Sukirti Kalra clinical project manager and Colin Newbould, head of Global Regulatory Affairs & Quality at Wasdell Group examine how clinical trials are adapting with the ongoing Covid-19 pandemic.
Kkolosov Konstantin Kolosov
Clinical trials
Clinical trials are evolving at a rapid pace, with many changes occurring as a direct result of the ongoing global pandemic. COVID-19 has shined a spotlight on how the industry delivers clinical trials, highlighting patient recruitment challenges, logistical hurdles and an urgent demand for new ways to run studies. The need for social distancing has caused many to question whether trials can continue in a clinical setting and how medicines can be supplied to patients.
However, Covid-19 has introduced many positive opportunities, including a sharp rise in demand for Direct-to-Patient (DtP) services where medicines are delivered direct to patients, as opposed to in clinical settings, such as hospitals. While this model is not new; the desire for more patient-centric trials has been mounting and Covid-19 has propelled this need. Therefore, adaptability and agility of supply chain partners, from contract manufacturers to packagers and distribution networks, is paramount to the success of both current and future trials.
Benefits of DtP Trials
Solutions like DtP shipments of Investigational Medicinal Products (IMP) and remote follow up and monitoring of study patients have obvious and necessary advantages when complying with strict lockdown laws across the globe. However, there are also longer-term benefits to patients and sponsors. These positive measures reduce unnecessary trips to hospitals, making trials more convenient for patients who are giving their time and energy. The patient can participate from the comfort of their own home, with less impact on their daily lives.
Such trials are more appealing to participate in, as the burden is minimised, enhancing patient experience and adherence while reducing droputs. Studies show that over 50 percent of patients are more likely to participate in a trial if home care is offered for two main reasons:
(1). Virtual trials are therefore easier to recruit for, retain and at times simpler to manage; data shows that the use of DtP helps maintain patient retention rates at more than 95 percent (2). As a result, sponsors can often complete trials faster, save money and accelerate drug development. Recently the FDA has updated guidance on switching to virtual models, further demonstrating regulatory backing.
Case Study: Direct Shipment of IMP to Patient Homes
DtP services require the establishment of procedures and agreements among all parties to ensure that the IMP is delivered to patients in good quality. So how does it work in practice?
Recently, a sponsor required a clinical trial service to reduce patient travel time. This was a timely service launch, coinciding with the impact of the Covid-19 pandemic. Working collaboratively, Wasdell and the sponsor enabled the delivery of IMP trial packages direct to patients’ homes, reducing time spent travelling to clinical sites and minimising the footfall at hospitals. Various aspects needed careful consideration, including patient safety, National Competent Authority acceptability, despatch information, transport and accountability.
A first step included analysing all risks that could be encountered during the process. Not all on-going or newly proposed clinical trials are eligible to meet the criteria for safety, so it is vital that the initial step reviews the IMP and any potential patient concerns. For example, this could be to the delivery mechanism, or that the product requires close patient monitoring during administration of the drug.
The most difficult challenges were through the despatch, transport and accountability parts of the process. Most courier organisations faced challenges including limited air and ship freight capacity, pressures caused by a surge in demand for DtP logistics, and some countries faced major road closures to ensure travel was restricted to essential only, causing considerable changes to delivery times.
Therefore, the risk assessment needed to capture both the change in route and the impact of temperature control. The most critical part was confirmation that the IMP had arrived at the final destination and was in the safe custody of the patient. Mechanisms to achieve verification had to be designed and include a process to verify the condition of the product upon arrival.
As the pandemic developed, more guidance became readily available from each National Competent Authority, which helped to provide a framework for DtP. This meant constant refinement and adaptability from delivery teams to ensure trials were continued compliantly and efficiently.
The DtP model made an immense difference to the study as the patients could continue to be recruited and provided with IMP in time, direct to their homes, with clear information about the package. Patient enrolment continued without severe impact, and study initiation also improved. The largest positive impact was continuation of supply of the clinical trial materials without suspending or disrupting the study.
Closing the Loop
DtP is not the only area that can realise the benefits of a more virtual, remote service. IMP returns (including accountability and destruction) is another field brought to attention during the current pandemic. Clinical trials in any phase need solutions so clinical pharmacies, hospital sites and patients can return IMP for destruction. This model, also known as direct-from-patient (DfP) closes the loop on the end-to-end supply chain for the patient.
As an example, a sponsor required a solution for returns, reconciliation and destruction of clinical trial material from patient homes during the Covid-19 crisis. The IMP had been packaged at Wasdell premises and QP released by the team. All hazards were assessed at various steps during the whole returns to destruction process and a risk assessment was implemented. The whole solution was managed with thorough acceptability by Wasdell’s Quality Management System (QMS). The resolution included arranging pick-ups with tracked delivery, full IMP traceability and returning of IMP material for destruction, with an issuance of a destruction certificate.
Key Considerations for Success
One of the first steps in adapting clinical supply practices to encompass DtP services is to analyse any risk. Patient safety is paramount, both in terms of administering medication, monitoring and reporting adverse events and in monitoring Covid-19 social interactions. Another key area is ensuring that packaging information is clear and accurate. All information and instructions must be easy to understand, and it should be simple to open the packaging and administer the medication. Often the storage information needs to be clearer to patients than if it were managed in hospitals.
Open channels of communication are vital in virtual trials. It is crucial to liaise with patient support sponsors who are in direct contact with patients to ensure training for adherence. Appropriate dispatch information and transport is another key consideration, and this may include liaising with sponsors and other partners to work collaboratively. Accountability and assigning clear roles are especially important to ensure everything runs smoothly.
Looking Ahead
Covid-19 is impacting clinical trials and creating lessons for future research. DtP trials are not around for the short haul, especially as the healthcare industry shifts to more patient-centric approaches. Once viewed as unrealistic due to safety and cost concerns, DtP approaches are now viewed as viable and valuable. Proactivity is crucial to success and enlisting the support of an agile, adaptable strategic partner can help guide sponsors through this ‘new normal’ procedure, often handling the entire process. When looking for a contract partner, consider clinical supply experience and understanding. Flexibility is also paramount, especially when it comes to manufacturing, packaging and distributing small batch sizes often required for more novel drug products.
A good partner will offer solutions-driven support and find a way to deliver a personalised approach to meet customers’ and patients’ needs within specific timeframes; when speed of service is critical to ensure a reliable supply of medicine when and where it is needed. Ultimately, DtP services can be an incredibly effective strategy for a successful clinical trial.
References
American Academy of Neurology. “Rare Disease Clinical Research: Caregivers’ Perspectives on Barriers and Solutions for Clinical Research Participation.” www.neurology.org
U.S. Department of Health and Human Services. “Examination of Clinical Trial Costs and Barriers for Drug Development” (Executive Summary). www.aspe.hhs.gov
FDA Guidance on Conduct of Clinical Trials of Medical Products during COVID-19 Public Health Emergency. Guidance for Industry, Investigators, and Institutional Review Boards. March 2020. Updated on June 3, 2020 Document