The growth of direct-to-patient (DtP) clinical trial strategies is expected to continue for the foreseeable future. Adopting a DtP approach has the potential to improve recruitment, retention and efficiencies, as well as reduce costs. However, legal and regularity barriers can hinder implementation. Emma Green considers the challenges.
For manufacturers, who can spend anywhere from $161 million to $2 billion to bring a new drug to market, the returns from investing in this important work have been gradually diminishing. Patient recruitment and retention, which cost around $2.3 billion a year, have become major challenges. These issues can cause trials to become longer, more expensive and less statistically robust, as well as result in poor morale among researchers, healthcare providers and patients.
In light of an ageing population, pharmaceutical manufacturers are shifting their focus to researching chronic and degenerative diseases. Resolving recruitment and retention issues in this population has thus become an increasing area of concern. The rapid developments in technology over the past few years have enabled the creation of direct-to-patient (DtP) strategies, which can help to address patient engagement challenges. This approach follows the standard blinding protocols but sends medication directly to the homes of participants. This means that they do not have to travel to medical facilities or wait for services. This convenience can be a key factor in boosting patient recruitment and retention.
In the traditional trial model, the investigational site plays a central part. All staff involved, including nurses, patients and researchers, must travel to the site. It must also be close to patients because they will be required to visit the site frequently, which can be challenging.
“It can be difficult logistically for patients to attend these appointments, especially if they work or care for family members,’’ says Deborah Collyar, president of Patient Advocates in Research.
The DtP approach eliminates these issues, and instead they are placed at the centre of the clinical trial process, in line with a more patient-centric model.
“This type of research can make the clinical-trial experience easier for patients and their families, which means they are more likely to join the trial and stay involved with it,’’ explains Collyar.
It is estimated that as many as 50% of site visits could be successfully relocated to a patient’s home. In light of the average dropout rate of 30%, DtP strategies are worth serious consideration.
Although not suitable for all clinical trials, they are particularly valuable for research on particular populations.
“They work well for patients who are sicker and older, and in settings where more frequent visits are required,’’ says Collyar. “The DtP approach can also be good for paediatric trials, especially for rare diseases, which tend to have difficulties recruiting enough participants.’’
The most important part of implementing DtP strategies is getting the initial plan right and ensuring that it is broad enough. This process should involve all stakeholders and clearly define the scope of work, required resources, project time frames and feasibility of practices.
“A disadvantage is that more time may be needed to set up the trial initially,’’ explains Collyar. “However, upfront planning can help the trial run more smoothly.’’
Depending on the location of participants, when more home visits are incorporated into trials, nurses or courier drivers may be travelling long distances to a patient’s home. Each home visit requires a coordinated approach from all stakeholders to ensure that the medication reaches the patient’s home on time, and at the perfect temperature and condition, regardless of the distance travelled. A single temperature excursion or delay in delivery can compromise the life of a patient as well as the entire study.
Sponsors also can face greater transportation costs due to a high volume of small shipments, and the reverse logistics of shippers and biological specimens. Ensuring that the drug is stored properly at the patient location can also be costly and challenging. To address these issues, some companies have started to use small, temperature-and-access-controlled refrigerators in patient’s homes. This can help to promote patient adherence as well as prevent medication wastage.
During the planning stage, it is also imperative to establish a strong relationship with a home trial company in order to gain insight into the regulatory landscape. Companies that can offer in-depth knowledge of the countries in which they operate can help to ensure adherence to both trial standards and local market regulations. Both of these can vary considerably from country to country and are subject to change, which makes this insight particularly valuable.
Confidentiality is an important issue to consider because the service provider and the couriers will not be fully trained in good clinical practices (GCP). While almost all of the communication goes through clinical personnel, it is the service provider’s responsibility to ensure that the courier complies with the delivery protocol. To achieve good practice in manufacturing and distribution, it is important therefore to not only have the patient’s name and address, but also a caregiver’s phone number. Ensuring privacy of this information is key.
Collaboration is also extremely important in dealing with complexities. In some cases, patients are just receiving medication. In other cases, their drawn specimens will need to be delivered back to labs for analysis, requiring careful planning and timing. Furthermore, patients are sometimes unwilling or unable to self-administer medication, especially when working with injectable drugs. Coordination with a healthcare professional or carer may therefore be required to administer the drug and/or help with returning the specimen to the lab.
