IRB Issues and PI Responsibilities and Conflict of Interest
Stacey Berg, MD, Texas Children’s Cancer Center, Texas Children’s Hospital, Baylor College of Medicine, Houston, Texas, USA
Authored by Alexander Bagley
Dr. Berg’s lecture ‘PI Role and Conflict of Interest’ discussed two important topics that are directly relevant to clinical investigators: the institutional review board (IRB) and conflicts of interest (COI). As Dr. Berg explained, the IRB is responsible for reviewing proposed research protocols and informed consent documents before ultimately deciding whether to approve, require modifications, or disapprove of the research proposal. She explained that for proposals involving multiple sites, a single IRB of record is now required. After defining research and human subjects, she reviewed the criteria for IRB approval, which mandate that “risks to subjects are minimized, risks to subjects are reasonable relative to benefits, selection of subjects is equitable, informed consent will be sought [and] documented, provisions [are] made for data and safety monitoring, provisions [are] made to protect confidentiality, [and] safeguards [are] in place for vulnerable subjects.” She reviewed the essential elements of an informed consent document (ICD), which must also be reviewed and approved by the IRB; particularly helpful here was the discussion of broad consent, which allows for the “storage, maintenance, and secondary research use of identifiable private information or identifiable biospecimens” and how this relates to secondary research for which more limited IRB review is required. Dr. Berg advised that by developing protocols that have a sound scientific foundation and statistical design, most of the IRB concerns can be anticipated and addressed in advance.
Dr. Berg then transitioned to a discussion of investigator conflicts of interest, a relevant topic for oncology investigators given the significant and growing role of industry-academic collaborations in the development of new therapies. She reviewed the NIH definition of a significant financial interest as “anything of monetary value, except […] salary, royalties, etc. received from the institution; income from lectures, advisory panels, etc. for government or academic entities; equity in publicly traded entity ≤ $5,000; or other payments ≤ $5,000” and explained that these would represent conflicts if these could directly and significantly affect the research. These definitions were contrasted with the FDA’s definition of financial interests. She highlighted that other sources including foreign financial or research support, positions or scientific appointments, or any significant research activities performed outside the United States must be reported. She then reviewed online resources including the CMS Open Payments database to identify financial COI. Dr. Berg concluded her lecture with a helpful discussion of the research COI committees, which are tasked with ensuring that bias in the design, conduct, and reporting of research is minimized; she reviewed typical management strategies including “public disclosures; monitoring by independent reviewers; modification of the research plan; disqualification from participation; and divestiture/severance of relationships” that apply for the life of the award and any time the grant is cited.
This lecture addressed two important concepts for clinical investigators in oncology. Having a clearer understanding of the role and concerns of the IRB ultimately helps investigators design better protocols that maximize clinical knowledge gained and minimize potential patient harm. Similarly, having an awareness for COI definitions and procedures will help investigators design and report research that minimizes biases while continuing to foster collaborations between academia and industry. Given the intricacies and complexities of each of these topics, Dr. Berg’s final advice (“When in doubt, ask for help”) rings especially true for younger investigators in the process of launching their careers.
Authored by Preetesh Jain
I had an opportunity to listen to Dr Berg’s excellent talk on understanding the basics of IRB, process, responsibilities of a principal investigator for running a clinical trial, conflict of interest, design, and conducting the trial in an appropriate manner. This was an excellent talk, which provided me a great learning experience on the basics of designing and running a clinical trial and the responsibilities which come with it.
During the presentation, Dr Berg spoke about the budgetary aspects, health care spending, and restrictions on NIH budget. This was a revelation for me and provided me a deep insight on how the budget process works behind everything we do for our patients in the clinical trial.
