Ethics in Research

Ethics in ResearchLanoza, Jazel MarieRoferos, Ralph FranciscoTan, SharleneEthicsEthics

the discipline concerned with what is morally good and bad, right and wrong.

a method, procedure, or perspective for deciding how to act and for analyzing complex problems and issues.

Why it is important to adhere to ethical norms in research?Promote the aims of researchPromote the values that are essential to collaborative workHelp to ensure that researchers can be held accountable to the public. Help to build public support for research. Promote a variety of other important moral and social values.First, norms promote the aims of research, such as knowledge, truth, and avoidance of error. Second, ethical standards promote the values that are essential to collaborative work, such as trust, accountability, mutual respect, and fairness. Third, many of the ethical norms help to ensure that researchers can be held accountable to the public. Fourth, ethical norms in research also help to build public support for research. Finally, many of the norms of research promote a variety of other important moral and social values, such as social responsibility, human rights, animal welfare, compliance with the law, and health and safety.

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Nuremberg CodeResearch OversightResearch involving human subjects require oversightWhy?5Why is oversight needed?Human subjects have not always been well protected.Privacy issues for individuals are a growing social concernResearch is big business with substantial financial interests.The future impact of such issues as genetic engineering, cloning, gene therapy, pharmacogenomics, etc. is unknown.

6HistoryCelsus, 1st century physicianperfomed experiments on condemned criminals in EgyptHis defense:"It is not cruel to inflict on a few criminals sufferings which may benefit multitudes of innocent people through all centuries." Times have changed .7The Nazi Experiment Though several codes were published earlier had never been officially repealed, and were in force during WW-II, but were ignored.

The excesses committed by the Nazis horrified the world8The Nazi ExperimentIn Nazi Germany, German physicians planned and enacted the Euthanasia Program, the systematic killing of those they deemed unworthy of life .

The victims included the mentally retarded, the institutionalized mentally ill, and the physically impaired.The Nazi ExperimentFurther, during World War II, German physicians conducted pseudoscientific medical experiments utilizing thousands of concentration camp prisoners without their consent.

Most died or were permanently crippled as a result. Most of the victims were Jews, Poles, Russians, and also Roma (Gypsies).

The Nazi ExperimentFor the most part they are nameless dead. To their murderers, these wretched people were not individuals at all. They came in wholesale lots and were treated worse than animals.

Some of the medical experiments, including those for typhus, sea water, high-altitude, bone transplantation, extreme cold, sterilization, poison bullets, and skeleton collection.

IncludingMalaria experiments, bone transplantation experiments, starvation experimentsTo be able to appreciate where you are at any point in time, a person must acknowledge and learn from the past good and bad - Or one is likely to repeat it. In 1947, after World War II, at the Nuremberg trials,the Nuremberg Code (http://www.cirp.org/library/ethics/nuremberg/) for ethical conduct of research involving human subjectswas developed. Why?The trial highlighted highly unethical medical research conducted by Nazi doctors on their many captives in the concentration camps in World War II. Much knowledge was gained from these studies. Should we not use this knowledge because of how it was gained?e.g. information on hypothermia how long a person can survive in cold water before dying?

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Mustard gas chamber

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Mustard gas chamber15

Original caption: 2/7/1947-Germany: These photographs were made by German doctors to illustrate experiments carried out with an unfortunate camp inmate "guinea pig". The man's death was recorded systematically, step by step, until untill he was finally killed by strangulation underwater. This particular series deals with an experiment in compression and decompression. The various panels illustrate the phases of the man's confusional state due to a combination of anoxia and the bends. He is in a pressure chamber. (See Notes)16NUREMBERG CODE

The Nuremberg Trial (1947)On December 9, 1946, Nuremberg, Germany, , an American military tribunal opened criminal proceedings Held at the Palace of Justice against 23 leading German physicians and administrators for their willing participation in war crimes and crimes against humanity.

known as the "Doctors' Trial" and the "Medical Case," the trial was officially designated United States of America v. Karl Brandt.

The trial described and documented some of the most gruesome and painful medical experiments carried out by Nazi Doctorshttp://www.myclinicalresearchbook.blogspot.com/Four American judges presided - Walter Beals, Johnson Crawford, Harold Sebring, and Victor Swearingen.

