What is New?-

We provide a demonstration of how to systematically address health equity considerations in rheumatology throughout the Evidence to Decision process for guideline and recommendation development.

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Our data synthesizes realities of six population groups facing inequities in Canadian rheumatology (those living in rural and remote locations, Indigenous Peoples, elderly persons with frailty, minority populations of first-generation immigrants and refugees, persons with low socioeconomic status or who are vulnerably housed, and the diversity of sex and gender populations) and contextualizes how different recommendations may be necessary to ensure desired rheumatoid arthritis outcomes.

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While centered on rheumatology care and outcomes, our findings may also apply to other chronic diseases where population inequities exist.

AbstractObjective

Health equity is a priority for clinical and public health practice and promoted in GRADE's Evidence to Decision (EtD) Framework, yet there is still limited integration of specific equity considerations in chronic disease guideline development and implementation. Our objective was to embed equity considerations for upcoming Canadian Rheumatoid Arthritis treatment guidelines.

Study Design and Setting

In parallel with the Guidelines Committee process, considerations for six population groups (rural and remote residents, Indigenous Peoples, elderly persons with frailty, minority populations of first-generation immigrants and refugees, persons with low socioeconomic status or who are vulnerably housed, and sex and gender populations) based on literature reviews and key informant interviews were identified and contextualized to each step in the GRADE EtD framework.

Results

The EtD Framework domains relevant to rheumatoid arthritis treatment and management were analyzed through patient-centric, social determinant and economic lenses, while considering implementation feasibility. This determined tailored considerations relevant to recommendations for the priority populations to mitigate potential intervention-generated inequities.

Conclusion

This approach provides a demonstration of the process of incorporating equity in the evidence to decision process and can be applied in future rheumatic disease guidelines while also informing a research agenda for equity in rheumatology outcomes.

Keywords

Funding:

C Barnabe: Canada Research Chair in Rheumatoid Arthritis and Autoimmune Diseases

E Pianarosa: Canadian Institutes of Health Research Institute of Musculoskeletal Health and Arthritis Undergraduate Summer Studentship

Project funding: Canadian Institutes of Health Research Foundation Scheme (Barnabe)

The funders had no role in any aspects of the study.

Declaration of Interest: none

Author Statements:

Cheryl Barnabe: Conceptualization, Project administration, Funding acquisition, Supervision, Methodology, Investigation, Formal Analysis, Writing Original Draft, Review and Editing, Visualization; Emilie Pianarosa: Funding acquisition, Investigation, Review and Editing; Glen Hazlewood: Conceptualization, Methodology, Formal Analysis, Review and Editing-

We provide a demonstration of how to systematically address health equity considerations in rheumatology throughout the Evidence to Decision process for guideline and recommendation development.

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Our data synthesizes realities of six population groups facing inequities in Canadian rheumatology (those living in rural and remote locations, Indigenous Peoples, elderly persons with frailty, minority populations of first-generation immigrants and refugees, persons with low socioeconomic status or who are vulnerably housed, and the diversity of sex and gender populations) and contextualizes how different recommendations may be necessary to ensure desired rheumatoid arthritis outcomes.

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While centered on rheumatology care and outcomes, our findings may also apply to other chronic diseases where population inequities exist.

