Addressing Multimorbidity in Evidence Integration and Synthesis

Abstract

To minimize bias, clinical practice guidelines (CPG) for managing patients with multiple conditions should be informed by well-planned syntheses of the totality of the relevant evidence by means of systematic reviews and meta-analyses. However, deficiencies along the entire evidentiary pathway hinder the development of evidence-based CPGs. Published reports of trials and observational studies often do not provide usable data on treatment effect heterogeneity, perhaps because their design, analysis and presentation is seldom geared towards informing on how multimorbidity modifies the effect of treatments. Systematic reviews and meta-analyses inherit all the limitations of their building blocks and introduce additional of their own, including selection biases at the level of the included studies, ecological biases, and analytical challenges. To generate recommendations to help negotiate some of the challenges in synthesizing the primary literature, so that the results of the evidence synthesis is applicable to the care of those with multiple conditions. Informal group process. We have built upon established general guidance, and provide additional recommendations specific to systematic reviews that could improve the CPGs for multimorbid patients. We suggest that following the additional recommendations is good practice, but acknowledge that not all proposed recommendations are of equal importance, validity and feasibility, and that further work is needed to test and refine the recommendations. INTRODUCTIONMost current clinical practice guidelines (CPG) are typically developed for managing individuals with a single disease, and also apply to patients with multiple conditions, provided that each can be managed separately from the others.1,2 Some patients, however, have conditions that must be considered jointly, perhaps because the management of one affects the management or the course of other. Uncritical adherence to guideline-recommended management of their isolated conditions can be impractical or even harmful for such patients. Tailored guidance is needed at least for specific combinations of conditions. Very few examples of CPGs providing such guidance exist, 1,2 perhaps because developing such guidance is hindered by deficiencies along the entire evidentiary pathway. Pivotal trials or observational studies often exclude individuals with multimorbidity. 4,5 Even when these individuals are included, the treatment effect is typically averaged over all participants, without report of whether and how it is modified in those with important multimorbid conditions. 6 Thus, systematic reviews that inform CPG recommendations often do not or cannot describe the pertinent evidence base. 7This manuscript describes the outcomes of a working session conducted with the goal of generating recommendations to help overcome some of the challenges in synthesizing the primary literature so that the results of the evidence synthesis are applicable to the care of those with multiple conditions that must be considered jointly, or in...

Decision Making for Older Adults With Multiple Chronic Conditions: Executive Summary for the American Geriatrics Society Guiding Principles on the Care of Older Adults With Multimorbidity

“…Current approaches to guideline development and implementation usually focus on single diseases, which may have limited relevance to those with MCCs. 13,[26][27][28][29] It is often unclear which condition(s) contribute to an individual's function, symptoms, quality of life, or survival, and consequently, which conditions should be the main treatment targets. 30 Interventions that benefit one condition may worsen or complicate treatment of another condition.…”

A Framework for Crafting Clinical Practice Guidelines that are Relevant to the Care and Management of People with Multimorbidity

“…While systematic reviews are often integral parts of CPG development, this is the focus of an accompanying paper and is only briefly discussed here. 16 Important issues considered outside of our scope included end-of-life issues, hospice, cost and resource use, CPG implementation, and performance measurement. 18 We organized our work by the generic CPG development steps extracted from the review of leading, collaborative CPG initiatives.…”

“…16 As discussed for Step 2, identification of potentially relevant publications requires specific skill and effort, with expansion of search terms and full text searches for analyses of subgroups or effect modifiers (e.g. when searching for hypertension trials in individuals with CKD, the search may be conducted without restriction to CKD, in order to capture hypertension trials in the general population of hypertensive individuals and review their full text publications for valid CKD subgroup analyses.)…”

An Official American Thoracic Society Workshop Report. A Framework for Addressing Multimorbidity in Clinical Practice Guidelines for Pulmonary Disease, Critical Illness, and Sleep Disorders

“…Ideally, studies would report treatment–comorbidity interactions or supply sufficient data to perform quantitative or qualitative summaries of trends (18). Given the paucity of randomized trial data with sufficient inclusivity of those with multimorbidity (19–24), evidence searches should anticipate including nonrandomized studies that estimate the differential effects and safety among those with comorbidity.…”