Everything You Need to Know About Virtual Clinical Trials

The landscape of clinical research is undergoing major changes with virtual clinical trials driving these transformations. These innovative trials promise to revolutionise the way medical research is conducted, making it more accessible, efficient, and patient-centric than ever before. Virtual clinical trials are not just a temporary solution to the challenges posed by global events like the COVID-19 pandemic. They represent a long-term evolution in clinical research, driven by the need for more flexible and inclusive trials with the increase in rare diseases, geographic barriers and understanding real world data. In this article we will cover what virtual trials are, their benefits and their challenges, and what the future might hold.

What are Virtual Trials?

Virtual clinical trials are trials which instead of having participants visit or stay at investigational sites, participants partake in studies remotely by collecting patient data via digital technologies such as wearable devices, mobile health apps, ePRO devices (electronic patient report outcomes like patient diaries) and use virtual patient monitoring techniques like remote SDV (source data verification).

In a traditional clinical trial, 70% of potential participants live more than 2 hours away from the closest trial site. This can lead to patient dropouts and inconveniences subjects with almost 4 hours travel every time they need to visit sites. It also limits the potential of who may enrol on a trial, as they can be easily influenced by the distance they would need to travel to sites.

Virtual trials break down the geographical barriers as participants can join and engage in the trial from the comfort of their own homes, and ensures continuous, real-time data collection, enhancing the accuracy and efficiency of data analysis. This approach not only caters to a broader, more diverse patient population, but also significantly reduces the logistical burdens and costs typically associated with traditional trials. The demand for virtual trials was increased by the COVID-19 pandemic but despite social distancing and isolation restrictions being long gone, drug developers realise the importance of more patient-centric, cost-effective, and adaptable clinical research models which virtual trials bring.

Table: Comparison of Traditional vs. Virtual Clinical Trials

The Benefits of Virtual Clinical Trials

Virtual trials bring many potential benefits compared to traditional clinical trial methods. These advantages not only streamline the research process, but also enhance participant engagement and data quality, marking a significant improvement in clinical research methodologies. 

Let’s explore some of these benefits in more detail:

1) Enhanced Participant Access and Diversity

One of the most significant benefits of virtual clinical trials is the broadening of participant access and diversity. Traditional trials often face challenges in recruitment and retention, limiting their participant pool to specific geographic locations. The challenge has been so prevalent that the FDA published guidance documents on the gap of under representation of minority groups, and states that by adopting a wide range of baseline characteristics it may create a study population that more accurately reflects how the new therapy will perform in the real world where this diversity is reflected if it is approved. On the other hand, virtual trials break down these barriers, enabling a more diverse and representative participant base which supports the consensus from the FDA’s guidance documents to resolve these issues. By having a global reach, patients can be potentially recruited from anywhere, this also helps improves the inclusion of underrepresented groups, for example, patients with mobility issues or living in remote rural locations. 

2) Improved Participant Engagement and Retention

Once the eCRF (electronic Case Report Form) has been created, you need to ensure the data you are capturing is accurate. This ensures the critical information linked to adverse events, concomitant medications and other key elements can be applied accordingly to the end point analysis. Clear quality control steps should be established such as data collection and validation guidelines. These will cover all aspects of how to collect and manage the data, as well as how to manage potential missing data, which should be backed up by robust quality gates to ensure that the methods mentioned are working correctly and in line with the rigorous regulatory requirements.

3) Informed Patients

Patients are more aware of the study conditions through study websites and consent portals and become better educated about the trial through the virtual approach. This supports the patient engagement and provides quick solutions to any queries or concerns patients may have which they can raise virtually as well.

4) Cost Reduction

The decentralized nature of virtual trials can lead to significant cost savings for sponsors and organizers, which is a significant incentive due to the cost of drug development. Recent articles estimate the cost of bringing a new drug to market ranges from $314 million to $2.8 billion, so you can understand the desire to find financial efficiencies. 

By reducing the reliance on physical sites and in-person visits, virtual trials can streamline the research process and reduce overhead costs.

