{"id":6257,"date":"2026-05-27T21:15:03","date_gmt":"2026-05-28T01:15:03","guid":{"rendered":"https:\/\/pressbooks.bccampus.ca\/pathophysiology\/?post_type=chapter&#038;p=6257"},"modified":"2026-06-09T14:56:18","modified_gmt":"2026-06-09T18:56:18","slug":"drug-development-and-pharmaceutical-trials","status":"web-only","type":"chapter","link":"https:\/\/pressbooks.bccampus.ca\/pathophysiology\/chapter\/drug-development-and-pharmaceutical-trials\/","title":{"raw":"Section 3 Drug Development and Pharmaceutical Trials","rendered":"Section 3 Drug Development and Pharmaceutical Trials"},"content":{"raw":"<span class=\"transcription-time-part\" data-time-start=\"5523.989\" data-time-end=\"5527.209\">How are new <strong>medications<\/strong> and <strong>treatments<\/strong> developed and tested before being approved for use?\u00a0 Understanding this process provides important insight into why finding cures for disease such as cancer is so difficult, costly, and time-consuming.\u00a0 Pharmaceutical companies fund approximately 80% of health research, with the rest funded by philanthropists and governments (including universities).<\/span>\r\n<h3><strong><span style=\"color: #1f5c99\">The Four Stages of Drug Development<\/span><\/strong><\/h3>\r\n<strong><span style=\"color: #2e75b6\">Stage One:\u00a0 Creating or Isolating the Compound<\/span><\/strong>\r\n\r\nAt this stage, a candidate compound is either:\r\n<ul>\r\n \t<li><strong>Created through<\/strong> <strong style=\"text-align: initial;font-size: 1em\">combinatorial chemistry<\/strong><span style=\"text-align: initial;font-size: 1em\">:\u00a0 A synthetic compound is developed, informed by knowledge of disease-specific cellular targets and what chemical properties (size, shape, charge, enzymatic qualities) are desired.\u00a0 Frequently the process of synthetic compound design is informed by detailed knowledge of disease-specific cellular targets that this new medical compound is being designed to interact with, and what type of interaction would be beneficial.<\/span><\/li>\r\n \t<li><strong>Purified from<\/strong> <strong style=\"text-align: initial;font-size: 1em\">natural sources<\/strong><span style=\"text-align: initial;font-size: 1em\">:\u00a0 A natural source (e.g., plant) suspected to have medicinal properties is analyzed to isolated and identify the specific compound(s) of interest.\u00a0 Purification is important because plants contain thousands of compounds, some of which may be harmful.<\/span><\/li>\r\n<\/ul>\r\n<strong><span style=\"color: #2e75b6\">Stage Two:\u00a0 Cell Testing<\/span><\/strong>\r\n\r\nPurified compounds are tested on animal or human cell lineages grown in Petri dishes (e.g., epithelial, muscle, or neural cells, including lineages that mimic disease conditions).\u00a0 Dose-dependent studies are performed to assess: whether cells are harmed, and whether the compound is effective in offsetting disease qualities in the cells.\u00a0 If the compound is found to be harmful, researchers return to Stage One.\r\n\r\n<strong><span style=\"color: #2e75b6\">Stage Three:\u00a0 Animal Testing or Organ-on-a-Chip Testing<\/span><\/strong>\r\n\r\nFor many decades, drug approval in Canada and other countries have had in place legal requirements that require that pharmaceutical compounds must be tested in animal models to evaluate toxicity, pharmacokinetics and safe dosage levels before being used in human studies.\u00a0 Therefore lab-bred mice and rats have been used to assess safety and ensure effectiveness.\u00a0 These mammals are chosen as they are genetically and physiologically similar to humans sharing approximately 95% of the same genes.\u00a0 The known genome, large litter sizes, short gestation times (~20 days) and frequent reproduction allow for sufficient sample sizes and robust testing efficacy and statistical analysis.\u00a0 As medical laboratory science continues to advance, the goal is eventually completely replace animal testing in Stage 3 through the use of utilizing <strong>human organ-on-a-chip (OoC) technology.<\/strong> \u00a0If successful in mitigating disease-like conditions, with minimal side effects, the compound moves to Stage Four.\r\n\r\n<strong><span style=\"color: #2e75b6\">Stage Four:\u00a0 Human Clinical Trials<\/span><\/strong>\r\n\r\nThe compound is tested in a double-blind study with a small group of humans affected by the disease, who have consented to participate.\u00a0 If successful, the study is expanded to larger groups.\u00a0 Important variables examined at this stage include responses across different age groups, biological, sexes, and other key factors.\u00a0 Different dosages and modes of administration (oral, injection) may also be tested.\r\n<div class=\"textbox textbox--key-takeaways\"><header class=\"textbox__header\">\r\n<p class=\"textbox__title\"><strong>What is a Double-Blind Study? <\/strong><\/p>\r\n\r\n<\/header>\r\n<div class=\"textbox__content\">\r\n\r\nIn a <strong>double-blind study<\/strong>, two conditions are in place once participants have been thoroughly informed and consented to the study.