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	<updated>2026-05-15T02:51:18Z</updated>
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		<title>Lawrence: /* Minimization */</title>
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		<updated>2025-06-04T11:11:29Z</updated>

		<summary type="html">&lt;p&gt;&lt;span class=&quot;autocomment&quot;&gt;Minimization&lt;/span&gt;&lt;/p&gt;
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				&lt;td colspan=&quot;2&quot; style=&quot;background-color: #fff; color: #202122; text-align: center;&quot;&gt;← Older revision&lt;/td&gt;
				&lt;td colspan=&quot;2&quot; style=&quot;background-color: #fff; color: #202122; text-align: center;&quot;&gt;Revision as of 11:11, 4 June 2025&lt;/td&gt;
				&lt;/tr&gt;&lt;tr&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-lineno&quot; id=&quot;mw-diff-left-l1&quot;&gt;Line 1:&lt;/td&gt;
&lt;td colspan=&quot;2&quot; class=&quot;diff-lineno&quot;&gt;Line 1:&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot;&gt;&lt;/td&gt;&lt;td style=&quot;background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;== Minimization ==&lt;/div&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot;&gt;&lt;/td&gt;&lt;td style=&quot;background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;== Minimization ==&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot;&gt;&lt;/td&gt;&lt;td style=&quot;background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;br&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot;&gt;&lt;/td&gt;&lt;td style=&quot;background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;br&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&#039;&#039;&#039;Minimization&#039;&#039;&#039; is a dynamic randomization technique used to achieve balanced allocation of participants across treatment groups in randomized controlled trials. It is especially valuable in studies with small sample sizes or when controlling for multiple prognostic factors is essential. Unlike simple randomization, which assigns participants without regard to prior assignments, minimization takes into account the characteristics of participants already enrolled and assigns new participants to the treatment group that will best preserve balance.&lt;/div&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;+&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&#039;&#039;&#039;Minimization&#039;&#039;&#039; is a dynamic &lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;[[&lt;/ins&gt;randomization&lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;]] &lt;/ins&gt;technique used to achieve balanced allocation of participants across treatment groups in randomized controlled trials. It is especially valuable in studies with small sample sizes or when controlling for multiple prognostic factors is essential. Unlike simple randomization, which assigns participants without regard to prior assignments, minimization takes into account the characteristics of participants already enrolled and assigns new participants to the treatment group that will best preserve balance.&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot;&gt;&lt;/td&gt;&lt;td style=&quot;background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;br&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot;&gt;&lt;/td&gt;&lt;td style=&quot;background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;br&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;The process begins by identifying key prognostic factors that are known to influence study outcomes, such as age, sex, disease severity, or presence of comorbidities. Once treatment groups are defined—typically two (e.g., Treatment A and Treatment B), but possibly more—the system calculates an imbalance score for each group based on how the new participant&#039;s characteristics would affect group balance. The participant is then allocated to the group that minimizes this imbalance. This can be done in two ways: &#039;&#039;&#039;deterministically&#039;&#039;&#039;, where the participant is always assigned to the group with the lowest imbalance, or &#039;&#039;&#039;probabilistically&#039;&#039;&#039;, where the participant is more likely (but not guaranteed) to be assigned to the better-balanced group. The probabilistic approach (e.g., 80:20 probability) is generally recommended because it maintains balance while reducing predictability and selection bias.&lt;/del&gt;&lt;/div&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;+&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;=== Key Concepts ===&lt;/ins&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot;&gt;&lt;/td&gt;&lt;td style=&quot;background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;br&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot;&gt;&lt;/td&gt;&lt;td style=&quot;background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;br&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;There &lt;/del&gt;are two &lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;main types of minimization&lt;/del&gt;. &lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;&#039;&#039;&#039;Deterministic minimization&#039;&#039;&#039; offers excellent balance but can be predictable&lt;/del&gt;, &lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;potentially introducing selection bias. In contrast&lt;/del&gt;, &#039;&lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;&#039;&#039;probabilistic minimization&#039;&#039;&#039; provides strong &lt;/del&gt;balance &lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;with added randomness, enhancing allocation concealment and methodological rigor&lt;/del&gt;. &lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;While minimization &lt;/del&gt;is &lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;more efficient than stratified randomization in handling multiple covariates—since it avoids creating numerous strata—it typically requires software tools like &#039;&#039;&#039;MinimPy&#039;&#039;&#039; or R packages such as &#039;&#039;&#039;rMinimization&#039;&#039;&#039; due &lt;/del&gt;to &lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;its complexity&lt;/del&gt;.