2022 Recap and What's Next for the U.S. GRADE Network

Thanks to you, 2022 was one of our best years yet.

We were relieved to see you in person, our first time since 2020, at our spring workshop in Chicago last June! Then, we reconvened online for a virtual workshop in November. Overall, we hosted over 100 participants from around the world, stretching from Canada and Spain to Colombia and Sweden. 

Facilitators and participants at the spring 2022 GRADE guideline development workshop in Chicago, IL - the first in-person USGN workshop since March 2020.

We also launched our new two-day virtual Systematic Review workshop offering and welcomed another 48 learners, including a record 13 scholars from across the globe!

We published our takeaways from our early experiences moving our workshop online in response to the Covid-19 pandemic in BMJ Evidence-Based Medicine, which you can read about here.

Finally, we launched the USGN Webinar Series and will host regular free webinars on all things GRADE. For our inaugural session, we were joined by Drs. Gordon Guyatt and Reem Mustafa. You can watch the recording and subscribe to our new YouTube channel here. 

We look forward to seeing you at our 18th Guideline Development Workshop, in person in sunny Austin, Texas, May 17-19, 2023! The workshop will have a special focus on assessing the certainty of evidence informed by non-randomized studies. Registration is now open.

From Risk of Bias to Living Evidence, Fall 2022 EF Scholars Present on Cutting-Edge EBM Projects

During our 17th GRADE Guideline Development Workshop, held virtually, the U.S. GRADE Network had the honor of introducing the three latest recipients of the Evidence Foundation scholarship to the virtual stage. On the third and final morning of the workshop, each scholar presented on their current projects to reduce bias in healthcare and move the field of evidence-based medicine methodology forward. 

Abrar Alshorman, MBBS, presented on her work to examine the tools used to assess risk of bias across various types of evidence. As choosing the wrong risk of bias tool at the start of an evidence synthesis effort might waste time and disrupt workflow, her project aims to guide systematic reviewers in choosing the best tool to use. The resulting list includes risk of bias tools for use in primary studies that were identified in a search of the evidence, including those with applications in randomized, non-randomized, diagnostic test accuracy, prognosis, and qualitative bodies of evidence. 

"The workshop struck the perfect balance between informative and interactive," said Alshorman. "[A]ll sessions have been extremely informative and provided by very knowledgeable presenters. This opportunity offered me insight into the key concepts of the GRADE approach for guideline development. I look forward to incorporating the information I've learned into practice."

Next, Brett Norling, a third-year medical student, discussed his project examining the use of the GRADE framework in systematic reviews in urology. The project reviewed literature published in the top 5 urology journals since 2000, using Perl programming code to identify articles using GRADE. The team then applied a 37-item checklist developed de novo from the "Criteria for Applying or Using GRADE." The results demonstrated that while most (95.8%) of the included reviews correctly applied GRADE on an outcome-level basis, nearly one-third (31.4%) of the 70 reviews summary of findings, evidence profile, or other from of table to present their findings.

"I came to the GRADE Workshop having performed a systematic review and a few other research projects regarding systematic review methodology," said Norling. "I felt that my understanding of GRADE was in the developing stages, though it felt a bit abstract prior to the workshop. Key GRADE principles of evidence assessment came to life as I worked with a small group to assess a body of evidence and arrive at a recommendation. I now feel well equipped to confidently assess evidence and perform systematic reviews with a greater level of autonomy than prior to this workshop."

Finally, Ariadna Alaudell-Rispau, a PhD candidate in the Biomedical Research Methodology and Public Health Doctoral Program at the Autonomous University of Barcelona, presented her proposal for the development of Living Evidence Structures Summaries (LESS). Auladell-Rispau described her project to lead a multi-design, iterative study that allows for a systematic and rigorous development of a "Living Evidence updates reporting model" that "accounts for the periodic and/or constant updates of the evidence syntheses developed under the Living Evidence model, permits the development of valid, reliable, and updated health information to health decision makers, including guideline or [health technology assessment] developers..., [and is] friendly and accessible." The project will include a systematic review, brainstorming meetings, a Delphi consensus process, and finally, testing and assessment of the newly developed model.

