Updates from the Director
I am happy to inform you of several changes with the Human Subjects Office in this issue. They are:
- IRB Connection frequency
- New “other committee review” workflow basket
The IRB Connection will now be offered to our research community on a monthly basis. We hope you find our articles pertinent and relevant to the important work you do every day. I welcome your feedback to the IRB Connection. In fact, please share any topics you wish us to address or feel may be missing from the monthly newsletter.
The second change is the way the HSO processes IRB applications. As many of you know, the IRB conducts a parallel review of human subjects research projects as outlined here. This process remains unchanged; however, you will now see a more distinct delineation of these activities within the IRB application. There will now be a new workflow basket to identify when HSO\IRB review is complete or on hold because of a pending Human Research Protection Program committee approval. This basket simply coined “Other Committee Review” basket may appear within three different review points:
- For any studies requiring PRMC, CIRC, IBC, &/or JOC review, this review is required before IRB full board or chair review can occur. Therefore, the project will be routed back to the PI in a PI "other committee review" basket. You, as the PI, will have the ability to edit documents in the event one of these HRPP committees requires edits. Once these committees’ approvals are in place an automated notice will be sent to the PI, contacts, and delegates. The project can then be returned to the HSO\IRB for further processing.
- For any studies reviewed by IRB full convened board with required action as pending a HRPP committee approval (P&T, P&T IDS, MRPC, or NRC) only will now have the project routed back by the HSO in a "pending required action other committee review" basket. The meeting minutes will reflect IRB review is complete with a request to hold the application until the appropriate committee approval(s) is\are in place. The HawkIRB system will not allow the return of the project to the HSO until the applicable committee approval is in place. An automated notice will be sent once all applicable approvals are in place and the project can be returned to the HSO\IRB for further processing.
- Finally, upon IRB approval a formal notice will go out to the PI reflecting IRB approval has been granted. However if the study is an industry funded clinical trial, the automated notice will reflect the project cannot be released until the contract (CTO) has been fully executed by the Division of Sponsored Programs. Once the contract has been fully executed, the project can be automatically released.
Any questions regarding this new process can be directed to the HSO via email email@example.com or phone (319) 335-6564.
Sex Bias and Clinical Trial - An Ongoing Concern
Uneven participation of males and females in clinical trials is a persistent problem. Concern about the effects of pregnancy and hormones on subjects causes many researchers not to recruit females for their studies. When women are recruited, should more males sign up for the trial researchers may not take the extra effort to obtain female subjects. Even in animal testing, more male than female animals are used because females cost more as they require additional experiments to control for their cycles.
In accordance with the regulatory requirements for IRB approval (45 CFR 46.111(a)(3)) the HawkIRB New Project application asks for the planned distribution of males and females to be enrolled in a study and requires a gender break down in reports of actual enrollment in the Continuing Review form. The IRB uses this information to assess whether there is equitable selection of subjects and looks for a scientific basis for the study inclusion and exclusion criteria based on subject gender. If females are excluded from research, deliberately or by oversight, it becomes more difficult for the IRB to determine that the study satisfies the regulatory requirements for IRB approval.
The efforts of women’s groups, researchers, and politicians to increase the participation of women in National Institutes of Health (NIH)-funded clinical trials has resulted in their participation overtaking that of men. But upon closer examination, that increase is the result of studies of single-sex diseases such as uterine or cervical cancer. Despite the fact that disease and pain can present differently in women, the bias against using females in clinical trials continues so that fewer than a quarter of trial participants are women. And studies of diseases that affect more women than men, such as thyroid disease and multiple sclerosis, continue to be based on research using only male animals.
To address this absence of females in studies, NIH Revitalization Act of 1993, PL 103-43 was enacted in 1993. It requires the inclusion of women and minorities in NIH-funded clinical research unless it is inappropriate for the health of the subjects, the research purpose, or as the Director of NIH may designate. Note that the argument about added expense for using female subjects is directly addressed in the regulation, “the costs of such inclusion in the trial is not a permissible consideration in determining whether such inclusion is inappropriate.”