There are cost savings across multiple formats such as:

• Patient Travel: Removing patient’s travel to site and transportation expenses which would always have been reimbursed. In addition missed appointments and potential rescheduled visits which require increase site staffing fees are eliminated as well.
• Site Operations: Site fees and site maintenance costs, and hospitalization/research center service charges are now completely removed from the requirements of the trial. In addition, investigator fees are reduced, and onsite management costs are eradicated. The trials activities are now centrally managed by a remote study coordination center at much lower overall cost to traditional trials.
• Monitoring Visits: The requirements for monitoring is dramatically reduced in virtual trials with the increase in technologies for remote data collection with wearables, mobile health apps and electronic report outcomes (ePRO) devices. With the removal of patients visiting sites, there is less requirements for source data verification (SDV) at investigational sites by clinical research associates as virtual trials take a risked based approach to monitoring. The reduction in traditional monitoring significantly reduces costs as less CRA costs such as travel and accommodation.
• Shorter Enrolment Periods: Virtual trials are able to enrol patients onto trials faster than traditional trials by using digital platforms and social media for recruitment, enrolment is online and these methods result in quicker time to reach the required patient numbers and less costs on traditional patient recruitment.
• Reduced Patient Dropouts: As mentioned, there is improved patient retention due to the ease of participating in the virtual trial. This results in fewer patient dropouts and means the trial can proceed as planned without the additional costs and delays of recruiting new participants to replace those who have left.
• Expedited Data Collection and Accuracy: Due to the real-time collection of data using digital and wearable technologies, the speed between data generation and analysis is dramatically shortened, which reduces the timelines of trials and improved costs. In addition, data is more accurate with inbuilt validation, data cleaning and verification, which removes the costs of time to query, correct and recapture inaccurate or uninterruptable data.

Table: Summary of Cost Reductions

Improved Quality and Efficiency with Real-Time Data Collection

As mentioned, virtual trials utilise digital technologies such as wearable devices and mobile health apps for data collection. This new method enables real-time data collection, which improves the timeliness to analysis, as well as enhances data quality and accuracy. The trial can become more efficient as the time from study initiation to completion is reduced with less human errors and rework being required.

As more data can be collected across longer periods, this will help with the statistical analysis on determining the effectiveness and safety of the IND (Investigational New Drug). Wearable devices reduce the reliance of self-reported data, which in turn can improve data quality with the removal of potential bias or less missing data. In addition, virtual trials are now using real world data, and this enables drug developers to see how the IND may interact with other drugs that participants may take, which perhaps wouldn’t be administered in a traditional on-site randomised trial. 

Challenges of Virtual Clinical Trials

Despite the benefits of virtual trials, they introduce a new set of challenges. Understanding and overcoming these hurdles is essential for researchers, sponsors, and stakeholders if they are to successfully conduct a virtual trial. 

Regulatory Compliance and Ethical Considerations

One of the major challenges is ensuring compliance with diverse regulatory requirements and ethical standards. The global nature of these trials often spans multiple jurisdictions, each with its own regulatory guidelines. 

Regulatory Guidance

You must ensure that the regulatory bodies you are submitting to are aware of all your trial techniques and follow their guidance. Regulatory bodies have been forced to publish new guidance and amending existing guidance to keep up with the emerging technologies available and virtual trial approaches. Make sure you engage with regulatory bodies early in the trial design process to ensure compliance and address any concerns they may have.

Source Data Verification

Questions are often raised, such as how does data get source verified if it is no longer being captured at site by clinicians.

Patient adherence 

How do we know that patients are not falsifying data? Think for examples of wearables being swapped to other individuals or all con meds and adverse events not being reported in ePRO devices.

Informed Consent

Informed consent in a virtual setting is a challenge, as perhaps the depth and risks of the trial have not been fully conveyed and patients can still accept to enrol without fully understanding what they may be getting into, not just from a safety perspective but the trial length and any restrictions.

Indication and Operational Issues 

Depending on the indication and treatment, virtual trial will not always feasible.  For example, participants in an oncology trial may have to go to sites to receive chemotherapy and require scans of their tumours to determining the effectiveness of the treatments. 

Data Privacy and Security

Due to the digital aspect of virtual trials, it raises data privacy and security concerns. Sponsors and CROs (Clinical Research Organisations) must ensure they are protected against any cybersecurity threats, as there is now an increased risk of data breaches and cyberattacks.

The security of devices used by patients is crucial, as they can be vulnerable points of entry for data breaches. Ensuring that the software and apps used for trial data collection are secure and regularly updated to fix any vulnerabilities is crucial. Ensure protocols and regular audits are in place. In addition, it is also important to educate patients on the safe use of these devices, the importance of confidential data, and how to monitor their devices for any security lapses.

It is also vital to comply to all data protection laws such as GDPR in Europe and HIPAA in the United States, also ensuring that all data protection policies are clearly documented and patient consent to the handling of such data is gained in enrolment.

