Announcing: ClinicalTrials.gov Office Hours
Beginning May 2, 2018, the Human Subjects Office (HSO) will hold weekly ClinicalTrials.gov Office Hours. These one hour help sessions will be Wednesdays, 11:00 am-12:00 pm, in 101 Hardin Library for the Health Sciences (HLHS).
In an ongoing effort to assist clinical trial researchers with ClinicalTrials.gov concerns, the ClinicalTrials.gov Compliance and Education Program will be available for investigators seeking extra help with registration and results reporting on ClinicalTrials.gov. The University of Iowa Protocol Registration and Results System (PRS) Administrator(s) will be available to help investigators on a first come, first served basis.
Examples of help topics include:
- Understanding the PRS
- Registering a trial
- Evaluating whether a trial meets the reporting requirements for FDAAA, NIH and/or ICJME
- Results reporting
- Responding to PRS reviewer comments.
The ClinicalTrials.gov Office Hours are being offered in addition to the regular IRB Office Hours, which are held three times a week during the spring and fall semesters and once a week during the summer. Click here for the complete schedule of IRB Office Hours. Researchers who have specific questions or need assistance with ClinicalTrials.gov should attend the ClinicalTrials.gov Office Hours to receive assistance from the University of Iowa PRS Administrator(s).
More information on ClinicalTrials.gov can be found on our website.
Time is running out: Conflict of Interest Disclosures
By Martha Hedberg
The deadline is fast approaching to submit your annual disclosure in the eCOI system. All researchers who will be named as a study team member on an IRB application must have an updated financial interest disclosure on file in eCOI by April 30th.
To submit your annual disclosure, visit eCOI. You will need your Hawk ID and password to log in. If you have specific financial interests to disclose, be sure to have that information available. Also, keep in mind that the disclosure requirement for individual entities includes a “zero-dollar” threshold. This means that when you are engaged in activities with an outside entity, even if you are doing it free-of-charge, you must still disclose the activity.
In addition to annual reporting, you are also required to update your eCOI disclosure within 30 days of any changes in specific financial interests.
Researchers must comply with this reporting requirement in order to be added as a research team member in a HawkIRB application. For sponsored research, you must complete this annual disclosure to be added to an electronic routing form. eCOI disclosures are now tracked in the HRIS Compliances & Qualifications (CQ) System. (See “My Compliances” in Employee Self Service.) Failure to comply also means that your disclosure will be considered “noncompliant,” even if you complete it after the April 30 deadline.
Call the Conflict of Interest in Research Office if you have questions about your disclosure (353-3052 or 384-4256). For more information, visit the UI Conflict of Interest in Research University of Iowa Conflict of Interest in Research | Conflict of Interest in Research.
Revised Common Rule – Delay in the Effective DateOn April 19, 2018, the U.S. Department of Health and Human Services (HHS) announced a proposal to delay for an additional 6 months the general compliance date for the revisions to the Federal Policy for the Protection of Human Subjects (the “Revised Common Rule”). The revised regulations, initially scheduled to take effect on January 19, 2018, had already been delayed once, with a current effective date of July 19, 2018. Under the new proposal, the new effective date will be January 21, 2019. This extension provides additional time for the preparations necessary for institutions like the UI and other regulated entities to implement the 2018 Requirements.
You can read the full announcement on the Office of the Federal Register website.
Determining Capacity to Consent
by Patricia Katopol, PhD
Past mistreatment of subjects by the Nazis during WWII and in the Tuskegee study in the United States resulted in ethical guidelines such as the Nuremberg Code and the Belmont Report that require subjects to be informed of the study’s risks and benefits and provide voluntary consent before participating in research. Federal regulations (45 CFR 46) require the IRB to determine that the study includes additional safeguards to protect subjects who may be vulnerable to coercion, undue influence, and/or may lack capacity, including “mentally disabled persons” (this is the term used in 45 CFR 46.111(b)). This article provides guidance for researchers to assess subject capacity to make an informed decision about enrolling in a research study. Read more…
Often used interchangeably, capacity and competence actually have different meanings. In a medical context, capacity is a person’s ability to use information about their illness and proposed treatment options. Competence is a legal term and requires a judicial decision. Research team members do not determine competence; they determine capacity.
