Human Subjects Laws and Regulations PDF

Human Subjects Laws and Regulations  Human Subject Definition Department of Health and Human Services Definitions (HHS)  Human subject- living individual about whom a research investigator (whether a professional or a student) obtains data through intervention or interaction with th...

Human Subjects Laws and Regulations  Human Subject Definition Department of Health and Human Services Definitions (HHS)  Human subject- living individual about whom a research investigator (whether a professional or a student) obtains data through intervention or interaction with the individual or from individually identifiable information.  Must be living, cadavers/decedents do not count, neither do biospecimens.  HOWEVER there are additional rules surrounding information and privacy Human Subject Definition Department of Health and Human Services Definitions Intervention- both physical procedures by which data are gathered (for example, venipuncture) and manipulations of the subject or the subject's environment that are performed for research purposes. Interaction- communication or interpersonal contact between investigator and subject. Human Subjects –Privacy vs Confidentiality Department of Health and Human Services Definitions  Private information- information about behavior that occurs in a context in which an individual can reasonably expect that no observation or recording is taking place, and information which has been provided for specific purposes by an individual and which the individual can reasonably expect will not be made public (for example, a medical record).  Identifiable information- information that is individually identifiable (i.e., the identity of the subject is or may readily be ascertained by the investigator or associated with the information). Human Subject Definition Privacy vs Confidentiality Privacy- Privacy refers to an individual’s desire to control who has access to him/herself. This includes access to the individual’s personal/private information. Things to keep in mind are:  The methods used to identify and contact potential participants;  The settings in which an individual will be interacting with an investigator. For example, persons may not want to be seen entering a place that might stigmatize them, such as a pregnancy counseling center that is clearly identified as such by signs on the front of the building;  The type of information being collected (i.e. personal, sensitive and/or identifiable);  How to access the minimum amount of information necessary to conduct the study. Confidentiality- Confidentiality refers to the researcher’s agreement with the participant about how the research participant’s identifiable private information will be handled, managed, and disseminated. In other words, it refers to how and where research documents and data will be stored. Things to keep in mind are:  Data retention plans for each should be detailed for storing, protecting, and retaining the data  If coding, use of pseudonyms, and/or other data protections will be in place, include those details as well as who will have the key/ability to link the data to the direct identifiers;  If signed consent forms will be used, details about storage, protection, and retention of the signed consent forms should be addressed;  This information should also be outlined on the consent form for participants; What’s the difference? Privacy concerns the people Confidentiality concerns the data Privacy versus confidentiality?  Practice question: Alan had been recruited to be in a study regarding whether men preferred chocolate or vanilla ice cream. The informed consent form he signed stated that his answer to the survey would be kept in a locked file cabinet and only the researchers would have access to it. The researchers did not follow this procedure and left his survey on their desks rather than locking it away when they were done. No one outside the research team saw the surveys. Is this an example of a violation of privacy or confidentiality? Privacy versus confidentiality?  Practice question 1 answer: Alan had been recruited to be in a study regarding whether men preferred chocolate or vanilla ice cream. The informed consent form he signed stated that his answer to the survey would be kept in a locked file cabinet and only the researchers would have access to it. The researchers did not follow this procedure and left his survey on their desks rather than locking it away when they were done. Is this an example of a violation of privacy or confidentiality? Confidentiality since it violated how the researchers would keep their data. Since no one else saw it, it is not considered a violation of privacy, however they did not follow the agreement about how his data would be stored. Confidentiality is about what is done with the data. History of Human Subjects Research Hippocratic Medicine  Based around the teachings of Hippocrates  Considered the father of medicine as a science  Meaning medicine used careful observation, experimentation, and record keeping.  