Authored by Akihiko Shimomura, MD, PhD, National Cancer Center Hospital, Tokyo, Japan

Investigators have many responsibilities, such as obtaining IRB approval, conducting the investigation according to IRB-approved protocol and applicable federal, state and institutional regulations, controlling all drugs/devices under investigation, protecting the rights, safety, and welfare of subjects, analyzing data, and reporting results.

The IRB reviews research in human subjects (and can approve, disapprove, or require modifications in a study), reviews informed consent, conducts continuing review, and possesses authority to observe the consent process and research. The IRB approval of research achieves many criteria: risks to subjects are minimized, risks to subjects are reasonable relative to benefits, selection of subjects is equitable, informed consent is 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.

The management of conflict of interests is another important issue for researchers. The king of conflict is the PI’s role. The physician-researcher has conflicting roles: as PI advocates for the study and as physician advocates for patients. Another significant source of conflict is fortune. In the United States, from 2012 to 2017, GDP was $18.56 trillion ($57,300 per capita), and total health care spending was $9900 per capita. Prescription drug sales were $450 billion. One cycle CAR-T cells costs $475,000. The NIH budget is $26.9 billion, and PhRMA R&D in 2015 was $58.8 billion. For perspective, the total of Major League Baseball salaries in 2018 is $4.2 billion. The typical management strategies for conflict of interest are public disclosure, monitoring by independent reviewers, modification of the research plan, disqualification from participation, and divestiture/severance of relationships. The last source of conflict is unethical behavior/misconduct. Falsification, fabrication, and plagiarism are the things researchers have to avoid.

In summary, the PI is responsible for everything, has to build a team, and must not cut corners. When in doubt or when not in doubt, PI have to ask.

Scholar Summary

Authored by by Catherine Spina, MD, PhD, Columbia University Medical Center, New York, New York, USA

Dr. Berg introduced the role of the IRB and the responsibilities of the investigators, including (a) obtaining IRB approval for human subjects research involving drugs and devices according to federal, state and institutional regulations, (b) ensuring protection of research subjects, and (c) conducting analysis of data and results reporting.

Dr. Berg explained that the IRB plays a critical role in research on human subjects by reviewing and approving/disapproving research protocols, reviewing informed consent, and, when necessary, observing the consent process and research.

The elements of informed consent were reviewed, including a discussion of the research and role of the subject, risks/benefits/alternatives, and the right to withdraw from the protocol at any time. Dr. Berg highlighted the importance of offering research subjects contact information for questions. Furthermore, subjects should be informed if their biological specimen may be used in the future for additional research projects without re-consenting.

The following definition of research was offered: “a systematic investigation, including research development, testing, and evaluation, designed to develop or contribute to generalizable knowledge.” According to the IRB, a human subject is a living individual from whom an investigator can obtain identifiable information or biospecimen. Importantly, if the information or specimen cannot accurately identify the human subject, or if private information is collected for purposes other than research, the IRB does not include this in the category of human subjects research. However, consent must be obtained for all biospecimen under the proposed Common Rule.

Regarding stewardship of data, the IRB requires that genomic research results (e.g., CLIA certified lab tests, germline findings, variants of unknown significance (VUS)) be disclosed to the patient and all large-scale genomic data be submitted to an NIH-designed data repository for data sharing.

For investigators interested in storing biospecimen for future work, a broad consent may be obtained. The IRB dictates that this consent must include a description of what (information, specimen, etc.) will be used, whether it will be shared (and with whom), and the duration of storage and must clearly indicate that consent for future investigations will not be obtained.

Dr. Berg emphasized that reporting negative results is critical to avoid publication bias. She noted that if the investigator thought that the experiment was worth doing, the results are worth publishing.

For clinical trials investigating drugs or devices, the FDA dictates that the trial must be registered within 21 days of the first subject enrolled and results should be reported within one year of completion of the study.

Dr. Berg discussed possible conflicts that may arise when a principal investigator interested in enrolling patients on his or her trial is also the patient’s treating physician; this potential conflict should be acknowledged and discussed with the patient. Other sources of conflict of interest include monetary gain. NIH dictates that equity or payments greater than $5,000 may have the potential to influence research and therefore should be disclosed. Management strategies to avoid unnecessary influence on research include public disclosure, independent review, modification of research plan and/or participation, and divestment strategies, if necessary. Finally, fame may also be a source of conflicts of interest, in rare cases driving investigators to conduct unethical behavior including plagiarizing or falsifying data.

In summary, it is the responsibility of the principal investigator to ensure consent and scientific conduct and to communicate results with utmost integrity and in accordance with NIH rules and federal laws.