We look forward to updating the blog about these projects as they move forward!

ANNOUNCEMENT: Applications for the Spring 2023 GRADE Guideline Development Workshop, held in Austin, Texas, May 17-19, 2023, are due February 28th! Learn more about the application requirements here and read about the workshop details here.

COVID-END Working Groups Call for Living Systematic Reviews and Considerations of Health Equity in Evidence Synthesis and Guideline Efforts

The COVID-19 pandemic was not only associated with a rapid worldwide spread of a virus, but also of large amounts of information across the globe - not all of which was trustworthy or credible. Experts call this an "infodemic." In order to improve the synthesis and dissemination of trustworthy information in a manner that could keep up with the fast pace and ever-changing landscape of knowledge on COVID-19, the COVID-19 Evidence Network to support Decision-making (COVID-END) was established.

In a paper published in this month's issue of Journal of Clinical Epidemiology, McCaul and colleagues describe how the COVID-19 pandemic ushered in an urgent need to rapidly understand the etiology and management strategies for the disease, and to disseminate this information far and wide. However, a lack of collaboration resulting in duplication of work across institutions and countries hampered these efforts. COVID-END, comprising two working groups  dedicated to overseeing the coordination and dissemination of trustworthy evidence syntheses and guidelines, was a result of these unprecedented needs. The effort also included an Equity Task Group that evaluated the impact of evidence synthesis and recommendations on matters of health and socioeconomic disparities arising from or exacerbated by the pandemic.

Figure from McCaul et al. describing the efforts of COVID-END

The goal of the project, in the authors' words, was to support the "evidence supply side" by promoting already available resources and work led by institutions across the globe, both for those involved in evidence synthesis or the formulation of recommendations based on the evidence. The avoidance of effort duplication was highlighted by, for instance, urging guideline developers to first search for existing high-quality and up-to-date guidelines before beginning work on new recommendations. The development and use of living systematic reviews, which are continually updated as new evidence becomes available, is further highlighted as a way to improve the timeliness of evidence syntheses while reducing efforts put into new projects.

McCaul, M., Tovey, D., Young, T., et al. (2022). Resources supporting trustworthy, rapid and equitable evidence synthesis and guideline development: Results from the COVID-19 Evidence Network to support Decision-making (COVID-END). J Clin Epidemiol 151: 88-95. Manuscript available at publisher's website here. 

8 Steps Toward Incorporating Equity in Rapid Reviews and Guidelines

Along with the mass mobilization of systematic reviews of evidence ushered in by the COVID-19 pandemic was also the need to synthesize evidence and disseminate results as rapidly as possible. As part of the process of formulating guidelines based upon rapid reviews, the impact of decisions and policies on equity should be considered. In a newly published paper, Dewidar and colleagues provide specific steps for incorporating stakeholders and improving the consideration of equity in the context of rapid guidelines.

The project was part of work conducted by the Equity Task Force of the global COVID-19 Evidence Network to support Decision-making COVID-END) network. The team was diverse in terms of the gender (70% women), regions (17% from low-middle-income countries), and career stages (40% early career) represented. The resulting guidance was created in line with the steps outlined in the Cochrane Handbook's chapter on equity and followed the PRISMA-Equity (PRISMA-E) extension for reporting. The team then identified published systematic reviews related to COVID-19 that focused on populations experiencing inequities as categorized by the PROGRESS-Plus paradigm - for instance, by Place of Residence (health systems in rural areas and their preparedness for outbreaks), Education (the impact of educational attainment on adherence to COVID-19 health guidelines), and Disability (the impact of COVID-19 on those with disabilities) - for examples that review authors can incorporate equity into their own reviews.

