From the Director
by Michele Countryman
Are you aware of the recent federal regulatory policy updates affecting the conduct of human subjects research? The federal government entities overseeing human subjects research have been busy. During the 2016 calendar year there have been ten, draft or final, policy updates issued from the three primary regulatory branches overseeing human subjects research. As a rule, draft guidance is generally open for public comment anywhere between 30-180 days. Once the public comment period closes, responses are reviewed and considered as part of the final rule making process. The comments and proposed guidance undergo a federal interagency review, review by the Office of Information & Regulatory Affairs (OIRA), and the President prior to the release of a final policy. Upon release, final policy guidance includes an “effective date” to allow for an adaptation period to adhere to the new policy.
Biomedical based researchers, IRBs, and Human Research Protection Program (HRPP) staff should be aware of these updates in order to assess potential impact to the conduct of individual human subjects research projects and the HRPP program as a whole. The University of Iowa HRPP, by means of the Human Subjects Office, is working to implement changes relative to the 2016 final policies. Federal and Institutional policies are the framework for all HRPP policies and procedures. University of Iowa HRPP policy updates are communicated to the research community via future IRB Connection issues, HSO website, HawkIRB, and email notifications so stay tuned.
Below is a list of those ten final and\or draft policies issued from the National Institutes of Health(NIH), the Office for Human Research Protections(OHRP), and the Food and Drug Administration(FDA).
The NIH has released three final policy updates directly affecting human subjects research. These are:
| September 16, 2016 | NIH Policy on the Dissemination of NIH-Funded Clinical Trial Information |
| September 16, 2016 | Policy on Good Clinical Practice Training for NIH Awardees in NIH-funded Clinical Trials |
| June 2, 2016 | Final NIH Policy on the use of Single Institutional Review Board for Multi-Site Research |
OHRP under the US Department of Health and Human Services (HHS) have jointly issued (draft and final) policy updates with both the NIH and the FDA. These are:
| August 2, 2016 | HHS and FDA, Institutional Review Board Written Procedures: Guidance for Institutions and Institutional Review Boards; Draft Guidance; Availability (PDF - 105KB) |
| June 21, 2016 | HHS, NIH, Final NIH Policy on the Use of a Single Institutional Review Board for Multi-Site Research (PDF - 124KB) |
Of note, the widely publicized “Notice of Proposed Rulemaking for the Federal Policy for the Protections of Human Subjects (NPRM)” issued by HHS in 2015 and closed for public comment on 1/6/16, is still under review on the federal level.
The FDA also issued a series of both final and draft guidance. These are:
If you have questions regarding how these policies affect your research, please contact the Human Subjects Office.
Ethical Principles in Research - Beneficence
by Brent Collinsworth
Ethical codes for the conduct of research put forth standards to promote truth, accountability, and the welfare of human research subjects. In the United States, the ethical standards in human subjects research are described in the Belmont Report.
Published in 1979, the Belmont Report specifies the difference between ‘research’ and ‘practice’ and also outlines the three primary ethical principles for activities that meet the definition of human subjects research. This article is part 2 of a three-part series discussing those ethical principles. Part 1, Respect for Persons, is available here. Part 2 will cover Beneficence and its application to research. Part 3, in December 2016, will conclude the series with a discussion of the ethical principle of Justice.
Part 2, Beneficence:
The ethical principle of Beneficence is focused on securing participant well-being in research. The principle of beneficence puts forth the ideas that researchers should purposefully do no harm, and should seek to maximize possible benefits and minimize possible harms in research. Applying beneficence to research means the researcher needs to ensure that all risks are identified and minimized, while maximizing the benefits of research to the individual and society. Strategies for maximizing benefits and reducing risks will vary based on the study design and procedures. This article is intended to assist the researcher with anticipating the risks subjects face from participating in the study, as well as identifying ways to increase the benefits to subjects and society as a whole.
