Eliminating the variables in decentralized clinical trials

The premise of the Direct-to-Patient (DtP) model is straightforward; investigational medicinal product (IMP) or drug is administered in the patient’s home. But the execution can be complex through unique challenges presented with the approach. To help better understand some of DtP’s unique challenges, we have compiled the top three areas that you will need to consider:

1. Regulatory requirements

Regulations governing home healthcare and DtP distribution vary worldwide. In some countries for instance, only physicians – not nurses – can draw blood from patients under 18 years of age in their home. In other countries, IV infusions cannot be given in the home. Conversely, more flexible regulations in some countries allow nurses to perform in-home virtually any procedure they are trained and capable of doing.

But what about the cultural component? In some countries, certain services such as infusions are not readily accepted in the home setting.

Strict rules also apply to the credentialing and documentation of nursing staff and, similarly, differ by country. While all nurses must, of course, meet local professional licensing requirements, do their individual names appear on the protocol application, or simply the name of the home nursing organization? Are nurses legally required to sign the delegation log, or are patient referrals by a physician adequate? Whose names should appear on the FDA 1572 Investigator’s Statement? What other conventions apply in other countries?

Also of crucial importance is that the intent to provide home-based treatments is detailed clearly in the protocol submission.

From a logistics perspective, regulatory requirements and import procedures related to IMP and other therapeutic product also vary widely from country to country and are subject to change.

Unique to DtP, however, is the fact that different countries have distinct regulations concerning drug dispensing for in-home use. Can a central pharmacy dispense? A site pharmacy? Or can they be collected directly from a licensed storage depot? Again, the answer will vary depending on the country in question. The recommendation is that appropriate descriptions of the DtP distribution strategy also be included in the protocol submission, typically with pre-approval from the Ministry of Health or other competent authority.

All of these regulatory considerations – shaped by the geographical realities of the study or commercial distribution – factor into the decision to adopt a DtP approach. As a relatively new model, it is conceivable that DtP may be subject to closer scrutiny by regulatory agencies than traditional clinical and commercial distribution models that have existed for decades.

2. Timing and temperature

It goes without saying that ‘on time’ and ‘in perfect condition’ are imperative. Consider the potential impact of failure should the product arrive late or out-of-spec. What if:

• The drug is no longer viable?
• The patient’s health suffers as a result?
• Drug replacement results in significant costs (high value or in short supply)?
• The nurse is scheduled for other patient visits?
• Treatments need to be rescheduled?
• Credibility is lost in the eyes of the patient or nurse?
• Patient and nurse frustration affects their interest in the program?
• A missed or delayed treatment disqualifies the patient or compromises the study results?

DtP demands that pick-ups and deliveries happen within a predetermined – and often extremely tight – timeframe and potentially over long distances. As with any pharmaceutical shipment, the integrity of the cold chain is incontrovertible. For DtP shipments, the impact of either a late delivery or a temperature excursion is immediate and critical.

3. Patient Confidentiality

Recognizing that patient confidentiality is the cornerstone of ethical healthcare, countries worldwide embrace and adhere to patient privacy laws similar to HIPAA or the EU’s General Data Protection Regulation (GDPR). Knowledge of all local patient privacy requirements and your partners’ ability to suitably support their adherence are of paramount importance within DtP. Adding to the challenge is the need to maintain patient anonymity during clinical trials and appropriately limit unnecessary outside access to information.

For those considering DtP, confidentiality is a very real and understandable concern. Operationally, however, it presents unique challenges. How do you assure accurate collaboration between the dispensing site and logistics provider – respecting patient confidentiality while delivering the correct medication to the correct patient – using only the common metrics of two anonymous ID numbers?

Or, on international shipments of patient samples, how do you accurately identify the ‘shipper’ on the commercial invoice while protecting patient confidentiality and adhering to customs regulations? The answers to these and similar questions will define and inform your DtP strategy.

All studies and therapeutic distribution programs are complicated, consisting of many moving parts. DtP adds another dimension as external partners take on many of the responsibilities traditionally assumed by clinicians. What should you look for as you attempt to integrate DtP into your study or commercial delivery system? How can you ensure you have an appropriate degree of control once the study rolls out? How will you know you have selected the right partners?