18The victims of these crimes are numbered in the hundreds of thousands.A handful were alive; a few of the survivors appeared in the courtroom.But most of these miserable victims were slaughtered outright or died in the course of the tortures to which they were subjected.The Nuremberg Trial (1947) http://www.myclinicalresearchbook.blogspot.com/After hearing 85 witnesses and examining 1,471 documents that were presented, judgment was pronounced on August 19, 1947 with sentencing following on the next day.

Of the 23 defendants, 7 were sentenced the death by hanging (carried out at Landsberg Prison), 8 were given prison terms, and 8 were found not guilty.The Nuremberg Trial (1947) http://www.myclinicalresearchbook.blogspot.com/The defendants in this case are charged with murders, tortures, and other atrocities committed in the name of medical science7 condemned to death by hanging8 sentenced to prison from 10 years to life8 acquitted

20The Nuremberg Trial (1947) The judgment by the war crimes tribunal at Nuremberg laid down 10 standards to which physicians must confirm when carrying out experiments on human subjects in a new code that is now accepted worldwide.

This judgment established a new standard of ethical medical behavior for the post World War II human rights era.

http://www.myclinicalresearchbook.blogspot.com/The Nuremberg Trial (1947) Amongst other requirements, this document set forth the requirement of voluntary informed consent of the human subject.

The principle of voluntary informed consent protects the right of the individual to control his own body.

http://www.myclinicalresearchbook.blogspot.com/

View of the defendants in the dock at the International Military Tribunal trial of war criminals at Nuremberg. Nov 1945

Karl GenzkenKarl GebhardtKarl BrandtPersonal physician to Adolf Hitler; Gruppenfhrer in the SS and Generalleutnant (Lieutenant General) in the Waffen SS; Reich Commissioner for Health and Sanitation (Reichskommissar fr Sanitts und Gesundheitswesen); and member of the Reich Research Council (Reichsforschungsrat)

Gruppenfhrer in the SS and Generalleutnant (Lieutenant General) in the Waffen SS; personal physician to Reichsfuehrer-SS Himmler; Chief Surgeon of the Staff of the Reich Physician SS and Police (Oberster Kliniker, Reichsarzt SS und Polizei); and President of the German Red Cross

Gruppenfhrer in the SS and Generalleutnant (Lieutenant General) in the Waffen SS; and Chief of the Medical Department of the Waffen SS (Chef des Sanittsamts der Waffen SS)23The Nuremberg Trial (1947) This code also recognizes that the risk must be weighed against the expected benefit, and that unnecessary pain and suffering must be avoided.

This code recognizes that doctors should avoid actions that injure human patients.http://www.myclinicalresearchbook.blogspot.com/Voluntary Consent1. The voluntary consent of the human subject is absolutely essential.

This means that the person involved should have legal capacity to give consent; should be so situated as to be able to exercise free power of choice, without the intervention of any element of force, fraud, deceit, duress, over-reaching, or other ulterior form of constraint or coercion; and should have sufficient knowledge and comprehension of the elements of the subject matter involved as to enable him/her to make an understanding and enlightened decision.

Nuremberg Code cont..1 Permissible Medical Experiments The principles established by this code for medical practice now have been extened into general codes of medical ethics. Most Important is Voluntary Consent

The court included in its judgment ten points describing required elements for conducting research with humans. These points became known as the Nuremberg Code, and included the following ideas:

25Scientific Studies2. The experiment should be such as to yield fruitful results for the good of society, unprocurable by other methods or means of study, and not random and unnecessary in nature.

Prior Knowledge3. The experiment should be so designed and based on the results of animal experimentation and knowledge of the natural history of the disease or other problem under study that the anticipated results will justify the performance of the experiment.

Injury and Suffering4 The experiment should be so conducted as to avoid all unnecessary physical and mental suffering and injury.

5. No experiment should be conducted where there is a prior reason to believe that death or disabling injury will occur; except, perhaps, in those experiments where the experimental physicians also serve as subjects.

28Protection against Risk6. The degree of risk to be taken should never exceed that determined by the humanitarian importance of the problem to be solved by the experiment.

7. Proper preparations should be made and adequate facilities provided to protect the experimental subject against even remote possibilities of injury, disability, or death.