Research Risks
Research participants always face some type of risk. There’s no such thing as a ‘no risk’ study. Keep in mind that there are different types of risk to subjects from participating in research, as we’ll discuss in this article. Most people think of physical harm or discomfort from a study procedure, but there are other risks subjects face, including:
- Psychological- Participation may cause the subject anxiety, sadness, or emotional distress. This occurs in many different types of research studies, not just behavioral research.
- Financial: Participants may incur costs associated with participation, such as travel, lodging, etc. Or a study may collect information that, if released, would negatively affect the subjects’ current or future employment or insurance premiums
- Social: A study may collect information that, if released, could negatively affect the subjects’ social standing or impact others’ perceptions of that person.
- Legal: The study could collect information about illegal behavior that, if released, could put the subject at risk for criminal or civil liability
- Physical- As mentioned earlier, participation in a study may cause pain, injury, or even discomfort in the subject. Even fatigue or eye strain can be a physical risk from long study visits or completing lengthy tests on a computer screen.
Subjects may face one or more of these types of risks when participating in research.
Minimizing Risks
For all possible risks, researchers should take steps to minimize them wherever possible. Of course, not all risks can be avoided or completely negated. Indeed, some risks are inherent to the purpose of the study (e.g., doing research on emotional or psychological trauma means researchers will ask subjects sensitive and possibly distressing questions). And some types of research risk may be completely unexpected (e.g., a stolen laptop with sensitive research data). In order to minimize possible harms to the participants, researchers will have to devise ways to anticipate and manage these risks. Here are some suggestions to minimize risk in research:
- If the research involves long interviews or questionnaires, give participants one or more breaks to reduce fatigue or eye strain.
- If there are financial, social, or legal risks to subjects’ information being made public, then use strong security data measures, including password-protected computers, encrypted folders, or even a laptop lock if the data will be traveling on a personal laptop.
- If the research involves asking sensitive questions that may provoke a negative response (for instance, asking about childhood abuse), then have a list of resources for psychological services to give to the participant.
- If the research in question involves blood draws or other invasive tests, researchers should have a plan if participants have any adverse reactions.
Maximizing Research Benefits
The ethical principle of Beneficence is not only concerned with reducing risks in research. Researchers should also make an effort to conduct to maximize potential benefits to subjects in their research. Researchers can do this in many different ways, but we’ll discuss two specifically: use of sound research design in research as well as a diverse subject pool.
One way to maximize benefits to subjects and others is by using sound research design. Poor scientific design affects the likelihood that a study will produce valid results, which means that participants were exposed to risk for no benefit at all. Conducting research that is soundly designed ensures that subject risk is justifiable in the context of research.
Having a diverse subject pool can also maximize the benefits of research. When research is conducted on a diverse group of people, benefits of research increase. For instance, pregnant women are often an underrepresented group in research, due to research investigator and sponsor fears about harms to the fetus. As a result, there are few studies designed to address health concerns of pregnant women, and health care and treatment decisions for pregnant women can be more difficult due to the lack of research. When research reflects the wide variety of people in the world, more people will benefit as a result.
When appropriate strategies are put in place to manage risk, researchers conduct both better and more ethical research.
Requiring Anonymous Qualitative Research: A Disservice to Investigators and Participants
by Patricia Katopol, PhD
Protecting participants’ personal information is vital in human subjects research. IRBs follow 45 CFR 46.111 (a7), Criteria for IRB Approval of Research, which states, “when appropriate, there are adequate provisions to protect the privacy of subjects and to maintain the confidentiality of data.” Appropriate situations for protecting participant information include studies with children or on culturally taboo activities; however, there are also situations in which the loss of participant identifiers may be inappropriate because it diminishes the research. This article seeks to illuminate some of the challenges that anonymity creates for researchers using qualitative methods and how to address them in the IRB application.
