Ron Jankowski and Kelly Cardello (both Cook Myosite, PA, USA) discuss the challenges involved in the production and trial administration of autologous therapies.
Cell therapy clinical trials, especially autologous trials, are extremely complex undertakings with an abundance of moving parts and ample opportunities for miscommunication or unexpected delays. In order to ensure the success of an autologous cell therapy trial, a tremendous effort must be put forth in overcoming these challenges.
One of the key challenges is setting and managing clear expectations.
One of the key challenges is setting and managing clear expectations. This applies to all parties involved — from the investigators to the research coordinators, and even the study team and vendors. Most importantly, expectations need to align and be clearly set for the study participants who are at the center of it all.
The number one tool to tackle expectation management is communication. The number two tool is risk management. These go hand-in-hand and are fundamental to any clinical trial.
Cell therapy trials, particularly of the autologous nature, inherently come with a host of unique complexities that can manifest in various forms, including:
- added layers of communication and coordination across the duration of the study,
- incorporation of specialized or uncommon procedures,
- scheduling challenges due to the variable manufacturing times of individualized investigational products,
- increased logistics for time-sensitive and temperature-controlled shipments,
- detailed management of perishable critical supplies,
- orchestration of cell collection and the delivery of the investigational product.
Even though many of these may be viewed as expected or routine complexities from the sponsor’s perspective, they present opportunities for risks that can derail the study if not planned for and properly communicated in advance.
Risk management is a systematic process to identify, assess, mitigate, communicate and review these types of risks, which can have varying tolerance levels and potential impacts on the outcome of the study.
There are often hundreds of individuals involved in the execution of a clinical trial and if stakeholders are confused, frustrated or overwhelmed by the complexities, they may become disengaged or lose their enthusiasm for the research. Fortunately, transparency and well-defined communication channels can prevent and combat these risks.
Traditionally, pharmaceutical companies manufacture a sufficient quantity of an investigational product for an entire study before it begins, allowing for a complete separation of manufacturing complications from clinical trial activities. For autologous therapies, the manufacturing activities are sandwiched into the trial itself, meaning that any difficulties experienced during the production, testing and approval processes can cause substantial ripple effects.
This variance from the supply process of typical investigational drugs is an identifiable risk, which warrants extra efforts to set the expectation appropriate for the trial during startup. The Belmont Report  reminds us that respect for subjects requires that they enter into the research voluntarily and with adequate information; if manufacturing complications can lead to delayed treatment or a prolonged duration of participation, this should be disclosed in the informed consent.
Autologous cell therapy trials, by nature, uniquely integrate the clinical sites in the first step, when the subject’s cells are procured, and the last step of the manufacturing process, when the product is administered. Therefore, the clinical sites and physicians must be invested to perform these additional duties and be aligned with the heightened expectations regarding the required level of collection, preservation, storage and transportation of the cellular starting material. This can be mitigated through additional qualifications or specialized procedure training. Such demanding requirements may also necessitate the routine presence of highly-trained field support personnel to help provide assurance of quality, compliance and thoroughness during critical collection and administration procedures due to the low threshold for risk tolerance in these areas.
Engaged and knowledgeable personnel are critical to every clinical study
Engaged and knowledgeable personnel are critical to every clinical study and communication barriers can form when knowledge gaps are present. Because many individuals on the study team or at the clinical sites are responsible for speaking to others about the investigational product, providing supplemental education on the manufacturing processes may be appropriate.
For example, at Cook MyoSite, we have discovered a great benefit from conducting manufacturing facility tours that enable the research coordinators and other key clinical study personnel to see where the product is made and to ask questions. These tours provide a more thorough and personal knowledge of the product by creating a tangible and realistic appreciation for what happens when a study participant’s tissue arrives at our facility. As a result, research coordinators are more confident speaking about the product with the subjects of the study. The tours also align perspectives if difficult, yet anticipated, events occur such as delays in the release of the product.
Finally, it is highly unlikely that a study will be successful without first asking ‘what are the expectations of the study subject at each step of the process?’ and ‘have we properly communicated and aligned those expectations with the realities of manufacturing an individualized cell therapy product?’
Thorough and realistic communication of challenges and study commitments are essential, and the opportunities for misalignment are many. For instance, it is possible that additional cell or tissue procurement procedures may be necessary to produce an acceptable investigational product meeting quality or functional specifications.
Unlike many conventional medicines with more direct pharmacodynamics, a cell therapy mechanism of action may not be expected to produce an immediate benefit and may take days, weeks or months to elicit an intended response. These expectations cannot be assumed and need to be intentionally set and reiterated through clear and timely communication during the lifecycle of the study.
Alignment of expectations is key to the success of any clinical study but becomes even more essential as the complexity increases. For investigational cell therapy studies, the clinical study site personnel and the study subjects are often making a significant time investment and commitment to participate, and it is the sponsor’s responsibility to proactively identify predictable risks and allocate resources accordingly.
There is no substitute for upfront education and continual communication
There is no substitute for upfront education and continual communication as challenges inevitably arise. Exceeding the expectations of everyone involved is essential, not only to ensure continued motivation and active engagement in the study but also to develop ambassadors of the technology moving toward commercialization.
101) Office for Human Research Protection. The Belmont report.
For more information about autologous therapies, please visit the Cook Myosite website >>>
The opinions expressed in this feature are those of Cook Myosite and do not necessarily reflect the views of RegMedNet and Future Science Group.