Cases & Commentaries

Overriding Considerations

Commentary By Neil A. Holtzman, MD, MPH

The Case

Mrs. G visited her obstetrician for first
trimester routine prenatal care. The obstetrician offered genetic
testing for a variety of conditions, including Tay-Sachs and
Canavan's diseases, since both Mrs. G and her husband, a healthy
35-year-old physician, were of Ashkenazi Jewish descent. Mrs. G
consented to be tested and told the obstetrician that she would
discuss with her husband that evening whether he wanted to have the
genetic tests. The obstetrician gave Mrs. G consent forms and
information to take home to her husband. The obstetrician also
entered laboratory test orders in the computerized order entry
system for the genetic screening panel for both Mrs. G, since she
had consented to be tested, and for Dr. G, assuming he would
consent to be tested. However, the obstetrician did not mention
this to Mrs. G.

At home that evening, Dr. G reviewed the
materials and told his wife that he definitely did not want to be
tested. Several weeks later, Dr. G visited his primary care doctor
for a check-up. The physician ordered routine screening laboratory
tests (fasting lipid profile, complete blood count, and urinalysis)
through the computerized order entry system, and the next morning
Dr. G presented to the laboratory for testing. The laboratory and
its computer system were the same as used by Mrs. G's
obstetrician.

Unbeknownst to Dr. G, the phlebotomist drew
samples not only for the routine testing ordered by his primary
care doctor but also for the genetic screening, because it was
listed in the computer even though Dr. G had not consented. In
doing so, the phlebotomist overrode the computerized alert that
prompted him to be sure the patient had consented; he assumed that
the physician must have obtained consent before ordering the tests.
Ten days later, the obstetrician called Mrs. G to give her "the
good news" that all her screening tests were normal. The
obstetrician mentioned incidentally that her husband tested
positive as a carrier of Canavan's disease. This disclosure caused
some distress, but no physical harm. No increased level of care was
needed.

The Commentary

Some health care providers will think Dr. G's
refusal to have genetic tests for serious disorders was irrational.
There are, however, a number of reasons why Dr. G's decision might
be rational. His decision reveals some of the complexities of
testing, particularly for individuals who belong to groups that are
at increased risk of possessing certain disease-related
mutations.

First, without a significant family history of
the disease, he may perceive the risk of having an affected fetus
as too low to warrant testing. The couple's estimated risk is 1 in
3600 for Tay-Sachs and 1 in 6400 for Canavan's. [ note that site calls it
Canavan disease ] Second, the utility of testing would be
limited if the G's were Orthodox Jews (whose beliefs generally
prohibit pregnancy termination, even if a fetus were found to be
affected).

Third, Dr. G could have concluded there was no
point in his being tested unless his wife was found to be a
carrier. If Mrs. G was tested on her first prenatal visit, there
would still be time after the result was returned for him to be
tested. If he also was positive, the couple could then consider
prenatal diagnosis. Since the chance of either of them being a
carrier of Tay-Sachs is about 1 in 30 and of Canavan's about 1 in
40 [ go to related site ], the chance of their both
being carriers is 1 in 900 and 1 in 1600, respectively. Couples in
whom both partners are carriers have a 1 in 4 chance of having an
affected fetus with each pregnancy. Hence, the overall risks
mentioned above of 1 in 3600 and 1 in 6400, respectively.

Fourth, once Dr. G knows he is a carrier he may
feel he has an ethical obligation to inform his brothers and
sisters that they each have a 50% chance of being a carrier.
Sharing of important genetic information can be problematic and
have significant consequences within families.(1) Fifth, Dr. G may be concerned about the ramifications
that a positive test might have on his access to, or costs of,
health care insurance, either for himself or his child. In sum, Dr.
G could have had any number of rational reasons for his decision.
His decision thus highlights the the complexity and potential
impact of carrier testing for an individual, and the need of all
patients who are offered genetic testing to completely understand
the risks, benefits, effectiveness, implications, and alternatives
to testing and, based on that understanding, to consent to
testing.

Thus, refusing informed consent for carrier
testing and other types of genetic testing is not irrational.
Unfortunately, many physicians take the matter of informed consent
lightly. Giardiello and colleagues found that only 17% of patients
who had a genetic test for familial adenomatous polyposis had given
written informed consent.(2) In
1996, we asked a representative sample of Maryland physicians
(including obstetricians) how important they thought it would be to
obtain consent from a woman at high risk of hereditary breast
cancer before obtaining a test for BRCA1. Only 56% of responding
physicians thought it was "very important."(3) As well, there are practical barriers to effective and
complete informed consent. Ensuring adequate patient understanding
of disease prevalence, risks of testing, and long-term consequences
takes significant time on the part of the clinician and may not be
adequately reimbursed as a physician service.