In addition, obtaining informed consent, which otherwise would seem to be a simple process, was discussed in detail by Dr Berg. This presentation provided me a deep learning on how the consent process works and the dos and don’ts for taking care of our patients and at the same time being very meticulous in obtaining informed consent. I really liked the way she explained the informed consent process and risks involved, precautions required, additional costs involved, sample collection consent, disclosures, and the circumstances for termination of participation. I was not deeply aware of the impact of these aspects while planning various clinical trials, and this presentation provided me a great amount of information on these aspects. These additional elements were very informative. Another novel aspect on informed consent was the disclosures in genomic sequencing results and profiling from the bio specimens obtained from the patient.
Dr Berg also talked about the responsibilities of an investigator, and I learnt about the protection of rights, safety, and welfare of subjects. There were highlights on responsibilities of an investigator for data analysis, reporting of results, and obtaining the IRB approval, which really requires a lot of work and input from various teams. IRB approval opens up a whole lot of process and communications with various teams. It is helpful to know the multistep approach for IRB approval in order to be successful in conducting clinical trials in oncology. Since academic oncology and translational research is exploding in various cancers, management of clinical trial proposals with the IRB is a pivotal step.
I believe that this presentation provided me a lot of insight on finer aspects of the informed consent process, conflicts of interest, and the responsibilities of a principal investigator for ethical conduct of clinical trials in academic oncology.
Authored by Sushma Jonna
Dr. Stacy Berg described the role of the principle investigator (PI) and also reviewed issues related to conflict of interest.
She began by broadly discussing the responsibilities of the investigator. These include obtaining IRB approval for research involving human subjects and conducting the investigation according to the IRB-approved protocol. In addition, the investigator must ensure that the trial follows federal, state, and institutional regulations. The PI must also protect the rights, safety, and welfare of subjects. Finally, the PI will oversee the analysis of data and reporting of the results.
The responsibilities of the IRB are to review, modify, and approve research protocols. In addition, the IRB reviews the informed consent. Some key criteria for IRB approval of research include minimal risks to subjects, documentation of informed consent, and adequate provisions for data and safety monitoring. There are additional safeguards in place for vulnerable subjects.
Dr. Berg then reviewed the basic elements of an informed consent. Adequate consent describes the research, the procedures involved, the benefits and risks of treatment, and the subject’s right to withdraw from treatment. Dr. Berg specifically noted that it needs to be clear whether information and specimens can be deidentified and shared. In clinical practice, it is also important to share contact information for reference in case patients have any questions about the informed consent. There are many other important elements of informed consent that were briefly reviewed. Broad consent is sometimes obtained for storing biospecimens for future work. This consent should adequately describe the possible types of research application, whether information/specimens will be shared, and the duration of storage.
Dr. Berg also discussed possible conflicts of interests and provided numerous examples. She described publication bias and the importance of publishing negative studies. Investigators may also have financial interests. These need to be disclosed if the value of compensation could be affected by study outcome, if there is proprietary interest, if equity is greater than $50,000, or there are other significant payments. She also reviewed the physician payments Sunshine Act and which payments are included.
To conclude, Dr. Berg emphasized the role of the PI in working with the IRB to protect patients from harm. In addition, conflicts of interests must be considered to prevent bias.
Authored by Gabriela Sanchez-Petitto
The principal investigator (PI) is the primary individual responsible for the preparation, conduct, and administration of a research grant, training, or project in compliance with the laws and regulations. The PI has the responsibility of obtaining Institutional Review Board (IRB) approval, conducting the research, controlling the drugs or devices under investigation, protecting the rights and safety of the patients, and analyzing the data and reporting the results.
The IRB is a constituted group that has been formally designated to review and monitor biomedical research involving human subjects; they have the authority to approve or disapprove research. The criteria for IRB approval include that: the risks of the subjects are minimized or are reasonable relative to the benefits, the selection of subjects is equitable, informed consent is sought and documented, there is safety monitoring, and confidentially is protected.
