A Framework for Crafting Clinical Practice Guidelines That Are Relevant to the Care and Management of People with Multimorbidity
Open accessAbstract
Many patients of all ages have multiple conditions, yet clinicians often lack explicit guidance on how to approach clinical decision-making for such people. Most recommendations from clinical practice guidelines (CPGs) focus on the management of single diseases, and may be harmful or impractical for patients with multimorbidity. A major barrier to the development of guidance for people with multimorbidity stems from the fact that the evidence underlying CPGs derives from studies predominantly focused on the management of a single disease. In this paper, the investigators from the Improving Guidelines for Multimorbid Patients Study Group present consensus-based recommendations for guideline developers to make guidelines more useful for the care of people with multimorbidity. In an iterative process informed by review of key literature and experience, we drafted a list of issues and possible approaches for addressing important coexisting conditions in each step of the guideline development process, with a focus on considering relevant interactions between the conditions, their treatments and their outcomes. The recommended approaches address consideration of coexisting conditions at all major steps in CPG development, from nominating and scoping the topic, commissioning the work group, refining key questions, ranking importance of outcomes, conducting systematic reviews, assessing quality of evidence and applicability, summarizing benefits and harms, to formulating recommendations and grading their strength. The list of issues and recommendations was reviewed and refined iteratively by stakeholders. This framework acknowledges the challenges faced by CPG developers who must make complex judgments in the absence of high-quality or direct evidence. These recommendations require validation through implementation, evaluation and refinement.
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Most clinical practice guidelines target specific diseases, ignoring their relevance for patients with various comorbidities.
“In addition to the aforementioned issues with diagnostic error definitions, most clinical practice guidelines target specific diseases, ignoring their relevance for patients with various comorbidities [148,149,150].”
From Toward Safer Diagnoses: A SEIPS-Based Narrative Review of Diagnostic Errors (2026) · cites this paper as [149]
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“Clinical guidelines build on EBM and are most often designed to treat single diseases or risk factors [43].”
BackgroundTinetti, M. E., Dindo, L. N., Smith, C. D., Blaum, C. S., Costello, D. M., Ouellet, G. M., Rosen, J. D., Hernandez‐Bigos, K., Geda, M. E., & Naik, A. D. (2019) · PLoS ONE · doi:10.1371/journal.pone.0218249 · Cited by 78 · see citing works
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Multimorbidity and Evidence Generation
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“Here, we focus on improving the generation, analysis and reporting of primary data, while companion papers discuss evidence synthesis and integration,(4) and the development of CPG recommendations themselves.(5)”
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Chronic obstructive pulmonary disease comorbidities
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“Persisting challenges include the implementation of this knowledge in clinical practice, for the design of clinical trials based on the identified clusters of comorbidities, and to tailor treatment guidelines into a more personalized but still practical approach [74,75].”
BackgroundNelson, M. L. A., McKellar, K. A., Yi, J., Kelloway, L., Munce, S., Cott, C. A., Hall, R., Fortin, M., Teasell, R. W., & Lyons, R. (2017) · Topics in Stroke Rehabilitation · doi:10.1080/10749357.2017.1282412 · Cited by 63 · see citing works
Facilitating Self-reflection about Values and Self-care Among Individuals with Chronic Conditions
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“To improve the quality of healthcare for individuals with MCC, the importance of orienting care around patients’ values is well-documented [6, 39].”
BackgroundNothelle, S. K., Sharma, R., Oakes, A. H., Jackson, M., & Segal, J. B. (2017) · Journal of the American Medical Directors Association · doi:10.1016/j.jamda.2017.06.005 · Cited by 68 · see citing works
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“To compound the problem, there is often a lack of explicit guidance with regards to multimorbidity in clinical practice guidelines [46].”
BackgroundMultimorbidity: Implications and directions for health psychology and behavioral medicine.
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“For example, depression commonly occurs with diabetes (Nouwen et al., 2010; Uhlig et al., 2014)).”
BackgroundSelf-citationAssociation of Multimorbidity with Mortality and Healthcare Utilization in Chronic Kidney Disease
Bowling, C. B., Plantinga, L., Phillips, L. S., McClellan, W., Echt, K. V., Chumbler, N. R., McGwin, G., Vandenberg, A. E., Allman, R. M., & Johnson, T. M. (2016) · Journal of the American Geriatrics Society · doi:10.1111/jgs.14662 · Cited by 55 · see citing works
“NSAIDs is prioritized over reducing risk of CKD progression, patients may be at increased risk of acute kidney injury or worsening hypertension.(6,7) The presence of concordant conditions may increase the likelihood of achieving chronic disease management goals as has been shown in diabetes.”
