Virtual patient registries: Real-world evidence for cell and gene therapies

This article first appeared in Cell and Gene

In recent years, cell and gene therapies have been generating highly promising results in clinical studies, advancing them toward the market. However, the small number of products launched to date have not been proven commercial successes, with a number of advanced therapies being withdrawn from the EU market and limited sales of CAR-T therapies in the U.S.

One of the key challenges companies looking to commercialize face is the lack of substantial clinical evidence at launch. Although many new products, such as biologic drugs, face a similar challenge, cell and gene therapies are particularly affected, for several reasons. First, since most cell and gene pipeline products cater to the rare disease market, data sets from clinical trials are typically small. Second, longitudinal studies that prove continued efficacy and safety over a patient’s lifetime are not available, so the curative ability of the therapy cannot be conclusively proved. Finally, the strict constraints and detailed inclusion and exclusion criteria of randomized clinical trials can mean it’s hard to project trial results to patients in the real world with any confidence. These factors can lead to concerns about trial data, hindering regulatory and payer decision-making and leading to time-consuming negotiations and burdensome demands on cell and gene therapy companies.

In efforts to accelerate access to these medicines, regulators and payers may still approve cell and gene therapies despite limited evidence, under certain conditions. However, there are still considerable hurdles to a successful product launch. Small patient bases and high price tags can lead to underwhelming sales. Furthermore, companies should be aware of competitors following suit into a disease area, which could further erode uptake. Finding innovative methods to engage with patients and physicians to increase value and maximize patient access within narrow markets will be a key success factor.

Well-designed and high-performing patient registries are powerful tools that can strengthen the clinical case for a therapy and bolster patient engagement, helping companies to overcome the challenges facing novel therapies in the cell and gene space. Post-launch patient registries enable long-term, real-world data collection, helping stakeholders understand the course of the disease, variations in treatments and outcomes, patterns of care, safety profiles of therapies, cost-effectiveness, and more. Regulatory authorities, including the FDA and EMA (European Medicines Agency), can mandate post-authorization safety and efficacy studies and have actively supported patient registries in the past. Payers will often require registry data to understand the value of therapies in real-world settings, and registry establishment can reassure payers and support health technology assessments (HTAs), laying the basis for risk-sharing or managed access agreements.

However, registries are typically long-term and costly commitments from the sponsoring company and require significant efforts on the part of investigators and participants. Virtual registries, enabled by modern technologies that support patient data collection (e.g., wearables and mHealth devices), are emerging solutions whereby patients enter most of the data themselves. This addresses some of the implementation and participation problems faced by traditional registries, which are limited to specific sites and require investigators to manually enter data into electronic data capture systems that are prone to transcription errors. This shift in data entry to the patient can result in significant cost reduction. Also, by putting the patient at the center of the registry, examining outcomes that matter to patients, and making participation easier, virtual registries will enhance patient engagement.

This type of patient registry is still in its infancy. There are a small number of virtual registries set up for products outside the cell and gene therapy space, as well as tentative steps to implement a more patient-centric approach to registries for certain advanced therapies (e.g., Strimvelis’ registry). However, there is still potential for further innovation. Building a fully virtual patient registry will face many challenges, such as:

• Patient privacy: When designing the registry, careful consideration must be given to local and regional data privacy laws and regulations, for example to meet requirements of informed consent. If the data will be shared (e.g., with regulatory authorities), care must also be taken to ensure interoperability and data completeness while protecting privacy.
• Data quality: With patients in control of data entry, there is a heightened risk of inaccurate or incomplete data, diminishing the possibility of meaningful analysis. This is of particular concern if the registry is part of a regulatory commitment. To mitigate this risk, there are number of strategies that can be pursued, for example designing electronic case report forms with patients; using character recognition software to allow scans of lab results, medication etc.; using wearables; random sampling of data by physicians; and using automatic reminders to prompt data entry.
• Regulatory frameworks: Regulatory and ethical review frameworks are still evolving in this space; however, guidelines and statements are beginning to be published. It is vital to work closely with regulators and stay alert to any developments.
• Adverse event reporting: Capturing adverse reactions is a critical function of many registries. Normally, physicians play a key role in judging causality. In virtual registries, patients could capture data related to events such as hospital visits and significant medical events, and sophisticated algorithms could be developed to show patterns and assess temporal relationships. However, it is likely that physician input will still be needed, so this should be considered during registry design.

Despite these initial challenges, there will be long-term rewards in pursuing virtual registries solution and working with stakeholders to overcome the barriers. Virtual registries can be run at a fraction of the cost of traditional approaches that have been used in the cell and gene therapy space, while also improving engagement of participants and capturing patient-centric outcome data.