• Retina/Vitreous

    Despite a proliferation of new ophthalmic drugs and technologies in recent years that require evaluation by well-conducted clinical trials, many physicians have encountered difficulty in  recruiting patients for clinical trials. Because few working physicians can spare the time to participate in these studies, the bulk of this type of work has traditionally fallen to physicians in academia who are based in university settings.  However, given the fact that the majority of clinical care in the United States is provided by physicians in a non-teaching setting, it is of paramount importance to increase the involvement of this latter group in clinical trials. This article makes the case for supporting well-conducted, well-designed clinical trials that are successful in attracting eligible patients to evaluate important questions.

    Moving Toward Evidence-Based Medicine

    In the past, the published medical literature in ophthalmology was mainly observational in nature and offered few controlled and randomized trials to help guide clinical decision making. As a result, clinical management of patients was not based on empirical evidence, and clinicians tended to draw mainly from their own experience, treating patients by recalling outcomes from previous cases.  The recent trend towards practicing evidenced-based medicine is largely a result of having a greater body of data from randomized and controlled clinical trials available (Circulation. 2004;109:2672-2679). As a result, the last 2 to 3 decades have witnessed the development of such randomized and controlled clinical trials in ophthalmology as the Diabetic Retinopathy Study (DRS), the Early Treatment Diabetic Retinopathy Study (ETDRS), and, more recently, the Age-Related Eye Disease Study (AREDS) and the Advanced Glaucoma Intervention Study (AGIS). 

    Physicians in internal medicine have also seen a similar increase in the number of clinical trials conducted in their field, some of which have been pivotal, such as the Studies of Left Ventricular Dysfunction (SOLVD).  The table below shows the increase in the number of clinical trials performed in a number of internal medicine disciplines.   


    Table 1. Increase in clinical trials performed in internal medicine disciplines.

    Discipline

    1980-1989

    1990-2000

    Percent Increase

    Pulmonary Medicine

    2997

    8248

    275%

    Gastrointestinal Medicine

    3293

    8779

    267%

    Cardiovascular Medicine

    5410

    14,845

    274%

    Lader EW, Cannon CP, Ohman M, et al. The clinician as investigator: participating in clinical trials in the practice setting. Circulation. 2004;109:2672-2679.

    The Rationale for Clinical Trials

    It is clear that clinical practice in ophthalmology as well as in medicine in general has changed in the last 20 to 30 years, and that some clinical trials have had significant impact on clinical practice. With so many new, unproven treatments and therapies available today, the need to increase clinical trial participation by working physicians has become even more crucial. If practicing physicians can meet the basic requirements for becoming an investigator (i.e., being knowledgeable in the area studied, having a good understanding of the ethical issues involved with clinical trial research, having the proper infrastructure in place, having a competent study coordinator to help administer the clinical trial, etc.), they should seriously consider joining or leading a clinical trial.  This is because participating physicians stand to gain many intangible benefits from their involvement in clinical trials such as increased prestige, the opportunity to contribute to a larger cause, and the opportunity to collaborate with colleagues who share their intellectual interests. 

    Indeed, a 2004 American Heart Association (AHA) Scientific Statement that was endorsed by the National Heart, Lung, and Blood Institute (NHLBI) listed a myriad of reasons for physicians to participate in clinical trials (Circulation. 2004;109:2672-2679):

      dot Participation in clinical trials by physicians helps to continue the important shift from an observational paradigm to an evidenced-based paradigm.
      dot Participation in clinical trials allows the clinician and study staff to remain on the “cutting edge” of their area of expertise
      dot There are often networking opportunities at study meetings that allow physicians to exchange ideas and observations, and which may provide the basis for future collaboration.
      dot Educational opportunities are often available.  For example, investigator meetings will often include scientific sessions.
      dot Physicians may be invited to become members of writing groups or co-authors of articles submitted for publication.  Although main results papers are generally authored by the entire group, a smaller group of investigators may make take a lead role in secondary and ancillary studies.
      dot Participation may add prestige to the investigator’s practice or institution.
      dot Patients that enroll in clinical trials tend to receive particularly high-quality care compared with similar patients that do not enroll in clinical trials.
      dot The greatest reward may stem from the fact that individual physicians have played a direct and important role in a study whose trial results add to the advancement of science and medicine.

    Physicians practicing in non-teaching settings, as well as those practicing in university based settings, should keep in mind the above-mentioned benefits of clinical trial participation as motivation.

    Establishing Equipoise

    Once physicians have made the decision to participate in clinical trials, they then need to ensure that the clinical site will be able to successfully enroll participants. Patient recruitment is often considered the largest hurdle faced by a clinical site, and poor recruitment is the most common reason why some clinical trials are unsuccessful. To ensure successful recruitment, the physician must have equipoise concerning the main question asked by the clinical study. 

    Equipoise is defined as a state of uncertainty in which the early data suggest but do not prove a drug or a treatment’s safety and efficacy, and the only way to resolve this uncertainty is with further study. A clinical trial is often the most effective way to address the uncertainty. The presence of equipoise helps to justify the existence of a clinical trial, because it fulfills one of the most important prerequisites for initiating a study: the desire of the investigator to evaluate the study question. If the investigator is passionate about the study, this will be easily conveyed to other physicians in the practice and study staff, increasing the likelihood that the clinical site will be successful in patient recruitment and beyond. When the investigator meets all the prerequisites for establishing a clinical study, from the knowledge requirements to equipoise and enthusiasm, the study site can look forward to a rewarding, exciting, and satisfying experience that will advance both scientific knowledge and patient care.

    References

    1. Lader EW, Cannon CP, Ohman M, et al. The clinician as investigator: participating in clinical trials in the practice setting. Circulation. 2004;109:2672-2679.
    2. Karlawish JH, Lantos J. Community equipoise and the architecture of clinical research. Camb Q Healthc Ethics. 1997;6:385-396.

    Author Disclosure

    The author states that he has no financial relationship with the manufacturer or provider of any product or service discussed in this article or with the manufacturer or provider of any competing product or service.