Patient recruitment has historically been a challenge for pharmaceutical clinical trials. Nationwide, less than three percent of patients participate in clinical trials due to the limited number of practices that take part in research. Issues with patient recruitment and enrollment are the primary cause for missing clinical trial timelines, and studies show that in 2015, more than half of trials were terminated due to low enrollment. With the rise of cell and gene therapies, participation issues are becoming magnified.
Cell and gene therapies often treat patients with rare diseases or very specific genetic or cellular characteristics. Cell and gene therapy trials require very specific genetic or disease-level requirements, further complicating recruitment and reducing the already limited pool of participants. To better position cell and gene therapy trials for success, innovators will need to carefully consider their clinical trial design to mitigate challenges around patient recruitment and retention.
Identifying the right patient
Today, cell and gene therapy clinical trials are being conducted across the country. However, due to the complexities of cell and gene therapy, the conduct of these studies occur at high volume of academic research facilities, typically in New York, Pennsylvania, Texas and California. Additionally, in a review of cell and gene therapies in the pharmaceutical pipeline, nearly 2,000 projects in development have received an orphan drug designation by the FDA, and a high percentage of development activities are potentially “first in class.” The scarce and geographically scattered nature of rare disease patients does not necessarily align with where the majority of the research is taking place, creating additional challenges for recruitment.
For a clinical trial where full participation means 20 to 100 patients, every patient’s participation is crucial. Often, trial sites are selected based on the principal investigator or institution reputation, rather than locations that are ideal for participants. Far or inconvenient trial locations can be a significant barrier, forcing patients to balance travel, financial constraints and other life considerations while managing their disease. These hurdles immediately eliminate a significant part of the potential patient pool. In addition, patients prefer to be treated in their own communities or may not know about the trial if it’s far from their home or community.
One solution to help connect with these specific patients is to integrate with community-based practices to create an active referral network where providers can play a more significant role in recruitment and the trial overall. IntrinsiQ Specialty Solutions and ION Solutions, both a part of AmerisourceBergen, recently launched the AdvanceIQ Network, a program designed to better match independent community practices with clinical trials and research opportunities. Through AdvanceIQ Network, practices have a more streamlined approach to identifying, qualifying for and enrolling in targeted clinical trials that offer groundbreaking treatment options for improved patient outcomes.
It’s a logical cause and effect: innovators that build relationships with providers and supply them with resources to educate and drive awareness of their trials will increase their abilities to identify the right patients for their studies. Community practice partners give innovators trusted access to additional qualified patient populations, outside of their traditional clinical trial partners, and efficient enrollment for those patients. They can also help sponsors and clinical researchers save time and resources by finding the right physicians treating the population of interest and broadening access to a targeted patient population. This is particularly important in the absence of a centralized database that links patient disease and symptoms with trial needs. There are many resources available to providers, innovators and patients to identify or self-identify, including patient registries and disease-specific advocacy groups, but providers often do not have the time to scan these resources and match patients.
Additionally, providers need to be armed with information about how the therapy works, the challenges for the patient undergoing the treatment – both symptomatic and holistic, and available scientific data. This will position the manufacturer as a resource for providers and patients and help streamline the often-difficult clinical trial process. If done correctly, innovators can ultimately use relationship building, education, and awareness to create a sustainable referral network with a reliable stream of potential candidates. These best practices also offer innovators the ability to act as an extension of the care team, through the provider, to help monitor patients and keep them enrolled.
Keeping patients on trial
Once recruited, it is critical for innovators to retain patients and ensure compliance. However, many challenges can cause a patient to drop out of a trial. They must navigate challenges, such as location and time, but also complications or adverse events may occur. The patient’s disease state may also progress and cause them to lose eligibility for the trial altogether. Because most cell and gene therapy patient pools – at least initially – are so small, any participation loss is a setback and extremely costly to innovators.
Common reasons for patient dropout include misunderstood expectations, financial constraints, forgetting visits and fear or anxiety. In fact, a recent study found that 38 percent of clinical trial patients who dropped out found the consent forms difficult to understand. In contrast, an analysis of patients in clinical trials found that, of patients who completed the trial, only 10 percent said the trial did not meet their expectations. This demonstrates the need for thorough communication from the manufacturer through to the patient from start to finish, especially since cell and gene therapy trials require several steps and touch points.
Most cell and gene therapies require several steps to, first, harvest the patient’s white blood cells and then prepare their personalized therapy. For example, patients participating in CAR-T trials require at least three individual, coordinated treatments. Clear, precise communications about the activities associated with the trial are crucial to ensure patients continue to participate. This also necessitates significant coordination of care, especially on the product logistics side.
Coordinating with a high-performance logistics partner can ensure that the pick-up of patient materials, delivery to the processing location, and the transport of the patient-specific therapy back to the treatment location are aligned with the patient schedule. This can only happen if every member of the supply chain is in constant, coordinated communication. From collection process to treatment creation to administration, innovators will need to use effective communications to manage expectations of the patient and the institution.
Since patient continuity in trials can also be impacted by lapses in continuity of care independent of the trial, a method to better communicate about patient care can be established with their local providers. For example, if a patient develops an illness independent of their trial, but doesn’t alert the trial team, their participation could be at risk. A patient’s community or primary medical provider can provide interim oversight between visits and retain connection with the patient throughout the course of the trial. These relationships will need to be nuanced, with an understanding of concerns providers, including the risk of losing their patient to a large, academic research center for their regular visits. The existing relationship with a patient’s community provider cannot be overstated, as these providers exist at a critical touchpoint wherein they are able to monitor adverse events, triage patients while not violating the requirements of the study and offer interim guidance to the patient.
Increasingly, patients are also finding online communities beneficial, allowing them to connect with others and share their experiences in the trial. Especially for rare disease patients, a community can help positively influence the patient experience and may encourage others to speak up about confusion or adverse effects. Where possible – and where it will not impact the trial results – sub-communities of trial members can help foster ongoing relationships with patients, advocates and providers resulting in valuable long-term data for the manufacturer. The word-of-mouth information shared on patient community platforms can give a manufacturer line of sight into the entire patient journey.
With new, novel therapies entering the market, there will be new, novel needs for clinical trials. innovators have much more to consider – from recruitment barriers and keeping patients compliant once engaged in the trial. They will need external partners who can support the broad range of strategies that must be implemented to recruit, enroll and retain patients to complete a successful trial and, ultimately, provide the foundation for a successful product.
Susan Weidner is Senior Vice President, IntrinsiQ Specialty Solutions, a part of AmerisourceBergen and a major provider of US oncology data and analytics that helps community oncologists make more informed treatment decisions with patients and helps life sciences companies understand the impact of those decisions. To learn more about cell and gene therapy commercialization strategies, download AmerisourceBergen’s latest white paper, Commercializing Cell and Gene Therapies.
Filed Under: Drug Discovery