A pharmacist discovered the mistake, and it was a big one. Gone unnoticed, the error would have corrupted an entire clinical trial.
The detection occurred at the outset of a phase I gene therapy trial at The Cancer Institute of New Jersey (CINJ) in New Brunswick. Patients with carcinoma of the bladder were to receive a vaccine composed of a recombinant fowlpox virus expressing two proteins (TRI-COM and GM-CSF). The virus would be injected directly into the bladder. When the research team’s pharmacist reviewed the National Cancer Institute (NCI)-approved protocol, she realized that the normal saline solution used to dilute the vaccine was too acidic to support virus stability. Had the vaccine been administered, the results would have been meaningless.
The pharmacist alerted Susan Goodin, Pharm.D., BCOP, associate director of clinical trials and therapeutics at CINJ and professor of medicine at the University of Medicine & Dentistry of New Jersey-Robert Wood Johnson Medical School in New Brunswick. Dr. Goodin agreed with the evaluation and notified the research team and the NCI. Both were stunned. Eventually, a more suitable diluting agent was used.
“She caught the error before any of the 33 patients received the vaccine,” said Dr. Goodin. “We would have gotten to the end and said, ‘It doesn’t work,’ without ever knowing why.”
From Fatal Disease to a Cure
It is hard to imagine a more conspicuous example that establishes the value of pharmacists in research.
Pharmacists who are involved in emerging medical sciences research say the field requires patience and persistence.
Dr. Goodin and her vigilant colleague are part of a growing trend: pharmacists who are deeply involved in emerging medical sciences research, which include pharmacogenomics, gene therapy, biosimilar drug therapy and nanomedicine, among others. This is not a calling for individuals who thrive on instant gratification, because the payoff—if there is a payoff—usually doesn’t arrive for years, maybe decades, after the work commences, noted Dr. Goodin, who has been a researcher and clinical pharmacist for 20 years. But those rewards can be enormous.
“I truly believe that these kinds of trials will make some cancers chronic illnesses or possibly cure them,” said Dr. Goodin, who oversees all of the clinical trials at CINJ. “Gene therapy may be among the best opportunities for managing diseases like bladder cancer, pancreatic cancer and melanoma.” The team at CINJ is currently conducting a clinical trial of PANVAC, a vaccine for pancreatic cancer patients.
Individualizing Drug Therapy
Orly Vardeny, M.S., Pharm.D., conducts research on the pharmacogenomics of cardiovascular medications, insulin resistance and heart failure, and immune function and influenza vaccine response in patients with cardiovascular disease. Considered broadly, pharmacogenomics is the study of how variations in genetic composition affect a patient’s response to medication. The presence of specific genetic markers may allow a heretofore unreachable level of individualization and accuracy in drug therapy.
“Pharmacists who possess information about a patient’s genetic profile could provide prescribers with highly specific therapeutic recommendations,” said Dr. Vardeny, an associate professor of pharmacy at the University of Wisconsin in Madison.
Dr. Vardeny’s recent work includes a study of nondipping nocturnal blood pressure, which is characterized by disruptions in the normal circadian rhythm that leads to a lack of normal declines in blood pressure during sleep. The absence of a normal drop in blood pressure at night has been associated with heart failure, myocardial infarction and stroke, as well as sudden cardiac death.
The authors found that a genetic predisposition involving the sympathetic nervous system may play a role in abnormal blood pressure dipping patterns. “Determining who, from a genetic standpoint, is predisposed to nondipping, may enable us to target individuals who require more vigorous control of their blood pressure,” said Dr. Vardeny.
Asking the Important Questions
For Daniel Crona, Pharm.D., the attraction of research boils down to a simple idea: “I like asking important questions, formulating hypotheses and figuring out the answers. The end game for me is that my work may eventually save lives.”
Crona conducts clinical pharmacologic research, focusing on pharmacogenetics, in patients with genitourinary malignancies at the University of North Carolina (UNC) Eshelman School of Pharmacy, and is pursuing a Ph.D. in the UNC ESOP’s Division of Pharmacotherapy and Experimental Therapeutics.
He is part of a team seeking to discover genetic biomarkers that predict differences in survival and adverse event profiles among patients taking oral small molecule tyrosine kinase inhibitors (i.e. sorafenib) for metastatic kidney cancer. Their efforts may one day be used to identify patients who can benefit most from these agents by mitigating dangerous side effects, optimizing chemotherapy doses and improving overall survival.
“The thought that what I’m doing will potentially have a far-reaching impact on patient care is gratifying,” said Dr. Crona. “I wouldn’t give it up for the world.”
John M. Valgus, Pharm. D., BCOP, CPP
Among the prominent emerging sciences, pharmacogenomics is one of the only disciplines to have produced applications used in mainstream medicine, according to John M. Valgus, Pharm.D., BCOP, CPP, hematology/oncology clinical pharmacist practitioner at the University of North Carolina Hospitals and Clinics, and a clinical assistant professor at UNC Eshelman.
“Several specific pharmacogenomic tests are used beyond the context of a clinical trial and are generally covered by insurance,” said Dr. Valgus.
An example is genetic testing for the presence and activity of the enzyme thiopurine methyltransferase (TPMT) in patients scheduled to receive azathioprine or mercaptopurine. Patients with low TPMT activity are at increased risk of drug-induced bone marrow toxicity. The information has a direct impact on treatment decisions.
Closing the Knowledge Gap
Despite the emergence of pharmacogenomics as a practical diagnostic option, many practitioners know little about it, said Sandra Oh Clarke, R.Ph., senior director, certification development and CE liaison in the ASHP Office of Resources Development, and former director of ASHP’s Section of Clinical Specialists and Scientists.
“We have a big knowledge gap,” she said. “The information is out there. What we need is a way to communicate the value of pharmacogenomics to clinicians and bring the technology to the bedside.”
ASHP’s Section of Clinical Specialists and Scientists’ (SCSS) Advisory Group on Emerging Sciences evaluates and implements recommendations of the ASHP 2008 Task Force on Science and assesses potential policy issues related to the emerging sciences. The group is currently developing several major initiatives for members who are involved or interested in research, including a resource center on ASHP’s website and proposed CE programs at the 2012 Midyear Clinical Meeting.
“Emerging sciences will play a big part in the future of pharmacy practice,” said Dr. Valgus, who chairs ASHP’s advisory group. “Almost anyone who cares for patients, regardless of specialty, will eventually need to understand them, particularly pharmacogenomics.”
