Preclinical detection of brain disorders presents multiple challenges
False-positives may harm patients
There are numerous ethical issues related to preclinical detection of brain disorders or conditions, says Karen S. Rommelfanger, PhD, director of the Neuroethics Program and assistant professor in the Departments of Neurology and Psychiatry and Behavioral Sciences at Emory University in Atlanta.
"As our health care system and research move to a model of risk management and disease modifying, we will only see more and more of these unaddressed ethical issues come to the fore," she predicts.
Recently, technologies have been developed that detect signs that precede clinically relevant symptoms. "These preclinical or prodromal assessments are being created for time points at virtually every stage in an individual’s life span: autism in infants, schizophrenia in youth, and Alzheimer’s in adults," says Rommelfanger.
These preclinical signs generally assess risk for developing the disorder, but do not guarantee the development of these conditions. "Conditions that target the brain not only impact our view of our physical health, but also who we are — and in the case of prodromal assessments, who we may become," Rommelfanger says.
Disclose with "extreme care"
Thomas Cochrane, MD, MBA, senior ethics consultant at Brigham and Women’s Center for Bioethics and assistant professor of neurology at Harvard Medical School in Boston, is aware of a case of preclinical testing for Huntington’s disease that resulted in the suicide of an asymptomatic patient.
"The disclosure of some diseases needs to be handled with extreme care and forethought," he underscores. "There are a number of worries about preclinical testing. How will patients react to knowing they’ve got an untreatable neurodegenerative condition?"
Technologies could provide early intervention to slow or prevent these conditions, says Rommelfanger. This would ultimately benefit patients and substantially reduce downstream health care burdens.
However, a false positive — suggesting a high risk for the disorder when really there is no chance that the condition will ever develop — can have serious deleterious consequences for patients and their families, she says.
"False positives could result in unnecessary changes in life course and family decisions, or iatrogenic harm by introducing pharmaceutical interventions, such as those used for schizophrenia, that also introduce a high risk of adverse effects," Rommelfanger says.
Net benefit or net harm?
The main concern about preclinical testing for any disorder is whether the results of the testing will represent a net benefit or a net harm to patients, according to Cochrane.
"The benefits of preclinical testing depend a lot on whether therapy is available for the disease," he says. "If there is preventive therapy available for a disease, then of course preclinical testing would represent a huge benefit."
If there is no preventive therapy, but there is a treatment that works best when initiated early, this also constitutes a benefit, says Cochrane. Knowing about the disease before symptoms begin would allow an individual to be monitored very closely for symptoms.
"If there is no therapy at all, as is currently the case for most neurodegenerative disorders, then the benefits of knowing the diagnosis are mostly psychological," says Cochrane.
Bioethicists can influence
The use of novel preclinical tests outside the research setting is fraught with risk, cautions Cochrane, and should be undertaken deliberately and carefully.
"Those who patent a test naturally want it to be used widely," he says. "Insurers will usually want it used sparingly or not at all — unless there is preventative therapy available."
Patients often want a test in order to know as much as possible, but they may not have thought carefully about the pros and cons of presymptomatic testing.
"Bioethicists can probably have the most influence at the medical society level, in helping develop and promote professional guidelines that are designed to ensure that novel tests are used wisely," says Cochrane.
Ethicists can be involved in designing how and when preclinical assessments occur, suggests Rommelfanger, and determining how results should be communicated to patients.
"Otherwise, the potential of these technologies, as enormous as their potential to substantially reduce human suffering may be, will be undermined by a loss of public trust," she warns.
- Thomas Cochrane, MD, MBA, Senior Ethics Consultant, Brigham and Women’s Center for Bioethics/Assistant Professor of Neurology, Harvard Medical School, Boston, MA. Phone: (617) 732-8046. E-mail: email@example.com.
- Karen S. Rommelfanger, PhD, Neuroethics Program Director, Assistant Professor in the Departments of Neurology and Psychiatry and Behavioral Sciences, Emory University, Atlanta. Phone: (404) 727-1150. E-mail: firstname.lastname@example.org.