Chapter 7: Issues in Clinical Research

Question 1

What is the Nuremberg Code?

Answer 1

The Nuremberg Code clearly emphasized that every individual should voluntarily consent to participate as a research subject and addresses the competence of the investigator

Question 2

What is the Declaration of Helsinki?

Answer 2

Requires independent review of research protocols by a committee of individuals who are not associated with the proposed project.

Question 3

What is the National Research Act?

Answer 3

In 1974, the National Research Act was signed, largely in response to public recognition of misconduct in the Tuskegee syphilis study. This law requires the development of a full research proposal that identifies the importance of the study, obtaining informed consent, and review by an Institutional Review Board (IRB).

Question 4

What is the Belmont Report?

Answer 4

Delineates the guiding ethical principles for human research studies. The Belmont Report also established the rules and regulations that govern research efforts of the Department of Health and Human Services (DHHS) and the Food and Drug Administration (FDA).

Question 5

What is the Common Rule?

Answer 5

Outlines the basic provisions for ethical research.
This rule codifies regulations adopted by many federal departments and agencies, with a focus on institutional guidelines, informed consent, and review of proposals for the protection of participants.

Question 6

The Belmont Report established three basic ethical principles that have become the foundation for research efforts, serving as justification for human actions. What are they?

Answer 6

respect for persons, beneficence, and justice

Question 7

What is respect for persons?

Answer 7

This principle incorporates two considerations. The first is personal autonomy, referring to self-determination and the capacity of individuals to make decisions affecting their lives and to act on those decisions.

Question 8

What is beneficence?

Answer 8

Beneficence refers to the obligation to attend to the well-being of individuals.
The analysis of the risk-benefit relationship measures the probability and magnitude of benefit against the probability of anticipated harm or discomfort.
Beneficence requires that an investigation be justified when studying a treatment to determine its benefits despite known risks, especially if these risks are substantial.

Question 9

What is justice?

Answer 9

Justice refers to fairness in the research process, or the equitable distribution of the benefits and burdens. This principle speaks to the fair selection of subjects who are appropriate for a given study, drawn from a defined population that is most likely to benefit from the research findings.

Question 10

What is the Institutional Review Board?

Answer 10

According to federal regulations, an IRB must review research proposals prior to implementation to ensure that the rights of research subjects are protected.

Question 11

Who makes up the IRB?

Answer 11

The IRB must have at least five members with diverse backgrounds that facilitate complete and adequate reviews of the scientific and ethical details of proposed research.
- At least one member must be concerned primarily with nonscientific issues and may be a lawyer, clergyman, or ethicist.

Question 12

Describe the IRB’s review of proposals.

Answer 12

The IRB considers the scientific merit of the project, the competence of the investigators, the risk to subjects, and the feasibility based on identified resources.
Reviewers will consider the risk-benefit ratio, based on evidence that the risks and discomforts to the subject are reasonable, have been minimized, and are sufficiently outweighed by the potential benefits of the proposed study.
The IRB also looks at the procedures for selecting subjects, ensuring that they are equitable, and that voluntary informed consent is based on complete and understandable descriptions and conforming to the applicable elements of privacy.

Question 13

When would a project qualify for expedition?

Answer 13

A project may qualify for expedited review in circumstances such as “recording data from subjects 18 years of age or older using noninvasive procedures routinely employed in clinical practice,” or “moderate exercise by healthy volunteers.” IRBs may expedite review of projects involving retrospective studies, when data are used from medical records, and all subjects are de-identified.

Question 14

When would a project qualify for exemption?

Answer 14

Exempt reviews may be allowed for surveys, interviews, or studies of existing records, provided that the data are collected in such a way that subjects cannot be identified.

Question 15

What is informed consent?

Answer 15

The informed consent process and all its elements address the basic principles of respect, beneficence, and justice.

Question 16

The components of the informed consent process include what two important elements?

Answer 16

information and consent

Question 17

What are the elements of information regarding informed consent?

Answer 17

• Concise introduction
• Purpose of the research
• Procedures
• Potential risks and discomforts
• Potential benefits
• Information on study outcomes
• Alternatives to participation
• Confidentiality
• Compensation
• Contact information and request for more information
• Consent statement
• Signatures

Question 18

What are the elements of consent regarding informed consent?

Answer 18

• Consent must be voluntary.
• The IRB will be particularly concerned with research that involves subjects who are vulnerable to coercion or undue influence, such as children, prisoners, those with impaired decision-making capacity, or those who are educationally or economically disadvantaged.
• Subjects must be free to withdraw consent at any time.

Question 19

What is research misconduct?

Answer 19

Research misconduct means fabrication, falsification, or plagiarism in proposing, performing, or reviewing research, or in reporting research results.

Question 20

What is fabrication?

Answer 20

Fabrication is making up data or results and recording or reporting them. This includes presenting observations that never occurred or describing experiments that were never performed.

Question 21

What is falsification?

Answer 21

Falsification is manipulating research materials, equipment, or processes, or changing or omitting data or results such that the data are not accurately represented in the research record.

Question 22

What is plagiarism?

Answer 22

Plagiarism is the appropriation of another person’s ideas, processes, results, or words without giving appropriate credit or attribution, and representing the work as one’s own.

Question 23

What are conflicts of interest?

Answer 23

a set of conditions in which a primary interest tends to be influenced by a secondary interest

Question 24

What is the purpose of peer review?

Answer 24

The purpose of peer review is to provide feedback to an editor who will make decisions about whether a manuscript should be accepted, revised, or rejected.

Question 25

In the statistical analysis of clinical trials, the ability to document significant effects is dependent on what two main elements?

Answer 25

The size of the effect of the intervention or test
The sample size included in the study

Question 26

Starting in the planning stages, researchers must engage in the process with commitment to established principles of design and statistical testing. This means following the “rules”:

Answer 26

• Formulating hypotheses and developing analysis plans before data are collected.
• Adhering to the research protocol.
• Taking responsibility to ensure a large enough sample to secure reasonable power.
• Choosing the appropriate statistical procedures and interpreting them without manipulation, even when outcomes are not as expected.
• Not being selective in choosing relevant findings after the fact but analyzing and reporting all data.