As part of educating patients about their ocular conditions and options for treatment, you may be called upon to advise them about participation in a clinical trial for a novel ophthalmic drug or device. In these discussions, it is important to be cognizant of patients' potential concerns.
THE PHYSICIAN'S PERSPECTIVE, IN BRIEF
The first issue for your consideration is whether the
study in question is one for which you are the clinical
investigator. In that case, you should examine your ability
and motivation to be a clinical trial investigator. The
opportunity to participate in the clinical evaluation of a
new diagnostic technique, medical device, or pharmaceutical
to improve the care of patients with glaucoma is an
exciting one. This work could help develop such a product
for marketing approval and lead to its more widespread
use by a large patient population. Trials involve a
trained and dedicated clinical research office staff that can
deal with the rigors of the protocol and data collection.
The work must be conducted consistent with good clinical
practices (http://www.fda.gov/oc/gcp/default.htm).
Rarely does involvement in a clinical trial generate a positive cash flow for the investigator. Compensation comes in other, nonfinancial ways such as the opportunity to be among the first to evaluate novel products and present the data in a scientific forum. It is important to realize that most products do not receive approval for a host of reasons (efficacy, safety, business). An issue to resolve is communication with your medical liability insurer to see if your work on the study is covered or not. Typically, the sponsor provides some coverage.
The author has reviewed the investigator's perspective previously.1,2 If the investigator is someone other than yourself, consider how the referral will work and how to assure the patient that you are still responsible for his or her care after the study is completed.
THE PATIENT'S PERSPECTIVE
Eligibility
Patients' primary perspective is in terms of their disease.
Thus, one of their first concerns may be, “How will
this new diagnosis or therapy affect my glaucomatous
disease?” The next issue, applicable primarily to treatment
studies, is, “Will I qualify for the study?” Here, you
must truly believe in the equipoise of the proposed
study: that the clinical trial is needed to determine the
utility of the therapeutic intervention over the alternative.
3 There are exceptions, notably vehicle-controlled trials.
In such studies, the investigator most likely already
“knows” that a novel formulation of a β-adrenoceptor
antagonist might be better than its vehicle for a 1-month
study. Nonetheless, the opportunity for a new product
may outweigh any risks in a given patient.
An issue in the field of glaucoma is that many treatment studies require a washout of ocular hypotensive medications prior to enrollment in order to achieve a valid unmedicated baseline IOP. You must believe that the washout will cause no appreciable harm to the patient. Indeed, there are some advantages to evaluating whether a patient needs to be on all of the medications he or she may currently be using.
For both situations, either washout or the chance to receive the vehicle for up to several weeks, you must explain to the very patient whom you have told “don't miss a drop” that it is acceptable to stop medical therapy for a set period. Obviously, only patients with relatively mild and stable glaucomatous disease should be considered for such studies.
Safety
The patient may ask, “Is this new treatment safe?” This
is especially an issue for new chemical entities being evaluated
in humans for the first time. It will behoove you to
have read all of the information from the sponsor, typically
provided in a clinical investigator's brochure, to
decide for yourself if adequate nonclinical studies have been conducted to justify the hypotheses of efficacy. Also look for an adequate
margin of safety of the maximal intended clinical dose versus the dose
that shows toxicity in these nonclinical studies. In that way, you can assure
the patient of the relatively low risk. Typically, documents provided to the
patient use the term investigational product. If you used the term experimental
product (equally valid), patients may show more concern.
Communication
Patients will observe both the verbal and nonverbal communication from
you and your staff about their disease, its progression, and the chance of possible
improvement. Thus, everyone in the office needs to be sensitive and
careful not to inadvertently cause the patient concern, imply disease severity,
or, for patient-masked studies, decode the treatment.
Motivation
Patients may wish to enter a study for reasons other than the explicit evaluation
of a new agent for themselves. Self-centered reasons include the hope
of better care and attention in the office. The trial may give the patient
“something to do.” Some individuals may choose to participate for altruistic
reasons such as a genuine desire to help other patients with glaucoma.
Continuity of Care
For studies to be conducted by physicians in the same office or at other
facilities, patients may be concerned about whether they will continue to
receive care from you. As the patient's eye care professional, you will need to
clarify that, although he or she is still your patient, another physician will be
taking care of the study-related activities. Explain that he or she will return to
you for regular care or at the end of the study.
Informed Consent
Patients need to be assured of the standard components of informed consent.
This information includes a clear statement about the procedure involved,
the expectations of the patients for clinical visits, compliance with
medications used and other practices, and their compensation (if any). They
should also be reassured that their name will be removed from any document
leaving the office. Finally, patients need to understand that they may
withdraw from the study at any time.
CONCLUSION
Clinical trials can represent a great opportunity for you and your patients. It
is important, however, to consider their concerns and motivation for participation
as part of their evaluation and any discussion with them of such studies.
Gary D. Novack, PhD, is the president of PharmaLogic Development, Inc., in San Rafael, California. He consults with numerous pharmaceutical and medical device firms, and he owns stock in Inspire Pharmaceuticals, Inc. Dr. Novack may be reached at (415) 472-2181; gary_novack@pharmalogic.com.
