The translation of pharmacogenomic technologies from a research methodology to a clinically-relevant tool will require addressing these issues of uncertainty, consent, confidentiality and access. Khoury et at.
] have recently proposed that the adaptation of novel scientific tools to the clinical environment requires the completion of four phases, enumerated T1-T4. In T1, epidemiological observations identify a so-called ‘candidate application’ for a new technology: the discovery of the role of the DRD3
polymorphism in TD would be such a scenario. In T2, the clinical utility of this new technology is assessed through epidemiological studies. In T3, challenges to the widespread implementation of the new technology are identified. In T4, the impact of this new technology on population health outcomes is documented. This article reflects an attempt to predict T3 concerns and to correct for them prior to the implementation of T2 epidemiological studies. We propose three steps which will help to overcome the epistemological and ethical challenges posed by the application of testing for the Ser9Gly polymorphism.
First, it will be necessary to conduct prospective, longitudinal observational studies of patients exposed to both typical and atypical antipsychotics to determine the relative risk of developing TD based on the DRD3
Ser9Gly polymorphism. These studies should control for dose-response relationships and also for drug-drug interactions. We recommend the use of a predictive statistical model that can incorporate testing for other genetic variants recently implicated in TD [56
] and that can accommodate genetic factors that may be discovered in future. International collaborations may be required to achieve the necessary sample sizes in a reasonable time frame. Parameters such as sensitivity, specificity, and positive and negative predictive values should be calculated. Ideally, such studies would then be replicated in independent samples. We will need to deepen our understanding of the pharmacogenomics of other adverse effects associated with antipsychotic use, most importantly the metabolic syndrome [57
] in the context of atypical antipsychotic exposure.
Second, scientists, ethicists and policy-makers will need to be involved in the design of these studies and in the development of guidelines in order to ensure the proper protection of patients’ rights to informed consent, confidentiality and access. This will likely require consensus building between governments, physicians, patient advocates and industry to establish how patients will be enrolled if they are unable to consent, and to determine in advance how acquired genetic information will be used.
One potential solution would be to establish a collaborative non-profit organization to determine capacity, obtain consent, collect and analyze the genetic samples. Only those data relevant to the study of DRD3
polymorphisms would be released to investigators, thereby creating a firewall between the acquisition of data and its content. Similar consortia could be established for each pharmacogenomic study, with specific consent and confidentiality policies established a priori
given the particulars of the effect being studied and the patient population involved. With a healthy, wealthy and informed population, potentially looser safeguards may be acceptable. Given the vulnerability of the DRD3
population to be tested, narrow consent (ie., providing access to samples only for the direct purpose of DRD3
testing) and double-coded confidentiality (ie., releasing information only for clinical decision-making related to that patient) would likely be warranted. Though this construction would limit the potential scientific benefit of samples collected for DRD3
testing, it protects those members of our society who are least likely to be able to advocate for themselves. In their 2010 statement on personalized medicine, the Nuffield Council on Bioethics highlights the need to safeguard privacy, to reduce harms, and to share responsibility for the protection of the most vulnerable among us [59
]. As it is beyond the scope of pharmacogenomic studies to resolve the gross inequalities present in the provision of health care across the world, we see such measures as the most reasonable means at our disposal of addressing issues of access as well as consent and confidentiality.
Ultimately, clinicians, patients and their caregivers will make the decisions about antipsychotic treatment, perhaps informed by pharmacogenomic testing. Therefore, our third recommendation is to ensure proper knowledge transfer from the scientists, ethicists, and policy-makers involved in studying DRD3
polymorphisms to front-line clinicians. The strengths and weaknesses of pharmacogenomic testing will need to be appreciated; as Nikolas Rose argues, pharmacogenomics will likely provide probabilistic information and not guarantees [60
]. Moreover, any pharmacogenomic testing for TD will need to be simple, quick and inexpensive form it to be relevant in clinics, emergency departments, and on hospital wards. Kathryn Montgomery writes that medicine is a science of individuals; this is true from genetic and clinical perspectives [61
]. As such we believe that a ‘genetically-informed’ approach to clinical decision-making will rationalize the management of patients with schizophrenia.