The process of informed consent occurs when communication between a patient and physician results in the patient’s authorization or agreement to undergo a specific medical intervention/treatment. The basic elements covered in an informed consent include: the reasoning for the research, the procedures/treatments involved, whether the specimens (if any used) will be deidentified and/ or shared, treatment options and alternatives, compensation (if any), and/or additional costs, as well as the risks or benefits of being included in the study. If biospecimens are used, or whole genome sequencing is performed, these need to be discussed. Informed consent is voluntary and confidential, and all the questions need to be answered in lay language.
A conflict of interest (COI) occurs when an individual who is involved in research has one interest that interferes with another. Conflict of interest can be associated with conscious or unconscious bias, coercion of human subjects, and potential risk of affecting the results of the study. Significant financial interest involves anything of monetary value except salary, royalties from the institution, income from lectures, advisory panels, equity in publicly traded entity less or equal of $5,000, or other payment less than or equal to $5,000/year.
Up to 94% of MDs “admit” to taking gifts or money from industry, according to USA Today. Based on the FDA rules, an interest must be disclosed if the value of the compensation could be affected by the study outcome, if there is proprietary interest, equity of more than $50,000, or there is significant payment of other sorts. Financial conflict of interest is addressed through a management plan designed to remove the bias, or the reasonable perception of bias. This plan involves: public disclosure of the financial interests, modification of the research plan if needed, disqualification/removal of the investigator as the principal investigator or the appointment of a co‐investigator, or declination of the sponsored award.
- The PI is the primary individual responsible for the preparation and conduct of research in compliance with the laws and regulations.
- The primary purpose of the IRB is to protect the welfare and right of the human subjects involved in research.
- Researchers should adhere to institutional and governmental requirements for identifying, disclosing, and managing conflicts of interest.
Authored by Elaine Walsh
Dr Berg discussed the role of the IRB and the responsibility of the principal investigator in disclosing conflict of interests with respect to clinical and laboratory based research. We discussed the roles and responsibilities of the IRB and defined pertinent aspects of research including human subjects and regulations for IRB and research.
The principal investigator is responsible for obtaining IRB approval to allow the research to take place and for conducting the research according to the IRB approval as well as federal, state or local regulations. The investigator is also responsible for controlling all drugs and devices being studied, for protecting the subjects with respect to their rights, safety and welfare, and for analyzing data and publishing the results. The criteria for IRB are quite clear and are put in place to ensure that the risks to the subjects are minimized and reasonable, selection of subjects is equitable, informed consent is obtained, data and safety monitoring is carried out, confidentiality is ensured, and vulnerable patients are protected. Dr. Berg discussed different IRB approval pathways such as regular approval and limited review. Dr. Berg also discussed the elements of informed consent, which forms an integral part of both IRB approval and the research itself.
Dr. Berg then moved on to discuss the subject of conflicts of interest, which incorporates conscious or unconscious bias and coercion of human subjects and has the potential to affect results and lose public trust. Interestingly, industry funded studies are more likely to report positive results. According to the NIH, significant financial interests are defined as anything of monetary value. The exceptions to this definition include salary or royalties received from the institution, income from lectures, advisory boards for government or academic entities, equity in publicly traded entities to the value of ≤$5000, and other payments to the value of ≤$5000/year. Other potential conflicts of interest relate to foreign activities. For example, positions or scientific appointments, and any significant research activities performed outside the US irrespective of remuneration, are potential conflicts of interest. The FDA has clear guidance concerning disclosure of conflict of interest and states that interests must be disclosed if the value if the compensation could be affected by the study outcome, if there is proprietary interest, equity interest to the value of >$50,000, or if significant payments of other sorts occur.
Dr. Berg also discussed conflict of interest as it relates to institutions. The IRB must be informed if the institution has an active role in the sponsor funding the research, has intellectual property rights in the product being tested, and when the institutional leader has significant financial interest in the sponsor or product. To ensure these requirements are met, each institution has a research conflict of interest committee. Dr Berg summarized by saying that prospective disclosure is always the best approach, and when in doubt, ask for help.
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