Update to Good Clinical Practice Training Certificates
By Kelly O’Berry, BS, CIP
Researchers who conduct, oversee or manage clinical trials funded by the National Institutes of Health (NIH) are required to complete training in Good Clinical Practice (GCP). NIH requires this training be completed every three years, although other sponsors may require more frequent training. The University of Iowa offers GCP training courses through the CITI Program. Links and information about this are available on the CITI page of the Human Subjects Office website and you will find specific information about GCP training in question #4.
The CITI Program recently updated the Certificate of Completion for the GCP training to reflect that the certification is good for three years. Anyone who completed this training prior to October 23, 2017 can now log in to CITI and print an updated certificate that has a three-year rather than a one-year expiration date. You may need to provide this updated certificate to NIH or another study sponsor.
For additional information, see the Frequently Asked Questions for Good Clinical Practice (GCP) Training or contact Joanie Neyens (Joanieemail@example.com).
Changes in Latitudes, Changes in Attitudes: The Mail-Out Consent Process
By Therese Barenz, BSN, CIP
Mailing (or e-mailing) the Informed Consent Document (ICD) to potential subjects provides flexibility in your consent process. In some cases, it may be the only option for obtaining and documenting informed consent. The downside is that it could increase the likelihood for errors in documenting consent. Investigators who use a mail-out consent process should expect that at least some subjects may return consent documents with errors that do not provide adequate documentation of consent – meaning aspects of their consent are not properly recorded or verified. This article will cover guidance and tools the Human Subjects Office (HSO) has developed to assist investigators when they choose to conduct the consent process by mail or email.
Inform the IRB
It is essential that you describe your plans to use a mail-out process in HawkIRB. Sections VII.D.29 (and VII.D.30 for parents/guardians of minors) allow you to describe the details of your consent process. Including a mail-out component requires you to provide the following additional details, as applicable:
Sending the ICD
Describe how and when potential subjects will receive a copy of the Informed Consent Document (ICD). This includes whether the investigator will mail/email the ICD to all or some potential subjects and, if so, how the subjects will return it - via postal mail or in person.
Essentials of emailing the ICD
If you choose to email the ICD to potential subjects, it is important to ensure that the IRB-approval stamp remains on the document when the subject opens and prints the document. The Human Subjects Office (HSO) recommends saving the IRB-approved ICD in portable document format (.pdf) when emailing it. To open files in .pdf format requires Adobe Acrobat–a software application that is free and readily available. You must remember to update the pdf version of the ICD each time the IRB approves a new version of the document in a Continuing Review form or a Modification form to change the ICD.
Since email is not considered a secure method of communication, the subject should not return the ICD via email. They should return it in person or via postal mail.
Contact With Subjects
In Sections VII.D.8-10, researchers indicate if they will discuss the study with the potential subject (in person or via phone) prior to consent. Subjects always need to be given the opportunity to ask questions before enrolling in research. With consent by mail or email, they may ask questions by phone, email or even in person. The response should describe the nature of the in-person or phone contact, if it will occur (e.g., who calls whom, what information is provided, etc). The researcher should always indicate that there could be phone contact with subjects if they provide a phone number for subjects to call with questions. You should also address this in the description of the consent process in Sections VII.D.29 (for adult subjects) and/or VII.D.30 (for minor subjects).
Minimize Coercion or Undue Influence
The last bullet of Sections VII.D.29 and VII.D.30 asks for the measures that researchers will take to minimize coercion and undue influence during the consent process with subjects. When a mail-out process is included, it is important to ensure the elements of consent are maintained in all applicable mailed materials.
- Emphasize the voluntary nature of participation
- Provide alternatives to participating in this research (offering standard treatments or other ways to earn extra credit)
- Allow them to discuss their participation with family and friends
- Explain they can withdraw at any time
- Explain they can skip questions on a survey and ensure the survey is designed to allow skipping questions
- Explain their participation will not influence their medical care.