BackgroundMethodInfluentialWilson, K. C., Gould, M. K., Krishnan, J. A., Boyd, C. M., Brożek, J., Cooke, C. R., Douglas, I. S., Goodman, R. A., Joo, M. J., Lareau, S. C., et al. (2016) · Annals of the American Thoracic Society · doi:10.1513/annalsats.201601-007st · Cited by 16 · see citing works
“Finally, guidelines can address multimorbidity in a non–disease-specific way, such as guidelines addressing the coordination of care or self-management (17).”
InfluentialSelf-citationZhao, Y. W., Atun, R. A., Anindya, K., McPake, B., Marthias, T., Pan, T., van Heusden, A., Zhang, P., Duolikun, N., & Lee, J. T. (2021) · BMJ Global Health · doi:10.1136/bmjgh-2020-004042 · Cited by 54 · see citing works
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“First, interactions were classified into the three accepted main categories: diseaseedisease (Di-Di-I), diseaseedrug (Di-D-I), and drugedrug interactions (DDI) [12].”
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“Current guidelines do not address the challenges in the care of patients with mutlimorbidity, as well as the quality of evidence available for summarizing benefits and harms and formulating recommendations for this specific population [28].”
BackgroundA Change in Perspective: From Dual Diagnosis to Multimorbidity.
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Multimorbidity and cardiovascular disease: a perspective on low- and middle-income countries
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“Limited evidence-based guidelines for MM (62), even for more prevalent forms of MM (60), enhances the reliance upon clinical guidelines that are intended for the treatment of single diseases (63).”
BackgroundTobacco and alcohol use disorders: evaluating multimorbidity
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Advancing multimorbidity management in primary care: a narrative review
Aramrat, C., Choksomngam, Y., Jiraporncharoen, W., Wiwatkunupakarn, N., Pinyopornpanish, K., Mallinson, P. A. C., Kinra, S., & Angkurawaranon, C. (2022) · Primary Health Care Research & Development · doi:10.1017/s1463423622000238 · Cited by 60 · see citing works
“A framework for the development of CPGs that consider multimorbidity has been developed (Uhlig et al., 2014), but CPGs regarding how to provide particular treatments given a particular set of multiple comorbidities are still limited (World Health Organization, 2016).”
BackgroundGoodman, R. A., Boyd, C. M., Tinetti, M. E., Kohorn, I. V., Parekh, A. K., & McGinnis, J. M. (2014) · The Annals of Family Medicine · doi:10.1370/afm.1646 · Cited by 42 · see citing works
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“111‐113 Clinical practice guidelines have traditionally focused on single diseases, which greatly limits their utility in patients with comorbidities, especially those with multiple serious illnesses, who require care that is person‐centered rather than disease‐focused.(119,120) Moreover, clinical guidance should be e…”
BackgroundCaring for Patients With Multiple Chronic Conditions
Tinetti, M. E., Green, A. R., Ouellet, J. A., Rich, M. W., & Boyd, C. M. (2019) · Annals of Internal Medicine · doi:10.7326/m18-3269 · Cited by 39 · see citing works
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An integrated model of multimorbidity and symptom science
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“Finally, although professional societies have largely taken the responsibility for clinical practice guideline development, clinicians and investigators must be sensitized to the current deficits in the single disease focused guidelines, as well as the recommendations from AHRQ and professional societies about strateg…”
BackgroundBennett, W. L., Robbins, C. W., Bayliss, E. A., Wilson, R. F., Tabano, H., Mularski, R. A., Chan, W., Puhan, M. A., Yu, T., Leff, B. A., et al. (2017) · Journal of General Internal Medicine · doi:10.1007/s11606-017-4039-5 · Cited by 30 · see citing works
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“2,4,7,12,16,17 Most of the evidence informing the development of clinical practice guidelines has derived from research on patients with only 1 medical condition or disorder.”
Polypharmacy and Multimorbidity Among Medicaid Enrollees: A Multistate Analysis
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“Current evidence-based clinical practice primarily follows single disease-specific treatment and prevention guidelines; however, this kind of practice paradigm may sometimes be detrimental and impractical for patients with multimorbidity.(4,5) For example, in Boyd et al, if all recommendations from the clinical practi…”
Spring, B. J., Stump, T. K., Penedo, F. J., Pfammatter, A. F., & Robinson, J. K. (2019) · Health Psychology · doi:10.1037/hea0000760 · Cited by 30 · see citing works
“Despite recent calls to update clinical guidelines to reflect the complexities of treating comorbidities (Arnett et al., 2014; Uhlig et al., 2014), the additional data collection needed and translation of research findings to practice probably will require more than a decade to accomplish (Morris,…”
BackgroundCharlson, M. E., & Wells, M. T. (2022) · Psychotherapy and Psychosomatics · doi:10.1159/000521952 · Cited by 25 · see citing works
Personalized Disease Screening Decisions Considering a Chronic Condition
Hajjar, A., & Alagöz, O. (2022) · Management Science · doi:10.1287/mnsc.2022.4336 · Cited by 24 · see citing works
Recommendations and quality of multimorbidity guidelines: a systematic review.
