{"id":251,"date":"2020-01-24T22:19:49","date_gmt":"2020-01-24T22:19:49","guid":{"rendered":"https:\/\/www.socra.org\/blog\/?p=251"},"modified":"2020-02-13T21:57:39","modified_gmt":"2020-02-13T21:57:39","slug":"steps-to-ensure-an-a-on-your-irb-audit-part-2","status":"publish","type":"post","link":"https:\/\/www.socra.org\/blog\/steps-to-ensure-an-a-on-your-irb-audit-part-2\/","title":{"rendered":"Steps to Ensure an A+ on Your IRB Audit (Part 2)"},"content":{"rendered":"\n
\"medical<\/figure>\n\n\n\n

Click here to read part 1<\/a><\/h3>\n\n\n\n

IRB Audits and Inspections<\/strong><\/h2>\n\n\n\n

IRB audits can be conducted\nby federal agencies overseeing research such as the FDA or the Office for Human\nResearch Protections, research bases, study sponsors, and IRBs. Pharmaceutical sponsors\ndo routine monitoring of their studies at regular intervals. The Toledo\nCommunity Oncology Program\u2019s research bases only audited the program every\nthree years. This can make it difficult to know about mistakes made years\nearlier and to put quality assurance processes in place when needed.<\/p>\n\n\n\n\n\n\n\n

For this reason, the IRB is\nthe most important auditor of their own IRB. When the author first started to work\nwith IRBs, internal audits were not conducted. At that time, clinical research\nsites had fewer studies, and studies were less complex. In today\u2019s clinical\nresearch environment, it would be very difficult to pass an audit or inspection\nwithout an internal audit process. Oversight of studies is a tremendous\nresponsibility, and internal audits enable IRBs to identify mistakes, correct\nthem, and take actions to prevent the same mistake from re-occurring. <\/p>\n\n\n\n

Someone on the IRB, either the\nchair or another IRB member, should be part of the internal auditing process.\nAt a minimum, the results of internal IRB audits should be reported to the IRB\nevery month.<\/p>\n\n\n\n

A full circle audit starts\nwith the initial IRB approval and continues through informing investigators of\nany new addendum or investigator-driven adverse events (Table 3) occurring after\nIRB approval. This author utilized the same process that an FDA investigator utilized\nwhile auditing the Toledo Community Oncology Program and then developed the\nfull circle audit process in her IRB office. A full circle audit consists of\nreviewing documents from point A to point Z on one study. If a study was\napproved, ensure that physicians were notified; if physicians were notified,\ndocument how the notification took place; if there was notification of approval\nof a study, did it follow the IRB policy? This is a full-circle audit. Review\nof A should take you to review of B, and end up back at review of A. The author\nalso incorporated suggestions such as putting protocol version dates on agendas\nso that these could be compared to the investigator\u2019s brochure. The IRB will\nlearn lessons during an audit that will help it improve its processes and\nresults.<\/p>\n\n\n\n

Research bases and other\norganizations that are auditing the IRB are the best sources of information\nabout IRB audit guidelines. The North Central Cancer Treatment Group, one of the\nToledo Community Oncology Program\u2019s research bases, utilized a checklist during\naudits with a cover sheet to note IRB deficiencies and whether  they were considered as major or lesser\ndeviations. The IRB at the Toledo Community Oncology Program reviewed these\naudit guidelines for each of its research bases, utilizing them for its own internal\naudits. This allowed the IRB to be audit-ready at all times, following the same\nprocess for auditing as their research base.<\/p>\n\n\n\n

FDA Inspections<\/strong><\/h2>\n\n\n\n

FDA inspections of IRBs\nensure the protection of the rights, welfare, and safety of human subjects and\nthe quality and integrity of the data submitted to the agency. Inspections are\nnot designed to make life difficult for clinical research professionals or IRB\noffices. They can serve as an education tool, which clinical research\nprofessionals and IRB\u2019s can utilize and find useful.  <\/p>\n\n\n\n

