As research activities go, the use of archival tissue has ranked pretty low on my list of ethical concerns. After all, the tissue has been or will be collected during a clinical procedure that patients would undergo regardless of their participation in research; there is no additional physical risk to subjects, and the primary ethical dilemma (or so the thinking goes) is the potential for a breach of confidentiality.
By the end of the full-day preconference program Biobanking in an Era of Precision Medicine Research: Approaches to the Ethical, Regulatory, and Practical Challenges, the presenters had changed my thinking on this topic. I now have a much better appreciation of the complex relationship between researchers, patient-participants, pathologists, and IRBs, particularly when specimens will be used to investigate precision medicine applications. Below are some of my take-aways.
Archival diagnostic specimens are integral to precision medicine research.
Precision medicine aims to treat disease based on individually specific characteristics—for example, selecting a first-line cancer therapy based on specific genetic markers in one’s tumor. Recent breakthroughs in precision medicine wouldn’t have been possible without archived tissue to test which therapies are best suited to a given genetic profile.
The demand for archival tissue for both research and clinical care is growing, while supply is decreasing.
As panelist and UCLA pathologist Dr. Sarah Dry, MD, noted, there is growing tension between the needs of the research community and the priorities of patient care. For example, a clinical diagnosis that previously required surgical excision can perhaps now be made via fine needle aspiration—a procedure that is much less invasive for the patient, but one that leaves a minute amount of cells available for further clinical and research use.
But it’s not just researchers and clinicians who have a stake in how archival specimens are used: patients who are candidates for targeted therapies themselves may expect pathological tissue to be available in order to obtain a second opinion, to enroll in one or more clinical trials, or to determine whether they are candidates for newly approved targeted therapies. Pathologists have the unenviable job of weighing research requests for specimens against potential clinical uses.
The panelists broadened my understanding of and appreciation for not only pathologists’ role in specimen research, but also the perspectives of this particular patient population, who are often desperate to find a targeted therapy for their condition and may not fully understand the ramifications of consenting to a study that requires a significant amount of archival tissue as a condition of enrollment.
So what does all this mean for me as an IRB professional?
There are a number of ways our HRPP could be improved, particularly in regard to review of precision medicine clinical trials:
- IRB staff could be trained to request that researchers clearly differentiate between use of archival tissue for cohort stratification versus correlative studies, as the latter presents no potential for direct benefit to the patient.
- Similarly, IRB members should consider whether the requested amount of tissue for correlative studies is appropriate for a given study/condition.
- If a subject is determined to be ineligible for a clinical trial, their archival tissue is rarely returned to pathology departments; given this subject population, it may be appropriate for consent forms to include such “key information,” clearly stating that merely participating in screening procedures may hinder one’s ability to enroll in subsequent clinical trials or to undergo testing for new therapies, as diagnostic tissue may have been depleted.
- Finally, when our institution is leading such clinical trials, the IRB should ensure that archival tissue collected for correlative studies is actually used: the risks of depleted archival specimens to individual subjects must be offset by the potential benefits to society of the correlative studies. An unused specimen benefits no one.
These are just some of the ideas I took away from the discussion of this topic during the biobanking preconference session (to say nothing of the other topics covered, such as issues related to specimen ownership/custodianship, repository governance, and return of results to biobank donors—all of which were incredibly valuable). Perhaps most importantly, I was challenged to recalibrate my ethical compass regarding research use of archival tissue and to carefully consider the broader needs and/or priorities of the proposed patient population in precision medicine research.
Erin Odor, MA, CIP, is an IRB Protocol Analyst II at The Ohio State University. She supports the operations of the Cancer IRB, Biomedical IRB, and Social & Behavioral Sciences IRB, as well as collaborative research with other institutions. She also regularly assists with outreach and education activities, staff training, and process improvement initiatives. She holds bachelor’s degrees in comparative cultural studies and Latin language, as well as a Master of Arts in East Asian studies.
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