Bringing the clinical trial home

pharmafile | November 18, 2019 | Feature | Business Services, Manufacturing and Production, Medical Communications, Research and Development, Sales and Marketing |  clinical trials, feature, research 

Clinical trials are the backbone of healthcare and drug research, but many key patient populations have in the past been unable to take part in these trials because of their traditional format. Fortunately, technology has risen to the challenges of modern research and provided a solution, as Matt Fellows discovers.

Even with the emergence of increasingly inventive and resourceful strategies and remarkable technologies that bring new and more streamlined methods for conducting studies and harvesting data, the humble clinical trial remains the gold standard and the most precious and coveted tool in the clinical research arsenal.  

However, for all its enduring utility, the clinical trial is only as robust and only as useful as its design and execution allows – “Garbage in, garbage out,” as the old computer science saying goes. If a study only focuses myopically on a non-representative patient population or its methodology mishandles its findings, the resulting data and its clinical value is compromised.

This can cause a raft of issues including duplication of effort and resources by other clinical studies as they try to ascertain what should have been clear in the original study, delays in regulatory approval due to insufficient data – meaning patients in need are denied access to therapies until more robust data can be resubmitted and reviewed – and in extreme cases ineffective or even dangerous drugs that could pose a threat to public health. 

One of the biggest obstacles in this regard, and one that is frequently cited in reviews and meta-analyses of conducted clinical trials, is that of patient recruitment. When the safety and efficacy of a drug is wholly dependent upon the research collected from the patients it is tested on, this becomes a critical issue. If certain populations or demographics are underrepresented or omitted entirely, how are we to know whether these treatments will affect those patients in a safe and effective way? And without these data, how are drug developers to convince global regulators to green light their products for the general public – a much more diverse and infinitely larger group than could ever be screened in a clinical trial?

Recruitment has long been lamented as a persistent and key challenge that can often make or break the validity or even basic functionality of a research trial. In reference to a study by Sully BG et al, a research paper authored by Karin Sygna, Safora Johansen & Cornelia M Ruland and titled ‘Recruitment challenges in clinical research including cancer patients and caregivers’ noted: “In many clinical studies, especially studies that include seriously ill patients, the recruitment process is described as challenging and time consuming. Sully and colleagues found that only 55% of trials recruited their originally specified target sample size, 78% of the trials recruited 80% of the original target, and almost one third of trials received an extension of some kind.”

Obstacles like this compound the biggest challenge in clinical trials: cost. According to data from the US Department of Health and Human Services, the cost of a clinical trial, running through Phase 1 to 4, can range from $44 million to a massive $115.3 million. On top of these dizzying sums, delays to a clinical trial launch as the result of insufficient patient recruitment can cost firms anywhere from $600,000 to $8 million per day, according to research conducted by CenterWatch.

Areas of concern

These problems are particularly notable in studies of dementia and similarly debilitating conditions which prohibit patients from travelling extensively to trial sites.

As Alzheimer’s Research UK put it in its paper ‘Getting people involved in dementia research policy statement’, a significant barrier to lack of involvement in clinical trials focused on these conditions “is the constraints inherent in the cognitive and physical impairments caused by dementia. The enrolment and trial processes can be confusing for people with dementia, and this may inadvertently deter individuals from continuing their involvement with research. Many trials require a person with dementia to have a ‘study partner’ who can assist with transportation to trials, providing medication and monitoring an enrolled patient’s condition. This requirement may exclude some people with dementia from enrolling in trials, particularly in those cases where a carer or family member is not capable of committing such support due to other obligations.”

In the UK, these issues are represented in the statistics available on the numbers of patients recruited into dementia studies. As the Alzheimer’s Research UK paper relays, over 24,000 dementia patients were recruited into studies organised by the National Institute of Health Research (NIHR) over 2015 and 2016, which represents 5.3% of the total of more than 451,000 people in the UK with a formal diagnosis of the condition.

Compare this to cancer, where one in five patients are enrolled in clinical studies, and it puts into perspective the challenges of recruitment in conditions like dementia, and by extension our failure to adequately address them.

Perhaps even more glaringly, this also falls short of the targets laid out in the ‘Prime Minister’s challenge on dementia 2020’, which aimed to have 10% of diagnosed dementia patients in the UK taking part in clinical trials. 

More than anything else, of course, this represents a failure on behalf of these affected patients, and this isn’t a problem specific to a small fringe group – as we continue to deal with the side-effects of an ever-ageing population, the condition will only increase in prevalence and affect even more lives, making it an imperative for wider society. If current forecasts on the increasing prevalence of the condition come to pass, over 43,000 additional patients would need to be enrolled in studies by next year if the Government was to meet its proposed target – almost double the number enrolled at the time it set that goal.

A virtual solution

Taking into account Alzheimer’s Research UK’s comments on the challenges of recruitment in dementia, it isn’t difficult to see why enrolment in clinical trials of this disease area is so low. This lays bare the shortcomings of the gold standard clinical study, such as its tendency to be executed at a fixed site or sites which do not always take into account the vulnerability or independence of the patient population it seeks to evaluate. But there is a solution to this: the virtual trial.

