Are Clinical Trials Right For You?

Three retina specialists share their insights and experiences

BY SUSAN WORLEY, CONTRIBUTING EDITOR

Less than half of all retina specialists in the U.S. choose to make involvement in clinical trials an integral part of their careers. If you think you might like to explore what clinical trials have to offer, you’ll be pleased to know that more opportunities for retina specialists to participate in developing innovative treatments or devices — or improving on existing interventions — have become available in recent years. However, these opportunities require commitment, hard work, and the willingness to accept a certain amount of risk.

“Clinical trials aren’t for everyone,” says Pravin Dugel, MD, Managing Partner of Retinal Consultants of Arizona and Chairman of the ASRS Research and Therapeutics Committee. “Whether you choose to participate in them really should depend on what your goals are. There are some brilliant, excellent physicians who don’t take part in clinical trial work. Interested retina specialists should be extraordinarily passionate about engaging in clinical trials — you should have the right mindset and the willingness to put in an enormous amount of effort.”

Dr. Dugel’s practice currently is involved in more than 30 clinical trials, but it took more than a decade for his practice to establish the infrastructure necessary to accommodate these trials.

“If you’re willing to put in the work, clinical trials can provide you with an outlet that is very intellectually satisfying, a chance to interact with students and fellows, and, most importantly, the opportunity to provide your patients with access to the latest and greatest of everything. When I first came to Phoenix, local patients were being sent to Boston and Philadelphia to participate in trials. Now, they’re coming to us. That has been very rewarding. It was worth the effort to bring this benefit to patients in my area, so they no longer have to travel long distances to participate.”

A NEW RANGE OF OPPORTUNITIES

In recent years, there has been growth in both the number and variety of clinical trials. Clinical trials today may be done in conjunction with government-sponsored studies, within academia, under the auspices of large healthcare institutions, in private practices, or, in some cases, may involve a mix of these entities.

“There weren’t many clinical trials when I was training,” says Dr. Dugel. “There were just a few, and all of them were being done in academic institutions or at the NIH. Now, there are many, and most are sponsored by industry, so our entire field has changed enormously.”

He adds that this welcome change has led to more major advances during the past 10 years than during the prior 50 years combined.

“There used to be a distinction between academia and private practice, but now there is a new breed of practice — an academic hybrid practice like mine — which blurs that distinction. Clinical trials often require high volume, the ability to quickly complete recruitment, to turn around trials quickly, and to interact with industry. A practice like mine is well suited for those things. And the mix allows us to have the volume and independence of a private practice, but still have the fellows, the involvement in teaching, and intellectual satisfaction that used to be largely restricted to academia.”

Perhaps because private practices are now the principal sites of so many clinical trials, the focus of trials at academic and large healthcare institutions has become somewhat more specialized.

“My first real involvement in clinical trials came during my fellowship at Duke,” says Paul Hahn, MD, PhD, Assistant Professor of Ophthalmology and Vitreoretinal Surgery at Duke University. “I served as a subinvestigator under my faculty and mentors, who were principal investigators. They were kind enough to include interested fellows, to give them a sense of how clinical trials work. I highly recommend this kind of introduction — it allows new specialists to learn what is involved in a clinical trial, but without the degree of responsibility or liability that a senior investigator typically assumes. It’s a way to get involved slowly, and learn a little about the back office work that’s involved.”

Since his fellowship, Dr. Hahn has significantly deepened his role in clinical trials with involvement in a wide range of projects, including acting as lead investigator at Duke in post-approval studies of the Argus II Retinal Prosthesis System. In addition, he helped to establish Duke’s Center for Artificial and Regenerative Vision, which will serve as a site for future innovative trials, including investigations of stem cell and other cutting-edge treatments. Clinical trial work in academia, he says, has both advantages and drawbacks.

“Duke has been an ideal place to conduct trials involving very specialized technologies, ones that may not as easily be conducted in some high-volume private practices. A trial involving a retinal prosthesis or work with stem cells, for example, is ideally conducted in an academic environment, where there are resources available for a very specialized kind of care. However, compared with private practices, there can be less flexibility in academia and it can take much longer to get things done. For example, review by the institutional legal team and the institutional IRB, along with negotiation of reimbursement contracts, can be time-intensive hurdles in a large academic center, which may lack the nimble decision-making of a private practice.”

At Kaiser Permanente, Vincent Hau, MD, PhD, is helping to lay the groundwork for engaging in clinical trials in a third type of environment.

“One of the reasons I joined Kaiser was because I saw the enormous potential to get involved in clinical trials,” says Dr. Hau. “Kaiser Permanente plays a major role as a leader in the field of population management, and we have very well-established and well-respected research programs, as well as extensive databases in a number of fields outside of ophthalmology. With so many new funding opportunities in ophthalmology, and especially in retina, it makes sense to utilize existing resources at Kaiser.

“In recent months, I’ve been collaborating with colleagues to tap into the potential for exciting research here. So far, we’ve put together a team of well-established and experienced project managers and clinical study coordinators. Another advantage Kaiser provides is a clinical investigators track for individuals motivated to perform research. For researchers on the track, Kaiser allots a certain amount of paid, protected time to engage in research outside of your clinical responsibilities. Kaiser is very supportive of individuals who are motivated to do clinical trial work.”

When it comes to funding, Dr. Hau recommends searching for local or internal funding opportunities first, because they’re less competitive and easier to obtain than national grants. He also notes that the NIH has programs geared toward supporting investigators who are still in the early stages of their careers — programs that have less stringent criteria than RO1 grants. Of course, new investigators also are likely to find many industry-sponsored opportunities.

