Announcement: FDA Draft Guidance for Electronic Records and Signatures
By Brent Collinsworth
In June, the Food and Drug Administration released draft guidance concerning the Use of Electronic Records and Electronic Signatures in Clinical Investigations. This guidance is designed to help the researcher comply with the FDA’s regulations for use of electronic records (21 CFR 11). It clarifies, updates and expands recommendations in the 2003 FDA guidance document, Guidance for Industry Part 11, Electronic Records; Electronic Signatures. FDA guidance represents the agency’s current thinking on a particular topic. The new draft guidance covers such topics as:
- Proper strategies for consent validation
- Data storage and maintenance requirements for electronic records
- Guidelines for outsourcing electronic services, including using cloud computing services
- Use of mobile technology (e.g., smart phones, biosensors) and proper security and validation techniques
- Proper use of electronic signatures
The FDA is currently accepting comments on this draft guidance. If you want to post a comment, follow this link to Regulations.gov. The comment period is open through Monday, August 21, 2017.
Other Human Research Protection Program Committees & Units
By Kelly O’Berry
Most researchers know they need to get IRB approval for human subjects research, but there are several other committees and units in the UI Human Research Protection Program (HRPP) that review, approve and oversee this type of research. On May 1, 2017, The Human Subjects Office hosted a panel discussion for representatives from several other committees/units involved in the UI research enterprise. This article provides highlights from their presentations and additional information about these committees/units. Follow the hyperlink in each unit/committee sub-title below for more resources.
P&T conducts a safety review for all studies that involve investigational medications. This review is independent from the involvement of the
- Risks – P&T ensures that subjects are informed about risks from study participation. The P&T Subcommittee reviews the study protocol, Investigator’s Brochure (IB), the G-12 (P&T Application form) and the risk sections of the HawkIRB application and the Informed Consent Document.
- G-12 form – P&T makes sure the G-12 form is properly completed and available for healthcare providers who are not involved with the study. This form is only for medications that do not have FDA approval for marketing in the U.S or are being tested for a different dose, indication, or route of administration. The information collected in this form synthesizes information from the Investigational Drug Brochure. The G-12 form is automatically uploaded into the medical record for all enrolled subjects when the medication is ordered in EPIC.
P&T reviews applications in the order they are received. Approval time varies depending on the number of applications under review and the length of time it takes the PI to respond to questions. The subcommittee communicates directly with researchers about changes that need to be made in the HawkIRB application and/or Informed Consent Document. Researchers should communicate directly back to P&T when those changes have been made. Although P&T can access the HawkIRB application, they do not receive notification when it is routed back to the Human Subjects Office/IRB to continue the review.
P&T review occurs concurrent with the IRB review but P&T approval is required before the IRB can release the HawkIRB application.
The MRPC is charged to ensure that all research use of radioactive materials and ionizing radiation in or on humans complies with the currently accepted radiation protection practices and regulations and the conditions specified in the UI Radioactive Material License. Prior to submitting the HawkIRB application, researchers often need to consult with a physicist for assistance with calculating the radiation exposure for research subjects. There is a specific e-mail account set up for this (firstname.lastname@example.org).
Researchers conducting studies that include research-related diagnostic radiation procedures must use either the MRPC’s Diagnostic Long Form or Short Form. The short form may only be used for research-related routine diagnostic x-ray procedures with a total effective dose equivalent less than 100 mrem, and cannot be used if subjects are pregnant or younger than the age of majority. The MRPC’s Therapeutic Long Form is used for research studies involving therapeutic radiation. The MRPC application forms and an example of a completed diagnostic long form are available in the Radiation Safety section of the forms page of the Environmental Health and Safety Office web site. A link is also provided from the Human Subjects Office web site (search for MRPC). The MRPC application forms provide a template for the required radiation risk statement language that must be included in the Consent Document along with a required pregnancy testing statement for studies when women of child bearing potential (on set of menses to age 60) will be included as subjects exposed to research-related radiation.
It typically can take 1-3 weeks to receive approval for the research study from MRPC, but short form protocols can usually be reviewed more quickly. The committee can access materials in the HawkIRB application and the MRPC long or short forms should be attached in the Other Committee section of your HawkIRB file. Following its review, the MRPC will attach a letter of approval or a letter requesting revisions directly in your HawkIRB file. Researchers should communicate directly back to MRPC when those changes have been made. Although the MRPC can access the HawkIRB application, the MRPC does not receive notification when the protocol is routed back to the Human Subjects Office/IRB to continue the review.
MRPC review occurs concurrent with the IRB review but MRPC approval is required before the IRB can release the HawkIRB application.
