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Monday, April 7, 2014

Is it time to review consent for STEMI clinical trials?

Eye on Intervention

The issue of informed consent timing for participants in interventional studies came under scrutiny at the American College of Cardiology Late-Breaking Clinical Trials session in Washington, DC, specifically with the presentation of HEAT-PPCI by Rod Stables, MD, and colleagues from the Liverpool Heart Centre in the United Kingdom.

HEAT-PPCI was a randomized controlled trial of bivalirudin [Angiomax, The Medicines Company] vs. heparin with glycoprotein IIb/IIIa inhibitor bailout that employed “delayed consent” to recruited participants, after they had been randomly assigned to receive the study medications. The study design overshadowed the result — that heparin was superior to possibly under-dosed bivalirudin — even though it had been approved by three independent U.K. research ethics committees, including a national committee, which also sanctioned inclusion of data from patients who had died prior to consent being obtained.

Stephen P. Hoole, MA, MRCP, DM

Stephen P. Hoole

The study design facilitated rapid recruitment of 1,800 STEMI patients in 22 months with a less than 10% drop out. HEAT-PPCI was an all-comers study, whereas similar studies with “prospective consent” frequently fail to recruit two-thirds of patients approached. As a result, these other studies take considerably longer, and some argue, may not even reflect real-world practice.

The panelists were not impressed. William O’Neill, MD, commented: “I think most of us have a very strong ethical concern. I would hold the leaders of your organization accountable. There just is an absolute social contract with our patients to make sure they’re not subject to research without their permission, and the biggest problem, I still am extremely bothered that you entered patients into a research study without getting their permission.”

Gregg W. Stone, MD, the session co-chair, expressed hope that, “We’ve not entered an era where we’re experimenting on humans without their consent. STEMI patients have been consented for 30 years.”

Importantly, the Nuremberg code states: “The voluntary consent of the human subject is absolutely essential. This means that the person involved should have legal capacity to give consent; should be so situated as to be able to exercise free power of choice, without the intervention of any element of force, fraud, deceit, duress, over-reaching, or other ulterior form of constraint or coercion; and should have sufficient knowledge and comprehension of the elements of the subject matter involved, as to enable him to make an understanding and enlightened decision.

“This latter element,” the code continues, “requires that, before the acceptance of an affirmative decision by the experimental subject, there should be made known to him the nature, duration and purpose of the experiment; the method and means by which it is to be conducted; all inconveniences and hazards reasonably to be expected; and the effects upon his health or person, which may possibly come from his participation in the experiment. The duty and responsibility for ascertaining the quality of the consent rests upon each individual who initiates, directs or engages in the experiment. It is a personal duty and responsibility which may not be delegated to another with impunity.”

Contrary to the panelists’ concerns, consent was obtained in HEAT-PPCI; the difference was in the timing. The presumed superiority of prospective consent begs a number of questions:

  • Do STEMI patients, who are unwell, in pain and frequently medicated with opiates, retain capacity to provide prospective consent?
  • Can anyone exert free choice when they are being wheeled into the cardiac cath lab and approached by the very person whom they hope will save their life?
  • Do patients with STEMI have adequate time to weigh the risks and benefits? The clock is ticking; time is muscle!
  • Yes, the consent form may be signed before the procedure, but is it valid?
  • On the other hand, delayed consent may result in more fully informed consent, but what if the patient does not want to participate? The bird has flown. 
  • Is the comparison of treatments already in mainstream practice more ethically amenable to delayed consent?

Surely we all agree informed consent remains absolutely essential for all clinical studies. However, we should acknowledge that consenting critically ill patients into research studies is inevitably a compromise. The disagreement on timing of consent should not be allowed to hamper important future research. Acknowledging that use of prospective or delayed consent, each with its own inherent limitations, does not take the interventional community down a slippery morality slope. 

What do you think? Please share your thoughts on HEAT-PPCI and its implications — positive or negative — for how we obtain consents.

  • Stephen P. Hoole, MA, MRCP, DM, is a consultant interventional cardiologist at Papworth Hospital in Cambridge, U.K. He leads interventional cardiology research in Cambridge and is one of 12 members of the 2013-15 class of Emerging Leader Mentorship (ELM) Fellows at SCAI.

  • Disclosure: Hoole reports no relevant financial disclosures.

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