Minimal Risk in the Tri-Council Policy Statement‪.‬

Scenario 1: An oncology researcher approaches the Research Ethics Board (REB) office of a Canadian institution to request guidance on an REB submission. The researcher, a neurosurgeon, intends to take part in a multi-centre trial of a new agent for the treatment of the intractable and fatal condition Glioblastoma Multiforme (GBM), a brain cancer for which currently available surgical, radiographic and chemotherapeutic approaches increase mean survival rimes to only 12-14 months. The experimental procedure involves implanting a device to deliver existing chemotherapeutic agents in a novel fashion; this implantation would take place during the surgical excision of the tumour in open-brain surgery, a treatment option that patients with GBM almost universally accept. The researcher points to Section C.1 of the Tri-Council Policy Statement and claims that his research project needs no more than expedited review. "The patients are all going to undergo brain surgery and chemotherapy anyway; clearly the risks involved in this procedure are minimal as they are within the risks of daily living for people with GBM for whom undergoing brain surgery is normal--and that's how the Tri-Council Policy Statement defines "minimal risk'." A month later, another neurosurgeon at the institution approaches the REB office with a research study for the same population: his procedure specifically targets the tumour as it reappears after initial treatment, and involves stereotactic surgery, which as a neurosurgical procedure is safer than the original surgery to excise the tumour. He points to the same Section C.I of the Tri-Council Policy Statement and argues that his research proposal should receive expedited review; after all the procedure is even safer than the craniotomy that such patients have already undergone, and the disease itself carries universal extreme morbidity and, for the patients eligible for his study, a very high likelihood of death within a matter of weeks or months. Hence, relative to the condition itself and the ordinary course of its treatment, the risks of his stereotactic surgery are well below the risks such patients face in the course of their lives. Scenario 2: A stem cell researcher approaches the REB office with a research protocol for an experimental neurosurgical intervention for the rare (and uniformly fatal) genetic condition called Batten disease. Children would undergo stereotactic brain surgery to implant neural fetal stem cells that are expected to provide the appropriate enzymatic activity to counteract the disease. The researcher is puzzled as to the correct interpretation of the restrictions the Tri-Council Policy Statement places on risk in research with children. "The Tri-Council Policy Statement says I can only do "non-therapeutic" research with children that exposes them to minimal risk--I looked up Section C1 on minimal risk in order to understand what this restriction in Article 2.5(c) amounts to. That section seems to suggest that what I'm doing is minimal risk, because these patients already live with significant risk. But we've never implanted fetal neural stem cells into children "s brains before--or adults, for that matter. The risks are significant indeed. When I looked at the Tri-Council definition, it seems to me that perhaps we've been far too cautious about our research all along. If your REB office just consults their risks of daily living--well, these are virtually certain death within a couple of years, even with out best medical care. There are much riskier procedures that fall within that range that I can take straight to human trials without so much time-consuming pre-clinical work with animal models!" (1)