Qualified Investigators8. The experiment should be conducted only by scientifically qualified persons. The highest degree of skill and care should be required through all stages of the experiment of those who conduct or engage in the experiment.

Freedom to withdraw9. During the course of the experiment the human subject should be at liberty to bring the experiment to an end if he has reached the physical or mental state where continuation of the experiment seems to him to be impossible.

Termination of the Studies10. During the course of the experiment the scientist in charge must be prepared to terminate the experiment at any stage, if he has probable cause to believe, in the exercise of the good faith, superior skill and careful judgment required of him that a continuation of the experiment is likely to result in injury, disability, or death to the experimental subject.

Effect of the Nuremberg codeThe Code had little impact on researchers in the United States, who thought that:the principles in the Code were already implicit in their workit was simply a document to condemn the Nazi atrocities and to convict the Nazi doctors. Problems with the code:did not have the strength of lawapplied to only non-therapeutic human subjects research.33Declaration of HelsinkiDeclaration of Helsinki 1964 Adapted from Nuremberg Code by the World Medical Association(WMA).First adopted in Helsinki, Finland.It highlighted the importance of informed consent

WMA Declaration of Helsinki35DECLARATION OF HELSINKI:Basic PrinciplesConform to accepted scientific principles.Conducted by qualified and trained persons.Importance in proportion to inherent risk.Assessment of risks vs. benefits.Safeguard subjects integrity (privacy).Abstain unless hazards are predictable.Preserve accuracy when publishing.Adequately inform or right to withdraw.Obtain true informed consent in writing.

WMA Declaration of Helsinki36WORLD MEDICAL ASSOCIATION DECLARATION OF HELSINKIAdopted by the 18th WMA General Assembly, Helsinki, Finland, June 1964, and amended by the:

29th WMA General Assembly, Tokyo, Japan, October 1975

35th WMA General Assembly, Venice, Italy, October 1983

41st WMA General Assembly, Hong Kong, September 198953th WMA General Assembly, Washington 2002

55th WMA General Assembly, Tokyo 2004

59th WMA General Assembly, Seoul, October 2008

WMA Declaration of Helsinki37 Seven Ethical Pillars of Clinical ResearchAUTONOMY

BENEFICENCE

NON MALFEASANCE

FIDELITY

TRUTHFULNESS

CONFIDENTIALITY

JUSTICEWMA Declaration of Helsinki38Declaration of HelsinkiAutonomy ConsentThe subjects must be volunteers and informed participants in the research project. After ensuring that the subject has understood the information, the physician should then obtain the subject's freely-given informed consent, preferably in writing .WMA Declaration of Helsinki39Declaration of HelsinkiBeneficenceIn medical research on human subjects, considerations related to the well-being of the human subject should take precedence over the interests of science and society.

Medical research involving human subjects should only be conducted if the importance of the objective outweighs the inherent risks and burdens to the subject.WMA Declaration of Helsinki40Declaration of HelsinkiNon Malfeasance Every medical research project involving human subjects should be preceded by careful assessment of predictable risks and burdens in comparison with foreseeable benefits to the subject or to others.malfeasancelaw : illegal or dishonest activity especially by a public official or a corporation

WMA Declaration of Helsinki41Declaration of HelsinkiFidelity duty of careMedical research involving human subjects must conform to generally accepted scientific principles, be based on a thorough knowledge of the scientific literature.

Medical research involving human subjects should be conducted only by scientifically qualified persons and under the supervision of a clinically competent medical person.

The responsibility for the human subject must always rest with a medically qualified person and never rest on the subject of the research, even though the subject has given consent. Medical research involving human subjects must conform to generally accepted scientific principles, be based on a thorough knowledge of the scientific literature, other relevant sources of information, and on adequate laboratory and, where appropriate, animal experimentation.

WMA Declaration of Helsinki42Declaration of HelsinkiTruthfulness - Honesty

Both authors and publishers have ethical obligations. In publication of the results of research, the investigators are obliged to preserve the accuracy of the results. Negative as well as positive results should be published or otherwise publicly available.WMA Declaration of Helsinki43Declaration of HelsinkiConfidentiality

Every precaution should be taken to respect the privacy of the subject, the confidentiality of the patient's information and to minimize the impact of the study on the subject's physical and mental integrity and on the personality of the subject.WMA Declaration of Helsinki44Declaration of HelsinkiJusticeAt the conclusion of the study, every patient entered into the study should be assured of access to the best proven prophylactic, diagnostic and therapeutic methods identified by the study.

