In preparing for this trends issue of Life Science Leader, there were numerous clinical topics I could have discussed. Many new technologies are emerging that will change how trials are conducted and impact everyone involved in the process. All of them are deserving of attention. But one long-standing issue that refuses to go away is patient recruitment and retention. For pharma to make headway in this area, build trust with patients, form partnerships with advocacy groups, and get feedback from patients incorporated into protocol design, patient-centricity must continue to be a priority in 2017.
While most pharmaceutical companies would agree that gaining insights from patients is a priority, figuring out how to best acquire that feedback remains a challenge. How do you find patients to query? What questions should you ask? Should you administer surveys or conduct simulations? How involved should you get in a patient’s life while trying to gain those insights? If there is one thing we know for sure, it’s that patient-centricity officers will have their work cut out for them.
While some companies try to figure out how to answer these questions, others are moving forward with innovative ideas and interacting with patients in new and novel ways. In this article, I look at two companies taking patient-centricity to new heights, and showing others what can and must be done to hear patients and solve recruitment challenges.
Abeona Therapeutics Puts Focus On Patient Travel
Mucopolysaccharidosis MPS III, also known as Sanfilippo syndrome, is a group of four genetic diseases, referred as MPS IIIA, MPS IIIB, MPS IIIC, and MPS IIID. It is a lysosomal storage disorder, and children afflicted with MPS III are missing the enzyme needed to break down long chains of sugar molecules. The result is cells unable to fully break down and replace HS, a material necessary for building connective tissues. Infants and toddlers may not show signs of the disease, but as more cells are damaged throughout the body, symptoms gradually appear. There is progressive neurological and physical decline, including speech, walking, eating, difficult behavior, and sleep issues. This regression continues to full loss of speech, walking, and the ability to feed oneself, leading to a severely shortened life span.
When Abeona Therapeutics began preparations for a clinical trial of MPS III patients, another challenge arose: Children and parents would have to travel to Nationwide Children’s Hospital in Columbus, OH, where the trial would be conducted. Some might choose to drive, but because of the location, others would have little choice but to fly. Lodging would also be required for the estimated five weeks that families would need to stay in Columbus on their initial visit, in addition to subsequent follow-up visits.
Discover The Concerns Of Caregivers
Before starting the enrollment process for this trial, Michelle Berg, VP of patient advocacy for Abeona, wanted to understand what the travel experience was like for the children and their parents. She felt the best way to gain that understanding was to engage and interact with a handful of families. Her hope was to understand the specific challenges they faced when traveling by plane or by car, and staying for an extended period of time in a city that’s unfamiliar and potentially far away.
“We had certain assumptions going in, based on what we had learned in the past, but it was amazing to hear input from the families on everything from how to arrange seating on an airplane to what type of accommodations would be most convenient,” says Berg. “The interactions took place via teleconference, and we selected families with children of different ages and different regions across the country. The teleconferences also included caregivers of patients with both MPS IIIA and MPS IIIB (two of the four types of Sanfilippo syndrome). These caregivers have jobs and are being asked to uproot their families for an extended period a time. We wanted to make what is surely a stressful experience as positive as possible.”
"These caregivers have jobs and are being asked to uproot their families for an extended period of time."
VP Of Patient Advocacy, Abeona
Regarding the flight, Abeona assumed that a seating location near the front of the plane, as close as possible to the exit, would be preferable. That assumption was correct, as it facilitated a quick boarding and off-boarding experience. But something the company hadn’t considered was the placement of caregivers. Berg found families had a preference for placing one caregiver or parent in the seat directly in front of the child, instead of seating everyone in a single row.
“That was a bit of a surprise, but after talking through it, we understood why,” says Berg. “These kids have behavioral challenges and might kick or pound on the seat in front of them. This could irritate the passenger sitting there and make for a stressful situation for the parent(s). It’s difficult to stop the child’s behavior, but placing a caregiver in that seat can alleviate an uncomfortable situation. The exit row also provides additional leg room for children over the age of 15.”
Another preference was bulkhead seating, if available. Having a panel in front of the child, rather than a passenger seat, allows both parents/caregivers to sit next to the child during the flight.
Safe And Comfortable Living Space
The next concern was lodging. Since trial participants and family members would be spending several weeks in Columbus, the facilities had to be both comfortable and accommodating. Because of the extended stay, rooms with a kitchenette were preferred, as they allowed families to eat in rather than dine out at a restaurant every night. Caregivers also preferred a site close to the hospital so as to minimize travel time.
Berg was able to locate a suitable apartment facility near Nationwide Children’s Hospital with the help of the Batten Disease Support and Research Association, a local organization working to support families impacted by all forms of Batten Disease, another area of focus for Abeona. It was selected based on both location and proximity to certain amenities the families indicated would be helpful, such as parks, grocery stores, and retail shops. Abeona selected a two-bedroom, two-bath unit that also happened to be handicap accessible. It includes a full kitchen, in-unit laundry facility, balcony, and living room, and was fully furnished by Berg and some helping hands. Even Tim Miller, Ph.D., CEO and president for Abeona, got involved by hanging curtains and assembling furniture.
Additional modifications still had to be made to the apartment to make it safe for the children. Berg put a lot of additional thought into this, as well as soliciting feedback from caregivers.