\r\n\r\n1)\u00a0 The person receiving the drug or treatment does not know whether they are receiving the new drug or a <strong>placebo<\/strong> \/ <strong>sham<\/strong> treatment.\r\n\r\n2) The health practitioner administering the treatment also does not know whether they are giving the experimental drug or the placebo \/ sham treatment.\r\n\r\nThis design controls for the <strong>placebo effect<\/strong> - the well-documented phenomenon in which approximately 30% of people receiving a placebo report feeling better, likely due to positive expectations and the comfort of being cared for.\u00a0 Studies have shown that even being in the presence of a health care practitioner can stimulate a placebo effect.\u00a0 Therefore, a new drug is only considered effective if its outcomes exceed those produced by the placebo \/ sham treatment.\r\n\r\n<\/div>\r\n<\/div>\r\n<h3><span style=\"color: #1f5c99\"><strong>Placebo Drugs and Sham Treatments<\/strong><\/span><\/h3>\r\n<table class=\"grid landscape\" style=\"border-collapse: collapse;width: 100%;height: 91px\" border=\"0\">\r\n<tbody>\r\n<tr style=\"height: 31px\">\r\n<td class=\"border\" style=\"width: 18.2111%;height: 31px\"><span style=\"color: #032c80\"><strong>Placebo Drug<\/strong><\/span><\/td>\r\n<td style=\"width: 81.7889%;height: 31px\">Most often the current best available drug (not a sugar pill) is used as the placebo so that participants continue to receive the best possible treatment during the study.\u00a0 This is more ethical and allows the experimental drug to be compared against the current standard of care.\u00a0 If a drug doesn't currently exist, a sugar pill may be used.<\/td>\r\n<\/tr>\r\n<tr style=\"height: 15px\">\r\n<td class=\"shaded\" style=\"width: 18.2111%;height: 15px\"><span style=\"color: #032c80\"><strong>Sham Treatment<\/strong><\/span><\/td>\r\n<td class=\"shaded\" style=\"width: 81.7889%;height: 15px\">A mock treatment that mimics the actual treatment without producing the therapeutic effect (e.g., sham acupuncture needles that look and feel real but do not penetrate the skin).<\/td>\r\n<\/tr>\r\n<\/tbody>\r\n<\/table>\r\n<div class=\"textbox textbox--key-takeaways\"><header class=\"textbox__header\">\r\n<p class=\"textbox__title\"><strong>Why is it Unethical to Treat All Patients with Placebos?<\/strong><\/p>\r\n\r\n<\/header>\r\n<div class=\"textbox__content\">\r\n\r\nEven though placebos make ~30% of people feel better, the positive effects do not last.\u00a0 After weeks to months, patients begin to feel the effects of the disease again - because the disease has not been treated.\u00a0 Placebos do not address the underlying pathophysiology.\r\n\r\n<\/div>\r\n<\/div>\r\n<strong>Movie Time: <\/strong> Click here to watch the 4 minute TEDEx animation: <strong><a href=\"https:\/\/www.ted.com\/talks\/emma_bryce_the_power_of_the_placebo_effect?language=en\" target=\"_blank\" rel=\"noopener\">The Power of the Placebo Effect<\/a> <\/strong>and then answer the following question:\r\n\r\n[h5p id=\"48\"]\r\n<div class=\"textbox textbox--examples\"><header class=\"textbox__header\">\r\n<p class=\"textbox__title\"><strong>* Personalized Medicine Development in the Futures<\/strong><\/p>\r\n\r\n<\/header>\r\n<div class=\"textbox__content\">\r\n\r\n<strong>Organ-on-a-chip (OoC) technology<\/strong> enables scientists to grow patient-derived <strong>organoids<\/strong> \u2014 tiny proxy organs \u2014 in 3D chip structures under physiological conditions, allowing personalized treatment testing in the lab. This is especially promising for cancer, where tumor characteristics vary widely between patients; testing organoids against multiple treatments could fast-track individualized therapy. Though currently costly, integrating robotics into the OoC process may make it more accessible for both <strong>drug discovery<\/strong> and <strong>personalized medicine<\/strong>.\r\n\r\n<\/div>\r\n<\/div>\r\n<h3><span style=\"color: #1f5c99\"><strong><span class=\"transcription-time-part\" style=\"text-align: initial;font-size: 1em\" data-time-start=\"5523.989\" data-time-end=\"5527.209\">Why Most New Drugs Fail<\/span><\/strong><\/span><\/h3>\r\nUnfortunately, most new drugs are discarded after Stage One or Stage Two for one of three reasons:\r\n\r\n<span class=\"transcription-time-part\" style=\"text-align: initial;font-size: 1em\" data-time-start=\"5523.989\" data-time-end=\"5527.209\">a) They don't work.<\/span>\r\n\r\n<span class=\"transcription-time-part\" style=\"text-align: initial;font-size: 1em\" data-time-start=\"5523.989\" data-time-end=\"5527.209\">b) They cause harm.<\/span>\r\n\r\n<span class=\"transcription-time-part\" style=\"text-align: initial;font-size: 1em\" data-time-start=\"5523.989\" data-time-end=\"5527.209\">c) They are not better than existing drugs, and are more expensive to produce.