&lt;/div&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;+&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;The process begins by identifying key prognostic factors that &lt;/ins&gt;are &lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;known to influence study outcomes, such as age, sex, disease severity, or presence of comorbidities. Once treatment groups are defined—typically &lt;/ins&gt;two &lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;(e.g&lt;/ins&gt;., &lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;Treatment A and Treatment B)&lt;/ins&gt;, &lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;but possibly more—the system calculates an imbalance score for each group based on how the new participant&lt;/ins&gt;&#039;&lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;s characteristics would affect group &lt;/ins&gt;balance. &lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;The participant &lt;/ins&gt;is &lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;then allocated &lt;/ins&gt;to &lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;the group that minimizes this imbalance&lt;/ins&gt;.&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot;&gt;&lt;/td&gt;&lt;td style=&quot;background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;br&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot;&gt;&lt;/td&gt;&lt;td style=&quot;background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;br&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;Minimization is ideal for trials with small sample sizes, supports unequal allocation ratios (e.g., 2:1 or 3:1), and effectively reduces confounding by balancing key variables. However, it does come with challenges. Specialized software is necessary, deterministic methods can introduce bias, and some regulatory agencies or ethics boards may favor conventional randomization for transparency.&lt;/del&gt;&lt;/div&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;+&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;=== Allocation Methods ===&lt;/ins&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot;&gt;&lt;/td&gt;&lt;td style=&quot;background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;br&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot;&gt;&lt;/td&gt;&lt;td style=&quot;background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;br&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;For example&lt;/del&gt;, &lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;in a trial comparing Drug A and Drug B for stroke prevention&lt;/del&gt;, &lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;key prognostic factors such as age &lt;/del&gt;(&lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;&amp;lt;65 vs. ≥65&lt;/del&gt;)&lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;, hypertension status, and diabetes status might &lt;/del&gt;be &lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;used. As each participant enrolls, the system assesses how their inclusion would affect balance and assigns them &lt;/del&gt;to the group &lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;that best maintains equilibrium, often using probabilistic minimization&lt;/del&gt;.&lt;/div&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;+&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;This can be done in two ways:&lt;/ins&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-deleted&quot;&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;+&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;* &#039;&#039;&#039;Deterministically&#039;&#039;&#039;&lt;/ins&gt;, &lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;where the participant is always assigned to the group with the lowest imbalance.&lt;/ins&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-deleted&quot;&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;+&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;* &#039;&#039;&#039;Probabilistically&#039;&#039;&#039;&lt;/ins&gt;, &lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;where the participant is more likely &lt;/ins&gt;(&lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;but not guaranteed&lt;/ins&gt;) &lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;to &lt;/ins&gt;be &lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;assigned &lt;/ins&gt;to the &lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;better-balanced &lt;/ins&gt;group.&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot;&gt;&lt;/td&gt;&lt;td style=&quot;background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;br&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot;&gt;&lt;/td&gt;&lt;td style=&quot;background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;br&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;In &lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;conclusion&lt;/del&gt;, minimization is a powerful and flexible technique that improves balance between treatment groups in RCTs. It is especially useful when multiple covariates need to be controlled, and its probabilistic variant offers a strong safeguard against selection bias while maintaining scientific integrity.&lt;/div&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;+&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;The probabilistic approach (e.g., 80:20 probability) is generally recommended because it maintains balance while reducing predictability and selection bias.&lt;/ins&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-deleted&quot;&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;+&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt; &lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-deleted&quot;&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;+&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;=== Types of Minimization ===&lt;/ins&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-deleted&quot;&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;+&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt; &lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-deleted&quot;&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;+&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;There are two main types of minimization:&lt;/ins&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-deleted&quot;&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;+&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;* &#039;&#039;&#039;Deterministic minimization&#039;&#039;&#039; offers excellent balance but can be predictable, potentially introducing selection bias.