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“As such, interactions between the treatment of multiple conditions and outcomes may be ignored [7], especially when multiple prescribers are involved in treating a single patient.”
BackgroundPaukkonen, L., Oikarinen, A., Kähkönen, O., & Kyngäs, H. A. (2021) · Health Expectations · doi:10.1111/hex.13306 · Cited by 23 · see citing works
Guidance on guidelines: Understanding the evidence on the uptake of health care guidelines
Brennan, C. A., Greenhalgh, J., & Pawson, R. (2017) · Journal of Evaluation in Clinical Practice · doi:10.1111/jep.12734 · Cited by 28 · see citing works
“We turn to the next adaptation, theory 1b, namely, to increase attention to comorbidity within condition specific guidelines.(36,37,42,43) Here, the idea is that guidelines should provide information to enable clinicians to more effectively apply the guideline to patients with multimorbidity; for example, by detailing…”
BackgroundThe HHS Strategic Framework on Multiple Chronic Conditions: Genesis and Focus on Research
Parekh, A. K., & Goodman, R. A. (2013) · Journal of Comorbidity · doi:10.15256/joc.2013.3.20 · Cited by 20 · see citing works
Evidence-Based Medicine and the Hard Problem of Multimorbidity
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“The association between number of drugs and PIMs used is probably confounded by the number and types of comorbidities (7, 8).”
BackgroundWhole person care, patient-centred care and clinical practice guidelines in general practice
Hansen, E., Walters, J., & Howes, F. (2016) · Health Sociology Review · doi:10.1080/14461242.2016.1170625 · Cited by 21 · see citing works
“This shortcoming of CPGs has resulted in calls for the formulation of CPGs for people with co-morbidities/multimorbidities (Uhlig et al., 2014).”
BackgroundRoberts, E. R., Green, D. J., & Kadam, U. T. (2014) · BMJ Open · doi:10.1136/bmjopen-2014-005429 · Cited by 24 · see citing works
Wahed, A. A. A., El-Dahiyat, F., Aljawamis, D. F., Ajimi, J. A., & Rafeea, K. J. B. (2021) · International journal of clinical practice · doi:10.1111/ijcp.14715 · Cited by 19
Lai, F. T. T., Beeler, P. E., Yip, B. H. K., Cheetham, M., Chau, P. Y. K., Chung, R. Y., Wong, E. L., Yeoh, E., Battegay, E. J., & Wong, S. Y. S. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.651925 · Cited by 22 · see citing works
Alimohammadian, M., Majidi, A., Yaseri, M., Ahmadi, B., Islami, F., Derakhshan, M. H., Delavari, A., Amani, M., Feyz-Sani, A., Poustchi, H., et al. (2017) · BMJ Open · doi:10.1136/bmjopen-2016-013548 · Cited by 105 · see citing works
New horizons in clinical practice guidelines for use with older people
Martin, F. C., Quinn, T. J., Straus, S. E., Anand, S. S., van der Velde, N., & Harwood, R. (2024) · Age and Ageing · doi:10.1093/ageing/afae158 · Cited by 18 · see citing works
“Most CPGs for chronic conditions focus on one disease [5], but considering any of these in isolation is likely to be inadequate as adults living with two or more long-term conditions outnumber those living with one, and multi-morbidity incidence increases with age [15].”