<\/span>\r\n<h3><span style=\"color: #1f5c99\"><strong><span class=\"transcription-time-part\" style=\"text-align: initial;font-size: 1em\" data-time-start=\"5523.989\" data-time-end=\"5527.209\">Special Cases in Drug Approval<\/span><\/strong><\/span><\/h3>\r\n<table class=\"grid landscape\" style=\"border-collapse: collapse;width: 100%;height: 91px\" border=\"0\">\r\n<tbody>\r\n<tr style=\"height: 31px\">\r\n<td class=\"border\" style=\"width: 18.2111%;height: 31px\"><span style=\"color: #032c80\"><strong>Fast-Tracked<\/strong><\/span><\/td>\r\n<td style=\"width: 81.7889%;height: 31px\">Very rarely, a new drug skips the large-scale human study and is immediately approved for use when it works so well that it is deemed most ethical to make it available immediately.\u00a0 This occurred with AZT (azidothymidine), an antiviral used in HIV treatment.<\/td>\r\n<\/tr>\r\n<tr style=\"height: 15px\">\r\n<td class=\"shaded\" style=\"width: 18.2111%;height: 15px\"><span style=\"color: #032c80\"><strong>Off-Label<\/strong><\/span><\/td>\r\n<td class=\"shaded\" style=\"width: 81.7889%;height: 15px\">A drug that has completed all testing stages and has been found effective for a different condition than what it was initially designed for.<\/td>\r\n<\/tr>\r\n<\/tbody>\r\n<\/table>\r\n<div class=\"textbox textbox--key-takeaways\"><header class=\"textbox__header\">\r\n<p class=\"textbox__title\"><strong>Examples of Off-Label Drug Use<\/strong><\/p>\r\n\r\n<\/header>\r\n<div class=\"textbox__content\">\r\n\r\n<strong>Thalidomide:<\/strong>\u00a0 Originally developed in the 1950s in Germany to alleviate morning sickness in pregnant women.\u00a0 It was later discovered to cause serious congenital defects - including blindness, deafness, cleft palate, and limb defects - and miscarriages.\u00a0 It took approximately six years to remove it from the market during which time thousands of babies across Canada, Germany, the United Kingdome, the US, and Europe were affected.\u00a0 Today thalidomide has been found effective in certain cancer treatments.\r\n\r\n<strong>Viagra:<\/strong>\u00a0 Originally developed as a vasodilator for heart disease (to dilate coronary arteries).\u00a0 Researchers discovered it also caused vasodilation of penile arteries.\u00a0 After completing all testing stages and being deemed safe and effective, its use for erectile dysfunction is considered an off-label application.\r\n\r\n<\/div>\r\n<\/div>\r\n\r\n[caption id=\"attachment_2215\" align=\"alignnone\" width=\"300\"]<a href=\"https:\/\/pressbooks.bccampus.ca\/pathophysiology\/wp-content\/uploads\/sites\/1961\/2024\/09\/thalidomide_birth_defects-scaled-1.jpg\" target=\"_blank\" rel=\"noopener\"><img class=\"wp-image-2215 size-medium\" src=\"https:\/\/pressbooks.bccampus.ca\/pathophysiology\/wp-content\/uploads\/sites\/1961\/2024\/09\/thalidomide_birth_defects-scaled-1-300x194.jpg\" alt=\"Congenital malformation of the feet due to exposure to thalidomide, a potent teratogen, during pregnancy.\" width=\"300\" height=\"194\" \/><\/a> Congenital malformation of the feet due to exposure to thalidomide, a potent teratogen, during pregnancy (photo provided by Otis Historical Archives National Museum of Health and Medicine). Thalidomide exposure during pregnancy leads to many severe birth defects, including phocomelia (abnormal limb development), and pre-mature death.[\/caption]\r\n\r\n<div class=\"textbox textbox--examples\"><header class=\"textbox__header\">\r\n<p class=\"textbox__title\"><strong>\u2217 Fun Fact:\u00a0 Natural Compounds as Medicine<\/strong><\/p>\r\n\r\n<\/header>\r\n<div class=\"textbox__content\">\r\n\r\n<strong>Antibiotics<\/strong> are antibacterial agents most often produced naturally by other microorganisms (including fungi\/yeast).\u00a0 Humans have found it useful to mass-produce some of these naturally-occurring antibiotics - such as penicillin - to combat bacterial infections, which can otherwise be fatal.\r\n\r\n<strong>Penicillin<\/strong> was discovered in 1928 by Scottish bacteriologist Alexander Fleming when upon returning from holiday, he found an uncovered petri dish containing <strong><em>Staphylococcus<\/em> bacteria<\/strong> had been contaminated with <strong><em>Penicillium notatum<\/em> mold<\/strong>.\u00a0 The bacteria around the mold was dead and this led scientists at Oxford University to purify the active compound in 1940.\u00a0 Large-scale production of penicillin began in 1941 and has saved millions of lives since that time.\r\n\r\nThis is a powerful example of a natural compound being harnessed for medicine.\r\n\r\n<\/div>\r\n<\/div>\r\n\r\n[caption id=\"attachment_6339\" align=\"alignnone\" width=\"300\"]<a href=\"https:\/\/pressbooks.bccampus.ca\/pathophysiology\/wp-content\/uploads\/sites\/1961\/2026\/05\/Alexander-Fleming.jpg\" target=\"_blank\" rel=\"noopener\"><img class=\"wp-image-6339 size-medium\" src=\"https:\/\/pressbooks.bccampus.ca\/pathophysiology\/wp-content\/uploads\/sites\/1961\/2026\/05\/Alexander-Fleming-300x153.jpg\" alt=\"Figure 1 - (A) Sir Alexander Fleming at his laboratory bench in London (1943). (B) Fleming observed that a colony of a fungus (Penicillum notatum) contaminated a Petri dish that was inoculated with S. aureus, a dangerous bacterial pathogen. Interestingly, S. aureus was unable to grow in the area surrounding the colony of P. notatum. Fleming deduced that the fungus was producing something that killed S. aureus in the zone of inhibition.