Stroke trials pose ethical challenges
Researchers voice diverse opinions
Acute stroke trials pose unique ethical challenges to researchers. Stroke interventions are extremely time-sensitive, meaning that decisions about treatment and research participation often must be made quickly.
Some symptoms of stroke affect the patient's cognitive abilities and even the ability to know that he or she is suffering a stroke, which raises consent issues. And because the degree of impairment can vary widely from patient to patient, hard-and-fast rules about how to handle consent of stroke patients is difficult, says Enrique Leira, MD, MS, assistant professor of neurology at the University of Iowa in Iowa City.
"It's very difficult to generalize the regulations about, for example, waiver of consent, in a situation like this that is so heterogeneous," he says.
Leira and his colleagues recently surveyed stroke investigators in 15 countries to get their opinions about various ethical questions related to stroke research.1 He says what they found was a wide diversity of opinion among researchers and review boards about how to handle some of the most pressing ethical questions related to stroke research: While 73% of investigators said that their review boards allowed surrogate consent in stroke trials, only 18% reported that they were allowed to obtain that consent by telephone, and 20% reported that they were allowed to obtain that consent by fax. 22% reported that there was an established procedure agreed to by review boards for assessing competency in stroke patients. Language ability and judgment of consciousness ability was evaluated using a variety of models.
That diversity of opinion can lead to delays in getting multisite international stroke trials off the ground, Leira says. He hopes that the group's recently published article will start a conversation in the stroke research community that leads to more standardized procedures for stroke trials. "Given that this is very time-dependent and that time is of the essence, if we could agree on some framework for determining eligibility for example, that would be ideal," Leira says.
A 'time-dependent emergency'
Leira says that in his own experience, review boards' requirements for conducting acute stroke trials are so onerous that they can sometimes delay the start of interventions.
"I think the most important thing for review board members to understand when evaluating an acute stroke research protocol is that this is a time-dependent emergency," he says. "The outcome of any intervention, including the intervention that is being tested, is going to be dependent on how soon that intervention is started. So while all the requirements on safety of research have to be maintained, we also have to understand that this particular research cannot be delayed too long because if it is, we enter another ethical problem, which is if we are testing interventions at too late a stage, then they are less efficacious or they are not efficacious at all."
In other types of research into emergency interventions, physicians have been able to use established procedures, including provisions in the federal regulations for emergency exception from informed consent. But Leira says there are important differences between stroke research and other types of emergency research. In some other emergency situations, a patient is unconscious, which makes the decision of how to obtain consent more cut-and-dried.
In that case "it is obvious when the patient and potential subject cannot provide consent, and a waiver of consent through community consultation can be approved," he says. "In stroke research, this is a little more complicated because we are talking about a variety of neurological deficits and degrees of impairment. There may be persons with mild cognitive impairment, no cognitive impairment at all, or totally impaired." (For more information about consent, see story below.)
In fact, some stroke patients might suffer from a condition known as anosognosia, meaning they don't recognize that they are impaired, "in which case getting informed consent for research or treatment can be challenging because the patient is not aware of having any problems," Leira says.
- Leira EC, Kaldjian LC, Ludwig BR et al. Lack of international consensus on ethical aspects of acute stroke trials. J Stroke Cerebrovasc Dis 2010 Aug 17 (epub). Web: http://www.ncbi.nlm.nih.gov/pubmed/20719537.
Consider the option of surrogate consent
In cases in which a person has been judged to be incapable of giving consent, surrogate consent is always an option. However, according to Enrique Leira, MD, MS, assistant professor of neurology at the University of Iowa in Iowa City, the time pressure involved in a stroke adds complications there, particularly for investigators such as him who work in rural areas.
"Patients often are evacuated by helicopter, and they often arrive much earlier than the relatives who usually come by ground," Leira says. "By the time the relatives become physically present, it may be too late to enroll the patient in the protocol."
He says many review boards, including his own, will not allow phone consent from a surrogate for research. "The requirement is that the informed consent has to be obtained with a legal document on paper. For an acute time-dependent trial in a rural center, that's going to be a problem."
While Leira says that a consensus on how to handle ethical issues in stroke research would need to come from the stroke research community, understanding the issues can help review boards to better facilitate these trials. As an example, he notes the complexity of required language in consent forms.
"It's important to really make an honest assessment of how long it would take to go through a complete standard consent form in an acute situation like this and be sure that true consent can be obtained without delaying the process," Leira says. "I personally think for an acute stroke situation, the consent forms are a little bit too legalistic and long. While that may be appropriate for studies where a person has more time to decide on participation, in a situation like this, it can really defeat the purpose."