A number of different technologies are being used to help manage deliveries in trials implementing DtP approaches. These include both GPS and Bluetooth Low Energy. These are helpful in monitoring shipments at each point in the supply chain, including when products are placed in the storage facility or pharmacy, when they are picked up by a driver and when they are delivered to the patient’s home.
When using monitoring technologies, it is crucial that they allow for full audit capability to determine whether the drug is usable or not. Currently, technologies are not able to provide in-flight visibility, which would allow for timelier problem resolution to take place in global trials. However, technology is evolving, and airlines are now working closely with device manufacturers to explore data-recording strategies, such as the use of wireless networks on flights.
A DtP approach could also boost supply-chain efficiencies by reducing the number of handoffs and investigator site costs. As patients are not required to visit a particular site, there is often only a single site for managing regulatory submissions. Trials can be managed centrally by a remote-study coordination centre that facilitates all research activities, including recruitment, screening, informed consent, enrolment and data collection. A medical team monitors the health and safety of participants by reviewing all data as reported in real time. By relying on only one site, or a small number of sites for global trials, the DtP approach is highly cost-effective. Research suggests that it could help reduce costs by up to 16% in phase-I trials, by up to 22% in phase-II, 17% in phase-III and by up to 13% in phase-IV.
Another advantage of having a small number of sites is the ability to collect a large amount of data from diverse sources. This is because, unlike site-based studies, data is not collected by investigators during site visits, but instead through the central study coordination centre. This enables data to be obtained from patients themselves, caregivers, healthcare professionals, electronic health records, existing registries, databases, labs and biospecimen repositories.
Depending upon the design of the trial, information collected could include basic demographic information; anthropometric, biological and lab measurements; medical, family, occupational and behavioural histories; disease status and natural history; drug treatment information; quality-of-life; disease-related disability; and treatment satisfaction feedback.
Calling for change
One obstacle when implementing DtP trial strategies is the fear of internal and external change. All companies have established habits, and decision-makers become accustomed to particular budgets, working practices and timelines. Making adjustments to these can be highly challenging, and require a positive and proactive approach. Externally, it can be difficult to navigate relationships with different stakeholders, many of whom may be invested in maintaining the current system of clinical trials. Such issues explain why, despite the rapid technological progress achieved over the past 30 years, many practices within clinical trials have remained relatively unchanged.
As the industry moves towards a more patient-centric approach, the DtP model has become a growing trend in clinical trials. A recent survey projected that DtP trials would increase from 24% of all clinical trials in 2017 to 33% by the middle of 2019. Once viewed as unrealistic due to quality and cost concerns, trials adopting a DtP approach are now viewed as viable and valuable. These strategies are undoubtedly opening up the possibility of more people participating in clinical trials than ever before. They could prove instrumental in boosting recruitment and retention, allowing for more efficient and effective clinical trial procedures.
Despite the fact that applying this approach raises a number of challenges, DtP strategies are clearly here to stay, and require contemplation and collaboration from all clinical-trial stakeholders.
Case study: Pfizer’s REMOTE study
The first virtual clinical trial was Pfizer’s Research on Electronic Monitoring of OAB Treatment Experience (REMOTE), conducted in 2011. This pilot study used mobile and web-based technologies to recruit and enrol patients, and collect data without any visits to clinical sites. The trial aimed to evaluate the safety and effectiveness of an overactive bladder treatment. By comparing results from REMOTE with a previously completed trial, sponsors aimed to determine whether a direct-to-patient approach could achieve similar results.
The pilot generated a large amount of interest, but struggled with recruitment issues, patient concerns about confidentiality of data, burdensome online research processes and a lack of human support through a study contact centre. Following feedback from patients, the trial was revamped to include a call centre that could provide support during the initial enrolment steps. This increased recruitment, but due to delays the trial was discontinued.
The REMOTE study demonstrates that despite the capabilities of technology to perform a range of tasks in clinical trials, a lack of human interaction could hinder participant engagement. It is thus important that when implementing DtP strategies that human involvement remains a central aspect of trial design in order to maximise both patient recruitment and retention.