By Ed Miseta, Chief Editor, Clinical Leader
Follow Me On Twitter @EdClinical
The world of clinical trials can sometimes seem to be a large, corporate machine of sponsors, vendors, regulators, and sites.
However, occasionally there are moments or experiences that can drive home the point that at the heart of all clinical research are individual patients struggling to overcome serious and life-threatening diseases and individual physicians at clinical research sites devoted to helping them. Peter Ronco, VP of global clinical operations at Bristol-Myers Squibb (BMS), had one of these moments and has spent a lot of time pondering these relationships. “Over the last 12 months, one of my close family members has been a patient on a BMS oncology trial,” he says. “I have directly seen what it is like to be part of a clinical trial from a patient’s and caregiver’s perspective — both the good and the bad. In most cases, the interaction with patients is through an investigator site. From the site’s perspective, when I sat back and compared how we were actually working with some sites, I was shocked by the number of sponsor interactions that occur. I was also amazed at how complicated we seemed to be making the whole process of interacting with these institutions we considered partners.”
Making clinical trial processes complicated for a site also means you’re making it complicated for patients. As someone who was focused on patient-centricity, that did not sit well with Ronco, and started him on a journey to find a solution.
“We knew to compete in immuno-oncology — and to be successful — we had to fundamentally change our model,” notes Ronco. “In addition to major academic oncology centers, we are also working with far more active and involved community networks and patient groups. To better serve them, we wanted to rethink the most basic aspects of our approach to these relationships.”
PUTTING A NEW MODEL IN PLACE
Ronco knew that whatever procedures were put into place would need to be embedded in how the company operates and why employees come to work every day. The new program, called Aspire, has been up and running for more than a year. Prior to the launch, it took approximately nine months to develop, and involved listening to ideas from sites and patients on how to connect with them and design better studies. Ronco says, “Patient-centricity is not a new idea, and it’s something BMS has been focused on for years. What we are really hoping Aspire will do is create a structure that allows us to pull together all of our efforts and accelerate them forward. Once in place, the model would simply become a key component of how everyone in clinical operations operates.”
A DIFFERENT APPROACH TO PATIENT-CENTRICITY
There are two main pillars of the Aspire program, and the first involves how the company works with patients. Every company today seems to be stressing patientcentricity, but Ronco notes the approach taken by BMS is slightly different since it includes measurable outcomes.
“When study participants, caregivers, and advocacy groups hear the term patient-centricity, it can sound like a buzzword,” says Ronco. “In many cases, that’s exactly what it is. Patients will always question how your actions are helping them. They need to see companies taking specific, concrete actions with the interests of the patient in mind. Simply hiring a chief patient officer does not fulfill your patient-focused requirements, and misses the point entirely.”
Ronco felt the first step in making patient-centricity a priority for all employees was putting the patient front and center in a very visible way. Today, if you walk into any BMS facility, you will see 20-foot high pictures of patients (as well as video screens with patient stories) placed around the entire lobby. Banners featuring patient pictures are spread across the parking lot. This effort, titled “Working Together for Patients,” was designed to serve as a motivational force and a reminder to employees of why they come to work every day.
Next, BMS spoke to patients, caregivers, and advocacy groups to discover any areas in which patients needed help. Through those interactions, it was determined that patients needed assistance understanding their disease and how they fit into the effort to find a cure. They also needed help finding the right study, getting through the trial experience, and getting back to their lives after the trials came to an end.
“We wanted patients to know they are part of a community. Participating in a trial will hopefully benefit them, but it will also benefit many others who are dealing with the same disease. Educating them on the trial process and addressing their concerns also alleviated a lot of the anxiety they had about participating in a trial.”
These in-depth conversations take many forms, including patient engagement networks (PENs), focus groups and protocol prototyping sessions, meetings with advocacy groups (including board members and patients), surveys, patient conferences, and meetings with partner sites. In addition, a lot of emphasis was put on the follow-up discussions with these stakeholders to further refine and improve study designs. After all, it’s common to hear of patients who completed a trial, only to never have any follow-up from the site or sponsor. Where does the drug currently stand? Was the trial a success? Did the drug get FDA approval? It seems study participants can often be the last to know.
“As part of the Aspire program, we assist patients in transitioning to the next available therapy,” says Ronco. “For example, should they continue with the therapy they’re on or should they be moved to another clinical trial? This approach takes patient-centricity from being a buzzword into very specific activities and actions that drive how we design and run studies.”
All of those interactions also uncovered a pet peeve of many patients — the fact that they are rarely thanked for their participation in a trial. One example of how BMS addressed this was to specifically thank patients and clinical staff in its DTC advertising in the U.S. for its Opdivo medicine. Ronco states the company received positive feedback from trial participants, who appreciated being recognized for the role they played in the development process.
THE VALUE OF PATIENT NETWORKS ON TRIAL DESIGN
Ronco says the PENs, which are composed of patients, caregivers, advocacy groups, and study site personnel, are among the key ways BMS hears patient perspectives on trial designs and materials. These groups also help BMS identify any barriers to enrollment and ways to make trials easier on participants, thus improving recruitment and retention rates.
The PENs are formed early on in a development program in a new disease area, usually prior to a protocol synopsis. The timing is important, because it allows BMS to understand the potential barriers and hardships patients and their families may face, due to decisions that are made very early in the design process.
When a PEN first convenes, time is spent educating the group on the BMS clinical drug development process, the compound(s) being studied, and how they will interact in the body. This ensures all participants will understand the clinical trial process and be able to make good, informed decisions. Once everyone is comfortable with the process, there are discussions about the disease journey. All of these meetings have formal agendas, designed to stimulate a flow of ideas in both directions.