In addition to providing supplemental grants to support the use of female tissues and cell lines and to procure the more expensive female mice, NIH also began to create policies that require applications to show how they will balance male and female cells and animals in preclinical studies as being more inclusive, even at the preclinical stage, might reveal sex differences that could influence clinical studies. In an article in Nature, Janine Clayton, MD (Director, NIH Office of Research on Women's Health) and Francis Collins, MD, PhD (Director, NIH) wrote that the “inadequate inclusion of female cells and animals in experiments and inadequate analysis of data by sex may well contribute to the troubling rise of irreproducibility in preclinical biomedical research, which the NIH is now actively working to address.”
Within NIH, the Office of Research on Women’s Health (ORWH) is charged with ensuring that research “conducted and supported by the NIH adequately addresses issues regarding women’s health. ORWH stimulates and encourages basic and clinical research on the role of sex and gender in health and disease, and sets NIH research priorities in diseases, disorders, and conditions that primarily affect women.”
Recognizing the need to encourage and support women’s health research, ORWH developed the following strategic goals:
- Increase sex differences research in basic science studies.
- Incorporate findings of sex/gender differences in the design and application of new technologies, medical devices, and therapeutic drugs.
- Actualize personalized prevention, diagnostics, and therapeutics for girls and women.
- Create strategic alliances and partnerships to maximize the domestic and global impact of women’s health research.
- Develop and implement new communication and social networking technologies to increase understanding and appreciation of women’s health and wellness research.
- Employ innovative strategies to build a well-trained, diverse, and vigorous health research workforce.
Failure to consider the differences inherent in female biology can have serious consequences for women. Eight of ten drugs withdrawn from the market from 1997-2000 were removed because of their increased risk to women. The FDA required the dosage for women to be reduced when it learned that the sleep aid Ambien was not metabolized as quickly in women as in men, with the result that women might be impaired longer than men. In trials, males taking statins had a lower incidence of heart attack and stroke, but women taking statins didn’t avoid a first heart attack, nor did statins save women’s lives. This may be significant because statins are not without their side effects. As Dr. Rita Redberg, the editor of JAMA Internal Medicine, stated, “If you’re going to tell a healthy person to take a medicine every day for the rest of their life, you should have really good data that it’s going to make them better off.”
Investigators who are interested in designing research that includes more women may find the list of resources or the ORWH Toolkit, How to Engage, Recruit, and Retain Women in Clinical Research, to be helpful. ORWH’s Strategic Plan for Women’s Health Research may be found here.
When considering why including women in clinical trials is important, Jill Becker, a University of Michigan senior research scientist studying gender differences in addiction, stated, “One of the underlying assumptions has been that females are simply a variation on a theme, that it isn’t a fundamentally different mechanism, that if you’ve learned about the male you’ve learned enough to deal with both males and females. We’ve discovered that’s not always the case.”
The IRB Advisor Newsletter: An educational resource
Are you looking for one more resource to expand your knowledge about protecting human research subjects? IRB Advisor (published by AHC Media) is a monthly newsletter that contains articles about regulatory issues, informed consent, current events in human subjects protections as well as articles about IRB administrative and management issues. The UI IRB subscribes to this publication as a resource for UI faculty, staff and student researchers as well as for IRB members and Human Subjects Office staff.
There is a link to IRB Advisor on the Education and Training page of the Human Subjects Office web site to access current and past issues of IRB Advisor. This link provides automatic access to the newsletter from all computers with a University of Iowa IP address.
The University of Iowa username and password cannot be posted on the Human Subjects Office web site. UI researchers may contact the Human Subjects Office to request the username and password to access IRB Advisor from a personal computer. Contact us by e-mail (firstname.lastname@example.org) or call us at 319-335-6564.
Individual newsletter subscribers can receive CME/CE credits for reading the articles and completing an online test. However, this is an institution-level subscription. UI researchers may purchase access to an issue for $40 to receive 1.5 AMA PRA Category 1 Credits™ or 1.5 nursing contact hours or purchase a full subscription. See the AHC Media web site for information about subscription options.
