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Approval Criteria

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The Children's Hospital of Philadelphia has chosen not to apply all of the requirements of the Common Rule (45 CFR 46) to all human subjects research under the institution's Federal Wide Assurance (FWA). Research that is funded by the federal government must meet all of the requirements of the Common Rule. In addition, research that is regulated by the FDA must adhere to its regulations for the protection of human subjects and other relevant FDA regulations (e.g., 21 CFR 50, 54, 56, 312, 314, 812, and 814).

The IRB's basic approach to all research, regardless of funding adheres to the principles outlined in the regulations. The IRB's SOPs delineate the ways in which it deviates from the federal regulations for non-federally funded, non-federally regulated research.

CHOP's human research protection program received initial certification in 2010 by the American Association for Human Research Protections Programs (AAHRP) (analogous to JCAHO accreditation for hospitals) and received 5-year re-accreditation in 2018. AAHRPP's standards meet and often exceed the federal regulatory requirements. The IRB's Policies and requirements therefore, not only adhere to the federal regulations, but when necessary, to the additional requirements imposed by AAHRPP.

Ethical Requirements for Conduct of Human Subjects Research

"What Makes Clinical Research Ethical"

  1. Social or Scientific Value
  2. Scientific Validity
  3. Fair Subject Selection
  4. Favorable Risk - Benefit
  5. Independent Review
  6. Informed Consent
  7. Respect for Potential and Enrolled Subjects

From JAMA 283:2701-11, 2000.

National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research was formed in 1974 n the wake of the Tuskegee scandal. The Commission provided a variety of reports which formed the foundation of our current research regulations.

The Belmont Report is the most famous of the National Commission's reports and it provides the basis for the ethical justification for conducting human subjects research. The Report establishes the ethical principles of Respect for Persons, Beneficence and Justice as essential for ethical human subjects research. Anyone conducting human subjects research should read this report in its entirety.

Emanuel and his colleagues propose 7 criteria that establish a framework for determining whether or not a proposed research activity satisfies the ethical requirements (panel to the right) articulated in the Belmont Report. Emanuel places great emphasis on the social value and scientific validity of clinical research. One of main points of this paper is that studies that are without value expose subjects to risk and inconvenience without any corresponding prospect of benefit to science, society or the participants. This article is an essential read for clinical investigators.

Basis of IRB Approval

The Federal regulations incorporate all of these concepts including the requirement for independent review of research. The IRB (Institutional Review Board, also known as an (REC) Research Ethics Committee) is the independent review committee that must review and approve all clinical research. The criteria in the panel below summarizes the Federal regulatory requirements. "Procedures consistent with sound research design" not only demands that the investigator demonstrate they are capable of conducting the study and producing scientifically valid results. Many protocols submitted to the IRB, particularly those that are investigator initiated provide insufficient evidence of sound scientific design to permit the IRB to approve the research.

Regulatory Approval Criteria

Criteria for IRB Approval of Research

45 CFR 46.111 and 21 CFR 56.111
(a)IRB shall determine that all of the following criteria are followed

  1. Risks to subjects are minimized by using: i) procedures consistent with sound scientific design and which do not unnecessarily expose subjects to risk ii) whenever appropriate by using procedures already being performed on subjects for diagnostic or treatment purposes
  2. Risks to subjects are reasonable in relation to the anticipated benefits
  3. Selections of subjects is equitable ...
  4. Informed consent will be sought from each prospective subject or the subject's legally authorized representative ... as required by #46.116.
  5. Informed consent will be appropriately documented ... to the extent required by §46.117
  6. When appropriate, the research plan makes adequate provision for monitoring the data collected to ensure the safety of subjects
  7. When appropriate, there are adequate protections to protect privacy of subjects and to maintain the confidentiality of data.

(b) When some or all of the subjects are likely to be vulnerable to coercion or undue influence, such as children, prisoners, individuals with impaired decision-making capacity, or economically disadvantaged persons, additional safeguards have been included in the study to protect the rights and welfare of the these subjects.

 

Regulatory Approval Criteria

Sound design, not unnecessarily exposing subjects to risk, combining research with clinical care.

Assessment on whether risks are reasonable in relation to the anticipated benefits.

Fair/appropriate selection criteria; no group unduly burdened or unfairly benefiting.

Guidance on the process of obtaining written consent/parental permission.

Plan to ensure/monitor compliance, study progress, subject safety, and data accuracy/security.

Provisions to protect the privacy of subjects and maintain the confidentiality of data.

Children, pregnant women & the fetus, adults with diminished capacity, and prisoners in the research context.

 

Regulations: Limits of IRB authority

  • 45 CFR 46.109 (a) IRB review of research An IRB shall review and have authority to approve, require modifications in (to secure approval), or disapprove all research activities covered by this policy.
  • 45 CFR 46.113 Suspension or termination of IRB approval of research. An IRB shall have authority to suspend or terminate approval of research that is not being conducted in accordance with the IRB's requirements or that has been associated with unexpected serious harm to subjects.

For a more complete discussion of IRB approval with required modifications see OHRP's Guidance on IRB Approval with Conditions.

Actions Available to the IRB

IRBs should limit their actions to those incorporated into the regulations. It is tempting to succumb to mission creep and to impose requirements on investigators above and beyond the IRB's charge. For example, an IRB may try to impose requirements on issues such as whether or not an investigator may include a subject or their data as part of an analysis. This decision is beyond the IRB's scope. While the IRB cannot make an investigator dispose of data, or impose conditions on research conducted outside of an approved protocol, investigators may not claim that the research had IRB approval for these activities when seeking to publish or use the data. It is up to the Institutional Official and others at the institution responsible for the oversight of research to impose sanctions and conditions that go beyond the IRB's authority.

In addition to the actions listed in the box above, the IRB may also impose conditions on the research such as the frequency of continuing review, it may audit the study or it may observe the conduct of the research or the consent process.