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Integrating multiple co-morbidities in guidelines
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Integrating multiple co-morbidities in guidelines

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Presentación realizada por Holger Schünemann, profesor y director del Departamento de Epidemiología Clínica y Bioestadísticas en la Universidad McMaster de Hamilton, Canadá, en las Jornadas ...

Presentación realizada por Holger Schünemann, profesor y director del Departamento de Epidemiología Clínica y Bioestadísticas en la Universidad McMaster de Hamilton, Canadá, en las Jornadas Científicas "Guías de Práctica Clínica y Pluripatología" de GuíaSalud, Madrid, 21 de febrero de 2013.

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Integrating multiple co-morbidities in guidelines Integrating multiple co-morbidities in guidelines Presentation Transcript

  • Holger SchünemannProfessor and Chair, Dept. of Clinical Epidemiology & BiostatisticsProfessor of MedicineMichael Gent Chair in Healthcare ResearchMcMaster University, Hamilton, CanadaMadrid, February 21, 2013 (recorded slides)Integrating multiple co-morbidities inguidelinesAcknowledgmentMr. W. WierciochDr. Pablo AlonsoCo-authors
  • Disclosure• No direct/personal for-profit payments to me or my research group• Co-chair of GRADE working group• Cochrane Collaboration – Co-convenor of the Applicability and Recommendations Methods Group – Various other functions• IQWiG Scientific Board
  • Content1. Intro to considering multiple co-morbidities2. How important are multiple comorbidities for guidelines?3. How have other organizations involved in the development of guidelines for single chronic disease approached the problem of multiple comorbidities?4. What are the implications of multiple comorbidities for pharmacological treatment?5. What are the potential changes induced by multiple comorbidities in guidelines?6. What are the implications of considering a population of older patients with multiple comorbidities in designing clinical trials?
  • Intro to considering multiple co- morbidities
  • Framing a foreground questionPopulation: Patients with COPDIntervention: Respiratory rehabilitationComparison: No respiratory rehabilitationOutcomes: Mortality, hospitalizations, resource use, adverseoutcomes Schunemann, Hill et al., The Lancet ID, 2007
  • Importance of multiple comorbidities for guidelines• COPD commonly exists in patients who often have multiple comorbidities: – e.g. heart failure, coronary artery disease, hypertension, diabetes mellitus, metabolic syndrome, cancer, depression• These comorbidities affect the epidemiology, pathophysiology, and care of COPD, as well as that of the comorbid disease(s)• For example, COPD and cardiovascular disease (a non-respiratory comorbidity): – Symptoms of COPD and comorbidities may overlap – Underlying pathology may be shared – Treatments may interact – Natural history of conditions may be altered
  • Relation between PICO and available evidence PICO
  • Indirectness - population Outpatient respiratory  rehabilitation in patients with  COPD COPD and heart  COPD and heart  failure failureNo concerns about directness (transferability)  Concerns about directnessNo lowering of confidence Lower confidence Same recommendation Separate recommendation
  • Indirectness - population Outpatient respiratory  rehabilitation in patients with COPD COPD and heart  failure Is the effect the same in patients who also have heart failureNo concerns about directness (transferability)  Concerns about directnessNo lowering of confidence Lower confidence Same recommendation Separate recommendation
  • Relation between PICO and available evidence PICO
  • Relation between PICO and available evidence PICO
  • Determinants of confidence: GRADE• Any evidence • 5 factors that can lower confidence 1. limitations in detailed study design and execution (risk of bias criteria) 2. Inconsistency (or heterogeneity) 3. Indirectness (PICO and applicability) 4. Imprecision 5. Publication bias• 4 factors can increase confidence 1. Randomization 2. large magnitude of effect 3. opposing plausible residual bias or confounding 4. dose-response gradient
  • Lowering confidence in RCTsTable: GRADEs approach to rating quality of evidence (aka confidence in effect estimates)For each outcome based on a systematic review and across outcomes (lowest quality across the outcomes critical for decision making) 1. 2. 3. Establish initial Consider lowering or raising Final level of level of confidence level of confidence confidence ratingStudy design Initial Reasons for considering lowering Confidence confidence or raising confidence in an estimate of effect in an estimate across those considerations of effect  Lower if  Higher if* High Risk of Bias Large effect HighRandomized trials confidence  Inconsistency Dose response Indirectness All plausible Moderate confounding & bias  Imprecision  would reduce a Low demonstrated effect LowObservational studies Publication bias confidence or   would suggest a spurious effect if no Very low effect was observed *upgrading criteria are usually applicable to observational studies only.
  • 1. How important are multiple comorbidities for guidelines? K2. How have other organizations involved in the ey questions development of guidelines for single chronic disease approached the problem of multiple comorbidities?3. What are the implications of multiple comorbidities for pharmacological treatment?4. What are the potential changes induced by multiple comorbidities in guidelines?5. What are the implications of considering a population of older patients with multiple comorbidities in designing clinical trials?