&lt;/ins&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-deleted&quot;&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;+&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;* &#039;&#039;&#039;Probabilistic minimization&#039;&#039;&#039; provides strong balance with added randomness, enhancing [[allocation concealment]] and methodological rigor.&lt;/ins&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-deleted&quot;&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;+&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt; &lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-deleted&quot;&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;+&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;=== Comparison with Stratified Randomization ===&lt;/ins&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-deleted&quot;&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;+&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt; &lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-deleted&quot;&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;+&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;While minimization is more efficient than stratified randomization in handling multiple covariates—since it avoids creating numerous strata—it typically requires software tools like &#039;&#039;&#039;MinimPy&#039;&#039;&#039; or R packages such as &#039;&#039;&#039;rMinimization&#039;&#039;&#039; due to its complexity.&lt;/ins&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-deleted&quot;&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;+&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt; &lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-deleted&quot;&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;+&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;=== Advantages and Challenges ===&lt;/ins&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-deleted&quot;&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;+&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt; &lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-deleted&quot;&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;+&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;Minimization is ideal for trials with small sample sizes, supports unequal allocation ratios (e.g., 2:1 or 3:1), and effectively reduces confounding by balancing key variables. However, it does come with challenges:&lt;/ins&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-deleted&quot;&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;+&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;* Specialized software is necessary.&lt;/ins&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-deleted&quot;&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;+&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;* Deterministic methods can introduce bias.&lt;/ins&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-deleted&quot;&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;+&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;* Some regulatory agencies or [[ethics]] boards may prefer conventional randomization for transparency.&lt;/ins&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-deleted&quot;&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;+&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt; &lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-deleted&quot;&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;+&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;=== Example ===&lt;/ins&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-deleted&quot;&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;+&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt; &lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-deleted&quot;&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;+&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;In &lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;a trial comparing Drug A and Drug B for stroke prevention&lt;/ins&gt;, &lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;key prognostic factors such as age (&amp;lt;65 vs. ≥65), hypertension status, and diabetes status might be used. As each participant enrolls, the system assesses how their inclusion would affect balance and assigns them to the group that best maintains equilibrium, often using probabilistic &lt;/ins&gt;minimization&lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;.&lt;/ins&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-deleted&quot;&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;+&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt; &lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-deleted&quot;&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;+&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;=== Conclusion ===&lt;/ins&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-deleted&quot;&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;+&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt; &lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-deleted&quot;&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;+&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;Minimization &lt;/ins&gt;is a powerful and flexible technique that improves balance between treatment groups in RCTs. It is especially useful when multiple covariates need to be controlled, and its probabilistic variant offers a strong safeguard against selection bias while maintaining scientific integrity.&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-deleted&quot;&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;+&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt; &lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-deleted&quot;&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;+&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt; &lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-deleted&quot;&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;+&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;----&lt;/ins&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-deleted&quot;&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;+&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt; &lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-deleted&quot;&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;+&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;=== Bibliography ===&lt;/ins&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-deleted&quot;&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;+&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt; &lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-deleted&quot;&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;+&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;# Treasure T, MacRae KD. Minimisation: the platinum standard for trials? &#039;&#039;BMJ&#039;&#039;. 