\" width=\"300\" height=\"153\" \/><\/a> Figure 1 - (A) Sir Alexander Fleming at his laboratory bench in London (1943).<br \/>(B) Fleming observed that a colony of a fungus (<em>Penicillium notatum<\/em>) contaminated a Petri dish that was inoculated with <em>S. aureus<\/em>, a dangerous bacterial pathogen. Interestingly,<em> S. aureus<\/em> was unable to grow in the area surrounding the colony of P. notatum. Fleming deduced that the fungus was producing something that killed <em>S. aureus<\/em> in the zone of inhibition.[\/caption]\r\n\r\n<div class=\"textbox textbox--exercises\"><header class=\"textbox__header\">\r\n<p class=\"textbox__title\"><strong>How to Assess Medical Information?\u00a0 Separating Fact from Fiction<\/strong><\/p>\r\n\r\n<\/header>\r\n<div class=\"textbox__content\">\r\n\r\n<strong><span style=\"text-align: initial;font-size: 1em\">Watch the following short video for important tips before moving to the next section:<\/span><\/strong>\r\n\r\n<span style=\"text-align: initial;font-size: 1em\">Watch the following short video for important tips before moving to the next section:<\/span>\r\n\r\n<span style=\"text-align: initial;font-size: 1em\">TEDEx\u00a0 <\/span><a style=\"text-align: initial;font-size: 1em\" href=\"https:\/\/www.facebook.com\/watch\/?v=507800973092339\">How to Hack HeadLines - Fake medical news or real?<\/a>\r\n\r\n<strong>Video Follow-Up Questions:<\/strong>\r\n\r\nWhat is healthium?\u00a0 Does it reduce cholesterol?\r\n\r\nDoes chocolate reduce stress?\r\n\r\nHow do you determine whether news about medical research is believable?\u00a0 Ask yourselves these questions:\r\n\r\nHas the research been submitted for peer-evaluation?\u00a0 \u00a0Has the research been found to be reproducible?\u00a0 Was a large enough sample size (# of people) used to ensure robust statistical analysis is possible?\r\n\r\nWhat is that actual difference?\u00a0 Is the difference\/cure\/alleviation of symptoms statistically significant?\u00a0 Were there negative side effects?\r\n\r\nHas this been proven to be a short-term effect or long-term effect?\u00a0 How long?\r\n\r\nWas the study double blind?\u00a0 Has it been reproduced by another research team?\u00a0 Was this study done in humans or mice or fish etc.?\r\n\r\n.\r\n\r\n<\/div>\r\n<\/div>\r\n[h5p id=\"22\"]","rendered":"<p><span class=\"transcription-time-part\" data-time-start=\"5523.989\" data-time-end=\"5527.209\">How are new <strong>medications<\/strong> and <strong>treatments<\/strong> developed and tested before being approved for use?\u00a0 Understanding this process provides important insight into why finding cures for disease such as cancer is so difficult, costly, and time-consuming.\u00a0 Pharmaceutical companies fund approximately 80% of health research, with the rest funded by philanthropists and governments (including universities).<\/span><\/p>\n<h3><strong><span style=\"color: #1f5c99\">The Four Stages of Drug Development<\/span><\/strong><\/h3>\n<p><strong><span style=\"color: #2e75b6\">Stage One:\u00a0 Creating or Isolating the Compound<\/span><\/strong><\/p>\n<p>At this stage, a candidate compound is either:<\/p>\n<ul>\n<li><strong>Created through<\/strong> <strong style=\"text-align: initial;font-size: 1em\">combinatorial chemistry<\/strong><span style=\"text-align: initial;font-size: 1em\">:\u00a0 A synthetic compound is developed, informed by knowledge of disease-specific cellular targets and what chemical properties (size, shape, charge, enzymatic qualities) are desired.\u00a0 Frequently the process of synthetic compound design is informed by detailed knowledge of disease-specific cellular targets that this new medical compound is being designed to interact with, and what type of interaction would be beneficial.<\/span><\/li>\n<li><strong>Purified from<\/strong> <strong style=\"text-align: initial;font-size: 1em\">natural sources<\/strong><span style=\"text-align: initial;font-size: 1em\">:\u00a0 A natural source (e.g., plant) suspected to have medicinal properties is analyzed to isolated and identify the specific compound(s) of interest.\u00a0 Purification is important because plants contain thousands of compounds, some of which may be harmful.<\/span><\/li>\n<\/ul>\n<p><strong><span style=\"color: #2e75b6\">Stage Two:\u00a0 Cell Testing<\/span><\/strong><\/p>\n<p>Purified compounds are tested on animal or human cell lineages grown in Petri dishes (e.g., epithelial, muscle, or neural cells, including lineages that mimic disease conditions).\u00a0 Dose-dependent studies are performed to assess: whether cells are harmed, and whether the compound is effective in offsetting disease qualities in the cells.\u00a0 If the compound is found to be harmful, researchers return to Stage One.<\/p>\n<p><strong><span style=\"color: #2e75b6\">Stage Three:\u00a0 Animal Testing or Organ-on-a-Chip Testing<\/span><\/strong><\/p>\n<p>For many decades, drug approval in Canada and other countries have had in place legal requirements that require that pharmaceutical compounds must be tested in animal models to evaluate toxicity, pharmacokinetics and safe dosage levels before being used in human studies.