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<h2 id="toc-title">Table of contents</h2>
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<li><a href="#measuring-comorbidity-burden" id="toc-measuring-comorbidity-burden" class="nav-link active" data-scroll-target="#measuring-comorbidity-burden"><span class="toc-section-number">3.1</span> Measuring comorbidity burden</a></li>
<li><a href="#proxy-adjustment-empirical-criterion" id="toc-proxy-adjustment-empirical-criterion" class="nav-link" data-scroll-target="#proxy-adjustment-empirical-criterion"><span class="toc-section-number">3.2</span> Proxy Adjustment Empirical criterion</a></li>
<li><a href="#additional-information-icd-10-cm" id="toc-additional-information-icd-10-cm" class="nav-link" data-scroll-target="#additional-information-icd-10-cm"><span class="toc-section-number">3.3</span> Additional information: ICD-10-CM</a></li>
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<h1 class="title d-none d-lg-block"><span class="chapter-number">3</span> <span class="chapter-title">Reducing residual confounding</span></h1>
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Pitfall of using observation data
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<p>Observational data sources like NHANES <mark>do not allow the user to control which variables are surveyed</mark>. Therefore, may variables necessary for a research questions may not be available.</p>
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<p>As example of unmeasured confounding in the observational data, measuring comorbidity within NHANES is not straightforward.</p>
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<h2 data-number="3.1" class="anchored" data-anchor-id="measuring-comorbidity-burden"><span class="header-section-number">3.1</span> Measuring comorbidity burden</h2>
<p>In health research, the <strong>overall health status/ Disease burden</strong> could be a potential confounding factor. In the original DAG, we had comorbidity as a known confounder.</p>
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</p><pre class="mermaid mermaid-js" data-tooltip-selector="#mermaid-tooltip-1">flowchart TB
A[Obesity] --> Y(Diabete)
L[Comorbidity measure unobserved] --> Y
L --> A
style A fill:#90EE90;
style Y fill:#ADD8E6;
style L fill:#FF0000;
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<li><p><strong>Charlson Comorbidity Index (CCI)</strong> is a measure that quantifies the burden of comorbidities or <strong>pre-existing medical conditions</strong> in patients (takes into account <strong>17</strong> comorbidities), which can impact their health outcomes and overall survival.</p></li>
<li><p><strong>Elixhauser Comorbidity Index (ECI)</strong> is a measure of the burden of comorbidities, based on <strong>30</strong> different comorbid conditions.</p></li>
<li><p><strong>Chronic Disease Score (CDS)</strong> is a weighted score of the number and severity of chronic diseases, calculated using self-reported data on diagnosed conditions (considers the presence of <strong>21</strong> chronic conditions).</p></li>
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<li><span class="citation" data-cites="charlson1987new elixhauser1998comorbidity von1992chronic">(<a href="references.html#ref-charlson1987new" role="doc-biblioref">Charlson et al. 1987</a>; <a href="references.html#ref-elixhauser1998comorbidity" role="doc-biblioref">Elixhauser et al. 1998</a>; <a href="references.html#ref-von1992chronic" role="doc-biblioref">Von Korff, Wagner, and Saunders 1992</a>)</span></li>
<li>NHANES does not include information on all of the comorbidities included in theses scores / indices.</li>
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Residual confounding
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<p>Comorbidity scores are widely used as a measure of comorbidity burden, and their calculation often relies on data that may not be available in certain contexts, such as in NHANES or Canadian health administrative databases. In such cases, when comorbidity burden is a known confounder, researchers may use proxy information to approximate and mimic the information. Not being able to adjust for such variable can introduce bias and residual confounding in the treatment effect estimation.</p>
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<li><span class="citation" data-cites="schneeweiss2000use lix2011performance lix2013predictive">(<a href="references.html#ref-schneeweiss2000use" role="doc-biblioref">Schneeweiss and Maclure 2000</a>; <a href="references.html#ref-lix2011performance" role="doc-biblioref">L. Lix et al. 2011</a>; <a href="references.html#ref-lix2013predictive" role="doc-biblioref">L. M. Lix et al. 2013</a>)</span></li>
</ul>
</div></div></section>
<section id="proxy-adjustment-empirical-criterion" class="level2 page-columns page-full" data-number="3.2">
<h2 data-number="3.2" class="anchored" data-anchor-id="proxy-adjustment-empirical-criterion"><span class="header-section-number">3.2</span> Proxy Adjustment Empirical criterion</h2>
<p><strong>Empirical criterion: Modified disjunctive cause criterion</strong></p>
<p><a href="https://doi.org/10.1007/s10654-019-00494-6">VanderWeele et al. 2019</a> European Journal of Epidemiology: <a href="http://creativecommons.org/licenses/by/4.0/">CC BY license</a></p>