1998;317(7155):362–363.&lt;/ins&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-deleted&quot;&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;+&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;# Taves DR. Minimization: a new method of assigning patients to treatment and control groups. &#039;&#039;Clinical Pharmacology &amp;amp; Therapeutics&#039;&#039;. 1974;15(5):443–453.&lt;/ins&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-deleted&quot;&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;+&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;# Altman DG, Bland JM. Treatment allocation by minimisation. &#039;&#039;BMJ&#039;&#039;. 2005;330(7495):843.&lt;/ins&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-deleted&quot;&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;+&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;# Scott NW, McPherson GC, Ramsay CR, Campbell MK. The method of minimization for allocation to clinical trials: a review. &#039;&#039;Controlled Clinical Trials&#039;&#039;. 2002;23(6):662–674.&lt;/ins&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-deleted&quot;&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;+&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;# Suresh KP. An overview of randomization techniques: an unbiased assessment of outcome in clinical research. &#039;&#039;Journal of Human Reproductive Sciences&#039;&#039;. 2011;4(1):8–11. Includes discussion of minimization among other methods.&lt;/ins&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-deleted&quot;&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;+&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt; &lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-deleted&quot;&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;+&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;----&lt;/ins&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-deleted&quot;&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;+&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;&#039;&#039;Adapted for educational use. Please cite relevant trial methodology sources when using this material in research or teaching.&#039;&#039;&lt;/ins&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;/table&gt;</summary>
		<author><name>Lawrence</name></author>
	</entry>
	<entry>
		<id>https://wiki.trialtree.ca/index.php?title=Minimization&amp;diff=47&amp;oldid=prev</id>
		<title>Lawrence at 13:47, 25 March 2025</title>
		<link rel="alternate" type="text/html" href="https://wiki.trialtree.ca/index.php?title=Minimization&amp;diff=47&amp;oldid=prev"/>
		<updated>2025-03-25T13:47:40Z</updated>

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				&lt;td colspan=&quot;2&quot; style=&quot;background-color: #fff; color: #202122; text-align: center;&quot;&gt;← Older revision&lt;/td&gt;
				&lt;td colspan=&quot;2&quot; style=&quot;background-color: #fff; color: #202122; text-align: center;&quot;&gt;Revision as of 13:47, 25 March 2025&lt;/td&gt;
				&lt;/tr&gt;&lt;tr&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-lineno&quot; id=&quot;mw-diff-left-l1&quot;&gt;Line 1:&lt;/td&gt;
&lt;td colspan=&quot;2&quot; class=&quot;diff-lineno&quot;&gt;Line 1:&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot;&gt;&lt;/td&gt;&lt;td style=&quot;background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;== Minimization ==&lt;/div&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot;&gt;&lt;/td&gt;&lt;td style=&quot;background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;== Minimization ==&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot;&gt;&lt;/td&gt;&lt;td style=&quot;background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;br&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot;&gt;&lt;/td&gt;&lt;td style=&quot;background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;br&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&#039;&#039;&#039;Minimization&#039;&#039;&#039; is a dynamic randomization technique used to achieve balanced allocation of participants across treatment groups. It is especially &lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;useful &lt;/del&gt;in &lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;trials &lt;/del&gt;with small sample sizes or when multiple prognostic factors &lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;need &lt;/del&gt;to &lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;be controlled&lt;/del&gt;.&lt;/div&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;+&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&#039;&#039;&#039;Minimization&#039;&#039;&#039; is a dynamic randomization technique used to achieve balanced allocation of participants across treatment groups &lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;in randomized controlled trials&lt;/ins&gt;. It is especially &lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;valuable &lt;/ins&gt;in &lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;studies &lt;/ins&gt;with small sample sizes or when &lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;controlling for &lt;/ins&gt;multiple prognostic factors &lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;is essential. Unlike simple randomization, which assigns participants without regard to prior assignments, minimization takes into account the characteristics of participants already enrolled and assigns new participants &lt;/ins&gt;to &lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;the treatment group that will best preserve balance&lt;/ins&gt;.&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot;&gt;&lt;/td&gt;&lt;td style=&quot;background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;br&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot;&gt;&lt;/td&gt;&lt;td style=&quot;background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;br&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;Unlike simple randomization&lt;/del&gt;, &lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;minimization considers the characteristics &lt;/del&gt;of &lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;participants already enrolled &lt;/del&gt;and &lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;assigns &lt;/del&gt;new &lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;participants &lt;/del&gt;to the group that &lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;would maintain &lt;/del&gt;balance.