Post-procedural Consent in STEMI Trials Debated

During a didactic symposium on trial design and interpretation, experts discussed whether post-procedural consent in STEMI trials is ethical and improves the generalizability of results.

The topic came to the forefront for interventional cardiologists earlier this year when results of the HEAT-PPCI all-comers trial of heparin vs. bivalirudin (Angiomax, The Medicines Company) in patients with STEMI were presented at the American College of Cardiology Scientific Session. HEAT-PPCI used a delayed-consent design where patients were asked after undergoing PCI — when they did not require emergency medical care and were not under sedation — to consent to have their outcomes used in trial data. At the time, some cardiologists strongly objected to this method and criticized the investigators for using it.

Sometimes a necessity

But Robert A. Harrington, MD, of Stanford University Medical Center, Stanford, Calif., argued that post-procedural consent is sometimes necessary in today’s health care climate in which research and clinical practice are intertwined.

“It is very difficult to carry out emergency research, including the issue of generalizability,” he said. “Post-procedural consent is appropriate, reasonable and ethical under certain conditions, as [it] was employed in HEAT[-PPCI], and what we really need going forward is some more empirical research on the patient-centeredness of informed consent, so that we can continue to advance therapy.”

Medical ethics have evolved over time, often in response to scandals, but also in response to the changing landscape of health care, Harrington said. He explained that what matters most is sticking to the core principles of research on human subjects as outlined in the Belmont Report of 1979: autonomy, beneficence and justice.

Harrington said he agreed with a recent editorial published in the Lancet by David Shaw, PhD, of the University of Basel, Switzerland, that the delayed consent used in HEAT-PPCI was ethical and that “this strategy was preferable to attempting to obtain consent from potentially incompetent patients needing extremely urgent cardiac treatment. … The use of delayed consent is particularly appropriate in pragmatic comparative effectiveness trials where equipoise exists.

“The majority of times, we’re not doing things based on the best quality evidence,” Harrington said. “So I think that for these kind of trials, it has to be carefully selected what the intervention is — I would not argue the same in a [trial of an] investigational new product — but I think when you truly have equipoise, it’s unethical not to randomize people.”

Strengthen preprocedural consent instead

On the contrary, William O’Neill, MD, of Henry Ford Hospital, Detroit, Mich., said that post-procedural consent for STEMI patients is not appropriate given that researchers have short consents at their disposal and that the United States has a long history of unethical medical experimentation.

“We have a legacy in America of doing some horrible, unethical research on prisoners, Down syndrome patients and other vulnerable populations,” O’Neill said. “An acute MI patient is probably the most vulnerable of all; they’re thinking they’re having a massive heart attack and are going to die. At least in America, we have to bend over backwards to make sure that these patients are treated both ethically and by current standards.”

He said that instead of getting postprocedural consent, researchers should strengthen their preprocedural consent practices. They should ensure that the mental state of the patient is stable, and also get consent from the family if in doubt; they should get consent from the family if morphine or another sedative has been administered; and they should not have the treating physician be the one to obtain consent, to “avoid the appearance of inappropriate influence,” he concluded.

He noted that a number of successful studies of patients with STEMI were completed with consent obtained beforehand, including three involving streptokinase, two involving tissue plasminogen activator and one involving the TandemHeart System (CardiacAssist). “Those are all great trials in the nomenclature of [STEMI] research, and all of these were done with informed consent,” he said.  

Disclosures:

• Harrington and O’Neill report relationships with multiple device and pharmaceutical companies.