In other words- it was evidence based  He was skeptical of witch doctors and medicine that was not backed by experimentation  We practice Hippocratic medicine today, and to do so we must perform medical experiments on humans to determine the best treatments. Pure Food and Drug Act (aka the Wiley Act)-1906  This law eventually led to creation of Food and Drug Administration (FDA)  Harvey Washington Wiley championed the law  What did the Pure Food and Drug Act do?  Defined "misbranding" and "adulteration" in food and drugs  Drug labels had to list any of 10 ingredients that were deemed Harvey Washington Wiley "addictive" and/or "dangerous  Such as alcohol, morphine, opium, and cannabis, cocaine, heroine, etc.  What were the punishments if it was violated?  Only minor financial penalties imposed, but goods found in violation were seized  I.E. fake Whiskey (ethanol colored brown), Eggs preserved in boric acid  How did the Pure Food and Drug Act come about?  There was a major problem with adulteration (added chemicals/ingredients) in food  Drugs did not have to be labeled correctly or proven safe  Watch this video on: Patent Medicines Video  Partially inspired by Upton Sinclair’s The Jungle  Passed on same day as the Meat Inspection Act that made it a crime to adulterate or misbrand meat Example of Food Adulteration Prior to the Wiley Act Problem: Prior to pasteurization milk would spoil before reaching the market -Typhoid, diptheria, bovine tuberculosis Solution: Add formaldehyde to kill germs. Side effects: Diverse damage to organ systems including the liver, kidney, spleen, pancreas, and the brain possibly resulting in death. Mostly children were injured/killed b/c chilren drink the most milk. Example of Food Adulteration Prior to the Wiley Act Problem: Real whiskey, coffee, & tea is expensive to make Solution: Many makers added dye and smoke flavoring to any grain alcohol to make whisky. Sticks, sawdust, dirt or chicory to make coffee or tea. Side effects: May accidentally contain methanol, which can cause blindness and death. Or may just taste like dirt. The Jungle Expose of Chicago stockyards Filthy conditions-feces, urine, rats Diseased animals processed into food Watch this video explaining why the Jungle was important - Upton Sinclair- The Jungle Video  Federal Food, Drug, and Cosmetic Act- 1938  This act was created in response to multiple poisonings, but one stood out:  Elixir sulfanilamide poisoning killed more than 100 people  Massengil company prepared sulfanilamide with diethylene glycol and added raspberry flavor  Sulfanilamide- sulfa drug and early antibacterial  Given primarily to children with sore throats  Diethylene glycol (similar to ethylene glycol) is toxic to humans  Kidney failure  Liver damage  Primary chemist was unaware DEG was toxic  No drug testing required at the time for new drugs  FDA used the Pure Food and Drug Act (aka the Wiley act) to prosecute Massengil  They received a fine because the definition of an elixir must contain alcohol  Federal Food, Drug, and Cosmetic Act- 1938 Note: This is a description of the original FDAC. It is still in used and has had many changes.  Replaced the 1906 Pure Food and Drug Act  Gave the government the power to inspect plants and manufacturers  FDA required manufacturers to file a New Drug Application prior to marketing  Manufacturers must prove safety, but not effectiveness  This changes following the Kefauver-Harris amendment – 30 yrs later  Label must not include false information about efficacy and purity  Read about cosmetics prior to the FDAC passing:  3 Horrifying Pre-FDA Cosmetics from Smithsonian Magazine  Food, Drug and Cosmetic Act The FDAC has been revised and added to many times over the years. It is still in use today and is the primary method by which the American government protects the people from harmful or useless drugs. What happens if you violate the FDAC now (i.e. 2024)? Contains both civil law and criminal law clauses. Civil meaning fines, criminal meaning you can go to jail. Most violations are civil, though repeated, intentional, and fraudulent violations are considered criminal. Click this link to read about the FDAs most wanted fugitives: Most Wanted Fugitives The people on this list have been convicted of violating FDA rules and have fled to other countries.  