By taking a more strategic approach to PASS, you can secure long-term market access, gain regulatory trust, and provide critical insights that support our understanding of rare diseases and the wider impact of these treatments.
Here, Sciensus experts, Dr. Raymond A. Huml, MS, DVM, RAC and Mathieu Loiseau, explore how PASS can be a powerful tool in rare disease management and a key driver of success for companies targeting this complex and highly regulated area of medicine.
What is PASS? Understanding regulatory obligations and strategic benefits
Post-authorisation safety studies (PASS) are often mandated by regulatory bodies such as the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) to monitor the long-term safety of therapies after they have been approved for market use.
While their primary role is to ensure patient safety, especially in the case of new or high-risk treatments, the strategic benefits of PASS extend far beyond regulatory compliance.
For rare disease therapies, PASS provides critical real-world data (RWD) on long-term safety, but also on efficacy and treatment durability. This evidence is invaluable for meeting regulatory requirements and also shaping your future development strategies, building relationships with regulatory bodies, and securing extended market access.
Unlike more prevalent disease areas, where we can gather substantial safety data in clinical trials, there are often limitations with rare diseases in terms of the size of patient populations and the availability of long-term data. PASS helps fill these gaps, offering a way to gather real-world evidence over a longer period of time. This totality of evidence can be essential for payers and healthcare systems, as well as regulatory bodies.
The critical role of PASS in rare diseases
There are of course many unique challenges to overcome in both the clinical and commercial sides of developing rare disease therapies.
With small patient populations, limited data, and a lack of long-term safety information, the post-approval phase can be a critical time for ensuring patient safety and demonstrating ongoing treatment value. It’s no exaggeration to say that each and every piece of data we can collect on the safety and efficacy of a rare disease therapy is gold dust.
For regulators, monitoring the long-term safety of rare disease treatments is particularly crucial. With cell and gene therapies, for example, which have the potential to permanently alter a patient’s DNA, it’s essential we understand the long-term impact.
Smaller clinical trials, with limited demographics, mean that unforeseen safety issues over time are more of a risk with orphan drugs and rare disease treatments. While PASS enables the collection of valuable RWD that can demonstrate safety, we can also use it to understand durability and efficacy in real-world settings. This data helps regulators understand the therapy’s broader impact and gives them confidence that the treatment is safe and effective over time.
Of course, rare disease treatments are typically expensive so being able to prove their long-term value is essential.
Healthcare technology assessment (HTA) bodies are increasingly using post approval data in their assessment of the cost-effectiveness of new treatments. PASS can provide long-term data on patient outcomes, which is vital in influencing reimbursement decisions.
With outcome-based pricing models becoming more common in both the US and European Union (EU), PASS can serve as a strategic route to demonstrating long-term value, helping your rare disease therapy gain ongoing market access.
How PASS impacts market access and pricing for rare disease therapies
Pricing and reimbursement discussions for rare disease therapies are also full of obstacles. The high costs associated with developing treatments for small patient populations and limited long-term efficacy data can make it difficult to negotiate favourable reimbursement terms.
In these conversations, data from PASS can prove to be critical in giving payers confidence in the value of their investment. Real-world data collected through PASS can play a huge role in enhancing the value proposition of rare disease therapies by offering evidence of long-term safety, durability of treatment effects and insight into real-world patient outcomes.
HTA bodies are increasingly looking for real-world evidence to support their assessment of the value of therapies. By incorporating PASS data into these assessments, you can provide the depth of evidence needed to satisfy HTA requirements and negotiate satisfactory pricing and reimbursement terms.
PASS can also help pharma companies meet increasing demands for outcome-based pricing models. As healthcare systems in the US and EU shift toward pricing models that reward long-term efficacy and patient outcomes, PASS provides a structured framework through which you can collect the real-world data you need.
This is especially critical for rare diseases, where the high cost of medications often comes under scrutiny. With PASS, you can demonstrate the long-term value of your treatment, securing market access and sustainable pricing.
Designing and implementing a successful PASS
Designing a PASS for a rare disease therapy requires careful planning and consideration of several key factors, including study design, protocol development, ethics approval, patient recruitment and retention, data collection, analysis, and reporting.
The first and most obvious challenge you’ll have to overcome to successfully run a PASS in Europe is the highly complex makeup of the European market. It’s not for the faint-hearted, with 27 countries, multiple languages, and complex and varied healthcare systems and regulatory and ethics approaches to understand. Now, if the EMA mandates a PASS, the process can be a little simpler.
But countries outside of the EU, such as Norway and the UK, may still require a local variation of the study. For this reason, many companies turn to local partners to help them design their approach, navigate regulatory hurdles, and ensure they gain approval for their PASS across as many markets as needed.
Another fairly obvious challenge in designing a PASS for orphan drugs is the limited patient population. Small patient numbers can make it difficult to conduct large-scale observational studies and long follow-up periods across multiple geographies are often required to gather meaningful data. To address these challenges, prospective, longitudinal studies can work well as they allow for more flexible data collection over time.
However, we still need to find a way to ensure we can gather enough information to generate meaningful results over that time. This means we need to not only identify the patients but find ways to support and encourage them, their families, and their clinicians to participate for the long term. Key to this is making it as easy as possible for them to share the data and to feel like they are getting something back as a result.
Digital solutions for capturing patient-reported measures have become more popular for this precise reason. While they can make it easy to report data, they also provide an opportunity to include add-on services and leverage behavioural science to motivate and incentivise participants. This is especially true where these tools offer patients and their families a way to look back on the data submitted and see trends and changes for themselves. Additionally, employing healthcare professionals such as clinical study nurses provides an opportunity to include education and emotional support activities.
Sciensus offers a comprehensive PASS design and implementation service that includes regulatory support, patient engagement, and data optimisation. By combining regulatory grade digital tools with extensive expertise in patient engagement strategies, the company helps its partners enhance the quality and quantity of data they collect through PASS, ensuring that the studies meet both regulatory and commercial objectives.
Digital innovation and real-world data: The future of PASS in rare diseases
Rare disease treatment continues to evolve at a rapid pace and digital innovation is playing an increasingly significant role in the design and implementation of PASS.
The rise of cell and gene therapies, in particular, has created a demand for long term RWD to demonstrate the durability and economic value of these treatments. Thankfully, new and emerging technologies such as AI, digital patient engagement tools, and remote monitoring have given us more options than ever before to enhance the data we collect through PASS.
AI specifically is playing an increasingly important role in enhancing the effectiveness of PASS, particularly in the context of rare disease therapies. For example, we can use AI to automate the collection of real-time RWD from a wide range of sources including electronic health records (EHRs), wearable devices, and patient-reported outcomes (PROs). And, through predictive analytics, we can identify safety concerns earlier by analysing patterns in the data, supporting proactive intervention and improving patient safety.
Similarly, AI can help us analyse and understand when and why patients may drop out of a PASS so that we can develop personalised engagement strategies. Advances in behavioural science and homecare models are also helping to improve patient adherence and safety tracking, ensuring that PASS are more accurate and more representative of real-world patient behaviour. This is especially important in rare diseases, where long-term adherence to treatment can be a challenge.
The success of any study or treatment also hinges on our attention to the patient’s voice. Social listening tools are increasingly popular for researchers seeking to extract valuable insights from unstructured data sources such as clinical notes, social media, or patient forums. This can help us develop a deeper understanding of patient experiences and treatment impact, which is especially useful in rare disease cases where traditional datasets are often limited.
As the demands for real-world data increase, investing in PASS today can secure your long-term success. Partner with Sciensus to design a PASS that not only meets regulatory requirements but adds strategic value for your rare disease therapies.