“There have been many useful outcomes from our PENs, including modifications to our inclusion/exclusion criteria, removing extra biopsies, and adding concierge services to one of our trials after learning about the hardships on the patient and the families,” says Ronco. “A PEN will typically meet several times a year, both in-person and virtually, and will stay together over the life of an asset/compound. In many areas we have multiple medicines that will hopefully address a specific disease. In those cases, the PEN will cover all of those medicines.”
Ronco is quick to note the PENs do not include scientists or thought leaders from BMS. Those individuals play a key role in designing the trials and protocols and determining the information that should be collected. The individuals working under the chief patient officer are generally more adept at dealing directly with patients. The groups are pulled together early on in the development process to get the patient voice involved in trial design. As Ronco notes, “Having them review a protocol after it has been developed and approved is of little value to the patient.”
BMS lets the group know it will be working on a particular disease for a number of years and would like to get a good understanding of the patient journey — what it is like to have to live with the disease or to be a caregiver to a patient. One of the primary questions asked is: What must be done to help them live better lives?
“Regulators now want to know that patients value the metrics you’re using to judge the success of a trial,” says Ronco. “Not measuring something they deem important is also a mistake. If patients and advocacy groups are telling us that a metric is the most important measure for them, that’s powerful, and that kind of input will have more influence with regulatory organizations.”
DON’T OVERLOOK THE IMPORTANCE OF SITE EDUCATION
One additional component of the Aspire program relates to having better interactions with investigator sites. This effort involves several pieces. First, the site has to believe in the benefits delivered by the medicine. Sites and physicians have personal relationships with patients and will always have the best interest of the patient in mind. If they do not believe the medicine being tested will fundamentally address the unmet medical needs of patients, it will generate less interest from the site and jeopardize the study. Therefore, educating site personnel on the medicine, the trial, and the benefits for patients is crucial.
Second, there has to be an aspect of customer service that is built into every site interaction. Ronco believes interactions will be improved when sites feel they are partners with BMS, not vendors being hired to provide a services. “When you call your cable provider with a question, you don’t want to be passed around from one department to the next,” says Ronco. “You want your issue to be handled quickly, efficiently, and directly. We want sites to have a similar experience with BMS.”
To accomplish this customer service component, the company has invested in site-facing staff who build longterm relationships with sites and are able to address issues in a timely and effective manner. A Monitoring Excellence program has been implemented to support and grow these critical roles. Dedicated relationship managers have also been put in place to manage key site networks and academic institutions. These individuals have a deep understanding of both the BMS portfolio as well as the operations of the local sites. They are then able to resolve issues as well as establish longer-term strategies.
“We are now stressing the importance of the customer experience across all site-facing roles,” says Ronco. “This is a cultural focus. We have to ensure that, regardless of which department or individual is contacted by a site, personnel will resolve the issue efficiently and directly.”
Third, Ronco notes there are basic tasks that must be performed flawlessly. Here he is referring to things like having the drug and lab kits available at the right place and time and having an electronic data-capture tool that is easy to use. While these are basic steps to performing a successful trial, they are also things that will drive site personnel crazy if not done correctly. A lapse here will also impact the care of the patient. A sponsor can have the best technology available, but if it is not easy for a site to access and use, the relationship will suffer.
Once all of those basic building blocks are in place, the sponsor can start looking at ways to further improve the site experience. One example Ronco cites is a concept called “study in a box,” which involves shipping all items necessary to start a patient on a trial in one convenient box. This alleviates having to ship supplies in multiple packages and expecting patients or site personnel to piece it all together. Technology also can be leveraged to scan drugs and supplies, allowing them to move through the system more quickly and efficiently.
“Today I can order a pair of shoes from Amazon. com and track the hour-by-hour progress of the shoes through the fulfillment and order process,” says Ronco. “We have investigators who have scheduled patients for visits. They need to be able to track drug and study supplies in a similar way so they can run their sites effectively. One of the most frustrating things for a site is when a patient is scheduled for a visit but cannot participate in a study because of missing drug or lab supplies. Our approach is to use multiple technologies, including bar codes and Q-codes, to more effectively communicate the supply chain to sites.”
EARLY SIGNS OF SUCCESS
Ronco has seen clear signs that the Aspire program is benefitting BMS, patients, and sites. From a patient standpoint, he spent some time late last year working with a PEN, and he had the opportunity to interact with a patient group for sufferers of Sjogren’s syndrome, an autoimmune disease.
"We knew to compete in immuno-oncology — and to be successful — we had to fundamentally change our model."
VP of global clinical operations, Bristol-Myers Squibb
“Members of the PEN initially had minimal understanding of the clinical trial process and how they could contribute. But after spending the day with us, they came away very excited and ready to be an integral part of the team,” says Ronco. “They felt we had a genuine desire to learn from them, understand them, and make a long-term commitment to them. We got a large number of thank-you notes.”
BMS now performs regular site surveys across all disease areas to get insights on the experience of working with the company as well as what was done well and what could be improved. The surveys are generally five questions or fewer. Sampling approaches are used to avoid overloading any individual site. BMS also works with CRO partners to help them implement similar approaches. Site personnel are asked if they would recommend BMS to a friend or colleague and the primary reasons behind the answer. Sites that respond will be called back within 48 hours.
“If someone tells us we’re doing great, that’s beautiful,” says Ronco. “We call them up and thank them for their comments. But more importantly, when someone says, ’Hey, your medicines are really benefitting our patients but your tools or the way you conduct your study could be improved,’ that’s when we get the most insight. We will immediately follow up with those sites to determine what we’re doing to make their life difficult and what we can change. Determining our shortfalls and making improvements is an ongoing process.”
Going forward, BMS will continue to refine the program, based on feedback received from sites and patients. Ronco notes if a new initiative, process, or technology is introduced, the first question now asked is how it will help make clinical trials better for sites and patients.