1. IntroductionGRADE (Grading Recommendations Assessment and Development Evidence) methodology is widely applied in the development of clinical practice, public health, and health system guidelines. GRADE promotes a systematic approach to evaluating the certainty of evidence and developing and grading recommendations [[1]Guyatt G Oxman AD Akl EA et al.GRADE guidelines: 1. Introduction-GRADE evidence profiles and summary of findings tables.]. In the GRADE Evidence to Decision (EtD) Framework, health equity is an essential element in the process for developing recommendations from a population health perspective, aimed at ensuring that the recommendations improve or do not worsen inequities in care. From an individual perspective, thoughtful consideration of health equity issues when informing treatment decisions should serve to support implementation of the approaches selected.While considerations of health equity may be considered as a unique and separate step in the EtD Framework [[2]Alonso-Coello P Schünemann HJ Moberg J et al.GRADE Evidence to Decision (EtD) frameworks: a systematic and transparent approach to making well informed healthcare choices. 1: Introduction.], it has also been proposed that health equity should instead be explicitly considered at each step of the Framework [3Welch VA Akl EA Guyatt G et al.GRADE equity guidelines 1: considering health equity in GRADE guideline development: introduction and rationale., 4Akl EA Welch V Pottie K et al.GRADE equity guidelines 2: considering health equity in GRADE guideline development: equity extension of the guideline development checklist., 5Welch VA Akl EA Pottie K et al.GRADE equity guidelines 3: considering health equity in GRADE guideline development: rating the certainty of synthesized evidence., 6Pottie K Welch V Morton R et al.GRADE equity guidelines 4: considering health equity in GRADE guideline development: evidence to decision process.]. Different populations may place different priorities on the questions addressed or outcomes considered. In some cases, evidence on benefits and harms or the certainty of this evidence may differ between population groups. Patient preferences, acceptability of interventions, economic considerations and feasibility of implementation may also vary by population. To facilitate conceptualizing which populations at risk for inequities should be considered, the PROGRESS-Plus acronym (Place of residence, Race/ethnicity/culture/language, Occupation, Gender/Sex, Religion, Education, Socioeconomic status, Social capital, and other characteristics (Plus) such as sexual orientation, age and disability) [[7]O'Neill J Tabish H Welch V et al.Applying an equity lens to interventions: using PROGRESS ensures consideration of socially stratifying factors to illuminate inequities in health.] is used for categorization.In rheumatoid arthritis, several important health inequities exist. As treatment is guided by subspecialists, access to care may be challenging for those in rural and remote locations [[8]Movahedi M Joshi R Rampakakis E et al.Impact of residential area on the management of rheumatoid arthritis patients initiating their first biologic DMARD: Results from the Ontario Best Practices Research Initiative (OBRI).]. Formulary policies may impede access to necessary medications [[9]Barnabe C Healy B Portolesi A Kaplan GG Hemmelgarn B Weaselhead C. Claims for disease-modifying therapy by Alberta non-insured health benefits clients.]. Instigated by our conviction that guidelines updates for our national rheumatology association should address equity, we undertook the development of an Equity EtD Framework contextualized to the Canadian rheumatology practice setting, specifically in rheumatoid arthritis. Here, we share as a demonstration how each step in the EtD Framework was approached for six priority population groups in Canada.2. Methods2.1 Development of draft frameworkThe draft Equity EtD Framework was developed by 2 authors (CB, GH). The context of the framework was drug therapy recommendations for rheumatoid arthritis in Canada. These recommendations are focused on individual clinical decision-making. Inputs for the Equity EtD Framework were the following:1Qualitative data: Themes related to population factors, initial and ongoing healthcare access, and medication access and strategy impacting rheumatoid arthritis care were reported in a prior study [[10]Pianarosa E Hazlewood G Thomas M Hsiao R Barnabe C. Supporting Equity in Rheumatoid Arthritis Outcomes in Canada: Population-Specific Factors in Patient-Centered Care.]. In brief, we conducted 35 stakeholder interviews with healthcare providers, researchers with expertise in equity, and patients with lived experience from six population groups at risk for inequities of particular relevance to Canadian rheumatology practice: those living in rural and remote locations, Indigenous Peoples (First Nations, Métis and Inuit), elderly persons with frailty, minority populations of first-generation immigrants and refugees, persons with low socioeconomic status or who are vulnerably housed, and the diversity of sex and gender populations. These six groups were selected following a survey of the Canadian Rheumatology Association's Quality Care and Guidelines operational committee memberships, a review of other Canadian chronic disease guidelines, and literature reviews evaluating the rheumatoid arthritis outcomes in the priority population groups, described in more detail below. The stakeholder interviews focused on identifying realities for the populations with regards to disease burden and preferred treatment approaches, challenges in health service access (care and medications) and solutions these experts were aware of to mitigate these issues and support equity in access and outcomes. Logic models were constructed by the research team members to promote understanding of barriers faced by these populations in accessing high quality rheumatology care, and we summarized mechanisms to mitigate threats to equity along the rheumatology care journey.2Literature reviews on RA outcomes by equity groups: This included a review of randomized trials of RA drug therapy to determine whether there was any evidence of different relative treatment effects that would be presented in a GRADE Summary of Findings Table. There were only two studies identified evaluating the association between outcomes and sex or age. In two other systematic reviews, we evaluated rheumatoid arthritis outcomes for two high-priority populations, Indigenous populations [[11]Systematic review of rheumatic disease phenotypes and outcomes in the Indigenous populations of Canada, the USA, Australia and New Zealand., [12]Loyola-Sanchez A Hurd K Barnabe C. Healthcare utilization for arthritis by indigenous populations of Australia, Canada, New Zealand, and the United States: A systematic review.] and rural and remote residents [[13]Pianarosa E Chomistek K Hsiao R et al.Global Rural and Remote Patients with Rheumatoid Arthritis: A Systematic Review.]. This evidence, largely non-randomized, was used to decide whether the absolute treatment responses and risks might vary by population groups. Finally, we used a published systematic review of RA treatment preferences [[14]Durand C Eldoma M Marshall DA Bansback N Hazlewood GS. Patient Preferences for Disease-modifying Antirheumatic Drug Treatment in Rheumatoid Arthritis: A Systematic Review.]. In this review, we had systematically identified whether treatment preferences are associated with patient characteristics. Indeed, we found that preferences were often more strongly associated with population membership than with disease characteristics.