For many qualitative researchers, projects are dictated by the researcher’s personal beliefs. For example, black investigators may choose topics of interest to the black community such as finding healthy food in inner-city ‘food deserts.’ Researchers in organizational science may prefer to focus on non-management female workers rather than male managers. Research as a political act becomes less valuable if the data has to be whitewashed to such an extent that meaningful data, or the wishes of study participants, are omitted.
In addition to what investigators may believe are IRB requirements for protecting information, a discipline’s norms may restrain researchers from using identifiable information. In one instance, in investigators conducting research in a clothing company felt they could not use publically available images of clothes with the anonymized company’s logo. As the aesthetics of clothing design were important to the company, showing the clothes might have helped readers understand the company’s viewpoint. Investigators also believed that since they could not name the company, they could not show how it was situated in public discussions of work and management, “Customers, employees, politicians, and media commentators interested in Ethico [the company’s fictionalized name] can all speak to each other, but our room in the ethical debate built around the company has no doorway to the rest of the building.”
Participants in qualitative research should be able to tell their story the way they want to tell it, including sharing their names and other identifiable details. For example, groups with a history of being excluded from research attention may desire to provide identifiable information because previously the group was ignored or silenced. Research suggests that participants want to be recognized for their contribution and to feel connected to it by providing identifiable details. A participant who did not initially agree to the use of her real name, regretted that decision when the research was published, “I have one major regret that I can now express…Looking back I was very disappointed not to see Stephen's and my name in print. Even though my words were there, I felt as though I had somehow lost ownership of them and had betrayed Stephen's memory. … I know that you followed my original wishes but this was a great mistake on my part. [My family and friends] expected and wanted...our names too.”
Ideas about the privacy and accessibility of personal information are changing. Provided with gender, zip code, and birthdate, researchers were able to identify Governor Weld of Massachusetts – who had stated that personally identifiable information was safe in the state’s Group Insurance Commission database. The Electronic Frontier Foundation commented that, “de-anonymization results achieved by researchers [in the study above] seriously undermine traditional privacy assumptions. In particular, the binary distinction between ‘personally-identifiable information’ and ‘non-personally-identifiable information’ is increasingly difficult to sustain. Our intuition that certain information is ‘anonymous’ is often wrong.” Technology may make it increasingly difficult to state with authority that private information will remain private.
In Protecting Respondent Confidentiality in Qualitative Research, Karen Kaiser found weaknesses in what she labeled the ‘dominant approach’ to protecting subject privacy and data confidentiality in sociology research. Although the approach seeks confidentiality, it is still possible for the respondent to recognize his/her comments; researchers decide what and how to alter data that might identify participants; there is no standard process for discussing confidentiality with participants after data collection; and restrictions may preclude the researcher from using some of the collected data. The dominant approach to confidentiality also assumes that the meaning of the data is not compromised when details are changed to protect participants. This works well for biological samples, but not very well for descriptive responses from individual participants. How is the research changed when facts about participants are omitted altogether, such as whether a participant is black or gay? How is the research diminished when alteration or omission makes the data less valuable for potential audiences? Thus, one of the very reasons for using qualitative research - to obtain rich, thick data about individuals and organizations - may be undermined because of discipline norms or an investigator’s mistaken belief that IRB rules or federal regulations regarding confidentiality prohibit using identifiable data.
In the IRB application, investigators should provide details about the identifiable information to be obtained from participants, why they believe it is needed to properly present the research findings, and how the information will be used. Rationales for using identifiable information might include respecting participants’ wishes to provide a name or group affiliation, in dissemination of study findings, using the information to compare studies using similar populations or organizations, and placing the research in context.
If individuals will be identified, the investigator should make it clear in the consent form. If supported by the research goals, an optional agreement indicating that participants can choose whether they want to be identified or not should be included in the consent. This allows the IRB to see that participants have the option of providing identifiable information or not. Should the investigator want to identify an organization, permission should be obtained, via a Letter of Agreement, from a person in the organization with the authority to do so. The onus is on the researcher to determine who has authority to provide permission to use the organization’s name. The IRB can only review what is in the application. If, for meaning and value, the research requires identifiable data, the investigator should present a case for it in the application. Transparency is key.
