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January 23, 2005
Risks in "at-risk" research
Prodromal interventions for schizophrenia vulnerability: the risks of being "at risk".
Corcoran C, Malaspina D, Hercher L.
Researchers have been trying to identify and treat teenagers and young adults who may be clinically at risk or “prodromal” for showing psychotic symptoms. This “prodromal” research (prodromal means early symptoms and signs of an illness that precede the beginning of the acute, fully developed illness) is trying to help avoid the damage that can occur once the illness begins especially since the longer the duration of untreated psychosis the worse the long term prognosis. But, this type of prodromal research has many controversies, ethical concerns and risks associated with it which are summarized in this article a leading schizophrenia researcher as follows:
Defining “at-risk”: Corcoran and colleagues point out that it is more complicated to identify those who are “at risk” for an illness than those who already show symptoms. While there are many studies that have been done to identify “at risk” factors, current standards for identifying those who are “At-Risk Mental State Prodromal” were developed in 1996 by a group of Australian researchers (Yung, McGorry and colleagues) and are seen in individuals fitting into one of three categories:
The three groups together are estimated to have about a 40% likelihood of developing psychosis by 12 months and a 50% likelihood of developing psychosis within the next 24 months. But the authors of this paper point out that it is important to keep in mind that not all measures of vulnerability are the same. A baby of two parents with schizophrenia has a 50% chance of developing the disease, which is the same statistical risk as a 17-year-old boy who is currently experiencing attenuated psychotic symptoms. But, the teenager is immediately at risk while the baby is not. This raises the ethical question of how useful is a preventive intervention that interrupts a time that could have been one of relative health and normalcy as compared to an intervention that actually addresses the immediate threat of a disease.
False Positives: In prodromal studies there is also a risk of false positives, i.e. many people who are identified to be “at-risk” do not go on to experience psychosis, at least not within the 2-year time frame that has been studied so far. This raises the risk of over-treatment for those who are unfortunate to fall in this false positive group. In any case, the use of antipsychotic medication for those who have not developed psychotic symptoms is controversial and the research is inconclusive about whether it is effective and safe. Some studies have suggested that newer medications like Risperdal and Zyprexa can be effective prodromally, although side effects have been prominent in these studies. Yet, it appears that antipsychotic medications are already being prescribed prodromally in the community and so the authors argue that there is a need for many more controlled studies to measure the effectiveness of such prescribing practices on preventing the onset of psychosis.
Stigma: There is also the risk that prodromal research subjects may experience stigma due to being “labeled” at risk for psychosis which can impact their sense of self, relationships with friends and family and possibly their choices in terms of education, employment, or other life plans. It could also impact the extent to which such plans and aspirations are supported by other family members. Interviews with parents of patients at prodromal clinics have shown that their concerns about stigma are strongly dependent on the behavior and symptoms of the patient prior to interaction with the clinic.
However, the authors point out that the stakes change if patients are younger or less symptomatic. In such a group that is not immediately at risk or impaired, the idea of being vulnerable for psychosis could leave false positive individuals with a lasting sense of being fragile or damaged. In some families this knowledge of risk could be productive, allowing them to protect the at risk person from stress and help redefine behavioral problems as due to the illness rather than character flaws. But in other families, the protective impulse might mean that the family stops encouraging growth and progress in the person identified as being “at-risk”. As a result, the authors suggest that it is important for family education be a part of prodromal research programs, especially since sometimes people forget that there is difference between being “at risk” and already having an illness.
Confidentiality: Confidentiality is an important tool for protecting the at-risk population from insurance discrimination and other forms of stigma. There are new laws involving the Health Insurance Portability and Accountability Act of 1996 and a Certificate of Confidentiality, issued by the Department of Health and Human Services, which protect privacy but yet they have no jurisdiction over what research subjects themselves disclose. The authors point out that it is important to evaluate what information is available to third parties, either directly or by implication. Relevant third parties can be insurance companies, as well as employers, schools, religious organizations and other community groups. It is not safe to assume that all people or institutions will appreciate the difference between a risk assessment and a diagnosis. As such, public education becomes important especially since these same issues have been debated in medicine for studies of insulin treatment for children at risk of Type 1 diabetes, women with a family history of breast cancer who pursue genetic testing and in pre-symptomatic testing for Huntington’s disease.
Autonomy or Self-rule: The right to make your own decisions or autonomy involves going through the informed consent process in research. The authors point out that in the prodromal period, patients are on the edge of competence – with respect to their age and mental status. Intervention at such an early stage suggests that these patients will be helped in terms of their future symptoms, but since they’re younger they would be less able to participate in the decision-making process. The authors suggest that there is no easy formula for balancing the obligation of families and doctors to protect vulnerable individuals while giving them some latitude for self-determination. But, there is a burden on the researcher or clinician to provide a high standard of informed consent since there are many who stand to gain from research in schizophrenia: families, particularly in light of familial predisposition; pharmaceutical companies with treatments to market; society at large in what can be learned about the disease. Nonetheless, the authors make it clear that these benefits cannot be earned at the expense of a vulnerable population.
Risks for true positives: Early intervention may pose some hazards for true positives as well, i.e. those who are in fact truly at risk (vs. false positives). The extent to which a treatment is a risk for true positives is directly related to two variables: current quality of life and the length of the interval between intervention and the onset of disease. But as much as early intervention looks promising, there are no guarantees that medical care is going to change the outcome for schizophrenia. Families are faced with many important questions prior to enrolling in prodromal interventions. Given that in some instances a bad result may be inevitable, and that the problem is perhaps years down the road, would a family prefer to have prior knowledge of the event? Or would they prefer to have the intervening years of relative normalcy? The authors point out that there has been limited interest in pre-symptomatic genetic testing for Huntington’s’ disease and breast cancer genetic research. This suggests that people put a high value on preserving their ability to be hopeful. While concern with insurance discrimination may have resulted in the avoidance of testing for these diseases, it also seems that when push came to shove, many people simply did not want to know their genetic risk status for these diseases. It is yet to be determined what lies ahead for schizophrenia.
Conclusions: Exploring the ethical and social implications of early intervention in schizophrenia gives us a chance to consider what measures might be taken that minimize risks without stopping improvements in treatment. It is important to keep in mind that despite the risks, current prodromal populations receiving treatment are symptomatic and well defined. But in considering people for early intervention, there is an important question of protecting any period of normalcy that the at-risk individual might have had prior to diagnosis or prior to the onset of symptoms that interfere with functioning and quality of life. Overall, decisions by doctors, patients and family members can be facilitated by being sensitive to all the ethics and risks involved, along with gaining accurate and balanced information on the proposed therapies that may impact the course of schizophrenia.
Support: This work was supported by RO1 MH59114: MH01699 K24 and by the G. Harold and Leila Mathers Charitable Foundation.Posted by Farzin at January 23, 2005 11:28 PM | TrackBack