With these sources of information, we drafted an initial Equity EtD Framework. The two authors (CB, GH) populated the EtD Framework components for each individual group, outlining the specific equity considerations raised during the interviews and in the available literature.

2.2 Feedback and revisionsFeedback was sought from members of two different guideline panels composed of rheumatologists, arthritis researchers and patient representatives. The first was the panel developing living guidelines for adult rheumatoid arthritis. The guideline panel was tasked with developing a recommendation for tapering treatment in patients who are in sustained remission. This was undertaken using the GRADE ‘adolopment’ approach [[15]Schünemann HJ Wiercioch W Brozek J et al.GRADE Evidence to Decision (EtD) frameworks for adoption, adaptation, and de novo development of trustworthy recommendations: GRADE-ADOLOPMENT.], meaning the group used a published recommendation from another group, and worked through the EtD process, contextualizing the recommendation to the Canadian context. During this process, the Equity EtD Framework was applied in the discussions for each step of the process. The second guideline group was developing recommendations for juvenile uveitis, again using a GRADE adolopment approach. This provided an initial opportunity to see whether the draft Equity EtD Framework might be useful outside of the population for which it was developed. The feedback on usability and content applicability from both groups was incorporated and circulated prior to finalizing. The resulting Equity EtD Framework, presented here, is as an initial version, open for discussion, and with the view to revise iteratively over time.3. Results

As our Equity EtD Framework includes considerations for six populations, we present a separate table and discussion for each step of the EtD Framework to summarize key aspects.

