RIGHT-PVG: A New Checklist for the Reporting of Patient Versions of Guidelines

 Patient versions of guidelines (PVGs) can provide crucial information about diagnoses and management options to patients in clear, plain language and can help guide shared decision-making between patients and their providers to improve the quality of care. However, the construction and reporting of PVGs is variable in terms of quality and content. Now, a new extension of the Reporting Tool for Practice Guidelines in Health Care - the RIGHT-PVG - aims to standardize the development of such documents.

Development of the RIGHT-PVG comprised 17 experts from around the world with experience in guideline development, patient communication, and epidemiology, and clinical practice. First, an initial list of items was generated from common themes in a sample of 30 PVGs. Then, four organizational guidance documents for the development of PVGs were identified and used to refine initial criteria. Two rounds of a modified Delphi consultation were used to further pare and refine checklist items from an original list of 45, with all panelist feedback anonymized. 

Final items included within the RIGHT-PVG fell under four main categories:

• Basic information: items 1-3 include the reporting of title and copyright, contact information, and a general summary of the PVG's key points.
• Background: items 4-6 include a general introduction to the topic at hand, information about the scope and target audience of the document, and a link to the original guideline off of which the PVG is based.
• Recommendations: items 7 and 8 comprise the meat of the PVG: what is the guideline recommending, for whom, and what are the potential desirable and undesirable effects of the intervention? 
• Recommendations should be easily identifiable via boxing, shading/coloring, or bold type.
• The strength of each recommendation should be included along with a transparent reporting of the certainty of the evidence behind it.
• Easy-to-understand symbols can be used to denote the differences between strong and more conditional recommendations.
• Other information: items 9-12 recommend the inclusion of suggested questions for the reader to ask their provider; a glossary of terms and abbreviations; information about how the guideline was funded; and disclosure of any relevant conflicts of interest.

Wang X., Chen Y., Akl E.A., ... and the RIGHT working group. (2021). The reporting checklist for public versions of guidelines: RIGHT-PVG. Implement Sci 6(10). 

Manuscript available from the publisher's site here. 

New Guideline Participation Tool Lays Out Roles and Responsibilities for New and Returning Guideline Group Members

Guideline development groups should contain a multidisciplinary panel of experts and key stakeholders to ensure the quality, relevance, and ultimate implementation of resulting recommendations. However, there are few tools in existence to ensure the effective participation of panel members when working to draft guidelines, and preparing panel members with little to no previous experience in guideline development can be an especially daunting task. A new paper published in next month's issue of the Journal of Clinical Epidemiology aims to provide a tool to guide these efforts, with a specific focus on guideline developed using the GRADE framework.

To develop the tool, Piggott and colleagues first established a draft tool that included 61 items based on a previously published systematic review of guideline development handbooks. They then conducted a series of ten key informant interviews comprising both past and prospective guideline development group members to narrow the tool down to three major themes: selection of participants, guideline group process, and tool format. The resulting 33-item Guideline Participant Tool (GPT) was then validated in a survey of 26 guideline group members from various societies including WHO and the American Society of Hematology (ASH). The tool itself breaks the process of guideline participation into three major time windows: 

• Before (Preparations): 12 items including clarifying objectives and one's role within the group and familiarizing oneself with the guideline development methodology to be used.
• During (Meetings): 15 items including avoiding undue interruptions, adhering to the specified methodology, and referring to the PICO question at hand as a way to stay on task.
• After (Follow-up): 6 items including maintaining proper confidentiality of information discussed, reviewing meeting minutes to identify any discrepancies in a timely fashion, and assisting with the promotion, dissemination, and evaluation of the guideline as requested.

According to the authors, "Most participants found that the tool is most useful before guideline group meetings explaining what to expect at each phase. Participants thought that the tool was useful beforehand as a reference for orienting themselves to the structure of meetings, understanding the guideline development process, and what might be required of them. Respondents agreed that the tool serves as a reference for them to stay on track with the required tasks and to support structuring the process of guideline development."

The authors go on to suggest that the tool be used as required reading for all group members ahead of their participation on a panel. 

Piggott T, Baldeh T, Akl EA, et al. 2021. Supporting effective participation in health guideline development groups: The Guideline Participant Tool. J Clin Epidemiol 130:42-48.

