Direct to Patient: The Basics & Quality Considerations
Making clinical trials more patient centric is among the many challenges facing the pharmaceutical industry. One method of improving the patient experience is by delivering study medication directly to patient homes, also known as Direct-to-Patient or DtP. However, the implementation of Direct-to-Patient may seem insurmountable in a highly regulated industry where specific regulations or guidance is lacking or vague. Additionally, Direct-to-Patient experiences can be inconsistent by country, trial, or therapeutic area.
Therefore, in follow up to the iSpeak blog post, Developing a Guide for Patient Centric Logistics - Get Involved1 a collaborating team of Direct-to-Patient Sponsors, Couriers, CROS, and QPs will, through a series of blogs, identify some of the direct-to-patient models, share considerations for establishing a Direct-to-Patient program from the stakeholders’ perspective and relative to specific models with a focus on quality standards.
The Direct-to-Patient models covered here are not exhaustive and even though we plan to set forth what we define as “Direct-to-Patient”, the interpretation of this (or more broadly, patient centric services) can vary and models are subject to change. While some of the varied and evolving landscape can seem overwhelming for those new to or investigating Direct-to-Patient, differences in approach are sometimes driven by very creative thinking and putting specific patient needs first.
Direct to Patient models should also not be considered as applicable across an entire study or for all patients. Typically, the models noted herein are subject to a hybrid approach on a number of levels. Some patients may opt out of home treatments or medication deliveries and the models below may differ by country or even locale.
As would be expected of any complex distribution network, each Direct-to-Patient model requires the establishment of procedures and agreements to be in place with all parties to ensure that the distribution of medication is handled properly and to confirm the Clinical Trial Material/Investigational Medicinal Product (CTM/IMP) is delivered to patient in good quality condition.
All Direct-to-Patient models require that patient confidentiality and personal privacy be maintained according to applicable regulations such as HIPPA or GDPR.
Investigator Site Pharmacy Direct to Patient
This model is sometimes called Site to Patient (StP), and it entails making scheduled (planned) shipments of CTM/IMP from a study site pharmacy to a specific patient’s home to provide improved access. In this model, the courier is contracted to collect CTM/IMP from the investigator site and to deliver directly to the patient’s home or to a named responsible person, such as home care nurse or relative. Critical to the Site to Patient model is ensuring patient privacy throughout the process, including the physical delivery of study medication. This can only be accomplished with advanced process development and collaboration between all distribution stakeholders.
As these shipments must ensure drug integrity during transit to the patient’s home, the product temperature conditions must be preserved, and, when necessary, appropriate packaging supplies, including monitoring must be utilized. Though typically short transit distances are involved, procedures and agreements must be in place to ensure that the distribution of medication is handled properly and to confirm the CTM/IMP is delivered to the patient in good quality condition. Documentation may be required to verify chain of custody requirements were followed and/or that no temperature deviations occurred in transit.
The investigator or site pharmacist may be asked to ship across borders to patients, whether state lines within the US or across international borders. In the US, advance checks of relevant licensing requirements should be conducted to ensure compliance in both the state where medication is dispensed as well as in the state of receipt. For international shipping, applicable regulatory requirements around the dispensing of medication, including export and import, must be checked in advance.
An option within Site to Patient is to coordinate delivery with a visit from a home healthcare provider that will administer the medication. This option requires additional coordination effort to ensure CTM/IMP is shipped while a homecare nurse is present to receive delivery. This can help mitigate issues around privacy by naming the home healthcare provider as the authorized recipient. Additionally, the homecare service can be trained on the appropriate receiving process of all study medications to ensure chain of custody and temperature verification procedures are followed.
Central Pharmacy or Depot Direct to Patient
The same basic criteria noted above are required for shipping direct to patient from a central pharmacy or depot. Delegation of responsibilities from the investigator either to the sponsor or to the local pharmacy may also be required. Additional focus on shipping CTM/IMP across state or country borders should be considered in this model since the nature of centralization makes border crossing shipments more likely.
It is important to verify service capabilities of your suppliers relative to pharmacy dispense, cold chain distribution, distribution across borders as well as any needs for compounding or reconstituting medication prior to patient dosing.
The Clinical Trials Transformation Initiative (CTTI) recently published recommendations for Decentralized Trials 2, which addresses various aspects of decentralization including telemedicine and dispensing/distribution plans. In practice today there are multiple dispense/distribution strategies applied particularly within the US driven in part by varying interpretations of dispense licensing responsibilities.
Country-specific requirements should always be checked in advance as regulations differ and are especially subject to change in this evolving area. Your patient centric plan, such as direct to patient model(s) and health home care, should be mentioned in Clinical Trial Authorization applications.
Investigator Site Pharmacy, Central Pharmacy or Depot Distribution to Local Pharmacy (for patient pick up)
While not dispatched directly to a patient’s home, another patient centric option to reduce patient site visits is to distribute study medication through a local pharmacy. Direct-to-Patient through a local pharmacy entails making scheduled (planned) shipments of CTM/IMP from a study site or central pharmacy to a local pharmacy, where the study medication may be picked-up by the patient. Delegation of responsibilities from the investigator either to the sponsor or to the local pharmacy may also be required.
Most pharmacies within the European Union can dispense study medication. However, there must be a contract in place designating the pharmacy as an investigational dispensary.
Direct from patient
This model essentially, also known as “DfP”, closes the loop on the end-to-end supply chain for the patient. It involves materials that originate from patient homes. Specialty couriers can supply packaging, refrigerants (including dry ice) and temperature monitors, as needed, and pick up patient laboratory sample collections that are then shipped for testing.
Additionally, return medication for reconciliation and ultimately destruction, can be picked up and returned to site or depot as required. Home healthcare providers may be able to assist with some medication accountability processes prior to any returns. There may also be requirements to pick up temperature monitors or packaging used during prior deliveries.
All of the above models can also be conducted in conjunction with traditional or at-site dispensing of the CTM/IMP. Investigators and sponsors will need the ability to decide on whether medication can be shipped directly to the patient or will be required at site for an in-person visit on a case-by-case basis.
Patient centricity has become a focus in clinical trial design and remains a challenge. Direct to Patient distribution of study medication can reduce the number of site visits and improve the patient experience. This introductory blog identified several Direct-to-Patient models. Each Direct-to-Patient model requires the establishment of procedures and agreements among all parties to ensure that the CTM/IMP is delivered to patient in good quality. Prior to implementation regional regulations for the distribution of medication at both the recipients & dispatchers locations must be considered realizing that the study may require a hybrid approach to meet all local requirements. Additionally, the supply chain must be flexible enough to allow patient, investigator, and sponsor discretion to determine if/when in-person visits are required.