Integrated Care for Multimorbidity Population in Asian Countries: A Scoping Review
Lin, J., Islam, M. K., Leeder, S., Huo, Z., Hung, C. T., Yeoh, E., Gillespie, J., Dong, H., Askildsen, J. E., Liu, D., et al. (2022) · International Journal of Integrated Care · doi:10.5334/ijic.6009 · Cited by 18 · see citing works
Defining Multiple Chronic Conditions for Quality Measurement
Drye, E. E., Altaf, F. K., Lipska, K. J., Spatz, E. S., Montague, J. A., Bao, H., Parzynski, C. S., Ross, J. S., Bernheim, S. M., Krumholz, H. M., et al. (2017) · Medical Care · doi:10.1097/mlr.0000000000000853 · Cited by 16 · see citing works
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Addressing Multimorbidity in Evidence Integration and Synthesis
Trikalinos, T. A., Segal, J. B., & Boyd, C. M. (2014) · Journal of General Internal Medicine · doi:10.1007/s11606-013-2661-4 · Cited by 15 · see citing works
Self-citationPrevalence and overlap of Disease Management Program diseases in older hospitalized patients
Juul‐Larsen, H. G., Petersen, J., Sivertsen, D. M., & Andersen, O. (2017) · European Journal of Ageing · doi:10.1007/s10433-017-0412-9 · Cited by 13 · see citing works
“…societies and researchers around the world have started developing guidelines or DMPs for older patients with multimorbidity (Fabbri et al. 2012; Uhlig et al. 2014; Weiss et al. 2014; Bernabeu-Wittel et al. 2014), but the complexity of the different treatment regimens and the interactions…”
BackgroundTrustworthy evidence-based versus untrustworthy guidelines: detecting the difference
Lima, J. P., Tangamornsuksan, W., & Guyatt, G. H. (2023) · Family Medicine and Community Health · doi:10.1136/fmch-2023-002437 · Cited by 16 · see citing works
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Clinical Guidelines in the Context of Aging and Multimorbidity
Guthrie, B., & Boyd, C. (2018) · Public Policy & Aging Report · doi:10.1093/ppar/pry038 · Cited by 13 · see citing works
“Active and explicit consideration of comorbidity and the consequences of aging at each step of guideline development is the core way in which single-disease guidelines could be improved, and there are published frameworks to guide this (Figure 3; Uhlig et al., 2014).”
BackgroundSelf-citationUse of surrogate outcomes in US FDA drug approvals, 2003–2012: a survey
Yu, T., Hsu, Y.-J., Fain, K. M., Boyd, C., Holbrook, J., & Puhan, M. (2015) · BMJ Open · doi:10.1136/bmjopen-2015-007960 · Cited by 12
Self-citationShared decision making for people living with multimorbidity: A concept analysis.
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Generalizability of Results from Randomized Controlled Trials in Post-Stroke Physiotherapy
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Determinants of depression in patients with comorbid depression following cardiac rehabilitation
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“Due to increased survival rates in CVD and an ageing population, there has been an increase in the number of comorbidities present with CVD which further complicates the management of a patient’s condition and service delivery options.(4) Depression is reported to be a prevalent comorbidity in cardiac patients; the pr…”
BackgroundClinical practice guidelines adaptation for internists - An EFIM methodology
Leśniak, W., Morbidoni, L., Dicker, D., & Marin-Leon, I. (2020) · European Journal of Internal Medicine · doi:10.1016/j.ejim.2020.05.016 · Cited by 12 · see citing works
Multimorbidity in health psychology and behavioral medicine.
Suls, J. M., & Green, P. A. (2019) · Health Psychology · doi:10.1037/hea0000783 · Cited by 13 · see citing works
Future Research Directions for Multimorbidity Involving Cardiovascular Diseases
Salive, M. E. (2016) · Clinics in Geriatric Medicine · doi:10.1016/j.cger.2016.01.008 · Cited by 8 · see citing works
A Novel Approach to Developing a Discordance Index for Older Adults With Chronic Kidney Disease
Hall, R. K., Zhou, H. C., Reynolds, K., Harrison, T. N., & Bowling, C. B. (2019) · The Journals of Gerontology Series A · doi:10.1093/gerona/glz248 · Cited by 12 · see citing works
“The traditional approach to caring for patients with chronic disease is particularly challenging because most CPGs focus on management of a single condition and its related concordant conditions and not the spectrum of comorbidities that often coexist (2).”
