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Study Design and Scientific Review

The IRB has an ethical obligation to review the design or other aspects of a study that may affect the scientific quality of the protocol. The following sections from internationally recognized ethical guides state that ethical research requires that:

  1. the study is designed to minimize the risks to subjects and
  2. the potential risks of the research are justified by the potential benefits.

The Ethical Codes:

Nuremberg Code  (1949)

Several sections including the following address the question.

Point 3. “The experiment should be so  designed and based on the results of animal experimentation and a knowledge of  the natural history of the disease or other problem under study that the  anticipated results will justify the performance of the experiment.”

Declaration of Helsinki  (2000)          

Several sections including the following address the question.

  • Section 11. “Medical Research involving  human subjects must conform to generally accepted scientific principles and be  based on a thorough knowledge of the scientific literature, other relevant  sources of information, and adequate laboratory and when appropriate, animal  experimentation.”
  • Section 18. “Medical research involving  human subjects should only be conducted if the importance of the objective  outweighs the inherent risks and burdens to the subject. This is especially  important when the human subjects are healthy volunteers.”
  • Section 29. “The benefits, risks,  burdens, and effectiveness of a new method should be tested against those of  the best current prophylactic, diagnostic or therapeutic methods. This does not  exclude the use of placebo, or no treatment, in studies where no proven  prophylactic, diagnostic or therapeutic method exists.”

Federal Research  Regulations

DHHS  and corresponding FDA Sections (21 CFR 56.111).

45 CFR 46.111 Criteria for IRB  approval of research.

In order  to approve research covered by this policy the IRB shall determine that all of  the following requirements are satisfied:

  1. Risks to subjects are minimized: (i) By using procedures which are  consistent with sound research design and which do not unnecessarily expose  subjects to risk, and (ii) whenever appropriate, by using procedures already  being performed on the subjects for diagnostic or treatment purposes.
  2. Risks to subjects are reasonable  in relation to anticipated benefits, if any, to subjects, and the importance of  the knowledge that may reasonably be expected to result. In evaluating risks  and benefits, the IRB should consider only those risks and benefits that may  result from the research (as distinguished from risks and benefits of therapies  subjects would receive even if not participating in the research). The IRB  should not consider possible long-range effects of applying knowledge gained in  the research (for example, the possible effects of the research on public  policy) as among those research risks that fall within the purview of its  responsibility.



Robert J. Amdur in Ch. 5-2 “Evaluating Study Design  and Quality” in IRB Management and Function by Elizabeth A. Bankert  and Robert J. Amdur notes the references above and offers the following  guidelines to IRBs when evaluating a study’s scientific design and benefit from  the perspective of risk to participants.
The IRB should use independent judgment and common sense. For  example if the design of a student research project for a course is flawed but  creates no effective risk to subjects, there is no ethical basis for the IRB to  require revisions for approval. There are only educational reasons to suggest  changes.
The IRB should NOT approve a  study without requiring revisions if:

  • revising the design will decrease the risks to participants in a  meaningful way without a major compromise to the persuasiveness of the study  results; OR
  • the study design is “so  flawed that the value of the study results will be almost zero.” In this  case, even though the risks may be low if the potential benefit is zero, the  overall risk/benefit ratio would be unacceptable; OR
  • the study involves a meaningful  risk and asks a question that was already answered in earlier research or  “not important” to the field of scientific inquiry.

Policies  and Procedures

UConn IRB, Submission to the IRB, Scientific Review

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