Becoming involved in a clinical trial gives patients the opportunity to have a seat at the table of innovation,” says Robert Hotchkiss, MD, Medical Director of Clinical Research at HSS. “Study participation is about taking a more active role in health care.”
From a medical research perspective, the benefits include a better understanding of disease, enhanced treatment measures, and improved quality of care. For patients, the decision to become a part of a scientific investigation requires a clear sense of what participation means. Currently, Hospital for Special Surgery is busy with over 400 active human studies and preparing for more to come.
Weighing the pros and cons of study participation requires careful consideration and information. Prospective candidates should learn as much as possible about the study, including facts about trial protocol, length and design, tests involved, randomization, potential risks and side effects, hospitalization, reimbursement for medical and related expenses, and how participation will affect everyday life.
“Some patients who enroll do not fully understand the commitment that is necessary,” notes Dr. Hotchkiss. “Study participation can be time consuming and inconvenient, a fact that can pose a problem in recruitment and in patients opting out.”
For many patients who decide to sign up for a clinical study, however, the benefits outweigh the risks or interruption of daily routine. Patients may volunteer for a clinical trial when standard treatment options are unsuccessful and with the expectation that, if proven effective, they will be “first in line” for a new therapy. Others hope to participate in the research process, help fellow patients, and contribute to the advancement of medical knowledge. Healthcare costs are also a consideration for clinical trial entry, as expenses associated with study treatment are typically covered. Patients are also likely to volunteer as a study subject when the goal of treatment is focused on improving quality of life. “If a treatment is novel and offers benefits with low risk,” observes Dr. Hotchkiss, “enrollment is more attractive to a patient.”
In addition, a bit of publicity can play an important role in generating interest in study enrollment. Dr. Hotchkiss points to the influence of Internet sources such as the NIH-sponsored ClinicalTrials.gov, as well as targeted announcements in other communication vehicles which help to spread the word about trials and recruitment. In fact, news about the current trial in the treatment of Dupuytren’s contracture, a degenerative disease of the hand, circulated so quickly that HSS reported immediate and overwhelming interest in participation.
For Beverly Lambert, singing and playing the piano would always go hand in hand, until a crippling disease took away mobility in her fingers. “As a vocal coach, I use the piano to practice scales with my students,” explains Ms. Lambert, age 58, of Fairfield, Connecticut. “The problem in my right hand not only impacted my ability to teach, it had a great effect on my livelihood.”
Dupuytren’s contracture is a progressive shrinkage of the connective tissue in the palm of the hand that can make fingers curl in. The cause is unknown although minor injury and genetics (in Ms. Lambert’s case, both her mother and father have the condition) may contribute to disease. Surgical treatment can restore normal movement to the fingers, but is often associated with lengthy recovery, potential nerve damage, and high rate of recurrence.
“During a visit for a second opinion about surgery for my condition, I was informed about a clinical trial to test a nonsurgical treatment and I wanted to learn more,” recalls Ms. Lambert. “After searching and waiting, I found Special Surgery and Dr. Hotchkiss.”
At HSS, Ms. Lambert signed up for a randomized, controlled clinical trial to explore the safety and efficacy of enzyme (collagenase) injections for Dupuytren’s contracture, which included 20 participants. A Phase III study, recent findings published in the New England Journal of Medicine revealed that the collagenase injection showed promise in restoring nearly full extension of the affected fingers. “The idea behind the collagenase is dissolving the diseased tissue, rather than surgically removing it,” explains Dr. Hotchkiss. Based on those findings, an FDA Advisory Committee has recommended approval of the injection, which would make it the first FDA-approved treatment alternative to surgery for this condition.
For three months, Ms. Lambert received the placebo injection in her fingers, and following her enrollment opted to receive the medication. Her results were immediate. “It was very frustrating to receive the placebo during the trial, but I knew that it was a possibility and that I could eventually get the medication,” says Ms. Lambert. “For me, participation was worth any reservations, pain, and time involved to get back to my life.”
Treating physicians who are also investigators recognize their primary duty is to promote their patients’ welfare.
“As a clinician and researcher, I have to be interested in the investigative aspect and also believe that I would be willing to subject myself or my family to the randomization process, even if I’m not sure if the treatment will work,” says Dr. Hotchkiss. “If it doesn’t pass that test [for me], then participation is most likely not possible.”
This approach to decision-making, known as clinical equipoise (or principle of equipoise), provides the ethical basis for medical research involving patients assigned to different treatment arms of a clinical study. For treating physicians considering participation in a trial, it raises important questions about study purpose, design, safety, bias, and research intent. Therefore, based on equipoise, if a clinician is contemplating research of a drug or treatment versus placebo control, and strongly believes that the study treatment is better than placebo, then the clinician is ethically bound not to participate in that study. An objective, unbiased study and its conclusions are achieved only when a clinician-researcher sets out not to prove a theory, but to challenge it.(1)
Using equipoise as a guide, Dr. Hotchkiss also advises health professionals to practice vigilance and choose words carefully when speaking to their patients about trial enrollment. “It should be presented as an opportunity to participate in a study of a drug or treatment, regulated by the FDA, that may show promise.” Accordingly, Dr. Hotchkiss stresses that “patient care comes first.” Thus, when interacting with an individual who is your patient and also a study subject, it is important to always be mindful of preserving the doctor-patient relationship.
Editor's note: Xiaflex - an injectable treatment option - is now approved by the FDA. HSS hand surgeons Drs. Aaron Daluiski, Robert Hotchkiss and Scott Wolfe are now using Xiaflex to treat Dupuytren's Contracture following its use in a clinical trial at HSS.
1. Kraemer, Helena. 2006. “Understanding Clinical Equipoise.” Available from 4researchers.org [cited 20 July 2006]; INTERNET.