Food, Drug and Cosmetic Act What does it cover (now in 2024)? Food (including gum) & Food additives Dietary Supplements Note: The FDA is not authorized to review dietary supplements for safety OR effectiveness. It is on the company selling the product to ensure it is safe. The FDA regulates the supplements by preventing adulteration- meaning that what is on the label is what is in the supplement. Drugs -Approval of a drug means that data on the drug’s effects have been reviewed and is determined to provide benefits that outweigh its known and potential risks for the intended population Cosmetics Tobacco Products Medical devices (that fall into 3 classes) Class 1- low risk, used externally. I.E. Bandages, bed pans, stethoscopes Class 2- Moderate risks. I.E. Pregnancy test kits, powered wheel chairs Class 3- High risk, usually sustain life and/or are implanted. I.E. Pacemakers and breast implants \ Class Question In the example question of Alan and chocolate, is that an example of privacy or confidentiality?  After going to https://aboutmyinfo.org/identity how identifiable were you by your birthdate and were you surprised? What God says He is like  The LORD passed before him and proclaimed, “The LORD, the LORD, a God merciful and gracious, slow to anger, and abounding in steadfast love and faithfulness, 7 keeping steadfast love for thousands,[a] forgiving iniquity and transgression and sin, but who will by no means clear the guilty Exodus 34:6-7ESV  Nazis and Nuremberg  The actions of the Nazi researchers had some of the greatest impacts on our human subjects laws.  Nazis transported people, primarily Jews, to concentration and work camps  Medical and physiological experiments were performed against the captives will, without consent, and most of the time without any form of anesthesia  ~ 15,400 victims, between 3500 and 5000 killed  Numbers are minimum estimates due to lack of documentation  Nuremberg trial- 1946-47  Prosecution of Nazi leaders for crimes against humanity  Also called the Doctors Trial due to the large number of physicians on trial  Punishments of doctors involved included execution and jail sentences.  Unethical experiments included:  Twins experiments (i.e. sewing twins together)  To test how to treat phosphorus burns, Performed by Josef Mengele  doctors at Ravensbruck concentration Exposing prisoners to conditions including freezing, seawater immersion. Sudden decompression and altitude changes camp applied a mixture of phosphorus  and rubber to inmates' skin, ignited it, Deliberately infecting patients with tuberculosis and malaria and let it burn for 20 seconds.  Nuremburg Code- 1946 One of the first documented set of research ethics principles. It was meant to prevent crimes like those committed by the Nazis *These were NOT adapted into FEDERAL law, but did inspire other laws. i.e. you cannot “break” the Nuremberg code in America. Kefauver Harris Amendment to the Food, Drug, & Cosmetic Act- 1962  Created in response to the thalidomide tragedy  This was an amendment to the Food, Drug and Cosmetic Act that included the following changes:  Overhauled the FDAC to require a lot of additional safety testing prior to approval  Required manufacturers to prove the effectiveness prior to approval (this was not required by earlier versions of the FDAC)  Required drug advertising to accurately portray side effects Kefauver-Harris Amendment to the FDAC  Thalidomide-  A hypnotic/sedative drug that also relieves the feelings of “morning sickness” (nausea/ discomfort) during pregnancy  Sold as easily accessible OTC (over the counter) in Germany, Great Britain, Australia, and multiple other European countries  Causes birth defects - phocomelia  1960- FDA did not provide approval in US due to safety concerns. So the majority of the victims were not in the US. Dr. Mückter, chief of research and production, was enriched by thalidomide  Watch: Shadow of Thalidomide Film sales and helped cover up the drug’s effects, left. At Nuremberg, mass murderer Otto Ambros was sentenced to eight years in prison. He came to head the Grunenthal’s advisory committee.  How does thalidomide cause phocomelia?  Metabolite of thalidomide (CPS49) has antiangiogenic effects  Thalidomide given during critical limb development results in phocomelia  Thalidomide is now used for leprosy and multiple myeloma Fish and chick limb absence following exposure to  Declaration of Helsinki- 1964  What is it?  World Medical Association met in Helsinki, Finland to create a document that describes internationally agreed upon ethical standards of human subjects research  Came out of the need for research but an attempt to prevent crimes like the Nazis  WMA purpose: “is to serve humanity by endeavoring to achieve the highest international standards in Medical Education, Medical Science, Medical Art and Medical Ethics, and Health Care for all people in the world.  