SATISFACTION AND REWARD

“I never undertake a clinical trial without thinking that it has the potential to be paradigm-changing,” says Dr. Dugel. “That’s probably the greatest motivating factor for me. And the clinical trials I find most exciting are the very early-phase trials. In some cases, these may be conducted only in my center. It’s a profound responsibility to know that an entire company, lots of people, and a huge investment are depending on us to make sure the trial is done right. Most importantly, of course, patients are depending on us. We must ensure that every trial is conducted in a way that will give us an answer — and an answer that has a great deal of scientific integrity. One of the worst things that can happen is to fail to arrive at an answer — that is not fair to patients or to anyone involved. It’s exciting to know that some of the advances we take for granted — drugs like Eylea^* or Lucentis^† — were once in phase 1 clinical trials. Whenever we work with a new drug or device, I wonder if it will have the same kind of impact those drugs had, whether it will change as many lives.”

It is this opportunity to advance medicine and enrich patients’ lives that should be the driving force for physicians looking to participate in clinical trials.

“Participation in clinical trials requires a great deal of extra work beyond your clinical responsibilities, and monetary compensation is rarely ever the primary motivation for undertaking this work. The true reward will be making a contribution to your field, and helping your colleagues and your patients,” says Dr. Hau.

Dr. Hahn agrees. “Clinical trials offer obvious advantages for patients. They allow physicians to offer patients cutting-edge therapies before they become widely available. Even if a trial isn’t testing a new treatment, it’s still typically testing something new — a new treatment paradigm or novel approach of some kind. Patients appreciate being part of a practice or institution that provides cutting-edge care.”

Observing firsthand the benefits that clinical trials can bring to patients, says Dr. Hahn, is incredibly rewarding. To offer just one example, he reflects on his experience with the first patient to receive the Argus II retinal implant, or “bionic eye,” at Duke.

“The first patient we implanted had essentially no light perception, and his modest improvement afterward was, for him, quite remarkable,” says Dr. Hahn. “Now, when he’s talking to someone, he can see some flashing lights that help localize that person, and he can get some sense of how far away that person is. If he’s at a restaurant, he can see where his glass or plate is, and he can tell where bright windows and doorways are. All these things have greatly increased his confidence in social settings. But perhaps what struck me most were the unexpected improvements in his relationships with others, particularly with his wife. His surgery has opened up a new journey that he and his wife are taking together — they’re finding out what these new flashing lights mean and exploring new opportunities together. Previously he had been self-conscious about being blind. Now, he’s really coming out of his shell. Witnessing this has been unbelievably rewarding.”

Clinical trial work also can lead to many long-term rewards. Dr. Hau, for example, hopes to help establish a clinical research platform that may launch an unlimited number of new collaborative trials.

“Kaiser has a very significant, very diverse patient database that allows researchers to examine a wide range of patient demographics, as well as their relationships to chronic disease, Dr. Hau says. We have access to information about diet, comorbidities, and medications that may have an impact on chronic diseases, such as cardiac disease or cancers. Many medications, for example, affect the body systemically and may positively or negatively impact diseases that affect all parts of the body, including the eyes. Data here offer an opportunity to obtain a more complete picture of how chronic diseases affect the body as a whole. We’ve already conducted impressive research in the areas of cardiology and oncology, so there are opportunities to learn from others outside the field of retina. In fact, cross collaborations can open up whole new perspectives. Sometimes we’re so focused on a particular hypothesis that we forget to look at the bigger picture. The opportunities here are unlimited and open-ended. I have no idea what we’ll be investigating 5 or 10 years from now; as we learn new things, they will lead to us to new questions and hypotheses.”

GETTING STARTED

“I don’t think there is a good primer on how to get involved in clinical trials,” says Dr. Hahn. “The best thing you can do is find a mentor who can help you get started. In my role on the committee of Research and Safety in Therapeutics at ASRS, we have discussed the possibility of keeping a list of clinical trials that specifically focus on retinal research. However, clinical trial information changes so rapidly that we haven’t yet found a way to keep such a list regularly updated. Visiting clinicaltrials.gov can be useful, but you might be more likely to learn about ophthalmology clinical trials through connections with peers and industry.”

Dr. Hahn and Dr. Hau recommend that new retina specialists choose areas of research that excite them first — whether these involve working with novel technologies or with models of disease prevention — and then identifying what is possible within a particular company or institution. Time spent exploring possibilities, they say, is a wise investment.

“When you’re a young physician just starting out, the first thing you have to do is build your reputation,” says Dr. Dugel. “And you build your reputation by taking care of patients well and running a good practice. So that is the first thing I would focus on after training. I frequently tell new specialists that ‘If you don’t have a good reputation, you don’t have anything.’ Next, you really have to go through a period of self-searching and ask yourself: ‘What it is that I really want to do?’ You shouldn’t take part in clinical trials because you think it is the ‘right thing to do.’ It’s not something that comes easily, and you should never underestimate the amount of time and effort it takes to have a clinical trials center. But if you have the right mindset, and you’re lucky enough to have a mentor, then I would reach out to that person. We’re fortunate enough to have a very collegial and small group of people who take part in clinical trials, and they’re always willing to help newcomers.”

Patience and timing, says Dr. Drugel, are key. “Progress has to take place in a step-wise fashion. You can’t decide that you’re going to conduct the next great clinical trial. No one who forgets about taking care of patients and establishing a reputation is going to succeed.” NRP