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<p><img src="images/proxy.png" style="width:100.0%" class="figure-img"></p>
<p></p><figcaption class="figure-caption">Hypothesized Directed acyclic graph with comorbidity measure being unmeasured, and approximated by the simple count measures based on the ICD codes</figcaption><p></p>
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<p>Adjust for variables that are (a) causes of exposure or outcome or both, (b) discard: known instrument, (c) <mark>including good proxies for unmeasured common causes</mark> <span class="citation" data-cites="vanderweele2019principles">(<a href="references.html#ref-vanderweele2019principles" role="doc-biblioref">VanderWeele 2019</a>)</span></p>
</div></div></section>
<section id="additional-information-icd-10-cm" class="level2 page-columns page-full" data-number="3.3">
<h2 data-number="3.3" class="anchored" data-anchor-id="additional-information-icd-10-cm"><span class="header-section-number">3.3</span> Additional information: ICD-10-CM</h2>
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<p>The International Classification of Diseases 10th Revision (ICD-10) is a <strong>standardized system of codes</strong> for the classification of <strong>diseases, disorders, and injuries</strong>.</p>
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<th>Role</th>
<th>Data Source</th>
<th>Variables considered</th>
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<td><mark>Role unclear</mark> as they may not directly relate to the research question</td>
<td><a href="https://wwwn.cdc.gov/Nchs/Data/Nhanes/Public/2017/DataFiles/RXQ_RX_J.htm">RXQ_RX</a></td>
<td>Prescription medication <a href="https://archive.cdc.gov/www_cdc_gov/nchs/icd/icd10cm_pcs_background.htm">ICD-10-CM code</a></td>
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<p><a href="https://wwwn.cdc.gov/Nchs/Data/Nhanes/Public/2017/DataFiles/RXQ_RX_J.htm">RXQ_RX</a> questionnaire (a) collects information on <strong>prescription medications taken in the past 30 days</strong>, (b) conducted by trained interviewers, and (c) with some quality control efforts.</p>
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<p></p><figcaption class="figure-caption">Examples of ICD-10-CM codes (3-7 characters, 1st character being alpha, 2-end are numberic, often with a dot) assigned to reasons for using medication (see Appendix in NHANES RXQ_RX component)</figcaption><p></p>
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<p>We have a lot of information through these ICD-10-CM codes, but for most of these information, it is unclear what role they play within the context of our research questions.</p>
</div></div><p><a href="https://pubmed.ncbi.nlm.nih.gov/16464140/">Count of prescriptions</a> is often used to measure <a href="https://bmchealthservres.biomedcentral.com/articles/10.1186/1472-6963-13-340">comorbidity burden</a>. This is not a perfect measure. But could serve as a proxy for our purpose.</p>
<div class="no-row-height column-margin column-container"><div class="">
<p><strong>Prescription medication</strong> (ICD-10-CM codes from all 3 cycles) data was liked with the initial data.</p>
</div></div><div id="refs" class="references csl-bib-body hanging-indent" role="doc-bibliography" style="display: none">
<div id="ref-charlson1987new" class="csl-entry" role="doc-biblioentry">
Charlson, Mary E, Peter Pompei, Kathy L Ales, and C Ronald MacKenzie. 1987. <span>“A New Method of Classifying Prognostic Comorbidity in Longitudinal Studies: Development and Validation.”</span> <em>Journal of Chronic Diseases</em> 40 (5): 373–83.
</div>
<div id="ref-elixhauser1998comorbidity" class="csl-entry" role="doc-biblioentry">
Elixhauser, Anne, Claudia Steiner, D Robert Harris, and Rosanna M Coffey. 1998. <span>“Comorbidity Measures for Use with Administrative Data.”</span> <em>Medical Care</em>, 8–27.
</div>
<div id="ref-lix2013predictive" class="csl-entry" role="doc-biblioentry">
Lix, Lisa M, Jacqueline Quail, Opeyemi Fadahunsi, and Gary F Teare. 2013. <span>“Predictive Performance of Comorbidity Measures in Administrative Databases for Diabetes Cohorts.”</span> <em>BMC Health Services Research</em> 13: 1–12.
</div>
<div id="ref-lix2011performance" class="csl-entry" role="doc-biblioentry">
Lix, LM, J Quail, G Teare, and B Acan. 2011. <span>“Performance of Comorbidity Measures for Predicting Outcomes in Population-Based Osteoporosis Cohorts.”</span> <em>Osteoporosis International</em> 22: 2633–43.
</div>
<div id="ref-schneeweiss2000use" class="csl-entry" role="doc-biblioentry">
Schneeweiss, Sebastian, and Malcolm Maclure. 2000. <span>“Use of Comorbidity Scores for Control of Confounding in Studies Using Administrative Databases.”</span> <em>International Journal of Epidemiology</em> 29 (5): 891–98.
</div>
<div id="ref-vanderweele2019principles" class="csl-entry" role="doc-biblioentry">
VanderWeele, Tyler J. 2019. <span>“Principles of Confounder Selection.”</span> <em>European Journal of Epidemiology</em> 34: 211–19.
</div>
<div id="ref-von1992chronic" class="csl-entry" role="doc-biblioentry">
Von Korff, Michael, Edward H Wagner, and Kathleen Saunders. 1992. <span>“A Chronic Disease Score from Automated Pharmacy Data.”</span> <em>Journal of Clinical Epidemiology</em> 45 (2): 197–203.
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