Fundamental principle from the first version is respect for the individual, their right to self-determination and the right to make informed decisions (AKA autonomy)  Researcher/physician’s first duty is to the subject.  Declaration of Helsinki (DoH)- 1964  Not legally binding in the US  BUT many countries have used it as a standard to guide their own laws and regulations  FDA has adopted most versions of DoH into law.  So you cannot “break” the DoH, but the FDA made its laws based on DoH recommendations.  Initially very strict and focused on the patient’s right to informed consent  Later revisions allowed for placebo trials,  Also added the requirement that studies in emerging countries be held to the same standards Declaration of Helsinki & Vulnerable Populations  First set of laws/regulations to consider the special needs of vulnerable populations  Groups that are “vulnerable” should be included in research only when a specific health need of that population cannot be addressed in any other way What constitutes a vulnerable population?  Children*  Prisoners*  Pregnant women*  Mentally disabled  Economically disadvantaged  Educationally disadvantaged  Workers  Students  *Only Children, Pregnant women, and Prisoners receive additional federal protections, the other groups still receive special protection from IRBs but NOT the FEDs. Willowbrook Hepatitis Study 1956-1970  Willowbrook State School in Staten Island  Closed permanently in 1987  Housed children with intellectual disability  Crowded conditions and poor care lead to a chronic hepatitis (primarily hepatitis A) outbreak &most children being infected  Dr. Saul Krugman  Deliberately exposed uninfected children to hepatitis to track the development of the virus  Also to study efficacy of gamma globulin on preventing infection  Considered one of the most unethical experiments  Read: Hideous Truth of Testing Vaccines on Humans Tuskegee Syphilis Study 1932-1972  When?  Began in 1932 in Macon, Alabama  Original Purpose?  Study the progression of untreated syphilis in black population  This is a prospective study – and still considered ethical IF NO CURE  In 1926 syphilis considered major health crisis- 35% of general population  Subjects?  600 African American Males  399 with syphilis  28 died directly of syphilis  100 died of syphilis related complications  40 wives were infected  19 children born with congenital syphilis  201 without syphilis  Why was this unethical?  1942- penicillin invented  1945 penicillin accepted cure for syphilis  No patients ever treated with penicillin  Men were hindered from getting treatment, never told of their true condition, and were allowed to spread the illness.  i.e. Prevented from entering draft and military  Tuskegee Syphilis Study 1932-1972  Termination occurred in 1972  Only due to a leak in the press 1972, only 74 of the test subjects were still alive.  Civil lawsuit resulted in out of court $10,000,000 settlement  Living syphilitic group participants received $37,500. (225K today)  Rest was divided amongst both controls and heirs of deceased  Controls are considered victims since they were not informed (i.e. informed consent) National Research Act- 1974  Tuskegee horrified the nation  In response congress created the “National Research Act”  This act results in the “National Commission for the Protection of Human Subjects in Biomedical and Behavioral Research”  This was a group of experts who attempted to describe the most important components of ethical research.  The components were written down into the “Belmont Report”  The Belmont Report is not a law. It is a set of principles.  These principles were turned into law by the Common Rule (see slides on the common rule)  The Common rule is how the Belmont Report is enforced.  Belmont Report - 1979  Three core principles  Respect for persons  Subjects treated as autonomous agents  Subjects with diminished autonomy should be protected  i.e. informed consent as much as possible  Beneficence  Subjects should not be harmed  Benefits of research should be maximized and any possible harm reduced  i.e. careful assessment of risks and benefits  Justice  Benefits and risks of research are fairly distributed  i.e. Which groups should receive research funds? How are subjects chosen? Understanding the Principles  Respect for persons  Subjects treated as autonomous agents  Subjects with diminished autonomy should be protected  i.e. informed consent as much as possible  Example of a violation:  The Tearoom Trade  1960’s- PhD student in sociology Laud Humphry acted as a “watch queen” for homosexual acts in public restrooms.  