Human Research Protection Program
As an institution engaged in the conduct of human subjects research, Loma Linda University Health maintains a comprehensive program that protects the rights and welfare of those individuals who participate in research. (See Institutional policy H-24: Human Research Participant Protection (HRPP) Program - Statement of Commitment and Institutional Oversight of Assurance). The key elements of this program are:
Policies and Procedures
The ethical commitment and practices of the institution are defined by policies and procedures that guide its research community with regard to human subject protections. This Institution is registered with the U.S. Office of Human Research Protection (IORG#0000226) and holds a FederalWide Assurance ( FWA#00006447) for research conducted with federal agencies that apply federal policies and for clinical investigations regulated by the Food and Drug Administration.
To support its research community in the pursuit of the highest standards of research integrity and respect for human subjects, Loma Linda University maintains an education program to provide investigators with training in the ethical and regulatory requirements that govern human research.
The principal investigator will ensure that all personnel associated with a study are certified for completion of human subjects research education from Loma Linda University Health. In the event that the certification lapses, the principal investigator will ensure that uncertified personnel do not participate in the study until certification is renewed.
Designated Institutional Official
The LLUH Vice President for Research Affairs is the individual designated to oversee the human subject protection program, including the following:
- Provide adequate resources to implement its Human Research Protection Program in accord with federal regulations and applicable ethical standards
- Grant the LLU Institutional Review Board the authority to function independently of other organizational entities in its role in protecting research participants.
- Assure that the IRB is free from undue influence and investigate all reports to the contrary.
- Implement safeguards to assure that no research involving human subjects is conducted without prior IRB review and approval.
- Serve as the signing official for legal documents.
See Institutional policy H-25: Institutional Official (IO) for Human Subject Research .
The following are designated as affiliated components of Loma Linda University Health (LLUH) for purposes of implementing Federal policy regarding human subject research:
- Loma Linda University Medical Center
- Loma Linda University Children's Hospital
- Loma Linda University Medical Center East Campus Hospital
- Loma Linda University Behavioral Medicine Center
- Associated faculty medical practice corporations
Institutional Review Board
The Institutional Review Board (IRB) operates under federal regulations, state laws, and institutional policy, reviewing all research involving human subjects to ensure the ethical and equitable treatment of those subjects. The IRB has the authority to approve, modify, or disapprove proposed studies and to modify, suspend or terminate approval of on-going studies. Its decisions may be modified by institutional officials to be more restrictive, but not less so.
The IRB is duly constituted to reflect the institution's research climate with both experience and expertise and is registered with the U.S. Office for Human Subject Research Protection (IRB#0000383). At Loma Linda University Health, the IRB also serves as the Privacy Board. See also: The Institutional Review Board (below).
The IRB Chair, appointed by the President upon the recommendation of the Vice President for Research Affairs, understands ethical issues and regulatory requirements related to human subject research. Primary responsibilities include conducting convened board meetings, making the final determination for level of IRB review, and generally representing the IRB in communicating with investigators, administrators, legal advisors, and community representatives.
The IRB Administrator is responsible for coordinating the functions of the IRB and supervising IRB staff. This includes developing and maintaining systems relating to IRB submissions and records and assuring that the IRB Chair is provided staff support to fulfill the Chair's responsibilities.
The Institutional Review Board
Purpose and Philosophy
Human subjects are a valuable resource that should not be utilized on meaningless investigations, even if participation carries no apparent risk. While the duty of the IRB is to review and make decisions on all protocols for human subject research, it serves to encourage and support quality research. Its primary responsibility is the protection of subjects from undue risk and from deprivation of personal rights and dignity. This protection is guided by the ethical principles set forth in the Declaration of Helsinki of the World Medical Association and the "Belmont Report"( Ethical Principles for the Protection of Human Subjects in Research). In summary, the three basic principles detailed in the Belmont Report are:
- Respect for Persons
- Acknowledge Autonomy
- Protect those with diminished autonomy
- Do no Harm
- Maximize possible benefits and minimize possible harm
- In selecting subjects, distribute the burdens and benefits of research equally among the various segments of society
The IRB follows these national standards of criteria for review and approval of human research:
- The risks shall be minimized as far as possible by sound research, safeguards against the risks, and avoidance of unnecessary risks.
- The risks are reasonable in relation to the benefits to the subject of the importance of the knowledge to be gained for humanity.
- The selection of subjects is equitable.
- The informed consent of subjects will be obtained and documented.
- Provision will be made for monitoring the data to protect subjects.
- The privacy and confidentiality of the subjects will be protected, as well as their rights and welfare.
IRB review processes are governed by Federal regulations which provide for both convened board and administrative review mechanisms. The IRB Chair makes the final determination for the level of review if a question arises and may upgrade the level of review if in the best interest of human subject protection.