Subjects have capacity to consent for research when they have four decision-making abilities:
- Understanding – Does the person understand the information?
- Appreciation – Does the person appreciate the effects of a decision?
- Reasoning – Does the person have the ability to compare the risks and benefits?
- Choice - Does the person have the ability to express a choice that is consistent and stable over time?
For most potential subjects there is a presumption of the capacity to consent. The principle of Respect for Persons found in the Belmont Report requires respect for the autonomy of individuals, giving them the freedom to make decisions for themselves. Researchers do this by giving people a choice about whether to participate in the research and by giving them enough information to make an informed decision. The issue is whether the person is capable of self-determination. According to the Belmont Report, “The capacity for self-determination matures during an individual’s life, and some individuals lose this capacity wholly or in part because of illness, mental disability or circumstances that severely restrict liberty.” The PI must propose adequate protections for individuals with diminished autonomy.
Investigators should not automatically assume that those with psychiatric conditions or cognitive impairments lack the capacity to make informed decisions about enrolling in a research study. Even mildly demented patients may still have reasoning capacity. In addition, refusal to participate in a study for which the subject might benefit does not indicate that the person lacks capacity to consent. Perhaps they are making an informed decision based on the risks or the study conflicts with religious or ethical values.
Educated or otherwise very capable individuals may have limited capacity to consent when they are newly diagnosed with a serious medical condition, depressed, grieving, in an Emergency Department, or an inpatient in the hospital. Their feelings of shock, fear, or anxiety may interfere with making a decision about participating in research. However, they may have the capacity to provide consent at a different time or in a different setting. Prospective subjects in the Emergency Department or in the hospital may appear disoriented or confused. Noisy medical devices, the coming and going of staff, and the presence of other patients and their families can contribute to anxiety and make it difficult even for subjects with capacity to think clearly. Asking others to leave the room, closing the door, pulling a curtain around the patient, or otherwise reducing visual confusion or noise, and providing privacy may be helpful.
On the other hand, researchers should be cautious if it seems that the subject consents too quickly. This may happen when the subject has not truly considered the risks and benefits of their participation, or because they believe that they will benefit from treatments received during the study, even though they have been told otherwise. They may agree to participate out of a false sense of obligation or to please the PI, especially if the PI is also their physician. In accordance with OHRP guidance, the UI IRB recommends that if potential subjects are patients of the PI, it may be more appropriate to have another research team member obtain consent to avoid having subjects think they are obliged to participate.
Capacity to give consent is not always a permanent state. Subjects may be temporarily incapacitated, become incapacitated over the course of the study, or may be able to indicate agreement (assent) even if they cannot provide legally effective informed consent. Where a subject is unable to give consent at the outset, if they regain capacity, they should have the opportunity to choose whether to continue participation.
Assessing Capacity to Consent
Researchers may face one of two scenarios regarding subjects’ capacity to consent.
Unexpectedly Encounter Someone Who Cannot Consent For Self
The first scenario occurs when team members unexpectedly encounter a prospective subject who may not have capacity to consent. The team needs a way to assess or evaluate the individuals’ capability for self-determination. Even if this was not described in the HawkIRB application, the research team can then use the UI IRB’s Evaluation to Sign an Informed Consent Document for Research or another assessment tool, such as this one from UCLA. These are a one-page documents with a list of questions about the individual’s ability to understand that s/he is participating in research, what will happen during the study, and ability to explain one or two risks associated with the research study. If the PI works with a specific community for which capacity is an issue, such as the elderly, s/he can work with community advocates to develop a useful assessment tool. The UI IRB does not require the use of any specific tool.