He would use license plates to locate and interview men  Found that >50% of men were closeted homosexual  Violated autonomy- the men did not choose to be involved. Understanding the Principles  Beneficence  Subjects should not be harmed  Benefits of research should be maximized and any possible harm reduced  i.e. careful assessment of risks and benefits  “The term 'beneficence' is often understood to cover acts of kindness or charity that go beyond strict obligation. In this document, beneficence is understood in a stronger sense, as an obligation. Two general rules have been formulated as complementary expression of beneficent actions in this sense: (1) do not harm and (2) maximize possible benefits and minimize possible harms” (The National Commission 1979).  Examples of beneficence: What is done with data after collecting it?  By ensuring the subjects privacy by doing data de-identification you have maximized the benefits and minimized risk, thus achieving beneficence Example of a violation: Tuskegee violated beneficence by not allowing subjects to receive treatment for their disease, thus directly causing them harm. Understanding the Principles  Justice  Benefits and risks of research are fairly distributed  i.e. Which groups should receive research funds? How are subjects chosen?  If a group will not benefit from the research, then it should not be a test subject.  For example: Using prisoners to test acne cream when they would not be able to purchase the acne cream in the prison. This is an example of a violation of justice.  “Who ought to receive the benefits of research and bear its burdens? This is a question of justice, in the sense of "fairness in distribution" or "what is deserved." An injustice occurs when some benefit to which a person is entitled is denied without good reason or when some burden is imposed unduly” (The National Commission 1979).  Examples of violations:  “During the 19th and early 20th centuries the burdens of serving as research subjects fell largely upon poor ward patients, while the benefits of improved medical care flowed primarily to private patients.“  I.E. Tuskegee, Nazi Experiments, Willowbrook, Holmesburg prison etc.. Class Question Do you think Dr. Krugman was justified in how he performed his experiment given the number of lives that were saved from both hepatitis and the development of the eventual vaccines? Explain your answer. Common Rule – 1981 This is the law that enforced the principles set down in the Belmont report. - This is accomplished primarily through Institutional Review Boards (sometimes known as ethical review boards) that oversee and approve research - Covers human subjects for ALL government funded research This law includes requirements for: assuring compliance by research institutions researchers' obtaining and documenting informed consent Institutional Review Board (IRB) membership, function, operations, review of research, and record keeping. Includes special protections for vulnerable groups including: Subpart B- pregnant women, in vitro fertilization, and fetuses Subpart C-prisoners Subpart D- children Institutional Review Boards What are they?  IRBs are required of all institutions that undertake federally funded research.  This group works at a local level (i.e. institutional level) to approve, monitor, and review all scientific research involving humans.  Their main job to evaluate a proposed experiment and perform risk/benefit analysis  Benefits MUST outweigh the risks to the subjects Institutional Review Boards Who must undergo IRB training? All persons included by name on the Institutional Review Board (IRB) application for a study that involves human subjects must become certified. -YOU CANNOT WORK ON A HUMAN STUDIES EXPERIMENT UNLESS YOU ARE IRB CERTIFIED This includes volunteers, students, and support personnel. Institutional Review Boards What power do they have?  Federal regulations stipulate that an IRB can:  Approve/Disapprove/Modify research  Conduct continuing reviews over the years  Observe/verify changes  Suspend or terminate approval  Observe the consent process and research procedures Additional Roles of the IRB Problems/ Continuous Amendments or Unanticipated Monitoring Modifications Events - - The IRB must re-review - The IRB must approve any The IRB must be notified studies at a minimum of amendments or within 24 hours if there are: once a year modifications prior to implementation. - This may require a full- board review each time - You cannot change your 1.Adverse events or unanticipated problems dependent on the experiment without IRB involving risks to subjects or experiment. approval others - If Tuskegee had happened today, the continuous 2. Incidents of noncompliance monitoring should have caught the fact that penicillin could cure 3. Deviations from an syphilis. approved study plan and violations of the terms of approval Types of Review What are they?  3 Types of review  Exempt  Expedited  Full Review  Regulated by the Office for Human Research Protections within the Department of Health and Human Services (HHS) Types of Review What are they?  