BackgroundHerzig, L., Mueller, Y. K., Haller, D. M., Zeller, A., Neuner‐Jehle, S., Déruaz‐Luyet, A., Cohidon, C., Streit, S., Burnand, B., & Zuchuat, J.-C. (2019) · BJGP Open · doi:10.3399/bjgpopen18x101622 · Cited by 10 · see citing works
“They must therefore try to set medical priorities, as the co-management of every condition present during the same consultation is often impossible.(17) FPs are trained to focus first on the clinical problems which pose the highest risk of mortality or morbidity to the patient (such as heart diseases and diabetes), an…”
BackgroundComorbidity Subgroups Among Medicare Beneficiaries Seeking Health Care for Musculoskeletal Pain
Lentz, T. A., Marlow, N. M., Beneciuk, J. M., Fillingim, R. B., & George, S. Z. (2018) · The Journals of Gerontology Series A · doi:10.1093/gerona/gly202 · Cited by 10 · see citing works
Engelmann, P., Eilerskov, N., Thilsing, T., Bernardini, F., Rasmussen, S., Löwe, B., Herrmann-Lingen, C., Gostoli, S., Andréasson, F., Rafanelli, C., et al. (2023) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2023.1186390 · Cited by 7 · see citing works
Nelson, M. L. A., Singh, H., Nie, J. X., MacDonald, S. L., Bayley, M. T., Fortin, C. D., & Upshur, R. E. G. (2023) · Journal of Multimorbidity and Comorbidity · doi:10.1177/26335565231211668 · Cited by 5 · see citing works
“10,11 In previously published work, stroke rehabilitation clinicians have questioned the applicability of stroke rehabilitation clinical guidelines to their ‘ real-world patients, ’ as the high quality evidence that underpins these guidelines often exclude patients on the basis of age, history of…”
BackgroundEliminating medication overload: A national action plan
Working Group on Medication Overload (2020) · doi:10.46241/li.ylbw4885 · Cited by 4 · see citing works
Methodology for senior‐proof guidelines: A practice example from the Netherlands
van Munster, B. V., Portielje, J. E., Maier, A., Arends, A., & de Beer, J. (2018) · Journal of Evaluation In Clinical Practice · doi:10.1111/jep.12738 · Cited by 7
“The framework for crafting clinical practice guidelines that are relevant to the care and management of people with multimorbidity of Uhlig was used as a useful example for the topics that had to be taken into account.(8) Two stages of guideline development were distinguished: the preparation stage and the development…”
Method
- Authors
- Uhlig, K., Leff, B., Kent, D., Dy, S., Brunnhuber, K., Burgers, J. S., Greenfield, S., Guyatt, G., High, K., Leipzig, R., Mulrow, C., Schmader, K., Schunemann, H., Walter, L. C., Woodcock, J., & Boyd, C. M.
- Affiliations
- Tufts University (US)
- Johns Hopkins University (US)
- Tufts Medical Center (US)
- BMJ Group (United Kingdom) (GB)
- Dutch College of General Practitioners (NL)
- University of California, Irvine (US)
- McMaster University (CA)
- Wake Forest University Health Sciences (US)
- Icahn School of Medicine at Mount Sinai (US)
- The University of Texas at San Antonio Health Science Center (US)
- Duke Medical Center (US)
- San Francisco VA Medical Center (US)
- University of Cambridge (GB)
- Corresponding author
- Boyd, Cynthia M.
- ORCID
- Venue
- Journal of General Internal Medicine
- Published
- 2014-01-18
- Volume
- 29
- Issue
- 4
- Pages
- 670-679
- ISSN
- 0884-8734 (ISSN-L)
- 1525-1497
- PMC
- PMC3965742
- OpenAlex
- W2146328920
- Cited by
- 158
- References
- 0
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 7 · 2023: 10 · 2022: 12 · 2021: 9 · 2020: 10 · 2019: 18 · 2018: 13 · 2017: 22 · 2016: 18 · 2015: 14 · 2014: 10 · 2013: 2
- FWCI
- 2.85
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Journal of General Internal Medicine (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Robert Wood Johnson Foundation
- John A. Hartford Foundation
- Hartford Foundation for Public Giving
- Atlantic Philanthropies
- Brown University
- Tufts Medical Center
- Johns Hopkins University
- Starr Foundation
- Agency for Healthcare Research and Quality (R21HS017653, R21HS018597, AHRQ R21 HS017653, AHRQ R21 HS018597-01)
- Johns Hopkins Bloomberg School of Public Health
- Medical Research Council (MR/K021796/1, MR/K023187/1)
- Economic and Social Research Council (ES/G007462/1)
- Center for Innovative Medicine
- National Institute on Aging (K23AG032910, K24AG041180, NIA K23 AG032910, P30AG028716)
- National Cancer Institute (R01CA134425)
- Topics
- Health Sciences › Medicine › Epidemiology › Chronic Disease Management Strategies
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Clinical practice guidelines implementation
- Health Sciences › Medicine › Geriatrics and Gerontology › Pharmaceutical Practices and Patient Outcomes
- Keywords
- multimorbidity, guideline development, comorbidities, clinical decision-making, guideline applicability, evidence quality assessment, benefit-harm assessment, consensus recommendations, stakeholder engagement
- MeSH terms
- Congresses as Topic, Patient Care, Humans, Comorbidity, Practice Guidelines as Topic, Evidence-Based Medicine, Disease Management
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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