\u00a0 Therefore lab-bred mice and rats have been used to assess safety and ensure effectiveness.\u00a0 These mammals are chosen as they are genetically and physiologically similar to humans sharing approximately 95% of the same genes.\u00a0 The known genome, large litter sizes, short gestation times (~20 days) and frequent reproduction allow for sufficient sample sizes and robust testing efficacy and statistical analysis.\u00a0 As medical laboratory science continues to advance, the goal is eventually completely replace animal testing in Stage 3 through the use of utilizing <strong>human organ-on-a-chip (OoC) technology.<\/strong> \u00a0If successful in mitigating disease-like conditions, with minimal side effects, the compound moves to Stage Four.<\/p>\n<p><strong><span style=\"color: #2e75b6\">Stage Four:\u00a0 Human Clinical Trials<\/span><\/strong><\/p>\n<p>The compound is tested in a double-blind study with a small group of humans affected by the disease, who have consented to participate.\u00a0 If successful, the study is expanded to larger groups.\u00a0 Important variables examined at this stage include responses across different age groups, biological, sexes, and other key factors.\u00a0 Different dosages and modes of administration (oral, injection) may also be tested.<\/p>\n<div class=\"textbox textbox--key-takeaways\">\n<header class=\"textbox__header\">\n<p class=\"textbox__title\"><strong>What is a Double-Blind Study? <\/strong><\/p>\n<\/header>\n<div class=\"textbox__content\">\n<p>In a <strong>double-blind study<\/strong>, two conditions are in place once participants have been thoroughly informed and consented to the study.<\/p>\n<p>1)\u00a0 The person receiving the drug or treatment does not know whether they are receiving the new drug or a <strong>placebo<\/strong> \/ <strong>sham<\/strong> treatment.<\/p>\n<p>2) The health practitioner administering the treatment also does not know whether they are giving the experimental drug or the placebo \/ sham treatment.<\/p>\n<p>This design controls for the <strong>placebo effect<\/strong> &#8211; the well-documented phenomenon in which approximately 30% of people receiving a placebo report feeling better, likely due to positive expectations and the comfort of being cared for.\u00a0 Studies have shown that even being in the presence of a health care practitioner can stimulate a placebo effect.\u00a0 Therefore, a new drug is only considered effective if its outcomes exceed those produced by the placebo \/ sham treatment.<\/p>\n<\/div>\n<\/div>\n<h3><span style=\"color: #1f5c99\"><strong>Placebo Drugs and Sham Treatments<\/strong><\/span><\/h3>\n<table class=\"grid landscape\" style=\"border-collapse: collapse;width: 100%;height: 91px\">\n<tbody>\n<tr style=\"height: 31px\">\n<td class=\"border\" style=\"width: 18.2111%;height: 31px\"><span style=\"color: #032c80\"><strong>Placebo Drug<\/strong><\/span><\/td>\n<td style=\"width: 81.7889%;height: 31px\">Most often the current best available drug (not a sugar pill) is used as the placebo so that participants continue to receive the best possible treatment during the study.\u00a0 This is more ethical and allows the experimental drug to be compared against the current standard of care.\u00a0 If a drug doesn&#8217;t currently exist, a sugar pill may be used.<\/td>\n<\/tr>\n<tr style=\"height: 15px\">\n<td class=\"shaded\" style=\"width: 18.2111%;height: 15px\"><span style=\"color: #032c80\"><strong>Sham Treatment<\/strong><\/span><\/td>\n<td class=\"shaded\" style=\"width: 81.7889%;height: 15px\">A mock treatment that mimics the actual treatment without producing the therapeutic effect (e.g., sham acupuncture needles that look and feel real but do not penetrate the skin).<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<div class=\"textbox textbox--key-takeaways\">\n<header class=\"textbox__header\">\n<p class=\"textbox__title\"><strong>Why is it Unethical to Treat All Patients with Placebos?<\/strong><\/p>\n<\/header>\n<div class=\"textbox__content\">\n<p>Even though placebos make ~30% of people feel better, the positive effects do not last.\u00a0 After weeks to months, patients begin to feel the effects of the disease again &#8211; because the disease has not been treated.\u00a0 Placebos do not address the underlying pathophysiology.<\/p>\n<\/div>\n<\/div>\n<p><strong>Movie Time: <\/strong> Click here to watch the 4 minute TEDEx animation: <strong><a href=\"https:\/\/www.ted.com\/talks\/emma_bryce_the_power_of_the_placebo_effect?language=en\" target=\"_blank\" rel=\"noopener\">The Power of the Placebo Effect<\/a> <\/strong>and then answer the following question:<\/p>\n<div id=\"h5p-48\">\n<div class=\"h5p-iframe-wrapper\"><iframe id=\"h5p-iframe-48\" class=\"h5p-iframe\" data-content-id=\"48\" style=\"height:1px\" src=\"about:blank\" frameBorder=\"0\" scrolling=\"no\" title=\"How does the Placebo Effect work?