Biorasi is a contract research organization (CRO) with a stated focus on accelerating execution. Its strategy includes taking innovative approaches to project management, data intelligence, and on-staff talent, and it specializes in a range of areas, including precision medicine, rare diseases and digital therapeutics.
Outsourcing-Pharma (OSP) recently discussed the field of precision medicine with Wayne Bowden, Biorasi’s vice president of program development, and how trials involving such therapies can best be approached.
OSP: What do we generally mean when we say, “precision medicine,” and how is that field impacting how pharma companies and research partners approach drug development?
WB: When the industry refers to “precision medicine,” it means a targeted, individualized approach to disease prevention, diagnosis, and treatment. This individualized medicine can be directed and differentiated around a patient’s own genetic makeup, lifestyle, or specific reaction to the environmental stimuli around them.
The goal is to improve outcomes for the patient by identifying and implementing therapies that take into consideration everything that makes that patient (and thus their disease) unique from another patient with a similar diagnosis or prognosis.
Precision medicine is still a relatively new and dynamic approach to therapy. Each year, the science gets stronger and the knowledge base gets wider, which then allows these medical approaches to become even more precise. Recently, there has been a renewed emphasis on the patient — with sponsors, manufacturing, and support teams focusing on treatment reaching individuals in need.
OSP: How does patient recruitment and engagement differ for precision medicine projects?
WB: As a CRO, we realize that patient recruitment and engagement is different for precision medicine clinical studies. Precision medicine studies are directed at a specific subpopulation of patients who share some set of criteria which can be identified within the broader pool of patients with a given disease.
This means that the criteria for participating in a clinical trial is very strict, which limits the number of patient subjects available. In this way, precision medicine trials are very similar to rare disease trials, where patient populations are likewise very small and potentially diffuse.
Biorasi uses its background and expertise in running rare disease studies, coupled with the knowledge of precision medicine and innovative approaches to patient enrollment, to proactively respond to recruitment challenges. Communication is paramount in these trials. CROs need to have strong connections to locate and enroll patients in precision studies — that means links to patient registries and advocacy groups for various disease types, reaching out to nonprofit organizations, and communicating with patients directly through outreach and education.
OSP: Similarly, how do study design and protocol optimization differ?
WB: Precision medicines are often so innovative that it is difficult to point to a similar study that may have been run in that patient pool. Perhaps it is a patient pool that has never been targeted by any study before, or even a unique rare disease. This is very different from a traditional pharmaceutical trial where sponsors and other trial stakeholders can often rely on previous trials to inform protocols and design.
In addition, there may be fewer key opinion leaders (KOLs) and clinical experts that understand the disease or how to treat it. This lack of a dependable blueprint derived from previous studies and medical experience is one major difference that must be taken into account when designing a precision medicine program.
Patients, too, lack such a blueprint. Many patients are unaware of their own disease state, particularly in the case of a precision medicine approach, where they may not have been tested for the purposes of subtyping.
In situations like this, many advocacy groups and nonprofits encourage patients with similar diseases to create patient-reported outcome measures (PROMs) — vital tools for informing trial protocols or acting as controls. PROMs are reports obtained from patients suffering from a specific disease that concern the status, condition, and treatment of the disease without the interpretation of a clinician; PROMs give a patient’s view of the disease, track data for determining trial protocols and endpoints, and provide support for medical labeling claims.
Another way to optimize precision medicine study design is through basket trials. Basket trials are clinical trials that focus on targeted treatment for patient groups with diseases that share similar biomarkers or genetic makeup — indications of a specific medical state.
An example of this type of trial could involve how a specific type of intervention affects different cancer types with similar biomarkers or genetic mutations. When applied to precision medicine, basket trials allow for patient groups that are limited in size and scope to participate in trials that would normally exclude them due to the specific presentations of their illness.
Trial sponsors benefit as well by increasing the patient pool size for more comprehensive study results. These types of trials are much more common in a precision medicine program when compared to other programs.
OSP: Could you please share some of the factors impacting logistics, and how sites and sponsors might best mitigate the associated challenges?
