This paper is intended to stimulate debate amongst stakeholders in the international research community on the topic of returning individual genetic research results to study participants. Pharmacogenetics and disease genetics studies are becoming increasingly prevalent, leading to a growing body of information on genetic associations for drug responsiveness and disease susceptibility with the potential to improve health care. Much of these data are presently characterized as exploratory (non-validated or hypothesis-generating). There is, however, a trend for research participants to be permitted access to their personal data if they so choose. Researchers, sponsors, patient advocacy groups, ethics committees and regulatory authorities are consequently confronting the issue of whether, and how, study participants might receive their individual results. Noted international ethico-legal guidelines and public policy positions in Europe and the United States are reviewed for background. The authors offer 'Points-to-Consider' regarding returning results in the context of drug development trials based on their knowledge and experience. Theses considerations include: the clinical relevance of data, laboratory qualifications, informed consent procedures, confidentiality of medical information and the competency of persons providing results to participants. The discussion is framed as a benefit-to-risk assessment to balance the potential positive versus negative consequences to participants, while maintaining the integrity and feasibility of conducting genetic research studies.

1 An acute model of focal ischaemia, which involves permanent occlusion of the middle cerebral artery of the rat with 4 h survival, was used to find the minimum effective plasma concentration of dizocilpine (MK-801) and to determine its dose-effect relationship. 2 MK-801 was administered at the time of occlusion and was given as an i.v. bolus followed by an infusion for 4 h to maintain a steady state plasma concentration of the drug throughout the study.MK-801 was given at 3 dose levels; 0.04mgkg-1 i.v. bolus + 0.6 pgkg 1 min'-infusion; 0.12mgkg-I i.v.bolus + 1.8#ugkg-min-1 infusion; 0.4mgkg-' i.v. bolus + 6pgkg-min-1 infusion, which gave mean plasma levels over the 4 h of 8.0 ng ml -1, 18.9 ng ml-1 and 113.2 ng ml-1 respectively. 3 MK-801 at 8.Ongml-' gave 10% reduction in the volume of ischaemic brain damage in the cerebral cortex which just reached significance. The middle dose of MK-801 (18.9 ngml-1) gave a highly significant reduction in the volume of ischaemic brain damage in the cerebral cortex and hemisphere, volumes of ischaemic tissue being reduced by 60% and 50% compared to saline-treated animals, respectively. The highest plasma concentration of MK-801 (113.2ngml-1) resulted in a 35% reduction in the volume of hemispheric damage and a 40% reduction in the volume of cortical damage, which were significant. 4 The reduction in the amount of protection afforded by the highest dose of MK-801 may be due to the hypotensive effect of this dose. There was no protection against the volume of damage in the caudate nucleus for any of the doses of MK-801 tested. 5 Therefore the minimum effective plasma concentration of MK-801 was 8.0 ng ml1, although the greatest protection was seen with a plasma level of 18.9 ng ml-1. This correlates well with the concentration of MK-801 required to block N-methyl-D-aspartate (NMDA) receptors and prevent NMDA receptor mediated neurotoxicity in vitro.

No single major HLA-related genetic risk factor was identified for lamotrigine-induced SCARs in patients of European origin. Only suggestive evidence was obtained for B*5801, A*6801, Cw*0718, DQB1*0609, and DRB1*1301. Confirmation of these results in a larger, independent sample is needed to determine whether any of the HLA alleles identified are truly associated with the development of lamotrigine-induced SCARs.

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The use of pharmacogenetics and pharmacogenomics in the drug development process, and in the assessment of such data submitted to regulatory agencies by industry, has generated significant enthusiasm as well as important reservations within the scientific and medical communities. This situation has arisen because of the increasing number of exploratory and confirmatory investigations into variations in RNA expression patterns and DNA sequences being conducted in the preclinical and clinical phases of drug development, and the uncertainty surrounding the acceptance of these data by regulatory agencies. This report summarizes the outcome of a workshop cosponsored by the Food and Drug Administration (FDA), the Pharmacogenetics Working Group (PWG), the Pharmaceutical Research and Manufacturers of America (PhRMA), and the PhRMA Preclinical Safety Committee (DruSafe). The specific aim of the workshop was to identify key issues associated with the application of pharmacogenetics and pharmacogenomics, including the feasibility of a regulatory “safe harbor” for exploratory genome‐based data, and to provide a forum for industry‐regulatory agency dialogue on these important issues.