GRADE Takes on the Planet: Introducing GRADE Guidance 46, Integrating Planetary Health in Health Guidelines

For decades, health guideline developers using the GRADE framework have worked to ensure that recommendations reflect the best available evidence on patient outcomes, values, costs, and equity. A major new addition to that framework asks guideline panels to consider something broader: the health of the planet itself. In a paper recently published in Annals of Internal Medicine, Piggott, Saadat, Herrmann, and colleagues from the GRADE Planetary Health Project Group present the first official GRADE guidance for integrating planetary health into health guideline development.

Health systems are not passive bystanders in the planetary health crisis; they actively contribute to it. Health care accounts for an estimated 5.2% of global greenhouse gas (GHG) emissions, and its impacts on freshwater use may be even more significant relative to national benchmarks. Until now, however, health guidelines have rarely systematically considered these environmental consequences. A scoping review cited in the paper found just four health guidelines that had addressed planetary health dimensions at all, and even those did so with limited methodological rigor. This guidance is designed to close that gap.

The project group, working from January 2023 through May 2025, developed 7 domains of guidance through iterative case study analyses, expert workshops, and a two-round global Delphi consensus process involving 85 international experts. The result is a structured framework that maps onto the familiar steps of guideline development, from scoping and question formulation through to evidence synthesis and the evidence-to-decision (EtD) framework. 

The most concrete addition is a new criterion within the GRADE evidence-to-decision (EtD) framework, which is the table guideline panels use at the final stage of a review to move from evidence to recommendations. Alongside existing criteria like "balance of effects," "costs," and "equity," panels now have a dedicated row for planetary boundaries. For each boundary relevant to their guideline topic, panels work through a set of signaling questions drawn directly from environmental science, then record a summary judgment ranging from "large desirable" to "large undesirable." 

Four case studies bring the guidance to life, ranging from the choice between anesthetic gases (sevoflurane versus desflurane, with dramatically different GHG profiles) to dietary recommendations around red meat consumption. In the red meat case, applying the planetary health lens would have reversed the direction of a previously published conditional recommendation, shifting it from continuing current intake to reducing it, based on the intervention's large undesirable effects on climate, land use, freshwater, and nutrient cycles. This underscores that planetary health evidence can and should be considered when making recommendations.

This guidance is meant to fit into the existing GRADE framework, ensuring a seamless adoption. The framework provides signalling questions for each planetary boundary to help panels make informed judgments without requiring in-house environmental science experts. Including a planetary health expert on the panel is suggested but optional and the guidance is clear that not every guideline needs to address every planetary boundary. The goal is transparency and consideration.

As the authors note, the crises facing our planet warrant the best effort guideline panels can offer, and this framework gives them the tools to start.

References

Thomas Piggott, Pakeezah Saadat, Alina Herrmann, et al. Integrating Planetary Health in Health Guidelines (GRADE Guidance 46). Ann Intern Med 2026;179:874-884. [Epub 12 May 2026]. doi:10.7326/ANNALS-25-04761

https://www.acpjournals.org/doi/10.7326/ANNALS-25-04761 

Extra Resources

GRADE guidance articles in the Journal of Clinical Epidemiology (JCE) series: https://www.cochrane.org/learn/courses-and-resources/cochrane-methodology/grade/jce-series

GRADE Book is the most comprehensive and up-to-date resource on the GRADE approach. It will replace the previous GRADE Handbook by 2026, with updated content being progressively released. https://book.gradepro.org/

GRADE working group: https://www.gradeworkinggroup.org/

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.

Summarizing Patient Values and Preferences Data to Better Inform Recommendations

The consideration of patients' values and preferences during the formulation of clinical recommendations requires that guideline developers have an understanding of how patients and other stakeholders weigh the potential desirable and undesirable effects of any given intervention against one another. This consideration of the Relative Importance of Outcomes (RIO) is crucial for developing clinical recommendations that are most relevant to the providers and patients who will be using them. But how can we ensure that guideline developers have a thorough understanding of these considerations when going from evidence to decisions?

In a new paper to be published in the July issue of Journal of Clinical Epidemiology, Zhang and colleagues developed and tested a standardized summary of findings table that presents the RIO evidence on a given clinical decision in order to better inform the development of recommendations while keeping the data on patients' values and preferences top-of-mind.