The FDA can conduct the\ninspection at clinical research sites or at central administrative offices such\nas the Toledo Community Oncology Program. The FDA can also visit clinical\ninvestigators at hospitals, and study sponsors. The agency provides advance\nnotice of where it will visit.<\/p>\n\n\n\n

The use of the word \u201cshould\u201d\nin the federal regulations means that something is suggested or recommended,\nbut not required. The author believes, however, that when the FDA says,\n\u201cshould,\u201d clinical research professionals or IRB offices should definitely follow\nthat suggestion or recommendation. The FDA is strongly suggesting or recommending\nthe action for a reason, and it is likely to become mandatory in a few years. For\nexample, the FDA states that the IRB members should not<\/em> all be the same gender. While the agency will not issue\na deviation for having an IRB with members of only one gender, it is in the\nIRB\u2019s best interest not to have a only one gender participating on the committee.<\/p>\n\n\n\n

There are two types of FDA\ninspections: surveillance and directed (Table 4). Surveillance inspections are usually\nregular inspections done every five years. Directed inspections are conducted\nwhen there is a reason for the FDA to inspect an IRB. The FDA will contact the\nIRB and issue a notice of inspection. When the investigator arrives, the IRB\ncoordinator should ask for his\/her credentials. Not doing this is a red flag\nfor the investigator, as it indicates that the IRB may show its files to anyone\nwithout asking for appropriate credentials. The inspection will include interviews\nwith key individuals and should definitely include the IRB coordinator and the\nIRB chair if he\/she is available.  <\/p>\n\n\n\n

One of the author\u2019s first\nexperiences with the FDA turned out to be a great experience. The FDA investigator\nwas new to cancer research, and it was a productive learning experience, not\nonly for the IRB Coordinator, but for the investigator as well.  <\/p>\n\n\n\n

During an IRB inspection, the\nFDA investigator evaluates the IRB\u2019s performance by reviewing its records,\nwhich must be in place. The IRB\u2019s processes are important. The records must\nshow that the IRB implemented the federal regulations in policies and\nprocedures and reviewed these regularly. The Toledo Community Oncology Program\u2019s\nIRB had a sub-committee that reviewed its policies and procedures every year to\nensure that they were up-to-date. The FDA investigator will also want to see\nthe IRB\u2019s roster. Rosters should be kept up-to-date at all times, and past\nrosters should be filed for review by an investigator.  <\/p>\n\n\n\n

An FDA inspection of an IRB can\ncreate anxiety. If, however, the IRB has been actively performing internal\naudits and is prepared for the FDA, there will be far less anxiety. The IRB\ncoordinator must develop a process to ensure that the office is prepared for all\naudits and be able to show an investigator the necessary IRB documents. The\nauthor had two days\u2019 notice for her first FDA inspection. The investigator\nprovided a list of what he wanted to see, and the author and her team were able\nto prepare and were audit ready.<\/p>\n\n\n\n

Most Common IRB Deficiencies and Notes of Caution<\/strong><\/h2>\n\n\n\n

Table 5 highlights the most common\nIRB deficiencies noted during FDA inspections. Inadequate initial and\ncontinuing review is the most common deficiency. The IRB completes an initial\nreview; however, a subject is enrolled before the IRB has approved the study.\nSubjects cannot be enrolled until the IRB provides its final approval for the\nstudy. Inadequate standard operating procedures and membership rosters are also\ncommon problems. The federal regulations clearly outline the necessary\nrequirements of an IRB.<\/p>\n\n\n\n

Inadequate meeting minutes are\na common deficiency found in FDA inspections of IRBs. The meeting minutes from\nthe Toledo Community Oncology Program\u2019s IRB were routinely about 10 pages long.\nMinutes must include everything that the IRB discussed at a meeting, showing\nactions, voting process, and final actions\/requests by IRB.<\/p>\n\n\n\n