Sometimes a subject will have capacity to consent, but may need some assistance with the study information. Investigators can use the following methods to help potential subjects make decisions about research participation that are in their own best interest:
- Create a simplified consent document or summary sheet
- Offer information sessions for the subject and family or friends
- Create videotapes, instructional materials, and models to explain the study
Expect to Enroll Individuals Who Cannot Consent for Themselves
In the second scenario, a study may anticipate encountering potential subjects who cannot consent for themselves. This may be the case at the outset or the researcher may expect enrolled subjects to lose capacity to consent during the study. For example, the aging or those with progressive disorders may have the capacity to consent when initially enrolled, but become decisionally impaired at some point during the study. The PI should propose a plan in the HawkIRB application to assess capacity to consent (such as the Evaluation to Sign Informed Consent tool described above) prior to enrollment or as needed throughout the study.
In some cases, the PI may decide to identify a legally authorized representative (LAR) at the beginning of the study in the event the subject becomes unable to make decisions. For cognitively impaired adults in Iowa, the LAR is chosen from a list of people with a relationship to the subject, which can include a designated proxy, a court-appointed guardian, or an adult sibling. The LAR is chosen from the first existing person on the list. The process for obtaining permission from an LAR for initial enrollment or ongoing participation must be described in the HawkIRB application.
If the research team expects to encounter people who lack the capacity to consent and does not plan to enroll them, Section VI of the HawkIRB application should describe the assessment of prospective subjects and state that those lacking capacity will be screened out.
Researchers should plan ahead for what they will do if they encounter a person who may lack capacity. Planning includes awareness of assessment tools and processes to determine capacity and to note them in the HawkIRB application. The application should also indicate the circumstances that prompt a capacity assessment, what tool or questions will be used, and when a Legally Authorized Representative will be chosen. PIs are advised that they are able to use the evaluation tool provided by the HSO, even if the study did not foresee the need and describe plans in the HawkIRB application to assess subject capacity to consent.
Data Use Agreements: You CAN Take it With You (with permission)
By: Kelly O’Berry
University of Iowa (UI) faculty, staff, student and trainee researchers might think they own their study data, but in fact, they do not. The UI owns all data collected from research conducted by individuals affiliated with the institution, whether the research was conducted on campus, off campus or outside the United States. You must get permission from your department, and you may need a Data Use Agreement (DUA), to take data with you when you leave the University or to share data with a researcher at another institution.
In February, the Human Subjects Office (HSO) and Division of Sponsored Programs (DSP) gave a joint presentation about DUAs, “Data Use Agreements: IRB and DSP Perspectives.” DUAs are contractual documents that outline the terms and conditions for the transfer of non-public data. They are used for incoming or outgoing data that have restrictions on their use. These restrictions can include:
- Limitations on the use of the data
- Obligations to safeguard the data
- Liability for harm arising from the use of the data
- Privacy rights associated with transfer of confidential or protected data
In the case of data collected in a human subjects research project, the restrictions on how the data will be used and stored are outlined in the HawkIRB application and subjects are informed about these restrictions in the Informed Consent Document. The Division of Sponsored Programs (DSP) reviews and negotiates and signs these agreements on behalf of the UI, in consultation with the Institutional Review Board (IRB) to ensure that data are used in accordance with the IRB approval. There is information about DUAs on the DSP website, including a detailed guidance document, a flowchart for deciding when a DUA is needed and a link to some DUA templates on the Federal Demonstration Partnership website. This is primarily for outgoing data. For incoming data, the other organization is responsible for determining whether a DUA should be executed prior to sharing.
It can take time to work out DUAs and other agreements that might be necessary, such as a Material Transfer Agreement (MTA). Researchers should contact DSP as soon as they know they want to share or take data from the UI. Initiate the request for data sharing/transfer via a Non-monetary Routing Form in the University of Iowa Research Information System (UIRIS). All agreements should be in place BEFORE sharing the data and/or BEFORE the researcher leaves the UI. In some cases, it may be necessary to incorporate plans for data sharing or transfer into the original contract or grant application.
Let’s look at a few case examples.
Case #1: Graduating PhD student taking data from dissertation project
First she needs to specify the data she will take and whether she needs subject identifiers (name, contact information, ID code linked to identifiers) or if she can remove identifying information and use the deidentified data. If no identifiers were collected/recorded, she would have anonymous data.
Then she needs approval from her department to take the data. This approval is typically granted by the faculty advisor or the Departmental Executive Officer (DEO).
