By Ed Miseta, Chief Editor, Clinical Leader
Follow Me On Twitter @EdClinical
Bert Hartog, Ph.D., innovation leader, in R&D Operations Innovation at Janssen Research & Development, has a plan in place to make trials more patient-friendly. Janssen’s goal is to incorporate the patient voice into clinical research, make patients a partner in the research process, and ensure all future collaborations are a two-way street.
Today, it seems every sponsor wants to incorporate the patient voice into clinical research. But for most, the challenge is figuring out how to successfully capture that feedback. To ensure the Janssen effort was successful, Hartog knew the company needed a method to generate those patient insights that helped better define and enhance studies.
The approach needed to involve two aspects: protocol design and study execution. “Both are equally important,” says Hartog. “You can design the best protocol in the world, but if you don’t know how to run it, then it’s going to be a failure. And you can run a study brilliantly, but if the protocol is not workable for patients and sites, it will likewise be a failure.”
The company tapped into disease-specific and general patient communities, hoping to apply market research methods to generate research insights. While helpful, these efforts still weren’t what Hartog considered to be “real” interactions. The problem was that the responses provided by potential participants were still far removed from the actual clinical trial.
TRIAL SIMULATIONS: A POWERFUL WAY TO GAIN INSIGHTS
When pondering this problem, a Janssen research team had the idea of a clinical trial simulation that would be an active exercise, much like a workshop, to truly understand how a study or proposed study will be received by patients and investigators.
Hartog says, “For us, this was a very powerful way to improve the design of the study. We were able to look into specific needs that came up during the simulation, but also look at logistics and other factors such as doctor/patient interactions that we normally may not spend much time thinking about.”
Hartog hopes simulations will become more common in clinical trials. The feedback and insights from patients and investigators will certainly help sponsors to better design and execute clinical trials. But more importantly, the simulations will give patients confidence that a study was properly evaluated, tested, and refined before the recruitment process began.
AGE-RELATED MACULAR DEGENERATION: THE FIRST TEST
The first simulation performed by Janssen was done to prepare for a Phase 2 study and involved a group of patients who were new to the company. All of the patients were suffering from age-related macular degeneration, a disease that was also fairly new to the company.
Going in, the goal was simply to understand how the proposed clinical trial would be perceived by patients and investigators. Hartog hoped to get to know the patients better and understand the subtleties of the interactions taking place between clinical investigators and patients who were progressing to loss of vision.
“We got a lot of very useful feedback, but we also learned that the methods used to run a trial simulation are quite intricate,” notes Hartog. “For example, we found you can’t just go into a simulation and start observing the interactions between people. You need to have a very thorough research plan in place. You need to spend time properly preparing the environment for the simulation. We also found you need to get the right individuals to participate, which includes patients, caregivers (dependent on the disease), investigators, and representatives from the sponsor company.”
In terms of preparation, Hartog notes it was no different in a simulation than in a trial, especially when it came to compliance. Compliance is necessary to ensure the privacy of the individuals and to properly secure the data. Hartog recommends a company’s internal compliance review team be involved from the very beginning.
“Getting compliance involved is something we do for every clinical trial,” shares Hartog. “But for a new therapeutic area like age-related macular degeneration, coupled with a new feature like the simulation, it was still a different experience. We had people reviewing the compliance requirements who did not have prior experience to lean on to judge the merits of the approach. This is one area where the innovation team was able to help them understand what the simulation was about, what we were trying to accomplish, and how it would be different from an actual trial.”
MORE SIMULATIONS PROVIDE ADDITIONAL INSIGHTS
The first age-related macular degeneration simulation helped Janssen better understand the trial and patient/ investigator concerns. The company then set up two new simulations. One was to understand more about the protocol design for an upcoming trial and took a closer look at the burden placed on participating patients.
