Guideline development in the age of COVID-19: A Q&A with Dr. Robby Nieuwlaat

Dr. Robby Nieuwlaat is an Associate Professor in the Department of Health Research Methods, Evidence, and Impact (HEI) at McMaster University. He is also the Director of HEI's Graduate Diploma in Clinical Epidemiology (GDCE) program and a member of Cochrane Canada.

The COVID-19 pandemic has resulted in unprecedented human and social impacts around the world. How has the pandemic transformed the way in which guidelines are developed?

Guideline development groups often consist of persons from different professional backgrounds and geographic areas. Before the COVID-19 pandemic, a lot of the work was already facilitated by videoconferencing and other online tools, but in-person meetings were also used primarily to discuss and finalize recommendations. Now the whole process is being done online, which seems to work well as it allows more flexibility for guideline group members. There are of course benefits of meeting in-person, including a sense of a closer connection between group members and being able to discuss details during full-day meetings that are dedicated to complete multiple recommendations. However, the accelerating development of more and better online tools have increasingly tackled the drawbacks of working online only.

How often are guidelines updated? Has this changed since the onset of COVID-19?

The frequency of updating depends on availability of new evidence that may change the recommendations. Typically, guidelines for important topics have been updated every few years. Now, there is increasingly a focus on creating ‘living’ guidelines, especially for important topics with an ongoing research output that provides new insights. COVID-19 is the ultimate example of this, and guideline developers have to sort through a very large volume of research publications to meet the challenge of providing up-to-date guidance to health care providers based on the best available evidence.

What makes a ‘good’ clinical practice guideline and why?

A good clinical practice guideline provides clear and actionable recommendations that address questions important to patients, providers and other key stakeholders. The development methodology needs to be transparent and based on current best practices, which includes Cochrane methodology. Explicit reporting has to provide enough detail so readers can determine which processes were used and understand the decisions that were made by the guideline development group.

Describe the ‘ASH Guidelines On Use of Anticoagulation in Patients with COVID-19’ you and our colleagues from Cochrane Canada have been working on.

Our group published guidelines with the American Society of Hematology (ASH) in 2018 that recommended using blood thinners to prevent blood clots in patients who are critically ill and in the intensive care unit (ICU), and suggested using blood thinners in patients who are acutely ill and hospitalized. These patients are at increased risk for blood clots, and although blood thinners put them at risk of bleeding, the guideline development group judged that the benefit of blood thinners at the recommended dosing will likely outweigh the bleeding risk in most of these patients. Since the beginning of the pandemic, research publications reported a very high risk for thrombosis in COVID-19 patients who were critically or acutely ill. Health care providers started to question whether the usual dose of blood thinners to prevent thrombosis would be sufficient in these patients, or if they needed higher doses which would also put them at higher risk of bleeding. Working with ASH and a guideline development group we have developed recommendations to address this issue, and will keep updating them as ‘living’ recommendations so providers can base their practice on the most recent trustworthy evidence.

What Cochrane tools/methods/approaches were used throughout the development of these specific Guidelines and why?

We used several methods and tools. Our overall guideline development methodology was based on the GIN-McMaster checklist and the GRADE handbook, and our systematic review methodology was based on the Cochrane Handbook. Our approach to develop ‘living’ systematic reviews and recommendations was informed by Cochrane guidance on these topics. Further, we used the online GRADEpro software throughout the development process, which integrates communication with the guideline development group, creation of research evidence summary tables, a framework to make recommendations based on the research evidence, and other helpful features that streamline the process from determining the questions to publishing the recommendations. Cochrane systematic reviews include tables called ‘Summary of Findings’ or ‘Evidence Profiles’ and these can be created in GRADEpro in a format that is ready for publication.

During the development process, how do you know you’re working with the best available evidence?

The systematic review process considers several aspects to ensure the best available evidence is found and summarized. This starts with having a clear question that informs us what evidence we need to look for. For example, for comparisons of treatments, studies called randomized controlled trials are typically the best available evidence. However, they are often not available, or they are available but have important limitations. In that case, we need to search for other types of studies that may represent the best available evidence. We search in multiple databases as there is not one database that publishes all research studies, and use search methods with the help from a librarian that minimize the risk of missing relevant studies. Further, we work with well-trained review team members who identify studies and extract data, independently and in duplicate. Sometimes a recent systematic review of high quality has already been published by other researchers and can be used as the best available evidence, which allows us to be efficient and not go through the same process. We also consult content experts from the guideline group who are already aware of many relevant studies. In the end, we put together the evidence and determine how certain we are that the answer approaches the truth, because even the best available evidence may still have important drawbacks.

Where can our readers find the latest ASH Guidelines on Use of Anticoagulation in Patients with COVID-19?

The guideline manuscript has been submitted for peer-review publication and is expected to come out soon. The draft recommendations with links to the best available evidence and guideline judgments are already available on the ASH website, as well as a webinar where we presented the methods and recommendations