Michael Sweeney

	As the healthcare industry continues to deepen its focus on patient-centricity, the popularity of Direct-to-Patient (DtP) services in the clinical trial setting has grown significantly. The DtP approach brings investigational medicinal products (IMP) and trained nurses directly to a patient’s home. The benefits of this are multi-faceted-not only are patients able to access customized care and novel therapies from the comfort of their homes, but manufacturers are also able to facilitate patient enrollment and increase patient adherence, which are central to the success of clinical trials. 

Understanding the Changing Clinical Trial Landscape

	Some of the most pervasive challenges in clinical trials revolve around patient recruitment and retention. Each year manufacturers spend approximately $2.28 billion

 recruiting participants, yet two-thirds of investigator sites still fail to meet the enrollment requirements. As a result, patient dropout rates remain at around 30 percent

, which can have a significant impact on the trial timeline. Each day that a study is delayed can result in hundreds of thousands of dollars in out-of-pocket costs, in addition to the potential lost revenue from the product being kept off the market.

	In an effort to address these challenges and improve clinical trial outcomes, more pharmaceutical manufacturers are exploring Direct-to-Patient services, often used in conjunction with home care, as an approach to their studies. While early patient visits may need to be conducted at a hospital to assess safety, suitability, and obtain informed consent, the Direct-to-Patient approach then reduces the need for the patient to travel to an investigational site throughout the remainder of the trial. This improves convenience and access, while also controlling costs. Studies have shown that over 50 percent of patients are more likely to participate in a clinical trial if home care is offered

. Meanwhile, the use of the Direct-to-Patient service helps maintain patient retention rates at more than 95 percent

, allowing sponsors to expedite trial timelines and bring products to market faster.

	The Direct-to-Patient approach offers significant benefits for patients, manufacturers, and the healthcare system; however, it also presents a number of unique challenges. To that end, there are multiple factors manufacturers should consider as they evaluate whether the approach is a good fit for their specific study.  

	Today, about 24 percent of clinical trial studies offer a home-based solution

. This figure is expected to significantly increase by 2020, according to a 2017 study by Arena International in which more than 30 percent of respondents said their company was likely to consider the approach within the next 12-18 months

. At World Courier, we’ve already begun to see Direct-to-Patient growth in terms of our shipment volume and the number of countries implementing the approach. Despite this anticipated increase in popularity, Direct-to-Patient services are not necessarily an appropriate solution for every clinical trial. To determine whether the approach is worth exploring, sponsors should closely evaluate their patient base, the medication being administered and any on-site requirements. 

	In evaluating the patient base, for example, the added convenience of the Direct-to-Patient model is particularly helpful for individuals who are disabled, geriatric, or pediatric, and those who may be lacking in mobility, transportation, or nearby access to an investigational site. When it comes to the medication itself, sponsors should by wary of ultra-sensitive or temperature-controlled therapies, unless an in-home storage solution can also be provided. If the therapy must be administered by a nurse or medical professional, sponsors must ensure these accommodations can be met on a consistent basis. Finally, sponsors should take into account any additional on-site equipment needs, as well as the frequency of nursing interventions for blood samples and other tests before moving forward with the approach. If the clinical trial calls for frequent procedures using equipment that cannot be brought to a patient’s home, Direct-to-Patient may not be the best strategy.

Navigating the Model’s Unique Challenges

	Once the decision to implement the Direct-to-Patient approach has been made, sponsors must prepare for the unique hurdles they will inevitably face in regulatory requirements, timing, and temperature demands and patient confidentiality.  

	Regulations governing home healthcare vary worldwide, so it is important to understand any potential legal restraints the study may face as a result of its location. For example, in some countries only physicians are authorized to draw blood from patients under the age of 18 in their home. Similarly, the required credentials and documentation from nursing staff also vary, and all nurses must meet local professional licensing requirements. Additional regulations to consider include whether the name of the home nursing organization needs to appear on the protocol application, as well as whether nurses are required to sign the delegation log, or if patient referrals by a physician are sufficient. Depending on where the trial is taking place, there may also be specific regulations concerning drug dispensing for in-home use, based upon whether the dispense involves the site pharmacy, a central pharmacy, or a depot. All of these regulatory logistics must be assessed before moving forward with the Direct-to-Patient approach.