&lt;/div&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;+&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;The process begins by identifying key prognostic factors that are known to influence study outcomes, such as age, sex, disease severity&lt;/ins&gt;, &lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;or presence &lt;/ins&gt;of &lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;comorbidities. Once treatment groups are defined—typically two (e.g., Treatment A &lt;/ins&gt;and &lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;Treatment B), but possibly more—the system calculates an imbalance score for each group based on how the &lt;/ins&gt;new &lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;participant&#039;s characteristics would affect group balance. The participant is then allocated &lt;/ins&gt;to the group that &lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;minimizes this imbalance. This can be done in two ways: &#039;&#039;&#039;deterministically&#039;&#039;&#039;, where the participant is always assigned to the group with the lowest imbalance, or &#039;&#039;&#039;probabilistically&#039;&#039;&#039;, where the participant is more likely (but not guaranteed) to be assigned to the better-balanced group. The probabilistic approach (e.g., 80:20 probability) is generally recommended because it maintains &lt;/ins&gt;balance &lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;while reducing predictability and selection bias&lt;/ins&gt;.&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot;&gt;&lt;/td&gt;&lt;td style=&quot;background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;br&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot;&gt;&lt;/td&gt;&lt;td style=&quot;background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;br&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;=== How Minimization Works ===&lt;/del&gt;&lt;/div&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;+&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;There are two main types of minimization. &#039;&#039;&#039;Deterministic minimization&#039;&#039;&#039; offers excellent balance but can be predictable, potentially introducing selection bias. In contrast, &#039;&#039;&#039;probabilistic minimization&#039;&#039;&#039; provides strong balance with added randomness, enhancing allocation concealment and methodological rigor. While minimization is more efficient than stratified randomization in handling multiple covariates—since it avoids creating numerous strata—it typically requires software tools like &#039;&#039;&#039;MinimPy&#039;&#039;&#039; or R packages such as &#039;&#039;&#039;rMinimization&#039;&#039;&#039; due to its complexity.&lt;/ins&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot;&gt;&lt;/td&gt;&lt;td style=&quot;background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;br&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot;&gt;&lt;/td&gt;&lt;td style=&quot;background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;br&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;# &#039;&#039;&#039;Define Key Prognostic Factors&#039;&#039;&#039;&lt;/del&gt;&lt;/div&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;+&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;Minimization is ideal for trials with small sample sizes, supports unequal allocation ratios &lt;/ins&gt;(e.g., &lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;2:1 or 3:1)&lt;/ins&gt;, &lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;and effectively reduces confounding by balancing key variables&lt;/ins&gt;. &lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;However&lt;/ins&gt;, &lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;it does come with challenges&lt;/ins&gt;. &lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;Specialized software is necessary&lt;/ins&gt;, &lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;deterministic methods &lt;/ins&gt;can &lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;introduce bias&lt;/ins&gt;, &lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;and some regulatory agencies or ethics boards may favor conventional randomization for transparency&lt;/ins&gt;.&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;* Factors known to influence outcomes &lt;/del&gt;(e.g., &lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;age, sex&lt;/del&gt;, &lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;disease severity, comorbidities).&lt;/del&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-added&quot;&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;# &#039;&#039;&#039;Determine Treatment Groups&#039;&#039;&#039;&lt;/del&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-added&quot;&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;* Typically two arms (e.g&lt;/del&gt;., &lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;Treatment A vs&lt;/del&gt;. &lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;Treatment B)&lt;/del&gt;, &lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;but &lt;/del&gt;can &lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;include more.&lt;/del&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-added&quot;&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;# &#039;&#039;&#039;Calculate Imbalance Scores&#039;&#039;&#039;&lt;/del&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-added&quot;&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;* For each new participant&lt;/del&gt;, &lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;the system evaluates the imbalance each treatment assignment would produce.&lt;/del&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-added&quot;&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;# &#039;&#039;&#039;Assign Treatment Based on Balance&#039;&#039;&#039;&lt;/del&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-added&quot;&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;* The participant is allocated to the group that minimizes imbalance:&lt;/del&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-added&quot;&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;** &#039;&#039;&#039;Deterministically&#039;&#039;&#039; – always to the better-balanced group.