3.1 Priority of the problemThis first step in the EtD Framework reflects on the seriousness of consequences of the problem (in terms of severity or importance for potential benefits or savings) and it being recognized as a priority politically or from a policy decision perspective, driving the need for a recommendation [[2]Alonso-Coello P Schünemann HJ Moberg J et al.GRADE Evidence to Decision (EtD) frameworks: a systematic and transparent approach to making well informed healthcare choices. 1: Introduction.]. In general, from a societal or health system perspective, high disease prevalence and more severe outcomes result in higher direct health costs, increasing the priority of setting treatment recommendations for populations facing inequities. At an individual level, the recommendation may be of lower priority for certain population groups due to competing health and social concerns [[10]Pianarosa E Hazlewood G Thomas M Hsiao R Barnabe C. Supporting Equity in Rheumatoid Arthritis Outcomes in Canada: Population-Specific Factors in Patient-Centered Care.].In our framework, several equity considerations were identified that may impact the priority of the problem (Table 1). This may differ related to geographic considerations, such that recommendations reflecting access to care or therapy may be more important politically for advocacy purposes for populations located in rural or remote settings [[13]Pianarosa E Chomistek K Hsiao R et al.Global Rural and Remote Patients with Rheumatoid Arthritis: A Systematic Review.]. Indigenous populations may choose to promote questions that focus on non-Western treatment recommendations [[16]Loyola-Sanchez A Hazlewood G Crowshoe L et al.Qualitative Study of Treatment Preferences for Rheumatoid Arthritis and Pharmacotherapy Acceptance: Indigenous Patient Perspectives.], or those that examine approaches to maintain function to fulfill their social roles [[10]Pianarosa E Hazlewood G Thomas M Hsiao R Barnabe C. Supporting Equity in Rheumatoid Arthritis Outcomes in Canada: Population-Specific Factors in Patient-Centered Care.]. Different priorities for treatment recommendations could emerge too, as exemplified by elderly persons with frailty where treatment questions that prioritize symptom control and quality of life would be of greater importance than questions to support long term disease outcomes [[10]Pianarosa E Hazlewood G Thomas M Hsiao R Barnabe C. Supporting Equity in Rheumatoid Arthritis Outcomes in Canada: Population-Specific Factors in Patient-Centered Care.]. For diverse sex and gender groups, treatment considerations remain of high importance but for differing reasons. For women and men and gender diverse people, treatment recommendations that support maintaining important social roles would be valued, whereas for females a higher priority may be placed on treatment questions that explore safety throughout reproductive phases [[10]Pianarosa E Hazlewood G Thomas M Hsiao R Barnabe C. Supporting Equity in Rheumatoid Arthritis Outcomes in Canada: Population-Specific Factors in Patient-Centered Care.].

Table 1Equity Considerations for ‘Priority of the Problem’

Table 2Equity Considerations for Health Benefits of Treatments and Adverse Effects

Table 3Variations in the Importance of Main Outcomes in Populations Facing Inequities

Table 4Resource Considerations for Populations Facing Inequities in Rheumatoid Arthritis

Table 5Considerations for Treatment Acceptability

Table 6Feasibility of Interventions for Different Population Groups

3.2 Health Effects

This aspect in the EtD Framework seeks to consider the magnitude of benefit related to a treatment or intervention, as well as undesirable health effects. These potentials may vary between populations, reflecting disease severity and the opportunity for improvement, underlying variations in medication metabolism, and comorbidities or other factors which limit effectiveness due to the development of adverse effects.

