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February 10, 2022

Direct to patient: rocky road to remote drug delivery in clinical trials

While an obvious solution to lockdown measures, sending study participants investigational drugs directly is still an untapped opportunity even in trials that would benefit. Clinical Trials Arena finds out why.

By Reynald Castañeda

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Direct-to-Patient Trials: How IRT Plays an Important Role in Bellerophon's Direct-to-Patient Trials

As the industry strengthens its focus on patient centricity, Direct-to-Patient clinical trials have emerged as a popular trial design that have the potential to increase patient recruitment and retention. IRT plays a crucial role in the success of a Direct-to-Patient trial. Because drug supplies are being managed and shipped from distribution facilities directly to patients’ homes, a sponsor must have a high-quality system in place to accurately track the chain of custody, ensure patient-blinding and handle other logistical challenges. What You Will Learn Benefits and challenges associated with the Direct-to-Patient model Bellerophon's top considerations when implementing this trial design How IRT can equip study teams to successfully track chain of custody, ensure patient blinding, and handle logistical challenges
by Suvoda
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  • At last week’s launch of Clinical Trials Arena’s Decentralised Clinical Trials (DCT) Adoption Tracker, which is based on publicly disclosed information, we observed that direct-to-patient drug delivery is one of the least utilised DCT approaches.
  • While sending investigational drugs directly to patients jumped in 2020 and 2021, likely due to Covid-19 lockdown measures and use in Covid-19 trials, this DCT element’s uptake is still slow compared to other decentralised approaches.
  • Clinical Trials Arena spoke to DCT experts to point to remote drug delivery obstacles and offer some solutions.

Direct-to-patient remote drug delivery, a decentralised clinical trial (DCT) approach that allows for an investigational drug to be sent directly to the trial participant, seems like an obvious study design element addition in response to Covid-19 lockdown measures. Indeed, in the past two years, there has been an uptick of trials using this design element compared to years prior, according to Clinical Trials Arena’s DCT Adoption Tracker

Beyond the pandemic environment, remote drug delivery has many perks. For instance, if a patient is too sick to physically go to the trial site, then such a direct-to-patient approach would be ideal, says Andrea Zobel, senior director, personalised supply chain at World Courier. Also, such an approach would widen the pool of potential trial participants and ease the risk of dropout rates, she notes. Direct-to-patient deliveries also allow for “patient-world datasets”, with the drug being used in a real-world setting, adds Dale Hanna, product strategy director at patient support services company Lash Group.

However, from a broader perspective, it is apparent that the use of direct-to-patient drug delivery is sluggish compared to other DCT approaches. While the idea may sound straightforward, there are many complicating factors for its execution, Zobel says. Experts interviewed by Clinical Trials Arena note that the challenges are multifactorial, ranging from regulators and the technology still needing to catch up, to practical challenges that may discourage uptake among trial sponsors.

Direct-to-patient regulatory framework needed

Outside of the pandemic setting, there is a lack of guidance from regulatory authorities on how to integrate remote drug deliveries into trial protocols, Zobel says. Before the pandemic, sending investigational medicinal products directly to patients was not typically mentioned in any regulatory document, she adds.

Due to the lack of a regulatory framework, sponsors would need to convincingly argue their case to regulators that remote drug delivery was essential to the trial, Zobel says. There would need to be evidence supporting the idea that this decentralised element would contribute to patient safety and improve access to therapy, she adds.

Covid-19 lockdown measures helped increase the profile of direct-to-patient drug delivery within the clinical trial industry, particularly for participants who are unable to visit hospital-based trial sites to access investigational drugs, says Bhausaheb Patil, head of business operations, decentralised clinical trials solutions, at IQVIA. The FDA, EMA and other regulatory bodies published emergency guidance that allowed for direct deliveries to happen, Zobel notes.

Our DCT Adaption Tracker shows that the use of remote drug delivery is higher among academic sponsors than industry sponsors. Academic centres do not have to comply with the same level of regulatory oversight in their trial design because they are not working towards commercial gain, so they are not audited and inspected as often as industry sponsors, notes Karla MacKenzie, head of site management and decentralised clinical trials Oceania at Leo Pharma. Also, academic centres do not often stage large, multicountry trials, which increases the complexity from a regulatory aspect, she adds.

Enthusiasm for drug delivery varies

There are countries like Denmark that recently specially amended their regulatory regulations to allow direct-to-patient drug deliveries to happen even outside of the pandemic setting, Zobel says. Australia’s regulatory body, the Therapeutic Goods Administration (TGA), is open-minded when it comes to decentralised approaches, primarily due to the sheer size of the country, MacKenzie notes.

However, there are also countries that are not as enthusiastic about remote drug deliveries. For example, a German-based patient may be blocked from being recruited from a trial based outside the country if the investigational drug would be delivered to the patient, Zobel notes. Yet the same patient can be enrolled in the trial if the patient travels to the trial site to pick up the drug, she adds.

To garner more widespread regulatory support, Hanna says sponsors should collect meaningful data from trials with a direct-to-patient drug delivery component that supports the worthiness of this decentralised approach. This could be improved quality of life or even more accurate clinical outcome measures. “It’s about creating that value story. It’s about the sponsor creating a compelling story on benefit,” he adds.