&lt;/del&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-added&quot;&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;** &#039;&#039;&#039;Probabilistically&#039;&#039;&#039; – with higher probability to the better-balanced group&lt;/del&gt;.&lt;/div&gt;&lt;/td&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-added&quot;&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot;&gt;&lt;/td&gt;&lt;td style=&quot;background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;br&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot;&gt;&lt;/td&gt;&lt;td style=&quot;background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;br&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;=== Types of Minimization Approaches ===&lt;/del&gt;&lt;/div&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;+&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;For example, in a trial comparing Drug A and Drug B for stroke prevention, key prognostic factors such as age (&amp;lt;65 vs. ≥65), hypertension status, and diabetes status might be used. As each participant enrolls, the system assesses how their inclusion would affect balance and assigns them to the group that best maintains equilibrium, often using probabilistic minimization.&lt;/ins&gt;&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot;&gt;&lt;/td&gt;&lt;td style=&quot;background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;br&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot;&gt;&lt;/td&gt;&lt;td style=&quot;background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;br&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;* &#039;&#039;&#039;Deterministic Minimization&#039;&#039;&#039;&lt;/del&gt;&lt;/div&gt;&lt;/td&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;+&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;In conclusion&lt;/ins&gt;, minimization is a powerful &lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;and flexible &lt;/ins&gt;technique that improves &lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;balance between &lt;/ins&gt;treatment &lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;groups &lt;/ins&gt;in &lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;RCTs. It is especially useful &lt;/ins&gt;when multiple covariates need to be controlled&lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;, and its &lt;/ins&gt;probabilistic &lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;variant offers a strong safeguard against &lt;/ins&gt;selection bias while &lt;ins style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;maintaining &lt;/ins&gt;scientific integrity.&lt;/div&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;** Always assigns to the group with the lowest imbalance.&lt;/del&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-added&quot;&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;** &#039;&#039;&#039;Pros&#039;&#039;&#039;: Excellent balance.&lt;/del&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-added&quot;&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;** &#039;&#039;&#039;Cons&#039;&#039;&#039;: Can be predictable, increasing risk of selection bias.&lt;/del&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-added&quot;&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt; &lt;/div&gt;&lt;/td&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-added&quot;&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;* &#039;&#039;&#039;Probabilistic Minimization&#039;&#039;&#039; (&#039;&#039;&#039;Recommended&#039;&#039;&#039;)&lt;/del&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-added&quot;&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;** Randomly assigns with higher likelihood to the group that improves balance (e.g., 80:20 probability).&lt;/del&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-added&quot;&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;** &#039;&#039;&#039;Pros&#039;&#039;&#039;: Good balance and less predictable.&lt;/del&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-added&quot;&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;** &#039;&#039;&#039;Cons&#039;&#039;&#039;: Requires software or algorithmic support.&lt;/del&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-added&quot;&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt; &lt;/div&gt;&lt;/td&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-added&quot;&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;=== Advantages of Minimization ===&lt;/del&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-added&quot;&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt; &lt;/div&gt;&lt;/td&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-added&quot;&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;* &#039;&#039;&#039;Ensures Treatment Group Balance&#039;&#039;&#039;&lt;/del&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-added&quot;&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;** Balances key prognostic factors, reducing confounding.&lt;/del&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-added&quot;&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;* &#039;&#039;&#039;More Efficient than Stratified Randomization&#039;&#039;&#039;&lt;/del&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-added&quot;&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;** Handles multiple covariates without creating numerous strata.&lt;/del&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-added&quot;&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;* &#039;&#039;&#039;Ideal for Small Trials&#039;&#039;&#039;&lt;/del&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-added&quot;&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;** Prevents major imbalances when sample size is limited.&lt;/del&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-added&quot;&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;* &#039;&#039;&#039;Adaptable for Unequal Allocation Ratios&#039;&#039;&#039;&lt;/del&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-added&quot;&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;** Works with designs like 2:1 or 3:1 allocation.