Introduction:
Informed consent recently made the headlines with Congress and the U.S. Food and Drug
Administration (FDA) expounding on circumstances where they will accept the alteration,
minimization or even outright elimination of informed consent in certain clinical research
trials. Some might argue that this continues the slide towards weakened protections
afforded to patients and clinical study participants. However, some courts have taken to
interpreting the requirements for informed consent rather strictly, especially as they apply
to the performer of the informed consent process.
Background:
According to the Code of Federal Regulations as applied by the Department of Health and
Human Services, an investigator may only involve a human being as a subject in research
if the investigator has obtained legally effective informed consent from the subject or the
subject's legally authorized representative. The Code of Federal Regulations, as applicable
to the FDA,echoes these expectations. However, FDA guidances further explaining these
practices4
allow not only the investigator, but also “other study staff” to “[conduct] the
informed consent interview [with] the subject.”
The FDA repeatedly states that the informed consent requirements in 21 C.F.R. § 50 do not
preempt any applicable federal, state or local laws that require additional information to be
disclosed for informed consent to be legally effective. Instead,“[w]here the regulations
differ, the regulations that offer the greater protection to human subjects should be
followed.”This approach ensures that clinical research subjects receive the maximum
protection offered under the law.
Who is an Investigator?
Informed consent laws and regulations apply to investigators and subinvestigators. The
regulations define an investigator as “an individual who actually conducts a clinical
investigation (i.e., under whose immediate direction the drug is administered or dispensed
to a subject). In the event an investigation is conducted by a team of individuals, the
investigator is the responsible leader of the team. Subinvestigators include other members
of the team that perform certain significant functions. Clinical research is almost always
conducted by a team of individuals, typically led by the principal investigator listed on FDA
Form 1572 as the “responsible leader of the team.” The FDA clarifies, however, that the
principal investigator need not be a medical doctor and that a “physician can be a
subinvestigator to perform those study functions requiring the appropriate level of medical
expertise.” This suggests a great deal of flexibility in federal regulations and their
interpretation as to who may be considered a principal investigator or a subinvestigator, and
it also means that an individual who is not a physician may be delegated the primary
responsibility to obtain a subject’s informed consent.
In recognition of the time constraints investigators might face, FDA guidance allows “other
study staff” to conduct the informed consent interview.Practically speaking, this typically
involves the study nurse or coordinator. Still, the regulations seem relatively clear that they
expect the principal investigator to obtain legally effective informed consent.
The Shinal Case :Although federal guidance is relatively flexible as to how the clinical research informed
consent process is to be performed, a recent court case may signal a change to a stricter
model. On June 20, 2017, a divided 4-3 Pennsylvania court, speaking on a seemingly
unrelated issue, interpreted the law to support the plain meaning of the regulations
themselves and not the interpretation of these regulations as seen in the FDA guidance. (It
is not clear whether the court was even aware of FDA’s guidance or if it deemed clinical
research relevant.) The case, Shinal v. Toms, involved a woman undergoing surgery to treat
brain cancer.The treating physician’s assistant obtained a signed informed consent form
from Mrs. Shinal prior to surgery. Unfortunately, during surgery, Mrs. Shinal suffered
permanent injury from complications and sued the physician, alleging his failure to explain
the risks of and alternatives to her surgery.
Until the Shinal case, physicians interpreted the duty to obtain informed consent as one that
could be delegated to a qualified staff member. This delegation could include the entire of
informed consent process, including talking with the patient, discussing the procedure in
question, and then obtaining the patient’s informed consent. However, the Shinal Court
found that effective informed consent stems from the contractual nature of the physician
patient relationship and consequently requires a “meeting of the minds” between the
parties, which could only occur by a physical interaction between the doctor and patient. In support of its holding, the Court quoted Kelly v. Methodist Hospital, noting that the
physician’s unique relationship with the patient, as well as the physician’s education and
training, mean that “the physician is in the best position to know the patient’s medical
history and to evaluate and explain the risks of a particular operation in light of the
particular medical history.”Further, the physician has a duty to disclose these risks to the
patient.Consequently, the Court held that, in the state of Pennsylvania, the duty to
provide informed consent belonged to the physician alone and was non-delegable, because
“obtaining informed consent results directly from the duty of disclosure, which lies solely
with the physician.
Implications for Informed Consent in Clinical Research
Although the Shinal case applied to medical practice, its reverberations can already be felt
in clinical trials, where some might argue that informed consent requirements are, if
anything, more stringent than for medical care. A prima facie interpretation of the Court’s
opinion suggests that informed consent by the physician is non-delegable. While this
reading is not any more burdensome than a strict reading of the regulations, which prima
facie require that only the principal investigator can perform the informed consent
interview, it does place an unexpected burden on clinical research facilities. Although it is
unclear whether the Court intended to apply this opinion to clinical research, there is little to
suggest that courts would not uniformly apply the same informed consent standards used in
the medical practice to clinical research.
If this interpretation of the law applies, the Court’s holding in Shinal will likely have a
significant implication on the speed of clinical research in the face of an already timeconsuming
informed consent process. The Court’s interpretation of this law suggests that
investigators will likely need to personally engage with each potential study participant to
discuss the procedure, possible alternatives, and to make all necessary disclosures.
Investigators are notoriously busy and typically delegate much of the process of obtaining
informed consent to qualified study personnel. However, they should, at minimum, ask the
person if he or she has any questions about the study and determine whether the person is
giving proper informed consent. This flexibility allows greater efficiency and smoother
process flow even as the investigators workflow grows more demanding. In fact, in some
cases, the study nurse might be more knowledgeable about certain study details than the
principal investigator. In addition, consent by the study nurse minimizes the chance of
undue influence that is inherent in the patient/physician relationship.
