From The Editor | August 12, 2021

The Four Essential Pillars of Successful Patient Centric Trials

Ed Miseta

By Ed Miseta, Chief Editor, Clinical Leader
Follow Me On Twitter @EdClinical

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Praxis Precision Medicines is a drug development company using genetic insights to focus on treatments for patients with CNS disorders, namely mood disorders, epilepsy, movement disorders, and pain. Praxis has patient centricity infused throughout the organization and believes taking care of patients and producing successful trials comes down to four essential factors: staff, sites, CROs, and patient insights.

That is the viewpoint of Bernard Ravina, the company’s CMO. He was hired because of his expertise working with patients, and he looks for that same background in everyone he hires.  

Ravina is a neurologist by training and has specialized in Parkinson's disease and movement disorders. He spent several years with The National Institutes of Health before serving as vice-chair of clinical research at the University of Rochester, where he ran trials as an academic CRO. He then entered the pharma industry, starting work at Biogen before helping to launch Voyager Therapeutics. Three years ago, he joined Praxis, drawn by the potential of the company’s pipeline.  

A Staff That Understands Patients

Bernard Ravina, CMO, Praxis Precision Medicines
Ravina notes he will intentionally hire people who are familiar with sites and the patient journey. That includes physicians, clinical scientists, and medical personnel from sites. “That is very important to us,” he says. “Neuroscience trials are not easy, and they have complications. We want people who know what the issues are, who understand the eligibility criteria, and have insights to the patient journey. Those with site experience are good at identifying potential trial patients, understanding their motivations, and knowing if they will be a good subject for the study.”  

As a neurologist, Ravina is an expert on movement disorders. Praxis is working on pediatric epilepsies and recently hired a pediatric epileptologist. The head of psychiatry has experience in trauma induced disorders such as PTSD and is also an expert in mood disorders. Other employees are hired based on the therapeutic expertise and patient insights they can bring to the company. Two other employees have children with genetic epilepsies and provide daily reminders to other staff members on what the patient and caregiver struggle is all about.

“Without that expertise, you cannot fully understand the patient journey,” says Ravina. “This is not fluff. I believe that expertise needs to be built into the DNA of the company. That understanding of the patient condition goes into the design of every one of our clinical trials and provides us with a 360-degree view of the disease and its impact on patients.”

An Objective Measurement

Objectively measuring endpoints in a CNS trial, especially mood disorders, is also a difficult task. Results cannot be determined by a simple blood draw or other diagnostic test. To ensure accurate eligibility and results, Praxis relies on an entirely independent psychiatric interview. Ravina notes the company has faith in the findings of the principal investigator but believes in the value of a second set of eyes.

“This is an established process that conducts an independent psychiatric interview,” states Ravina. “They confirm that a patient has the diagnosis of major depressive disorder and the severity of the disorder. A similar process is used in trials that look at patient tremors. We video the patient and make a determination, then a central video review will look at the recording and confirm the reading. For us it’s like an extra level of scrutiny.”

Using depression trials as an example, Ravina notes a group at Mass General has developed an independent review process, used in many countries, that has been shown to reduce placebo effects.

Know Your Sites

Being a small company, Praxis does seek help conducting trials from CRO partners. However, the company does not approach these relationships in a traditional manner. Ravina notes that traditional approach involves finding a CRO with experience in your therapeutic area and letting them drive the site selection process. He believes that approach is inadequate.

Ravina believes that study sponsor needs to know every site. That is necessary to know the study coordinators and the quality of the investigators. Sponsors also need to be aware of things like staff turnover at the sites. Site staff needs to know the disease and the patients and understand prescriptions and billing. If staff is coming and going, they cannot form the necessary relationships. A knowledgeable staff drives and maintains quality in a study and monitoring that staff should not be left entirely to your CRO.