If the organization\nestablishes an IRB whose members take their responsibilities seriously, having\na quorum at meetings should never be an issue. Quorum issues, however, are a\ncommon deficiency found in FDA inspections of IRBs. If an IRB member routinely cannot\nmake meetings, the IRB chair must talk to the member about stepping down. <\/p>\n\n\n\n

The Toledo Community Oncology\nProgram\u2019s IRB met monthly and never had a quorum issue. The IRB members took\ntheir responsibilities very seriously. Having a dedicated IRB committee, who are\nable to meet quorum, reflects on the efficiency of the IRB as a whole. <\/p>\n\n\n\n

Inadequate communication with\nthe investigator or the institution is another common deficiency found in FDA\ninspections of IRBs. The FDA wants proof of IRB discussions, requests from\/to\nthe investigator and institution, and notification and discussions regarding\napprovals\/disapprovals.  <\/p>\n\n\n\n

Notes of caution include use\nof central IRBs. In 2014, the Toledo Community Oncology Program was mandated to\nstart using a central IRB. The program used a central IRB for all new studies and\nutilized a local IRB for historical studies and industry trials. <\/p>\n\n\n\n

The author gave out a major\ndeviation to a clinical research site that did not have a study re-approved within\n365 days of the initial approval. This particular study had a central IRB as\nIRB of record, but a re-approval was not received in the appropriate time\nframe. The site felt responsibility for the deviation should fall to the\ncentral IRB; however, the responsibility always falls back to the institution\nand investigator. The author strongly recommends a 10-month re-approval period\nto ensure that a study is re-approved on time.<\/p>\n\n\n\n

Assistants can be a great\nresource for an IRB office. However, the IRB coordinator must be the\ncoordinator in charge of the office, overseeing all processes. An IRB\ncoordinator should never solely rely on the assistant to complete a task. When\nthe FDA investigator arrives, the IRB coordinator, not the assistant, will be\ninvolved in the inspection and responsible for all actions.<\/p>\n\n\n\n

An IRB Coordinator should\nensure that documents are reviewed by IRB members, safeguarding that items are\nnot being \u201crubber-stamped\u201d for approval without first being reviewed. Having a\nprimary review system can ensure that IRB agenda items are being carefully\nreviewed by an IRB member and that all items have been completed as\nneeded.  <\/p>\n\n\n\n

Tunnel vision and lack of new\nprocesses can be detrimental to your IRB procedures. The IRB must continually\nmove forward and improve its processes. It cannot rely on old policies or the\nway things have always been done. The IRB must also make changes necessary to\ncomply with new or revised federal regulations.<\/p>\n\n\n\n

Lessons Learned<\/strong><\/h2>\n\n\n\n

As IRB coordinator at the Toledo\nCommunity Oncology Program, the author learned several lessons, including the\nneed to ensure that appropriate processes are in place. Without solid processes,\nit will be very difficult to manage an IRB office. The IRB coordinator can use\nthe processes developed by a previous IRB coordinator, but he\/she should always\nidentify and implement improved <\/em>processes.<\/p>\n\n\n\n

Following the federal\nregulations and the organization\u2019s processes is crucial. If the IRB does not follow\nthe regulations and its own processes, it will not pass an inspection. Internal\naudits must be \u201cclean.\u201d<\/p>\n\n\n\n

Continued education on IRB\nmatters is crucial. This is necessary in order to keep IRB members updated on changes\nto regulations. Be sure to document completion of education by your IRB\nmembers, obtaining appropriate certificates when possible. Utilize IRB meetings\nas an avenue for your IRB chair to provide education. Education stimulates more\ninterest in serving on the IRB and illustrates how to be a responsible IRB\nmember. <\/p>\n\n\n\n

The IRB should never cram for an FDA inspection. If the correct processes are in place as outlined in the FDA regulations, and if the IRB has an internal auditing program, the IRB will always be ready for an FDA inspection.<\/p>\n\n\n\n

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TABLE 1<\/strong>
IRB Authority and Functions<\/strong><\/h3>\n\n\n\n