Since informed consent is a time-consuming process, reserving the responsibility to just the
principal investigators — who probably have the least amount of time — raises other issues
about the adequacy of consent. It adds one more burden to physicians who already feel
overburdened by clinical research duties and are not always available when it is convenient
for the patient.
Issues with the Shinal Ruling
The court found for the plaintiff because the physician relied on a subordinate to obtain
informed consent from the patient, which the court held was a duty non-delegable by the
physician. This raises several issues:
First, it is not clear whether the explanation was inadequate because the physician
possessed a duty inherent in his or her role to obtain informed consent, or whether the
informed consent process must simply be performed by the professional in the best position
to do so. In medical practice, it is reasonable to expect that the physician is the individual
best-placed to discuss the clinical implications of a potential procedure. The physician will
know the patient’s health condition better than the other individuals participating in the
procedure, will have the most experience and training in performing the patient’s procedure,
and will best understand the risks and alternatives.
However, informed consent in clinical studies requires a broader discussion that might need
the involvement of additional team members. For example, clinical trial subjects must be
informed of the possibility of compensation in the event of injury caused by the trial.Although the physician might be the best individual to obtain a subject’s informed consent
with respect to medical procedures, other team members might need to participate in the
informed consent process to ensure the patient is adequately informed in all aspects of the
clinical study. If the study involves a technical procedure, an expert in that procedure might
be better qualified to explain it to the subject. Similarly, the investigator might not be the
best person to explain the logistics or financial ramifications of the study. In some cases, a
subinvestigator might be more expert in the specifics of the medicine than the principal
investigator, who might be more knowledgeable in the mechanics of clinical research.
Ultimately, the Shinal court found that the reason the physician is in the best position to
obtain informed consent is the “education, training and expertise” upon which the patient relies.Requiring the physician to serve as the sole touchpoint for informed consent in
clinical studies might not accomplish that objective.
Exacerbating this issue is the time span for informed consent. In medical practice, the
informed consent process begins when the patient meets with his or her physician for the
first time to discuss treatment. However, the time span is much longer in clinical trials and
does not always involve human interaction. Many human subjects protection experts assert
that the informed consent process starts with the first advertisement the potential subject
sees and continues through the end of a clinical study. Considering the extended time span
of informed consent in the clinical trial setting and the additional procedures and issues that
might arise not involving the original investigator, it is impractical to expect the investigator
to manage all aspects of the informed consent process from beginning to end. Accordingly,
additional team members will become involved as different aspects of the trial process call
for their unique expertise.
Causing further confusion is the difference in professional designations between medical
practice and clinical trials. While the Shinal Court refers to the “physician,” the term
“physician” is not synonymous with the term “principal investigator.” This might cause
confusion as to who obtains the subject’s informed consent. As mentioned above, the
principal investigator in a study might not even be a physician, so under a strict reading of
Shinal suggesting that only a physician performing the procedure can obtain informed
consent, the Shinal case might not apply. However, in the scenario where the
subinvestigator is a physician, then that physician might have the duty to the patient. Under
a looser reading of Shinal, where the person obtaining informed consent must be the
individual in the best position to do so, this duty might fall ultimately on the principal
investigator or on other team members, depending on their areas of expertise.
Causing further confusion is the difference in professional designations between medical
practice and clinical trials. While the Shinal Court refers to the “physician,” the term
“physician” is not synonymous with the term “principal investigator.” This might cause
confusion as to who obtains the subject’s informed consent. As mentioned above, the
principal investigator in a study might not even be a physician, so under a strict reading of
Shinal suggesting that only a physician performing the procedure can obtain informed
consent, the Shinal case might not apply. However, in the scenario where the
subinvestigator is a physician, then that physician might have the duty to the patient. Under
a looser reading of Shinal, where the person obtaining informed consent must be the
individual in the best position to do so, this duty might fall ultimately on the principal
investigator or on other team members, depending on their areas of expertise.
Additionally, as stated above, the Shinal Court found that effective informed consent stems
from the personal, interactive nature of the physician-patient relationship, noting that
“[w]ithout direct dialogue and a two-way exchange between the physician and patient, the
physician cannot be confident that the patient comprehends the risks, benefits, likelihood of
success, and alternatives [to treatment].”If this ruling were to be fully applied, it could
invalidate all consent obtained without a physical physician-patient interaction. While the
relationship is justifiably special, there is nothing in the contractual aspect of that
relationship that requires physical interaction. The success of telemedicine even argues
against the need for physical interaction in the medical part of the relationship.
Additionally, if the principal investigator is in the process of explaining the study to a
potential participant, it is unlikely that the court would prohibit the study nurse from
interjecting a clarification or providing supplemental information. Or, if the principal
investigator and the study participant cannot converse fluently in the same language, it is
doubtful that the court would disallow the use of an interpreter.
Conclusion
The Shinal case, like many, raises more questions than it answers, especially when applied
to clinical research, which does not constitute traditional medical care due to its
investigative nature.Physicians conducting clinical research in Pennsylvania should obtain advice from their legal
counsel, should probably be involved in the consent process if they are the principal
investigator, and, in consideration of the potential demands placed on researchers regarding
adequate informed consent, should certainly strive to obtain informed consent using either
their physician researchers or their experts best positioned to obtain effective informed
consent.
With the issues discussed above, the mere existence of the ruling invites plaintiff attorneys
to argue it in other cases, even outside Pennsylvania
Author
Darshan Kulkarni, Pharm.D, MS, Esq., is Principal Attorney at The Kulkarni Law Firm. He is
also a Visiting Professor at the University of the Sciences and is Vice Chair of the Life
Sciences Interest Group of the American Bar Association. Contact him at 1.215.948.8183