The need for informed consent must also be
examined rationally. When the benefits of any intervention outweigh
its risks by a wide margin, and when the risks are minimal, a
formal consent process is less important.(4) For procedures that have reproductive and family
ramifications, which is the case for prenatal and carrier genetic
testing, informed consent is always important.

What can be done to provide clinicians with the
necessary tools to obtain truly 'informed' consent and protect
patient autonomy? More medical education focused on patient
autonomy and the importance of informed consent in genetic testing
is an important foundation. Some evidence shows that current
curricula may have an impact: at two medical schools, approximately
two-thirds of first and fourth-year students thought obtaining
consent before testing was important.(3)

Steps must also be taken to ensure patients are
better informed. We are told that Dr. G was given "information" to
review at home, but it is unclear how detailed or explicit the
materials were. Given physician time constraints, information
technology through the use of audiotaped, videotaped, or web-based
materials could facilitate patient education and understanding. One
site, available both to physicians and consumers, that might be
helpful is http://www.genetests.org. Interactive Web sites or
CD-ROM programs could present alternative scenarios in a clear,
easy-to-understand format. These materials could be supplemented by
quizzes whose purpose is to ensure that patients understand the
disclosure/consent documents they have been given before making
complicated decisions. A recent systematic review of consent for
participation in research trials indicated that there might be a
benefit to multimedia presentations.(5) The same review indicated that one-on-one discussions
with neutral educators might be the most effective means of
improving understanding.

Once patients are adequately informed, how can we
document that patient consent has or has not been obtained? The
computerized physician order entry in this case appeared to have a
mechanism to ensure consent at multiple levels, but it was
overridden by the phlebotomist. Fewer than 20% of all hospitals
nationally have computerized physician order entry, especially in
the outpatient setting, so most systems probably do not have
similar rigorous checks in place.(6) But
even when there is an adequate information technology background,
this case demonstrates that the procedure for documenting informed
consent often needs to be strengthened. Physicians should be
responsible for obtaining and documenting written informed consent
from all patients. The written consent should be placed in the
permanent medical record, whether electronic or paper. Signed paper
copies can easily be scanned into the permanent electronic record,
as some institutions have done in the case of advance directives.
Phlebotomists could then be allowed to draw blood for genetic tests
only if they see the written consent signed by the patient and the
ordering physician.

In this case no permanent harm was done.
Nonetheless, protection of patient autonomy for many forms of
genetic testing, or any procedure in which reasonable people may
have doubts about its safety or effectiveness, should receive
priority. We must ensure patients are truly informed and
subsequently establish safeguards to ensure consent has been
provided.

Take-Home Points

  • Some patients will have rational
    reasons for declining genetic testing.
  • For
    many forms of genetic testing, physicians must obtain written,
    informed consent from patients and must document it in the
    chart.
  • Patients must be
    fully educated and informed prior to providing consent for any
    genetic testing when reproductive and family issues arise and when
    the safety and effectiveness of the interventions that are based on
    test results are questionable.
  • Consent safeguards should never be overridden in
    the absence of signed informed consent.

Neil A. Holtzman, MD,
MPH
Emeritus Professor of Pediatrics, Health Policy, and
Epidemiology
The Johns Hopkins University School of Medicine and the Bloomberg
School of Public Health

References

1. Harmon A. As gene
test menu grows, who gets to choose? New York Times. July 21, 2004.
Section A, Page 1, Column 1.

2. Giardiello FM,
Brensinger JD, Petersen GM, et al. The use and interpretation of
commercial APC gene testing for familial adenomatous polyposis. N
Engl J Med 1997;336:823-7.[ go to PubMed ]

3. James CA, Geller
G, Bernhardt BA, Doksum T, Holtzman NA. Are practicing and future
physicians prepared to obtain informed consent? The case of genetic
testing for susceptibility to breast cancer. Community Genet.
1998;1:203-12.[ go to PubMed ][ go to abstract ]

4. Faden RR, Holtzman
NA, Chwalow AJ. Parental rights, child welfare, and public health:
the case of PKU screening. Am J Publ Health. 1982;72:1396-1400.[ go to PubMed ]

5. Flory J, Emanuel
E. Interventions to improve research participants' understanding in
informed consent for research: a systematic review. JAMA.
2004;292:1593-601.[ go to PubMed ]

6. Kuperman GJ,
Gibson RF. Computer physician order entry: benefits, costs, and
issues. Ann Intern Med. 2003;139:31-9.[ go to PubMed ]