
{"id":23554,"date":"2024-05-30T05:32:21","date_gmt":"2024-05-30T05:32:21","guid":{"rendered":"http:\/\/staging.avdheshsharma.com\/strategies-to-prevent-the-placebo-effect-from-obscuring-clinical-trial-results\/"},"modified":"2026-04-09T14:14:24","modified_gmt":"2026-04-09T08:44:24","slug":"strategies-to-prevent-the-placebo-effect-from-obscuring-trial-results","status":"publish","type":"post","link":"https:\/\/www.editage.com\/insights\/strategies-to-prevent-the-placebo-effect-from-obscuring-trial-results","title":{"rendered":"How to reduce the placebo effect in medical research"},"content":{"rendered":"<p>To reduce the placebo effect in medical research, especially clinical trials, use strategies like matching, blinding and double-blinding, incorporating a run-in period, or using a two-phase sequential parallel comparison design.<\/p>\n<p><a href=\"#_Toc226636315\">What is the placebo effect?<\/a><\/p>\n<p><a href=\"#_Toc226636316\">What is the impact of the placebo effect on clinical trials?<\/a><\/p>\n<p><a href=\"#_Toc226636317\">How do we handle the placebo effect in clinical trials?<\/a><\/p>\n<p><a href=\"#_Toc226636318\">Matching groups<\/a><\/p>\n<p><a href=\"#_Toc226636319\">Blinding and double-blinding<\/a><\/p>\n<p><a href=\"#_Toc226636320\">Run-in period<\/a><\/p>\n<p><a href=\"#_Toc226636321\">Two-phase, sequential parallel comparison trial design<\/a><\/p>\n<p><a href=\"#_Toc226636322\">Other strategies<\/a><\/p>\n<p><a href=\"#_Toc226636323\">Does study power reduce the placebo effect?<\/a><\/p>\n<p><a href=\"#_Toc226636324\">Conclusion<\/a><\/p>\n<p>&nbsp;<\/p>\n<p>\u201cMy baby had GERD, so I tied a red ribbon to her stroller and she was cured!\u201d<\/p>\n<p>\u201cWhen I was diagnosed was Type 2 diabetes, I rubbed turmeric paste on the soles of my feet every night. Within a month, my blood sugar levels were normal!\u201d<\/p>\n<p>\u201cIf your knees hurt, keep a bowl of freshly ground rock salt in your room for 3 nights. Your pain will vanish.\u201d<\/p>\n<p>Do these claims sound like nonsense to you? Yet, for a few people, this medical advice will actually work, no matter how absurd it sounds. The reason&#8212;the mysterious placebo effect.<\/p>\n<h2><a name=\"_Toc226636315\"><\/a>What is the placebo effect?<\/h2>\n<p>The placebo effect is when a person experiences a perceived improvement in their condition after receiving a treatment that has no therapeutic effect (i.e., placebos are physically and pharmacologically inert). More plainly put, people think that they are getting better even if they\u2019re receiving an ineffective treatment or no treatment at all.<\/p>\n<h2><a name=\"_Toc226636316\"><\/a>What is the impact of the placebo effect on clinical trials?<\/h2>\n<p>Obviously, if someone is going to feel better in spite of receiving random or nonsensical treatments, what\u2019s the use of the billions of dollars and years of hard work spent on rigorous, statistically sound clinical trials? The placebo effect\u00a0can significantly influence the results of research on therapeutic interventions. Participants in clinical trials may show improvements simply because they believe they are receiving a beneficial treatment, even if they are actually receiving a placebo. This can make it difficult the true efficacy of the treatment being tested, making it crucial to account for placebo effects in study design and analysis.<\/p>\n<h2><a name=\"_Toc226636317\"><\/a>How do we handle the placebo effect in clinical trials?<\/h2>\n<p>First of all, let\u2019s understand how exactly a placebo is used in clinical trials. Researchers sometimes conduct a placebo-controlled trial: a trial in which one group of participants gets the active treatment while the other gets the placebo.<\/p>\n<h3><a name=\"_Toc226636318\"><\/a>Matching groups<\/h3>\n<p>Ideally, the researcher ensures that all other variables are the same between the two groups (e.g., disease status, age, comorbidities), so that any difference in trial outcomes between the two groups can be attributed to the active treatment.<\/p>\n<h3><a name=\"_Toc226636319\"><\/a>Blinding and double-blinding<\/h3>\n<p>Now obviously, it\u2019s better if the participants DON\u2019T know they\u2019re receiving the intervention or a placebo, so that their own beliefs about their treatment don\u2019t influence the results. That\u2019s where we use blinding, to make sure participants don\u2019t know whether they belong to the treatment group or the control group. And of course, it\u2019s even more effective to use double-blinding, where neither the researchers nor the participants know who is in which group until the very end of the trial.