From The Editor | January 29, 2019

Otsuka: Real-Time Data Changes Trial Paradigm

Ed Miseta

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

Wearables mHealth

At any given time, Otsuka Pharmaceutical Development & Commercialization, Inc. (OPDC) has between 60 and 100 ongoing clinical trials. Like many pharma companies, Otsuka is highly outsourced.

As the Otsuka VP of Applied Innovation and Process Improvement, Debbie Profit spends a lot of her time thinking about the future of clinical trials. “There are changes occurring in the industry that will force clinical development executives to shift their mindset,” says Profit. “I am trying to understand what clinical trial sites will look like going forward. I think we also need to change our vision of where and how we will leverage CROs in the future and think about whether CROs as we know them today will even be in our future. Ten years from now, I am not sure if the current CRO model will exist.”   

Technology is changing the paradigm of clinical trials. At the same time, companies are trying to look at clinical trials through the eyes of the patient, caregiver, and other involved stakeholders. This convergence is changing how Otsuka looks at trials. For years, the company viewed technology as a tool to create trial efficiencies. Today, the company is focused on how technology can enhance the experience of patients.

Poor Medication Adherence Is A Key Issue Facing Industry

Debbie Profit
Otsuka has a heavy focus on serious mental illnesses. Approximately 75 percent of the company’s business is in mental illness and central nervous system. Profit notes it’s an area that many companies have abandoned, but one where Otsuka is dedicated to making an impact for patients.

Unfortunately, professional help for patients can be difficult to acquire. Today, there are not enough medical professionals to fill the growing demand for mental health treatment in the U.S. The number of psychiatrist job postings increased by more than 97 percent between 2010 and 2014. The problem is so bad that many patients no longer have access to treatment. The report found that 60 percent of counties in the U.S. (and 80 percent of rural areas) do not have a single psychiatrist. It now takes mental health patients an average of 25 days to get an appointment with a psychiatrist.

“Community mental health centers are grossly under-funded and under-resourced,” states Profit. “They have very little funding for growth and innovation. I worked at a community mental health center for seven years, and today that facility in New Hampshire looks exactly as it did when I left there 26 years ago. I went there in 2012 to speak to the staff about digital medicine and was literally sitting on the same furniture.”

Medication adherence is an even bigger problem. Adherence is a problem across all patient groups but is lowest for patients with mental illness. The Mental Illness Policy Organization notes the failure of individuals with schizophrenia and bipolar disorder to take prescribed medications (usually antipsychotics and/or mood stabilizers) is one of the most serious problems in psychiatric care. Non-adherence can lead to relapse of symptoms, rehospitalization, homelessness, incarceration, victimization, or episodes of violence. The same report found more than half of these patients do not take their medications because they do not believe they are sick.

Further contributing to the problem is a clinical trial process that is antiquated and not patient centric. Profit states clinical trials today are conducted no differently than they were 26 years ago when she left the clinical setting. Most trials are still paper-based and involve little technology. When she was in a clinical setting, Profit provided informed consent forms to hundreds of patients. When she moved to a sponsor company, she contributed to writing many informed consent forms. “My sister passed away from ovarian cancer 15 years ago,” says Profit. “The informed consent form she received was 18 pages long and difficult to comprehend. Today, according to Johns Hopkins, the average consent form is even longer – about 22 pages. We are not making progress, and we must do better.”

Technology May Be The Answer

The challenges with psychiatrists and clinical trials are what got Profit to start looking at technology for answers. She believes greater use of technology is necessary for the industry to transform clinical trials. For example, she notes up to $30,000 could be spent on EKGs in a 20-person trial that spans just eight weeks. Therefore, why not spend an additional $499 to give each patient an Apple watch and keep them better engaged with the study? Not only would the study subject be more engaged, but the watch would allow researchers to gather more data from sensors that read to a wearable device, upload data to the cloud, and then provide information to the patient or to a physician.  

“Think about that parent sending a child with depression off to college,” says Profit. “All they want to know is that their child is taking their medicine. Physicians have told me how great it would be simply to know that a patient is taking their medicines. If a patient has a relapse, their doctor will want to know if the medication didn’t work or if it wasn’t taken. We now have technologies that can inform that.”

The real beauty of data from wearables is that researchers can receive that data in real-time or near real-time. Researchers can receive terabytes of data from clinical trial patients throughout the day. Without wearables, Profit laments the lengthy data collection process:  the data is collected at the clinical site, sent to the CRO, then to the data management folks, then to a biostats team, and finally to the clinical operations team. “That process can take six or eight weeks,” says Profit. “If I want to know how the patients are doing in a trial, we need to see the data in real time.”

Think About The User Experience

Profit also believes clinical trial participants need to have a better user experience. For example, for a clinical trial that included the development of a smartphone app, Otsuka needed to apply user experience testing of the app with the patient and caregiver at every visit; a very non-traditional methodology of collecting consumer feedback in a clinical trial. Initially there was apprehension by the clinical trial team, who felt the company’s compliance and legal colleagues would never allow it. These were patients with serious mental illnesses, and there were risk factors and rules that applied, particularly around informed consent and protected health information. But the team stood firm and worked with those colleagues to find acceptable solutions. “We needed to do this,” she said. “This is our future. Medicine, science, and technology are converging. We need to know whether bipolar or schizophrenia patients can use the tools we are designing to help support their treatments.”

It turns out patients and caregivers were not a problem at all. They were willing to participate in these visits. Legal and compliance were also not a problem as the proper approvals, privacy measures and requirements were followed. But in looking into the situation, Profit did discover a bigger problem that revolved around the physicians and psychiatrists. When dealing with patients, Profit found they often use qualitative rather than quantitative data.  

