Streamlining post-trial treatment access for rare disease patients
Rare diseases are finally being seen as an issue of public health. The 78th World Health Assembly (WHA) adopted the milestone Resolution on Rare Diseases in May of this year, recognising rare diseases as a health priority and raising awareness of the scale of impact that these diseases have on patient lives.
With over 10,000 known rare and genetic diseases and this number growing annually and 350+ million people living with rare disease, the need for rare disease-focused clinical trials is becoming increasingly urgent. Fewer than 1,000 diseases benefit from even minimal amounts of scientific knowledge, according to the European Parliament. Increasing the number of trials is essential for addressing the unmet needs of small patient populations with limited treatment options.
Life sciences is one of the eight priority sectors under the UK’s new industrial strategy and 10-Year Health Plan, showing promise for the growth of the global healthcare and life sciences sector. However, the greater challenge often arises once a clinical trial concludes. While many patients may benefit from the treatment, there can be significant delays – sometimes months – before the treatment becomes available in their region.
For rare conditions, some treatments may never be licensed or may remain unaffordable due to regional regulations and restrictions. The reality is that some patients on the active arm of a clinical trial may still be mid-treatment when data collection ends. Withdrawing the treatment at that point – especially if it has proven effective in the eyes of the patient's physician – is generally considered unethical. Similarly, patients under any placebo arm may become eligible for the active product once the trial concludes, even though they did not previously receive the treatment.
For that reason, it’s widely agreed that companies have a practical and ethical responsibility to consider these patients when planning for a clinical trial and develop a strategy for their continued treatment.
Challenging the status quo - OLEs
When a clinical trial ends, ensuring continued access to the study drug for participants is a critical issue. Historically, companies have addressed this by planning for Open Label Extension (OLE) studies: follow-up trials in which all participants continue receiving the study drug to gather long-term safety and efficacy data. While OLEs have traditionally provided a way to extend access to promising treatments, they can become costly and inefficient if they need to remain open indefinitely to treat only a small number of participants. They may also be producing data the pharmaceutical company no longer needs once the trial is over and take up valuable resources to continue.
As clinical trials are increasingly conducted in low- and middle-income countries (LMICs) due to lower costs – up to 40-60% less than in high-income countries – OLEs can present additional logistical challenges. To avoid leaving patients behind, pharmaceutical companies must explore more sustainable methods for continued access, ensuring that no patient, whether currently benefitting from the study drug or potentially able to benefit in the future, is left without treatment.
What is post-trial access?
Post-trial access (PTA) is a mechanism that provides continued access to an investigational medicine to those who benefitted from the drug during the trial. This is particularly valuable to rare disease patients, with fewer treatment options.
Without proactive planning for PTA, the service can be limited. There are often siloes between healthcare providers and research partners that can cause delays in care. Cost and regulatory barriers can also cause poorly planned PTA to be delayed or impossible. While the Declaration of Helsinki introduced PTA as a required ethical consideration in 1964, it is still only mandatory in five countries globally.
There has, however, been a significant increase in demand from pharma and biotech companies for support in implementing PTA programmes in line with an increase in trial participants. Last year in England alone, over one million people participated in research supported by the NIHR Clinical Research Network – an 11% increase from the previous year. With this volume increase, it’s becoming less realistic to offer OLEs and providers need to question the status quo.
That said, PTA is still not as standardised as it should be. Pharmaceutical companies need to see what options for post-trial success are available to them; it’s critical that regulatory bodies around the world promote the accessibility of PTA, and that advice and guidance is available where needed.
A patient-benefit analysis
Beyond direct patient benefits, there are broader healthcare benefits to be realised by PTAs. Healthcare providers lean on data and previous drug use cases to prescribe medicines; if a patient has been selected for a clinical trial, their trial data may be useful for clinicians exploring options for their own patients. This controlled trial data is critical. However, once the patient is taking the drug through a PTA, this becomes data sourced outside of a trial environment and can add colour to the potential benefits and side effects of the treatment in the real-world environment.
It should be noted that PTA is very different from post-trial care. PTA refers solely to the provision of the treatment, whereas post-trial care is much broader and relates to supportive care, tests and monitoring, in-patient stays, and other care protocols associated with the usage of the medicine. It's crucial to distinguish between providing PTA and addressing the full scope of post-trial care. PTA is relatively straightforward, whereas ensuring comprehensive post-trial care involves more complex and extensive provisions, making it important for pharmaceutical companies to engage.
Looking ahead to more PTA programmes
Proactive planning for PTA is essential to ensure patients – especially those with rare diseases – continue to receive potentially life-saving treatments once clinical trials end. For patients with rare diseases, who often have limited treatment options, continuity of care post-trial is even more critical. It is the responsibility of legislators to create a regulatory environment that supports advancements like PTA, while pharmaceutical companies must challenge the status quo.
By addressing regulatory barriers, cost issues, and logistical challenges, we can create a more seamless transition from trial to continued care. Establishing a global definition and consistent practical guidelines for PTA will help ensure equitable access to treatments worldwide.
About the author
Suzanne Aitken is senior vice president, managed access, at Clinigen. She has more than 20 years industry experience, joining Clinigen in January 2013. Since then, Aitken has been intricately involved in managed access programmes; first setting up and running on behalf of clients and, since 2015, leading the growing Program Management function and now Business Unit and with oversight and governance responsibility across the Clinigen MAP portfolio. Prior to joining Clinigen, Aitken worked client side in large pharma R&D within a range of technical, leadership, and project management roles. She has a PhD in Chemistry.
