A Strategic Approach to Mitigating Risks While Advancing Clinical Trial Methods

When it comes to decentralized clinical trials (DCTs), the pharmaceutical industry finds itself at a crossroads.

The global health crisis marked a tipping point where DCTs transitioned from being seen as cutting-edge innovation to more business-as-usual across many areas of research. When McKinsey surveyed its Clinical Operations Roundtable in December of 2020, 100% of participants said virtual trials will be a major component of their portfolios in the coming years. Meanwhile, 89% expect to run a trial with most activities conducted in participants’ homes.

Pharmaceutical industry leaders have broadly acknowledged that traditional clinical trials are costly, slow, reactive, and burdensome for patients. Yet many of those same stakeholders still view DCT solutions with skepticism, believing virtual and hybrid trial models to be insufficiently tested and unproven—akin to the “Wild West” of clinical research.

This raises the question of how to help justifiably risk-averse pharmaceutical sponsors to more readily embrace DCTs. The answer, in a word, is hybrid. Hybrid trials combine certain digital modalities with other site-based components, offering a way for cautious sponsors to benefit from DCT advantages while mitigating the risks inherent in going fully virtual.

In this eBook, you’ll learn how the strategic adoption of a hybrid model can improve your clinical research operations, by:

·      Optimizing study design

·      Enhancing patient safety

·      Improving participant engagement and retention

·      Accelerating study milestones

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Optimizing Hybrid Study Design

Determining which decentralized elements to include at the study design stage helps sponsors to maximize quality, compliance, and outcomes throughout the trial. In this phase, you can leverage the flexibility of a hybrid model, selecting tools and methods that are likely to generate effective outcomes for your specific study.

A modular study platform lets your team incorporate the most relevant components of a DCT based on the therapeutic area, patient population, and study goals. With this a la carte approach, you can choose from decentralized and/or traditional methods across functions and phases:

A Selective Approach

McKinsey analysts note that although fully decentralized trials are ideal for a narrow range of use cases, the prospects for hybrid trials are abundant: “While most clinical trials are not likely to be entirely virtual, they will use one or more decentralization elements based on suitability for their endpoints, patient populations, and treatments.”

Plan B consultants underscore this argument, writing: “DCTs are part of a flexible continuum where it is possible to start with a minimum investment (e.g., eConsent only) and build to a full-fledged virtual trial where all components of a DCT technology platform are utilized (e.g., eConsent, ePRO/eCOA, telehealth, and wearables) to gain maximum efficiencies.”

A selective strategy for decentralization can be more feasible and cost effective for sponsors in the early stages of hybrid trial adoption. This incremental approach allows your team to validate the efficacy of various technologies and methodologies for your therapeutic areas and treatment indications before adopting them on a wider scale.

The Interoperability Imperative

You may wonder whether blending decentralized and traditional methods could compromise a study’s data quality. Hybrid models expand flexibility in many ways, but data integrity and reliability are nonnegotiable. Successful decentralized, site-based, and hybrid trials all depend on good data.

This is exactly why platforms designed for interoperability are critical in a hybrid trial. Your platform should be flexible enough to integrate with a range of virtual and traditional site-based tools, so your team can:

·      Preserve data integrity across multiple media and formats (e.g., validated questionnaires that must look identical on all mobile devices)

·      Ensure smooth workflows and prevent duplicated processes

·      Support participants and study teams through user-friendly interfaces

·      Provide maximum flexibility for study teams

·      Facilitate tracking and decision-making for sponsors

Enhancing Patient Safety

You might worry that a hybrid model hampers the ability to detect and address any safety issues in a trial. In fact, the opposite is true in a well-designed hybrid study, where real-time data collection and patient monitoring allow for early detection of adverse events.

In a site-based study, patients may save their concerns for their next scheduled appointment. With the delay, their memories of symptoms become subject to change, and patients may even forget or downplay their symptoms.

Virtual sites allow participants to report symptoms in real time—on their own, or via the devices and instruments they’re using for the study. Hybrid trial sponsors can configure the study platform to flag potentially adverse outcomes long before these results would appear in a traditional trial.

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Improving Participant Engagement and Retention

In a hybrid trial, technology and human interface ensure the patient is always front and center. On the technology side, event-based notifications can remind both patients and study teams that there is a task to be completed or tracked. Preprogrammed alerts for whenever a task is not completed, or when a data point falls outside the norm, ensure that issues are followed up and addressed in near real time.

The steady stream of inputs also creates a continuous feedback loop to sponsors and contract research organizations (CROs) so they can tackle problems with enrollment, compliance, and retention sooner rather than later, tweaking or refining protocols while the trials are still in progress. For example, if participants consistently struggle to complete a certain study task, your team can simplify that step, clarify the instructions, or offer support such as event-based reminders. The ability to rapidly spot and address protocol deviations directly improves adherence and safety.