\"><\/iframe><\/div>\n<\/div>\n<div class=\"textbox textbox--examples\">\n<header class=\"textbox__header\">\n<p class=\"textbox__title\"><strong>* Personalized Medicine Development in the Futures<\/strong><\/p>\n<\/header>\n<div class=\"textbox__content\">\n<p><strong>Organ-on-a-chip (OoC) technology<\/strong> enables scientists to grow patient-derived <strong>organoids<\/strong> \u2014 tiny proxy organs \u2014 in 3D chip structures under physiological conditions, allowing personalized treatment testing in the lab. This is especially promising for cancer, where tumor characteristics vary widely between patients; testing organoids against multiple treatments could fast-track individualized therapy. Though currently costly, integrating robotics into the OoC process may make it more accessible for both <strong>drug discovery<\/strong> and <strong>personalized medicine<\/strong>.<\/p>\n<\/div>\n<\/div>\n<h3><span style=\"color: #1f5c99\"><strong><span class=\"transcription-time-part\" style=\"text-align: initial;font-size: 1em\" data-time-start=\"5523.989\" data-time-end=\"5527.209\">Why Most New Drugs Fail<\/span><\/strong><\/span><\/h3>\n<p>Unfortunately, most new drugs are discarded after Stage One or Stage Two for one of three reasons:<\/p>\n<p><span class=\"transcription-time-part\" style=\"text-align: initial;font-size: 1em\" data-time-start=\"5523.989\" data-time-end=\"5527.209\">a) They don&#8217;t work.<\/span><\/p>\n<p><span class=\"transcription-time-part\" style=\"text-align: initial;font-size: 1em\" data-time-start=\"5523.989\" data-time-end=\"5527.209\">b) They cause harm.<\/span><\/p>\n<p><span class=\"transcription-time-part\" style=\"text-align: initial;font-size: 1em\" data-time-start=\"5523.989\" data-time-end=\"5527.209\">c) They are not better than existing drugs, and are more expensive to produce.<\/span><\/p>\n<h3><span style=\"color: #1f5c99\"><strong><span class=\"transcription-time-part\" style=\"text-align: initial;font-size: 1em\" data-time-start=\"5523.989\" data-time-end=\"5527.209\">Special Cases in Drug Approval<\/span><\/strong><\/span><\/h3>\n<table class=\"grid landscape\" style=\"border-collapse: collapse;width: 100%;height: 91px\">\n<tbody>\n<tr style=\"height: 31px\">\n<td class=\"border\" style=\"width: 18.2111%;height: 31px\"><span style=\"color: #032c80\"><strong>Fast-Tracked<\/strong><\/span><\/td>\n<td style=\"width: 81.7889%;height: 31px\">Very rarely, a new drug skips the large-scale human study and is immediately approved for use when it works so well that it is deemed most ethical to make it available immediately.\u00a0 This occurred with AZT (azidothymidine), an antiviral used in HIV treatment.<\/td>\n<\/tr>\n<tr style=\"height: 15px\">\n<td class=\"shaded\" style=\"width: 18.2111%;height: 15px\"><span style=\"color: #032c80\"><strong>Off-Label<\/strong><\/span><\/td>\n<td class=\"shaded\" style=\"width: 81.7889%;height: 15px\">A drug that has completed all testing stages and has been found effective for a different condition than what it was initially designed for.<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<div class=\"textbox textbox--key-takeaways\">\n<header class=\"textbox__header\">\n<p class=\"textbox__title\"><strong>Examples of Off-Label Drug Use<\/strong><\/p>\n<\/header>\n<div class=\"textbox__content\">\n<p><strong>Thalidomide:<\/strong>\u00a0 Originally developed in the 1950s in Germany to alleviate morning sickness in pregnant women.\u00a0 It was later discovered to cause serious congenital defects &#8211; including blindness, deafness, cleft palate, and limb defects &#8211; and miscarriages.\u00a0 It took approximately six years to remove it from the market during which time thousands of babies across Canada, Germany, the United Kingdome, the US, and Europe were affected.\u00a0 Today thalidomide has been found effective in certain cancer treatments.<\/p>\n<p><strong>Viagra:<\/strong>\u00a0 Originally developed as a vasodilator for heart disease (to dilate coronary arteries).\u00a0 Researchers discovered it also caused vasodilation of penile arteries.\u00a0 After completing all testing stages and being deemed safe and effective, its use for erectile dysfunction is considered an off-label application.<\/p>\n<\/div>\n<\/div>\n<figure id=\"attachment_2215\" aria-describedby=\"caption-attachment-2215\" style=\"width: 300px\" class=\"wp-caption alignnone\"><a href=\"https:\/\/pressbooks.bccampus.ca\/pathophysiology\/wp-content\/uploads\/sites\/1961\/2024\/09\/thalidomide_birth_defects-scaled-1.jpg\" target=\"_blank\" rel=\"noopener\"><img loading=\"lazy\" decoding=\"async\" class=\"wp-image-2215 size-medium\" src=\"https:\/\/pressbooks.bccampus.ca\/pathophysiology\/wp-content\/uploads\/sites\/1961\/2024\/09\/thalidomide_birth_defects-scaled-1-300x194.jpg\" alt=\"Congenital malformation of the feet due to exposure to thalidomide, a potent teratogen, during pregnancy.