Dr. Wojtek Wiercioch is a postdoctoral fellow and research methodologist at the McMaster GRADE Centre in the Department of Health Research Methods, Evidence, and Impact at McMaster University. His research focus is in evidence synthesis, guideline development methodology, and the guideline development process. His main research activities include development of guidelines and systematic reviews in collaboration with various medical professional societies, healthcare organizations and ministries of health, as well as development and evaluation of guideline methods.
What are clinical practice guidelines and how are they developed?
Clinical practice guidelines consist of recommendations about alternative options or management strategies to optimize patient care and outcomes. When faced with a healthcare decision, guidelines seek to inform health care providers and patients on the recommended course of action to prevent, diagnose or treat a health condition.
Developing clinical practice guidelines involves a multi-step process and a multi-disciplinary team. It starts with selecting the clinical questions for which recommendations are needed and desired. This can include areas where there is uncertainty in practice, variation in practice, or new research evidence that may be practice-changing, where clinicians and patients would most want guidance. The questions are typically framed as a comparison of one option versus one or more alternate options; for example, a commonly used drug therapy versus one that has been newly developed.
Next, systematic reviews are conducted to identify all research studies that compare these options. This is undertaken by researchers who specialize in searching and synthesizing research evidence. A summary of the outcomes of those research studies is prepared and presented to a guideline panel - we use a table format called a Summary of Findings table.
The panel consists of clinical experts and representatives from groups that would be affected by the recommendations, which typically includes patient representatives and may include other stakeholders such as healthcare administrators and policy-makers. The panel reviews the summary of research evidence and discusses the benefits and harms of the options - for example, how effective each treatment is in reducing mortality and to what extent they cause adverse effects. Other key issues need to be considered as well, such as costs of the alternate treatments and feasibility of administering them. When interpreting and discussing the evidence the panel makes judgements and seeks to reach a consensus on which option is the best alternative and issues a recommendation statement.
Typically, who is involved in developing clinical practice guidelines?
The guideline panel is responsible for selecting the questions to address in a guideline, reviewing evidence summaries, and issuing recommendations. A clinical practice guideline panel is usually chaired by a content expert as well as a guideline methodology expert who guide the process. A research team supports the panel in summarizing and appraising the quality of the best available research evidence that will inform the recommendations. To support the overall guideline development project, an oversight committee from the guideline organization and administrative team may also be involved to make sure the pre-defined steps and methods are followed and to provide support for steps such as organizing meetings, managing conflict-of-interest disclosures, and setting timelines.
Describe the ASH Venous Thromboembolism (VTE) Guidelines you and our colleagues from Cochrane Canada have been working on
In our guideline development project with the American Society of Hematology we set out to develop a comprehensive set of 10 guidelines addressing key questions about management of venous thromboembolism (VTE). VTE refers to blood clots that form in the veins, which can be a life-threatening condition or have serious consequences that are not fatal. Hospitalized patients, those undergoing major surgery, pregnant women, cancer patients, and people with risk factors such as immobility or blood clotting disorders are at high risk for VTE. These patient populations, as well as issues related to using blood thinners and treating children, are covered in the ASH VTE guidelines that altogether include over 250 recommendations.
We used innovative methods to ensure that the guidelines met the highest standards of development. The guideline development was centrally coordinated by researchers from Cochrane Canada and the McMaster University GRADE Centre to help achieve consistency across the 10 guidelines. ASH implemented a rigorous conflict-of-interest management policy to ensure the recommendations were free of potential biases due to conflicts. All recommendations were based on the latest evidence by updating or conducting new systematic reviews, and we used the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) approach to appraise the evidence as well as GRADE Evidence-to-Decision frameworks to guide panels through formulating recommendations. Throughout the project we also incorporated research on new guideline methods, such as setting up living systematic reviews, how to best formulate recommendations when faced with a scarcity of research evidence, and using online tools to facilitate the panels’ work.
Where can our readers find the latest ASH VTE Guidelines?
The complete set of guidelines is available on the ASH website, with links to the guideline publications in the Blood Advancesjournal. Readers will also find links to the VTE guideline resources and implementation tools that include one-page summaries, pocket guides and slide sets produced by ASH. The ASH Clinical Practice Guidelines mobile app includes the VTE guideline recommendations in an easy to access format. An accompanying methods paper describing our complete process and a user guide for the ASH guidelines are also available in Blood Advances.
What Cochrane tools/methods/approaches were used throughout the development of the ASH VTE Guidelines and why?
We used a number of Cochrane methods and tools to ensure that the systematic reviews supporting each recommendation were rigorous, thereby also improving the quality of our guidelines. This included conducting the systematic reviews using Cochrane methods for searching, screening, and appraising the evidence, with use of tools such as the Cochrane Risk of Bias tool for randomized controlled trials. We included in our systematic reviews the Cochrane Central Register of Controlled Trials (CENTRAL) when searching for trial evidence. In addition to conducting reviews of effects of interventions for the guideline questions, we also conducted systematic reviews of patients’ values and preferences, costs and cost-effectiveness, and feasibility and acceptability of the interventions. Finally, we used the GRADE methodology for creating Summary-of-Findings tables for our reviews that is also used for all Cochrane systematic reviews.
How have clinical practice guidelines helped to standardize care and curb non-evidence-based practice?
Guidelines produced with an expert panel and research team not only take care of the time-consuming task of synthesizing and reviewing all available research studies on a given topic, but also provide clear evidence-based recommendations that clinicians and patients can follow. They become a go-to source for busy clinicians who cannot take on these tasks individually, and may otherwise need to rely on past training, knowledge of some but not all new research evidence, or advice of their colleagues, which might not reflect current best evidence. Guidelines provide an up-to-date source to inform healthcare decisions as new research is produced, best practices change, and new healthcare options become available over time. Patient versions of guidelines also offer an evidence-based resource for informing decisions in a more user-friendly format for the public.
What makes a ‘good’ clinical practice guideline and why?
A good clinical practice guideline is one that is based on a systematic review of all best available research evidence, provides a transparent justification of how the panel arrived at their recommendation to avoid biases and conflicts-of-interest, and includes recommendation statements that offer clear advice for which action to take. Recommendations need to clearly indicate which option is recommended and whether it should be used in most scenarios - what we refer to as a ‘strong’ recommendation - or whether in some scenarios the best option to use will vary based on an individual patient’s values and preferences and shared decision-making - what we refer to as a ‘conditional’ recommendation.
During the development process, how do you know you’re working with the best available evidence?
We conduct systematic reviews to identify all available research evidence to inform a given guideline question. This involves searching multiple databases for published evidence as well as well as working with the panel to identify any relevant unpublished evidence. What is important for developing rigorous guidelines is that often the best available evidence is not necessarily only the high-quality evidence appraised using GRADE methods, such as large randomized controlled trials. Many questions that are of interest to guideline users are the ones where there is uncertainty and often only low or very low-quality evidence available. In those cases, that becomes the best available evidence and the panel is tasked with interpreting it and building consensus to issue a recommendation that will be informative to guideline users.