  • Importance of multiple comorbidities for guidelines• Increase in the prevalence of multiple comorbidities with advanced age – 33% in 65-69 year-old age group, and ≥50% in 85+ year-old age group, have 3 or more chronic conditions• Multiple comorbidities influence the clinical manifestations and natural history of a chronic disease• Multiple comorbidities must be taken into account in considering diagnosis, assessment of severity, prognosis, and management of a chronic disease (i.e. the topics covered in a clinical guideline)• Implementing single disease guidelines presents a challenge to clinicians treating the average population of patients with multiple comorbidities
  • 1. How important are multiple comorbidities for guidelines? K ey questions2. How have other organizations involved in the development of guidelines for single chronic disease approached the problem of multiple comorbidities?3. What are the implications of multiple comorbidities for pharmacological treatment?4. What are the potential changes induced by multiple comorbidities in guidelines?5. What are the implications of considering a population of older patients with multiple comorbidities in designing clinical trials?
  • Approaches of other organizations in addressing problem of multiple comorbidities• Recent guidelines for COPD: – Acknowledge the importance of considering multiple comorbidities in diagnosis, prognosis, and management – Acknowledge the lack of evidence and specific guidance for clinicians to make these considerations – Provide few recommendations on how to modify care based on multiple comorbidities• Recent guidelines for other common chronic diseases – CHF, hypertension, and diabetes mellitus guidelines address poorly some comorbidities, including COPD, one at a time, failing to address coexistence of multiple comorbidities at the same time – Underrepresentation of individuals 80 years and older – Few adequately address issues directly related to elderly patients with comorbidities
  • Approaches of other organizations in addressing problem of multiple comorbidities• There are some examples of collaborative guideline development that may serve as a model for future work• European Society of Cardiology participating in joint development of cardiovascular disease prevention recommendations with 9 other societies• American Geriatrics Society/California HealthCare Foundation guideline for care of the older patient with diabetes mellitus: – Selected six chronic conditions common in people with diabetes mellitus and reviewed literature on each topic – Limited availability of data specific to older adults for most topic areas – Extrapolation of findings based on data for persons of younger ages – Example Recommendation Statement: “The older adult who has diabetes mellitus is at increased risk for major depression and should be screened for depression during the initial evaluation period (first 3 months) and if there is any unexplained decline in clinical status. (IIA)” Brown AF, Mangione CM, Saliba D, Sarkisian CA.  Guidelines for improving the care of the older  person with diabetes mellitus. J Am Geriatr Soc 2003;51:S265–S280.
  • Approaches of other organizations in addressing problem of multiple comorbidities• All chronic disease guidelines should have a separate section on comorbidities, with a summary of basic recommendations on diagnosis, assessment of severity, and treatment of each comorbid condition that can be derived from other high-quality guidelines or developed de novo
  • 1. How important are multiple comorbidities for guidelines? K ey question2. How have other organizations involved in the development of guidelines for single chronic disease approached the problem of multiple comorbidities?3. What are the implications of multiple comorbidities for pharmacological treatment?4. What are the potential changes induced by multiple comorbidities in guidelines?5. What are the implications of considering a population of older patients with multiple comorbidities in designing clinical trials?
  • Implications of multiple comorbidities for pharmacological treatment• Primary focus on the management of a single disease may inadvertently lead to undertreatment, overtreatment, or inappropriate treatment: – Excess medication administration from adding treatments for the same condition when other causes are not considered and there is a lack of response to therapy – Therapeutic efficacy of a medication is often evaluated for treatment of a single index condition and the medication may have unanticipated effects on patients with other illnesses
  • Implications of multiple comorbidities for pharmacological treatment• Problem of adverse effects of pharmacological agents in patients with COPD: – Systemic steroids are recommended for treatment of exacerbations of COPD, but increase risk of hyperglycemia in patients with COPD and diabetes mellitus, and may worsen osteoporosis – Beta-blockers are recommended for treatment of CHF, but can exacerbate respiratory symptoms in patients with COPD who also have asthma
  • Implications of multiple comorbidities for pharmacological treatment• Strategies can be used to account for possible effect modification and interaction of different pharmacological agents: – Demonstrate whether the effects will differ in the population for whom the recommendation is intended from that in whom the evidence is obtained – Or, demonstrate that there is evidence of an interaction between different interventions that would change the benefit-downside profile compared with when the interventions are administered alone• Key Message: Evidence that is less direct, compared with evidence that directly supports the recommendations, influences the confidence in how the obtained effects relate to the population of interest.
