UNIT 3

Question 1

includes medical ethics, which focuses on issues in health care; research ethics, which focuses issues in the conduct of research.

Answer 1

Bioethics

Question 2

did a great deal of human experimentation.

Answer 2

During World War II the Axis Powers

Question 3

Both Imperial Japan and Nazi Germany subjected human beings to ___ in order to obtain data that might prove useful in their war effort

Answer 3

torturous ordeals`

Question 4

Issued by the Nuremberg Military Tribunal in 1947, the Nuremberg Code is a 10-point statement meant to prevent future abuse of human subjects. It states that, above all,

Answer 4

1. Participation in research must be voluntary.
2. The results of the research must be useful and unobtainable by other means.
3. The study must be rationally based on knowledge of the disease or condition to be studied.
4. It must avoid unnecessary suffering.
5. The study cannot include death or disabling injury as a foreseeable consequence.
6. Its benefits must outweigh its risks.
7. The study must use proper facilities to protect participants.
8. The study must be conducted by qualified individuals.
9. Participants may withdraw from the study if they wish.
10. Investigators must be prepared to stop the study should participants die or become disabled as a result of participation.

Question 5

was created by opining on the testimony of physician witnesses and was said to represent current thoughts on the topic of human experimentation.

Answer 5

The Nuremberg Code

Question 6

has been tremendously influential—becoming the basis of later documents that are highly relevant to research today.

Answer 6

the Nuremberg Code

Question 7

an international medical association that had been effectively disbanded during World War II.

Answer 7

Organized in 1945, the World Medical Association (WMA) took the place of l’Association Professionnelle Internationale des Médecins—

Question 8

. Physicians from the WMA were appalled at the atrocities revealed at the Nuremberg Trial and, in 1949, issued a code of medical ethics to condemn what Nazi doctors had done. This code came to be known as the ____ for the city in which it was officially adopted.

Answer 8

Declaration of Geneva

Question 9

its vague language did not allow accurate interpretations in the newly emerging field of medical ethics.

Answer 9

Declaration of Geneva,

Question 10

To clarify a physician’s duties as an investigator, the WMA began reexamining the issue in

Answer 10

1953.

Question 11

The subject was discussed and debated for several years before the resulting document, _____, was approved in 1964

Answer 11

Ethical Principles for Medical Research Involving Human Subjects

Question 12

The subject was discussed and debated for several years before the resulting document, Ethical Principles for Medical Research Involving Human Subjects, was approved in 1964. Again taking its name from the city in which it was adopted, this paper became known as the

Answer 12

Declaration of Helsinki.

Question 13

has been revised several times—most recently in 2000. Minor clarifications were also added in 2002 and 2004. Its current form contains 3 sections in 32 separate paragraphs—each on a specific topic.

Answer 13

Beginning in 1975, the Declaration of Helsinki

Question 14

sets the stage of what human research is and why it is necessary and stresses the obligation of the physician to prioritize participant health. This section reminds physicians that special populations involved in research must be closely monitored.

Answer 14

Declaration of Helsinki Section A

Question 15

Section B discusses basic principles for medical research and reaffirms points of the Nuremberg Code—such as the need for basing a human trial rationally on available evidence.

Answer 15

Declaration of Helsinki Section B

Question 16

Section C discusses research combined with medical care and states that research can only be combined with clinical care if it has the potential to prophylax, diagnose, or treat.

Answer 16

Declaration of Helsinki Section C

Question 17

Experimental care may be offered to individuals outside a formal research study if standard care has been ineffective for their condition. ___ also contains the 2 most controversial statements in the document: Paragraphs 29 and 30.

Answer 17

Declaration of Helsinki Section C

Question 18

asserts that new treatments should be tested against standard treatment; thus proscribing the use of placebo-controlled studies when a known treatment exists. This statement was clarified to allow exceptions in cases where a placebo is “scientifically” necessary to evaluate a treatment or when the condition being investigated is “minor” and a placebo does not entail additional risks to the subject.