Participant Engagement and Retention

Despite the benefit of improving patient retention and engagement as subjects do not have the burden of having to regularly visit sites, there are potential issues regarding retention and engagement in virtual trials such as: 

• Digital Fatigue: Some participants may become overwhelmed or disinterested if there are too many digital interfaces and requirements over the duration of the study. For example, a constant wearable device could easily become too uncomfortable and a patient could remove the device.
• Lack of Face-Face Interactions: Without human interactions between participants and study staff, fostering a sense of connection and commitment can be challenging. Sponsors and CROs should be mindful of ways to keep patients engaged in this virtual setting and should try to utilise interactive technologies and personalise communication to try to maintain participant engagement.

Technology and Infrastructure

Virtual trials have a heavy reliance on technology throughout the entire study. This presents several challenges such as:

• Interoperability: Ensuring different technologies and platforms can work together seamlessly.
• User-Friendliness: Designing digital tools that are accessible and easy to use for participants of all ages and tech-savviness levels. Training should be given to ensure participants can use the technology required on the study.
• Technology Accessibility: Ensuring all participants have access to the necessary technology and internet connectivity.

Data Management and Integrity

With more real-time data being collected, new technologies to enable more data to be collected, and improved patient compliance in virtual trials, there is the potential to generate vast amounts of data compared to traditional trials. Study data still requires robust data management and data integrity practices. Having a skilled clinical data management team that can handle this increase data and the challenges that virtual trials present to data will be important to the success of the trial. These challenges may look like: 

• Data Collection Errors: Participants may enter in incorrect data values in the devices and digital technologies during the trial.
• Larger Quantities of Data: Handling and managing the larger volumes of data.
• Real-Time Data Collection: Managing and validating the vast amounts of data collected in real-time.
• Standardisation of Data: Ensuring data standardisation across various digital platforms and devices.

Non-Sterile Environments and Real-World Settings

One key challenge of a virtual trial is the potential pitfalls of studies being conducted in a home-based environment. In these real-world settings there are fewer controls on potential drug-drug interactions. For example, subjects may take other con meds if they fall ill and take prescription medicines or over the counter painkillers. There is also the potential of recreational drugs, alcohol and tobacco to been taken and not declared or controlled. A controlled clinical trial environment would be able to govern and monitor any additional con meds and also ensure a trial is conducted in a sterile environment which presents more security, whereas unsterile home environments could lead to more discrepancies and aliments.

The Road Ahead

The future of virtual clinical trials is bright, with ongoing technological advancements and increasing regulatory support paving the way for their expansion.

Key trends to watch include:

• Integration of Real-World Data: Leveraging data from electronic health records and other real-world sources to complement trial data and enhance study outcomes.
• Patient-Centric Designs: Trials designed with input from patients to ensure they meet their needs and preferences, further improving participation and engagement.
• Global Collaboration: Increased collaboration between pharmaceutical companies, technology providers, and regulatory agencies to standardise and optimise virtual trial processes.
• Market Growth: Currently the global virtual clinical trial market was valued at USD 7,025.02 million in 2022 and is expected to grow at a CAGR of 15.5% and reach USD 28,544.08 million by 2032. The growth is driven by the benefits virtual trials bring, the rising drug development in rare diseases and the requirement for diverse patient populations.

Hybrid Trials

One of the key positives for the future of virtual trials is the emergence of the hybrid trial approach. This is where elements from traditional trials are still used and combined with elements from virtual trials. By combining both trial approaches, it addresses some of the operational challenges raised by certain indications. Patients can go to sites for certain elements when required and use remote visits unless in person visits are needed. Virtual trials will require careful planning and designs and sponsors must ensure its clear when a site visit is needed and when certain data can be collected remotely. These trial types act as a great way to modernise all clinical trials and doesn’t limit virtual trial approaches to only specific therapeutic areas.

Conclusion

Virtual clinical trials are not just an alternative to traditional methods; they are a forward-looking solution that addresses the evolving needs of clinical research. By embracing the advantages of virtual trials, the life science industry can unlock new possibilities in the quest to advance human health and develop drugs more efficiently and cost effectively.

As we move forward, the lessons learned from the challenges of virtual clinical trials will undoubtedly contribute to their evolution. Virtual trials offer a pathway to more accessible, efficient, and patient-friendly clinical studies. Traditionally the life science industry is one of the slowest adopters to new technologies due to the high regulations, but virtual trials allow for this bad habit to shift. By utilising new digital technologies, learning from the current challenges, and focusing on patient-centric approaches, virtual trials can significantly accelerate the pace of medical advancements, ultimately leading to better health outcomes for patients worldwide.

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