Chronic Diseases: A vital investment. 2005. www.who.int/chp/ chronic_disease_report/contents/en/index.html. Accessed October 11, 2010.
5. Chan JC, Gagliardino JJ, Baik SH, et al; IDMPS Investigators. Multifaceted determinants for achieving glycemic control: the International Diabetes Management Practice Study (IDMPS). Diabetes Care. 2009;32:227-233.
6. Grimshaw J, Thomas R, MacLennan G, et al. Effectiveness and efficiency of guideline dissemination and implementation strategies. Health Technol Assess. 2004;8:1-72.
7. Field MJ, Lohr KN, eds. Clinical Practice Guidelines: Directions for a New Program. Washington, DC; National Academy Press: 1990.
8. Colagiuri R. Implementing evidence based guidelines: Unlocking the secrets. Diabetes Res Clin Pract. 2009;85:117-118.
9. International Diabetes Federation website. http://www.idf.org/. Accessed October 11, 2010.
10. International Diabetes Federation Guide for Guidelines. http://www.idf.org/ guide-guidelines. Accessed October 11, 2010.
11. Gæde P, Lund-Andersen H, Parving H-H, Pedersen O. Effect of a multifactorial intervention on mortality in type 2 diabetes. N Engl J Med. 2008;358:580- 591.
12. Duke S, Colagiuri S, Colagiuri R. Individual patient education for people with type 2 diabetes mellitus. Cochrane Database Syst Rev. 2009;21:CD005268.
13. Clar C, Barnard K, Cummins E, Royle P, Waugh N; Aberdeen Health Technology Assessment Group. Self-monitoring of blood glucose in type 2 diabetes: systematic review. Health Technol Assess. 2010;14:1-140.
14. UKPDS Study Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes. (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352:837-853.
15. UKPDS Study Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352:854-865.
16. Grimshaw J, Eccles M, Tetroe J. Implementing clinical guidelines: current evidence and future implications. J Contin Educ Health Prof. 2004;24(suppl 1): S31-S37.
17. de Belvis AG, Pelone F, Biasco A, Ricciardi W, Volpe M. Can primary care professionals’ adherence to evidence based medicine tools improve quality of care in type 2 diabetes mellitus? A systematic review. Diabetes Res Clin Pract. 2009; 85:119-131.
18. Gagliardino JJ, Colagiuri S. An approach to implementing international diabetes guidelines. Int J Ther Rehabil. 2009;16;470. Editorial.

Keywords: evidence-based medicine; diabetes; guidelines