The Use of Direct-to-Patient Methods in Decentralised Clinical Trials in Israel

Abstract:

Direct-to-patient (DtP) methods in clinical trials have gained significant attention worldwide as they aim to improve patient access, engagement, and participation in research studies. This paper explores the status of DtP strategies in the context of clinical trials in Israel. It discusses the current landscape, challenges, benefits, and regulatory aspects of DtP initiatives in Israeli clinical research and the adapting of Decentralised Clinical Trials. By examining the Israeli experience, we can gain insights into the broader implications and potential for DtP models in global clinical trials.

Introduction:

Clinical trials are essential for advancing medical science and developing new treatments. However, patient recruitment and retention have long been significant challenges in the clinical research process. Direct-to-patient (DtP) approaches seek to address these issues by engaging patients directly in clinical trials, outside the traditional healthcare system. In Israel, a country known for its thriving healthcare and life sciences sector, the adoption of DtP strategies in clinical trials is of particular interest.

The Current Landscape of Clinical Trials in Israel:

Israel has an advanced public healthcare infrastructure with a robust clinical research ecosystem, numerous hospitals, research centres, key-opinion investigators and pharmaceutical companies actively conducting clinical trials. The diverse patient population in Israel makes it an attractive location for clinical research. However, despite these advantages, recruiting and retaining patients in trials remains challenging as in other places in the world.

Israel is a small geographical size country, which is very convenient for managing the required logistical operation of DtP shipments, especially for the delivery of time and temperature-sensitive products.

Direct-to-Patient – what is being done today in Israel?

• Decentralised trials, which minimise the need for patients to visit physical research sites, are becoming increasingly feasible. By offering convenience and flexibility, DtP approaches can increase patient engagement and adherence to study protocols.
• Mobile Health (mHealth) and Wearables: The widespread use of digital health by smartphones and wearable devices among Israelis presents opportunities for real-time data collection and patient engagement in clinical trials.
• Patient Advocacy Groups: Patient advocacy groups in Israel play a vital role in connecting patients with clinical trial opportunities and advocating for DtP approaches.

The Benefits of DtP approaches contributes to all stakeholders across the supply chain:

• Real-World Data Collection: DtP strategies allow for the collection of real-world data, which can complement traditional trial data and provide valuable insights.
• DtP methods can be provided together with home care treatments by professional personnel to improve patients’ recovery.
• Non-hospitalization reduces the number of infections, a big patient risk while under hospitalisation, saving excessive costs (hospital beds) and maintaining the continuity of the treatment.

Challenges and Considerations:

• Regulatory Hurdles: Adherence to Israeli and international regulatory standards remains a challenge for DtP clinical trials
  • • Israeli MoH approved DtP deliveries during the COVID 19 pandemic as an emergency solution for patients participating in clinical trials that that were unable or unwilling to visit medical centers. The DtP shipments could be performed either from the medical centre pharmacy or even directly from the clinical depot that released the product for use in the clinical trial. The responsibility in both options relies on the responsible pharmacists.
    • The current situation after COVID-19 includes DtP deliveries only from the clinical sites’ pharmacies in order to maintain the randomization process of each patient in a secured and accurate way. The technology progression may have solutions for this process which allows for future DtP shipments directly from the clinical depot. This reduces the risk of temperature excursions or other damage to the investigational product in transit.
    • Aside from COVID-19, emergency procedures during unfortunate times like the current war in Israel provide supply chain managers with more options to help patients, and there is a higher demand for creative solutions like DtP.
    • The Ethics Committee approval of each clinical study should include in the request form an approval to perform part of the treatment, including the delivery of products, to the patient’s home. After gaining the approval a contract needs to be signed between the parties (sponsor, medical centre & service provider) defining the responsibilities of each party and assuring the compliance to the study protocol to GCP/GDP requirements. As a note – the contract between the medical centre and the service provider for allowing IMPs to be sent to the patient home is not study specific and sets the foundation for other studies to enable DtP options in the future. This can be helpful as a mitigation plan in times like these and can also help sites retain patients. Specific sites can use this as a point of leverage over other sites.
• Maintaining Patient Privacy Throughout the Supply Chain: The shift of activity into patients’ homes also introduces new considerations around data privacy and patient confidentiality. The stakeholders need to determine how patient data will be captured, stored, and protected prior to study initiation. Means such as access limitations, digital platforms, etc. required to use to anonymize patient information while also providing traceability to patient ID are key considerations.
• Data Privacy and Security: Safeguarding patient data in DtP models is a critical concern that requires robust cybersecurity measures, but is a well discussed topic and not specific to Israel.
• The Israeli Ministry of Health: Israel’s regulatory framework for clinical trials is evolving to accommodate DtP approaches while ensuring patient safety.
• International Collaborations: Israel’s participation in international collaborations can facilitate the adoption of standardised DtP practices.

Conclusion:

Direct-to-patient approaches are gaining traction within clinical trials in Israel, driven by advancements in technology and a growing recognition of their potential benefits. However, challenges related to regulation, data security, and equity must be addressed to maximise the effectiveness of these approaches. As Israel continues to adapt and innovate in the field of clinical research, its experiences can serve as a valuable case study for the broader global research community.

Neta Bendelac, Senior Client Director, 4G Clinical
	Neta is a seasoned professional in the field of clinical supply chain and Interactive Response Technology (IRT) management. Currently serving as a key contributor at 4G Clinical, Neta brings over a decade of invaluable experience to the pharmaceutical industry. Prior to her role at 4G Clinical, Neta held a pivotal position as the Head of the Clinical Supply Chain team at Teva Pharmaceuticals. In this role, she demonstrated exceptional leadership and expertise in managing complex clinical supply chains, contributing significantly to the success of critical pharmaceutical projects. Neta’s journey in the pharmaceutical sector began after a successful stint as a consultant in supply chain areas. Armed with a wealth of knowledge and insights gained through consulting, she seamlessly transitioned into the dynamic and challenging landscape of clinical supply chain management. Neta holds an M.Sc. in Business Management from Tel Aviv University, Tel Aviv, Israel and a B.Sc. in Industrial Engineering from Ben Gurion University Beer Sheva, Israel.
Limor Teomim, MSC, CEO of IMP
	Limor has over 25 years of experience in the pharmaceutical and cannabis industries. At the establishment of IMP, Limor joined the team and has been an integral part of the company structure. She has taken a lead part in building the company culture, quality management, and systems. As CEO, Limor is leading the strategic and operational growth of the company to become a significant service provider for clinical studies sponsors. Limor brings her experience in both manufacturing and development of commercial and Investigational Medicinal Products, quality management systems, cGMP, GDP and local regulations to develop IMP into a top-quality leader in the field. Certified by both the American and Israeli quality societies as a Certified Manager of Quality (CMQ), she has served as a Quality Director of IMP and as VP Quality of Bioforum Group. Prior to that, Limor held positions as Quality Manager for LycoRed Bio and Nesher Solutions and as a member of the Quality Assurance team at RAFA. Limor holds an M.Sc. Pharm in Pharmaceutical Chemistry and a B.Sc. in Chemistry from The Hebrew University of Jerusalem, Israel.