Medidata: collaboration furthers decentralized trial progress
While decentralized trial technology is rapidly advancing, and adoption of such technology is climbing, many professionals in the field feel a need for standards and consensus. Through a new group within the Association of Clinical Research Organizations (ACRO), leaders in the industry are working toward that goal.
Outsourcing-Pharma (OSP) recently discussed the rapid advancements of decentralized trials and the work of the ACRO Decentralized Trials Working Party with Fiona Maini (FM), global compliance and strategy principal for Medidata.
OSP: Could you share your thoughts on the evolution of decentralized trial technology?
FM: Almost all the components of decentralized clinical trials (DCTs) have been around for some time. Telemedicine, for example, has been around for more than 20 years.
DCTs have been advanced and facilitated by the fundamental availability of technology developments such as the internet, smartphones and mobile technology. Through advances in these technologies, patients have become more aware of the world around them.
There are a lot of different ways to share information. News and social media platforms, accessible and sharing content 24 hours a day, are methods of getting information back and forth.
Patients are interacting with social media platforms and sharing information amongst themselves as well as with their researchers and others. Patients are more informed about their specific disease or treatment type and are also more willing to share information. Patients now have better access to information about upcoming clinical trials and are better informed prior to joining a clinical trial.
Pfizer’s REMOTE trial in 2011 was a study of overactive bladder disease and was the first ever 100% decentralized fully randomized clinical trial under an investigational new drug (IND) application. The study used secure patient consent online using video/multimedia and online testing.
Study investigators shipped all blinded study medication to patients at home rather than dispensing it at a clinic visit. Researchers managed study conduct remotely. This trial was fundamental in establishing a foundation for these types of technologies and a pioneering trial towards virtualizing clinical trials.
OSP: How were industry attitudes toward and acceptance of using decentralized trial technology changing in the months and years before COVID-19 hit?
FM: Certain parts of an end-to-end trial are already partly virtualized. For example, the use of electronic clinical outcome assessment (eCOA), which is electronically captured data to evaluate patient safety and quality of life, has been around for many years. Hybrid trials, where elements of a trial are decentralized, are more common than a fully decentralized model.
The slow adoption (pre-pandemic) is due to multiple factors. There has been a perceived lack of end-to-end regulatory guidance and a hesitation and risk averse attitude in changing to a slightly different model. Adopting a new model also requires investment - as clinical trial timelines are typically tight, moving to a DCT model would take upfront investment which may not be realized immediately but in the longer term.
OSP: Then, how has the research industry looked at decentralized differently since the pandemic hit?
FM: Since the pandemic, DCTs are seen as an opportunity and a mechanism to continue clinical research, even when movement and travel is restricted. Many clinical trials were halted or delayed due to the pandemic, and patients and sites were significantly impacted. COVID-19 has created a sense of urgency to adopt new models and approaches and has acted as a catalyst in the acceleration to adopt decentralized clinical trial models.
OSP: Please talk about some of the challenges and benefits of decentralized, compared to hybrid, and then conventional trial models.
FM:Some of the benefits which can be realized by using a decentralized clinical trial (DCT) model include: faster trial participant recruitment; improved trial participant retention; decreased patient burden; greater control and comfort for participants; and increased participant diversity due to the ability to reach a broader population. The opportunity for home administration and direct to patient supply also means improved data quality, patient experience and clinical trial continuity.
The challenges of adoption are largely related to perceived concerns and risks, including: perceived regulatory barriers to the use of a different model; data protection and data privacy concerns; increasing site burden by use of multiple systems and variety of different logins; and often a lack of knowledge and insight into DCT processes and technologies. Additionally, patients and trial participants may actually prefer a more traditional approach without technology.
OSP: How have regulatory bodies like the FDA and EMA helped companies put decentralized and hybrid trials in place?
FM: Given this unprecedented and humanitarian situation, regulators have developed and published urgent guidance on the management of clinical trials during this COVID-19 pandemic. This guidance has focused on the continuation of current clinical trials (or postponement or cancellation), the initiation of new trials, and the acceleration of COVID-19 trials and general support for vaccine development.
Outside of the pandemic, patients with cancer and other life-threatening diseases and adults and children with rare diseases still need life-saving therapies and cures. And often these are time-sensitive conditions, so research into these areas need to be continued.
The guidances are pragmatic and flexible. The COVID-19 guidance from the regulators emphasizes the safety of trial participants, maintaining compliance with good clinical practice (GCP) and minimizing risks to trial integrity. In this situation, the safety of the site staff and others working operationally on clinical trials is also paramount.
There is a shift to a different mode of operating with more remote and virtual elements, like virtual visits and interactions, remote and centralized monitoring, and investigational medicinal products being shipped direct to a trial participants home. The concepts are not new and the technologies already exist to support these scenarios, but the broader adoption is something we’re seeing now.
OSP: Please tell us about the ACRO DCT Working Party. How did it get started?
FM: Members of the Association of Clinical Research Organizations (ACRO) had been presenting on DCTs at the SCRS EU Summit in 2018, and the comments from the audience had overwhelmingly been around what was holding up the industry to DCT adoption when DCTs had been around for many years already. We discussed within the ACRO membership group how we could create an initiative in the EU to engage with authorities to progress discussion and guidance on DCTs.
In October 2019, ACRO established the Decentralized Clinical Trials Working Party (ACRO DCT WP) - composed of ACRO member experts on DCTs - to examine barriers to adoption of DCTs and to study the benefits to clinical trial participants and gains in efficiency.
OSP: Who are the players?
FM: The Association of Clinical Research Organizations (ACRO) represents the world’s leading, global clinical research and technology organizations, which provide specialized services that are integral to the development of drugs, biologics and medical devices. ACRO and its members advocate on a global basis for safe, ethical, high-quality medical research so patients can benefit from the development of new treatments and therapies. ACRO members are dedicated to helping bring efficiency, innovation and value to the clinical research process.
Medidata chairs the ACRO DCT Working Party.
OSP: What has the organization accomplished so far?
FM: The Working Party quickly came to consensus on a broad range of DCT topics. Firstly, there was a clear need to address stakeholder hesitation regarding modernization and change - and how the creation of end-to-end best practices could help mitigate this hesitation.
Secondly, there was a need to identify and help resolve change-management burdens on stakeholders - for example, initial site burden and initial investment in a new clinical trial model. The ACRO DCT WP developed a work plan that included two primary objectives and deliverables - a customized map for DCTs and a toolkit dedicated to DCTs.
A Customized Map for Decentralized Clinical Trials: The Working Party comprehensively examined a “map” of each step of a clinical trial from beginning to end. This examination of every step in the clinical trial process enabled the Working Party to identify the areas in a trial that could be decentralized, and move away from the conventional, or traditional, trial model.
A Toolkit Dedicated to Decentralized Clinical Trials: The Working Party then began its work on two important new tools dedicated to decentralized clinical trials - a new quality-by-design framework dedicated to DCTs, providing stakeholders with much-needed quality-based, beginning-to-end guiding principles for the construction of DCTs, and a risk assessment tool, providing questions, considerations and potential mitigations to facilitate a quality-by-design and risk management approach to decentralized trial design.
OSP: What are your goals for the short- and long-term future?
FM: We are continuing discussions with UK authorities and also engaging with other EU authorities and authorities outside the EU. We are developing an ACRO DCT landscape survey to define the usage for DCT components which is planned to run on an annual basis. This should provide an indication of adoption. We are also creating an abridged, shortened version of the quality-by-design manual for use in training on DCTs and to help support the update of procedures.