Based on our prior literature review, we did not find evidence to suggest there are differences in the relative benefits and risks of drug therapy (effect-modification) in relation to the population groups facing inequities. However, we did find direct and indirect evidence that certain equity groups experience worse RA outcomes overall, which would impact the absolute treatment effects. Indigenous populations are recognized as having a higher frequency of poor prognostic factors which impact outcomes [[11]Systematic review of rheumatic disease phenotypes and outcomes in the Indigenous populations of Canada, the USA, Australia and New Zealand.], thus treatments with a greater chance of benefit may be preferred. This must be weighed against the potential risk of adverse events and potential medication interactions with the increased frequency of comorbidities and chronic diseases in the population, as also exists for persons from rural and remote communities and the elderly with frailty [[10]Pianarosa E Hazlewood G Thomas M Hsiao R Barnabe C. Supporting Equity in Rheumatoid Arthritis Outcomes in Canada: Population-Specific Factors in Patient-Centered Care.]. Refugees and first-generation immigrant populations may have an increased risk of latent infections, increasing the risk of adverse treatment effects if sufficient screening for such infections is not undertaken [[10]Pianarosa E Hazlewood G Thomas M Hsiao R Barnabe C. Supporting Equity in Rheumatoid Arthritis Outcomes in Canada: Population-Specific Factors in Patient-Centered Care.]. With an increased frequency of substance misuse and addictions for persons from low socioeconomic status and vulnerably housed populations, treatment adverse effects may arise [[10]Pianarosa E Hazlewood G Thomas M Hsiao R Barnabe C. Supporting Equity in Rheumatoid Arthritis Outcomes in Canada: Population-Specific Factors in Patient-Centered Care.]. For females, disease severity is increased [[17]Sokka T Toloza S Cutolo M et al.Women, men, and rheumatoid arthritis: analyses of disease activity, disease characteristics, and treatments in the QUEST-RA study.], thus there is increased potential for beneficial health effects, however with variations in the magnitude of a treatment effect depending on the outcomes examined. Safety of treatments for females in their reproductive years is typically not available from available trial data.3.3 Certainty of Evidence of EffectsThis step in the GRADE EtD framework requires that available evidence be categorized by its’ strength. As detailed above, most of the populations facing inequities will not be adequately represented in clinical trials, nor will available evidence have been stratified to examine population-specific outcomes. This raises the concern that the evidence may be judged as insufficient for the population group. Further, a hierarchy of knowledge that privileges western-based evidence exists, and questions on treatments outside of western medicine may not be amenable to mechanisms of inquiry such as randomized controlled trials. Together, these factors increase the potential for worsening health inequities by not being able to make any recommendations. Following GRADE guidance [[5]Welch VA Akl EA Pottie K et al.GRADE equity guidelines 3: considering health equity in GRADE guideline development: rating the certainty of synthesized evidence.], unless there is specific evidence for the population that can be appropriately rated for certainty, then guidelines committees should proceed assuming effects would be similar to the general population.3.4 Outcome ImportanceIn this step, variability in the importance or value of main study outcomes should be evaluated. Many Indigenous Peoples value holistic health and wellness, and outcomes that reflect impact on all aspects of physical, mental, emotional and spiritual health will be higher in importance for them [[18]Loyola-Sanchez A Pelaez-Ballestas I Crowshoe L et al."There are still a lot of things that I need": a qualitative study exploring opportunities to improve the health services of First Nations People with arthritis seen at an on-reserve outreach rheumatology clinic.]. For refugee and immigrant populations, cultural practices and approaches, and health literacy, will be reflected in the values placed on main outcomes [[10]Pianarosa E Hazlewood G Thomas M Hsiao R Barnabe C. Supporting Equity in Rheumatoid Arthritis Outcomes in Canada: Population-Specific Factors in Patient-Centered Care.]. In elderly persons with frailty, outcomes that reflect quality of life and simplified medication regimes will be of higher importance than remission or interruption of damage progression [[10]Pianarosa E Hazlewood G Thomas M Hsiao R Barnabe C. Supporting Equity in Rheumatoid Arthritis Outcomes in Canada: Population-Specific Factors in Patient-Centered Care.]. Those experiencing homelessness and with low socioeconomic status, and gender groups, may value outcomes that reflect effect of treatment on participation in society, such as work productivity [[10]Pianarosa E Hazlewood G Thomas M Hsiao R Barnabe C. Supporting Equity in Rheumatoid Arthritis Outcomes in Canada: Population-Specific Factors in Patient-Centered Care.]. Females that are pregnant may value treatment outcomes differently than their provider, placing higher importance on reducing risk to the fetus, whereas clinicians may strive for optimal disease control [[10]Pianarosa E Hazlewood G Thomas M Hsiao R Barnabe C. Supporting Equity in Rheumatoid Arthritis Outcomes in Canada: Population-Specific Factors in Patient-Centered Care.].3.5 Resource UseThis domain of the EtD Framework considers cost-effectiveness, but also the magnitude of the resource requirements. These are typically substantial in rheumatoid arthritis, and cost coverage variations are encountered for persons from populations facing inequities. Here, the guideline committee is asked to consider not only societal costs, but also those of individuals from population groups with inequities voiced during previous data collection [[10]Pianarosa E Hazlewood G Thomas M Hsiao R Barnabe C. Supporting Equity in Rheumatoid Arthritis Outcomes in Canada: Population-Specific Factors in Patient-Centered Care.]