	Timing and temperature are also critical considerations. Successful Direct-to-Patient services demand that all pick-ups and deliveries happen within a predetermined, and often tight, timeframe. Therapies may also require cold chain integrity and shipment over long distances. One late delivery or temperature fluctuation can comprise a study, endanger a patient, or damage credibility. As a result, all of the parties impacted by the logistics of Direct-to-Patient services (e.g., potentially the home care nursing company, central laboratory, site, or central pharmacy, etc.) must carefully coordinate detailed procedures for pick-ups and deliveries that can be consistently executed. 

	Finally, protecting patient confidentiality and data privacy is of the utmost importance for an ethical Direct-to-Patient clinical trial. A thorough understanding of all local patient-privacy requirements, as well as your external partners’ ability to suitably support their adherence, is paramount. In addition, there is a need to maintain patient anonymity and appropriately limit unnecessary outside access to information. For example, the dispensing site and the logistics provider must collaborate to ensure the correct medication gets to the correct patient using only the common metrics of anonymous ID numbers to safeguard patient information. Preparing for these privacy concerns will be a large part of the overall Direct-to-Patient strategy.

	The Direct-to-Patient approach adds a layer of complexity, with external partners taking on many of the responsibilities that would traditionally be assumed by clinicians. That said, engaging the right partners early on in the planning process is crucial. 

	Proactive planning with all partners helps identify potential pitfalls before they occur, which can then lead to practical solutions. For instance, each home visit may require a coordinated approach from all stakeholders to ensure the therapy is delivered from the pharmacy to the patient’s home on time, at the appropriate temperature, and in the perfect condition. All entities must fully understand the temperature control and monitoring needs of the product being delivered to be able to identify an appropriate packaging solution and outline specific delivery windows. Quality control and assurance are vital to both the health of the patient and the success of the trial. Given all of these potential variables, partners should also develop detailed contingency plans to ensure they are prepared to overcome any unforeseen obstacles.

	At the same time, the unique challenges associated with the Direct-to-Patient approach mean it is important to identify partners that have significant experience and a proven track record of safely transporting and administering the products in a timely manner. It is helpful to partner with a specialty logistics company that possesses an existing understanding of these requirements and has a local presence in the market. Conversations with this prospective partner should cover all logistical details, such as packaging and temperature requirements, pick-up and delivery locations, and returns management. It is also beneficial to partner with a home healthcare company at the onset, since they bring an in-depth knowledge of the countries they operate in and help ensure adherence to both clinical practice standards and local market regulations.

Recognizing the Value of Direct-to-Patient 

	As Direct-to-Patient services evolve, clinical trial sponsors should not only view this approach as a viable alternative to the traditional model, but also as an opportunity to improve patient recruitment, expedite trial timelines, and reduce overall cost burdens. If the approach is deemed a good fit for the study and the proper due diligence is undertaken, Direct-to-Patient services can be an incredibly effective strategy for a more successful clinical trial. 

	In the coming years, innovations in technology-particularly advanced monitoring technologies-will continue to strengthen the approach, further enhancing the patient experience and providing stakeholders with greater visibility of the supply chain. With that in mind, it is wise for sponsors to begin exploring now whether this approach is feasible for their studies in the future. 

, Senior Director of Patient-Centric Logistics at World Courier

U.S. Department of Health and Human Services. “Examination of Clinical Trial Costs and Barriers for Drug Development.” 

Clinical Leader. “Considerations For Improving Patient Recruitment Into Clinical Trials.” 

American Academy of Neurology. “Rare Disease Clinical Research: Caregivers’ Perspectives on Barriers and Solutions for Clinical Research Participation.” 

U.S. Department of Health and Human Services. “Examination of Clinical Trial Costs and Barriers for Drug Development” (Executive Summary). 