Manuscript available from the publisher's website here. 

WHO Guidelines are Considering Health Equity More Frequently, but Reporting of Judgments is Often Incomplete

The GRADE evidence-to-decision (EtD) framework was developed as a way to more explicitly and transparently inform the considerations of the implications of clinical recommendations, such as the potential positive or negative impacts on health equity. A new analysis of World Health Organization (WHO) guidelines published between 2014 and 2019 - over half (54%) of which used the EtD framework - examines the consideration of health equities in the guidelines' resulting recommendations.

Dewidar and colleagues found that the guidelines utilizing the EtD framework were more likely to be addressing health issues in socially disadvantaged populations (42% of those developed with the EtD versus 24% of those without). What's more, the use of the EtD framework has risen over time, from 10% of guidelines published in 2016 (the year of the EtD's introduction) to 100% of those published within the first four months of 2019. Use of the term "health equity" increased to a similar degree over this period.

Just over one-third (38%) of recommendations were judged to increase or probably increase health equity, while 15% selected the judgment "Don't know/uncertain" and 8% provided no judgment. Just over one-quarter (28%) of the recommendations utilizing the EtD framework provided evidence for the judgment. When detailed judgments were provided, they were more likely to discuss the potential impacts of place of residence and socioeconomic status and less likely to explicitly consider gender, education, race, social capital, occupation, or religion.

Click to enlarge.

The authors conclude that while consideration of the potential impacts of recommendations on health equity has increased considerably in recent years, reporting of these judgments is still often incomplete. Reporting which published research evidence or additional considerations were used to make a judgment, as well as considering the various PROGRESS factors (Place, Race, Occupation, Gender, Religion, Education, Socioeconomic status, and Social capital) will likely improve the transparency of recommendations in future guidelines where health equity impacts are of concern.

Dwidr, O., Tsang, P., León-Garcia, M., Mathew, C., Antequera, A., Baldeh, T., ... & Welch, V. 2020. Over half of WHO guidelines published from 2014 to 2019 explicitly considered health equity issues: A cross-sectional suvey. J Clin Epidemiol 127:125-133.

Manuscript available from the publisher's website here.

Rapid, Up-to-Date Evidence Synthesis in the Time of COVID

In emergent situations with sparse and rapidly evolving bodies of research, evidence synthesis programs must be able to adapt to a shortened timeline to provide clinicians with the best available evidence for decision-making. (See our previous posts on rapid systematic review and guideline development, here, here, here, and here). But perhaps no health crisis in the modern era has made this more clear than the coronavirus disease 2019 (COVID-19) pandemic.

Recently, Murad and colleagues published a framework detailing a four-pillar program through which they have been able to synthesize evidence related to the COVID-19 pandemic. This system has been tried and tested within the Mayo Clinic, a multi-state academic center with more than 1.2 million patients per year.

 

Launched within two weeks of the World Health Organization’s declaration of COVID-19 as a pandemic, Mayo Clinic’s evidence synthesis program consisted of four major components:

• What is New?: an automatically generated list of COVID-19-related studies published within the last three days and categorized into topic areas such as diagnosis or prevention
• Repository of Studies: a running list of previously published studies since the first case report of COVID-19, including those that move from the “What is New?” list after three days’ time
• Rapid Reviews: reviews published within three to four days in response to pressing clinical questions from those on the frontlines and utilizing the study repository. To facilitate evidence synthesis, studies are often screened and selected by a single reviewer and evidence is rarely meta-analyzed.
• Repository of Reviews: a collection of reviews including those developed at Mayo and elsewhere, identified in twice-weekly searches and through a list of predetermined websites. To supplement knowledge, some reviews included indirect evidence borrowed from studies of other coronaviruses or respiratory infections, when appropriate.

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Within one month of the framework’s establishment, the team had conducted seven in-house rapid reviews and had indexed more than 100 newly published reviews into a database housing over 2,000 total.

 

The authors conclude that while an intensive system such as this may not be feasible in smaller health systems, cross-collaboration and sharing of knowledge can allow for informed and up-to-date clinical care that adapts in the face of a rapidly changing landscape of evidence.

