The importance of ethics and patient centricity in managed and early access programmes
Matt Fellows explores how early and managed access schemes are mutually beneficial to sponsors and patients alike, as well as how to ensure they can be as effective as possible in a rapidly changing world.
Despite the best efforts and intentions of clinical researchers, commercial teams, patient advocacy groups and other key players, the needs of patients often outpaces the progress of clinical drug development. Early and managed access programmes can provide a unique and invaluable pathway for patients with serious or even life-threatening conditions to access innovative treatments which have not yet navigated regulatory systems and secured approval.
Patients relying on these programmes commonly have no other available treatment options available to them, or cannot gain access or are not eligible to trial a developing therapy in clinical studies, despite an urgent need. It could also be the case that, even when a treatment is available, the benefit/risk profile of a therapy on offer through an early or managed access programme would offer greater benefit to a patient in need than with their current therapy.
These programmes can take several forms and under a number of different monikers. They can originate from pharmaceutical firms that offer their investigational therapies to patients pre-approval in a compassionate use programme (often under the firm’s own specified criteria), or through regulatory agencies that authorise access to unapproved treatments on a case-by-case basis, with an example being the Early Access to Medicines Scheme (EAMS) offered by the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK.
However, while early and managed access programmes offer the key benefit of providing crucial treatment to those who cannot otherwise access it, patients are not the only ones who stand to benefit. The advantages of these programmes are a mutual, two-way street, and to their sponsors, they provide an invaluable means to harvest real-world data on a therapy early in its development cycle, while at the same time providing access to patients in need. These data can then be leveraged to help reinforce the case for marketing approval or help influence reimbursement decisions with watchdogs and regulators.
This is particularly significant in the case of rare diseases, where it may be difficult to build a comprehensive safety and efficacy profile for a therapy because the intrinsic rare nature of the condition means that it is very difficult to enrol enough patients in order to generate sufficient clinical data, thereby complicating its route to clearing regulatory hurdles.
Sheela Upadhyaya, Highly Specialised Technology Specialist at NICE, spoke to Pharmafocus to discuss the benefits that early and managed access programmes can provide for both drug developers and patients, particularly in the realm of rare disease.
“In my view, early access to therapy, pre-launch and pre-licence, can offer benefits for all stakeholders,” she explained. “For patients, access to therapy can slow disease progression and manage symptoms, and, in rare diseases, provide treatment and hope where there has not been anything available that is better than best supportive care. Rare diseases have many challenging features and securing reimbursement of new therapies is just one of many; the lack of knowledge, evidence and natural history of disease progression can become a barrier to securing access. Early and managed access programmes can go some way to reducing the uncertainty gap and providing treatments for those that need it most.”
On this note, Pharmafocus also reached out to Haseeb Ahmad, Global Head of Value & Access and Commercial Development at Novartis and Country President of Novartis UK, to get the pharma giant’s perspective on the utility of these programmes. He agreed that while they can prove to be a unique and valuable tool in generating data pre-approval, it’s important to remember that they can never be a substitute for the traditional clinical trial, especially in light of the current global climate.
“We believe that while early and managed access programmes are necessary in this context, they do not replace the robustness of a clinical trial to enable the systematic collection of information on an investigational medicine,” Ahmad explained. “It is crucial that such clinical research is prioritised now and beyond the COVID-19 pandemic. Clinical trials are fundamental to the development of new medicines and help to enhance the quality of, or even prolong life, while progressing scientific understanding and enabling earlier access to new, innovative medicines.”
Putting the patient first
While early and managed access programmes do indeed provide incentives on both sides, their utility at their core hinges on the patient – without that key element, the effectiveness of the system for all stakeholders collapses. It is crucial, therefore, to ensure that all such programmes have the patient at their heart, and that patient centricity is baked into their design. Upadhyaya explained why this is such an essential consideration:
“In order to ensure patients are at the heart of the process, it’s important to ensure they are helping and supporting the design and implementation of an early or managed access programme,” she said. “Without this input, programmes can be difficult to operate and deliver as they may have been designed in a way that makes the treatment inaccessible or difficult to administer.
“The objective of the programme can be unclear, and how to manage long-term expectations of a product can also be better understood and managed if patients are involved,” she continued. “Patient centricity is important because programmes in this space need to be fit for purpose, and be easy to be taken up by patients. The outcome of lack of patient centricity could result in a lack of uptake of these programmes by patients, which could result in a lack of data showing efficacy, therefore creating a potential issue for reimbursement decisions in the future.
“Creative and innovative ways to deliver the treatment should be taken into account, such as home delivery of medicines, and [ways to] capture the data – for example, using wearable technologies – will support the increase the engagement of patients.”
Ahmad agrees, and explains how Novartis is already leveraging some of these methodologies to ensure the patient remains front and centre in its clinical research.
