Four ways concomitant medications can complicate your clinical trial

Concomitant medications (con-meds) are prescription medications, over the counter (OTC) drugs or dietary supplements that a clinical trial participant happens to be taking at the time of the trial, in addition to the drug under investigation.

The presence of con-meds can have a serious impact on the length and cost of a clinical trial, particularly around the issues of patient eligibility and safety. Con-meds are a frequent source of rejection for people wanting to participate in clinical studies. A systematic review of randomized controlled trials identified 54.1% of trials to have at least one medication-related exclusion criterion. Add to that the fact that 85% of clinical trials fail to meet patient enrollment timelines and the potential impact of con-meds becomes clear.

The issues are magnified by the fact that use of con-meds amongst potential study participants is common. A review of clinical trials show that 78% of subjects enrolled in a trial of ziprasidone (an antipsychotic agent for treatment of schizophrenia) were found to be taking concomitant medications. Several other studies found similar results: participants reported taking at least one other medication as much as 83% of the time.

Con-meds can also have an impact on outcomes. Interactions with the investigational drug can lead to faulty conclusions. As such, Good Clinical Practice (GCP) regulations mandate that investigators pay attention to con-meds used by study participants.

Given all of the benefits of the capture and analysis of con-med data, why isn't it a bigger deal?

After enrollment, con-meds are important for their relationship to adverse events. The analysis of con-med data can help investigators identify issues that were not previously reported as adverse events, or explain adverse events that were caused by drug interactions.”

Bruce Palsulich VP of safety, Oracle Life Sciences

Four challenges of tracking concomitant medications

While the issue of con-meds during clinical trials is clearly an important consideration for pharmaceutical companies looking to validate the safety and efficacy of their investigational drugs, many clinical studies still do not adequately track and/or analyze con-meds. Here's why:

  1. The industry is playing catch-up: Until recently, effective tracking and analysis of con-meds in clinical trials was simply not on the radar for many pharma companies. However, as the use of con-meds continues to increase in popularity in the general population the potential impact on the validity of clinical trial data is becoming more apparent. As such, both pharma companies and regulators are beginning to take notice and pay more attention to con-med use by study participants.
  2. The data can be unreliable: Many study protocols require capturing con-med usage into a subject’s study record. This, however, can be an extremely difficult task as it relies on the honest and accurate reporting by the trial participant, as well as a detailed review of medical records.
  3. The data is complicated. 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.
  4. The adoption of new technology has been slow. Traditionally, if con-med information was collected at all during a clinical trial, it was done on paper. Trial participants might be asked to bring in a personal diary of any additional medications they might be taking, or even to bring their medications in for documentation at the site. This kind of paper-based documentation is cumbersome, and certainly does not lend itself well to any kind of effective or efficient analysis of possible con-med-study drug interactions.

The future of con-meds in clinical trials

Fortunately, new electronic technologies are now available to address this challenge. If study participants were given access to an eDiary, for example, they could electronically access lists and dosage amounts of various medications, and then immediately upload their con-med information into a trial database—enabling pharma companies to capture data effortlessly and have it easily accessible for analysis, thus enabling greater insights into the different variables impacting a patient.

The arrival of new tools is well-timed, as new regulations about con-med data may be around the corner. Although FDA guidelines have always called for an analysis of the impact of con-meds in clinical trials, this has not always been strongly enforced. Concomitant medications have always been a part of inclusion and exclusion criteria used to allow patients to take part in trials, but once admitted to a study, there was typically very little, if any, tracking by sponsors of the subtle impacts those medications taken by participants might have on trial results. This is beginning to change as regulators are starting to encourage more thorough con-med analysis in clinical study reports.

Accurate con-med documentation does more than just make it easier to characterize adverse events and drug interactions for an investigative drug's safety profile. The reality is that almost every person participating in a clinical research study uses some form of concomitant medication—a multi-vitamin, dietary supplement, or common OTC medications used to treat pain or allergies. With sponsors facing tremendous financial pressures to run their trials on-time and on-budget, it is important to recognize the impact of concomitant medications in meeting patient enrollment timelines.

“The emphasis in a clinical trial has been the drug under study,” says Dr. Sameer Thapar, director of global pharmacovigilance at Oracle. “But the whole gamut of drug therapies needs to be considered for optimal interpretation of results. Concomitant medications, while necessary to the patient, can confuse the results and should be factored into the analysis.”

The fact is we can no longer afford to rigidly apply inclusion/exclusion criteria to studies, without taking a critical look at the nuances involved. The key is to track the concomitant medication data correctly and routinely across sites, so that the appropriate conclusions can be drawn—to enable further studies or inform potential side effects. This is important for, not only reducing the overall cost of healthcare, but speeding the delivery of life-saving therapies.

At Oracle, we celebrate the medical heroes who make clinical trials possible and work tirelessly to advance medical research with partners such as CISCRP. Oracle has been at the forefront of the fight against COVID-19, helping to speed clinical development efforts and participating in innovative industry initiatives such as the Therapeutic Learning System & COVID-19 vaccination passport.