At any one time, Penn Medicine investigators are running as many as 3,000 studies involving human subjects, generating knowledge about disease and finding new cures. And making sure these studies run smoothly are 700 clinical research coordinators who do everything from recruiting patients and administering medication to collecting the data that proves –- or disproves -– the study’s goal.
“The principal investigator is the brain of the research, and the coordinators are the hands,” said Jun Mao, MD
, of Family Medicine and Community Health. “The brains and the hands have to coordinate, but, without the hands, nothing can happen.”
The job demands respect for patients’ rights, a keen eye for symptomatic relief or side effects, and a dedication to rigorous data collection. “These are the unsung heroes of the research world,” said Nancy Pultorak, director, Clinical Research Operations in the Office of Human Research. “They are the hub that makes it all happen.”
Clinical research coordinators come from many backgrounds. Some are medical students while others are nurses or college graduates with an interest in research. All are required to be certified through the Penn Medicine certification program that includes 20 hours of regulatory and operational management training offered by the Office of Human Research as well as by 10 hours of online human subject protections training.
Nurse practitioner Lester Lledo, associate director of Translational Research, Clinical Trials Unit, manages a clinical research unit that conducts research of novel investigational therapy for patients with late-stage cancer to determine if these treatments are feasible and safe. Many of these patients have exhausted the standard definitive therapeutic interventions. Lledo’s unit has 10 active cancer studies and several others for patients with HIV. The trials enroll a small number of subject -– up to 20 -– and, typically, participation lasts for several years; the clinical research coordinators follow up with patients to assess long-term side effects of the investigational therapeutic product. Lledo explained that new therapies which are genetically engineered cells have additional risks to monitor. “It’s high risk, very different than giving a drug,” he said. “It’s a living cell, which has the potential to destroy cancer cells, but it can also have severe side effects. With a drug, you can mitigate the side effects by withdrawing it. But the cell therapy can continue to proliferate in the patient’s body. You have to essentially turn off the cells’ activity to dampen or stop the adverse effects.”
Recruitment stands as the greatest challenge in many studies, as principal investigators need a large enough sample to determine the significance of a clinical trial’s findings. Recruiting subjects in studies for an HIV vaccine has brought Annett Vogel-Davis to places you might not expect to find a 64-year-old nurse, including gathering spots for gay and bisexual men and transgendered women who have sex with men. In early October, she spent all day at Philadelphia’s Out Fest. On other evenings, she’ll show up at gay bars with the mobile assessment unit at 10:30 pm and stick around until 1:30 am. When she did HIV vaccine research with subjects who injected drugs, she’d frequent syringe exchange sites and places where IV drug users gathered to shoot up. “We did street outreach, walking around various neighborhoods,” she said, noting that “our recruitment strategies are somewhat different than what most clinical research coordinators do.”
In another study, Vogel-Davis developed a prevention intervention trial with women, ages 14 to 19, to increase condom use. She worked with the principal investigator to write the curriculum and pilot it with focus groups. Then she helped organize the recruitment effort and implement the retention strategy, which required a follow-up visit after three months.
Recruitment takes considerable tact and understanding for studies on oncofertility, which are run by Maureen Prewitt, director of Clinical Research in Oncofertility. These studies address fertility among women who were treated for cancer with radiation or chemotherapy. Studies have shown that some chemotherapeutic interventions may cause premature aging of a woman’s ovaries and early menopause.
In addition to recruitment, Prewitt’s research team observes menstrual cycle patterns by reading the diaries kept by subjects. They test the levels of reproductive hormones with serum hormone assays. And they count a woman’s egg follicles by using pelvic ultrasound. “Our studies will follow women daily, quarterly or annually, for as long as we have funding, to see when fertility declines and in whom.”
When fertility is compromised, her team offers opportunities to freeze the woman’s fertilized or unfertilized eggs or ovarian tissue. These decisions usually have to be made very quickly, before cancer treatment begins. “A woman who just learned she has cancer has enough to occupy her mind,” said Prewitt. “She is being told about chemotherapy,radiation and surgery and, at the same time, she learns that her fertility may be compromised. We’re asking her to make decisions about something she has never considered before.” Most have appreciated the intervention, she added.
“When I’m recruiting for my studies, I always think about the relationship with the patient over time,” she said. “I get to be part of their lives at a very crucial time, and I believe I’m offering a service that’s very meaningful -– the ability to have children at the end of their treatment. That provides a great deal of hope, and it’s a privilege to be part of that.”
Mary Lou Mayer, senior clinical research nurse coordinator, helps carry out clinical research studies on mitral valve (MV) surgery for people with moderate ischemic mitral regurgitation (MR) caused by coronary artery disease. The studies evaluate the safety and efficacy of MV repair surgery for these patients combined with coronary artery bypass grafting (CABG) versus CABG alone, as well as the impact these two surgical approaches have on left ventricular remodeling.
Mayer screens potential study patients to make sure they meet the study criteria and discusses results with the surgeon. Then she takes the time to sit down with patients and their families, to explain the details of the study, how it is conducted, why it is conducted in this manner, and the patients’ responsibility for coming to follow-up visits to monitor their progress. Mayer sees the patient every day in the hospital following surgery. Follow-up visits occur at 30 days, 60 days, 12 months, and 24 months. A detailed study echocardiogram is performed at each visit.
To help with physician referrals and study recruitment, Mayer stays in touch with cardiologists and cardiac surgeons in the region with a newsletter that provides updates on enrolling studies, outcomes and publications on completed studies and information on new protocols that will soon be enrolling study subjects. She also attends cardiology and cardiac surgery grand rounds and CME dinners in hopes of increasing physician referrals for patients to take part in the studies.
“The greatest thing is the patients themselves,” she said. “We ask a lot of them, to keep coming back to be tested. They do so much, and they do it for others, who will be helped by the research.”
Photo caption: Clinical research coordinator Mary Lou Mayer performs a yearly follow-up exam on Dennis Hatfield, who participated in one of her clinical trials three years ago.