<\/p>\n<h3><a name=\"_Toc226636320\"><\/a>Run-in period<\/h3>\n<p>Researchers have tried out incorporating a \u201crun-in period\u201d into their trial design (e.g., <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/33388382\/\">Hui et al., 2021<\/a>). This is a period at the start of the trial where EVERYONE gets a placebo, though they don\u2019t know it\u2019s a placebo. Those participants who report an improvement in the concerned symptoms (deemed \u201chigh placebo responders\u201d) are then excluded from the actual clinical trial. However, this practice has been found not particularly effective (<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/7743788\/#:~:text=A%20prerandomization%20placebo%20run%2Din,take%20medication%20during%20the%20trial.\">Davis et al., 1995<\/a>; <a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6377048\/\">Laursen et al., 2019<\/a>).<\/p>\n<h3><a name=\"_Toc226636321\"><\/a>Two-phase, sequential parallel comparison trial design<\/h3>\n<p>Another strategy to counter the placebo effect involves a two-phase, sequential parallel comparison trial design (see, for example, <a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC5686483\/\">Mathew et al., 2017<\/a>). In the first phase, participants are randomly assigned to receive either a placebo or an active treatment. Those who do not respond to the placebo proceed to the second phase, where they are once more randomized to receive either a placebo or an active treatment. The ultimate analysis incorporates combined data from both phases.<\/p>\n<h3><a name=\"_Toc226636322\"><\/a>Other strategies<\/h3>\n<p><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8719632\/\">Evans et al. (2021)<\/a> provide a comprehensive review of various other strategies to counter the placebo effect, which include modifications to messaging around intervention vs placebo and specific training to subjects on accurate responding.<\/p>\n<h2><a name=\"_Toc226636323\"><\/a>Does study power reduce the placebo effect?<\/h2>\n<p>If the study has a sufficiently large sample and adequate statistical power, the results are likely to be robust. In contrast, if the study has low power and very few participants in the intervention and control groups, even 1-2 persons experiencing the placebo effect can skew the results.<\/p>\n<h2><a name=\"_Toc226636324\"><\/a>Conclusion<\/h2>\n<p>The placebo effect, though \u201ca pain in the neck\u201d to researchers, can\u2019t be ignored altogether. Even if the placebo itself isn\u2019t capable of doing anything, the placebo effect may elicit neuroendocrine responses, which can in turn interact with the autonomic nervous system and immune system (<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6013051\/\">Wager &amp; Atlas<\/a>, 2015). It may not be possible to completely prevent the placebo effect from obscuring your study results. However, with a well-thought-out study design and adequate statistical power, you can be more confident about the quality of the evidence you\u2019re generating.<\/p>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>To reduce the placebo effect in medical research, especially clinical trials, use strategies like matching, blinding and double-blinding, incorporating a run-in period, or using a two-phase sequential parallel comparison design. What is the placebo effect? What is the impact of the placebo effect on clinical trials? How do we handle the placebo effect in clinical [&hellip;]<\/p>\n","protected":false},"author":15,"featured_media":28109,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"inline_featured_image":false,"footnotes":""},"categories":[2420],"tags":[589,1319,366],"new_categories":[],"new_tags":[],"series":[],"class_list":["post-23554","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-data-analysis","tag-clinical-trial","tag-statistical-analysis","tag-statistical-reporting"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v25.0 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>How to reduce the placebo effect in research | Editage Insights<\/title>\n<meta name=\"description\" content=\"Know more about placebo effect and strategies to prevent the placebo effect from obscuring clinical trial results\" \/>\n<meta name=\"robots\" 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