Institutions that perform research using human subjects are required to meet specific standards and obtain formal approval from a governing body known as an Institutional Review Board (IRB). From informed consent of participants to delineated responsibilities of all investigators, from protected health information to payment of research subjects, from blood draw and tissue sampling guidelines to accessing medical records; investigators submit, and IRBs carefully examine, a large laundry list of required elements for each proposal. For collaborative research projects performed across international boundaries, such as those within the Joint Institute for Translational and Clinical Research (JI), this means securing approval from the IRBs of both institutions involved as well as meeting country-specific standards when governmental funds are used.
According to Dr. Michael Geisser, Professor of Physical Medicine & Rehabilitation at the University of Michigan and a member of the JI IRB and Human Protection Core, “from a human subjects protection standpoint, meeting the ethical standards that satisfy both institutions with regard to collaborative projects has certainly involved more work and oversight than were we treating the investigator at each institution as separate investigators. Cultural differences make their way into the research world and have an influence on the IRB standards and protocols that have been established.” “Although most countries follow basic ethical principals,” he explains, “clearly-defined international ethical codes for human subjects don’t exist. This has challenged us to be thoughtful and strategic in guiding JI investigators to submit research proposals that meet the IRB guidelines of both institutions.”
Two specific areas where JI proposals have required the most consideration are informed consent and criteria for genetics research. Generally speaking, US institutions consider rights of privacy to be of utmost importance in participation of human subjects, granting autonomy to the individual and disallowing the use of any personal identification. China, on the other hand, has typically viewed right to consent in the historic lens of a paternalistic society. There are also ethical challenges for banking, sharing, and using genetic data and samples. “China has long felt that international researchers have come in and taken advantage of their genetic resources,” points out Geisser. “So, in the 1990s,” he adds, “they developed stringent criteria for genetics research and now have a separate governing panel that reviews whether or not it is okay to share genetic data/samples with researchers ouside of China.” As all of the JI projects involve some type of genetic sampling, the new criteria apply. Though most JI data are now stored on a central server at U-M, a genetics firm in China handles all of the analyses and all samples are approved before transfer.
Advanced technology has further enlivened the conversation by pushing both informed consent and genetics research into an arena that few could have predicted. IRBs are now faced with consent considerations for future research. “Technology is advancing at such a fast rate that it is brings its own challenges,” Geisser explains. “A research consent form 15 years ago couldn’t foresee how valuable some samples might be, and all of the possible uses of these materials. So do you re-consent past subjects? Do you alter current language so that participants consent to future research with few details as to what this might be? How do we articulate or even envision what future research on stored samples may look like?”
Ethical challenges from biospecimens and health information:
A perspective from PUHSC
With the development of the JI, the PUHSC and the U-M IRB Core team has worked hard to facilitate the research ethics challenges of the JI investigators. Due to the different research styles and resources, the IRB Core partnership has gradually discovered and confronted differences that exist between institution-wide and country-wide IRB requirements. Privacy information, for instance, is regulated by HIPPA in the United States, yet lacks similar regulation in China; and while China has recently established some mutual biobanks, implementing the secondary use of the biospecimens is still an evolving process. Sending sample information from China to the United States requires careful collaboration, and human genetic data is a particularly sensitive topic given that China has very specific national regulations that collaborating international institutions must adhere to.
Professor Yali Cong, Chair of the Institutional Review Board and faculty in the Department of Medical Ethics at PUHSC, also echoes Dr. Geisser’s concern about the challenges in obtaining re-consent from past subjects. Identifiable blood samples that were once obtained for research purposes hold informed consent for original studies, but the original consent forms made no mention of continuous or future use. Once an original study has been completed, it may be difficult to contact patients to obtain re-consent due to insufficient contact information on the Informed Consent Form (ICF). Some researchers don’t keep samples after the projects are complete and the challenge ends there. Most researchers, however, reject the thought of discarding samples that may still provide value and then have to wrestle with the nuances of previously unanticipated ethical practices.
According to Professor Cong, the JI IRB Core has been, and will continue to be, essential in helping researchers deal with issues by reviewing risks to subjects, practicability for re-consent, research values, and balancing all of the factors involved. In union with Dr. Geisser’s perspective, she poses similar considerations for JI projects:
- When informed consent for tissue/blood collection was for a clinical diagnosis purpose, and the clinical work is complete, what happens when future researchers want to do research using these identifiable biospecimens? Is there an honest broker to separate the individual information from researcher? How can privacy information be protected?
- When original ICF forms note that samples will be used in a general disease area, but the description is not specific enough for current regulations; or whether the proposed secondary research can reasonably be understood to fall within the scope of research that was described in the original consent form; what are the available options?
- The set up of the bio-repository now requires a separate application for IRB approval. But oftentimes this procedure didn’t previously exist. What does one do in this situation?
- When new research use imposes new or significantly greater risks not described in the initial consent form, what are our responsibilities?