&lt;/del&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-added&quot;&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt; &lt;/div&gt;&lt;/td&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-added&quot;&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;=== Challenges and Limitations ===&lt;/del&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-added&quot;&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt; &lt;/div&gt;&lt;/td&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-added&quot;&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;* &#039;&#039;&#039;Requires Specialized Software&#039;&#039;&#039;&lt;/del&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-added&quot;&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;** Manual minimization is complex—use tools like &#039;&#039;&#039;MinimPy&#039;&#039;&#039; or &#039;&#039;&#039;rMinimization&#039;&#039;&#039; in R.&lt;/del&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-added&quot;&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;* &#039;&#039;&#039;Potential for Selection Bias&#039;&#039;&#039;&lt;/del&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-added&quot;&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;** Deterministic approaches may allow predictability; probabilistic methods reduce this risk.&lt;/del&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-added&quot;&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;* &#039;&#039;&#039;Regulatory Acceptance&#039;&#039;&#039;&lt;/del&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-added&quot;&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;** Some ethics boards and agencies prefer conventional randomization for transparency.&lt;/del&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-added&quot;&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt; &lt;/div&gt;&lt;/td&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-added&quot;&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;=== Example of Minimization in an RCT ===&lt;/del&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-added&quot;&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt; &lt;/div&gt;&lt;/td&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-added&quot;&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;&#039;&#039;&#039;Study Objective:&#039;&#039;&#039; Compare Drug A vs. Drug B in stroke prevention.&lt;/del&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-added&quot;&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt; &lt;/div&gt;&lt;/td&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-added&quot;&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;&#039;&#039;&#039;Key Prognostic Factors:&#039;&#039;&#039;&lt;/del&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-added&quot;&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;* Age: &amp;lt;65 vs. ≥65&lt;/del&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-added&quot;&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;* Hypertension: Yes vs. No&lt;/del&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-added&quot;&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;* Diabetes: Yes vs. No&lt;/del&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-added&quot;&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt; &lt;/div&gt;&lt;/td&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-added&quot;&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;&#039;&#039;&#039;Process:&#039;&#039;&#039;&lt;/del&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-added&quot;&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;* As each participant enrolls&lt;/del&gt;, &lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;their characteristics are compared with the existing cohort.&lt;/del&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-added&quot;&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;* The imbalance score for each treatment group is calculated.&lt;/del&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-added&quot;&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;* The participant is allocated to the group that maintains optimal balance (often using probabilistic &lt;/del&gt;minimization&lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;).&lt;/del&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-added&quot;&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt; &lt;/div&gt;&lt;/td&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-added&quot;&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;=== Conclusion ===&lt;/del&gt;&lt;/div&gt;&lt;/td&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-added&quot;&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt; &lt;/div&gt;&lt;/td&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-added&quot;&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;tr&gt;&lt;td class=&quot;diff-marker&quot; data-marker=&quot;−&quot;&gt;&lt;/td&gt;&lt;td style=&quot;color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;&quot;&gt;&lt;div&gt;&lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;Minimization &lt;/del&gt;is a powerful technique that improves treatment &lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;group balance &lt;/del&gt;in &lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;RCTs—especially &lt;/del&gt;when &lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;sample sizes are small or &lt;/del&gt;multiple covariates need to be controlled&lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;. A &lt;/del&gt;probabilistic &lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;approach enhances methodological rigor by reducing &lt;/del&gt;selection bias while &lt;del style=&quot;font-weight: bold; text-decoration: none;&quot;&gt;preserving fairness and &lt;/del&gt;scientific integrity.&lt;/div&gt;&lt;/td&gt;&lt;td colspan=&quot;2&quot; class=&quot;diff-side-added&quot;&gt;&lt;/td&gt;&lt;/tr&gt;
&lt;/table&gt;</summary>
		<author><name>Lawrence</name></author>
	</entry>
	<entry>
		<id>https://wiki.trialtree.ca/index.php?title=Minimization&amp;diff=34&amp;oldid=prev</id>
		<title>Lawrence: Created page with &quot;== Minimization ==  &#039;&#039;&#039;Minimization&#039;&#039;&#039; is a dynamic randomization technique used to achieve balanced allocation of participants across treatment groups. It is especially useful in trials with small sample sizes or when multiple prognostic factors need to be controlled.  Unlike simple randomization, minimization considers the characteristics of participants already enrolled and assigns new participants to the group that would maintain balance.  === How Minimization Works...&quot;</title>