Figure 1 of the paper provides the route map of the table's user testing process

The methods included four rounds of user testing comprising semi-structured interviews with clinical researchers and guideline developers. Guided by Morville's Honeycomb Model, the authors aimed to assess the usability, credibility, usefulness, desirability, findability, and value of the table while addressing identified issues. Overall, 20 individuals participated, 19 of whom had experience in guideline development and all of whom had experience with Summary of Findings tables.

In terms of the table's usability, problems interpreting and understanding the health utility were present; the introduction of a visual analogue scale (VAS) improved this. The combination of quantitative and qualitative evidence when considering RIOs, in addition to the presentation of the variability surrounding given estimates, were other sources of confusion. However, the participants generally found the table useful, valuable, and easy to navigate.

Zhang, Y, Li, S-A, Yepes-Nuñez, J.J., Morgan, R.L., Pardo-Hernandez, H., Alonso Coello, P., Ren, M., ... & Schünemann, H.J. (2022). GRADE summary of findings tables enhanced understanding of values and preferences evidence. J Clin Epidemiol 147: 60-68. Manuscript available at the publisher's website here.

A New Template for Standardized Wording when Reporting Evidence-to-Decision Considerations in Guidelines

One of the major tenets of GRADE is that certainty of the evidence is just one component of decision-making. Ultimately, decision-makers also need to take into account important factors such as values and preferences, feasibility, and considerations of the impact of a decision on health equity and resource utilization. These factors and others are part of the Evidence-to-Decision (EtD) framework that guides the process from the assessment of certainty of evidence to the final formulation of recommendations in a structured, transparent manner.

Often, multiple teams and individuals involved in the development of a guideline will need to work together to compete the EtD process, which can be a source of confusion. Additionally, until now, no official guidance existed for the use of standardized wording when considering and reporting each EtD framework component. Earlier this year, Piggott and colleagues aimed to address this issue with an article published in the Journal of Clinical Epidemiology.

The project, comprising ten guideline development groups and over 250 recommendations, set out to develop a standardized framework for clear, transparent, and efficient wording when reporting Evidence-to-Decision components within a guideline. This template was then used in two guidelines in development - the European Commission Initiative on Breast Cancer (ECIBC) and the Endocrine Society guidelines on hyperglycemia, hypoglycemia and hypercalcemia. During this process, the authors were able to pilot the wording, receive feedback, and refine the template. The real-life guidelines were also used to provide examples of wording recommendations.

The article includes suggested wording structure and examples for reporting the magnitude and certainty of effect estimates, for conclusions of each portion of the EtD framework, and for justification of recommendations as well as notes on implementation considerations, monitoring and evaluation, and research priorities. 

The authors note that these suggestions are preliminary and may require further refinement. Additionally, current examples of consistent and clear wording of EtDs continues to be lacking, though the dissemination of this guidance may improve future publications. While the suggestions within the article are focused on clinical decisions related to management of conditions, future efforts may expand this to guidelines for diagnostic testing, coverage, and other important areas.

Piggott, T., Baldeh, T., Dietl, B., Wiercoch, W., Nieuwlaat, R., Santesso, N., ... & Schünemann, H. (2022). Standardized wording to improve efficiency and clarity of GRADE EtD frameworks in health guidelines. J Clin Epidemiol (online ahead of print). Manuscript available at the publisher's website here.

   

Digging Deeper: 5 Ways to Help Guide Decision-Making When Research Evidence is "Insufficient"

A key tenet underlying the GRADE framework is that the certainty of available research evidence is a key factor to be considered in the course of clinical decision-making. But what if little to no published research exists off of which to base a recommendation? At the end of the day, clinicians, patients, policymakers, and others will still need to make a decision, and will look to a guideline for direction. Thankfully, there are other options to pursue within the context of a systematic review or guideline that ensures that as much of the available evidence is presented as possible, although it may be from less traditional or direct sources.