Murad, M.H., Nayfeh, T., Suarez, M.U., Seisa, M.O., Abd-Rabu, R., Farah, M.H.E..., & Saadi, S.M. 2020. A framework for evidence synthesis programs to respond to a pandemic. Mayo Clin Proc 95(7):1426-1429.

Manuscript available at the publisher's website here.

Research Revisited: "Quality of Evidence is a Key Determinant for Making a Strong GRADE Guidelines Recommendation" (2015)

This month in 2015, Djulbegovic and colleagues published a paper that examined the impact of quality of evidence, balance between benefits and harms, patient values and preferences, and resource use (the four GRADE factors) on the strength of resulting clinical recommendations.

The four major GRADE factors that drive clinical recommendations 

The authors circulated a survey among 18 members of a guideline panel of the American Association of Blood Banking (AABB) who had recently convened to develop guidelines for the use of prophylactic versus therapeutic platelet transfusion in patients with thrombocytopenia. Using the panel members’ assessments of the GRADE factors with regards to the evidence that had been presented and their resulting recommendations for strong or weak recommendations, a logistic regression was conducted in order to examine the relative impact of each of the four GRADE factors.

The guideline panel had reviewed the evidence for ten key questions. Overall, the consistency of judgments across panel members was good (Cronbach’s alpha = 0.86). Those questions with a high quality of evidence were 4.5 times more likely to result in a strong recommendation (p < 0001), whereas none of the three remaining GRADE factors were significantly associated with the strength of the resulting recommendations. Moreover, the model suggested that in cases where the quality of evidence was high, there was a 90% chance of the resulting recommendation being strong; when the quality of evidence was very low, this chance dropped to 10%.

The figure from Djulbegovic shows the associations between increasing quality of evidence and strength of resulting recommendations

The authors concluded that the quality of evidence was far and away the most important contributing factor to the resulting strength of recommendations, at least within the studied guideline panel. However, it’s important to note that patient values and preferences, the balance between benefits and harms, and issues of resource use should all be involved in the process of moving from evidence to decisions, but the relative nebulousness around these considerations and a lack of determined structures for eliciting the data they require (such as the use of a patient panel or survey) likely make them less impactful on the overall strength of recommendation. 

The Evidence-to-Decision framework, which makes these additional considerations more explicit in the formulation of recommendations, was introduced just a year later. It’s worth wondering whether the relative impact of the remaining three GRADE factors has changed since the introduction and adoption of this framework – perhaps presenting an opportunity to revisit this research.

Djulbegovic, B., Kumar, A., Kaufman, R.M., Tobian, A., and Guyatt, G.H. Quality of evidence is a key determinant for making a strong GRADE guidelines recommendation. J Clin Epidemiol 68(7): 727-732. 

Manuscript is available at the publisher's website here. 

Rapid Guidelines in GRADE Pt. III: A checklist for rigorously rapid recommendations

In recent posts, we have introduced the concept of rapid recommendations as well as how developers of these recommendations at the World Health Organization (WHO) perceive facilitators and barriers to this process. This information was gathered as part of a published series on rapid guidance in 2018.

In the final part of the series, Morgan and colleagues propose an extension of the G-I-N/McMaster Checklist for Guideline Development aimed at those producing rapid guidelines. Comprising 21 discrete guideline principles that align with the original Guideline Development Checklist, the checklist is a tool for developers to take stock of the resources available for their rapid guideline development goals and identify areas in need of improvement. Important considerations include:

·      Make use of virtual meetings (Principle 7) and pre-meeting voting (Principle 15) to expedite the drafting of recommendations.

·      If possible, limit guideline panel composition to those not reporting financial COIs, or if not possible to provide necessary topic expertise, transparently declare any modifications of existing COI policies for the topic at hand (Principle 9).

·      Limiting the number of PICOs (Principle 10) and limiting the assessment of outcomes to only those deemed critical (Principle 11).

·      Consider ways to facilitate systematic review stage, such as updating existing reviews, developing rapid reviews, or tailoring search criteria to a smaller scope (Principle 13)

·      Arrange for external reviewers early on in the process so that they are quickly deployed when a draft is available for review (Principle 18).

The full checklist extension for rapid guidelines can be viewed here.