Reportable Events
by Brent Collinsworth
Under University of Iowa IRB policy, there are five categories of events investigators may encounter in research that may qualify as a Reportable Event. Study investigators under IRB-01 or 02 (biomedical or socio-behavioral) are required to report any Reportable Events within ten working days of the occurrence of the event or the investigator being made aware of the event. This article is a brief overview of the nature of reportable events and how to fill out a Reportable Events Form (REF) in HawkIRB. This article will focus on requirements for IRB-01 and 02 researchers. Since there are additional criteria and reporting requirements, VA researchers are encouraged to read the section on reportable events in the VA Investigator Guide. External and commercial IRBs may have their own requirements for reportable events as well. For more information on Reportable Events, please plan to attend an IRB presentation on this topic in November.
Serious Adverse Drug Events
A serious adverse drug event occurring in a subject enrolled at the University of Iowa (UI) or Veterans Administration Health Care System (VAHCS) would be reportable. A serious adverse drug event would be any adverse experience associated with the use of a drug in a study that results in a serious outcome for the subject, such as:
- Death
- Life-threatening symptoms
- hospitalization (or extending existing hospitalization)
- A persistent disability/incapacity
- A congenital anomaly/birth defect
Any other medical events that jeopardize the subject and may require treatment to prevent one of the above outcomes would also qualify as a serious adverse drug event. These events may be expected during the course of the intervention or unexpected. Unexpected events would be any adverse drug experiences that are not consistent in frequency, specificity, or severity with the investigator brochure or risk information presented to the subjects and IRB.
Serious Adverse Device Effects
Serious adverse device effects that occurred in subjects enrolled by a UI or VAHCS investigator or team member or enrolled by a non-UI investigator at another site would also be reportable. Contrast this with serious adverse drug events, which are only reportable when they occur in subjects enrolled by UI Investigators or research team members. A serious adverse device effect is any serious adverse effect on health or safety or any life-threatening problem or death caused by, or associated with, a device being tested in a research study.
Receipt of New Information
Another reportable event would be any receipt of new information that may impact the willingness of subjects to participate or continue participation in the research study. This new information may be positive or negative. So it could make people want to enroll in the study or not want to stay enrolled. This information could come from the research team’s own interim analysis or from other studies about similar treatments.
Unanticipated Problems
The forth category of reportable event would be an unanticipated problem involving risks to subjects or others (UPIRTSO) which occurs in a subject enrolled by a UI investigator/research team member or that would impact subjects or conduct of the study at UI. According to guidance from the Office for Human Research Protections (OHRP), the event/problem during research would have to meet specific criteria to be called an unexpected event:
- It was not expected given the nature of the research, the study population, and the approved study procedures or protocol for the conduct of the study
- It suggests that the research places subjects or others at a greater risk of harm than was previously known or recognized
- It is either directly related to participation or there is a reasonable possibility that it was caused by the research procedures
This would include events like an unexpected breach of confidentiality or a subject complaint that indicates unexpected risks.
Finally, biomedical researchers should be aware of the FDA Guidance on reporting unanticipated problems to IRBs as well. This guidance also defines what adverse events may also be unanticipated problems.
Noncompliance
Lastly, any incidents of noncompliance with federal regulations would also be considered a reportable event. Noncompliance would be considered any failure to follow the federal regulations with respect to protection of human research subjects or failure to follow institutional research policies or the determinations of the IRB. This is more of an umbrella category that includes any incidents in which the study procedures were not conducted as approved by the IRB. For instance, if a subject was enrolled, even though they did not meet the study’s inclusion criteria, this would be an incident of noncompliance.