- Ensure that subjects are aware of ways to contact the research team with questions
Corrections to the Signed ICD
When researchers use a mail-out consent process, you should anticipate that some subjects may return the consent document with missing signatures or dates, etc. The description of the consent process in Sections VII.D.29 and VII.30 must describe how researchers will make corrections to the signed document as outlined below.
Ensure Proper Documentation of Consent
Review the ICD
When an investigator receives a signed ICD by mail, s/he must review it for completeness and correctness, i.e., to ensure the signature/date fields and optional agreements are filled out with the correct information. If there are omissions or erroneous entries, the investigator must return a copy of the original document to the subject for the necessary corrections. The investigator should keep the original in case the subject does not return the ICD with corrections.
Cover Letter to Request Corrections
Researchers must have IRB approval for written communications to subjects, including a cover letter to ask them to make corrections to the signed ICD. To assist researchers with implementing corrective action plans, there is guidance and a sample Mail-out Correction Letter on the HSO website. This document is ‘watermarked’ so researchers don’t inadvertently use this document without IRB approval. This guidance and template document are also available in the drop down menu of the Miscellaneous Attachment section of the HawkIRB application.
The Mail-out Correction Letter contains multiple options that investigators can tailor to his/her specific situation. For example, when questionnaires or sample collection kits or ICDs are returned with unanswered questions or incomplete responses and it includes a generic section to correct errors that may not have been anticipated or were not addressed in other sections. If an investigator plans to utilize a mail out process from the onset of the study, s/he can submit the plan and the Mail-out Correction Letter with the New Project Application so the IRB can approve it prior to enrollment. Whereas, if an investigator adds the mail-out process later in the study, s/he will submit the plan and template correction letter via HawkIRB Modification form.
The Right Way to Make Corrections
If subjects need to correct an item in the ICD, researchers should instruct them to draw a single line through the erroneous entry, place their initials, and the current date next to the correction. Alternatively, if they omit the date of consent initially, the subject should enter the date they correct the consent, not the original date of consent. It is not appropriate to white out, scratch out, write over or erase a previous entry!
Document Corrected Consent
When the research team member receives the corrected ICD, they should document the following information either directly on the corrected ICD or in a separate Note to File in the research records:
- The date consent was originally obtained
- That there were erroneous entries/omissions
- The date the ICD was returned to the subject for corrections
- The date the corrected ICD was received
- The research team member/Person Who Obtained Consent (PWOC) should sign and date the note
Investigators should store the corrected version of the consent (with the original version) as described in the Section X.4 of the HawkIRB application
Mail-Out Consent Signature Block
Occasionally, investigators obtain signed consent without a designated consent discussion with individuals. This may occur in minimal risk research conducted in K-12 classrooms where the investigator sends a cover letter and the ICD home to the parents/guardians of students with instructions to call the investigator if they have questions. If the parents do not have questions and agree to have their child participate, they will sign the ICD and return it. This may also occur in studies where there has been continued interaction with a subject who was enrolled as a minor, and the investigator needs to obtain consent when the subject reaches the legal age to consent (18 years of age in Iowa).
The standard Informed Consent Document template (for teenagers and older) offers an optional template signature block for use in these types of studies (see below). This signature block is located in the Appendix at the very end of the ICD template in HawkIRB. Whenever there is a mail or email consent process, this entire signature block should be inserted below the subject signature block. This allows the researcher to indicate if consent was obtained with or without a verbal consent process. The researcher only signs the ICD if they discuss the details of the study and conduct the consent process verbally with the subject.
No Verbal Consent Process
If the investigator does not conduct a verbal consent process with the subject, the investigator should check the first box but does not sign or date the Signature of Person Who Obtained Consent line. That statement indicates that the research team member discussed the entire consent document with the subject and feels that the subject understands the study procedures, risks and benefits. The research team member could only sign that statement if they discussed the study with the subject prior to enrollment.