Next she should contact DSP to see if she needs a DUA (firstname.lastname@example.org or 335-2123). Sharing would only be permitted if there are no restrictions on future use of data outlined in the Informed Consent Document and/or HawkIRB application. There could also be restrictions from a study sponsor, an outside party that provided data for the study or other policies, laws or regulations.
Case #2: Faculty member sharing data with collaborators at three other institutions
The first step is to specify what data will be shared. If the outside researcher does not need subject identifying information, they should be removed. If the data are coded, the researcher could assign different codes that are not linked to subject identifying information OR specify in the DUA that the outside researcher will not be provided with the link between the ID code and subject identifiers.
The next step is to submit the Non-monetary Routing Form in UIRIS. That initiates the process of determining whether a DUA is required. DSP will verify whether the sharing is allowed by the IRB, sponsor, and any applicable laws or regulations. The IRB will examine the following documents and sections of the HawkIRB application:
- Section X – Confidentiality Protections and Data Storage
- Section XII – Future Research
- Informed Consent Document
You can watch a recording of the February 26 DUA presentation in the IRB ICON Course for Researchers. You can only access this ICON course from the Education & Training page of the Human Subjects Office website. (You cannot enroll in this course from the ICON home page.) Log in with your UI HawkID and password and scroll down to the section called “Additional Topics.”
Human Subjects Office and Division of Sponsored Programs staff are available to assist you with having all of the necessary agreements in place to either share or take data from research conducted at the UI.
History of Human Research Protections: Research In the Early Modern Era
By Brent Collinsworth
Many major events and decisions over the past century have brought us to the state of modern human subjects protections; both great advancements and horrific tragedies. This first article of a 3-part series will discuss historic events prior to the 1940s.
Before World War II, there were very few regulatory requirements for human subjects research
In 1916, Walter Cannon, the famous physiologist and researcher, asked the American Medical Association (AMA) to mandate proper informed consent in research. The AMA refused, stating that trust in researchers and the research enterprise was superior to regulation, and that misconduct in research was not a systemic issue (New England Journal of Medicine). This left open the possibility for an individual researcher to cause serious harm to participants with little recourse. Guiseppe Sanarelli was one of those researchers.
Guiseppe Sanarelli was an Italian researcher working at the Pasteur Institute in Paris. In 1897, he found the cause of yellow fever, the bacillus icteroides bacteria. He injected five recent immigrants with this strain of bacteria without informing them or receiving proper informed consent. Three of these nonconsenting participants later died. Some doctors and clinicians called it a ridiculous experiment. But the Canadian physician and one of the founders of modern medicine, Sir William Osler, stated that, "to deliberately inject a poison of known high degree of virulence into a human being, unless you obtain that man's sanction, is not ridiculous, it is criminal." (Georgetown)
Immediately after World War II, information came out of a series of experiments that were so horrific, the western world began to discuss establishing formal ethical principles for research involving human subjects. During World War II, Nazi Germany conducted horrific experiments on thousands of concentration camp prisoners without their consent. Once the war was over, the doctors and soldiers involved in the experiments were prosecuted in the Nuremberg Doctor’s Trial, one of thirteen trials after the war. During the trial, the lawyers for the defense argued that the doctors and soldiers had followed common research practices at the time, citing studies in the United States, France, and other countries that had done highly risky research without consent. At some point, the prosecution realized that, to win the case, they had to come up with a standard establishing under which conditions risky research involving human subjects would be ethically permissible.
Over the course of a 4-day testimony and cross-examination, Andrew Ivy (the medical advisor to the Nuremberg prosecution) presented to the judges three principles for the ethical conduct of human subjects research. The judges further expanded these and finalized a list of 10 ethical standards for research Involving human participants. They then published the list of these principles as what we know today as the Nuremberg Code. The list of principles included an emphasis on research subjects understanding the experimental and voluntary nature of research, the protection of research subjects, and developing foundations of testing potentially risky treatments in animals before human studies.