This second trial featured a protocol with a long list of skills assessments and questionnaires. There were also questions about the interactions between participants and investigators. Hartog knew that many patients find these questionnaires to be tiresome. “Completing the surveys and questionnaires can take three or four hours,” he says. “We felt a second simulation would be an ideal opportunity to see when participants get tired or needed a break so that we could determine when best to stop the assessment or even schedule a followup visit.”
While that may not seem like a major concern, Hartog notes that discovering this type of information during the trial could result in damage to the integrity of the data or force a company to halt the trial and redesign it. By determining a patient’s fatigue level during the simulation, the trial can be designed with those insights in mind.
These first two simulations were organized in a market research center with see-through mirrors where researchers can observe participants without interfering in the workshop. The rooms were designed and equipped for that specific purpose and resembled an actual physician’s office. This helped patients and physicians feel as natural as possible while still being in a market research facility.
The third simulation was for Alzheimer’s patients. This simulation was conducted in a hospital, which Hartog believes was the first time a simulation was conducted in the same setting where the trial will take place.
The first two simulations mentioned also were conducted in just one country, one in the U.S. and one in the Netherlands. The Alzheimer’s simulation was run in three countries: Spain, the Netherlands, and the U.S. This is because the Alzheimer’s trial will be a multinational study.
“We felt doing the simulation in parallel in Europe and the U.S. would give us a good feel for potential differences in outcomes,” says Hartog. “Based on the insights received, we could decide if we wanted to expand the study into South America and Asia or keep it confined to the U.S. and Europe.”
Still, conducting the simulation in three different countries was a challenge. In fact, the complexity surprised Hartog. Clinical trials are generally conducted in a similar manner around the world. That is not the case with market research, which is done differently in various countries and regions. For Hartog, the challenge wasn’t that it couldn’t be done, but that it hadn’t been done. Aligning the effort in Europe and the U.S. was a complexity he had to work through, to allow the same simulation to take place in different countries.
Additionally, two of the sites recruited patients from a 2a study to participate in a simulation with the 2b study. These individuals had experience participating in a trial and would be seen as experts in providing insights to the clinical trial process. Researchers were also able to determine if their insights were different from simulation participants who have never taken part in a study.
Hartog states simulations are best suited for Phase 2 and Phase 3 trials, noting Phase 1 trials are exploratory in nature, making the relevance of the simulation less impactful. Phase 2 and Phase 3 trials tend to be riskier, both in terms of potential failures and cost implications. They also involve substantially more patients.
"We felt doing the simulation inparallel in Europe and the U.S. would give us a good feel for potential differences in outcomes."
Bert Hartog, Ph.D.
Innovation Leader, R&D Operations Innovation Janssen Research & Development
HELP FOR RECRUITMENT AND RETENTION
Recruitment and retention remain a challenge for pharmaceutical companies conducting trials. Any innovation that can make trials easier on patients will certainly help overcome this problem, and simulations are a step in the right direction.
Hartog believes future trials will show improved recruitment and retention based on the insights generated through simulations. In the age-related macular degeneration simulation, Janssen learned that patients appreciated the sharing of scientific information regarding their condition, along with models of the eye used with the explanations. This enabled them to not only listen, but to see the model, understand the problem, and know how the treatments would impact their condition.
Investigator engagement may also be improved by the simulations and could further impact patient recruitment. Hartog believes engagements with investigators will improve because of researchers observing their struggles and coming up with better solutions. For example, one issue for investigators is the informed consent process, and the learnings from the study can be used to better train investigators on how to approach informed consent conversations with patients.
Best of all, since the simulations are conducted by Janssen R&D Operations Innovation, the best practices learned will allow the company to build an internal knowledge base, or information repository. One study team might be running the simulation, but they are not the only ones who will benefit from it.
“This is not information that will be available for only one-off use,” adds Hartog. “Since it relates to the interaction between patients and investigators, it will be valid regardless of the therapeutic area and whether a study is performed in-house or outsourced to a CRO.”