Verbal Consent Process
If a research team member conducts the consent process verbally with the potential subject by phone or in person (as in the K-12 example above), the investigator will check the second box, sign the Person Who Obtained Consent line, and include the date the Informed Consent Document was received by mail. **Please note this is different from when you obtain consent in person and you enter the date you verbally conducted the consent process.**
We hope the tools and guidance in this article will assist you with using a mail or email consent process. As always, if you have questions, contact the HSO at 319.335.6564 or firstname.lastname@example.org.
Exploring the Concept of Vulnerability
By Patricia Katopol, PhD
The National Bioethics Advisory Commission described vulnerability “as a condition, either intrinsic or situational, of some individuals that puts them at greater risk of being used in ethically inappropriate ways in research.” The federal regulations for the protection of human subjects include specific subparts regarding research with pregnant women and neonates, children, and prisoners. This article will explore other potentially vulnerable populations in human subjects research.
The federal regulations include several references to a more expansive and inclusive list of potentially vulnerable research subjects. All research studies must meet eight criteria to be approved by the IRB. One criteria for approval states that subject selection must be sensitive to not only children, prisoners and pregnant women but also to “mentally disabled persons or economically or educationally disadvantaged persons.” The final criteria for approval states that additional safeguards may be necessary to protect the rights and welfare of these subjects who are vulnerable to coercion or undue influence (45 CFR 46.111(b)). The following are a number of circumstances in which an individual may be vulnerable in the recruitment and consent process for human subjects research:
People who are homeless – Economic disadvantage, mental illness, and addiction are just some of the issues raised when recruiting people without shelter. If they lack access to medical care or are in need of funds to support an addiction, they may consent to participation without fully understanding the risks involved or may dismiss the risks because they need a place to stay and an income. From an article on recruiting homeless people for drug trials, “These guys have no job, no home, and a [illegal drug] habit. You have people at their lowest state, and they’ll say yes to anything.” This population is frequently used to test antipsychotic drugs – drugs with serious and sometimes permanent side effects, such as tardive dyskinesia. The HawkIRB application should clearly describe how research team members would protect the rights and welfare of subjects who might take risks that other potential subjects would avoid.
Recently released prisoners – Special protections for prisoners grew from the many abuses by researchers who used readily available incarcerated persons. The book, Acres of Skin, provides firsthand accounts from prisoner subjects themselves, many of whom suffered permanent scarring or serious physical injuries from their participation. Because of unethical investigator behavior, research including prisoners is now constrained by 45 CFR 46.301 Subpart C. Concern for prisoners should not end when they are discharged, however. Newly-released prisoners may be homeless and mentally ill, or may be addicted to drugs or alcohol. They are often educationally disadvantaged and functionally illiterate, with a need for easy to understand consent documents. The educationally disadvantaged remain vulnerable, even if the study is discussed with them, because they may lack the vocabulary to understand the discussion or feel too intimidated or embarrassed to ask for explanations. Compensation may be problematic because of limited access to financial institutions (to cash or deposit compensation checks) and high financial need, which can encourage subjects to remain in a study after they would prefer to leave. For more information on proper compensation, see the Human Subjects Office.
Supervisor / subordinate - Where power is exerted over another, the subordinate may be vulnerable to assuming risks that s/he normally would not accept. This power differential is present in relationships such as employer / employee, student / teacher, and superior / subordinate in the military (such as officers and enlisted personnel). At the University of Iowa, the IRB may permit enrollment of a subordinate or team member in a study that offers otherwise unavailable medical treatment. In this case, best practices suggest that someone other than the supervisor obtain consent, to avoid coercion. Students often want to please the instructor or may be concerned that their grade will suffer if they do not participate in the instructor’s study. The HSO website has more information about doing research with students as research subjects. Another power differential can exist between physician and patient, with the patient agreeing to participate to please the physician or not differentiating between treatment and research.