\" width=\"300\" height=\"194\" srcset=\"https:\/\/pressbooks.bccampus.ca\/pathophysiology\/wp-content\/uploads\/sites\/1961\/2024\/09\/thalidomide_birth_defects-scaled-1-300x194.jpg 300w, https:\/\/pressbooks.bccampus.ca\/pathophysiology\/wp-content\/uploads\/sites\/1961\/2024\/09\/thalidomide_birth_defects-scaled-1-1024x663.jpg 1024w, https:\/\/pressbooks.bccampus.ca\/pathophysiology\/wp-content\/uploads\/sites\/1961\/2024\/09\/thalidomide_birth_defects-scaled-1-768x497.jpg 768w, https:\/\/pressbooks.bccampus.ca\/pathophysiology\/wp-content\/uploads\/sites\/1961\/2024\/09\/thalidomide_birth_defects-scaled-1-1536x994.jpg 1536w, https:\/\/pressbooks.bccampus.ca\/pathophysiology\/wp-content\/uploads\/sites\/1961\/2024\/09\/thalidomide_birth_defects-scaled-1-2048x1326.jpg 2048w, https:\/\/pressbooks.bccampus.ca\/pathophysiology\/wp-content\/uploads\/sites\/1961\/2024\/09\/thalidomide_birth_defects-scaled-1-65x42.jpg 65w, https:\/\/pressbooks.bccampus.ca\/pathophysiology\/wp-content\/uploads\/sites\/1961\/2024\/09\/thalidomide_birth_defects-scaled-1-225x146.jpg 225w, https:\/\/pressbooks.bccampus.ca\/pathophysiology\/wp-content\/uploads\/sites\/1961\/2024\/09\/thalidomide_birth_defects-scaled-1-350x227.jpg 350w\" sizes=\"auto, (max-width: 300px) 100vw, 300px\" \/><\/a><figcaption id=\"caption-attachment-2215\" class=\"wp-caption-text\">Congenital malformation of the feet due to exposure to thalidomide, a potent teratogen, during pregnancy (photo provided by Otis Historical Archives National Museum of Health and Medicine). Thalidomide exposure during pregnancy leads to many severe birth defects, including phocomelia (abnormal limb development), and pre-mature death.<\/figcaption><\/figure>\n<div class=\"textbox textbox--examples\">\n<header class=\"textbox__header\">\n<p class=\"textbox__title\"><strong>\u2217 Fun Fact:\u00a0 Natural Compounds as Medicine<\/strong><\/p>\n<\/header>\n<div class=\"textbox__content\">\n<p><strong>Antibiotics<\/strong> are antibacterial agents most often produced naturally by other microorganisms (including fungi\/yeast).\u00a0 Humans have found it useful to mass-produce some of these naturally-occurring antibiotics &#8211; such as penicillin &#8211; to combat bacterial infections, which can otherwise be fatal.<\/p>\n<p><strong>Penicillin<\/strong> was discovered in 1928 by Scottish bacteriologist Alexander Fleming when upon returning from holiday, he found an uncovered petri dish containing <strong><em>Staphylococcus<\/em> bacteria<\/strong> had been contaminated with <strong><em>Penicillium notatum<\/em> mold<\/strong>.\u00a0 The bacteria around the mold was dead and this led scientists at Oxford University to purify the active compound in 1940.\u00a0 Large-scale production of penicillin began in 1941 and has saved millions of lives since that time.<\/p>\n<p>This is a powerful example of a natural compound being harnessed for medicine.<\/p>\n<\/div>\n<\/div>\n<figure id=\"attachment_6339\" aria-describedby=\"caption-attachment-6339\" style=\"width: 300px\" class=\"wp-caption alignnone\"><a href=\"https:\/\/pressbooks.bccampus.ca\/pathophysiology\/wp-content\/uploads\/sites\/1961\/2026\/05\/Alexander-Fleming.jpg\" target=\"_blank\" rel=\"noopener\"><img loading=\"lazy\" decoding=\"async\" class=\"wp-image-6339 size-medium\" src=\"https:\/\/pressbooks.bccampus.ca\/pathophysiology\/wp-content\/uploads\/sites\/1961\/2026\/05\/Alexander-Fleming-300x153.jpg\" alt=\"Figure 1 - (A) Sir Alexander Fleming at his laboratory bench in London (1943). (B) Fleming observed that a colony of a fungus (Penicillum notatum) contaminated a Petri dish that was inoculated with S. aureus, a dangerous bacterial pathogen. Interestingly, S. aureus was unable to grow in the area surrounding the colony of P. notatum. Fleming deduced that the fungus was producing something that killed S. aureus in the zone of inhibition.\" width=\"300\" height=\"153\" srcset=\"https:\/\/pressbooks.bccampus.ca\/pathophysiology\/wp-content\/uploads\/sites\/1961\/2026\/05\/Alexander-Fleming-300x153.jpg 300w, https:\/\/pressbooks.bccampus.ca\/pathophysiology\/wp-content\/uploads\/sites\/1961\/2026\/05\/Alexander-Fleming-65x33.jpg 65w, https:\/\/pressbooks.bccampus.ca\/pathophysiology\/wp-content\/uploads\/sites\/1961\/2026\/05\/Alexander-Fleming-225x115.jpg 225w, https:\/\/pressbooks.bccampus.ca\/pathophysiology\/wp-content\/uploads\/sites\/1961\/2026\/05\/Alexander-Fleming-350x179.jpg 350w, https:\/\/pressbooks.bccampus.ca\/pathophysiology\/wp-content\/uploads\/sites\/1961\/2026\/05\/Alexander-Fleming.jpg 765w\" sizes=\"auto, (max-width: 300px) 100vw, 300px\" \/><\/a><figcaption id=\"caption-attachment-6339\" class=\"wp-caption-text\">Figure 1 &#8211; (A) Sir Alexander Fleming at his laboratory bench in London (1943).<br \/>(B) Fleming observed that a colony of a fungus (<em>Penicillium notatum<\/em>) contaminated a Petri dish that was inoculated with <em>S. aureus<\/em>, a dangerous bacterial pathogen. Interestingly,<em> S. aureus<\/em> was unable to grow in the area surrounding the colony of P. notatum. Fleming deduced that the fungus was producing something that killed <em>S. aureus<\/em> in the zone of inhibition.<\/figcaption><\/figure>\n<div class=\"textbox textbox--exercises\">\n<header class=\"textbox__header\">\n<p class=\"textbox__title\"><strong>How to Assess Medical Information?