We’re all familiar with the long warnings found on the packaging of medications – from over-the-counter cold remedies to powerful prescription drugs. Warnings that caution people against everything from drowsiness to stomach issues, and even advise against driving.
Pharmaceutical companies don’t add warning labels to their products on a whim. Before adding any words of alert, companies conduct extensive tests, or clinical trials.
According to the FDA, clinical trials, or studies, test treatments on human volunteers to determine their effectiveness for the general population. It’s the responsibility of the company who wants to start selling a new medication to prove that it is both safe and effective to the FDA before being approved for sale.
Once a new drug is introduced to the market, the FDA maintains a system of post-marketing surveillance and risk assessment programs. They keep track of complaints of adverse effects through an extensive database and monitoring system, and every so often they might request further testing once unanticipated side effects come to light.
The Bizarre Case of Sleep Driving
One such request by the FDA concerned sedative hypnotic drugs. These are drugs meant to slow down activity in the brain and induce or maintain sleep. While there were already warning labels on this class of drugs, the FDA wanted to require even stronger language about possible side effects and potential risks. Though many of the prescription sleep aids seemed to be effective and generally tolerated, “post-marketing adverse event information” became available and the FDA concluded that there needed to be some changes in the labels.
Manufacturers of widely prescribed sedative hypnotic drugs (like Ambien and Lunesta) were required to conduct clinical trials to discover how often dangerous behaviors, like sleep-driving, were actually occurring. The FDA wanted to know the differences between the various products and how frequently complex sleep-related behaviors were happening.
To Drive or Not to Drive
Given the dangerous nature of driving in an impaired state, especially when there are so many well-established cognitive, visual, and psychomotor tests that can be used in clinical trials, one might wonder, “Why use driving tests at all?”
The answer is fairly simple. Driving is a task universally known that challenges all a driver’s modalities within the context of real-world experiences.
- Driving is the most universal and ordinary task people perform every day as well as the most complex and dangerous;
- Driving requires a full range of sensory, perceptual, cognitive and motor functions, all of which can be affected by new pharmaceutical compounds;
- Driving has measurable, real-world impact and consequences for everyone;
- Driving performance can be carefully evaluated to assess for impaired cognitive, visual, and psychomotor function.
As we’ve seen countless times, an impaired driver can have dire consequences (in terms of personal injury and property loss) for themselves and society as a whole. In short, driving is something we all do and there are universally accepted rules and behaviors for driving.
Comparing Driving Simulation with On-Road Driving Tests
To perform driving clinical trials, there are really two options available. On-road driving, or driving simulation. While some European countries allow actual on-road testing, this is generally not the case in the United States. For our discussion, on-road tests will be limited to tests performed on a closed test track.
When it comes to researchers deciding between on-road or driving simulation testing, there are several factors that can contribute to a final decision. Figure 1.1 shows some of the more important aspects of a driving component as it relates to pharmaceutical research. The components are:
- Performance measures
While there might actually be more details that go into deciding between the two, let’s look at the five primary components.
The most important thing in any clinical trial is the overall safety of the subjects during their participation. Simulated driving allows driving tests to be conducted within very controlled environments, like a doctor’s office, clinic, or laboratory setting, without putting the subject in harm’s way. It also permits the subject to be placed into situations that would be extremely dangerous to attempt on a test track (for example, collision avoidance interactions with other vehicles, obstacles, and pedestrians).
Within the simulated driving environment, the subject never puts him or herself (or anyone else) into danger. Plus, since a driving simulation takes place inside a controlled environment, should a subject experience any adverse affects to the drug being tested, he or she can be promptly evaluated and treated.
Of course, safety steps can be put in place during on-road testing (a co-driver with independent controls, for example), but this allows for the introduction of too many variables. And should a participant feel any adverse effects from the drug, that could create a much more dangerous situation.
Winner: Driving simulation
Aside from the safety aspect of the trial, another significant component of the driving test is documentation of how well the driver performed. The quality and integrity of the collected driving data are of utmost importance in a clinical trial. Specific scenarios the driver will navigate must be developed and implemented so that the desired performance outcomes are obtained and the results are repeatable.
This is where a driving simulation clearly beats on-road test. Anything within the simulated environment can be measured and repeated, and the outcome is totally objective. On-road tests are much more subjective because they may rely on experimenter observation rather than objective measurements. This also makes driving performance outcomes from on-road tests difficult to repeat.
Winner: Driving simulation
In a similar line of thought, clinical driving assessments must be able to investigate target outcome measures and provide repeatable results. With a driving simulator, every single aspect of the driving environment can be completely controlled and scenarios specific to the pharmaceutical trials can be employed. This even includes environmental conditions like weather, light, and wind.
This is a definite advantage for driving simulators. There’s no way to control an on-road test with this degree of precision.
Winner: Driving simulation
Unfortunately, cost is harder to assess. Unlike most of the other parameters, cost can vary greatly depending on the required driving outcome measures.
To make a valid comparison, take a look at some of the factors that contribute to cost for both a driving simulator and on-road tests.
- Driving simulator
- Simulator equipment (hardware)
- Scenario design (software)
- Installation of hardware
- Processing of simulation tests
- On site staff training to use the equipment
- Validation costs
- On-road testing
- Purchase or rental of customized on-road vehicles
- Test track rental fees
- Liability insurance
- Transporting the subject population to a test track
- Housing the subject population
Winner: Once again, this is task dependent, but a slight edge goes to driving simulation because it can be done locally where the subject populations exist.
This is one area where on-road testing is superior to a simulated driving environment. Actual on-road driving is what subjects are used to and expect. Though with a realistic enough simulation, a scenario can be created where subjects really believe they are driving.
Winner: On-road testing
The Clear Winner for Clinical Trials: Driving Simulation
When going through the above analysis it appears that simulation is the clear winner when it comes to performing driving tests in clinical trials. Driving simulators are valuable tools that can be used to assess the potential risks related to driving behavior associated with taking sleeping medications.
How to Use a Driving Simulator in Clinical Trials
When choosing driving simulation to use in clinical trials, the next step is to create the simulated environment, and to properly document and validate it so that the quality and integrity of the measured outcomes satisfy FDA requirements.
As with any new clinical trial, a Data Safety Monitoring Plan (DSMP) and Standard Operating Procedures (SOP) for the driving simulator hardware and software development, validation, implementation and training are required. In addition, as most driving simulators create their own self-contained electronic data records, they, like all new electronic testing devices, must comply with FDA requirements for Electronic Records and Electronic Signatures (21 CFR Part 11).
Finally, to ensure that the quality and integrity of the data being collected are maintained, a master validation plan is also required. This is used to show that the simulator provides accurate and consistent performance measures specified by the clinical trial sponsor. Creation of these documents is a collaborative effort between the study sponsor and the simulation manufacturer.
A Driving Simulator with Real-World Experience
Systems Technology, Incorporated (STI) was approached by a pharmaceutical company that was required by the FDA to include a driving component as part of their Phase III trials. After a process very similar to the one presented earlier, they decided to use driving simulation to meet the FDA’s requirements.
One of the primary factors in the decision was the ability to deploy simulators throughout the United States. This was necessary to meet the requirements of a diverse subject population at multiple clinical sites without having to move and house these populations.
Systems Technology Incorporated’s STISIM Drive™ driving simulator has a vast and varied history of use at research centers across the globe and has been successfully utilized in pharmaceutical research trials and university settings.
Clinical trials are necessary to determine how people react to certain stimuli while driving under the effect of drugs. Despite the illusion that on-road testing should be a more accurate option, it’s worthwhile to take a look at a driving simulator with a proven research track record and experience with clinical trials.