Full Board (Convened) Review. Review by the convened board is required for all studies involving greater than minimal risk or which do not qualify for administrative review (See Exempt or Expedited , below). Examples include randomized studies, phase I, II, III and IV trials, studies using investigational drugs and/or devices, and some behavioral interventions.
The convened IRB usually meets twice a month (see IRB Calendar ). Unscheduled meetings may be called at the IRB Chair's discretion, and are subject to all standards of a routine IRB meeting, including requirements for a quorum.
Expedited Review. Studies involving no greater than minimal risk AND fitting one of nine specific categories (per applicable regulations) may be reviewed administratively by a single designated IRB member or a small review panel, as determined by institutional procedures. Examples include blood sampling by finger stick, heel stick, ear stick, or venipuncture from healthy individuals, collection of data through noninvasive procedures (not involving general anesthesia or sedation) routinely employed in clinical practice, and low risk behavioral research.
Exempt Certification. Studies involving minimal risk AND fitting one of four specific categories may be exempted from annual reporting requirements. However, the investigator must apply to the IRB for certification of exemption and review for compliance with other applicable institutional policies and procedures. Examples of Exempt research include research conducted in established or commonly accepted educational settings; the collection or study of existing data, documents, records, pathological specimens, or diagnostic specimens; collection of information where publicly available; information recorded by the investigator in such a manner that subjects cannot be identified, directly or through identifiers linked to the subjects.
Emergency Use of an Investigational Drug or Device. Under very limited circumstances, the U.S. Food and Drug Administration allows use of an investigational drug or device without IRB pre-approval for treatment of a patient. The use is not considered research, and no data from this use may be included in a research analysis. All the following conditions must be met, documented, and reported to the IRB (see Emergency Use Form):
- A life-threatening situation
- No standard acceptable treatment is available
- Insufficient time to obtain IRB approval
Review by the convened IRB results in one of the following decisions and is subsequently communicated to the Principal Investigator in writing:
- Approved: The protocol is approved as submitted. This decision may include stipulations limiting IRB approval.
- Conditionally Approved: Changes are specified that require only the concurrence of the principal investigator or non-substantive clarifications that, when met, will allow the release of IRB approval. Generally the IRB Chair is authorized by the IRB to review and approve the investigators' resolution of these problems. If more significant problems are identified, the IRB may stipulate how such issues will be resolved. If more significant problems are identified, the IRB may stipulate how such issues will be resolved. If the investigator does not accept such amendments, he/she must resubmit a justification to the full IRB for review and approval.
- Tabled: Significant outstanding issues were identified that cannot be resolved by IRB stipulations to the proposed research and must be resubmitted for further review.
- Disapproved: The research reviewed does not meet regulatory and/or institutional requirements for approval as submitted.
IRB Continuing Review
On-going review of approved studies is conducted by the IRB as the research progresses to monitor for safety and effectiveness. IRB approval is a temporary authority that may be withdrawn at any time if warranted by the conduct of the research. The following factors are reviewed as the study progresses:
- the accruing of safety and effectiveness data that may warrant revision to the protocol
- changes in key contact personnel
- changes in research regulations
- any unanticipated problems associated with the study which could include patient complaints, staffing issues, etc.
- new, pertinent information that needs to be assimilated into future protocol approvals
Continuing review is conducted by the convened board unless the specific report does not affect subject safety or falls within the minimal risk categories defined under Expedited review.
Renewal Requests. The IRB must re-evaluate approved research at intervals appropriate to the degree of risk. At initial review, the IRB determines the length of this approval period, not to exceed one year. Continuing approval is required as long as subjects are recruited or participating in the research or identifiable data are being analyzed.
Amendments. Any change to what has been IRB approved must be submitted for review and approval by the IRB PRIOR to implementation. Such changes include: revision, deletion, or addition to the protocol; modification to the recruitment or consent documents; changes in study personnel; change or addition of sponsor(s).
Adverse Events/Unanticipated Problems. At time of initial approval, the IRB provides the principal investigator with study specific guidance as to what safety information shall be reported, when, and to whom. The IRB review these reports and makes appropriate determinations regarding risks, potential benefits, the adequacy of the consent documents, the provision of updated information to subjects, and that safeguards are in place to protect human subjects, including subject privacy and the confidentiality of data.
IRB official files are retained for at least 3 years after completion of the research. Such records will be accessible for inspection by authorized representatives of the institution, federal agencies, and sponsors. Research Affairs maintains a computerized database profiling on-going research approved by the IRB in order to support the administrative activities of the research community. Official files include:
- Minutes of IRB meetings
- Copies of all research proposals reviewed
- Copies of all correspondence between the IRB and investigators
- List of IRB members
- Written procedures for the IRB