A new project conducted by the Evidence-based Practice Center (EPC) Program of the Agency for Healthcare Research and Quality (AHRQ) developed guidance for supplementing a review of evidence when the available research evidence is sparse or insufficient. This guidance was based on a three-pronged approach, including:

• a literature review of articles that have defined and dealt with insufficient evidence, 
• a convenience sample of recent systematic reviews conducted by EPCs that included at least one outcome for which the evidence was rated as insufficient, and
• an audit of technical briefs from the EPCs, which tend to be developed when a given topic is expected to yield little to no published evidence and which often contain supplementary sources of information such as grey literature and expert interviews.

Through this approach, the workgroup identified five key strategies for dealing with the challenge of insufficient evidence:

1. Reconsider eligible study designs: broaden your search to capture a wider variety of published evidence, such as cohort or case studies.
2. Summarize evidence outside the prespecified review parameters: use indirect evidence that does not perfectly match the PICO of your topic in order to better contextualize the decision being presented.
3. Summarize evidence on contextual factors (factors other than benefits/harms): these include key aspects of the GRADE Evidence-to-Decision framework, such as patient values and preferences and the acceptability, feasibility, and cost-effectiveness of a given intervention.
4. Consider modeling if appropriate, and if expertise is available: if possible, certain types of modeling can help fill in the gaps and make useful predictions for outcomes in lieu of real-life research.
5. Incorporate health system data: "real-world" evidence such as electronic health records and registries can supplement more mechanistic or explanatory RCTs.

Some of these challenges can be more efficiently addressed up-front, before the scoping of a new review even begins. For instance, identifying topic experts and stakeholders who are familiar with the quantity and quality of available evidence can help a group foresee potential gaps and plan for the need to broaden the scope. Care should be taken to identify the outcomes that are of critical importance to patients, and through this lens, develop strategies and criteria within the protocol that will best meet the needs of the review while tapping into as much evidence as possible. Finally, researchers should avoid using the term "insufficient" when describing the evidence, and instead explicitly state that no eligible studies or types of evidence were available.

Murad MH, Chang SM, Fiordalisi CV, et al. (2021). Improving the utility of evidence synthesis for decisionmakers in the face of insufficient evidence. J Clin Epidemiol, ahead-of-print. 

Manuscript available from publisher's website here.

Help for Choosing Among Multiple Interventions Using GRADE

It is not uncommon for a health guideline to compare two or more interventions against one another. However, while sophisticated statistical approaches such as network meta-analyses allow us to compare these interventions head-to-head in terms of specified health outcomes, they do not take other important aspects of clinical decision-making into account, such as patient values and preferences, resource use, and equity considerations. A new paper from Piggott and colleagues aims to provide initial suggestions for using the GRADE evidence to decision (EtD) framework when choosing which of multiple interventions to recommend.

The authors identified a need for more direction when undertaking a multiple intervention comparison (MC) approach while working on recently released guidelines for the European Commission Initiative on Breast Cancer in which multiple screening intervals were compared against one another. Based on this experience, the group drafted a flexible yet transparency-minded framework to help guide similar efforts in the future, which was then added as a module in GRADE's official guideline development software, GRADEpro. 

The new module was pilot-tested for feasibility with several additional guidelines. The module allows the user to select and then compare multiple pairwise comparisons against one another (for instance, with one column for "Intervention 1 vs. Comparator 1" and "Intervention 2 vs. Comparator 2"). A five-star system is used to judge various components of the EtD, such as cost effectiveness, for each individual intervention and comparator, whereas a column on the right-hand side allows the user to input the relative importance of these components in decision-making.

Finally, the user can review all judgments across interventions and summatively recommend the most favorable intervention(s) overall.

Piggott T, Brozek J, Nowak A, et al. (2021). Using GRADE evidence to decision frameworks to choose from multiple interventions. J Clin Epidemiol 130:117-124.

Manuscript available from the publisher's website here.

Practical Tips for Finding and Assessing Patient Survey Data

 An essential part of translating a body of evidence into a clinical recommendation within the GRADE framework is the consideration of patients' values and preferences. Not only should the likely treatment preferences and values placed on outcomes among the patient population be considered; if there is likely a great amount of variability within these, this may also influence the ultimate strength of recommendation.

