Involving patients in enrolment decisions for acute myocardial infarction trials
BMJ 2015; 351 doi: https://doi.org/10.1136/bmj.h3791 (Published 29 July 2015) Cite this as: BMJ 2015;351:h3791
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The authors are wrong to state that “there is no basis” for the claim that HEAT-PPCI’s mode of consent was the only ethical solution in this context. The basis is stated clearly in my article, although the authors do not mention it.[1] They thereby completely ignore a key argument against seeking prospective consent: doing so could lead to the deaths of patients who would otherwise be saved. Reading their proposed consent script might only take one minute, but a minute’s delay in treatment could be the difference between life and death, as seen in the CRASH trial.[2] It is irresponsible of the authors to suggest that prospective consent should be used in situations such as this while neglecting to mention this vitally important issue. It is also disappointing that the BMJ’s peer reviewers did not spot this omission.
1. Shaw D. HEAT-PPCI Sheds Light on Consent in Pragmatic Trials. Lancet, 2014; 384:1826-7.
2. Roberts I et al. Effect of consent rituals on mortality in emergency care research. Lancet, 2011; 377: 1071–1072.
Competing interests: No competing interests
We read your debate about patient consent in STEMI trials with interest [BMJ 2015; 351:h3791].
We randomised critically ill patients with an admission diagnosis of ruptured abdominal aortic aneurysm to either a strategy of endovascular repair or to open surgical repair [BMJ 2014;348:f7661].
Out of the 652 patients approached for initial brief consent, 42 (6.4%) refused because they had a preference for either no treatment or a specific treatment. 613 patients were randomised, 509 patients (83%) were able to provide brief witnessed verbal or written consent, a relative or carer provided consent for 44 (7%) and a further 60 (10%) were randomised using the Mental Capacity act, with a clinician from outside the immediate management team confirming that this route was appropriate. For those patients that survived to discharge, a further full consent was obtained and at this point 6/384 (2%) patients refused consent.
It seems important to allow patients the option of immediate consent whenever possible, and in our experience nearly all agree to participate, and to allow them to reconsider this decision when their health has improved. This type of flexible arrangement also could be used in STEMI trials.
Competing interests: No competing interests
‘Deferred consent’ appears to be an ill-disguised instrument to pre-emptively circumvent many trial problems.[1] For one, it nearly eliminates the possibility of patient refusal. It also helps reduce subject bias- since the subjects are unaware of recruitment in the trial during the intervention phase. In addition, it reduces the risk of contamination- again, due to subject ignorance.
The recurring theme is that of patient ignorance about recruitment in the trial. At the most fundamental level, this seems to constitute a lack of respect for the subject(s).
Autonomy is one of the cornerstones of medical ethics, and is a principle that echoes through many statements of the Helsinki Declaration.[2]
Some of the principles stated in the Helsinki Declaration that may be compromised through the use of ‘deferred consent’ are:
“7. Medical research is subject to ethical standards that promote and ensure respect for all human subjects and protect their health and rights.”[2]
When researchers choose to decide for their study subjects, they are demonstrating a lack of respect for the patient and patient autonomy.
“9. It is the duty of physicians who are involved in medical research to protect the life, health, dignity, integrity, right to self-determination, …. of research subjects…”[2]
Researchers must remind themselves that they are duty-bound to protect the right to self-determination of subjects. By deciding on behalf of the patient in situations where the subject can provide informed consent, one neglects that duty.
“25. Participation by individuals capable of giving informed consent as subjects in medical research must be voluntary. ……, no individual capable of giving informed consent may be enrolled in a research study unless he or she freely agrees.”[2]
Adherence to this principle may result in greater refusals on part of potential subjects, but it hinges on the fundamental right to freedom. Just as one would scant accept an infringement of one’s personal freedom and the right to choose, the same must be extended to potential subjects.