After publication, the Nuremberg Code was not met with a wave of support around the world. No countries officially adopted it as a code for ethical research, and American researchers in particular only discussed it to condemn the Nazis at Nuremberg (Georgetown). However, over the years, it was influential in the creation of many human subjects research ethics standards. The US National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research used the Nuremberg Code as a jumping-off point when developing their document of foundational ethical principles of human subject research, The Belmont Report. However, the Commission would not come along for another 30 years, after some truly horrific research studies in the US entered the public eye. The next article in this series will discuss some of those research studies, like the Tuskegee Syphilis Study and the Tearoom Trade Study. We will also discuss the reaction to these studies and the creation of the National Research Act, the Belmont Report, and the Code of Federal Regulations for the Protections of Human Subjects.
Herky Hints: HawkIRB Workflow and You
By Brent Collinsworth
HawkIRB Workflow is the system that allows Human Subjects Office (HSO) staff, IRB members, and researchers to communicate back and forth about a form in HawkIRB. Any questions and requests for clarification will be sent to the investigator in HawkIRB through the Workflow system. The Workflow system is also used to track correspondence between the HSO, IRB, and the research team for posterity. We do this because the IRB is required to keep a record of all correspondence between the IRB and investigators (45 CFR 46.115(a)(3)).
When HSO staff or an IRB Chair sends a form back to a Principal Investigator (PI) in workflow, it will be in the PI’s Inbox. The PI, his/her HawkIRB delegates and all contact persons on the research team receive an email notification from HawkIRB. HawkIRB will also send these individuals reminder emails if the study is not returned in a timely manner.
Once you receive your study back in Workflow, it will show up in your inbox in bold. To look at the workflow for an application routed back to the research team, click on the “wkflw” hyperlink to the far right of the screen. When you reach the Workflow screen, you will see in the top left the title of your study, the IRB ID number, the type of the form this workflow is for (New Project Application, Modification, etc.), and an option to view or edit the form. Clicking on the “edit” link here will send you to the Project Index for the form. On the top right of the screen is important information about the Workflow system, how to navigate it, and what to do when you complete all actions and need to return the form to the HSO/IRB.
Below that are numbered correspondence items requesting additions, changes or clarification in the HawkIRB form. Typically, there is a link to the specific section of the HawkIRB form to make the change. Workflow items follow a similar format, shown in the example below:
Correspondence From: IRB Reviewer
Contact Email: email@example.com
1. In Section I.4, provide an overview of the study as you would describe it to someone who is not an expert in this field of research. This provides the IRB with a general description of the research project. This is a two-part question. Describe the purpose of the study -AND- a brief overview of the procedures involved. edit answer now
[ ] I have made the requested form changes
Enter any optional comments about your change(s) here:
Save answers to correspondence
Each workflow item is individually numbered, and if a form is sent back and forth to and from the PI and HSO/IRB multiple times, the numbers will proceed sequentially. On the workflow page there is a link to view previous workflow correspondence. Finally, at the bottom of the screen is an open text box for optional comments, as well as the link to “Return Routing Slip to the HSO” after you have made the requested changes.
Now that you understand how to look at the Workflow system, here are some helpful hints when working in Workflow:
- Make changes in response to questions in the HawkIRB form. It is not enough to provide additional information in the comment section in Workflow. The full study description must be in the HawkIRB application form. The “Edit answer now” link will send you directly to the HawkIRB question referenced in Workflow (Section I.1 in the example above).
- Address all items on the workflow form. If you skip workflow items or do not fully address them, the staff reviewer will send them again in another round of workflow. Your application will go through the review process more quickly if you address the questions the first time.
- Ask for clarification or assistance. All workflow comments have a review staff member’s email and phone number attached to the comment. If you have any questions or comments about the item in workflow, don’t hesitate to contact that staff member.
- Save all changes in the form. Once you have made the edits necessary, click on the “Back/Save,” “Index/Save,” or “Continue/Save” button on the top or bottom of the page in order to save the changes. Once you save the changes made to your application, you can click on the workflow shortcut link at the top right of your screen by your name to get back to the workflow item.
- Let the IRB know that you addressed each Workflow question. Verify that each item was addressed and then click on the “I have made the requested form changes” box by each Workflow item. The HawkIRB system will not let you send the form back to the HSO/IRB without checking this box.