“The power of data and digital can be harnessed here in order to transform clinical research. Digital technologies are enabling a new approach to administering clinical trials that could be faster, safer, and could allow a much broader patient participation,” he remarked. “We have partnered closely with NHS trusts and healthcare professionals to enable home delivery of study drugs and to conduct simple clinical study assessments in patients’ homes, thus enabling patients to remain on their trials. This commitment to research has led to the development of a much more patient-centric philosophy, which is a model we aim to continue implementing in future clinical trials.”
Upadhyaya also put forward another key strategy in this regard: “It’s also important that there is as much publicity about the opportunity to engage in these programmes as possible to ensure all have an opportunity to participate, particularly taking into account BAME communities who can often be affected but not engage as well. Working with relevant patient groups and other umbrella organisations that have relationships with patients can be beneficial in ensuring all relevant people are made aware of the existence of the programme.”
Inequities in the way these programmes are handled may exist across different regions too, which is at odds with the philosophy of fairness and equal access that should form the foundation of a patient-centric approach. Peter Martin, Head of Medical, Oncology, UK & Ireland at Merck KGaA, explained to Pharmafocus how collaboration and transparency are key in overcoming this problem:
“Much like the implementation of funding decisions, it is imperative that there isn’t a ‘postcode lottery’ when it comes to patient access to early access programmes. There will always be different local practices across the UK, but all patients should have equal access. To ensure this, we always ensure that we work quickly and collaboratively with every trust that shows interest. This may be supported with additional information to ensure the access programme can go through the local ethical or therapeutic considerations, or helping to ensure timely delivery of stock. We also make sure that there is information provided as part of an access programme that supports the patient to make the decision about whether the treatment is right for them.”
On the topic of ethical considerations, it is important to note that a sponsor must, in the spirit of equity, tread carefully when collaborating on these programmes with patients who may be vulnerable, terminally ill, unable to consent, or may require other special attentions. Just like patient centricity, this must factor into a programme’s design for the ground up in order for it to be properly successful.
“Ensuring that a treatment is right for a patient is the major ethical consideration when starting an early access programme,” explained Martin. “The MHRA’s EAMS is a great example of ensuring an early access programme is ethical: the company needs to prove to the MHRA that, first, there is an unmet need, and then that the risk/benefit profile supports the use of the treatment in this setting. We then reactively work with the clinical community so that they understand this risk/benefit profile and can select appropriate patients to discuss this with.”
Upadhyaya, meanwhile, gave her thoughts on the most important things to consider from an ethical standpoint when designing and executing an early or managed access programme, especially when it comes to rare diseases:
“From my perspective,” she said, “it’s important to understand:
– Consent issues: how can the system ensure that patients receiving a therapy in an early access to medicines scenario can consent objectively? Especially if they are in a terminally ill situation
– Would patients do whatever it takes to get on the programme? For example, stop taking other therapies to ensure they meet the eligibility criteria?
– The risk of potential of exploitation of patients who are desperate and terminally ill and could be used as easy research subjects
– Parents making decisions on behalf of their children, and how there needs to be a way of ensuring these decisions are made autonomously and objectively, keeping the child’s best interest at heart
“With rare diseases, patients and families are desperate for a treatment and are in a lot of cases more willing to take bigger risks,” she continued. “However, this may result in the potential harms or adverse effects being underreported by them in order to maintain access to treatment.
“In addition, if there is another experimental drug for their condition available, they may wish to change trials in the middle to get access to something else. This can cause issues for data collection and completion. Ethically, what mechanisms are in place to stop that from happening, and can the company compel people to stay on their trial? What responsibility do individuals have to the trial they are in, and to the populations within that trial to complete it before moving onto another?
“The COVID-19 landscape is uncertain and it would be, in my opinion, difficult to implement these without all of the checks and balances needed to ensure patients are kept safe and secure when participating in such programmes,” she added.
So where does this all fit in a world that has changed radically, both socially and politically, from just a few years ago? The COVID-19 pandemic has changed the rules of the game across the board, especially for the life sciences industry, healthcare and patients around the world, while in the UK the disruptive force of Brexit also looms. But it may be more beneficial to see the current situation as an opportunity rather than a challenge, as Martin explains:
“In the UK post-Brexit, there is an opportunity for the UK to allow access to medicines quicker than the current standard timelines, and the EAMS offers a way for the MHRA to review and allow access to medicines within an expedited timeline. The UK needs to get this right to ensure patients benefit from innovation as quickly and safely as possible.”
Ahmad agrees, stressing that collaboration will be the guiding light in these strange times: “We believe that, in order to maximise the UK’s strengths in innovation and clinical research, we must continue to work together with government, NHS England, industry and wider healthcare stakeholders to ensure trials can be set up quickly, efficiently and with increased patient recruitment, for the UK to continue to remain competitive as a global hub for life sciences now and beyond the COVID-19 pandemic.”