“29. When a potential research subject who is deemed incapable of giving informed consent is able to give assent to decisions about participation in research, the physician must seek that assent in addition to the consent of the legally authorised representative. The potential subject’s dissent should be respected.”[2]
This principle effectively sums up our view on the matter-
• if a potential subject is capable of giving informed consent, there is no reason not to obtain it;
• if a potential subject is incapable of giving informed consent, the same should be obtained from those competent to do so on behalf of the patient;
• whenever a patient who was previously unable to give informed consent recovers enough to be able to do so, his/her opinion should be sought and respected.
The use of instruments like ‘deferred consent’ is fraught with the potential for mischief. Researchers may not consciously seek to undermine the status of a potential or actual subject, but having the power to do so may subconsciously influence crucial decisions. That risk is something medical research in general and medical researchers in particular can ill afford.
References:
1. Dickert NW, Miller FG. Involving patients in enrolment decisions for acute myocardial infarction trials. BMJ. 2015;(351:h3791).
2. World Medical Association. World Medical Association Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects. JAMA. 2013; 310(20): p. 2191-94.
Competing interests: No competing interests
Re: Involving patients in enrolment decisions for acute myocardial infarction trials
We appreciate the recent responses to our paper. Powell’s and Johnson’s comments are in agreement with our argument that involvement of potential participants in enrollment decisions should be sought where possible as part of respecting patients. We encourage efforts to generate evidence regarding how best to do this.
We strongly disagree with Shaw’s claim that our recommendation for maximizing patient involvement in STEMI trial enrollment decisions neglects the time-sensitivity of care delivery. His critique is mistaken in suggesting that there is evidence of harm to patients related to consent processes in STEMI trials like HEAT-PPCI. The processes that we propose considering in STEMI research could be executed within at most several minutes. Shaw’s claim that this would harm patients is clinically groundless. There is simply no reason to assume that a delay of this magnitude would negatively impact outcomes, especially in the context of a high-volume center with short times to reperfusion, as was the case in HEAT-PPCI. In general, STEMI trial enrollment utilizing prospective consent has been associated with slightly longer time to reperfusion, though whether the delay is due to consent is unknown. More importantly, trial enrollment has not been associated with negative clinical outcomes [1, 2]. Furthemore, marginal reductions in time to reperfusion have not been shown to be of significant benefit [3,4]. Even more problematically, the report that Dr. Shaw cites as demonstrating evidence that consent processes are harmful in emergency care research is irrelevant to the STEMI context. That report describes the projected negative clinical impact of a delay of more than an hour in a trial involving patients with traumatic head injury [5]. In addition to being a different condition and a radically greater delay in treatment, the potentially harmful delay in treatment referenced in that report was generally not due to the process of soliciting consent from patients but rather to the fact that patients were incapacitated and appropriate surrogates are often not immediately available.
It is Dr. Shaw’s analysis and not ours that fails to appreciate the clinical context of STEMI and the impact of minimal delays. His accusation that both we and the peer reviewers of our manuscript failed to consider these issues is false.
1. Juliard JM et al. “Impact of participation in randomized trials of reperfusion therapy on the time to reperfusion and hospital mortality in ST-segment elevation myocardial infarction: A single-centre cohort study.” European Heart Journal Acute Cardiovascular Care. 2015 Feb 27.
2. Blankenship JC et al. “ST-elevation myocardial infarction patients can be enrolled in randomized trials before emergent coronary intervention without sacrificing door-to-balloon time.” American Heart Journal. 2009 Sep;158(3):400-7.
3. Bates ER and Jacobs AK. Time to treatment in patients with STEMI. New England Journal of Medicine. 2013 Sep 5;369(10):889-92.
4. Menees DS et al. Reduced door-to-balloon time and mortality in patients undergoing primary PCI. New England Journal of Medicine. 2013;369:899-907
5. Roberts I et al. Effect of consent rituals on mortality in emergency care research. Lancet. 2011; 377: 1071–1072.
Competing interests: No competing interests