Medical research is subject to ethical standards that promote respect for all human beings and protect their health and rights. Some research populations are vulnerable and need special protection.

WMA Declaration of Helsinki45Belmont ReportApril 18, 1979

Ethical Principles and Guidelines for the Protection of Human Subjects of Research

Belmont ReportCreated by the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research

Named after the conference room Smithsonian Institutions Belmont Conference Center held in 1976

Created in reaction to previous human subject violations

47Historical PerspectiveNuremberg War Tribunal (1947)Horrifying procedures were conducted for research purposes on thousands of concentration camp prisoners without their informed consent

Syphilis Study in Tuskegee, GA (1932-1972)400 low-income African-American males who were infected with syphilis, were monitored for 40 yearsNever given antibiotics when they became available in 1947Many participants died of syphilis during the study

Syphilis - The study was stopped in 1973 by the U.S. Department of Health, Education, and Welfare only after its existence was publicized and it became a political embarrassment.

48Historical PerspectiveThalidomide use Thalidomide was used in the 1950s to combat unpleasant symptoms associated with pregnancyWas discovered that the drug had teratogenic effects, causing severe deformities in the fetus

Radiation experiments (1940s 1960s)The effects of radiation was studied through experiments on humansFew of the participants of the experiments gave informed consent; most had no knowledge that they were being subjected to radioactive materialsThalidomide use - At the time it was being used it was not usually disclosed to patients that the drug was investigational and still in the testing phase of the regulatory process. Thalidomide was soon banned worldwide. Unfortunately, approximately 12,000 babies were born with severe deformities due to thalidomide.

Tetratogenic - Of, relating to, or causing malformations of an embryo or fetus.

493 Basic Principles Respect for PersonsIndividuals should be treated as autonomous agentsPersons with diminished autonomy are entitled to protection

Treat individuals as autonomous persons; allow individuals to choose for themselves

Persons with limited autonomy need additional protection, even to the point of excluding them from activities that may harm them. The extent of protection should depend upon the risk of harm, and the likelihood of benefit.

503 Basic Principles BeneficenceHuman participants should not be harmedResearch should maximize possible benefits and minimize possible risks

Obligations of beneficence affect both the researcher and society -investigators are required to give forethought on maximization of benefits and reduction of risk that may be involved in the research-society should recognize the longer term benefits and risk that may result from the improvement of knowledge, and from the development of novel medical, psychological, and social processes and procedures

513 Basic Principles JusticeThe benefits and burdens of research should be justly distributed5 FormulationsEveryone gets an equal shareDistribution according to needAccording to individual effortAccording to societal contributionAccording to merit

52Application of Respect for PersonsInformed Consent ProcessInformation - Does the consent form provide all the information necessary for the individual to make a reasoned decision? Comprehension - Is the consent form crafted in language understandable to the potential participant?Voluntariness - Does the consent form and clearly indicate that participation in the research is voluntary? A critical component of respecting human participants is the informed consent process. The consent document is a written summary of the information that should be provided to the participant.

What additional protections can be in place to protect those with limited autonomy? How to determine whether one lacks the autonomy to make a reasoned decision?

53Applications of BeneficenceAssessment of Risks and BenefitsWhat are the risks of harm to the participants (consider physical, psychological, social, and economic harms)? Are the risks justified? Can they be minimized? Can the research design be improved to minimize risk and maximize benefit?What are the benefits (to the participant; to society)?The researcher needs to assemble all data that explains why the research will obtain the benefits that are sought by the research project. 54Applications of JusticeSelection of SubjectsIs the potential subject pool appropriate for the research? Is it appropriate to involve vulnerable populations (e.g., economically disadvantaged; limited cognitive capacity) in the research or are they being enrolled because it is convenient or because they are easily manipulated as a result of their situation?Are the recruitment procedures fair and impartial? Are the inclusion and exclusion criteria fair and appropriate?

