Lecture 23 PDF: Medical Research Ethics

Guinea pig (Cavia porcellus) -​ Not from Guinea, not closely related to pigs -​ Metaphor for a subject of scientific experimentation -​ Used by scientists since the 17th century -​ Koch used guinea pigs to fulfill his postulates for tuberculosis -​ Guinea: “the price one paid for the...

Guinea pig (Cavia porcellus) -​ Not from Guinea, not closely related to pigs -​ Metaphor for a subject of scientific experimentation -​ Used by scientists since the 17th century -​ Koch used guinea pigs to fulfill his postulates for tuberculosis -​ Guinea: “the price one paid for the friendly rodent that speaks like a pig” -​ Still used in research today, mainly in the areas of allergies, nutrition, hearing, and safety testing -​ Cannot synthesize vitamin C (just like humans), helped with study of scurvy -​ Today, they are largely replaced in research by other rodents such as mice and rats Ethics of Lab Animal Testing -​ Three R’s (guidelines for ethical animal research) -​ Replacement -​ Avoid animal models when possible (use non-animal models) -​ Reduction -​ Design experiments to use the minimum number of animals -​ Refinement -​ Improve methods to reduce animal pain or suffering -​ Beyond the Three R’s: Repayment? -​ Retire to sanctuaries -​ Adopt out as pets and help with vet care -​ Memorials for animals -​ Earmark parts of grants for better enclosures -​ Donating to animal sanctuaries “Professional Guinea Pigs” (People) -​ Medical research subjects that voluntarily sign up -​ Typically PHASE I clinical trials with healthy individuals to test safety or side effects of a potential drug  -​ For some, it is a job -​ Concern about exploitation (economic incentives may be used to exploit people) Placebo -​ An inactive substance or other intervention that looks the same as, and is given the same way as an active drug or treatment being tested. The effects of the active drug or other intervention are compared to the effects of the placebo -​ Control group receives the inactive substance (the placebo) -​ Experimental group receives the active drug -​ “Experimental control” subjects -​ The control group -​ given an inert pill, told that it may improve his/her condition, but not told that it is in fact inert -​ “Test” subjects -​ The treatment group -​ given a real pill, told that it may improve his/her condition, but not told that it is in fact a real pill In a clinical trial… -​ A placebo response is the measured response of subjects to a placebo -​ The placebo effect is the difference between the placebo response and the no treatment response -​ The drug effect is the response obtained with the drug minus the placebo response -​ Any measurable placebo effect is termed either objective (e.g. lowered blood pressure) or subjective (e.g. a lowered perception of pain)  single-blind Double-blind (gold standard) -​ The participants in the clinical trial do -​ Both the participants and the not know if they are receiving the experimenters do not know which placebo or the real treatment group got the placebo and which got the experimental treatment -​ The experimenter monitoring the participants knows which individual -​ More likely to produce objective received the placebo and which ones got findings because researcher bias the treatment under examination cannot alter the outcome Open-label placebo -​ What is the mechanism for the placebo effect? -​ Expectations -​ Conditioning -​ When you tell a patient that they are receiving a placebo -​ Mind / body healing effect Ted J. Kaptchuk “It’s the positive health benefits people receive in the context of a clinical interaction that’s due to the rituals, symbols, and behaviors that surround the pill,” he says. “When a person’s sick and goes to a healer, the drama of medicine by itself is a potent form of healing.” Unethical Human Research -​ Dachau hypothermia experiments -​ Eduard Pernkopf’s anatomical atlas -​ Atlas of Topographical and Applied Human Anatomy The Nuremberg Code -​ Outlines what is required to conduct ethical human research and experimentation  -​ Informed consent -​ Benefits must outweigh risks -​ Participants must understand possible risks -​ They must understand how the experiment is run The Tuskegee Syphilis Study -​ Clinical study by the U.S. Public Health Service and Tuskegee University (then Institute) -​ Conducted b/w 1932 and 1972 in Macon County, Alabama -​ Purpose: to study the natural progression of untreated syphilis -​ Subjects were black men -​ 600 enrolled: 399 had syphilis, 201 did not -​ Sharecroppers living in poverty -​ Were offered incentives: free medical exams, free meals, and burial insurance -​ Were not told of their syphilis diagnosis; they were told that they were being treated for “bad blood” -​ No cure/treatment at the time the study started (1932) -​ But in 1947: penicillin (the cure) became available as a standard, effective treatment -​ But subjects were not given penicillin (so that researchers could study the natural progression of untreated syphilis) Peter Buxtun (whistleblower) -​ Heard about The Tuskegee Syphilis Study from one of his coworkers -​ Leaked information to reporter Jean Heller of the Associated Press -​ Resulted in the ending of the study Result of The Tuskegee Syphilis Study -​ Official apology by the U.S. government in 1997 -​ 1974: $10 million class-action lawsuit on behalf of participants and their families settled with U.S. Government -​ Medical benefits provided to participants, wives, and children The Belmont Report -​ The Tuskegee Syphilis Study led to enactment of the National Research Act in 1974 -​ Created the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research -​ The Belmont Report (1979) -​ Identified basic ethical principles underlying conduct of biomedical and behavioral research involving human subjects -​ Developed guidelines to assure research is conducted in accordance with those principles 1.​ Respect for persons = Informed consent 2.​ Beneficence = Assessment of risks and benefits 3.​ Justice = Careful selection of subjects -​ Established institutional review boards (IRBs) at institutions receiving federal support Syphilis: sexually transmitted infection caused by the bacterium Treponema pallidum -​ Effects -​ Development of tumors (gummas) on skin, bones, liver -​ Hearing loss -​ Decreased vision/blindness -​ Dementia -​ Aneurysms (aorta and other blood vessels) -​ Heart valve damage -​ Stroke -​ Congenital syphilis