Risk Mitigation in Direct-to-Patient Clinical Trials

04 May 2021

Nicole Gray / FierceBiotech

The COVID-19 pandemic has made society very aware of the need to be flexible in the approach to daily life. Every part of “normal” day-to-day life has been disrupted. Clinical trials and the traditional way of conducting them has been no different. Flexibility became an immediate need for sponsors, CROs, clinical sites, and patients. Quick adjustments had to be made, along with finding new ways to make sure that patients had the appropriate care, oversight of the clinical sites continued to be managed, and drug supply and accountability were maintained. Many clinical sites found themselves acting as a shipping department, trying to make sure all of their patients received their drug safely and on time. CRAs performed remote oversight visits, virtual site tours, and virtual accountability audits. Sponsors quickly began to rethink their Direct-to-Patient (DTP) approach as patients increasingly requested that their study drugs be shipped to their homes.

Use and acceptance of DTP may have grown faster due to the pandemic, but the overall trend toward the decentralized clinical trial (DCT)/DTP model was on the rise pre-2020 and is projected to grow significantly over the next few years. As more and more DCTs come on board, it is important to remember that clear roles and responsibilities and experienced management are vital to success. Sponsors that can add flexibility into their protocol designs, standard operating procedures and quality oversight process will be able to effectively benefit from utilizing the DTP model. The DTP model can help mitigate risks in patient enrollment (including diversity), patient retention, and adherence to overall study timelines and budget. A well-planned DTP study can be beneficial to patients and sponsors, but this model can prove to be more complex to get started than the traditional model. An efficient approach requires rethinking Standard Operating Procedures (SOPs) and just about every other aspect of how trials have been traditionally managed, including the protocol design and dosing windows. Forming a diverse team knowledgeable in all aspects of the study oversight and supply chain prior to finalizing the protocol should be considered.

How to Mitigate Risk in DTP Studies

The decentralized model, as well as the traditional site-based model with a DTP component, can open up sponsors to new risks in addition to those found in the conventional model. Some concerns that are fairly straightforward to resolve in conventional studies can cause problems for unprepared sponsors of trials with a DTP component. By identifying the risks associated with a study upfront, sponsors can mitigate these risks and position themselves to better realize the benefits of DTP supply for their clinical trial operations and patients alike.

Successful studies start with a clear understanding of the goals tied to the use of DTP and knowledge of regional requirements and possible constraints. There is considerable country-to-country variation in DTP regulations, making it critical to work with local experts to understand what is and is not possible in a particular region, as well as how to approach key tasks such as consent and clinical label content. A different plan is strongly recommended for each country; there is no “one size fits all” approach to deploying DTP globally. Individual country plans allow for easier adjustment on a country-by-country basis if necessary, without having to disrupt or delay the entire study.

There are some elements, however, that are the cornerstones of all DTP deployments. If using a CRO, selecting one with a solid track record of running decentralized studies is important. Equally important is having a strong clinical supply partner with DTP experience, as is a flexible Interactive Response Technology (IRT) capable of managing the unique requirements of DTP, especially in a hybrid model consisting of site-to-patient shipments, direct-to-patient shipments from a depot, and clinical site dispensing visits.

All parties need to communicate well and have a clear view of their roles and responsibilities. Failing to confirm all the details, no matter how minor they may seem at first glance, and otherwise prepare for the study upfront can lead to the persistence of assumptions and other issues that can result in surprise costs and delays down the line.

Specific points that teams need to consider include handling of patient information, how to prevent the study drug from being given to someone other than the participant, temperature storage/distribution requirements, returns/accountability, and home health care involvement. Vendors with access to patient information should be audited to ensure they are following all local privacy laws and that only those who “need to know” the patient information to carry out a specific task have access. Couriers can be instructed to only deliver to the named patient or authorized representative to mitigate some of the risk, including the safety problems it could create if the drug were delivered to a minor, for example. The handling of returns and CRA oversight of accountability will require a different approach — a virtual audit of documents and reports may be required if the clinical site is not storing the drug. Involving home health care can also help mitigate some risk: they can ensure that the patient is taking the drug appropriately, and they can also assist with packing up returns and completing reconciliation paperwork. 

Virtual “visits” on the day of drug delivery, coupled with quizzes and task reminders in a mobile app can help mitigate the risk of a patient receiving and taking the incorrect drug, as well as ensuring a full understanding of how and when to take their drug.

How DTP Studies Mitigate Operational Risks

Conventional clinical trials carry their own risks. The COVID-19 pandemic exposed some of the risks of the site-based model, but it is far from the first event to disrupt the ability for patients to receive study drug on time.

Risk mitigation is possible when DTP is used as an enabling component in the decentralization of clinical trials. By decentralizing trials, sponsors can reduce the risk of slow enrollment and dropouts. DCTs eliminate the need for subjects to be physically located close to a clinical site in order to participate, thereby expanding the geographic area and reducing the socio-economic and diversity barriers that deter or preclude patients from enrolling or cause them to drop out if the burden becomes too great.

Decentralization of studies also supports patient compliance and adherence by preventing missed visits and increases the diversity of the pool of potential participants. Collectively, the benefits support the swift enrollment and strong retention that improve adherence to overall study timelines and budgets.

Faster recruitment and increased retention are just two of the ways that decentralization and DTP from a central location can drive cost savings. Sponsors also benefit from having to produce less drug overage as there is no need to stock sites just in case a patient enrolls, thereby reducing the amount of study drug that is potentially wasted over the course of the trial.  Additionally, sponsors may see a reduction in clinical site fees for storage, visits, and handling. These savings help offset any upfront costs from using DTP.

Putting DTP Into Practice

The benefits of DTP are now well-validated, with the COVID-19 pandemic having accelerated the transition to the model and having shown all stakeholders just how it can improve clinical trial operations and reduce risk. As DTP becomes an increasingly routine part of drug development in the post-pandemic period, sponsors and their vendor partners will need to stay abreast of the evolving best practices regarding use of this approach and cognizant of opportunities to use DTP in order to help mitigate operational risk and maintain patient centricity.

Sponsors are rising to that challenge in a fast-changing sector that is subject to country-to-country variations in regulations by partnering with experienced clinical supply providers that have a track record of success and knowledge of the evolving DTP space.

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