- Limit changes to only address items in workflow, if possible. Additional changes beyond the ones requested by HSO staff or IRB members may delay the review. Of course, go ahead and make additional changes if there is an error in the description of study procedures or the procedures have changed since you submitted the application.
- Click the “Return Routing Slip to the HSO” button once you have addressed all Workflow questions. Once the HSO staff or IRB Chair sends your application back to you in workflow, review on your study stops until you route the application back to the HSO. Address the comments and return it as soon as possible to continue the review process.
Addressing requested changes in the Workflow system promptly and accurately is key to keep IRB review of your study moving forward. If you have any questions about specific workflow items, it is best to contact the HSO staff reviewer directly. If you have general questions about the HawkIRB forms, don’t hesitate to contact the Human Subjects Office at firstname.lastname@example.org or 319-335-6564. Additionally, we can answer questions in person at IRB Office Hours:
- Mondays 2-4 PM in S108 LC
- Wednesdays 2-4 PM in 101 HLHS
- Thursdays 10 AM – 12 PM in 101 HLHS
Beginning in June, IRB Office Hours will be once a month through the summer. Whatever your concerns, the Human Subjects Office is ready and willing to help.
IRB Advisor, April 2018: The Search for Justice in the Human Genome
By Brent Collinsworth
Modern researchers have made astounding strides in understanding the human genome and have developed a wide variety of new treatments that have the potential to usher in a new era of genome-based medicine. However, there are ethical issues entwined with these new advancements in medicine. Some of the drugs developed through genomic medicine are prohibitively expensive, which could lead to a massive rift in healthcare between the haves and the have-nots. Dr. Jenny Reardon, the founder of the Science and Justice Research Center at the University of California at Santa Cruz, wrote a book on this, entitled The Postgenomic Condition: Ethics, Justice, and Knowledge After the Genome. She compares it to the real estate bubble and lack of awareness that led into the Great Recession of 2008, stating “a lot of people are making a lot of money off of it, but on the other end of the spectrum it is really aggravating the inequalities in the healthcare system.”
Reardon wants the research community to frame this inequality of benefits in the context of the principle of justice. Justice, one of the three ethical principles outlined in the Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research, is often overshadowed by the principles of respect for persons and beneficence. Patricia King, a legal scholar who sat on the committee that wrote the Belmont Report, refers to justice in contemporary research culture as the “forgotten principle.” However, the principle of justice is quite relevant, especially in discussions like those surrounding genomic medicine. Those with health insurance that includes high deductibles may never see the benefits of the research. Additionally, some populations that may benefit from this medicine also bear the scars of unjust human experimentation. There is evidence to believe that African-Americans could benefit from treatments derived from CRISPR (a genome editing technology) to treat conditions such as sickle cell disease, but these populations may also be reluctant to participate in research, remembering all too well the horrors of studies like the Tuskegee Syphilis Experiment. It is up to researchers and society in the future to find a middle ground, advancing this new technology while still considering how to translate these advances to individuals without great wealth.
Other articles in the April issue of IRB Advisor include:
- “Respect Tribal Sovereignty in Indigenous Research”
- “Code of Ethics for IRBs Working With Indigenous Tribes”
- “Try These Strategies for Improving Review Consistency
- “Smart Checklists Keep IRB on Track With Study Reviews”
- “Preparation, Communication Key to Establishing IRB of Record”
- “Five Years in the Making, FDA Issues Final Rule on Data and Devices”
- “Into the Gray: Local IRBs Must Define Research”
Current and Past Issues
IRB Advisor (a publication of Relias) is a monthly newsletter with articles about issues facing IRBs and individuals involved with human subjects research. The University of Iowa subscribes to this publication as a resource to UI faculty, staff and student researchers as well as for IRB members and Human Subjects Office staff.
Current and past issues of IRB Advisor are posted in the “IRB ICON Course for Researchers” which is accessible to anyone with a UI HawkID and password. You must access this ICON Course from the Education and Training page of the Human Subjects Office web site. Due to our licensing agreement, we are no longer able to post a link to this publication on the Human Subjects Office website.