Consent and privacy in pharmacogenetic testing
Date accessed: 9 October 2001
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Consent
and privacy in pharmacogenetic testing John A. Robertson School of Law, The University of Texas, Austin, Texas 78705
USA. The clinical use of pharmacogenetic
drugs will require that a sample of a patient's DNA be tested before a
drug is prescribed. Although pharmacogenetic tests pose fewer risks than
genetic tests for disease mutations, they might still reveal personal
information that could be used adversely to a patient's interests.
Informed consent and privacy of pharmacogenetic test results may be
essential in most clinical uses of pharmacogenetic drugs. The benefits of
genetics-based medicine depend on a better understanding of the genetic
causes of disease and on applying those insights in clinical practice.
Clinical applications of genetic knowledge often require testing of a
patient's DNA to identify disease-related mutations or other polymorphisms
that have clinical relevance. Genetic testing, however, raises ethical,
legal and social issues that need attention in order to realize the
benefits of genomic knowledge. Most ethicists now agree that genetic
testing for late-onset diseases as well as, susceptibility, presymptomatic
and carrier testing, should take place only after the person to be tested
has given informed consent to the risks and benefits of the test, and has
received genetic counseling appropriate for that test1-3.This
ethical consensus flows from the importance and sensitivity of the
resultant information, and the difficulty that even educated laypersons
have in understanding the probabilistic nature of test results. A person's
knowledge of variations in his genotype may radically change his
self-image and his life and reproductive plans. If preventive or
ameliorative action is possible at all, it may be highly intrusive and not
covered by health insurance. If other persons become aware of the
information, they might stigmatize the person or use it adversely in
insurance and employment decisions. |
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Pharmacogenetics (PGx), which is now a
central focus of pharmaceutical endeavor and on the near horizon of
clinical practice, aims to identify genome-wide polymorphisms or mutations
that will reliably predict an individual's response to drugs before they
are prescribed. Used clinically, PGx information could identify
nonresponders and those likely to suffer adverse drug reactions, and thus
save them the burden of unsafe or ineffective drugs. In addition, PGx
information can identify new drug targets and streamline the drug-testing
and approval processes. Although the field is still too new to project
medical or economic effects with certainty, some in the pharmaceutical
industry have argued that, ultimately, the cost savings from unnecessary
or harmful drug prescriptions may more than outweigh the increased costs
of developing pharmacogenetic agents for smaller subgroups of the
population4. If PGx is to become an effective tool
of clinical practice, however, it too will require genetic testing of
individuals. Although some PGx testing will identify disease mutations,
most PGx testing will identify single-nucleotide polymorphisms (SNPs) in
an individual that can be compared to known SNP profiles for drug or
disease outcomes. It has been suggested that such tests are different from
other genetic tests because their intent is not specifically to determine
or predict risk of disease4.
Accordingly, they should not be subject to the same informed consent,
genetic counseling, and regulatory requirements that apply to mutational
disease testing. Indeed, applying those standards to PGx testing could
block the easy integration of PGx into clinical practice, thus depriving
patients and the health care system of the great benefits that PGx testing
potentially makes possible4.
(See editorial5
on page 195
for further discussion of the balance between privacy and facilitating
medical research.) Although PGx tests based on SNP
comparisons will convey different information than mutational testing, and
thus may not be quite as fraught with medical, social or personal
significance, SNP-based PGx tests may still affect a person's image of his
future or be used adversely against him. Even if genetic counseling is not
required before PGx tests are given, clinicians should still inform
patients of the risks and benefits of those tests, obtain their consent
(before testing), and ensure them that they have taken adequate measures
to assure the privacy of test results (Box
1). The absence of such protections could affect the willingness of
persons to be tested and the ready integration of PGx testing into
clinical practice. |
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The risks of pharmacogenetic testing A PGx test showing that someone is
unable to metabolize a drug by a given pathway may also be informative
about that person's ability to metabolize other drugs, and thus indicate
the likelihood that physicians can effectively treat the person with drugs
for other diseases. Although the frequency of such collateral information
about other drug responses is unknown, many drugs may share common
metabolic pathways. If such cases occur, physicians and insurers may
attach the label of 'nonresponder', derived from a PGx test for one drug,
to an individual more generally (A. Buchanan et al., manuscript
submitted). This label could affect the patient's perception of self, her
future medical care, and her ability to obtain insurance or employment. In some cases, the PGx test might
identify polymorphisms in coding regions that are themselves mutations
that indicate the likelihood of other diseases or of progression of his
present disease. PGx test results may also indicate that family members
carry a high risk of having the same SNPs and thus have the same PGx
limitations. Some PGx tests, when combined with SNP-related PGx tests of
offspring, might also lead to unintended revelations of non-paternity. In short, although generally not as
important as mutational disease testing, PGx tests may reveal information
that has medical, personal, social and family consequences. It is unknown
at present how often PGx tests will have such effects, but the chance is
sufficiently great to warrant attention now. To treat patients fairly,
reassure the public, and encourage patients to undergo PGx testing,
providers and policymakers should pay careful attention to issues of
informed consent and protection of the privacy and confidentiality of PGx