Morgan, R.L., Florez, I., Falavigna, M. et al. Development of rapid guidelines: 3. GIN-McMaster Guideline Development Checklist extension for rapid recommendations. Health Res Policy Sys 16, 63 (2018). https://doi.org/10.1186/s12961-018-0330-0

Manuscript available at the publisher's website here.

Rapid Guidelines in GRADE Pt. II: Rapid Recs in the Real World

In Part I of our series on rapid guidelines, we discussed the utility and terminology of rapid recommendations: those recommendations made in response to an urgent public health issue with timeframes ranging from a few short hours up to three months' time.

Who develops rapid guidelines?

In the first of a three-part series on rapid guidance published in 2018, Kowalski and colleagues conducted a systematic survey of the methodologies and processes of rapid guideline-producing organizations. Nomenclature used to identify these documents varied by organization, from “rapid advice guideline” to “interim guidance” to “short clinical guideline.” While the quality of these documents as assessed with the AGREE II tool was variable, it was greater in documents from the WHO and NICE than it was for the CDC or other smaller organizations. While NICE guidelines were of higher quality as assessed with the domains of AGREE II, they took substantially more time to develop than those from WHO.

It's important to note that while terminology differs between organizations, the word "interim" has been used to connote a response to an emergent public health issue with shorter time frames than a rapid guideline - typically on the order of 1-3 weeks. 

Organization	Nomenclature	AGREE II domain score range (lowest – highest)	Development timeline (from manual)
WHO	Rapid advice guideline	54 - 92	1-3 months
NICE	Short clinical guideline	81 - 94	11-13 months
CDC	Interim guidance	10 - 82	Not reported
Other	Interim guidelines, interim position statement, clinical guidelines	21 - 67	Not reported

Common Challenges and Facilitators to Rapid Guideline Development

While both the World Health Organization (WHO) and the National Institute for Health and Care Excellence (NICE) reported the use of a systematic review of the evidence to guide recommendations, common issues among developers included a lack of reporting on the management of conflict of interest, external review, and of the process for the drafting of recommendation.

In follow-up qualitative interviews with guideline-developing staff from WHO, participants cited a lack of adequate staffing, monetary resources, and evidence as key obstacles to the development of rapid guidelines. While the development of a systematic review is likely one of the more time-consuming elements of a rapid guideline process, most participants agreed that it is a fundamental part of developing trustworthy guidance that should not be skipped if possible. 

Participants also indicated that the external/peer review process can add unwanted time to the development of rapid guidelines. To this effect, developers can consider limiting the reach of peer review to the final draft only as well as reducing the ability to drastically change recommendations in a way that would require a reconvention of the guideline panel. Virtual conferencing technology was named as a facilitator to developing guidelines on a quicker schedule by reducing the need for face-to-face meetings. 

For a checklist to guide the development of rapid recommendations, see the G-I-N/McMaster checklist extension for rapid guidelines.


Kowalski, S.C., Morgan, R.L., Falavigna, M. et al. Development of rapid guidelines: 1. Systematic survey of current practices and methods. Health Res Policy Sys 16, 61 (2018).

Manuscript available at the publisher's website here.  

Florez, I.D., Morgan, R.L., Falavigna, M. et al. Development of rapid guidelines: 2. A qualitative study with WHO guideline developers. Health Res Policy Sys 16, 62 (2018).

Manuscript available at the publisher's website here.  

Rapid Guidelines in GRADE Pt. I: Needed Advice when Time is of the Essence

While most clinical practice guidelines take 2-3 years to develop and publish, the emergence of a public health crisis or urgent humanitarian need requires the dissemination of evidence-based guidance in a more rapid manner. To this effect, several national- and international-level guideline-producing organizations, such as the Centers for Disease Control (CDC) and the World Health Organization (WHO), have developed processes for the development of evidence-based guidance for these more urgent situations.

WHO’s 2006 recommendations for the pharmacological management of avian influenza in humans is one example of a rapidly developed guideline. Of current relevance, WHO has recently published interim guidance on the management of severe acute respiratory infection when novel coronavirus is suspected, and the UK’s National Institute for Health and Care Excellence (NICE) has also developed interim guidelines for the treatment of COVID-19 in patients receiving critical care, kidney dialysis, and systemic anticancer therapy. Because this matter is rapidly evolving and advice is needed immediately, the protocols used by NICE, WHO and other organizations are different than it would be for less urgent topics.