WB: Because of the strict criteria involved and the small pool of patients to choose from (based on the disease), precision medicine clinical trials can be greatly affected by logistics. And, in most circumstances, you have a very rare disease and a specific treatment or intervention to address in the trial.
Sample logistical burdens that may come into play include biopsies, genetic testing, and novel assays. These burdens are common in these trials, so identifying labs and central reading facilities can be challenging within a single country, not to mention in global studies.
In these situations, sponsors rely on a CRO with robust operational expertise to handle trial logistics. As mentioned previously, a decentralized strategy can reduce the logistical burden.
For example, is your recruitment pool too small? Remote solutions let you expand your reach on a global scale to enroll larger groups of patients that meet your trial criteria.
Do your patients live in rural or remote areas, far away from clinical sites? Reduce the burden on your patient subjects through telemedicine and mobile devices as well as shipping tests or drugs delivered right to their homes.
Decentralization can also be an important strategy for precision medicine trial design. In a decentralized trial, studies are not bound by the confines of clinical sites. There is a spectrum of options available that can relieve the burdens on patients, sponsors, and other stakeholders during a precision medicine study. These may include online patient portals, which remove the need for immunocompromised and ill patients to visit a clinical site on a regular basis; mobile vans and home nurse visits for completing blood draws and other testing in the patient’s home; and eSourcing solutions for capturing study data through electronic devices and other means.
Decentralization offers a myriad of solutions to keep precision medicine trials moving forward, avoiding future delays.
Additionally, engaging a CRO with international expertise, not just global locations, can help ease the logistical burden as well. CROs that have site relationships around the world and understand the regulatory requirements of different countries can support removing operational obstacles before the start of the trial.
OSP: Do regulatory challenges differ with such research—and if so, how?
WB: The precision medicine industry is evolving quickly, and regulatory agencies, such as the FDA, are doing their best to adapt and keep pace with innovative treatments. In fact, a few years ago, the FDA approved more precision medicines and companion tests compared to any prior year.
However, while guidance documents have been developed, regulatory pathways are not always clear. The understanding and application of real world evidence (RWE) is very helpful in this capacity. RWE accounts for data obtained outside of randomized controlled trials. Coupled with the nuance and innovation of precision medicine, RWE allows for better identification of results during long-term trials, risk mitigation, and post-market follow up — all of which can help to forge more formal pathways.
OSP: Please tell us about the rare disease trial checklist—why you created this informational tool, what it is designed to do, and highlights from the resource.
WB: Biorasi’s rare disease checklist is designed for sponsors, encouraging them to ask themselves tough questions ahead of their upcoming precision medicine clinical trials. It is essentially a to-do list highlighting recruitment, patient centricity, and logistics.
A precision medicine or rare disease trial is rewarding in its success but challenging in its facilitation. This checklist keeps these items at the forefront of the project, even before developing clinical trial protocols.
For sponsors who are unsure of how to proceed, or are missing some of the required core competencies, Biorasi is able to step in to provide guidance and support throughout all stages of a precision medicine trial.
OSP: How is the pandemic impacting work in the realm of precision medicine research and drug development?
WB: The COVID-19 pandemic has had a big effect on clinical trials as a whole: delaying study starts, disrupting funding milestones, and causing the closure or major disruption of operations at clinical sites. The result has been a huge, negative impact on enrollment and treatment milestones.
Surely, research in the precision medicine sphere is feeling the same impact. In these challenging times, though, precision medicine clinical trials could actually be viewed as a blueprint for adapting and continuing clinical trials in the ever-changing coronavirus landscape.
While precision medicine trials are subject to the same COVID-19 obstacles as other trials, their strategies for success have a lot to teach us.
Precision medicine trials rely on a patient-centric approach, utilizing, as appropriate, decentralization to accommodate for their limited demographic, and using remote solutions to target and enroll the right patients for the study on a global scale. This strategy also allows patients that are unable to travel to the clinical site on a regular basis to participate in trials from their own home through telemedicine or mobile device data capture, and with remote monitoring options to track the status of the trial without endangering site staff, these operational solutions can prevent existing and upcoming trial delays caused by closed sites or quarantine protocols.