Managing Transitions: Lessons From ERCOT

Interruptions to trial timelines are occurring with increasing frequency as sponsors and investigator sites feel the effects of the COVID-19 outbreak. Both pharmaceutical companies and clinical research organizations are searching for ways to mitigate the disruption caused by travel restrictions and self-isolation. It is increasingly likely that they will incorporate remote ways of working to enable some elements of the trial life cycle to be performed without the need for patient visits.

This hastened transition away from the traditional site-based model is expected to drive immediate and accelerated adoption of telehealth technologies, eConsent platforms and remote site monitoring solutions. The implication for eClinical providers is that they must be prepared for rapid growth, suitably equipped with the commercial teams and innovative product portfolios required to capitalize on evolving customer needs and competitive dynamics.

Short-term challenges caused by COVID-19

As the number of COVID-19 confirmed patients continues to rise, industries around the world are trying to navigate the uncertainty that inevitably accompanies a global pandemic of such magnitude. Within the life sciences sector, the impact of the pandemic runs far deeper than the immediate increase in demand for pharmacological countermeasures and diagnostic tests. As containment measures imposed upon pharmaceutical companies and research institutions take hold, a number of challenges to clinical research are becoming increasingly apparent.

New and ongoing clinical trial operations are being disrupted

The Biotechnology Innovation Organization, a biotech industry trade group, is currently collating data from member companies. Early insights point to the ongoing crisis translating into two distinct and significant challenges for clinical trial management: difficulty recruiting for new trials due to patient hesitancy and increasing social restrictions, and delayed or missing data collection from active trials due to hospital sites becoming inundated with COVID-19 cases.

In addition to this, research facilities themselves are beginning to take decisive action as the outbreak spreads. Penn Medicine released guidance advising that non-essential in-person clinical research appointments and procedures should be canceled and new trials utilizing Penn facilities should not be initiated. Columbia University has paused all study procedures involving in-person contact or travel for research purposes within the Greater New York area. As a host of other institutions emulate these precautions, disruption to clinical trials is becoming more of a certainty than a possibility.

Trial disruptions are leading to trial delays that risk funding milestones for biotechs

With the attention of the healthcare and pharmaceutical industries turning toward combating the virus and alleviating the burden of healthcare systems worldwide, biotech companies are beginning to feel the spillover effects on their R&D operations.

On March 16, New Jersey-based Provention Bio became one of the first to disclose a delay to one of its key clinical trials, citing the global pandemic as the reason it paused enrollment into a Phase III study of a drug in development for type 1 diabetes. Investors and analysts are shifting to more pessimistic outlooks as similar announcements from around the world occur with increasing frequency. U.K. biotech investor Syncona expects delays of at least three months to a number of clinical-stage programs being conducted by its portfolio companies, and Eli Lilly became the first large pharmaceutical company to formally announce disruption to its R&D programs, with plans to halt new study starts and enrollment for most ongoing studies and to consider continued dosing for ongoing studies on a case-by-case basis.

Small-scale biotechs often rely on novel endpoint data and tangible study progress to maintain investor confidence and access further funding, and many are likely to be subjected to increasing financial pressures as key milestones and funding opportunities are missed.

Short-term implications from COVID-19

While delays and postponements as a result of the pandemic are likely, it’s important to note that the actions taken by trial sites and sponsors typically come with a crucial caveat: that the continuation of trials that are of significant benefit to patients’ health should continue if at all possible. Along with the inherent aspiration of sponsors to continue trials in order to ensure progression of pipeline products and subsequent financial security, the pandemic could act as a catalyst to drive the adoption of novel technologies and ways of working across the trial landscape.

Appreciating the need for flexibility, both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have acknowledged that COVID-19 is likely to result in more protocol deviations than normal. Most trial protocol modifications now being considered involve conducting some elements of the clinical trial life cycle remotely to facilitate continuation.

Regulators are advocating for greater use of technology

A number of regulatory authorities have released formal guidance outlining the obstacles a trial might now face. The FDA guidance, released on March 18, emphasizes that participant safety is paramount and that sponsors should consider the fact that participants may no longer be able to attend study sites or access the investigational product due to travel restrictions. The EMA reiterated this sentiment days later, highlighting the fact that self-isolation of both participants and investigators is likely to introduce difficulties in maintaining medical oversight. This lack of qualified support is compounded by the reallocation of resources away from clinical trials to combat the spread of the virus, restrictions on site visits for sponsors and a growing strain on pharmaceutical supply chains globally. Ultimately, unless sponsors prove capable of adapting to the situation, it will become increasingly challenging to ensure continuity of their research operations and avoid protocol deviations as policies around trials continue to evolve at a rapid pace.

Sponsors are accelerating adoption of technology to mitigate disruption

Of the various processes within a trial, three particular patient contact points have been highlighted by the FDA and EMA as possible targets for replacement by virtual equivalents:

1. Patient consultation

Sponsors are being encouraged to evaluate alternative methods for safety assessments and consultations, given that trial participants may be unable to attend a protocol-specified visit. Providing they do not include a practical procedure or the administration of a drug requiring a healthcare professional, many of these visits are likely candidates to be substituted for a virtual consultation. The recent release of a white paper by Science 37, a provider of multiple remote trial solutions, on navigating the COVID-19 era through virtual trials might provide an indication that telehealth providers are already anticipating this transition.