Can rapid guidelines use GRADE?

In short, yes. Recommendations can be made based on the transparent grading and reporting of the certainty of evidence that lie at the heart of GRADE, whether this is over the timeframe of hours, days, weeks, or months. The key word here is transparent: no matter the speed of development, recommendations should always be couched within the terms of the certainty of evidence behind them, and judgments of the evidence should be clearly presented. In a 2016 paper on the use of GRADE to respond to health questions with different levels of urgency, Thayer and Schünemann provide terms for the various speeds of response, and considerations for recommendations therein:

• Ultra-short emergency response: 1 or more hours

• Urgent response: 1-3 weeks

• Rapid response: 1-3 months

• Routine response: More than three months

Recommendations can still be formed based on the certainty of the evidence that's available, whatever that evidence may be. While systematic reviews of all available evidence are a foundational aspect of non-urgent guidelines, evidence in the form of narrative syntheses, modeling, or late-breaking data from the field can be used when time is short and systematically compiled data are sparse. Regardless of the source, the domains of GRADE still allow for evidence to be appraised and to guide the resulting direction and strength of recommendations.

Stay tuned for Pt. II coming soon, where we'll take a closer look at organizations that have developed rapid recommendations in response to time-sensitive public health issues.

For a checklist to guide the development of rapid recommendations, see the G-I-N/McMaster checklist.

For more information about appraising the certainty of evidence in the lack of meta-analyzed data, see this paper.

Thayer KA & Schünemann H. Using GRADE to Respond to Health Question With Different Levels of Urgency. Environment international. 2016 July-August: 585-589.

Manuscript available at the publisher's website here.

Research Shorts: From test accuracy to patient-important outcomes and recommendations

Contributed by Madelin Siedler, 2019/2020 U.S. GRADE Network Research Fellow

The potential risks and benefits of a screening or diagnostic testing strategy extend beyond the immediate impact and accuracy of the test itself. The result of testing will determine the available next steps and options for follow-up and management, and therefore will affect various patient-important outcomes in addition to potential resource utilization and equity considerations. These downstream consequences, and the certainty of evidence in these consequences, need to be considered when formulating recommendations surrounding testing. In a July 2019 paper published as part 22 of the Journal of Clinical Epidemiology’s GRADE guidelines series, Schünemann and colleagues provide suggestions for assessing certainty of evidence and determining recommendations for diagnostic tests and strategies.

While a collection of randomized controlled trial evidence examining the downstream consequences of various testing strategies is ideal in this scenario, such data are sparse. In lieu of this, guideline authors should develop a framework that includes each possible testing and follow-up treatment scenario, starting with the test in question and ending with patient-important outcomes.

 H.J. Schunemann et al. / Journal of Clinical Epidemiology 111 (2019) 69e82

As seen in this USPSTF sample framework, evidence begins with accuracy studies and ends with patient-important end-points.

This will allow the panel to visually link all relevant existing data together and develop clinical questions that are answerable with the evidence at hand. Data on the accuracy of a given test will help inform the expected number of false negatives and positives, which would then lead to potentially important downstream consequences - such as anxiety or a missed diagnosis - in addition to the effects of treating a diagnosed condition. The estimates of these beneficial and harmful potential outcomes should ideally come from a systematic review of evidence which can then be assessed for certainty. 

H.J. Schunemann et al. / Journal of Clinical Epidemiology 111 (2019) 69e82

The authors suggest providing one overall rating of the quality of evidence that takes into account the certainty of the diagnostic, prognostic, and management data that are available. Guideline panels should determine which outcomes of these bodies of evidence are critical and ascribe an overall rating based on the lowest level of certainty of the critical outcomes. 

Schünemann HJ, Mustafa RA, Brozek J, Santesso N, Bossuyt PM, Steingart KR, Leeflang M, Lange S, Trenti T, Langendam M, Scholten R. GRADE guidelines: 22. The GRADE approach for tests and strategies—from test accuracy to patient-important outcomes and recommendations. Journal of clinical epidemiology. 2019 Jul 1;111:69-82.

Manuscript available here on publisher's site.