Full Review  Must be used for the initial review of all studies that are not eligible for expedited review or exemption status.  The review must be conducted at a convened meeting of the IRB. A majority of IRB members (a quorum) must be present at the meeting.  A majority of the members present at the meeting must approve the research.  The IRB must notify (in writing) researchers and the organization of its decision to approve, modify, or disapprove the research. Types of Review  Expedited-  This means that an “Expedited Review” happens. The research may not involve more than "minimal risk." Minimal risk means "the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests" (Protection of Human Subjects 2009; Institutional Review Boards 2015). Must fall into one of 9 federally defined categories.  What is minimal risk?  “The probability and magnitude of harm or discomfort anticipated in the research are not greater than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests.”  Examples of Minimal Risk Studies (YES YOU MUST KNOW THESE)  Collection of blood samples by venipuncture from healthy, non-pregnant adults  Collection of data through non-invasive means (excluding studies that require general anesthesia or sedation for research purposes) routinely employed in clinical practice, including MRI, ECG, ultrasound  Research involving materials (data, documents, records—including medical records--or biological specimens) that have been collected or will be collected solely for research purposes  Collection of data from voice, video, digital or image records made for research purposes  Research on individual or group characteristics or behavior (e.g., focus groups, surveys, interviews)  Mobile applications that only track information and do not directly inform care of the research subject Greater than Minimal Risk  If a study requires greater than minimal risk then review at the IRB is ‘full review’  Examples of Greater than Minimal Risk Studies  Punch biopsies or extra biopsy when other biopsies are already being taken for standard diagnostics  X-rays  MRIs when contrast media and/or sedation is used for research purposes  Research on investigational drugs or devices  Research in which the identification of the subjects and/or their responses would reasonably place them at risk of criminal or civil liability or be damaging to their reputation or be stigmatizing to their group  Mobile medical applications that use health information to directly inform care of the research subject (e.g., applications that provide insulin dosing recommendations)  Research using vulnerable groups (children, prisoners) Types of Review Cont. Exempt - This does NOT mean that the IRB does not need to be informed, it is just a very fast review normally with only one or two people signing off on the experiment. 1. Research conducted in established or commonly accepted educational settings, involving normal educational practices. 2. Research using anonymous or no-risk tests, surveys, interviews, or observations. (Anonymous is not the same as confidential) 3. Most research involving public officials. 4. Research involving the collection or study of existing data if it is publically available or if subjects cannot be identified. 5. Research examining public benefit or service programs. 6. Taste and food quality evaluation and consumer acceptance studies. Types of Review Cont. Never Exempt If the research meets the following categories it can never be considered exempt or expedited.  It includes prisoners  Surveying or interviewing of children  Observations of public behavior of children when the researcher(s) participates in the activities being observed IRB Approval To Receive IRB Approval These Requirements Must Be Met  The risks are minimized and are reasonable in relation to any benefits.  The selection of subjects is equitable.  Informed consent will be sought & documented  Protection the privacy of subjects and to maintain the confidentiality of data.  Where any of the subjects are likely to be vulnerable additional safeguards have been included in the study to protect subjects.  