Guideline panels and public health decision-makers may use self-reported patient survey data to better understand the range of patient values and preferences when formulating recommendations or policies. However, like all sources of evidence, patient surveys may be at risk for specific sources of bias which can ultimately affect the results. What should decision-makers look out for when applying patient survey data to a recommendation for care? In a recently published paper, Santesso and colleagues propose a practical guide for finding, interpreting, and applying patient data to better inform healthcare decision-making.

Click to enlarge.

Because 97% of published surveys have been found to use the words "survey" or "questionnaire" in the title, the authors suggest using these terms in title, abstract, and topic fields when conducting a search for relevant data. When assessing the risk of bias of a given survey, decision-makers should ask whether the population was adequately representative of the patient population in question, taking care to consider the use of random sampling and the potential impact of nonresponse. A survey should also be assessed for whether it measures the intended constructs adequately. Survey authors should report the variability around reported measures whenever possible, and these data can be used to judge the overall variability in patient values and preferences. Finally, decision-makers should take care to discern how directly the survey data applies to the patient population in question; the table of survey respondent characteristics is a useful place from which to draw judgments of directness.

Using these helpful and practical points of guidance, guideline panel members and clinical decision-makers can better inform their retrieval, critical appraisal, and application of patient survey data to important healthcare questions, ultimately resulting in more informed guidelines and policies.

Santesso N, Akl E, Bhandari M, Busse JW, Cook DJ, Greenhalgh T, Muti P, Schünemann H, and Guyatt G. (2020). A practical guide for using a survey about attitudes and behaviors to inform health care decision making. J Clin Epidemiol 128:93-100.

Manuscript available from the publisher's website here. 

U.S. Guideline-Producing Organizations Show Some Promise, Room for Improvement in their Application of GRADE

As many as one-third of guideline-producing health organizations in the United States report using the GRADE framework, but exactly how closely these organizations follow the key tenets of GRADE - such as using evidence summaries of each identified outcome to inform the overall certainty of evidence, and linking this certainty to a strength of recommendation - is a matter of debate.

In study by Dixon and colleagues published earlier this year in the Journal of Clinical Epidemiology, the authors set out to evaluate the use of GRADE in U.S.-based guidelines published between 2011 and 2018 and available in the National Guidelines Clearinghouse. Assessing up to three of the most recent guidelines from each of 135 identified U.S.-based organizations, the authors used several criteria to examine how closely each of the 67 resulting guidelines adhered to core GRADE concepts, including:

• defining the certainty of evidence,
• explicitly considering the GRADE domains when assessing the certainty of evidence, and
• consistently defining the strength of resulting recommendations as strong or weak/conditional.

While most (89.6%) defined the certainty of evidence in a matter consistent with GRADE, only 10.4% explicitly reported examining certainty through all 8 GRADE criteria. Only 13.4% of guidelines assessing the certainty of evidence sourced from non-randomized trials reported assessing the potential reasons to upgrade the certainty of evidence (i.e., large magnitude of effect, dose-response gradient, and residual confounding). Finally, only about half (53.7%) provided an evidence profile or summary of findings table describing the assessments, and while reporting of the certainty of evidence and the balance between desirable and undesirable effects was most common (100% and 97%, respectively), explicit consideration of resource use and patients' values and preferences were also fairly common (73.1% and 77.6%, respectively) .The use of GRADE in line with the authors' established criteria appeared to grow somewhat more frequent over time, indicating a general trend toward proper use of GRADE.

Figure from Dixon et al. shows the relative reporting frequency of the various GRADE criteria for assessing certainty of evidence in years 2011-14 versus 2015-18, suggesting a trend for improved reporting over time. Click to enlarge.

The authors conclude that continued training of guideline developers and dissemination of education on the appropriate application of GRADE should further improve adherence, including the explicit consideration of all eight domains for assessing the certainty of evidence and of all aspects that inform the translation of this evidence into clinical recommendations.

Dixon C, Dixon PE, Sultan S, Mustafa R, Morgan RL, Murad MH, Falck-Ytter Y, and Dahm P. (2020). Guideline developers in the United States were inconsistent in applying criteria for appropriate Grading of Recommendations, Assessment, Development and Evaluation use. J Clin Epidemiol 124:193-199.

Manuscript available at 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.