		<link rel="alternate" type="text/html" href="https://wiki.trialtree.ca/index.php?title=Minimization&amp;diff=34&amp;oldid=prev"/>
		<updated>2025-03-24T22:13:01Z</updated>

		<summary type="html">&lt;p&gt;Created page with &amp;quot;== Minimization ==  &amp;#039;&amp;#039;&amp;#039;Minimization&amp;#039;&amp;#039;&amp;#039; is a dynamic randomization technique used to achieve balanced allocation of participants across treatment groups. It is especially useful in trials with small sample sizes or when multiple prognostic factors need to be controlled.  Unlike simple randomization, minimization considers the characteristics of participants already enrolled and assigns new participants to the group that would maintain balance.  === How Minimization Works...&amp;quot;&lt;/p&gt;
&lt;p&gt;&lt;b&gt;New page&lt;/b&gt;&lt;/p&gt;&lt;div&gt;== Minimization ==&lt;br /&gt;
&lt;br /&gt;
&amp;#039;&amp;#039;&amp;#039;Minimization&amp;#039;&amp;#039;&amp;#039; is a dynamic randomization technique used to achieve balanced allocation of participants across treatment groups. It is especially useful in trials with small sample sizes or when multiple prognostic factors need to be controlled.&lt;br /&gt;
&lt;br /&gt;
Unlike simple randomization, minimization considers the characteristics of participants already enrolled and assigns new participants to the group that would maintain balance.&lt;br /&gt;
&lt;br /&gt;
=== How Minimization Works ===&lt;br /&gt;
&lt;br /&gt;
# &amp;#039;&amp;#039;&amp;#039;Define Key Prognostic Factors&amp;#039;&amp;#039;&amp;#039;&lt;br /&gt;
* Factors known to influence outcomes (e.g., age, sex, disease severity, comorbidities).&lt;br /&gt;
# &amp;#039;&amp;#039;&amp;#039;Determine Treatment Groups&amp;#039;&amp;#039;&amp;#039;&lt;br /&gt;
* Typically two arms (e.g., Treatment A vs. Treatment B), but can include more.&lt;br /&gt;
# &amp;#039;&amp;#039;&amp;#039;Calculate Imbalance Scores&amp;#039;&amp;#039;&amp;#039;&lt;br /&gt;
* For each new participant, the system evaluates the imbalance each treatment assignment would produce.&lt;br /&gt;
# &amp;#039;&amp;#039;&amp;#039;Assign Treatment Based on Balance&amp;#039;&amp;#039;&amp;#039;&lt;br /&gt;
* The participant is allocated to the group that minimizes imbalance:&lt;br /&gt;
** &amp;#039;&amp;#039;&amp;#039;Deterministically&amp;#039;&amp;#039;&amp;#039; – always to the better-balanced group.&lt;br /&gt;
** &amp;#039;&amp;#039;&amp;#039;Probabilistically&amp;#039;&amp;#039;&amp;#039; – with higher probability to the better-balanced group.&lt;br /&gt;
&lt;br /&gt;
=== Types of Minimization Approaches ===&lt;br /&gt;
&lt;br /&gt;
* &amp;#039;&amp;#039;&amp;#039;Deterministic Minimization&amp;#039;&amp;#039;&amp;#039;&lt;br /&gt;
** Always assigns to the group with the lowest imbalance.&lt;br /&gt;
** &amp;#039;&amp;#039;&amp;#039;Pros&amp;#039;&amp;#039;&amp;#039;: Excellent balance.&lt;br /&gt;
** &amp;#039;&amp;#039;&amp;#039;Cons&amp;#039;&amp;#039;&amp;#039;: Can be predictable, increasing risk of selection bias.&lt;br /&gt;
&lt;br /&gt;
* &amp;#039;&amp;#039;&amp;#039;Probabilistic Minimization&amp;#039;&amp;#039;&amp;#039; (&amp;#039;&amp;#039;&amp;#039;Recommended&amp;#039;&amp;#039;&amp;#039;)&lt;br /&gt;
** Randomly assigns with higher likelihood to the group that improves balance (e.g., 80:20 probability).&lt;br /&gt;
** &amp;#039;&amp;#039;&amp;#039;Pros&amp;#039;&amp;#039;&amp;#039;: Good balance and less predictable.&lt;br /&gt;
** &amp;#039;&amp;#039;&amp;#039;Cons&amp;#039;&amp;#039;&amp;#039;: Requires software or algorithmic support.&lt;br /&gt;
&lt;br /&gt;
=== Advantages of Minimization ===&lt;br /&gt;
&lt;br /&gt;
* &amp;#039;&amp;#039;&amp;#039;Ensures Treatment Group Balance&amp;#039;&amp;#039;&amp;#039;&lt;br /&gt;
** Balances key prognostic factors, reducing confounding.&lt;br /&gt;
* &amp;#039;&amp;#039;&amp;#039;More Efficient than Stratified Randomization&amp;#039;&amp;#039;&amp;#039;&lt;br /&gt;
** Handles multiple covariates without creating numerous strata.&lt;br /&gt;
* &amp;#039;&amp;#039;&amp;#039;Ideal for Small Trials&amp;#039;&amp;#039;&amp;#039;&lt;br /&gt;
** Prevents major imbalances when sample size is limited.&lt;br /&gt;
* &amp;#039;&amp;#039;&amp;#039;Adaptable for Unequal Allocation Ratios&amp;#039;&amp;#039;&amp;#039;&lt;br /&gt;
** Works with designs like 2:1 or 3:1 allocation.&lt;br /&gt;
&lt;br /&gt;
=== Challenges and Limitations ===&lt;br /&gt;
&lt;br /&gt;
* &amp;#039;&amp;#039;&amp;#039;Requires Specialized Software&amp;#039;&amp;#039;&amp;#039;&lt;br /&gt;
** Manual minimization is complex—use tools like &amp;#039;&amp;#039;&amp;#039;MinimPy&amp;#039;&amp;#039;&amp;#039; or &amp;#039;&amp;#039;&amp;#039;rMinimization&amp;#039;&amp;#039;&amp;#039; in R.&lt;br /&gt;
* &amp;#039;&amp;#039;&amp;#039;Potential for Selection Bias&amp;#039;&amp;#039;&amp;#039;&lt;br /&gt;
** Deterministic approaches may allow predictability; probabilistic methods reduce this risk.&lt;br /&gt;
* &amp;#039;&amp;#039;&amp;#039;Regulatory Acceptance&amp;#039;&amp;#039;&amp;#039;&lt;br /&gt;
** Some ethics boards and agencies prefer conventional randomization for transparency.&lt;br /&gt;
&lt;br /&gt;
=== Example of Minimization in an RCT ===&lt;br /&gt;
&lt;br /&gt;
&amp;#039;&amp;#039;&amp;#039;Study Objective:&amp;#039;&amp;#039;&amp;#039; Compare Drug A vs. Drug B in stroke prevention.&lt;br /&gt;
&lt;br /&gt;
&amp;#039;&amp;#039;&amp;#039;Key Prognostic Factors:&amp;#039;&amp;#039;&amp;#039;&lt;br /&gt;
* Age: &amp;lt;65 vs. ≥65&lt;br /&gt;
* Hypertension: Yes vs. No&lt;br /&gt;
* Diabetes: Yes vs. No&lt;br /&gt;
&lt;br /&gt;
&amp;#039;&amp;#039;&amp;#039;Process:&amp;#039;&amp;#039;&amp;#039;&lt;br /&gt;
* As each participant enrolls, their characteristics are compared with the existing cohort.&lt;br /&gt;
* The imbalance score for each treatment group is calculated.&lt;br /&gt;
* The participant is allocated to the group that maintains optimal balance (often using probabilistic minimization).&lt;br /&gt;
&lt;br /&gt;
=== Conclusion ===&lt;br /&gt;
&lt;br /&gt;
Minimization is a powerful technique that improves treatment group balance in RCTs—especially when sample sizes are small or multiple covariates need to be controlled. A probabilistic approach enhances methodological rigor by reducing selection bias while preserving fairness and scientific integrity.&lt;/div&gt;</summary>
		<author><name>Lawrence</name></author>
	</entry>
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