Improving Patient Care

As practitioners, we play the role of detective. In order to do what's best for our patients, we are constantly asking questions and forming hypotheses, from diagnosis to selection of the best course of treatment. Physicians inherently look beyond what is obvious. We don't say, "Here's the edge of the frontier, I'm going to stop here." We always ask, "Am I offering the best I can, or are there new avenues, new knowledge I can offer? Are there other ways to attack and solve this problem?"

Clinical research gives us the opportunity to integrate research into our practice and contribute to medical progress by developing new approaches to preventing and treating disease and injury in our patients. Not everyone chooses to pursue a research-focused career, but that doesn't mean we can't all be engaged in clinical research. In fact, private practice clinicians are at the front line of approaching patients to become involved in clinical studies, which is a vital ingredient in the transfer of research into the clinical setting, and also in bringing questions back to the researchers who are working to develop new therapeutics.

Our ability to gain greater understanding leading to new interventions that make a difference in people's health is dependent on a well-informed population — people who not only support clinical research but who are willing to participate.

More than ever, today's research paradigm depends upon a broad spectrum of research activities and research partners, including collaborators and volunteers representing a wide range of ethnic, cultural, and socioeconomic groups, ages, and genders.

The National Institutes of Health Roadmap describes four basic steps in the research continuum: from preclinical studies to humans (safety studies); to patients (controlled observational studies); to practice (dissemination and implementation research); to outcomes evaluation, where new questions and gaps in care are identified. For these last steps, the involvement of a diverse community well beyond the academic or research enterprise is critical. But what does the average patient think of when he or she hears the word "research," and as clinicians how can we help our patients participate in research if they are interested?

When many of our patients hear "clinical research," they often think first of experimentation, but that isn't necessarily true. Clinical research can involve studying a new drug or therapy, but it can also be outcomes or quality improvement research, or large-scale epidemiology studies. Participants in such a study might be asked just to give a tissue sample or fill out a questionnaire.

UC San Diego's Institutional Review Board (IRB) has a database of more than 3,500 active human research protocols. More than 650 of these are clinical trials involving FDA-regulated drugs and devices. Collectively, these studies offer a variety of options for participation, from clinical trials of promising new therapies for specific diseases, including surgical interventions, to studies of behaviors and other factors associated with disease risk in large, or very specific, populations. A few examples:

• The UC San Diego Shiley-Marcos Alzheimer's Disease Research Center is launching a phase 2 clinical trial to test a gene therapy treatment for Alzheimer's disease called CERE-110, which has been shown to safely induce long-term production of Nerve Growth Factor (NGF), a natural brain cell-survival molecule. CERE-110 will be injected directly into the nucleus basalis of Meynert (NBM) of the brain, the site of the cholinergic system, where neuron death occurs in AD. Exposing these cells to NGF may preserve function, prevent further cell loss, and potentially slow intellectual decline seen in Alzheimer's patients.
• Researchers at the Moores UCSD Cancer Center are using a modified herpes virus to treat advanced melanoma, hoping to kill the cancer cells while boosting immune defenses against the disease. Dr. Gregory Daniels and his team are comparing OncoVEX GM-CSF to general immune system stimulation with the immune-boosting protein GM-CSF in an international phase 3 trial. The injected virus appears to preferentially infect cancer cells, leading to tumor death. The expression of the GM-CSF protein may also direct an immune attack against infected and non-infected tumors.
• A new clinical trial is evaluating whether or not diet intervention, prompted by phone calls, may be effective in managing bladder cancer. Evidence suggests that dietary counseling can be beneficial in weight loss, smoking cessation, and breast and prostate cancer prevention. This study, open to men and women over 50 who have bladder cancer, will provide phone-based dietary counseling or print materials to guide nutritional decisions.
• Drs. Santiago Horgan and Mark Talamini and colleagues are conducting clinical trial surgeries to evaluate the safety and effectiveness of performing abdominal procedures through the body's natural openings. The experimental procedure, called Natural Orifice Translumenal Endoscopic Surgery (NOTES), involves passing surgical instruments and a tiny camera through a natural orifice, such as the mouth or the vagina, to the diseased organ such as the gallbladder or appendix, which can then be removed through the orifice. This study and others involving single-incision surgeries are providing scientific evidence to show whether minimally invasive techniques that avoid major incisions through the skin, muscle, and nerves result in quicker recovery with less pain and scarring, and reduced-risk of post-operative hernias.
• In 1972, UC San Diego professor Elizabeth Barrett-Connor launched a long-range population study involving 6,000 residents of Rancho Bernardo. Health and lifestyle data collected from participants over several decades have been analyzed by scores of investigators, resulting in more than 400 scientific papers, and greatly increasing our knowledge of cardiovascular disease, diabetes, cancer, osteoporosis, and exogenous and endogenous hormones. The robust database continues to provide a basis for ongoing studies, and the connections between lifestyle, behavior, and healthy aging.

For the clinician interested in getting involved in research, there are a number of options. As a starting point, you can provide information to a patient who might be interested in or benefit in some way from joining a clinical trial. When advising patients about volunteering for a research study, it's important to ensure they understand that a clinical trial isn't the same as clinical care, and it may or may not be beneficial. But I find that many people want to participate in helping to gather new knowledge and in driving innovation. The physician can explore these possibilities with the patient and assist the patient in finding appropriate studies.

A more active approach is actually recruiting patients into a study; and more active still is to learn methodology and become a collaborator.

When evaluating an opportunity to be engaged in a research study, carefully review the protocol and the sponsor, and do a feasibility assessment. Ask questions: Is the protocol ethical and scientifically sound? Is it consistent with clinical practice? Do I have an adequate and appropriate patient population, or will I need to recruit? What are the staffing and budgetary needs of this study, and can I cover the costs?

Physicians interested in becoming more engaged in clinical research should consider enhancing their skills and knowledge of clinical trials principles and methodology as a first step. There are courses available, such as the UC San Diego master's degree in clinical research, designed for healthcare professionals seeking advanced training in research methods and protocols. Further details on the MAS program can be accessed at http://clre.ucsd.edu.

Next, learn about what research opportunities are available by contacting commercial research organizations, pharmaceutical companies, or academic centers like UC San Diego. Attending lectures and symposia is another way to get information and to engage with a clinical and translational research network.

My message to colleagues is that every physician can play a role in changing and improving the practice of medicine. You don't have to commit a great deal of time to becoming a "researcher" to get involved in clinical research.