. Gender disparities in income potential are recognized and not yet resolved in society, impacting access to cost coverage for women. Additionally, maternity and parental leaves reflect a period of vulnerability for access. Transitions in time are a factor here, where some medications may not be trialed related to teratogenicity for females in the pre-conception, pregnancy and lactation periods (e.g. methotrexate, leflunomide). When these periods end, women may be mandated to return to these lower cost medications, despite having their disease well controlled on advanced (and more costly) therapy. Persons living in rural and remote locations may be impacted by additional costs to attend appointments for therapies requiring provider intervention such as intravenous infusions or intra-articular injections. Indigenous patients, refugee and first-generation immigrant populations, and those of low socioeconomic status will potentially have limitations in available medication coverage through federal benefits, or through provincial or territorial government public programs, and frequently experience delays in having newer options added to the formularies they access. In addition, refugees and first-generation immigrant populations may face re-trialing previously used therapies to meet their coverage requirements if sufficient documentation from their home country cannot be obtained. Elderly persons with frailty may experience a transition to senior public insurance, or as frailty increases, to the hospital formulary, and lose cost coverage for established therapies.3.6 Acceptability to StakeholdersThere is evidence that lower educational attainment is associated with a heightened aversion to risk when choosing therapy [[14]Durand C Eldoma M Marshall DA Bansback N Hazlewood GS. Patient Preferences for Disease-modifying Antirheumatic Drug Treatment in Rheumatoid Arthritis: A Systematic Review.], and many populations facing inequities in health also face these inequities in education. For persons of low socioeconomic status and those who are vulnerably housed, associated medical and mental health comorbidities may limit understanding of risks and benefits of treatment options presented and thus acceptance of a treatment [[10]Pianarosa E Hazlewood G Thomas M Hsiao R Barnabe C. Supporting Equity in Rheumatoid Arthritis Outcomes in Canada: Population-Specific Factors in Patient-Centered Care.]. Refugees and first-generation immigrant populations may have low trust or belief in western medical approaches, or choose to continue seeking treatment from familiar integrative health providers. Low health literacy in these populations may impact effective patient-provider communication, contributing to low patient trust which may limit follow up and regime adherence [[10]Pianarosa E Hazlewood G Thomas M Hsiao R Barnabe C. Supporting Equity in Rheumatoid Arthritis Outcomes in Canada: Population-Specific Factors in Patient-Centered Care.]. For Indigenous populations, acceptability of a treatment approach will be reduced if it interferes with use of traditional healing practices, or traditional lifestyle approaches. Further, there is stigmatization experienced by those engaged in pill-based treatment approaches related to the epidemic of opioid use disorders in the population, but also for some a preference to avoid invasive therapies. Family and community members support decision making for Indigenous patients, and trust with the healthcare provider strongly influences treatment acceptance [[16]Loyola-Sanchez A Hazlewood G Crowshoe L et al.Qualitative Study of Treatment Preferences for Rheumatoid Arthritis and Pharmacotherapy Acceptance: Indigenous Patient Perspectives.]. Additional perspectives should also be welcomed for elderly persons with frailty, as family and the extended sphere of healthcare providers are integral to supporting care. While acknowledging differences in treatment goals exist and that polypharmacy reduces adherence, this should be balanced with avoiding stigmatization and concluding that there are not any therapies acceptable to elderly persons with frailty. Medication regimes with the potential for teratogenicity will not be acceptable to persons of the female sex pursuing conception and pregnancy, nor will regimes with potential toxicity for those who are lactating. Rural and remote patients may not find complex regimes requiring travel for administration acceptable to take.3.7 Feasibility of the intervention for individuals and system implementationUnique circumstances will impact the implementation of treatment recommendations for each of the population groups considered. This may be related to accessibility of health care providers and system navigation to obtain assessment for therapy and associated monitoring, which are challenges faced by Indigenous populations [[19]Barnabe C Jones CA Bernatsky S et al.Inflammatory Arthritis Prevalence and Health Services Use in the First Nations and Non-First Nations Populations of Alberta., [20]Thurston WE Coupal S Jones CA et al.Discordant indigenous and provider frames explain challenges in improving access to arthritis care: a qualitative study using constructivist grounded theory.], rural and remote dwellers [[13]Pianarosa E Chomistek K