The principle of justicethat benefits and risks of research be distributed fairly. Researchers are not just if they only select disadvantages persons for risky research or only provide beneficial research to groups they favor. 55The Ethics of Animal Research56Animal TestingWhile controversial, it is an unavoidable fact that animal research has allowed the development of medicines and vaccines, surgical techniques and advanced scientific understanding in many areas

57The Three RsThe guiding principles for the use of animals in research are the three Rs:Replacement: Use alternative, non-animal methods to achieve the same scientific aimReduction: Use statistical methods so that a smaller number of animals are requiredRefinement: Improve the experiments so that animals do not suffer58Animal Welfare Act of 1998 It is the purpose of this Act to protect and promote the welfare of all animals in the Philippines by supervising and regulating the establishment and operations of all facilities utilized for breeding, maintaining, keeping, treating or training of all animals either as objects of trade or as household pets

When can animals be used?When there are no other alternatives.

When confirmation has been made that research activities are not unnecessarily duplicating previously conducted experiments.

Experiments involving animals are relevant to human or animal health, will advance scientific knowledge, or will be for the good of society.

Ethics of Animal ResearchWhen animals are used for research a scientist must avoid or minimize discomfort, distress, and painful situations.If a procedure involves more than momentary or slight pain or distress, it must be performed using appropriate pain relieving drugs (e.g. sedatives, analgesia or anesthesia).If animals are to be transported, appropriate arrangements must be made to ensure the process is comfortable and occurs with as little stress as possible. The living conditions of animals must be clean and appropriate for the species.

Dog Experiment

Soviet Dr Sergei S. Bryukhonenko

Russians re-attaching dog headsVladimir Demikhov created a two headed dog for an experiment. In 15 years, above 20 dogs were created.

This infamous propaganda film from 1940 shows Soviet Dr Sergei S. Bryukhonenko removing the head of dogs, and keeping them alive on a heart-lung machine. While possibly a Soviet fake, it produced a major stir in the west.62Research Ethic IssuesAuthorshipIt is the process of deciding whose names belong on a research paperResponsible authorship practices are an important part of research

Plagiarism It is the act of passing off somebody elses ideas, thoughts, pictures, theories, words, or stories as your ownPlagiarism is both an illegal act and punishable, considered to be on the same level as stealing from the authorPlagiarism takes many forms:People who intentionally take a passage word-for-word, put it in their own work, and do not properly credit the original authorParaphrased and fragmented texts the author has pieced together from several works without properly citing the original sources

Peer ReviewIt is the process in which an author submits a written manuscript or article to a journal for publication and the journal editor distributes the article to experts working in the same, or similar, scientific disciplineThe process involves the following: Reviewers and editors read and evaluate the article.Reviewers submit their reviews back to the journal editor.The journal editor takes all comments, including their own, and communicates this feedback to the original author.

Conflicts of InterestConflicts of interest arise when a persons (or an organizations) obligations to a particular research project conflict with their personal interests or obligations

Conflicts of interest are particularly important to examine within the context of biomedical research because research subjects may be particularly vulnerable to harm

Data ManagementData management, in respect to research ethics, references three issues: The ethical and truthful collection of reliable data The ownership and responsibility of collected dataRetaining data and sharing access to collected data with colleagues and the public

Research MisconductResearch misconduct is the process of identifying and reporting unethical or unsound research. Its components are as follows: Fabrication is making up data or results and recording or reporting them.Falsification is manipulating research materials, equipment, or processes, or changing or omitting data or results such that the research is not accurately represented in the research record. Plagiarism is the appropriation of another persons ideas, processes, results, or words without giving appropriate credit.

Research misconduct does not include honest error or differences of opinion.

69Research with AnimalsAnimals play a significant role in researchNecessary first step towards research involving new medical treatments and pharmaceuticals intended for human useMany dedicated organizations and individuals are interested in protecting and safeguarding animal subjects as regards their use in researchResearch with Human SubjectsRespect for Persons Informed Consent exists to ensure that all research involving human subjects allows for voluntary participation by subjects who understand what participation entails. Respect for Persons Privacy and confidentiality. People have a right to protect themselves, and information gathered during research participation could harm a person by violating their right to keep information about themselves private. Risk benefit and beneficence. Beneficence is a principle used frequently in research ethics. It means, doing good. While research findings may one day help do good, they may also cause harm to todays research participants. Justice. Particular interest has been paid lately to preventing the overburdening of some populations in order to apply research findings to other groups.