The authors conclude that greater involvement of diverse stakeholders can encourage the consideration of more diverse social factors in the development and interpretation of systematic reviews and resulting guidelines and policies. Rapid reviews also benefit from having a translation plan that includes methods for disseminating findings in a way that is consistent with the goal of reducing inequities. 

Dewidar, O., Kawala, B.A., Antequera, A., et al. (2022). Methodological guidance for incorporating equity when informing rapid-policy and guideline development. J Clin Epidemiol 150: 142-153. Manuscript available at the publisher's website here. 

U.S. GRADE Network Describes Experience Moving to All-Virtual Workshop Format

On March 4-6, 2020, the U.S. GRADE Network held an in-person workshop in Phoenix, Arizona, much like any of the 11 workshops to have come before it. Participants and facilitators enjoyed a taco buffet bar together at the first night's reception, sat together in small and large rooms to learn and collaborate, and mingled over coffee and pastry refreshments during breaks.

One week later, the World Health Organization announced that COVID-19 had reached pandemic proportions. 

Over that summer, the USGN took our workshops online, hosting three consecutive fully virtual workshops in October 2020, May 2021, and October 2021. While some changes were made (the addition of multiple, 45-60 minute breaks, for instance, to accommodate eating times in multiple time zones), much of what lay at the heart of a GRADE workshop remained: a three-day format  including plenary lectures from PICOs to recommendations, presentations by Evidence Foundation scholars, and small-group, hands-on experiential learning opportunities.

The USGN's shift to an all-virtual setting, and its challenges as well as opportunities for growth, are presented in a new paper by Siedler and colleagues published online in the BMJ Evidence-Based Medicine journal. Using routine feedback survey data collected both before and after the pandemic, the authors (all GRADE workshop facilitators) found that...

• Perceived understanding of GRADE improved to the same extent in virtual and in-person formats,
• At least half of attendees (54-62%) indicated that the virtual format was important for their ability to attend, and
• Participants indicated a high degree of workshop satisfaction and perceived educational value. Similar results were observed for the level of knowledgeability of speakers, value of plenary sessions, and helpfulness of small-group sessions.

The major takeaway from the USGN's experience in an all-virtual format is that, based upon positive feedback and the ability to reach a global audience of learners, it will continue to offer learning opportunities in a virtual setting this year and beyond.

In fact, the next all-virtual workshop will take place November 30-December 2, 2022, and registration is now open at www.gradeconf.org.

Siedler MR, Murad MH, Morgan RL, et al. (2022). Proof of concept: All-virtual guideline development workshops using GRADE during the COVID-19 pandemic. BMJ Evidence-Based Medicine (online before print). Manuscript available from publisher's website here.

Use of an Evidence-to-Decision Framework is Associated with Better Reporting, More Thorough Consideration of Recommendations

In the guideline development process, a panel should use a defined framework to consider multiple aspects of a clinical decision, including but not limited to the certainty of the underlying evidence, potential impact on resource use, or variability in the values and preferences of patients and other stakeholders. Such frameworks include the GRADE Evidence-to-Decision (EtD) format as well as others such as the "decision-making triangle" and Guidance for Priority-Setting in Health care (GPS Health). 

To better understand the prevalence and use of these various frameworks within guidelines, Meneses-Echavez and colleagues systematically searched for guidelines and related guideline production manuals published between 2003 and May 2020. Items were screened and extracted by two independent authors, with a total of 68 full text documents included and analyzed.

Of these documents, most (93%) reported using a structured framework to assess the certainty of evidence, about half (53%) of which used GRADE or adapted systems based on GRADE (10%). Similarly, 88% of documents reported using a framework to rate the strength of recommendations, with about half (51%) using the GRADE approach. However,  only about two-thirds (66%) of the included documents explicitly stated the process for formulating resulting recommendations. 