\u00a0 Separating Fact from Fiction<\/strong><\/p>\n<\/header>\n<div class=\"textbox__content\">\n<p><strong><span style=\"text-align: initial;font-size: 1em\">Watch the following short video for important tips before moving to the next section:<\/span><\/strong><\/p>\n<p><span style=\"text-align: initial;font-size: 1em\">Watch the following short video for important tips before moving to the next section:<\/span><\/p>\n<p><span style=\"text-align: initial;font-size: 1em\">TEDEx\u00a0 <\/span><a style=\"text-align: initial;font-size: 1em\" href=\"https:\/\/www.facebook.com\/watch\/?v=507800973092339\">How to Hack HeadLines &#8211; Fake medical news or real?<\/a><\/p>\n<p><strong>Video Follow-Up Questions:<\/strong><\/p>\n<p>What is healthium?\u00a0 Does it reduce cholesterol?<\/p>\n<p>Does chocolate reduce stress?<\/p>\n<p>How do you determine whether news about medical research is believable?\u00a0 Ask yourselves these questions:<\/p>\n<p>Has the research been submitted for peer-evaluation?\u00a0 \u00a0Has the research been found to be reproducible?\u00a0 Was a large enough sample size (# of people) used to ensure robust statistical analysis is possible?<\/p>\n<p>What is that actual difference?\u00a0 Is the difference\/cure\/alleviation of symptoms statistically significant?\u00a0 Were there negative side effects?<\/p>\n<p>Has this been proven to be a short-term effect or long-term effect?\u00a0 How long?<\/p>\n<p>Was the study double blind?\u00a0 Has it been reproduced by another research team?\u00a0 Was this study done in humans or mice or fish etc.?<\/p>\n<p>.<\/p>\n<\/div>\n<\/div>\n<div id=\"h5p-22\">\n<div class=\"h5p-iframe-wrapper\"><iframe id=\"h5p-iframe-22\" class=\"h5p-iframe\" data-content-id=\"22\" style=\"height:1px\" src=\"about:blank\" frameBorder=\"0\" scrolling=\"no\" title=\"Double-Blind Studies, Placebos, and Sham Treatments\"><\/iframe><\/div>\n<\/div>\n<div class=\"media-attributions clear\" prefix:cc=\"http:\/\/creativecommons.org\/ns#\" prefix:dc=\"http:\/\/purl.org\/dc\/terms\/\"><h2>Media Attributions<\/h2><ul><li about=\"https:\/\/www.flickr.com\/photos\/22719239@N04\/2241322031\/\"><a rel=\"cc:attributionURL\" href=\"https:\/\/www.flickr.com\/photos\/22719239@N04\/2241322031\/\" property=\"dc:title\">Private: thalidomide_birth_defects<\/a>  &copy;  <a rel=\"dc:creator\" href=\"https:\/\/www.flickr.com\/people\/22719239@N04\" property=\"cc:attributionName\">Otis Historical Archives National Museum of Health and Medicine<\/a>    is licensed under a  <a rel=\"license\" href=\"https:\/\/creativecommons.org\/licenses\/by\/4.0\/\">CC BY (Attribution)<\/a> license<\/li><li about=\"https:\/\/kids.frontiersin.org\/articles\/10.3389\/frym.2019.00159\"><a rel=\"cc:attributionURL\" href=\"https:\/\/kids.frontiersin.org\/articles\/10.3389\/frym.2019.00159\" property=\"dc:title\">Alexander Fleming<\/a>  &copy;  Letek M (2020) Alexander Fleming, The Discoverer of the Antibiotic Effects of Penicillin. Front. Young Minds. 8:159. doi: 10.3389\/frym.2019.00159    is licensed under a  <a rel=\"license\" href=\"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/\">CC0 (Creative Commons Zero)<\/a> license<\/li><\/ul><\/div>","protected":false},"author":1370,"menu_order":5,"template":"","meta":{"pb_show_title":"on","pb_short_title":"","pb_subtitle":"","pb_authors":["zoe-soon"],"pb_section_license":"cc-by-nc-sa"},"chapter-type":[],"contributor":[60],"license":[57],"class_list":["post-6257","chapter","type-chapter","status-web-only","hentry","contributor-zoe-soon","license-cc-by-nc-sa"],"part":3,"_links":{"self":[{"href":"https:\/\/pressbooks.bccampus.ca\/pathophysiology\/wp-json\/pressbooks\/v2\/chapters\/6257","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/pressbooks.bccampus.ca\/pathophysiology\/wp-json\/pressbooks\/v2\/chapters"}],"about":[{"href":"https:\/\/pressbooks.bccampus.ca\/pathophysiology\/wp-json\/wp\/v2\/types\/chapter"}],"author":[{"embeddable":true,"href":"https:\/\/pressbooks.bccampus.ca\/pathophysiology\/wp-json\/wp\/v2\/users\/1370"}],"version-history":[{"count":16,"href":"https:\/\/pressbooks.bccampus.ca\/pathophysiology\/wp-json\/pressbooks\/v2\/chapters\/6257\/revisions"}],"predecessor-version":[{"id":6283,"href":"https:\/\/pressbooks.bccampus.ca\/pathophysiology\/wp-json\/pressbooks\/v2\/chapters\/6257\/revisions\/6283"}],"part":[{"href":"https:\/\/pressbooks.bccampus.ca\/pathophysiology\/wp-json\/pressbooks\/v2\/parts\/3"}],"metadata":[{"href":"https:\/\/pressbooks.bccampus.ca\/pathophysiology\/wp-json\/pressbooks\/v2\/chapters\/6257\/metadata\/"}],"wp:attachment":[{"href":"https:\/\/pressbooks.bccampus.ca\/pathophysiology\/wp-json\/wp\/v2\/media?parent=6257"}],"wp:term":[{"taxonomy":"chapter-type","embeddable":true,"href":"https:\/\/pressbooks.bccampus.ca\/pathophysiology\/wp-json\/pressbooks\/v2\/chapter-type?post=6257"},{"taxonomy":"contributor","embeddable":true,"href":"https:\/\/pressbooks.bccampus.ca\/pathophysiology\/wp-json\/wp\/v2\/contributor?post=6257"},{"taxonomy":"license","embeddable":true,"href":"https:\/\/pressbooks.bccampus.ca\/pathophysiology\/wp-json\/wp\/v2\/license?post=6257"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}