On the human side, having access to virtual, visiting, and/or site-based staff for assessments and any follow-up ensures that patients feel safe, supported, and engaged. Hybrid trials improve compliance and retention by bringing studies to patients in the ways that are most convenient and reassuring to them.

Research from European patient organization JamesLind Care shows that patients embrace decentralized trials: 57% prefer participating mostly from home with only a few site visits. Meanwhile, 19% prefer a virtual trial design, participating entirely from home. Fewer than one in eight prefer a classical clinical trial model.

An effective hybrid trial balances high-tech and high-touch methods that align with the drug’s safety profile. For example, teams can:

·      Enroll and oversee patients at a remote “meta” site, with a virtual site team to complement site-based coordinators

·      Allow patients to participate and report from the comfort of their homes

·      Incorporate any complex assessments, blood draws, or other medical interventions in the most convenient and proximate way

·      Eliminate unnecessary site visits by offering a range of options, such as telehealth, in-home nurse visits, and/or clinic visits

·      Give participants more avenues for rapidly reporting symptoms, including potential adverse outcomes

·      Provide ongoing support from a readily accessible virtual study team, closing the gap between participants and researchers

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Prioritizing Patient Centricity

Virtual study participation addresses the traditional barriers—such as lack of transportation, inadequate childcare, and schedule conflicts—that lead to patient dropout. Alleviating the participant burden ultimately expands access for underrepresented patients.

For too long, individuals in disadvantaged communities—which have been disproportionately affected by the COVID-19 pandemic—have been largely underrepresented in clinical trials,” Craig Lipset, a DCT pioneer who co-chairs the Decentralized Trials & Research Alliance, wrote in a co-authored STAT article. “Decentralized research that leverages available technologies can help recruit a more broadly representative patient population by gender, ethnicity, geography, income, and more.

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Driving Digital Collaboration

A virtual hub facilitates unification of standard operating procedures, protocols, and patient training materials. This alignment creates a single source of truth and sets expectations for participants and staff, a proven solution to increase compliance and retention.

Digital collaboration requires careful training and coordination among sites. When team members understand their respective workflows, they can communicate in ways that prioritize patient centricity.

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Accelerating Study Milestones

Hybrid trials allow study teams to work more efficiently while maintaining the same standards of quality. Technology extends your team’s capacity by streamlining repetitive processes and automating manual tasks. Hybrid trials can help teams move more quickly on several fronts:

·      Recruitment: Patient recruitment is the single biggest cause of clinical trial delays. Digital recruitment eliminates geographic boundaries, so you can target a broader pool of patients, reach people where they are, and complete enrollment faster. An article in Dermatology noted that, in an AOBiome virtual trial, “online recruitment was relatively fast … and the trial was cheaper to administer than a traditional trial.”

·      Patient adherence: Reduced drop-out rates and higher compliance help your team complete studies on time and on budget. Both technology and team play a role in boosting patient engagement. Virtual and site-based teams must collaborate closely and have clear and distinct roles for hybrid trials to ensure that patients don’t get confused during the trial. Here again, technology can drive collaboration among distributed teams, as a urogynecology study led by ObvioHealth recently showed.

“The platform would alert us whenever an issue arose,” says Matty Culbreth-Notaro, ObvioHealth’s Chief Operating Officer. “A joint team consisting of representatives from the virtual site, the traditional sites, and the sponsor would huddle for 15 minutes each morning to review and troubleshoot any issues with device use. The virtual site team would then follow up with patients.”

·      Data capture and analysis: Hybrid trials can capture and assess vitals and unstructured data from a range of devices, allowing you to harness richer insights and course correct as needed. Preprogramming and automatic data checks also allow you to decrease the time required to reach data lock.

·     Study monitoring: Costly CRO rescues can derail a trial, especially when you find out too late that a study hasn’t progressed as expected. With a hybrid trial, live dashboards enable you to see the study’s status in realtime. You can check whether milestones are on track, make informed decisions, and intervene quickly if issues arise.

The Need for Regulatory Expertise

Of course, technology complements—but doesn’t replace—industry expertise and relationships. Prospective CRO partners for hybrid trials should have deep familiarity with regulatory environments in the relevant countries and therapeutic areas. Early collaboration with regulators facilitates approvals, regardless of which technologies your team uses.

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Bringing It All Together

Hybrid decentralized models offer pharmaceutical sponsors a gradual way to incorporate digital clinical trial capabilities that can improve their outcomes. While conservatism has recently prevented some from embracing this model, sponsors are increasingly rejecting the “all or nothing” mindset in favor of an incremental approach to innovation—even in the most rigorous niches of scientific research.

Selectively adopting DCT principles gives your organization a competitive advantage for recruitment, compliance, and retention, while helping you maintain strict standards for quality and safety. With an experienced CRO partner and the willingness to tailor hybrid methods to your team’s unique needs, a hybrid trial is the low-risk, high-reward way to run your next trial.

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