Finally, the GRADE framework  was most commonly used for the evidence-to-decision, being cited in 42% of the included articles, with other reported frameworks including NICE (8%), SIGN (8%) and USPSTF (4%). Articles using the GRADE EtD framework reported considering more criteria than those using alternative approaches. The most commonly used criteria across documents included desirable effects (72%), undesirable effects (73%), and the certainty of evidence of effects (73%); the least commonly applied criteria were acceptability (28%), certainty of the evidence of required resources (25%), and equity (16%). 

The use of any EtD framework was associated with a greater likelihood of incorporating perspectives (odds ratio: 2.8; from 0.6-13.8) and subgroup considerations (odds ratio:7.2; from 0.9-57.9), as was the use of GRADE compared to other EtDs (odds ratios: 1.4 and 8.4). These differences also affected whether justifications were reported for each judgment as well as the inclusion of notes to consider for the implementation of recommendations and for monitoring and evaluating recommendations.  

The authors conclude that guidance documents stand to benefit from the more explicit reporting of how recommendations are formulated, from the initial grading of the certainty of underlying evidence to the consideration of how recommendations will affect various criteria such as resource use and equity. These changes, in the words of the authors, may "enhance transparency and credibility, enabling end users to determine how much confidence they can have in the recommendations; facilitate later adaptation to contexts other than the ones in which they were originally developed; and improve usability and communicability of the EtD frameworks." 

Meneses-Echaves JF, Bidonde J, Yepes-Nuñez JJ, et al. (2022).  Evidence to decision frameworks enabled structured and explicit development of healthcare recommendations. J Clin Epidemiol 150:51-62. Manuscript available at publisher's website here.

Only One-Third of a Sample of RCTs Had Made Protocols Publicly Available, New Report Finds

Earlier this year, a study in PloS Medicine found that nearly one-third (30%) of a sample of randomized controlled trials (RCTs) had been discontinued prematurely, a number that had not improved over the previous decade. Furthermore, for every 10% increase in adherence to SPIRIT protocol reporting guidelines, RCTs were 29% less likely to go unpublished (OR: 0.71; 95% confidence interval: from 0.55 to 0.92), and only about 1 in every 5 unpublished trials had been registered.

Now, in this month's issue of Journal of Clinical Epidemiology, Schönenberger and colleagues have released a study of the availability of RCT protocols from a sample of published works.

Public availability of study protocols, the authors argue, improves research quality by promoting thoughtfulness in methodological design, reducing selective outcomes reporting or "cherry-picking," and reducing the misreporting of results while promoting ethical compliance. This is especially the case when trial protocols are made available before the publication of study results. 

From a random sample of RCTs approved by ethics committees in Switzerland, Germany, Canada, and the United Kingdom in 2012, the authors examined the proportion of studies that had publicly available protocols and the nature of how the protocols were cited and disseminated. Of the resulting 326 RCTs, 118 (36.2%) had publicly available protocols. Of the protocols, nearly half (47.5%) were available as standalone peer-reviewed publications while 40.7% were available as supplementary material with the published results. A smaller proportion (10.2%) of protocols were available on a trial registry. 

Studies with a sample size of >500 or that were investigator- (non-industry)-sponsored were more likely to have publicly available protocols. The nature of the intervention (drug versus non-drug) did not appear to affect protocol availability, nor did whether the trial was conducted in a multicenter or single-center setting. The majority (91.8%) of protocols were made available after the enrollment of the first patient, and just 2.7% were made available after publication of trial results. Protocols were commonly published shortly before the trial results, at a median of 90% of the time between the start of the trial and its publication.

As this sample comprised only RCTs published in 2012 and by relatively high-income countries, it is unclear whether public protocol availability has improved over time or may be different in other global regions. However, the authors argue, these numbers lend credence to the need for efforts to improve the public availability of RCT protocols, such as through trial registries or requirements by publishing or funding bodies.

Schönenberger, C.M., Griessbach, A., Heravi, A.T., et al. (2022). A meta-research study of randomized controlled trials found infrequent and delayed availability of protocols. J Clin Epidemiol 149:45-52. Manuscript available at publisher's website here.