Situational Cognitive Vulnerability - This vulnerability can occur during illness or after an injury and is a temporary or emergency situation that negatively affects an otherwise capable subject’s ability to consent or appreciate study risks. An inability or diminished ability to communicate may also increase vulnerability, as subjects are unable to communicate concerns and their understanding of risk. For example, someone who comes to the Emergency Department after an accident and is in extreme pain, temporarily may be unable to comprehend a study’s risk or be focused enough to ask meaningful questions or express concerns.
Social Vulnerability - The entire research team should be aware of their personal biases about subjects of a different ethnicity, social standing, or educational level than the investigator. Researchers may unintentionally or unknowingly treat some individuals with less respect than subjects who are more like the investigator.
While it is good to protect the vulnerable, labeling groups as vulnerable and may stigmatize individuals. Some minority populations may be vulnerable, for example, but simply being a member of a racial or ethnic minority does not make an individual vulnerable. Labeling any group as ‘other’ can cause investigators to omit them from research if investigators find it too difficult or time consuming to include individuals from these populations in their research. In addition, vulnerable groups may not be ‘completely’ vulnerable or not vulnerable all of the time. For example, not every person over 65 is vulnerable due to age, but may be temporarily vulnerable when seriously ill.
Investigators should not exclude otherwise eligible homeless alcoholics or substance abusers simply because the investigator thinks they might use the compensation to fund their addictions. Such concerns are paternalistic and do not demonstrate the ethical principle of respect for persons as described in the Belmont Report. Concerns about the influence of compensation may be alleviated by using payment amounts large enough to incentivize someone to finish the study, but without a completion bonus that is so large subjects remain in a study when they should withdraw. The IRB cannot approve a completion bonus or withholding compensation until the end of the study as these payment schedules may be coercive. Many people with mental illness are capable of making decisions and evaluating risk. They should not be summarily excluded from research unrelated to mental health. Similarly, the existence of power differentials should not preclude people with less power from participation. For example, the Department of Defense permits subordinates to be recruited if superiors are not present and students can be consented by someone other than their teacher and their identities students not revealed until after grades are posted.
Vulnerable populations such as people who are homeless, those with mental illness, or with situational or social vulnerability, deserve protection during recruiting and consent. Their vulnerabilities, however, should not preclude them from contributing to research.
IRB Advisor November:
IRBs Could Address Ethical Issues Related to Tracking Devices
Around 12 percent of US consumers own some kind of smartwatch or fitness band. Around the world, use of wearable ECGs and other health devices is also increasing. These devices collect data in real time and can provide a wealth of information to the user. These wearable devices also provide researchers a unique opportunity; they can collect data points continuously from participants for a variety of purposes. The use of these devices also bring with them important ethical and regulatory questions, including issues related to:
- Data security. Since an independent company usually gathers the data, researchers would need to ensure that these companies have proper protections in place.
- Instant disclosure of research information to subjects. Clinical trials researchers usually discuss collected information with participants at discrete times and in controlled environments, and these wearables allow participants to see their data instantly.
- Incidental findings. Wearable devices may pick up findings about the subject’s health that are not directly related to the research question, so researchers must have a plan in place to address these incidental findings and take appropriate steps.
- Transmission of data. Researchers and biostatisticians must ensure that the gathered data is properly protected from hacking or incidental disclosure. They must also make sure that the data are not being altered during transmission.
It is not feasible for federal regulatory agencies to update the federal regulations rapidly to address new technology, but they have begun to release guidance documents interpreting the existing regulations in a new context to assist IRBs and researchers. For instance, the Food and Drug Administration (FDA) recently released guidance on Mobile Medical Applications and research.
You can read this article, “IRBs Could Address Ethical Issues Related to Tracking Devices,” in this month’s IRB Advisor. Other articles in the November issue of IRB Advisor include:
- Bypassing an IRB Review, Researchers Held Herpes Vaccine Trial on an Island
- IRB Collaborations With Tech Companies Could Mean What to the IRB?
- The Choice: A Decision to Decline a Clinical Trial
- HHS to Take Action to Protect Research Whistleblowers
- Brain Reanimation Investigator Reports Dramatic Results
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.