The CRU operates under the Institute for Clinical and Translational Services (ICTS), which is one of 62 National Institutes of Health (NIH)-supported entities in the United States. They currently support over 300 active, NIH-, Industry-, and PI-initiated research studies of all phases. About half of these projects involve a drug intervention. The CRU reviews all protocols that plan to use CRU resources (which include the CRU and Clinical Research Coordination Core).
The CRU staff have combined research experience of over 200 years. They can take care of all aspects of a clinical trial and can even provide overnight staff or extended evening hours. Researchers can request a meeting with the CRU Nurse Manager to discuss the study prior to submitting an application to the CRU. It takes at least one week or more to obtain CRU approval, depending on the complexity of the study. The Protocol Review Oversight Committee meets weekly on Wednesdays to review and approve requests.
CRU review and approval is completely independent from the IRB review process and does not affect the timing of IRB approval and the release of the HawkIRB application.
HCCC is a National Cancer Institute (NCI)-designated comprehensive cancer center. The HCCC Protocol Review and Monitoring Committee (PRMC) reviews all cancer clinical trials. PRMC approval is required to access HCCC patients or resources.
The PRMC is made up of medical oncologists, surgeons, nurses and other staff. They meet twice a month (on the 2nd and 4th Tuesdays) to review the scientific merit and all study-related materials. Projects must be submitted one week prior to one of these two meetings but then there is typically a two business day turn around for the administrative review.
The HawkIRB application review can be conducted concurrent with PRMC review. However, the study will only be scheduled for review at an IRB meeting after the project receives final approval from PRMC.
Within the Joint Office for Compliance (JOC), the JOC Research Billing Compliance streamlines and centralizes the research billing process in an effort to protect the hospital and researchers from the consequences of billing errors. JOC Research Billing staff develop a research billing plan in advance, in conjunction with the IRB review and approval process. When the study begins enrolling subjects, the subjects’ charges are held in the UIHC billing system and JOC Research Billing staff direct the charges (to be paid by the study or the patient’s insurance) according to the approved research billing plan.
Additional information is available on the Research Billing Compliance page on The Point (the intranet site for UIHC employees). JOC Research Billing review and approval of the study can take 1-2 weeks or more, depending on the complexity of the project and the timeliness of the researchers’ responses to questions from JOC Research Billing staff as they develop the research billing plan.
The JOC Billing Compliance review occurs concurrent with the IRB review but the study will only be scheduled for review at an IRB meeting after the project receives final approval from JOC.
The NRC assures the protection of the rights and welfare of patients as well as nursing personnel. They review studies that involve:
- Patients or nursing staff as subjects
- Procedures that are beyond the scope of regular patient care or nursing activities on the unit
- The development of instruments or procedures
Researchers are encouraged to talk to the Nurse Manager of the unit before submitting the HawkIRB application, to confirm that you can conduct the research study procedures as planned.
The Nursing Research Committee meets twice a month. The submission deadline is the Friday ten days before a Wednesday meeting and their response is usually provided two days after the meeting. The reviewer may ask questions of the PI and/or study coordinator prior to the meeting where a study application is discussed. The HawkIRB application review is conducted concurrently with NRC review. However, NRC approval is required before the IRB can approve and release the application.
NRC review occurs concurrent with the IRB review but NRC approval is required before the IRB can release the HawkIRB application.
Additional HRPP Units and Committees
There are some additional HRPP units/committees involved with the review and approval or processing of research projects. A future IRB Connection Newsletter article will provide information about: Division of Sponsored Programs (DSP), Conflict of Interest in Research Committee (CIRC), Institutional Biosafety Committee (IBC) and the P&T Investigational Drug Service (IDS). We will also provide information about the mandate, purpose, regulatory basis and institutional policies related to the all components of the UI HRPP.
Risk Communication and Consent
By Patricia Katopol, PhD
Communicating research risks to subjects can be difficult. Risk Communication research provides understanding of the interplay between the messenger, the message, and the receiver and suggests best practices for communicating study risk when obtaining consent. Communicating risk is difficult because those receiving the message filter it through their individual reality and experience. They may not hear the risks, despite being told about them, or that they may think they will personally benefit from participation because that is what they want to believe. Alternatively, subjects may judge a situation to be riskier than it is because of negative beliefs about the health system.
The UI IRB suggests that for most studies, Informed Consent Documents should be written in plain language. Subjects cannot appreciate risk if they do not understand the language used in the form or by team members who obtain consent. Subjects, including parents consenting for their children, may have limited understanding of risk because they do not understand medical or technical terminology or, they may not unde
Subjects may also fail to appreciate risk if, due to its length, they do not read the entire document. Proposed changes to the Common Rule will require a consent form to present “concise and focused” information about the study, and what the subject may expect, at the beginning of the document. Considering these proposed changes, the HSO\IRB currently requires a consent summary for all new clinical trial submissions under review by the IRB-01, IRB-03, NCI CIRB, or any other external IRB. A consent summary template is available in the Informed Consent category on the HawkIRB attachments page. The HSO recommends that existing IRB-approved clinical trials consider creating and obtaining IRB approval for a consent summary.
