Off-label Usage within Medical Devices: Navigating Challenges and Opportunities
By Tonika Chester and Isabel Bradshaw
Collecting Off-Label data in Post Market Clinical Follow Up
In addition to confirming the safety and performance of a medical device throughout its expected lifetime, another purpose of PMCF is to identify possible systematic misuse or off-label use of a medical device. As a result, it is essential for medical device manufacturers to establish a clear approach for evaluating this data, but also consider if and how off-label data obtained from PMCF studies can be utilised to support the use of a medical device outside of its intended purpose and indications for use.
Understanding Off-label Usages
Although ‘off-label’ usages have not been defined within the Medical Device Regulation (MDR), they are widely understood to refer to the use of a medical device in a way that is not specifically approved by regulatory authorities. According to the Medicines and Healthcare products Regulatory Agency (MHRA):
“You should use medical devices as described by the manufacturer in the instructions. If you use the device in any other way, it is considered ‘off-label use’”
Off-label usages of medical devices can be acceptable in certain cases, particularly when there are no approved alternatives available. It is crucial to still collect clinical data from these off-label usages, which can be used to confirm the safety and performance of a medical device.
Off-label usages often occur when there is limited evidence for specific populations, such as paediatric patients or those with rare diseases, to tailor treatment for individual medical needs, or when treatment options have not been officially approved.
Challenges in Paediatric Populations and Rare Diseases
Using the paediatric population (birth to 18 years of age) and the treatment of rare diseases as examples, it becomes evident that there are significant barriers to gaining market approval or officially expanding the intended purpose or indications for use of a medical device:
Financial barriers include high research and development costs for extensive clinical trials, coupled with low return on investment from limited sales and market size, which reduce incentives for expanding intended use.
Regulatory barriers involve stringent requirements for evidence generation and challenges in collecting sufficient data, absence of on-label paediatric devices for comparison, and lengthy approval processes.
Social barriers may include limited awareness or acceptance of off-label uses among healthcare providers and patients.
Ethical considerations include the need for Institutional Review Board (IRB) approval and the complexities of enrolling young patients in clinical trials.
Key Considerations
Viable Treatment Options: Off-label usages can be a viable treatment option for specific patient populations, such as paediatric populations, due to the limited number of medical devices approved for use in this group.
Issues Related to ‘Sufficiency’: Clinical data is required to hold sufficient quantity and quality. While off-label data may be sufficient in ‘quantity’, it can be difficult to collect data that is sufficient in ‘quality’ to draw meaningful conclusions. A strong protocol and appropriate statistical analysis plan are steps to address this.
Steps for Expanding Intended Purpose: Medical device manufacturers must follow outlined steps to formally expand the intended purpose or indications of a medical device that has already been approved and are required to follow the same steps in pre-market clinical investigations. This includes conducting a clinical investigation, additional clinical trials and submitting sufficient data that can be leveraged to support a conformity assessment to regulatory bodies.
Reasons to Pursue Label Expansion: Pursuing label expansion can result in increased patient access, market expansion, enhanced patient safety, and if a device can be utilised for multiple indications or uses, it may be perceived as a valuable treatment option.
The Importance of Off-label Usages
Off-label usages of medical devices play a significant role in providing treatment options for specific patient populations, particularly in paediatric medicine and the treatment of rare diseases. While it offers essential benefits, it also presents challenges that require careful consideration and management. Continued research, improved regulatory frameworks, and enhanced communication between healthcare providers and patients are essential to optimise the safe and effective use of medical devices in an off-label way.
Purdie Pascoe’s Dedicated PMCF Survey Team
Our dedicated and expert team has extensive experience in implementing PMCF surveys that have been accepted by Notified Bodies. We work closely with our clients to gain a thorough understanding of the intended purposes and indications of their medical devices. With this insight, we design surveys that allow for the capturing and evaluation of off-label use, which can be used alongside a body of evidence for potentially expanding the medical device’s approved uses.