Pamela Shoup, CCRP
Past Executive Director, Toledo Community Oncology Program
Current Research Manager and IRB Coordinator for the Toledo Clinic, Inc. <\/p>\n\n\n\n
Abstract:<\/strong> A well-organized institutional review board (IRB) ensures excellent quality assurance in the regulatory area and enables the IRB to score an A+ on regulatory inspections conducted by the U.S. Food and Drug Administration (FDA). This article describes best practices in IRB management and tools to help prepare for an FDA audit. Lessons learned from experiences at the Toledo Community Oncology Program are highlighted. <\/em><\/p>\n\n\n\n\n\n\n\n The Toledo Community Oncology\nProgram was established in 1984. It had a central administrative office and was\nIRB of record for its central IRB and 19 affiliate sites. The IRB, which had\nextensive experience overseeing studies and was well organized, had 16 primary\nmembers and 16 alternate members. During monthly meetings, the IRB reviewed\nthree to five new studies, about 40 re-approvals that ranged from full-board review\nto expedited review, and about 20 study addendums and various other materials\nthat required IRB review. <\/p>\n\n\n\n To ensure a great audit, an excellent\nIRB coordinator is crucial to developing a well-organized IRB. The IRB\ncoordinator must have strong organizational skills and an eye for detail.\nHaving IRB experience is not enough. You may find that a well-organized IRB\ncoordinator may tend to be a little compulsive, and this is a good thing!<\/p>\n\n\n\n To ensure a good sound basis\nfor the IRB office, the IRB must know where to find the federal regulations and\nguidelines on oversight of clinical research, keep them handy, always staying informed\nof changes in regulations. There are several websites that provide this\ninformation, including those of the FDA and the Office for Human Research\nProtections. The IRB must implement the regulations through policies and\nprocedures, and members must be educated on the regulations, policies, and\nprocedures.<\/p>\n\n\n\n It is important that the IRB\ndoes not rubber stamp approvals on clinical research. Be sure that the IRB\nmembers are reviewing documents prior to a meeting and asking appropriate\nquestions at the meeting for discussion. IRB members must be dedicated to their\nresponsibilities and understand why they have been asked to serve on the IRB\nand the importance of the IRB function. Members must be willing to attend\nmeetings to meet the quorum requirements. <\/p>\n\n\n\n Documenting the IRB\u2019s members\nand work is necessary. Although the Toledo Community Oncology Program was completely\nelectronic, it was also helpful to have printed documents handy. This is\nespecially helpful for FDA inspections. The past IRB office maintained a tabbed\nbinder with a separate tab for each IRB member that included completed human\nprotections training, annual continuing education, and the member\u2019s credentials\nand CV. <\/p>\n\n\n\n All primary and alternate members\nwere listed in the front of the binder. This also served as a reminder to update\nthe list as necessary. An IRB roster is very helpful to IRB coordinators. The IRB\nroster should contain all of the information required for IRB registration with\nthe Office for Human Research Protections or another organization. During an\ninspection, the FDA will want to see the IRB roster, and it is important to\nkeep your roster up-to-date.<\/p>\n\n\n\n The federal regulations must\nbe used to develop IRB policies and procedures. The FDA regulations clearly\nstate what IRBs must do and are not difficult to understand. The policies describe\nhow the IRB will comply with the regulations. IRB members must receive adequate\ntraining about the regulations because most IRB members join the IRB with no\nexperience and little knowledge of the regulations and how IRBs function. <\/p>\n\n\n\n The IRB must be in compliance\nwith its own policies and procedures. For example, the Toledo Community\nOncology Program had a policy stating that local deviations for a particular\nclinical research study must be reported to the IRB within in 30 days. The FDA asked\nwhether the site had a policy on reporting to the IRB during their last\ninspection, and the Toledo Community Oncology Program was able to share the\npolicy with the investigator. All anticipated actions of the IRB should be\nclearly outlined in the IRB policies. Not complying with specific site IRB policies\ncould result in a deviation.<\/p>\n\n\n\n The purpose of FDA inspections\nis very simple – to ensure the protection of the human subjects participating\nin research. The FDA investigator visits an IRB to ensure that it is following\nthe regulations in order to protect human subjects. Table 1 provides an\noverview of the IRB\u2019s authority and functions. IRB members must know what the\nIRB can and cannot do. Often, IRBs tend to rubber stamp things because they are\nafraid to take the actions that they are authorized to take. <\/p>\n\n\n\n IRBs have the right to\nrequire a progress report from investigators. When the author served as a consultant\nand helped revamp an IRB, she found that the IRB was reviewing studies or\nre-approving studies without any update from the investigators. When the IRB\nrequested a progress report from an investigator, the response was that the investigator\ndid not have time to write the report. The author informed the IRB that it should\nsuspend the study because it could not possibly do the review if it did not\nknow what was happening with the study.<\/p>\n\n\n\n IRBs also have the authority\nto suspend or terminate the approval of a study and to place restrictions on a\nstudy. Although the regulations require re-approval within 365 days, if there\nis an issue with the study, the IRB can require re-approval sooner, for\nexample, in six months.<\/p>\n\n\n\n As per the regulations, the\nIRB must conduct an initial review of a study before subjects are enrolled and re-approve\nthe study within 365 days of the approval. The IRB must report findings and\nactions to the investigator in writing. The FDA will ask to see this during an\ninspection. Determining which studies require review more often than annually\nis a function of the IRB.