The Pros & Cons of Conducting Clinical Trials in a Private Practice
Opportunities to innovate are at hand, but not without hard work and risk.
Michael D. Ober, MD
Retina subspecialists have proved to be creative, innovative interventionists who quickly implement new ideas. There is an ever-expanding pool of hard data to guide our treatments, yet we often find ourselves confronting each case and disease as an individual challenge, rather than following algorithms by rote. It is part of what drew us to the profession and much of what continues to make it so rewarding. Dr. Philip J. Rosenfeld's pioneering use of intravitreal bevacizumab aptly exemplifies the type of bold thinking and action to which we aspire when faced with less than optimal treatment options. The speed with which our community adopted this technique is perhaps equally astounding as the initial revelation itself.
Historically speaking, commercial interest in the treatment of retinal disorders is at a high point. The overwhelming success of Lucentis, whose annual sales continue to exceed $1 billion despite stiff competition from Avastin, has demonstrated that retinal conditions recently considered virtually unassailable can be treated successfully while generating considerable profits for the pharmaceutical industry. There remain abundant opportunities to advance current therapies as well as implement new ones, and companies are eager to meet this demand.
Consequently, there is a great demand for competent retina specialists and their patients to conduct clinical trials. In the past, these responsibilities usually fell to academic institutions, but manufacturers are now increasingly open to, and often prefer, partnerships with physicians in private practices. The efficient, cost-conscious, high-volume environment essential to a successful private practice is inherently attractive to those organizing a clinical trial.
So if your professional goals include contributing peer-reviewed knowledge to the field, the timing might be right. Here are some pros and cons to consider before embarking on this course of action.
• Pros: Once your practice becomes established as a site where clinical studies take place — when you have the right staff, office setup, equipment and experience under your belt — you can use this infrastructure to pursue your own ideas.
I began my career at Henry Ford Hospital, where, with the help of my colleagues, I pursued and successfully procured many clinical trials. The patients enrolled in these trials were already being seen within our department; the change involved reorganizing a research division, educating technicians and investigators to screen for potential patients, and designating space. The additional trials required and paid for additional coordinator staff. Once this system was firmly established, we were then able to easily pursue unfunded “mini-trials” of our own as well as investigator-initiated trials, resident projects, etc.
In 2006, Seenu Hariprasad (associate professor of ophthalmology at the University of Chicago) and I founded a 501(c)(3), the CONNECT Network (www.retinaconnect.org), as a forum for a group of young retina specialists to pursue their own, original research projects. For one of our first projects, Jay Stewart, MD (associate professor of clinical ophthalmology at the University of California, San Francisco, and director of the vitreoretinal service at San Francisco General Hospital) proposed and designed a trial conducted at several CONNECT Network member sites analyzing the bacterial contamination of needles used for intravitreal injection.1 Having this infrastructure in place is essential to participating in these trials that provide little or no money for coordinators or staff.
When I moved into private practice, one of my goals was to continue work in this vein. The first step, however, was to firmly establish a healthy practice of my own, which took nearly all my time, effort and concentration. A healthy practice is dependent upon earning the confidence of referral sources, which is best gained through taking care of patients. The same model I used to establish a research infrastructure in an academic setting applied to my current practice.
From a public relations standpoint, involvement in clinical trials lends a practice the imprimatur of a cutting-edge organization. Not only does this improve patients' perception of your services, it can also positively impact your referral volume and enhance the quality of your professional life. The satisfaction of helping expand the sphere of medical knowledge can impart an element of enthusiasm to all your employees.
But perhaps the most positive aspect of being an innovator is the chance to offer treatments unavailable to the general public. It is still difficult to tell patients who are losing vision that there is nothing to offer them. Clinical trials allow patients the choice to pursue further action when alternative treatments don't exist or are not effective. The patients who received off-label Avastin therapy at Dr. Rosenfeld's clinic one year before anti-VEGF became available now likely know how lucky they were. There is a good chance that somewhere right now a cohort of dry AMD patients is undergoing experimental therapy that will preserve vision that would otherwise have been lost.
Of course, innovation on one front can have the potential to stifle it elsewhere. After Dr. Rosenfeld's breakthrough in delivering affordable anti-VEGF therapy to the profession, the pharmaceutical industry was decidedly skittish about funding other investigational therapies that might one day be undermined in the marketplace by a cheaper, off-label alternative. Such is the power one wields when designing one's own clinical trial. It can certainly feel exhilarating, but be mindful that the effects may reverberate in unintended ways.
• Cons: Converting a private practice into a clinical trial site is a time-consuming, painstakingly difficult process. It requires years of commitment, new staff hires, increased office space and mountains of paperwork. It basically entails up-ending the status quo and implementing some pretty fundamental changes to your professional life and those of your staff; hence, it is not something to be entered into lightly.
In addition, desirable as innovation is, patient safety must supersede any attempt to write our names into the medical history books. This is discussed later in the article.
• Cons: In my opinion, clinical trials should not be viewed as a rescue strategy for underperforming revenue streams, nor should they serve as a start-up approach for fledgling practices. Only successful, thriving practices that treat large, diverse patient bases should consider adding this component. While participating in clinical trials for specific disorders may provide comfort for potential referral sources and patients, for the most part clinical trials will not bring new patients to your door. On the contrary, it takes a healthy, thriving practice to spend the extra time and incorporate the staff necessary to properly facilitate a trial.
Pharmaceutical companies will want to gain access to your stream of new and existing patients. They will attempt to screen for a practice's ability to enroll based upon your past/current patient population. While advertising costs are sometimes included in clinical trial budgets, the extra time, space and staff required render clinical trials a poor choice to rescue or revamp an underachieving office.