2. Patient consent

Gaining and correctly documenting participant consent is a key step in any clinical trial, and participants are typically required to attend a trial site to provide an ink-on-paper signature. In addition to the challenge of circumventing this visit for new enrollments, there may now also be a need to reconsent participants in ongoing trials due to changes to trial conduct.

Technology-enabled solutions for obtaining such information remotely already exist, and sponsors are likely to integrate this capability into their standard operating procedures as swiftly as possible. Recognizing this need, ClinOne has already offered its eClinical platform, which contains an eConsent module, free of charge to all trials researching a vaccine for COVID-19.

3. Site monitoring

Sponsors are responsible for monitoring and quality assurance of the various investigator sites where a trial is being conducted. The inescapable fact that on-site monitoring becomes increasingly difficult under containment measures means that sponsors will be obliged to seek alternative mechanisms to maintain oversight of their clinical operations.

Evidence that the market is already transitioning to remote monitoring of study conduct, data quality and compliance can be found in the recent surge in demand reported by Cluepoints. The company’s central monitoring platform is capable of web- and phone-based site follow-ups when potential risks are detected, with the company’s chief commercial officer commenting that the current crisis is forcing a rapid move toward central monitoring.

Once sponsors better understand the options available for running clinical trials, other than simply delaying or postponing them, it’s likely that a new, streamlined model focused on minimizing patient contact will emerge. Built around sophisticated virtual trial platforms enabling the centralization of processes, trials will increasingly rely on remote capabilities. The participant’s home will gradually replace the clinical site, with physician visits and endpoint data collection being conducted virtually by leveraging telemedicine software, electronic clinical outcome assessments (eCOAs) and smart devices such as wearables. At-home nurse visits may be utilized to perform physical examinations or monitor vital signs in an effort to mitigate travel to hospital sites overwhelmed by COVID-19 patients. Study drugs and materials could be shipped directly to the participant’s home rather than having them picked up at the trial site or pharmacy.

Fundamentally, this new model will evolve as a direct consequence of the current outbreak and the urgent need to eliminate patient touch points wherever possible (although it will have more limited application for trials where a hospital visit is necessary, e.g., for many cancer protocols).

Long-term implications for technology adoption

The clinical trials market is already shifting toward digital ways of working, and the COVID-19 outbreak is likely to both accelerate this trend and drive long-term changes to historically accepted trial management norms. If virtual and remote working prove to be sustainable methods of conducting a trial, it is unlikely early adopters will revert back to the more laborious and time-consuming methods involved in the current, high-contact model. Consequently, sponsors will require comprehensive trial platforms that address their changing unmet needs and evolve their expectations of what eClinical businesses can provide.

Full virtual trial technology bundles will emerge as adoption accelerates; providers will need to develop their portfolios

Providers of eClinical solutions need to mature their product portfolios, catering to the specific needs of the modern clinical trial and identifying suitable adjacent product categories. Developing platforms and bundles that include eCOAs, eConsent, telehealth services, live centralized data monitoring, virtual site visits and live patient notifications will be paramount. Successful companies in this space will be able to support sponsors as they implement the new distributed configuration of a clinical trial, offering products that connect multiple trial sites and enable novel ways of reaching both physicians and patients.

Scalability is essential, and the level and ease of integration between products in the portfolio is likely to be a critical factor for those looking to capitalize on a fast-growing market. Operationally, those providing tech-enabled services (as opposed to tech-only solutions) need to reflect on how to expand their human capital to maintain service standards for an expanding customer base. Establishing appropriate and capable commercial teams is vital to capturing the momentum, as is deploying those teams effectively as eClinical businesses pursue their long-term strategies. It appears likely that the customer landscape will shift as a result of the economic uncertainty reverberating through the industry, and commercial road maps should be assembled with particular consideration for the emerging needs of capital-rich pharmaceutical and biotech companies.

Pharma technology ecosystems will become more sophisticated as virtual trial adoption grows

Widespread adoption of the digital infrastructure needed to provide remote services not only serves current market needs, it also equips eClinical providers to take a significant step toward the next generation of capabilities. Participant mobile devices and wearables will become increasingly commonplace instruments for continuous data monitoring, providing holistic, real-time insights into participants’ health status and a deeper understanding of an individual participant’s response to treatment.

As eClinical businesses become adept at remote data collection, they will require effective ways to integrate the vast amounts of available data into their systems. Blockchain technology provides a secure and decentralized ledger to ensure a high level of regulatory compliance when sharing and storing this type of sensitive information, while the application of artificial intelligence algorithms for data analysis has the potential to transform trial processes and efficiency.

Ultimately, the pressing need to adapt clinical trials as a result of the COVID-19 outbreak may stimulate the market to create the digital infrastructure that will define drug approval processes for years to come.