Robert A. Byrne, MB, BCh, PhD; Adeel Shahzad, MBBS, MRCP; Rodney H. Stables, DM, FRCP

Disclosures

April 03, 2014

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Editor's Note:
This discussion was recorded before the official presentation of the HEAT-PPCI findings at the American College of Cardiology (ACC) Scientific Sessions 2014 in Washington, DC. Both the trial findings and the methodology sparked controversy, as covered by heartwire.

True Informed Consent in the Throes of a STEMI?

Robert A. Byrne, MB, BCh, PhD: Hi. My name is Robert Byrne, from the Deutsches Herzzentrum in Munich. I am delighted to be here at ACC 2014 in Washington, DC. We have just heard some very interesting findings from the HEAT-PPCI study[1] which was looking at ST-segment elevation myocardial infarction (STEMI) and outcomes in patients who were treated with bivalirudin vs those who were treated with heparin.

Apart from the very interesting results, the study highlighted some interesting issues in relationship to obtaining informed consent in patients who present to the hospital with a heart attack. I am delighted to be joined by 2 of the investigators, Adeel Shahzad and Rod Stables, both from Liverpool. Welcome.

Adeel Shahzad, MBBS, MRCP: Thank you very much, Robert.

Rodney H. Stables, DM, FRCP: Thank you.

Dr. Byrne: Adeel, by way of introduction, could you tell us how you handled the issue of informed consent in this trial, because that is always a thorny issue. Patients come in with chest pain, maybe they have received sedative medications or morphine, and some may be in cardiogenic shock. How did you handle it in this patient collective?

Dr. Shahzad: As you pointed out correctly, Robert, this was a primary percutaneous coronary intervention (PCI) setting. We received full United Kingdom ethical approval for the strategy of delayed consent. Patients were randomly assigned and treated in the acute phase, with no mention of the trial upfront. Once the acute phase was over, they were approached for full informed consent to use the data and for the follow-up procedure. I am very happy to inform you that out of almost 1800 patients who were recruited in the study, the response was very positive. Only 4 patients refused consent.

Dr. Byrne: It is a question that always comes up, because we do many studies in patients with STEMI and patients undergoing primary PCI. I like to divide it into a couple of categories: You have those who give full informed consent, those who give abbreviated consent or maybe oral consent, and then those who give consent after the fact. You have chosen a model of delayed consent. Are there any regulatory issues in your jurisdiction in the UK that made this a difficult undertaking? How did you manage that in discussion with the ethics committee?

Three Levels of Ethics Approval

Dr. Stables: We obtained full UK approval because of the details of this study. We were required to have it evaluated by 3 separate bodies. There was the standard regional ethics committee that independently looks at all research endeavors on a regional basis in the UK. Because it was a drug trial, it was further assessed by our Medicines and Healthcare Products Regulatory Agency. Finally, and this is an important aspect of the trial, in primary PCI there is quite a stark and disappointing early hazard. Some patients will die early in the clinical course. We faced the situation in which some of our randomized population would die before we could approach them for consent. To resolve this issue, there is a mechanism within the legislation of the National Health Service that one can make special application to a body in London that will consider such applications. They granted approval for the use of clinical data from patients who, tragically, died soon after presentation. These 3 bodies all basically agreed with our fundamental approach, but that is what we are here to debate.

The choices are full consent, delayed consent, or abbreviated consent.

Now, most people would probably agree that it is essentially impossible to obtain true full informed consent in this setting. There are issues with the ability of the patient to form and make a judgment because of pain and medication, but there are also time constraints. In the HEAT-PPCI trial, 50% of the population was randomly assigned within 5 minutes of ambulance arrival and 75% within 9 minutes. The available time is short.

Dr. Byrne: In some of our STEMI studies, we have tended to go the route of the abbreviated-consent model. For example, in the TASTE study,[2] which was an important study from last year, they used oral consent. The patient would be read a statement. Am I right in thinking that in your study, the patient wasn't read a statement beforehand, so there was no oral consent, and everything was done after enrollment in the study?

Dr. Stables: That's correct. The patient was randomly assigned and treated without discussion. Our rationale for that has a number of elements. The first consideration is that patients in this situation are not able to make any form of informed consent, even a fast consent. Hence, their statement is not necessarily valid. Some patients may consent and subsequently withdraw. Some patients may say no but on mature reflection, they wished that they had participated. There is an additional ethical concern that we won't resolve today, which is that some observers might feel that it is inappropriate to burden a patient in the throes of a STEMI with a transient brief discussion of a research trial on top of all of the difficulties they are already facing.

Delayed Consent: Established Therapies Only

Dr. Byrne: Yes. It's a very important question and one that all of us doing research in STEMI are confronted with on a regular basis. Are there any lessons from this study going forward? Do you think this is a format that you will use again when you are studying patients with STEMI?

Dr. Shahzad: We are not advocating the strategy of delayed consent for all trials and all studies. Every study's conditions are different. In our study, both treatment medications were in routine use. Both treatment medications were applied as their licensed indication and dosing. There was nothing experimental about it.

Dr. Byrne: That is an important point. When you are going to do a study like this, this is a very important prerequisite.

Dr. Stables: Absolutely, and every case must be judged on its merits, with full respect for the ethical principles.

Dr. Byrne: How did you handle the patients who died before consent could be achieved? Is there any additional paperwork you have to do to resolve this issue?

Dr. Stables: No. The central national approval allows us full access to the presentation data, and obviously the outcome, without further reference. This avoids the necessity to approach relatives at a time of grief, again with the discussion of a difficult concept for them to grasp.

Dr. Byrne: Of the patients who were enrolled in this study, what proportion then withdrew consent once they had survived and were able to read through the study documentation?

Dr. Stables: We believe that is the greatest endorsement of the methodology. Only 3 patients refused and only 1 withdrew. Although it may be inappropriate to contemplate the reasons why, each of them had reasons independent of the research itself.

Dr. Byrne: It is a very interesting study design. The Declaration of Helsinki[3] makes specific provision for this. It was recently revised. You can see there in Article 30 a further discussion of this point. It's a study design that we are going to be hearing more about, particularly in the setting of STEMI where enrollment has to occur very quickly.

Dr. Stables: A peripheral benefit to the approach, although not necessarily its primary driver, is that it allows more comprehensive recruitment. The trials will then recruit patient populations who are truly unselected and provide better data which can be generalized to everyday patient care.

Dr. Byrne: We have abbreviated consent, oral consent, and now delayed consent. We look forward to hearing more about this study in due course and seeing more work from your group. Thanks for joining us today.

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