Navigating EAPs: Clinical trials and the path to investigational drugs

Medical breakthroughs have always been milestones lighting our path to better health. Clinical trials, pivotal in their nature, act as diligent sentinels, ensuring that potential treatments undergo precise scrutiny, honing, and eventual endorsement. However, amidst this stringent process, a segment of patients finds themselves waiting in the wings.

These are the patients grappling with severe or life-threatening conditions, for whom time is a luxury they can't afford. They are the ones who, due to stringent eligibility criteria or geographical limitations, find themselves locked out of the very trials that hold the key to their survival.¹ Here is where the heart of Expanded Access Programmes (EAPs) beats the strongest.

EAPs, often referred to as "compassionate use" initiatives, shine a light of hope for these brave souls. These programmes are a beacon, offering routes to explore investigational drugs outside the typical confines of clinical trials.² They stand as lifelines for those who have journeyed through every available treatment avenue without success. With vigilant oversight from the FDA, these programmes ensure that the projected benefits for the patient surpass any potential risks.³

This vigilant care ensures EAPs remain robust, serving as an authentic pillar of support for patients. However, for us to appreciate the full spectrum of what EAPs bring to the table, it's essential to explore their benefits for not just patients, but also researchers and pharmaceutical organisations.

EAPs in rare disease clinical trials

The role of EAPs in clinical trials is multifaceted. EAPs offer patients hope and a chance to improve their quality of life or extend their survival. They provide an alternative when all other doors seem to have closed.⁴ This is particularly significant for patients with rare diseases, who often have limited treatment options and may not be able to participate in clinical trials. 

For researchers, data gathered from EAPs can supplement clinical trial data, providing additional insights into a drug's safety and efficacy.⁵ This can be particularly valuable in understanding the long-term effects of a drug or its impact on a specific subset of patients. It also provides an opportunity to observe the drug's performance in a real-world setting, outside the controlled environment of a clinical trial. This real-world data can be instrumental in shaping future research and refining the drug development process.

Pharmaceutical companies, too, stand to benefit. EAPs can help foster relationships with physicians and patients, potentially boosting the uptake of the drug once it's approved,⁶ thereby helping companies solve problems at scale. But it's crucial to remember that EAPs are not a substitute for clinical trials. They are a parallel pathway designed to provide access to investigational drugs for patients who cannot participate in clinical trials.⁷

The challenges of EAPs

Despite the promise, the journey of EAPs isn't without its challenges. Critics argue that EAPs may undermine the clinical trial process by offering an alternative route to investigational drugs. There are also concerns about equity. Do EAPs inadvertently favour patients with resources and connections over those without?⁸ 

Moreover, there are logistical and financial challenges to consider. Obtaining an investigational drug through an EAP can be complex and time-consuming, requiring coordination between the patient, physician, pharmaceutical company, and FDA.⁹ This can be a significant barrier for patients who are already dealing with a severe illness.

Financially, while the FDA prohibits companies from profiting from an investigational drug provided through an EAP, the company can charge the patient for the cost of manufacturing the drug.² This can make access to these drugs prohibitively expensive for some patients, particularly those without insurance coverage for investigational drugs.

There's also the challenge of limited supply. Pharmaceutical companies often have a limited supply of an investigational drug, which may not be sufficient to meet the demand from both clinical trials and EAPs.⁴ This raises difficult questions about how to allocate scarce resources.

Finally, there's the ethical challenge of balancing hope with realism. While EAPs offer hope to patients with severe or life-threatening conditions, it's important to remember that investigational drugs are, by definition, unproven. They may not work as hoped and may have unforeseen side effects.⁵ Patients seeking access to these drugs must be fully informed of the risks and uncertainties involved.

Mitigating the challenges, providing solutions

Addressing the challenges raised by compassionate use programmes requires a multifaceted approach. Firstly, to address concerns about undermining the clinical trial process, it is vital to establish clear guidelines and criteria for the use of EAPs. These guidelines should ensure that EAPs are only considered as a last resort when all other treatment options have been exhausted and that they do not compromise the integrity of ongoing clinical trials. By promoting open communication and reinforcing collaborative efforts among regulatory bodies, pharmaceutical leaders, and committed healthcare professionals, we can pave a clear and purpose-driven path forward. 

To tackle the issue of equity, steps should be taken to improve accessibility to EAPs for patients without resources or connections. One solution is to establish a centralised and streamlined process for EAP applications, reducing the burden on patients and healthcare providers. Additionally, efforts should be made to increase transparency and public awareness about the availability of EAPs, ensuring that patients from all backgrounds have equal opportunities to benefit from these programmes. Furthermore, introducing financial assistance initiatives can act as a bridge, bringing investigational drugs within reach for those who would otherwise find them elusive due to financial constraints.

To address the logistical and supply challenges, collaborations between pharmaceutical companies can be fostered to share resources and increase the production of investigational drugs. This strategic approach not only addresses supply limitations, but also assures that both clinical trials and EAPs have a consistent flow of vital medications. Moreover, by crafting a symbiotic relationship between regulatory agencies and pharmaceutical entities, we can streamline the process of sourcing and distributing investigational drugs via EAPs, making the journey more efficient and less cumbersome for patients seeking these treatments.

Lastly, addressing the ethical challenge of balancing hope with realism requires robust patient education and informed consent processes. Patients should be provided with comprehensive information about investigational drugs' benefits, risks, and uncertainties. This includes clear explanations of the potential efficacy and side effects, as well as the experimental nature of the treatment. This will enable patients to make well-informed decisions about participating in EAPs, ensuring they have realistic expectations and are fully aware of the possible outcomes.

EAPs: A lifeline for patients in need

By implementing these solutions, we can mitigate the challenges associated with compassionate use programmes, promoting equitable access to investigational drugs, streamlining the process for patients, addressing supply constraints, and maintaining ethical standards in providing hope to patients in need. These measures can help ensure EAPs are used as intended - as a lifeline for patients in need, rather than a loophole in the clinical trial process.

EAPs, at their core, illuminate the crossroads of science and compassion. In every pill, procedure, or protocol lies not just research, but a profound pledge to humanity. As we address the complexities inherent to EAPs, we must strive for a framework rooted in equity, transparency, and shared value, so we can successfully bridge the gap between the rigorous scientific processes and the human need for hope.