NOTE: Vulnerable subjects can be used (i.e. children etc.) but there MUST be additional oversight and special protections. Consequences if Regulations Not Followed  Suspension of research project  Inability to use data or publish results  Debarment by FDA from using investigational products  Inability to receive funding from federal grants  Additional monitoring and oversight by the IRB  Termination of employment  Loss of licenses  Immediate shut-down of all research at an organization IRB Membership Guidelines  > 5 members  They must have varying backgrounds to promote complete and adequate review of research activities commonly conducted by the institution  Diversity- members must be diverse, no single group  Gender  Race  Cultural background  Sensitivity to community attitudes  * * * If an IRB reviews research that involves a vulnerable group, then specialists who are experienced in working with those subjects should be consulted. IRB Membership Guidelines Cont…  IRB may NOT consist entirely of members of one profession.  At least one member whose is a scientist & one member who is a nonscientist.  At least one member who is not affiliated with the institution  i.e. a member of the public  No IRB member may participate in the IRB review of their own project  except to provide information requested by the IRB. Informed Consent Additional reading on Informed Consent  Must be obtained PRIOR to research  Must be fully documented in writing  3 Key Features  1. disclosing to potential research subjects information needed to make an informed decision  2. facilitating the understanding of what has been disclosed  3. promoting the voluntariness of the decision about whether or not to participate in the research  Informed Consent  This information must be conveyed for the subject to be considered “informed”  Describe the overall experience  Describe reasonable benefits  Describe alternatives that may benefit the subjects  Subjects must be told the extent to which their identifiable information will be held  If research-related injury greater than minimal risk is possible, an explanation must be given of whatever voluntary compensation and treatment will be required  Regulations prohibit waiving or appearing to waive any legal rights of subjects (i.e. you can’t tell the subject that if they get hurt, they can’t sue you).  Emphasize that the subject has a right to withdraw at any time  Informed Consent  Informed consent can be granted by:  An adult capable of providing consent;  The legally authorized representative if an adult is unable to give consent;  One or both parents/guardians when the participant is a child;  Children also require “assent” & parental permission – children must be told in age-appropriate language what is involved in the procedure  Researcher must answer questions of children  Children can withdraw assent, thus withdrawing from a study  If child and parent disagree, child preference wins- unless there is direct proven benefit but special exceptions must be sought of the IRB  Assent is not required if children are unable to provide it (due to age)  Additional Unethical U.S. Human Experiments Holmesburg Prison Experiments  Post-WWII Used as testing ground for many drugs/toxins  Immediately after WWII inmates were injected with toxins in consideration for biochemical warfare  Many dermatological tests on over 1,200 inmates  Alfred Kligman 1952-1970  Mostly for CIA & Dow Chemical  Examples of experiments:  Injected over 70 prisoners with dioxin  Component of Agent Orange  Causes chloracne  Radiation dosing testing  Exposed prisoners to pathogens  Staphylococcus, herpes simplex A Prisoners as a Vulnerable Group  Subpart C defines a prisoner as :  Any individual involuntarily confined or detained in a penal institution  work release and house arrest still count  So do alcohol and drug treatment facilities, who are under court order.  Parolees do not count as prisoners.  4 Categories of possible experiments- All must be no more than minimal risk  Study of the possible causes and effects of incarceration, and of criminal behavior.  Study of prisons as an institution  Research on conditions particularly affecting prisoners as a class  I.E. vaccine trials and other research on diseases such as hepatitis and HIV which are more prevalent in prisons than elsewhere; and research on social and psychological problems such as alcoholism, drug addiction, and sexual assaults.  Research on practices that improve the health or well-being of prisoners. Prisoners Special Considerations  Consent- Prisoners have reduced autonomy therefor regulations exist to reduce undue influence on the prisoner to participate.  At no time can participation effect parole- either positively or negatively  Incentive- Prison cultures are such that incentives that might seem trivial in the outside world could carry great significance within a prison- i.e. typical salary is $1.00 a day, 20.00 therefor would be seen as an outsized incentive.  