FDA-approved technology links dosage responses
Clinicians hope it will improve dosing accuracy
Several clinicians are testing technology that they hope will help them prescribe the most effective drug dose for an individual patient more accurately.
"I am optimistic about [the technology]," says Omer Kucuk, MD, oncologist at the Barbara Ann Karmanos Cancer Institute in Detroit. Kucuk is testing the Intelligent Dosing System (IDS) in a chemotherapy setting. "I think it has great potential." He hopes that prospective studies taking place at various health care centers will confirm his enthusiasm. "We have to prove it in clinical practice first."
IDS, developed by The RxFiles in Sarasota, FL, is a computerized decision support system that was reviewed and approved as a Class II medical device by the U.S. Food and Drug Administration last year. IDS is a suite of three software applications designed for use on a handheld personal digital assistant or computer. The three applications include DoseRx, a next-dose calculator; InterchangeRx, a therapeutic interchanger that switches patients between drugs — either from brands to generics, or between drug classes while maintaining the original agent’s established therapeutic effect; and Practice PrescribeRx, a graded prescriber training simulator.
Technology can decrease side effects
A chemotherapy setting is an ideal area to test the technology, Kucuk suggests. "Many times [chemotherapy] drugs have to be pushed up to the maximum dose. Then we start getting into trouble with toxicity."
The technology would be an improvement over the archaic way that chemotherapy drugs often are prescribed, he says. "We give chemotherapy, and then we see what the side effects are. Then we go down by 20% or 25% or 50%, based on the
toxicity, which usually is based on blood counts. [This method] is quite crude."
Once the doses are reduced, they might stay that way forever. As a result, patients may be grossly underdosed for the remainder of their therapies because they had a low count at the initial one or two treatments, Kucuk says.
"That might affect the therapeutic efficacy and might mean that some patients who are potentially curable end up not being cured. So we are talking about very important implications of this new technology."
The IDS claims to provide dosing precision and accuracy of 90-97%. Accuracy is defined as the exact dose needed for the patient to reach a specific response or marker on that next dose.
Before the IDS can predict an amount for a chemotherapy dose, Kucuk must tell it what marker he wants it to consider. "It could be a positive marker or a negative marker," he says. "In chemotherapy, we give negative markers, meaning toxicity markers."
The technology can use any marker, explains Michael Singer, president and chief operating officer of The RxFiles. "The marker can be one of efficacy, how well it is working, or a marker of toxicity. For instance, we can adjust an immunosuppressant downward or a chemotherapeutic downward to improve blood cell counts."
For example, Kucuk can tell the IDS what dose a patient received and what his blood cell count was at that time. Then he tells the IDS the patient’s current white blood count and what it should be after the therapy. The technology then gives Kucuk the dose amount to achieve that response.
What happened three or four cycles ago is not important to the IDS. "The most relevant information for the [technology’s] formula is previous and current data," Kucuk says. "What happened last time, what is happening today, and what you want to happen tomorrow."
The technology accounts for variation in patient response to the drugs, Kucuk says. "From day to day, there is a great variation [in responses] in a single human being. You can imagine the variation between human beings." The intra- and inter-individual variations can be drastic due to effects such as surgery, infections, or changes in body weight or metabolism. "You have to constantly adjust your dose."
The formula also can accommodate for drug interactions, he adds. "If we are giving three drugs and the blood count goes down, we usually lower all three drugs by 25%, for example. The formula, however, may lower one of them 25% and another one not at all. The formula is able to predict the contribution of each drug to that particular toxicity by [analyzing] the history of that particular drug."
The IDS sometimes requires more information about the history of a particular drug. "You may have to enter some data from 10-15 patients for that particular drug. The IDS then knows how people react to that particular drug. That allows the formula to predict the contribution of each drug."
Correlation between doses discovered
The IDS is based on a scientific discovery made by an associate of Singer’s, who was doing research in Canada. The associate was able to draw a correlation between previous doses and previous responses to the current dose. "He did that by illustrating the dose response curve of the agent using three-dimensional surface mapping," he says. "That was essentially the fit of the agent part of the technology."
The next component deals with the overall vagaries of the patient. To do this, the associate applied an advanced mathematical control system called the stochastic open loop. "This part learns whether the patient was a 150% responder or a 50% responder. [The system] reserves a small amount of the dose to titrate upward or downward based on the specific needs of the patient."
The IDS has been available in trial fashions in the areas of immunosuppression for nearly 12 years. Kucuk was impressed with some of the retrospective data in oncology from studies done three or four years ago. "We looked at the actual blood counts and actual doses given and then we asked the [IDS] formula what it would have given and what it would have predicted the blood counts to be. There was about a 95% correlation based on what the formula predicted and the actual results."
Now he is involved in a prospective study in patients who are getting chemotherapy. Half of the patients will receive their chemotherapy dose based on this new formula with IDS. The other half will have their doses prescribed the "old-fashioned way."
"After a few cycles, we will know the answer," Kucuk says. He anticipated having the protocol completed as Drug Utilization Review went to press. It will be used at three different sites: Ann Arbor, MI; Detroit; and Toledo, OH. "We are hypothesizing that the formula will allow us to give more chemotherapy with less toxicity. Not less with less toxicity — anyone can do that," he says.
Actual clinical practice will prove whether the technology makes it safer to administer more chemotherapy. "You may end up making it more effective and also safer at the same time," Kucuk says.
The IDS is being used in other areas of medicine, as well. Emory University endocrinologists at Grady Memorial Hospital in Atlanta are testing the development and application of the IDS to diabetes management.
"The goal is to put a tool into the hands of the practitioner that will allow him or her to more precisely adjust diabetes medications, in particular insulin," says Curtiss Cook, MD, associate professor of medicine at the Emory School of Medicine. "The hope is that this will allow better standardization of therapy and to better achieve glucose goals more reliably and quickly."
Emory is using the IDS at the point of care, such as at the time of the patient visit, to assist the practitioner in making dosage adjustments. Preliminary results of using the technology look encouraging, Cook says. "The diabetes nurse educators, who perform most of the management, are reporting that the IDS is making recommendations that agree very closely with their clinical judgment. In addition, personnel appear to be adapting to the new technology. Initial analyses indicate good agreement between what the IDS is suggesting and what is actually taking place, but longer-term study is needed with additional follow-up."
You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content