  • Population indirectness: Does the recommendation apply to the population treated/managed by the decision maker?Relative effect Assumed & described applies? baseline risk estimate Interaction? May be related if from same evidence base applies? Risk group correct (same features)? Influenced by the confidence in the estimate of the baseline risk estimate that was assumed when modeling? Risk of bias, imprecision, publication bias, inconsistency, upgrading criteria apply
  • 1. How important are multiple comorbidities for guidelines? K ey questions2. How have other organizations involved in the development of guidelines for single chronic disease approached the problem of multiple comorbidities?3. What are the implications of multiple comorbidities for pharmacological treatment?4. What are the potential changes induced by multiple comorbidities in guidelines?5. What are the implications of considering a population of older patients with multiple comorbidities in designing clinical trials?
  • Potential changes induced by multiple comorbidities in guidelines• Underlying Question: How should physicians make treatment recommendations for people with multiple comorbidities, particularly if they are elderly? – Clinical decision-making in such patients requires estimation of the often subtle balance of benefits and harms, i.e. the net benefits or net harms – This frequently involves considerable uncertainty, and requires estimation of a baseline risk over a given time period – Values and preferences patients place on treatment options and outcomes• Patient-oriented guidance must incorporate these judgments
  • Potential changes induced by multiple comorbidities in guidelinesTo address these issues, comorbidities could be considered in alldisease guidelines in several aspects:1. Explicitly discussing whether patients with the most common comorbidities were included in the disease- specific trials – Is the patient, to whom the study results are being applied, sufficiently like, or exchangeable to, the average patient in the trial? – When high-quality randomized studies are available, the evidence will frequently be indirect for the multi-morbid population, and the quality of evidence may be downgraded – Review of the evidence in layers considering both people with and without multiple comorbidities, as well as people of different ages2. Considering the absolute risk reduction from therapy for a patient with multiple comorbidities – Recognize that a person with multiple comorbidities may be at either higher or lower absolute risk than the ‘average’ person – Is it known whether the relative benefit of therapy increases or decreases in people with each combination of the multiple
  • 1. How important are multiple comorbidities for guidelines? K ey questions2. How have other organizations involved in the development of guidelines for single chronic disease approached the problem of multiple comorbidities?3. What are the implications of multiple comorbidities for pharmacological treatment?4. What are the potential changes induced by multiple comorbidities in guidelines?5. What are the implications of considering a population of older patients with multiple comorbidities in designing clinical trials?
  • Implications of considering a population with multiple comorbidities in designing clinical trials• Patients in clinical trials do not adequately reflect the true population of people with any chronic disease in terms of the burden of multiple comorbidities – Older patients and patients with multiple comorbidities are specifically excluded from most clinical trials – The number of trials with explicit age exclusions for older patients has decreased, but exclusions for comorbidities have increased• Exclusion and inclusion criteria are less important than who is the ‘average’ patient in a trial. Few exclusion criteria may still not prevent few people with comorbidities being enrolled and results will be of questionable relevance.
  • Implications of considering a population with multiple comorbidities in designing clinical trials• Key Message: Developing recommendations for patients with multiple comorbidities requires careful consideration of the directness of evidence Fails to reflect diversity  of the population Broadly representative of  the population in terms of  risk, responsiveness, and  vulnerability Individuals who benefit  much more from treatment  than average members of  the population From: Kravitz RL, Duan N, Braslow J. Evidence‐based medicine, heterogeneity of treatment effects, and the trouble with averages. Milbank Q 2004;82:661–687.
  • Summary Framework for Development of Multiple Comorbidity Clinical Practice Guidelines and Patient Involvement Step How Example for COPD1. Define all problems for a  Ask patients or review the literature Primary concern: Dyspnea, given patient depression, swelling of legs?2. Which outcome is of  Use tools to elicit values and preferences  Ranking techniques, e.g. greatest importance (e.g. ranking exercises, visual analog  comparing dyspnea with to a patient with multiple  tools) fatigue and hospitalizations co‐morbidity (described in detail)3. Define possible options  Literature search (focus on SR), expert  LABA, diuretics, beta‐blockers, to intervene input on what might work antidepressants4. Evaluate whether  ‐ Evaluate subgroup effects/  ‐ LABAs may be worse in benefits or downsides  heterogeneity patients with dyspnea differ across ‐ Did trials include subgroups and are  from COPD and CHFpopulations (in particular  subgroup effects credible? ‐ Treatment of dyspnea those with different  ‐ Evidence that biology differs? leads to improvement in comorbidity) ‐ Judgement about directness of evidence depression5. Evaluate greatest net  ‐ Systematically judge expected benefits  ‐ Beta‐blockers with greatest benefit across populations against potential downsides after  net benefit in pop. of interestbased on evidence profiles  considering various interventions ‐ Treatment of depression and present to panel  ‐ Explain to patients second largest net benefitmaking recommendations  ‐ LABA and diuretic net benefit and to patients smaller than beta‐blockers