<\/p>\n\n\n\n The IRB must ensure that\nchanges in the research are not initiated prior to IRB approval except where\nnecessary to eliminate apparent immediate hazards to subjects. Ensuring prompt\nreporting of unanticipated problems involving risks to subjects or others to\nthe IRB, appropriate institutional official, and the FDA is another IRB\nfunction. Research does not always show positive results, but it is necessary\nto protect future subjects by prompt reporting of unanticipated problems.<\/p>\n\n\n\n The FDA requires IRBs to have\nwritten procedures (Table 2). During an inspection, the investigator will ask\nthe IRB to demonstrate the way in which it meets the federal regulations. The\nIRB will need to show the investigator the processes that it uses for its\noperations, step by step. The processes can be adapted from other organizations\nas long as they enable the IRB to meet the regulations.<\/p>\n\n\n\n The FDA will want to see the\nIRB\u2019s recordkeeping requirements and the information provided to investigators\non its decisions. The IRB must use the communication method (e.g., email or\nletter) stated in its own policy. As a large consortium with about 70\ninvestigators, the Toledo Community Oncology Program emailed approvals to their\ninvestigators. During the last inspection, the FDA asked to see copies of the\nemail approvals. The investigator even asked to see approvals sent to the\ninvestigator on one study in a particular month.<\/p>\n\n\n\n Required written procedures\nalso include IRB procedures and guidelines, documents related to the studies\ngiven by investigators to the IRB, and documents related to studies sent by the\nIRB to investigators. IRBs must keep these documents and have them available\nduring an audit. For studies sponsored by a pharmaceutical company, this includes\ndocuments that the investigator sends to or receives from the pharmaceutical\ncompany. The Toledo Community Oncology Program belonged to a national research\nbase and was required to maintain all documentation from the research base. This\nenabled the IRB, for example, to show the FDA that a change to a study was made\nbecause the research base requested an addendum to the study.<\/p>\n\n\n\n When the author first joined\nthe IRB office at the Toledo Community Oncology Program, there were three file\ncabinets full of study documents. When she reviewed each study, the necessary\ndocuments were there; however, a more organized system was required and was implemented.\nThe author developed a cover sheet for each study where all actions are listed\nand marked off when completed. Actions include the dates of the IRB meeting, initial\nstudy review, re-approval, amendments, study suspension or closure, data safety\nmonitoring reports, and adverse events. <\/p>\n\n\n\n The cover sheet is also an\nappropriate place to make specific notes about the study, such as why a\ndeviation occurred. If the FDA inspects the IRB five years later, a cover sheet\nis helpful, as the IRB coordinator will not remember what happened on a\nparticular study, or the IRB may have a new coordinator. A cover sheet also\nenables the IRB coordinator and IRB members to quickly review all IRB actions on\nthat particular study. <\/p>\n\n\n\n It is impossible to have too\nmuch IRB documentation. The more the IRB documents, the better it protects itself.\nIRB documentation includes meeting minutes and materials. The Toledo Community\nOncology Program IRB maintained a file folder for each study and each IRB\nmeeting. IRB actions related to a particular study were kept in the study\u2019s\nfolder and the folder for the particular meeting where the action was taken.\nThe folder for the IRB meeting contained everything related to that meeting,\nincluding the minutes, agenda, and attendance. If continuing education was\noffered, this was included in the folder as well. Voting sheets and adverse\nevent reports were also part of the folder. Having a well-organized IRB office\nwith a detail-oriented IRB coordinator is the key to ensuring an A+ on an FDA\ninspection.<\/p>\n\n\n\n In terms of study oversight,\nthe IRB must be aware of changes to the protocol and to informed consent forms.\nThis requires having a process in place to receive those changes. The process\ndepends upon the type of studies conducted at the clinical research site and\nthe type of sponsor. Investigators at the Toledo Community Oncology Program\nreceived broadcast emails about national studies and emails from pharmaceutical\nsponsors.<\/p>\n\n\n\n The IRB must also have a\nprocess in place for notifications to physician investigators and clinical\nresearch coordinators, especially for anything that must be forwarded to them\nprior to IRB approvals, such as information on safety issues. The Toledo\nCommunity Oncology Program IRB developed an email notification system. The\nauthor knows, however, that many physicians do not have time to read emails. For\nthis reason, notifying the clinical research coordinator to inform or share the\ninformation with their physicians is helpful, and this action should be noted\nin the IRB\u2019s policies and procedures.<\/p>\n\n\n\n It is mandatory to have the current protocol and informed consent form in place at all times. The author has been to many audits where investigators or clinical research coordinators have displayed an old version of the protocol. This does not mean that they were not following the current protocol, only that they did not have the current version of the protocol available in the file. The FDA will want to see the process for maintaining the current protocol and the current informed consent form. The Toledo Community Oncology Program maintained all study documents on its website so that its clinical research sites and affiliate sites could access them. Whenever the IRB approved a new protocol or informed consent form, it was posted on the website as a just-in-time document.<\/p>\n\n\n\n Pamela Shoup, CCRPPast Executive Director, Toledo Community Oncology Program Current Research Manager and IRB Coordinator for the Toledo Clinic, Inc. Abstract: A well-organized institutional review board (IRB) ensures excellent quality assurance in the regulatory area and enables the IRB to score an A+ on regulatory inspections conducted by the U.S. Food and Drug Administration (FDA). … <\/p>\nThe Well-Organized IRB <\/strong><\/h2>\n\n\n\n
IRB Authority and Functions <\/strong><\/h2>\n\n\n\n
Written Procedures and Study Oversight<\/strong><\/h2>\n\n\n\n
Click here to read part 2<\/a><\/h3>\n","protected":false},"excerpt":{"rendered":"