Limits to confidentiality- certain things are never confidential i.e. threats of harm to self or others, threats to escape. Special Considerations- Breach of Confidentiality  Nature of Conviction  Scenario: A researcher is studying child abuse history of pedophiles in order to develop treatment strategies for use within the prisons. He wants to call 25 pedophiles out of the general prison population for interviews.  Discussion: There is a great deal of offender information that is freely available to the public: an inmate's name, age, race, sex, conviction, court where sentenced, and length of sentence.  Within prisons some crimes are more "acceptable" than others. Given the culture of a prison, the identification of a research participant as a pedophile may expose that individual to harm. Even though convictions are public information, researchers do not have the right to disclose information about a person's conviction to other prisoners. Special Considerations- Breach of Confidentiality  Nature of Conviction  Scenario: A researcher is studying child abuse history of pedophiles in order to develop treatment strategies for use within the prisons. He wants to call 25 pedophiles out of the general prison population for interviews.  Discussion: There is a great deal of offender information that is freely available to the public: an inmate's name, age, race, sex, conviction, court where sentenced, and length of sentence.  However, some of this information, though publicly available in free society, becomes private within the prison. Within prisons some crimes are more "acceptable" than others. Given the culture of a prison, the identification of a research participant as a pedophile may expose that individual to harm. Even though convictions are public information, researchers do not have the right to disclose information about a person's conviction to other prisoners.  A possible strategy for managing this particular risk is to interview 50 people who had committed a variety of crimes so that 25 pedophiles included among the 50 would not be identified to other prisoners.  -Adapted from CITI training program  Additional Unethical U.S. Human Experiments MK ULTRA – Early 1950s-1973  CIA “mind control” program  Manipulated mental states using LSD, hypnosis, sleep deprivation, sensory deprivation, psychological torture.  CIA Director Richard Helms ordered all MK ULTRA documents destroyed in 1973  Issues with informed consent  Many subjects dosed without consent  Resulted in deaths- i.e. CIA biochemist Frank Olsen who was given LSD without his knowledge  Lawsuits were mostly settled out of court, but Supreme Court affirmed the CIAs defense in United States vs. Stanley in 1987.  Sandra Day O’Connor dissented “No judicially crafted rule should insulate from liability the involuntary and unknowing human experimentation alleged to have occurred in this case. Indeed, as Justice Brennan observes, the United States played an instrumental role in the criminal prosecution of Nazi officials who experimented with human subjects during the Second World War, and the standards that the Nuremberg Military Tribunals developed to judge the behavior of the defendants stated that the 'voluntary consent of the human subject is absolutely essential... to satisfy moral, ethical, and legal concepts.' If this principle is violated, the very least that society can do is to see that the victims are compensated, as best they can be, by the perpetrators. https://www.youtube.com/watch?v=1f7_aSkfnoY MK Ultra Summary  Additional Unethical U.S. Human Experiments Stanford Prison Experiment  Guards and prisoners were chosen randomly from volunteers  So everyone started off equal  Guards took on the role and imposed authoritarian rules on the prisoners  Prisoners rebelled & guards used fire extinguishers on prisoners and forced them to strip  This resulted in mental breakdowns  Examined the roles of social norms and expectations influenced their behavior  Zimbardo was prison warden, so was present for everything  Ethical issues with informed consent- participants not protected from psychological harm  Video  https://www.youtube.com/watch?v=GePFFf5gRKo  Additional Unethical U.S. Human Experiments  Henrietta Lacks – HeLa cells  First immortalized cell line  Major cell line for tissue  > 60,000 scientific papers published using HeLa cells  DNA sequence available freely- creates issue of privacy, confidentiality, & autonomy  Private companies have made billions from this cell line via drug testing  No compensation for the family  HeLa Cells Class Question What exactly did Dr. Pavuluri do wrong, and how did her IRB fail?