Because the children may have hyperactivity or sensory limitations and will be staying in an unfamiliar environment, their safety was a primary concern. Abeona took all of the furniture with sharp edges, such as tables and stands, and placed padding on the edges. Another concern was children pulling heavy objects upon themselves. For that reason, items such as televisions and lamps are securely mounted to tables and walls to prevent them from being moved. Other miscellaneous items in the apartment (soap dishes, for example) were selected on the basis of containing nonbreakable materials and rounded edges. Locks were also placed on doors to prevent kids from making unplanned escapes.
“In the apartment we also installed blackout draperies, because sleep can be another challenge for patients and, therefore, caregivers,” adds Berg. “Having the room as dark as possible will help create a better sleep environment for everyone.”
Pfizer And Ethnographer Focus Camera On Patient Lives
Sickle cell is a disease that affects both men and women via their hemoglobin, the molecule in red blood cells that delivers oxygen throughout the body. Patients with the disorder have atypical hemoglobin, which distorts red blood cells. Although it can affect any race, it is much more common in the African American population.
“The red blood cells with the abnormal hemoglobin will collapse into a sickle shape,” says Brenda Cooperstone, VP and chief development officer for rare diseases at Pfizer. “These cells bump up against the blood vessel wall, causing endothelial damage. That, in turn, starts a cascading effect in terms of inflammation and blocking of small blood vessels. This results in terrible pain which can occur anywhere but is often felt in the bones.”
Other symptoms of sickle cell include anemia, repeated infections, strokes, and lung clots. But pain is the greatest challenge, and patients can be faced with the onslaught of a pain crisis at a moment’s notice. As a result, it can be uncomfortable and very disruptive to patients and caregivers.
Patient Recruitment Raises Concerns
In 2011, Pfizer entered into an agreement with biotech firm GlycoMimetics to develop Rivipansel, a molecule for the treatment of vaso-occlusive crisis in sickle-cell patients. Per the agreement, GlycoMimetics would take the treatment through a Phase 2 trial, and Pfizer would be responsible for all future development. Although the treatment produced hopeful results in a Phase 2 trial, Pfizer knew performing a Phase 3 trial would not be easy. It took GlycoMimetics three years to recruit just 76 patients for the Phase 2 study. For the Phase 3 trial, Pfizer would need over 300.
“We knew we did not have nine years to recruit them,” says Cooperstone. “None of us wanted to wait that long to bring what could potentially be a life-changing medication to these patients. We knew we had to do something different, and felt a good place to start was with an understanding of the patient community.
Cooperstone did not know much about the sickle-cell community, but she did know many of these patients were not willing to participate in trials, and retaining them in studies was also a challenge. If she was going to partner with them to advance a clinical program, she needed to understand their condition and needs.
Look Into Patient Lives For Insights
To help with that understanding, Pfizer contracted with an ethnographer who had access to sickle-cell patients. Ethnographers study people and cultures, and she was someone who could get to patients, insert herself into their lives, and see what it was like to live with this disease. By viewing a video of their journey, Pfizer could design and conduct a trial that would be more conducive to patient participation.
Pfizer received hundreds of hours of tape, which was watched by Cooperstone and members of the development team. That team included up to 15 individuals including clinicians, medical monitoring physicians, statisticians, and staff from market research and development. Much of the footage showed patients experiencing their episodes of pain and the treatments received. Footage also included patients being interviewed about their experience with the healthcare system and the treatments they received.
“The videos brought us very specific insights about what we could do differently to enroll this trial faster,” says Cooperstone. “One of the things we concentrated on was the vernacular. For example, we noticed these patients never refer to what they were going through as a vaso-occlusive crisis, even though that’s both the medical and regulatory term used to describe it.”
That simple finding was important to Pfizer, as the material it had, including the protocol and all patient-facing materials, referred to the situation as a vaso-occlusive crisis. Physicians, investigators, and other healthcare providers know the term, and assumed patients would know what they were talking about. The videos clearly showed patients were not familiar with it at all, instead referring to it as a crisis, pain crisis, or simply pain. The experience changed how investigators refer to the crisis and led Pfizer to change the wording in its materials.
"The videos brought us very specific insights about what we could do differently to enroll this trial faster."
VP And Chief Development Officer For Rare Diseases, Pfizer
Preplanning Helps Recruitment
A second discovery was far more telling. Patients are generally placed into a trial and randomized to receive either the treatment or placebo when they are rushed to the emergency room with a pain crisis. Unfortunately, when patients are in that situation, Cooperstone notes they are in no condition to make important decisions.
“When in the middle of a crisis, they are in absolutely no shape to go through an informed consent process,” she says. “In the Phase 2 trial that recruited 76 patients, these individuals were in the emergency room, writhing in pain, with someone in front of them requesting informed consent. After listening to patients, we knew that had to change the way we consent patients.”
In the current Phase 3 trial, patients can be brought in and informed of the consent process prior to the onset of a crisis. An investigator will go through the informed consent form and all of the study procedures, after which the patient can agree to participate. By signing the consent form at that time, patients simply reaffirm the consent when they enter the emergency room.
Transportation was also an issue, since individuals participating in a trial would have to be taken to the correct hospital. With the early consent process in place, Pfizer could arrange for that transportation. Today, patients who consent to the trial have an app installed on their phone. When they have a pain crisis, the app will send a text message to a transportation service that delivers them to the correct emergency room.
“For us, that emergency room visit was where patients entered the trial and became a partner with Pfizer,” adds Cooperstone. “We knew it was the place where we needed to make improvements for both the patient and sites. Without some of the positive outcomes we put in place, it would have been very difficult to get patients to become part of the trial and receive the treatment they needed.”