Other possible incidents of noncompliance may include, but are not limited to:
- Exceeding IRB-approved enrollment numbers without a Modification to the study
- Improperly consenting subjects (e.g., without having them sign a consent document or agree to participate)
- Changing study procedures without IRB approval (including failure to do procedures you reported to the IRB that you were doing)
- Conducting any research without IRB approval
Reportable Event Form (REF) in HawkIRB
When any of these events occur, regardless of the IRB of record, researchers report them via a HawkIRB Reportable Event Form (REF). This form is available in the Project Summary page of each study. Researchers can create a REF by clicking on the “Reportable Event Form” hyperlink in the Create Form menu on the main Project Summary page. Researchers can also create a REF by selecting the REFs tab in the top right of the study, which allows them to see all previous REFs that have been reported as well. Researchers can create and submit more than one Reportable Event Form at a time. And it is possible to submit a Reportable Event Form at the same time as a Modification or Continuing Review form. Researchers may need to submit a REF after reviewing information for the Continuing Review, or they might need to submit a Modification to alter study procedures to prevent the event from occurring again. In either case, the forms submitted alongside the REF would be reviewed concurrently.
Once a researcher opens a Reportable Event Form, they will need to specify which type of reportable event they believe it best fits. Since the criteria for each reportable event overlaps somewhat, it may seem to fit more than one category. In such cases, researchers should use their own judgment to decide what type it best fits. The IRB may also ask the PI to change this in the form if they believe it fits another type of event better. The PI will also need to answer some questions about the reportable event before submitting it to the IRB. When submitting a REF, describe the circumstances of the event in as much detail as you can, and add any pertinent attachments in the Attachments section. You may also need to describe how you plan to communicate this to the research subjects, as well as describe a corrective action plan to prevent the event from occurring in the future. As with other HawkIRB forms, HSO staff or an IRB Chair may return the REF to the research team to address questions or provide additional information.
More information about these types of reportable events, as well as the IRB review process for REFs, will be discussed further in the IRB presentation, “Reportable Events: REFining your Reporting,” on November 10, 2016 from 2-3 pm at HP Smith. Register now to ensure a seat!
IRB Advisor
EU Will Require More Clinical Trial Transparency — Will U.S. Be Next?
In 2017, researchers and sponsors of clinical trials with sites in the EU will be required to create lay summaries of study results and make the explanations available to participants. These actions appear to be following a trend that is also growing in North America: the importance of transparency in research.
Individuals involved in research want to know what they have contributed to research, and whether their contribution made a difference. Communicating research results to subjects is a way to thank them for their service, and can also help with participant retention. The push for more transparency in research has been growing recently, as more and more participants want to know how their engagement in research made a difference. In the United States, sponsors who have registered studies on ClinicalTrials.gov are required to return study summary results on the website. But there is no requirement to write these results in a language that the lay public could understand, something mandated in the EU’s requirements. The US Department of Health & Human Services’ SACHRP committee began to address this issue in 2013, calling on federal agencies to take steps to promote the return of results to subjects. The committee also requested the FDA to provide clear guidance to investigators and sponsors on how they can communicate results to subjects while avoiding promotion of their medical products. But time will tell whether the United States will follow the example of the EU and mandate their own lay reporting requirements.
[NOTE: The US Department of Health and Human Services recently issued a final rule that strives to make clinical trial summary results more accessible to all. The policy can be found here.]
Read the full article in the October issue of IRB Advisor. The October issue also includes articles about:
- The EU’s requirements for returning trial results and why and how to return trial results
- Olympic athletes and staff being enrolled in a study to monitor symptoms of Zika virus
- Direct, in-person IRB-to-researcher meetings and how they improve the review process
- Strategies to improve IRB office workflow
- Sex biases in research, and how they may be damaging in the long run
- The DEA rejecting a call to reclassify cannabis from its current status as a Schedule I drug
- Language creep: how a “Human Experiment” morphed into a “Clinical Trial”
What is IRB Advisor?
IRB Advisor 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. Each month the IRB Connection Newsletter features an article from the current issue of IRB Advisor.
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 faculty, staff and students and VA 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 (irb-outreach@uiowa.edu) 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.