Answer 18

Paragraph 29

Question 19

states that, at study conclusion, all participants should be assured access to the “best” treatment as identified in the study. It is not the purpose of this article to debate the pros and cons of these statements, but it should be obvious that well-intentioned and informed investigators could come to conclusions different than those allowed by Paragraphs 29 and 30 in the Declaration of Helsinki.

Answer 19

Paragraph 30

Question 20

was created for the U.S. Department of Health, Education, and Welfare (DHEW—now known as the Department of Health and Human Services after a separate Department of Education was established in 1979).

Answer 20

In 1974, the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research

Question 21

The commission’s charge was to identify ethical principles underlying research and develop guidelines for respecting these principles. Although acknowledging the existence of other codes governing human research, the commission thought that other codes amounted to lists of regulations that might not allow the resolution of complex ethical questions.

Answer 21

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

Question 22

The commission postulated that looking at the topic more generally would allow recognition of fundamental principles. Researchers could then appeal to these principles to resolve dilemmas for which other codes have no answer.

Answer 22

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

Question 23

The report, issued in 1979, is entitled Ethical Principles and Guidelines for the Protection of Human Subjects of Research. It came to be known as the _____, after the Smithsonian Institution’s Belmont Conference Center (where most of the meetings of the commission took place).

Answer 23

Belmont Report

Question 24

The commission concluded that the primary principles underlying ethical research with human beings are as follows:

Answer 24

1. Respect for Persons:
2. Beneficence:
3. Justice:

Question 25

This principle acknowledges the dignity and freedom of every person. It requires obtaining informed consent from research subjects (or their legally authorised representatives)

Answer 25

1. Respect for Persons:

Question 26

This principle requires that researchers maximise benefits and minimise harms associated with research. Research-related risks must be reasonable in light of the expected benefits.

Answer 26

2. Beneficence:

Question 27

This principle requires equitable selection and recruitment and fair treatment of research subjects.

Answer 27

3. Justice:

Question 28

requires that information be shared with a potential subject, that he or she comprehend the information given, and that the person voluntarily agree to participate in the research.

Answer 28

Informed consent

Question 29

. Information shared should “generally include:

Answer 29

The research procedure, their purposes, risks and anticipated benefits, alternative procedures (where therapy is involved), and a statement offering the subject the opportunity to ask questions and to withdraw at any time from the research”.

Question 30

Another component of informed consent is the

Answer 30

voluntariness of the decision to participate.

Question 31

Assessment of risks and benefits begins by determining the soundness of the research design. Next, risk is discussed in both the probability that a harm will occur and “the severity of the envisioned harm.” Benefits are likewise discussed. It is pointed out that, compared to risks, benefits are more amenable to generalization. Studies could benefit a patient group, “society,” and/or “scientific knowledge.” Recognizing that there is as yet no perfect means of doing so, the committee recommends that risks and benefits be studied by a “systematic, no arbitrary analysis.”

Answer 31

2. Risks and Benefits

Question 32

are that no “brutal or inhumane treatment of human subjects” could ever be justified and only risks necessary to achieve the experimental ends should be tolerated.

Answer 32

Caveats

Question 33

In patient selection, the principle of justice is cited most often. This means, more or less, treating equals equally—therefore, people with the same illness should be offered research participation equally (or maybe bear the risks of research equally?). However, in the interest of fairness, people should not be used for research simply as a matter of “administrative convenience”. Therefore, classes of people like prisoners or “the mentally infirm” may be invited to participate in research, only on certain conditions.

Answer 33

3. Selection of Participants

Question 34

is rooted in medicine but has quickly been embraced by the entire health care community.

Answer 34

Evidence-based practice

Question 35

is “the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients”.

Answer 35

Evidence-based practice

Question 36

involves being aware of the various levels of existing evidence underlying a given intervention approach and carefully appraising that evidence as it applies to a specific patient encounter.

