Sunday, May 04, 2008

Ethics in Emergency Medicine Research

You may have heard this week about research on artificial blood substitutes for emergency use. In an article published on the website of JAMA – the Journal of the American Medical Association, Charles Natanson, Sidney Wolfe, et al, publish a review of published and unpublished studies on synthetic blood products (Cell-Free Hemoglobin-Based Blood Substitutes), which determined that existing studies, taken together, suggest that these products were less safe than hoped.

The article reviews studies of different products from different companies. They were also tested in different conditions. Some tested in trauma situations, although most tested in surgical cases. Over all according to the authors of the review article, “Based on the available data, use of HBBSs is associated with a significantly increased risk of death and MI.” (myocardial infarction, or heart attack)

The interest in these products is very high. The possibility of a product that would support brain and body, but would have a long shelf life, and not require refrigeration, is exciting. It's particularly exciting to trauma surgeons in military hospitals abroad and trauma centers at home. It's also exciting to pharmaceutical companies: the company that succeeds stands to make a lot of money.

Research in emergency medicine is difficult, and particularly difficult ethically. First, patients are rarely able themselves to consent, and commonly family members are not available. Then, too, exposing a patient to an unproven therapy, when the risk to life is so great and a proven therapy exists is hard to justify. At the same time, if new procedures and products aren't tried, how is emergency medicine to improve? And these issues are especially important if the therapy needs to be offered in the "Golden Hour," whether in the field or in the hospital.

Researchers have tried various ways to address the various ethical issues. One method, and one used with at least one such product, was community consent. Researchers approached local governments, essentially asking them to consent on behalf of their citizens. As emergency services, and especially ambulance services, are matters of public health, there is some logic to approaching public officials on what is arguably a public good. At the same time, concerns remained about patient autonomy, and specifically about patients receiving experimental therapies who would have declined if they'd had the capacity to do so.

(There have been other means tried to address consent issues in Emergency Medicine research. Perhaps another time I'll write about my experience with neomorts.)

I have one concern about the article. The published article addresses worse outcomes; but, worse compared to what? All the studies appear to have been treatment studies; and, after all, it would be unethical, especially in the trauma studies, to accept patients without intent to treat. Certainly, adverse outcomes were more likely for those who received the synthetic product than for those who received blood products. However, these products are particularly intended for situations in which blood would be difficult, if not impossible, to maintain or provide. So, one question is whether adverse outcomes would be more likely for those who received the synthetic product than for those who received no oxygen-carrying product at all (synthetic or natural). It's an important question. While the blood supply in the United States is safe, and not currently in short supply, there are circumstances in which it is limited. Since those are specifically the circumstances for which the products are intended, it seems an important point.

However, the authors do have a significant point. If, as they suggest, the greater risk of research subjects was known as early as 2000, there is an important ethical concern in continuing to enter subjects into studies. It creates a situation where risks counterbalance benefits to patients.

These are matters worthy of attention. We want the best available emergency care, and to that end we want the best available emergency medicine research. Of course, "best available emergency medicine research" requires good processes, including a good consent process. In a way, I could wish we had simply waited a few weeks and considered the primary review article. This secondary article identifies important issues but doesn't provide enough detailed information. However, these issues are important. For these, and for other new products, we need to be attentive to protecting patient safety and patient rights. That's how we best protect all of us.

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