Beginning this month, each issue of the IRB Connection newsletter will feature IRB Advisor articles that may be of interest for the UI research community. We hope you find the IRB Advisor articles to be useful and interesting. Happy reading!
This month's featured article: Top Medical Journals Propose Mandating Data Sharing
The International Committee of Medical Journal Editors have issued a bold proposal to researchers doing clinical trials: your data must be shared with the journal in order to be considered for publishing. The Committee, a working group of medical journal editors from prestigious journals like the New England Journal of Medicine and JAMA, is telling researchers that deidentified individual-patient data that is underlying the findings present in their manuscripts must be shared with the journal “no later than six months after publication.” If these proposals are adopted as proposed, researchers would have to acknowledge in their consent documents that their data could be used by future researchers.
The proposal is open for comments through April 18, 2016, at http://www.icmje.org/
Got a Minute to Talk About IRB Meeting Minutes?
For studies reviewed at an IRB full, convened board meeting and approved pending required actions, the Principal Investigator (and his/her HawkIRB delegates) need to know how to find and respond to the IRB meeting minutes.
Be aware, you will not receive immediate results after the IRB meeting. The results are only provided in written format within the HawkIRB application. The minutes must be approved by the IRB Chair before they are provided to the Principal Investigator. If your proposal was approved with no changes necessary, the IRB Chair will approve the study and minutes concurrently in HawkIRB.
Alternately, if IRB approval was granted at the meeting contingent on changes to the application, the IRB Chair will approve the IRB meeting minutes and you will be notified of these requirements. The minutes are attached to the HawkIRB form and the HawkIRB system automatically sends an email notice to the PI, his/her HawkIRB Delegates and the Contact Persons named on the research team. If you are the PI, you can follow the link in the email right to the meeting minutes. If you are a delegate, you will sign in to HawkIRB as the PI, then go into the workflow link for the study in question, on the workflow page is a “Click here to review the meeting minutes for this form.” Entering that link will take you right to the minutes.
As soon as they are approved you will receive an e-mail notice with a link to the meeting minutes. You can also find a link to the minutes on the study summary page in HawkIRB. Once minutes are approved, the IRB meeting date becomes a clickable link to the minutes of that IRB review. If the date field is not a hyperlink, then that means the minutes are not yet approved by the IRB Chair.
According to regulatory requirements, the IRB meeting minutes must include:
- the name of members present,
- the outcome of the vote,
- any required actions,
- specific regulatory references and
- a summary of the discussion of controverted issues discussed during the meeting
The required actions needed for final approval are listed in the center of the document. These required actions may include securing approvals from other review committees, or making changes to your HawkIRB application and/or documents. If your study was approved pending, each of the required actions will need to be completed in order for your study to be approved. Do not make changes outside of the stated required actions, or you risk the study being sent back for another full board review. Keep in mind that any changes to Microsoft Word documents should be made with tracked changes, and uploaded as a new version using the “Edit” link for the document. Do not delete or remove previous versions of any type of document. Follow the three-step Edit process to save the new version on top of the previous version
Typically, there is a two-week deadline for the response to the minutes. You are strongly encouraged to open the minutes and complete the required actions as soon as you receive the e-mail notice.
The IRB office will adjust ‘respond by’ date if your study will lapse IRB approval in less than two weeks. If you need more time to complete the required actions, please simply route the study back to HSO, indicate in workflow that you need more time to complete the required actions with a reason for the delay. Generally additional time will be granted if it is evident that the research team is making a good faith effort to comply with the requirements.
Once you have addressed the required actions, click the button at the bottom of the Workflow page to “Return Routing Slip the HSO.” The staff person reviewing your study may return the form if any required actions are not completed or addressed.
When required actions have been addressed the HawkIRB form will be routed to the IRB Chair. If the chair agrees the required actions are completed the study will be approved. However, if you were unable to complete one or more of the required actions, the full convened board will need to review your justification and/or your proposal for a different action to resolve IRB concerns.