There are a lot of things that can sink your clinical trial. Low patient recruitment, poor data, or issues with safety or efficacy, for instance. But what shouldn’t be a problem are issues arising with concomitant medications (two or more drugs used or given at or almost at the same time.)
“Many of the companies I work with don’t really see concomitant medication tracking as a topic that is particularly important,” says Paul O’Donohoe, Director, Health Outcomes, for CRF Health. “Traditionally, if the information is being captured at all, it is being recorded on paper. Participants in a clinical trial might be asked to bring in a personal record of any additional medications they might be taking. In some cases they may even bring in packets of their medications.”
The most basic solution being used is a simple patient diary which notes other medications consumed on a particular day. Patients could note the medicines consumed (and for what reason), dosage amounts, and any effects they experienced. This method is easy and inexpensive especially if an electronic diary is already used in the study, but can also be inaccurate if patients forget to log the medications. Having to fill in all of the information is also not the most user-friendly solution for patients, especially when they may not know the names of the medications they are taking or the dosage amounts.
Concomitant medications were always important for the inclusion and exclusion criteria used to allow patients to take part in trials. This was essential to avoid adverse reactions between two drugs that were known to exist. But once an individual was admitted to a study, there was little, if any, tracking of the more subtle impacts those medications might have on trial results.
As an example, O’Donohoe points to a study examining the effects of a pain medication. If a participant is taking a pain medication, but at the same time taking over-the-counter pain remedies, the combination could have a significant impact on the participant’s reporting of their symptoms and the relief they obtained from the treatment.
“To get a true understanding of the treatment effects, you also need to get a true understanding of what other medications the patient might be taking,” says O’Donohoe. “This includes not only medications they might be taking, but other treatment options they may be getting as well, such as acupuncture. All of those things will have an impact on their condition.”
Should You Be Concerned?
While the issue of concomitant medications seems to be one that pharma companies should be looking into, in many studies it is not closely tracked. O’Donohoe believes for many large pharma companies, this is simply not a major concern. But that situation might be changing.
Similar issues, such as patients concurrently enrolling in multiple studies, are suddenly getting more exposure. Trials are also becoming increasingly more complex. And now it seems regulators will be taking a closer look at the problem as well.
“This concept of pharma getting a full understanding of the patient experience and all of the various factors that might be feeding into it, including patient reported symptoms, is going to become increasingly important,” says O’Donohoe. “This is especially true as trials continue to become more complicated. Often the signals we are looking for in a clinical trial can be quite subtle. As a result, they can be completely drowned out or boosted up by additional things a patient is doing off protocol.”
While recognizing the need to do something is extremely important, having the capabilities to do it is equally vital. In the past, tracking concomitant medications was a challenge. Today it is a far simpler task because of the technologies that we have available. Technology provides pharma the opportunity to capture far more data and at the same time provide greater insights into the different variables having an impact on a patient.
O’Donohoe notes it is also difficult to get a sense of many factors impacting a patient simply by looking at data on a sheet of paper. For example, if a patient has a paper diary that must be completed every morning, a review of that diary will not tell you when the information was actually filled in. “They could have been sitting out in the parking lot filling out the information five minutes before walking into the clinic,” he notes. “But if the patient has access to an eDiary, they could electronically access lists and dosage amounts of various medications, and have that information immediately uploaded to a trial database, where it could serve as an additional data point.”
Will Regulators Get On Board?
O’Donohoe has had conversations with sponsor companies that indicate a change is coming. A number of customers have approached him about a better solution based on discussions s they have had with a representative from the FDA. According to O’Donohoe, these companies were told they will need to capture the information electronically, because it was important to the outcomes they were trying to measure.
Having spoken about this topic more broadly with other sponsors, he notes many feel the way they have been capturing the information is adequate. That may be true for now, since most have not yet been asked to do it any other way. But going forward that is likely to change as more sponsors receive additional guidance from regulators.
This is an issue that will not be going away,” he adds. “In fact, we see it as growing in importance. Some sponsors have been asked by regulators to collect this data specifically on electronic diaries, others see the value in getting more accurate data and will move to this method as they increasingly eliminate the no-longer satisfying method of transcribing con meds into EDC systems. As more sponsors have similar conversations with regulators, we believe interest will expand and recording this information electronically will become the norm.”