“The value of being involved is we know our patients,” he states. “We understand them, not just as a patient but as a person. We need that experience at the sites. We need the sites to tell us if someone is a good trial candidate. Are they enrolling for the right reasons? Are they going to take their medication? Does the potential participant trust the site team? Those are complex and important relationships.”

Find The Right Partner

Praxis currently has three clinical stage programs underway and all three are engaged with a different CRO partner. Understanding that model goes back to understanding the clinical goals of the company.

The company’s trials got their start in Australia, where Praxis opted to engage with local service providers. When those trials migrated to the U.S., that necessitated engaging with new, larger partners. Ravina’s initial focus when evaluating potential partners is therapeutic expertise. But right on the heels of that is trying to understand which partner is best equipped to help Praxis realize trial efficiencies.

“Who can help us run multiple trials using the same sites?” he asks. “Who will be best at working with those sites, better engaging with study coordinators, ensuring adherence to study protocols, and shortening start-up times? Those are all things we evaluate in study partners. There is always an opportunity for a CRO to excel and show us how they can provide us with economies of scale, quality metrics, getting the right patients into our studies, and ensuring adherence to the study drug. It does not matter if they are a large or midsized partner provided they have a pathway to help us get to where we need to be. We don’t need lip service. We need their attention. There are a lot of companies out there that have the experience we desire, but we also need them to be an engaged partner, so our business does not get lost in the shuffle.” 

A Focus On Patient Centricity

Having worked with patients prior to getting into drug development, Ravina is aware of the patient journey and the importance of patient centricity in trials. But he also believes it is a term that is overused in the industry. While many companies use the term, it is not always clear what they mean by it.

For him, the definition is simple: Centricity means reducing barriers for patients and making study drugs easy to take. Ravina cites his company’s depression drug as an example.

“Many treatments have food restrictions,” he states. “That is a major issue for patients, many of whom have appetite disturbances. With our treatment, there are no eating restrictions, which is one additional thing patients and caregivers do not need to be concerned with. The challenge for us is coming up with the right formulations that allow for that.”

During the pandemic, when it was more difficult for patients to travel to clinics, the company pivoted to a platform that enabled patient-reported outcomes via their phones and scheduled remote visits whenever possible.     

Adherence to prescribed medications is also important to the patient and the study. Praxis engaged with technology provider AiCure to assist with that.

“After conducting a vendor search, we felt their technology would best allow us to help our patients,” notes Ravina. “The software can be used on almost any device or phone. The software can record the patient as they are taking the study drug. That helps us confirm they have taken it as prescribed. We know when they took it, and we are notified if there is a possibility that they did not take it or did not take it properly. Our depression drug is taken before bedtime, so we can be aware of their adherence on our dashboard the following morning. It also gives us the ability to send out medication reminders. Patients find it helpful, and the interface is easy to use. We are using it in all of our depression studies, and it has resulted in very good compliance.”

Patients Are Research Partners

Some of the therapeutic areas Praxis works in do not yet have organized patient communities. Some patient groups are sophisticated while others are nascent. In some of these populations no one has conducted a real systemic clinical trial. Still, that has not kept the company from performing outreach and trying to gain as much feedback as possible. The insights gained help the company go beyond study protocols and understand what is most important to patients. Ravina considers patients and patient groups to be strategic partners in the drug development process.

“They help us understand recruitment concerns, they review protocols where appropriate, and when we produce study requirements, they are first shared with patient groups to gain their thoughts and feedback. Even when there isn’t an organized patient community, we will perform outreach on social media to gather patient concerns.”    

Moving forward, Ravina feels Praxis is in a good position to deliver needed medicines to patients dealing with CNS disorders. He believes the company is unusually well positioned with a broad and extensive CNS portfolio.

“We are at the point where we are ramping up and looking forward to achieving our goals,” he adds. “We are executing on these trials and doing so in a high-quality manner. By partnering with the right CROs, sites, and patients, we are confident that we will be able to bring relief to patients with all of these disorders.”