Tina Silverstein, Yann Joly, Denise Avard
- To identify ethical issues related to research ethics in a pharmacogenomic research context.
- To identify important information to communicate to participants in pharmacogenomic studies.
- To stimulate a reflection on the sensitive nature of pharmacogenomic information concerning large population group of similar ethnic ancestry.
In the context of a clinical trial with Geneticeuticals, Dr. Smith is studying the role of genetic factors in cardiac disease and the available treatments options. He has recruited patients from his practice to participate in both a clinical trial and exploratory pharmacogenomic add-on study. Geneticeuticals financially supported Dr. Smith to conduct the study. However, he received no additional financial compensation per subject recruited.
In the trial, half of the participants are being treated with a new medication, drug "New,"? while the other half are being treated with a standard medication, drug "Old."? Participants originating from North Africa, Central Europe and Japan are split relatively evenly between the study groups. The patient samples are being double-coded and, for the add-on pharmacogenomic research, studied in conjunction with pre-selected genetic markers to determine the efficacy of drug "New"?, which is produced by Geneticeuticals.
Before the samples were collected, the participants went through a detailed consent process during which Dr. Smith informed them of both the clinical and pharmacogenomic aspects of the study. The form included permission concerning the use of the samples, in an anonymized form, for "future pharmacogenomic researches about cardiovascular disease."? The patients were also informed that because of the exploratory nature of pharmacogenomic aspects of the study and since the results of such a small study would need to be revalidated by other researches in a larger setting; results from that portion of the study would not be returned. They were given a signed copy of the consent form for their personal records.
The clinical study concluded with a finding that drug New was as effective (no better and no worse) than drug Old. The participants experienced no side-effects. However, the pharmacogenomic portion of the study revealed that drug New was metabolized more quickly than drug Old in a third of the Japanese participants and in three-quarters of the African participants. For these participants, a higher dose of drug New was needed to produce the same effect as a smaller dose of drug Old; they would therefore have to take drug New two additional times per day in order for it to be as effective as drug Old. While a higher dose is not necessarily worse for the patient, some may prefer to take an equally effective lower-dose treatment.
- Was the consent process sufficient? Consider this question in light of the potential for conflicts of interest, the inclusion of a pharmacogenomic add-on study in the clinical trial and the consent to future research.
- Should Dr. Smith inform his patients of the results of the pharmacogenomic add-on study? Consider this in terms of the value of the information for the patient, their expectations and their right to know.
- Are the ethnicity-related exploratory results relevant for publication of the study? How should they be communicated?
- Tri-Council Policy Statement. Ethical conduct for research involving humans. Ottawa: Interagency Secretariat on Research Ethics; 2005. Available from: http://www.pre.ethics.gc.ca/english/pdf/TCPS%20October%202005_E.pdf.
- Health Canada. Guidance document for pharmacogenomics. Ottawa: Health Canada; 2008.
- Halushka v. University of Saskatchewan et al. 53 DLR (2d) 436 (Sask. CA) 1965.
- Knoppers BM, Joly Y, Simard J, Durocher F. The emergence of an ethical duty to disclose genetic research results: International perspectives. European Journal of Human Genetics 2006; 14: 1170�8.
- Trikalinos TA, Ntzani EE, Contopoulos-Ioannidis DG, Ioannidis JP. Establishment of genetic associations for complex diseases is independent of early study findings. European Journal of Human Genetics 2004; 12: 762�9.
- International HapMap Project. Guidelines for referring to the HapMap populations in publications and presentations. Available from: http://www.hapmap.org/citinghapmap.html.en.
- Foster MW, Sharp RR, Mulvihill JJ. Pharmacogenetics, race, and ethnicity: Social identities and individualized medical care. Therapeutic Drug Monitoring 2001; 23: 232�8.
- Secretary�s Advisory Committee on Genetics, Health, and Society (SACGHS). Realizing the potential of pharmacogenomics: Opportunities and challenges. Bethesda, MA: National Institutes of Health (2008): Available from: https://repository.library.georgetown.edu/bitstream/handle/10822/512867/SACGHS_PGx_report.pdf?sequence=1&isAllowed=y.
- For additional and updated laws and policies, consult: http://www.humgen.org/home
Isaacson Barash C. Ethical issues in pharmacogenetics. Actionbioscience, 2001. Available from: http://www.actionbioscience.org/biotechnology/ethical_issues_in_pharmacogenetics.html. (This is an excellent article featuring case studies pertinent to the use of pharmacogenetics in clinical settings).
- Anderson DC, Gomez-Mancilla B, Spear BB, Barnes DM, Cheeseman K, et al.; Pharmacogenetics Working Group. Elements of informed consent for pharmacogenetic research; perspective of the pharmacogenetics working group. Pharmacogenomics Journal 2002; 2 : 284-92
For answers to FAQs (frequently asked questions) about pharmacogenetics, and information about the ethical, legal and social issues it raises, consult: www.humgen.umontreal.ca.
Acknowledgments: The authors would like to acknowledge the financial support of Genome Quebec/Genome Canada for this work.