Answer 36

The process of evidence-based practice

Question 37

Ethical Considerations in Evidence-Based Practice
Selecting and Using Intervention for a Given Patient

Answer 37

 Base decision on best evidence for given patient, condition, and setting
 Involve patients in the choice of intervention
 Appreciate the importance of research evidence over tradition or expert opinion
 Recognize the psychological and resource costs of ineffective intervention
 Avoid the use of unethical studies

Question 38

Participating in or Advocating for Research

Answer 38

 Monitor ethical practices in research in which one participates
 Assure complete and appropriate informed consent
 Advocate for research balancing survival with quality of life
 Respect the right of participant autonomy
 Involve consumers in strategic decisions about research directions

Question 39

is a harmonized standard that protects the rights, safety and welfare of human subjects, minimizes human exposure to investigational products, improves quality of data, speeds up marketing of new drugs and decreases the cost to sponsors and to the public.

Answer 39

ICH-GCP

Question 40

Importance of GCP

Answer 40

1. Increased Ethical Awareness
2. Improved Trial Methods
3. Clinical Trial Concept Better Understood
4. Public/Political Concern over Safety Aspects
5. Frauds and Accidents during Trials
6. Growing Research and Development Costs
7. Increasing Competition
8. Mutual Recognition of Data
9. New Market Structure

Question 41

There are 13 core principles of ICH-GCP and they are as follows:

Answer 41

1. Clinical trials should be conducted in accordance with ethical principles that have their origin in the Declaration of Helsinki, and that are consistent with GCP and the applicable regulatory requirement(s).
2. Before a trial is initiated, foreseeable risks and inconveniences should be weighed against anticipated benefit for the individual trial subject and society. A trial should be initiated and continued only if the anticipated benefits justify the risks.
3. The rights, safety and well-being of the trial subjects are the most important considerations and should prevail over interest of science and society.
4. The available non-clinical and clinical information on an investigational product should be adequate to support the proposed clinical trial.
5. Clinical trials should be scientifically sound, and described in clear, detailed protocol.
6. A trial should be conducted in compliance with the protocol that has received prior institutional review board (IRB)/ independent ethics committee (IEC) approval/favorable opinion.
7. The medical care given to, and medical decisions made on behalf of subjects should always be the responsibility of a qualified physician or, when appropriate, of a qualified dentist.
8. Each individual involved in conducting a trial should be qualified by education, training, and experience to perform his or her respective task(s).
9. Freely given informed consent should be obtained from every subject prior to clinical trial participation.
10. All clinical trial information should be recorded, handled, and stored in a way that allows its accurate reporting, interpretation and verification.
11. The confidentiality of records that could identify subjects should be protected, respecting the privacy and confidentiality rules in accordance with the applicable regulatory requirement(s).
12. Investigational products should be manufactured, handled and stored in accordance with applicable Good Manufacturing Practice (GMP). They should be used in accordance with the approved protocol.
13. Systems with procedures that assure the quality of every aspect of the trial should be implemented.

Question 42

should be easily accessible and retrievable for accurate reporting, verification and interpretation.

Answer 42

Records

Question 43

Company or institution/organization which takes responsibility for initiation, management and financing of clinical trial

Answer 43

The sponsor

Question 44

Usually appointed by sponsor

Answer 44

The project monitor

Question 45

Responsible for conduct of clinical trial at the trial site. Team leader.

Answer 45

The investigator

Question 46

Responsible for maintenance, storage and dispensing of investigational products eg. Drugs in clinical trials

Answer 46

The pharmacist at trial location

Question 47

Human subjects

Answer 47

Patients

Question 48

Appointed by Institution or if not available then the Authoritative Health Body in that Country will be responsible

Answer 48

Ethical review board or Committee for protection of subjects

Question 49

Overseas Sponsors eg. Drug Companies

Answer 49

Committee to monitor large trials

Question 50

The events that led up to the culmination of the ___ brought forth public awareness that there was a need to control and regulate clinical trials dealing with drugs and human subjects.

Answer 50

ICH-GCP guidelines