test information. |
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Informed consent Although it is important to convey this
information in an understandable form, the consent process need not be
elaborate or unduly burdensome. An oral explanation of the "need to
get some DNA to tell whether we can prescribe a drug," and
reassurance that the provider will protect the privacy of the results,
might suffice, with more elaborate discussion as needed. In addition to
oral communications, much 'informing' may occur through brochures or forms
written to be easily understood by patients. As PGx tests become
integrated into clinical practice, patients will better understand the
function of PGx testing in their consultation with a physician. Providers should request that patients
sign a consent form before obtaining and testing DNA from a patient, a
practice now common for many clinical laboratory tests. The genetic
counseling widely recommended for genetic testing of late onset,
susceptibility, and carrier conditions should not ordinarily be necessary
for most PGx tests. However, physicians, hospitals and other health care
providers should be prepared to inform patients of the importance of not
qualifying for a drug based on results of PGx testing, and counsel them
accordingly. Pharmacists may also be involved in educating patients and in
assuring that PGx testing has occurred or been offered to patients. An important policy issue is whether a
patient who has not satisfied the PGx indications for prescription of a
drug may still receive it. Some patients may refuse a PGx test. In other
situations, testing equipment or facilities may be unavailable. Still
other patients who do undergo the PGx test may not qualify for
prescription of the drug according to the terms of Food and Drug
Administration or regulatory approval. In many of these cases, the
physician may still think that the drug is the best course for the
patient, or the patient may independently request the drug, despite the
risk of adverse reactions or low efficacy. An important policy question is
whether existing practices that allow off-label use of drugs will carry
over to off-label use of PGx-based drugs, and whether health insurers and
drug benefit plans will cover 'off-label' use6.
If so, physicians should fully inform patients of the risks of taking a
drug that has not been approved for someone with his PGx profile and the
availability of alternative treatments. |
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Privacy and confidentiality One way to reassure the public is to
enact laws that protect the privacy of DNA samples and information
resulting from them (Box
1). Most states do not have specific protection for a person's
ownership or control over DNA samples, although every state does protect
to some extent against the unauthorized disclosure of some medical
information7.
Such protections would almost certainly apply to the results of PGx
testing contained in medical or hospital records, even if they did not
extend to the DNA samples themselves. The scope of legal protection varies
widely, however, and legal restrictions may not directly apply to many
holders of medical and genetic information8.
Federal privacy regulations issued under the Health Insurance Portability
and Accountability Act of 1996 at the end of the Clinton administration,
which President Bush has accepted with a few exceptions, would greatly
extend the legal protection against unauthorized disclosure of medical
information9,
10.
Those regulations define"individually identifiable health
information" broadly enough to cover the results of PGx testing, thus
providing a more extensive protection of privacy for genetic tests than
now exists in most state laws. In addition to explicit legal
protection of DNA samples and PGx test results, it would also be useful if
health care providers were to develop secure methods of deriving and
storing PGx test information (Box
1). One technique would be to create effective 'firewalls' between
genetic data and unauthorized users, for example, by having the results of
PGx tests in the medical record only with regard to whether a particular
drug might be prescribed, rather than including the patient's actual SNP
or genetic profile (A. Buchanan et al., manuscript submitted).
Although privacy 'firewalls' would not protect against disclosure of
medical information requested by insurers and employers, they could be
effective against unauthorized disclosures beyond the control of the
patient or physician. |
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A second technique would be to use
trusted intermediaries as repositories of genetic information or DNA
samples11.
These intermediaries would release genetic information about a person only
when that person specifically requested it. Although not necessary for
every PGx test or interaction, privacy intermediaries may become important
in ensuring the privacy of genetic information in research settings, in
clinical settings in which multiple tests are run on the same DNA sample,
or whenever full genetic profiles on individual patients are obtained. As
PGx tests and uses develop, providers and policymakers should consider how
to structure and use privacy 'firewalls' and intermediary holders of
genetic information to protect privacy. These devices are essential
components in reassuring the public that a PGx test will not lead to
violation of their privacy or to other adverse consequences. Finally, policymakers should consider
enacting laws that protect a person against insurers, employers or other
persons using the results of PGx tests adversely to that person's
interests. Such laws would not protect people generally against the use of
genetic information in insurance and employment, but they would protect
against adverse use of PGx test results. This protection would encourage
patients to obtain PGx tests in connection with their clinical care, even
if similar protection against the use of mutational test results were not
also provided. Conclusion Received 13 April 2001; Accepted 25 May 2001. |
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REFERENCES
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ACKNOWLEDGEMENTS The author
acknowledges discussions with B. Wilfond and C. Freund, and with his
colleagues in the Pharmacogenetics Consortium (A. Buchanan, B. Brody, A.
Califano, E. McPherson and J. Kahn), a project of The University of
Arizona funded by GlaxoSmithKline, First Genetic Trust and IBM.
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Categories: 48. Privacy, 59.
Genetic Testing