Intravenous drugs sent to the patient?

Some investigational drugs are better suited for remote drug delivery than others. According to the tracker, infectious disease and central nervous system trials are leading the way in terms of using this DCT approach. However, Zobel notes the ideal drug for patient deliveries is not necessarily disease-dependent, but perhaps depends more on dosing frequency, such as a therapy needing continuous treatment at home. It would also be less ideal if the medication has a complicated application procedure, she adds.

One additional concern with direct-to-patient drug delivery is participant compliance. There could be questions regarding whether the patient is taking the investigational drug at the right time. Worse, questions could arise about whether the participant is taking the drug at all, and ensuring that the drug is not given to someone else, Patil says. All of this is hard to monitor without a coordinator on hand, he adds.

Where appropriate, adding a nurse home-care element could solve these issues. While oral or topical drugs may seem more ideal for remote drug delivery, IV drugs could also be sent directly to the patient with a visiting nurse assisting with the administration, adds Alexander Pytlarz, President of Operations at Infuserve America, an infusion and compounding pharmacy. Nurses can also assist with recording trial data, which can bolster data quality, he notes.

Yet, with a nurse visit element, the challenge is still coordination between the patient and the nurse. Has the patient done the required tests before the visit? Has the drug order arrived? Reassuringly, while such issues may lead to rescheduled nurse visits, they do not lead to cancellations, Pytlarz says. Apart from nurse visits, telehealth could also be used where appropriate, Hanna adds.

How about temperature-sensitive drugs?

Some investigational drugs are temperature sensitive, and the patient’s home may not be the ideal place for storage, Zobel says. If the drug is shipped to a pharmacy, staff would know how to manage any temperature fluctuations, MacKenzie adds.

Oversight of the consistency of investigational therapies is much more stringent than for approved therapies, Zobel notes. There are limited volumes for investigational drugs, so every dose is important, MacKenzie adds.

However, when investigational drugs are shipped to the patient, they are already in temperature-controlled shippers and the patient is advised not to open them until needed, Pytlarz says. The shippers can hold the right temperature for multiple days. If the drug needs to be stored in a refrigerator, it would be specifically defined in the protocol, he adds.

Privacy needs consideration

Patient privacy is another consideration with remote drug deliveries. Participant names and addresses should not be accessed by a trial sponsor, Zobel says. There should be clear procedures whereby this information is hidden from sponsors but accessible to the logistics company, she adds.

An option to overcome privacy concerns is to send the investigational drug to the nurse, instead of the patient, Pytlarz says. That said, blinding sponsors to patient identities is standard in clinical trials, he adds. Trials with such a design would still be under privacy regulatory oversight, such as the Health Insurance Portability and Accountability Act of 1996 (HIPAA) Privacy Rule in the US, Hanna notes.

Tracking drug location is vital

In a world where food deliveries can be tracked on a digital map, this technological advance is not yet easily accessible in clinical trials, Zobel says. Tracking is key as it would ensure the investigational drug reaches the patient at the right time, she notes. In clinical trials, the chain of custody needs to be under total control the entire time to be compliant with Good Manufacturing Practice, MacKenzie adds.

From a pharmacy or a clinical trial site perspective, the challenge is ensuring that every logistics element is in place, Pytlarz says. For example, some trials require specific vials to be sent to specific patients, but these cannot be done if the details have not been sent through, he adds. At present, communication between people handling investigational drugs is mostly done manually, Zobel notes.

Nonetheless, there are short-term goals to fast-track technology improvements, such as having the functionality of a dispensing order becoming a shipment order, Zobel says. Also, data collection standardisation would help move the needle, Hanna adds. This would then lead to valuable datasets that would provide insights on how to bolster remote drug delivery uptake, he explains.

Takeaways:

  • Enthusiasm for direct-to-patient drug delivery across different regulatory countries is uneven. The inconsistent appreciation for this decentralised approach can make it hard to integrate in trial protocols, particularly in multicountry studies.
  • There are execution challenges that need to be considered, such as the drug’s administration method and if the drug is stored properly at the patient’s home. There are also privacy issues that need to be reviewed. A potential solution is to integrate home health nurses into the protocol, particularly with investigational drugs that require a higher level of monitoring.
  • While investigational drugs need to have their chain of custody under control the entire time, the technology to do so has not yet caught up. However, there are practical, easy-to-accomplish goals that can speed up the use of remote drug delivery in more trials.

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Direct-to-Patient Trials: How IRT Plays an Important Role in Bellerophon's Direct-to-Patient Trials

As the industry strengthens its focus on patient centricity, Direct-to-Patient clinical trials have emerged as a popular trial design that have the potential to increase patient recruitment and retention. IRT plays a crucial role in the success of a Direct-to-Patient trial. Because drug supplies are being managed and shipped from distribution facilities directly to patients’ homes, a sponsor must have a high-quality system in place to accurately track the chain of custody, ensure patient-blinding and handle other logistical challenges. What You Will Learn Benefits and challenges associated with the Direct-to-Patient model Bellerophon's top considerations when implementing this trial design How IRT can equip study teams to successfully track chain of custody, ensure patient blinding, and handle logistical challenges
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