Concomitant medications (con-meds) are any prescription or over-the-counter drugs and supplements taken in addition to an investigational therapy by a study subject. Many study protocols require capturing con-med usage into subject’s study record. This can be an extremely difficult task as it relies on the honest and accurate reporting by subjects as well as detailed review of medical records. It is not enough to simply submit the name of a medication, as most con-med reports typically require dosage, frequency, and duration of usage. Often, multiple con-med entries will need to be created in the study record for the same medication if the dosage changes or if the subject stops and restarts the medication. This can potentially lead to dozens or more errors of data point entries for a single study subject. So why are con-meds so important in research trials and how can researchers ensure that con-meds are being accurately reported?
To start, con-meds are often part of a study inclusion and exclusion criteria. If a study subject is taking a medication that is known to adversely interact with the investigational therapy, this subject would most likely be excluded from the study for safety concerns. Additionally, a Sponsor may want to exclude subjects who are taking certain medications for similar indications as the study treatment in order to remove confounding variables from the final study analysis and isolate the effect of their product.
After enrollment, con-meds are also important for their relationship to adverse events. Their usage can help Investigators identify issues that were not previously reported as adverse events. Con-meds may also help to explain adverse events that are actually caused by drug interactions instead of the study treatment itself. Furthermore, having all the details of a subject’s con-med usage will better inform the investigator for the treatment of adverse events which can help the validity of the study-endpoints of a trial.
While con-med recording may not be a regulatory requirement, they do appear in an FDA guidance which recommends that con-meds should be incorporated into an investigational plan:
“Which drugs or procedures were allowed before and during the study, whether and how their use was recorded, and any other specific rules and procedures related to permitted or prohibited concomitant therapy should be described. How allowed concomitant therapy might affect the outcome due either to drug-drug interaction or to direct effects on the study endpoints should be discussed, and how the independent effects of concomitant and study therapies could be ascertained should be explained.”
Also Good Clinical Practice requires that monitors verify that con-meds are reported in accordance with the study protocol. Most Sponsors realize the importance of con-meds to their clinical trials but ensuring that they are correctly recorded can be challenging. Often, study subjects wait to report con-meds at follow-up visits which causes more time for them to forget the details regarding their usage. Obtaining medical records from other hospital visits that occur between study visits can help Investigators identify con-meds but these records may not always be kept up-to-date. To combat these issues, studies can utilize paper or electronic diaries where the subject can record their medication usage in real time; however, subject compliance can be a challenge utilizing these measures too
What other challenges do you experience with con-med reporting? How do you overcome these challenges?Dream Weaver via photopin (license)