Clinical Researcher—April 2023 (Volume 37, Issue 2)

RULES & REGULATIONS

Neta Bendelac

 

Traditionally clinical trials have been conducted at specific clinical trial sites, to which patients had to travel. However, over the last three years, the demand for decentralized clinical trials (DCTs) has spiked, and a consensus has emerged that DCTs will become permanent fixtures. The aim of DCTs is to make it easier for patients to participate in clinical trials by reducing the need to travel to central trial sites. This approach has the potential to make clinical trials available to a wider demographic of participants and reduce drop-out rates.

While decentralization might increase the accessibility of clinical trials to participants, regulatory bodies, including the European Medicines Agency (EMA), have recently published recommendations that aim to facilitate the conduct of DCTs while safeguarding the rights and well-being of participants, as well as the robustness and reliability of the data collected.

Challenges and Considerations

One unique challenge to DCTs is managing investigational medicinal product (IMP) integrity. The EMA suggests that when sending IMPs to a participant’s home, it is essential for logistics providers and vendors to have a contract in place outlining how the product is handled and shipped. This is an area in which the industry should strive to achieve better visibility and drug integrity. Additionally, while not considered a requirement, through digital solutions such as barcodes, logistics providers can verify that IMPs are dispensed at the appropriate time, ensuring that the correct product is used in the study and that the integrity of the product is maintained.

The EMA has also recommended that sponsors further consider the storage and administration of IMPs at the participant’s home when designing a DCT. Patients should have sufficient measures at home to ensure the IMP’s inclusion and exclusion criteria are adequately met. For example, appropriate storage conditions should consider temperature controls and unexpected light exposure. To maintain the safety and efficacy of a product, digital sensors can be used to monitor environmental indicators such as temperature, humidity, vibration, and light. If a patient does not have proper conditions to store a product, then local pharmacies can be utilized as an alternative to shipping the IMP directly to the patient’s home. In that case, the pharmacists should be trained to dispense the IMP using the correct protocol.

DCTs should also require drug-centric procedures that consider recall actions in case a return is necessary. If a drug is unexpectedly compromised, it is essential to have a plan for how IMPs will be collected. Real-time tracking can report precisely where IMPs are located until the product is delivered. Recording data is just one consideration to take into account when designing a study that involves proper recall procedures when administrating an IMP at a patient’s home.

With this in mind, it is also essential to inform patients participating in the trial that third-party vendors will use their data to correctly and safely send an IMP to their homes. This information should be explicitly stated in the consent process, and participants should be made aware of their rights and any potential risks associated with using their data in this way.

The EMA further recommends that healthcare professionals still be involved in preparing and administering an IMP, even in a decentralized setting. When a participant self-administers an IMP, there should be step-by-step instructions to ensure the correct and safe use of the product. In addition, electronic instructions via accessible methods, such as QR codes, should be considered.

A New Mandate

In the United States, regulations such as those included in the recently passed Public Law 117-328 (otherwise known as the 2023 omnibus appropriations bill) have recently gone one step further, no longer recommending certain procedures, but mandating clinical trials create diversity action plans. The outbreak of the pandemic accelerated the implementation of digital technology, resulting in a significant increase in the use of digital solutions including mobile health tools and tele-healthcare in clinical trials (e.g., video consultations), health data analytics (e.g., data processing systems that support bioinformatics modelling), and digital record systems.

Once stakeholders are confident that technologies are adequately validated, selection based on scientific and ethical considerations can be presented to regulators in accordance with applicable legal and regulatory frameworks. The possibilities are virtually limitless, and in the context of trial participation and access to medicine, technologies could assist in:

• Reducing assessment times and hence increasing patient compliance
• Improving access to individuals with rare diseases in remote settings
• Making reasonable adjustments to allow equal access for individuals with disabilities
• Enabling patient engagement from marginalized groups with a preference for remote access

Conclusion

It is critical for sponsors to work closely with regulators to ensure DCTs are conducted safely and in compliance with all regulatory expectations. In the coming years, recommendations such as those posed in this article by EMA will further allow DCTs to advance, teaching sponsors lessons and revealing the full benefits of this novel approach. Stabilizing guidelines and encouraging the use of digital tools will drive continued adoption and innovation.

Neta Bendelac is Senior Director of Strategy for 4G Clinical, based in Wellesley, Mass.