“If you ask a psychiatrist how often their patient takes their meds, they will tell you it happens 60 to 80 percent of the time,” she says. “The reality is that number is closer to 30 to 40 percent. Physicians and psychiatrists want to believe their patients are taking their meds, and that’s part of the challenge with serious mental illness. Doctors will keep changing medicines (or increasing dosage amounts) for patients because they think the drugs are not working. In many cases the patients are simply not taking them.”

Redesign The Trial

Those discoveries led Profit to rethink clinical trial design and how technology was being used in trials. She realized that if OPDC wanted to get clinical trial data in real-time, she would need to use tools that could deliver it. For the company’s second clinical trial using digital medicine, Otsuka used eConsent, eSource, and eScanning of clinical supplies. This was also the first time Abilify MyCite (aripiprazole with sensor), a combination drug/device approved to track drug ingestion, was used as a study drug.

“I remember being at home working at my computer,” says Profit. “I was watching my computer screens and I was able to see the exact moment when a patient ingested our drug. I was so happy I hugged my golden retriever and exclaimed, ‘Otsuka did it!’”

Profit was able to see that the patient had completed their eConsent. She was also able to see the eSource data coming in. She was able to verify that the patient checked the chart and could see in real time the patient had ingested their dose. The trial was taking place in California and she was able to view all of this in real time from her home in Maine.   

Profit was excited about the data she was seeing, but she knew it wouldn’t have real value unless it was integrated. “Our platform has 64 APIs coming from various data sources including CROs, central lab and ECG vendors, wearables and other sources across 40 clinical trials,” she says. “We needed to get all our data in one place and allow decision makers to visualize relevant data points in real time. Data-related solutions that facilitate data integration and analytics across clinical study teams was the next step. We previously managed complex tables and listing documents that can stretch to more than 1,000 pages. With features like data dashboards and automated alerts, these solutions make it easier to review trial monitoring reports, manage clinical supplies, and comply with regulations and adhere to internal data governance structures.”

Incorporate Digital Therapeutics

For many in the pharma space, digital therapeutics are quickly becoming the new reality. Digital therapeutics are treatment options that use digital (often online) technology to treat a medical or psychological condition. It relies on behavioral and lifestyle changes spurred by a collection of digital impetuses. The methodology uses a variety of digital implements to help manage, monitor, and prevent illnesses in at-risk patients. These treatment options include mobile devices and technologies, apps, sensors, computers, and various Internet of Things devices to modify patient behavior.

“There are currently 490 digital therapeutics in development just in the mental health space,” says Profit. “Pharma companies have to realize they are not just competing against other pills. Today, they are competing against digital therapeutics that could potentially take the place of the pill or supplement a pill. There could be no drug involved at all and the therapy could be less invasive. We now know behaviors can be changed by use of a smartphone.”

That means pharma must start thinking about new competitors. Partnering with digital therapeutics companies is certainly a possibility and Otsuka just recently announced a collaboration agreement with Click Therapeutics to develop and commercialize a prescription digital therapeutic for treatment of Major Depressive Disorder (MDD). But pharma will also be competing with them for talent. Profit saw an infographic recently that showed companies need data scientists and machine learning talent. In the New York area alone, 3,000 job openings exist, but there are far fewer individuals available who meet the criteria. Therefore, partnering might be necessary to gain access to the available talent. 

"More and more companies are getting into the health science space,” states Profit. “Companies like Best Buy and home security company ADT. These consumer product companies are in constant contact with the public and that is an advantage for them. Best Buy has invested around $6 billion in life sciences, and we already know that Google and Apple are also making large investments to transform the industry.”

Is Your CRO Along For The Ride?

Now that pharma companies are changing how they get their data, will their CROs be adopting those changes as well? Profit thinks their CROs are trying to change as well. She notes Otsuka’s CROs are primarily using all of OPDC’s internal platforms.

“When it comes to technology, some CROs think they have the Lexus and we have the Toyota,” she quips. “The reality is, what they have is less than a Toyota. Still, the system that each company has is not relevant. The need for real-time data is what’s important. If you are using smart watches in a study, you want to get the data in real-time. Waiting to get that data is no longer a viable option for us. It was hard for our own teams to make that change, and it will be hard for the CROs to do so as well. Using new, available technologies requires a change of mindset.”

In the future, will it be possible for sponsors to get the data they need direct from sites and digital devices? Will bypassing the CRO altogether become an option? If all that becomes required from a CRO is monitoring visits to sites and having discussions with physicians, should pharma take on that responsibility? And will they want to?

“Going forward, not all clinical sites will look like they do now,” says Profit. “Will CVS and Walgreen’s become clinical trial sites? Will urgent care centers? Will we see more trials going to the patient, as opposed to having the patient come to the trial? These are things we must consider. We need to put our focus on the patient and not the site. That will involve having real discussions about how to truly make trials patient-centric.”

There will certainly be naysayers who complain this vision will not work. Profit notes there are colleagues who told her she was crazy when she promoted the idea of conducting trials using a completely e-based platform to deliver digital medicine in patients with serious mental illness. She now makes a point of inviting those naysayers to meetings.

“We know they are going to say that it can’t be done,” she says. “They will tell you there is no way the FDA will approve your plan. When everyone tells you what you can’t do, you begin to have discussions about what you can do. We have a dialogue and discuss what the challenges will be and map out the road forward. We discuss what the trial will look like, the resources required, what the timeline will look like, and what we need to do to manage the change. You can’t say, ‘We’re now going to go direct to patient,’ and not change your process. Mapping out the entire process will allow you to stay on track and ultimately deliver better products to patients and consumers who need our speed and flexibility. The reality is everyone wants progress, but no one wants change. Our job as industry leaders is to help people see the significant benefit of changing the clinical trial process for all in the value chain, most especially the patient.”