In this retrospective study of brain MRIs from adult subjects recruited to research studies as healthy volunteers, we found an age-specific effect for incidental findings. We detected few findings considered to have required referral in the younger cohort, but the majority was of high clinical significance. In the older cohort, we detected findings in >50%, although of those classified to require referral, all were classified as routine. Insufficient numbers precluded a discrete analysis of the data by age and decade; therefore, the coarse separation of the cohort into younger and older groups is a limitation of this study. The significant gender difference in the older cohort may be consistent with greater incidence of vascular disease in men than in women but merits specific examination in future research. Nonetheless, the double dissociation between age and severity underscores the imperative to consider the significance of unexpected brain anomalies in healthy control subjects and the means to manage them. This is especially the case as a large majority of adult brain imaging research studies involve either college students easily accessible in the academic environment for studies of normal cognition or older adults in studies of normal aging and those who serve as controls for studies of age-related diseases. To our knowledge, most findings identified in the present study were not detected or reported to participants at the time that the original imaging studies were conducted.
Informed consent is essential to respect the autonomy of parties participating in any form of medical research, as is understanding of each person's underlying motivation to participate. However, the issue of autonomy becomes complicated when pathology is uncovered in someone who has not asked to be screened for his or her own immediate benefit or when a discovery has downstream impact on another party. Such issues take on even greater importance as the number of studies and procedures further accelerate and as CNS anomalies that are not only of structural but also of functional significance are discovered.
In light of these issues, we propose that informed consent and protocols generated on an institution-by-institution basis are not adequately responsive to the problems of incidental findings, at least for the CNS. With recent attention paid to incidental findings on brain MRI, the no-clinical benefit clause has been updated in consent forms at our own institution (Stanford University) to include a request for primary physician contact information and a statement that any follow-up treatment decision lies solely with the subject and physician. However, some investigators may consider that even this augmented text is insufficient because the risk of anxiety associated with the discovery of an abnormality, financial costs of additional diagnostic testing, and the potential for related medical complications are not addressed.
Beyond explicit recommendations for consent, guidelines also should be considered for other protocol issues. For example, we must balance the benefit of involving medical personnel trained to read scans and interact with participants against the legal risk and financial burden of clinician assessment of all participant MRIs and the workload challenges associated with sheer volume. Further, careful consideration must be given to standards for the lag time between image acquisition and reading given the differing types and severity of abnormalities, and to professional level and training appropriate to primary operation of medical equipment such as MRI scanners so that participant safety and confidentiality are ensured (Illes et al, submitted for publication, 2004).6
To achieve this goal and an appropriate evenness in the way that guidelines are ultimately adopted by laboratories, journals, and research sponsors, discussion and debate are needed among investigators, physicians, and even participant representatives themselves who can bring valuable information about their expectations to the discussion. These measures will ensure the protection of participants, provide safeguards for clinicians and investigators, and enhance the overall integrity of the research.