Because the ability to understand and appreciate study risk is central to obtaining informed consent from subjects, it may be useful for researchers to develop effective ways to communicate risk, including:
- Make a plan – Research teams may improve communications with subjects about study-related risks by creating a plan identifying potential risks and deciding how best to communicate them during the consent process. For example, the plan may include scheduling more time for consenting subjects in higher risk studies. IRB review of the consent document will provide an additional perspective on how best to describe the risks in lay language. Consider whether your target population would benefit from a video or graphics to describe the study and/or the potential risks. Planning puts all those who obtain consent on the same page and provides consistency in communicating with subjects during the life of the study. Describe all of these plans for conducting the consent process in Section VII.D. 29 and/or VII.D.30 of the HawkIRB application.
- Engage the subject – Create a feedback loop by asking specific questions about the study and/or parts of the ICD to make sure that the subject has heard your message. Don’t just ask, “Do you understand everything?” or “Do you have any questions?” Quantify and define terms that communicate risk, such as ‘significant’ or ‘minor.’ Doing a ‘walk through’ of the consent process, preferably with someone from the same population as the study subjects, can help you determine if those who receive your message hear what you think you are telling them. You may want to incorporate the “teach back” method into the consent process and ask the subject to repeat the potential risks back to you.
- Consider the environment – Make sure that during the discussion of risk and study procedures, you and the prospective subject are physically comfortable. You might want to offer water or coffee. Have the consenting process take place in private so that the subject will feel at ease when asking questions.
- Use visual aids – When using pictures of people, it is helpful if they include people who look like subjects, that is, include minorities or images that portray working, disabled, or rural people, if they are in your target population. Design the visual aid so that it tells people about risks; not just smiling faces that have nothing to do with the study. You may also want to include information that people should know about the study, but may not think to ask, or know enough to ask. An infographic can be a particularly engaging and attractive way to visualize this information. If using technology or visual aids make sure they are set up in advance and ready for use during the consent process.
- Evaluate your communication – When recruiting ends, or at designated times during the study, evaluate your process and the results. If possible, ask subjects if they thought the study matched what they heard during the consenting process.
In all research, but especially in research that is greater than minimal risk, subjects need to know the risks involved in order to provide informed consent. By adapting best practices from risk communication, research teams can help subjects make a truly informed decision about whether to participate in the study.
IRB Advisor August: New Data Sharing Requirements for Publishing Clinical Trials
Sharing clinical trials data with other researchers and the public has become a popular topic in the world of research ethics. Recently, a case was uncovered that further supports the need to share data
The article, entitled Data Sharing Statements for Clinical Trials: A Requirement of the International Committee of Medical Journal Editors, discusses ICMJE’s belief that there is “an ethical obligation to responsibly share data generated by interventional clinical trials.” Beginning July 1, 2018, all manuscripts with clinical trial results submitted to an ICMJE journal must contain a data-sharing statement that addresses the following:
- Will individual de-identified participant data be shared?
- What data will be shared?
- Are related documents, such as a study protocol and statistical analysis plan, available?
- When, and for how long, will data become available?
- What access criteria data will be shared, and by whom?
These changes were not implemented just for data to be used by other researchers. This change will also maximize the utility of the data from clinical trials and allow everyone to learn from the results of a trial. The full article is available here.
Other articles in the August issue of IRB Advisor include:
- Assent Is Not Consent: Children in Clinical Trials Are Not Little Adults
- FDA’s Draft Guidance on eRecords Could Have Unintended Consequences
- Small IRB Revises Forms, Updates Policies and Procedures to Obtain FWA and Reach Next Level
- Gray Zone Remains Between Clinical Research and Quality Improvement Efforts
- Very Strict Clinical Trial Criteria Can Pose Ethical Problem
- Paper Calls for More Transparency of Industry-sponsored Clinical Trials
Current and Past Issues
There is a link to current and past issues of IRB Advisor on the Education and Training page of the Human Subjects Office web site. 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 (email@example.com) or call us at 319-335-6564.
Continuing Education Credits
Individual newsletter subscribers can receive 1.5 AMA PRA Category 1 Credits™ or 1.5 nursing contact hours for reading an issue and completing an online test. However, since this is an institution-level subscription, UI researchers must purchase access to an individual issue for $40, or purchase a full subscription, to receive CME/CE credits. Visit the AHC Media web site for information about subscription options.