While most clinical trials are held at clinics or research institutions in static, often urban areas, virtual trials can collect data from patients pretty much anywhere, including their own home, through smartphone apps, wearable technology or online correspondence. This opens the door to a huge number of patients who otherwise cannot participate through the traditional route, thereby engaging with this otherwise underserved population and improving trial diversity.

Dementia as a therapeutic area is a prime example to illustrate where these problems lie and where virtual trials can bring benefit, but these recruitment challenges exist elsewhere in other therapeutic areas. While cancer sees much greater engagement from patients in terms of clinical trials compared to conditions like dementia, these obstacles are still very valid.

To learn more about how these concerns can impact clinical trial design approaches and how virtual trials can help, Pharmafocus spoke to Jenny Royle, Patient-Centricity Senior Program Leader, digitalECMT at the Cancer Research UK Manchester Institute. Off the bat, she asked:  

“The first thing fundamentally is the question of: what is stopping effective clinical trials today? What is stopping people participating? That itself is a key challenge: getting people in the front door and getting people to stay in the trial. The first consideration is eligibility, and when it comes to diversity, eligibility is key. We have the ability, with the bigger datasets that are coming along, to actually start to change things and make a trial far more adaptive and far more suitable.

“Then there’s motivators and facilitators: what motivates people to take part and how can we make sure that they are respected and encouraged in a data-driven way? And then you have people’s barriers to taking part, and virtual clinical trials remove one of those barriers: the geographical barriers. But there are lots of other barriers to taking part, such as perception, the number of assessments, the phraseology around it, the perceived benefit people get from these things.”

Removing this geographic factor from the equation is a huge boost when it comes to widening the potential pool from which trial participants can be drawn, facilitating, potentially, a more robust platform from which to develop effective drugs. But it can also provide patients with greater flexibility in their care. 

Royle expanded on the benefits that a virtual approach can bring to the table for both researchers and patients: “It can be an affordable, patient-centric way of delivering a trial, because people don’t have to leave their own home that much or travel as far. That means that it keeps people far more in their own environment, which is not only a physical environment – it’s their own social support network.

“It also supports personalised medicine far more. For example, in cancer, if your tumour has a particular genetic change in it, and you live in Dundee, the best trial for you might be in Bristol, so if the trial is mostly virtual – so you only have to go down for your scans twice during that time – it’s achievable to be in the best one specifically for you. But if you have to go down every week, you haven’t got that option.”

Knowing the limits

But, just like the traditional clinical trial, which remains an enduring mainstay of medical research, the virtual trial’s strengths are tempered by some striking shortcomings, as Royle explains:

“The first shortfall is that not all tests can be done virtually. Even if you make seven out of eight trials virtual, if patients still have to be pulled in fairly frequently for the eighth, that is actually of very little benefit to them,” she remarked.  “Another downside is engagement and communication: there are some patients that actually get a lot of reassurance from speaking to an oncologist or a research nurse. If it’s pushed 100% virtual there is no option of having such a strong face-to-face connection that is physically present.

“Another one is that a lot of the virtual trial processes actually rely on technology, and that brings in the whole ethical question: if you have a technophobe and you’re trying to get them set up 100% virtually with nobody there to support them, are you excluding a particular population?

“The next one is test and sample validation,” she continued. “There are loads of different ways of doing sampling at home, but you have to make sure it’s up to the correct GCP standard for the trial and that is something that’s a bit of an evolving area.

“If you’re asking patients to self-test at home and you’re relying on information that they’re pushing from home to the clinic, there may be a perception that the responsibility for their test results, and their care, and the clinical decisions that the clinician makes, rests far more on the patient and the carer themselves than ever before. Is that something that they actually want – that responsibility for getting an accurate result? Is it something that they want? Is it something that people are training them up to do appropriately? Or is it a source of worry? Again, there’s ways to address it, but it’s not going to be taken lightly.”

Finding balance

No one ever said the traditional clinical trial was perfect – it is burdened with limitations that have challenged clinicians and researchers for years in the face of increasing healthcare demands. A raft of strategies have been devised to circumvent these, and virtual trials are a key tool in this war chest, able to boost recruitment rates, diversity, and by extension cut costs by minimising or eliminating avoidable expenditure incurred by delays. But it’s not a panacea; virtual trials come with considerations of their own. For this reason, Royle argues that the pros and cons of both approaches must be carefully weighed in order to achieve a balanced strategy where both techniques complement each other’s strengths and weaknesses in order to address the challenges that modern clinical trials present.   

“I think the combination of the two is probably preferable, first of all because it gives people choice,” she explains. “If people really get a lot of motivation and a lot of reassurance from their clinician and their healthcare team regularly, that in itself is likely to help them get a better patient experience through the trial. They should have the choice of having that improved experience. If patients prefer to stay at home, we should try to facilitate that.

“People only take part in trials where it’s ethically correct for them to do so,” she continued. “For every single test result and every single action, the trial has to be done in an ethically sound way. If you have a test result that is better done in the clinic, keep it in the clinic until you have it to the level that it would be just as informative from home. Or you can actually combine results from home to get a better result than in the clinic, so stage the way that you go depending on how you can address the research questions quickly and optimise the patient experience. It’s one of those areas where healthcare is driven by science, fundamentally, but it’s always delivered by people. Because of that, how you deliver your trial needs to respect the people involved, give them choice, and actions that are appropriate, as well as address the scientific question. Because otherwise you don’t get a medicine.”