When the numbers are crunched, clinical trials should generate more revenue per patient than ordinary practice, but usually not more profit. The additional time, space, staff, paperwork, scheduling, etc., necessary to treat study patients will offset at least some of that extra revenue. Also bear in mind that once this aspect of your business is up and running, the revenue stream must be maintained. Trials end, but employees continue to draw salaries until they are no longer employed.
• Pros: On the other hand, you probably will not risk going bankrupt either. Next to energy conglomerates, pharmaceutical companies are the most profitable in the world, and they spend lavishly to develop new products. A great place to start in this field is early-phase trials. Drug companies will go the extra mile to assist your practice, offering advice and sending support staff to your site, sometimes even covering the salaries of study coordinators. And with so many potential new therapies in the pipeline, opportunities for such studies are on the rise.
For high-volume practices, an active, diverse number of clinical trials can provide a healthy profit to a retina practice; however, it takes time, effort and substantial risk to achieve this end. Perhaps the most important aspect in deciding to participate in clinical trials is the interest of the investigators. If this is something that appeals to you, then it is worth the extra hassle involved.
• Pros: Drug company largesse sometimes extends to the instrumentation needed to administer care during trials. For example, in order to standardize trials, in some cases OCT devices required for participation have been provided to practices that had used a different brand. Most times, the equipment provided involves smaller, more specialized items that are required for a particular study, such as a centrifuge, refrigerator, flare-meter, visual acuity projector, etc.
• Cons: Most trials will now base selection upon prospective sites that already have the vast majority of equipment required for the trial.
One of the largest potential costs is never provided for: office space. Depending on your location, an extra examination lane, storage space, refrigerator and so on can consume valuable space. Most practices with multiple trials set aside designated, sequestered areas where trial patients undergo study and counseling, very often one or more extra-long examination lane.
The most vital and time-consuming overhead consideration is additional staff. There is no doubt in my mind that a diligent study coordinator is by far the most critical component to a successful clinical trials operation. It is the topnotch study coordinator who can minimize the time required by the investigators. There has to exist a significant amount of trust between investigator and coordinator for things to be accomplished efficiently. These are the people who handle the bulk of the paperwork, scheduling and detail-oriented minutiae, freeing physicians to practice medicine. The ideal would be to hire a study coordinator with experience, but when first starting out you will likely need to train an ophthalmic technician or nurse on the job so that they can still provide other services outside the trial.
Technicians and photographers are another essential component. Photographers must be certified by whatever reading centers you will be partnering with, and each reading center has a unique certification process. The process, although not difficult for a talented photographer, can be time-consuming with strict requirements. In general, it takes over twice as long to prepare and shoot images on a study patient vs a non-study patient.
Technicians also must be certified for some studies and this too can be time-consuming. The work-up takes significantly longer for a study patient. Given these factors, it is often best to have multiple certified photographers and technicians available to allow for the extra time needed.
Finally, prepare for greater difficulty scheduling staff. Because many studies require masked and unmasked examinations, very often two physicians will be required to be at the same office at the same time. It is preferable that those physician pairs remain consistent throughout the course of the study. For this reason, satellite offices may not be appropriate. The more participating physicians that are in a single office at the same day multiple days per week, the easier it will be to schedule follow-up visits for patients.
Keep in mind that most clinical trials require frequent, time-consuming visits, and arrangements can be very difficult when trying to balance the schedules of masked physicians, unmasked physicians, masked/unmasked certified techs, coordinators and certified photographers. The more duplication on hand for each category, the easier it will be.
• Cons: One ethical question I ask myself for each potential study is, “What are the chances this patient could be harmed from participating in the trial?” In evaluating potential trials, I look carefully at the comparison arm. Occasionally I am offered a trial whose control arm fails to adhere to what I consider to be the standard of care. This could potentially put me in the position to relegate a patient for whom I believe there is a beneficial treatment to the placebo arm. This is one factor that has made me decline participation in the past.
There is great pressure from the sponsor to maximize enrollment from each site. Each investigator is in turn incentivized to enroll as many patients as possible. Despite this, it is imperative that each patient have some potential benefit for their participation in a trial. Not all patients who meet enrollment criteria are good study candidates.
• Pros: At the beginning of this article, I characterized retinal physicians as creative and innovative. I might also add independent-minded and not fond of taking orders from the government or corporations. Thus there is often concern that somehow our autonomy will be “compromised” by involvement in NIH- or corporate-funded trials. I can only speak for myself here, but in my experience, this has never been the case. Of course pharmaceutical companies want to put the best spin possible on their products, but they have no means of coercing or strong-arming us into doing or saying anything against our wishes. Again, speaking for myself only, I have never been given less than my due in respect and autonomy.
Re-outfitting a practice to conduct clinical trials is not for everyone. But for those willing to devote sufficient time and navigate some obstacles, the rewards can continue paying dividends throughout a career. RP
1. Stewart JM, Srivastava SK, Fung AE, et al. Bacterial contamination of needles used for intravitreal injections: a prospective study. Occul Immunol Inflam. 2011;19:32-38.
|Michael D. Ober, MD, practices ophthalmology at Retina Consultants of Michigan in Southfield, Michigan. His clinical trials experience includes work for Alcon (Retaane), Alimera & pSivida (Iluvien), Allergan (Ozurdex), Eyetech & Pfizer (Macugen), Genentech (Lucentis), L-Path & Pfizer (iSONEP), OD-OS (Navilas laser) and Regeneron (Eylea), as well as the NEI-funded studies SCORE, ACCORD, AREDS II and several DRCR.net protocols. He can be contacted at email@example.com.|