Clinical Trials Arena. “Arena International Survey reveals Current and Future Trends in the Clinical Trial Supplies market.” 

Articles

The exponential growth in the use of Direct-to-Patient clinical trials and the strategies pharmaceutical manufacturers should consider when implementing this model.

Direct-to-Patient Clinical Trials: Strategies for Success

	Recently, the direct-to-patient (DTP) model, which brings certain medical procedures and protocols to a patient’s home, has emerged as a popular solution. In 2015, the Medical Research Network (MRN), a provider of home healthcare for patients in clinical trials, entered a partnership with World Courier, a global specialty logistics company and a part of AmerisourceBergen, to elevate the reach and effectiveness of DTP clinical trials. The partnership’s aim is to increase patient recruitment and

 retention and provide an integrated supply chain in the transportation of patient samples and the storage and distribution of investigational medicinal products (IMPs).  

	In the following Q&A, Michael Sweeney, senior director of global service development at World Courier, and Stuart Redding, vice president of global business development and marketing at MRN, share insights on the evolution of community-based trials.

Q: How does the DTP model improve the recruitment and retention of qualified patients?

: As clinical trials continue to grow more complex, patient recruitment and retention will remain a major challenge that sponsors face. Today’s protocols are more demanding than ever and frequent travel to a clinical site can deter patients from long-term participation in studies, especially when the site is far from their homes. In fact, about 25% of patients drop out before study completion. 

	In many studies, as many as 50% of the visits could be relocated to a patient’s home. The added convenience is a critical factor in retaining patients, who otherwise might have to regularly travel to a clinical trial site for procedures, such as IMP administration, that can take hours to complete.

Q: How do organizations ensure the clinical products are safely transported in a timely manner?

When more home visits are incorporated into trials, nurses or courier drivers may travel long distances to a patient’s home. Some trips require flights, while others call for long drives to remote areas. In order to reduce the number of deliveries, we are in the process of deploying small, temperature- and access-controlled refrigerators in patients’ homes. The solution stores medication securely and at an optimal temperature, providing in-home access to the product. It features a real-time remote temperature monitoring system as well as security features and inventory management capabilities that to track product access. We’ve found that such in-home solutions help improve patient adherence and reduce medication waste. 

Every home visit requires a coordinated approach from all stakeholders-which includes nurses, the pharmacy, the logistics company, the site and the central lab-to ensure IMP is delivered from the pharmacy to the patient’s home on time, at the appropriate temperature and in the perfect condition, no matter the distance. 

	When planning the home visits, the entities must understand the temperature control and monitoring needs of the product being delivered, identify an appropriate packaging solution and outline the specific timing. Given all the potential variables, flexibility is critical to our success. That’s why we develop detailed contingency plans for all studies to ensure we are prepared to overcome any unforeseen obstacles. 

Q: Varying country regulations, compliance with GxP policies and global logistics support are often the main challenges associated with the DTP model. How can sponsors overcome those hurdles? 

 Perhaps the most important step is partnering with a home trial company early in the process, in order to maximize the number of home visits and gain insight into the regulatory landscape. Such companies that bring an in-depth knowledge of the countries they operate in can help ensure adherence to both good clinical practice standards and local market regulations. It’s critical for sites to be well-educated in the homecare service as well. For example, they need to understand who is seeing their patients, how their source data will be provided and what their responsibility is to maintain oversight of the patient’s progress. 

 Partnering with a specialty logistics company that has an understanding of the requirements and a local presence in the market can be extremely helpful for sponsors, especially smaller biotechnology firms that may have limited resources or exposure to a country’s regulatory environment. Regulatory requirements and import procedures related to clinical trial products vary from country to country and are subject to change. Through integrated, GxP-compliant supply chain solutions, specialty logistics partners can meet the quality requirements and ensure the integrity of products and chain of custody. 

Q&A explores the evolution of community-based studies-and the related sample management, regulatory, compliance, and logistics support considerations.

Michael Sweeney

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Direct-to-Patient Clinical Trials: Strategies for Success

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